Prions and Prion-like assemblies in neurodegeneration and immunity: The emergence of universal mechanisms across health and disease.

Prion-like behaviour is an abrupt process, an "all-or-nothing" transition between a monomeric species and an "infinite" fibrillated form. Once a nucleation point is formed, the process is unstoppable as fibrils self-propagate by recruiting and converting all monomers into the amyloid fold. After the "mad cow" episode, prion diseases have made the headlines, but more and more prion-like behaviours have emerged in neurodegenerative diseases, where formation of fibrils and large conglomerates of proteins deeply disrupt the cell homeostasis. More interestingly, in the last decade, examples emerged to suggest that prion-like conversion can be used as a positive gain of function, for memory storage or structural scaffolding. More recent experiments show that we are only seeing the tip of the iceberg and that, for example, prion-like amplification is found in many pathways of the immune response. In innate immunity, receptors on the cellular surface or within the cells 'sense' danger and propagate this information as signal, through protein-protein interactions (PPIs) between 'receptor', 'adaptor' and 'effector' proteins. In innate immunity, the smallest signal of a foreign element or pathogen needs to trigger a macroscopic signal output, and it was found that adaptor polymerize to create an extreme signal amplification. Interestingly, our body uses multiple structural motifs to create large signalling platform; a few innate proteins use amyloid scaffolds but most of the polymers discovered are composed by self-assembly in helical filaments. Some of these helical assemblies even have intercellular "contamination" in a "true" prion action, as demonstrated for ASC specks and MyD88 filaments. Here, we will describe the current knowledge in neurodegenerative diseases and innate immunity and show how these two very different fields can cross-seed discoveries.

Learning from remote decentralised clinical trial experiences: A qualitative analysis of interviews with trial personnel, patient representatives and other stakeholders.

AIMS: The aim of the study was to identify actionable learning points from stakeholders in remote decentralised clinical trials (RDCTs) to inform their future design and conduct. METHODS: Semistructured interviews were carried out with a purposive sample of stakeholders, including senior managers, trial managers, technology experts, principal investigators, clinical investigators, research scientists, research nurses, vendors, patient representatives and project assistants. The interview data were coded using a thematic approach, identifying similarities, differences and clustering to generate descriptive themes. Further refinement of themes was guided by empirical phenomenology, grounding explanation in the meanings that interviewees gave to their experiences. RESULTS: Forty-eight stakeholders were interviewed. Actionable learning points were generated from the thematic analysis. Patient involvement and participant engagement were seen as critical to the success of RDCTs where in-person contact is minimal or nonexistent. Involving patients in identifying the research question, creating recruitment materials, apps and websites, and providing ongoing feedback to trial participants were regarded as facilitating recruitment and engagement. Building strong relationships early with trial partners was thought to support RDCT conduct. Multiple modes of capturing information, including patient-reported outcomes (PROs) and routinely collected data, were felt to contribute to data completeness. However, RDCTs may transfer trial activity burden onto participants and remote-working research staff, therefore additional support may be needed. CONCLUSION: RDCTs will continue to face challenges in implementing novel technologies. However, maximising patient and partner involvement, reducing participant and staff burden, and simplifying how participants and staff interact with the RDCT may facilitate their implementation.

A systematic review of methods used to conduct decentralised clinical trials.

AIMS: To evaluate, using quantitative and qualitative approaches, published data on the design and conduct of decentralised clinical trials (DCTs). METHODS: We searched MEDLINE, EMBASE, CENTRAL, PsycINFO, ProQuest Dissertations and Theses, ClinicalTrials.gov, OpenGrey and Google Scholar for publications reporting, discussing, or evaluating decentralised clinical research methods. Reports of randomised clinical trials using decentralised methods were included in a focused quantitative analysis with a primary outcome of number of randomised participants. All publications discussing or evaluating DCTs were included in a wider qualitative analysis to identify advantages, disadvantages, facilitators, barriers and stakeholder opinions of decentralised clinical trials. Quantitative data were summarised using descriptive statistics, and qualitative data analysed using a thematic approach. RESULTS: Initial searches identified 19 704 articles. After removal of duplicates, 18 553 were screened, resulting in 237 eligible for full-text assessment. Forty-five trials were included in the quantitative analysis; 117 documents were included in the qualitative analysis. Trials were widely heterogeneous in design and reporting, precluding meta-analysis of the effect of DCT methods on the primary recruitment outcome. Qualitative analysis formulated 4 broad themes: value, burden, safety and equity. Participant and stakeholder experiences of DCTs were incompletely represented. CONCLUSION: DCTs are developing rapidly. However, there is insufficient evidence to confirm which methods are most effective in trial recruitment, retention, or overall cost. The identified advantages, disadvantages, facilitators and barriers should inform the development of DCT methods. We recommend further research on how DCTs are experienced and perceived by participants and stakeholders to maximise potential benefits.

To be more precise: the role of intracellular trafficking in development and pattern formation.

Living cells interpret a variety of signals in different contexts to elucidate functional responses. While the understanding of signalling molecules, their respective receptors and response at the gene transcription level have been relatively well-explored, how exactly does a single cell interpret a plethora of time-varying signals? Furthermore, how their subsequent responses at the single cell level manifest in the larger context of a developing tissue is unknown. At the same time, the biophysics and chemistry of how receptors are trafficked through the complex dynamic transport network between the plasma membrane-endosome-lysosome-Golgi-endoplasmic reticulum are much more well-studied. How the intracellular organisation of the cell and inter-organellar contacts aid in orchestrating trafficking, as well as signal interpretation and modulation by the cells are beginning to be uncovered. In this review, we highlight the significant developments that have strived to integrate endosomal trafficking, signal interpretation in the context of developmental biology and relevant open questions with a few chosen examples. Furthermore, we will discuss the imaging technologies that have been developed in the recent past that have the potential to tremendously accelerate knowledge gain in this direction while shedding light on some of the many challenges.

Pathological mutations differentially affect the self-assembly and polymerisation of the innate immune system signalling adaptor molecule MyD88.

BACKGROUND: Higher-order self-assembly of proteins, or "prion-like" polymerisation, is now emerging as a simple and robust mechanism for signal amplification, in particular within the innate immune system, where the recognition of pathogens or danger-associated molecular patterns needs to trigger a strong, binary response within cells. MyD88, an important adaptor protein downstream of TLRs, is one of the most recent candidates for involvement in signalling by higher order self-assembly. In this new light, we set out to re-interpret the role of polymerisation in MyD88-related diseases and study the impact of disease-associated point mutations L93P, R196C, and L252P/L265P at the molecular level. RESULTS: We first developed new in vitro strategies to characterise the behaviour of polymerising, full-length MyD88 at physiological levels. To this end, we used single-molecule fluorescence fluctuation spectroscopy coupled to a eukaryotic cell-free protein expression system. We were then able to explore the polymerisation propensity of full-length MyD88, at low protein concentration and without purification, and compare it to the behaviours of the isolated TIR domain and death domain that have been shown to have self-assembly properties on their own. These experiments demonstrate that the presence of both domains is required to cooperatively lead to efficient polymerisation of the protein. We then characterised three pathological mutants of MyD88. CONCLUSION: We discovered that all mutations block the ability of MyD88 to polymerise fully. Interestingly, we show that, in contrast to L93P and R196C, L252P is a gain-of-function mutation, which allows the MyD88 mutant to form extremely stable oligomers, even at low nanomolar concentrations. Thus, our results shed new light on the digital "all-or-none" responses by the myddosomes and the behaviour of the oncogenic mutations of MyD88.

Extending the assessment of patient-centredness in health care: Development of the updated Valuing Patients as Individuals Scale using exploratory factor analysis.

AIMS AND OBJECTIVES: To update and re-validate the Valuing Patients as Individuals Scale for use as a patient appraisal of received healthcare. BACKGROUND: Healthcare in the United Kingdom and beyond is required to deliver high quality, person-centred care that is clinically effective and safe. However, patient experience is not uniform, and complaints often focus on the way patients have been treated. Legislation in United Kingdom requires health services to gather and use patients' evaluations of care to improve services. DESIGN: This study uses scoping literature reviews, cognitive testing of questionnaire items with patient and healthcare staff focus groups, and exploratory factor analysis. METHODS/SETTING/PARTICIPANTS: Data were collected from 790 participants across 34 wards in two acute hospitals in one National Health Service Health Board in Scotland from September 2011-February 2012. Ethics and Research and Development approval were obtained. RESULTS: Fifty six unique items identified through literature review were added to 72 original Valuing Patients as Individuals Scale items. Face validity interviews removed ambiguous or low relevance items leaving 88 items for administration to patients. Two hundred and ninety questionnaires were returned, representing 37% response rate, 71 were incomplete. Thus 219 complete data were used for Exploratory Factor Analysis with varimax orthogonal rotation. This revealed a 31 item, three factor solution, Care and Respect; Understanding and Engagement; Patient Concerns, with good reliability, concurrent and discriminant validity in terms of gender. A shortened 10 item measure based on the top 3 or 4 loading items on each scale was comparable. CONCLUSIONS: The Updated Valuing Patients as Individuals Scale is sufficiently developed to capture patient appraisals of received care. RELEVANCE TO CLINICAL PRACTICE: The short scale version is now being routinized in real-time evaluation of patient experience contributing to this United Kingdom, National Health Service setting meeting its policy and legislative requirements.

Supporting 'work-related goals' rather than 'return to work' after cancer? A systematic review and meta-synthesis of 25 qualitative studies.

BACKGROUND: This study aimed to systematically review and synthesise qualitative studies of employment and cancer. METHODS: A rigorous systematic review and meta-synthesis process was followed. A total of 13,233 papers were retrieved from eight databases; 69 were deemed relevant following title and abstract appraisal. Four further publications were identified via contact with key authors. Screening of full texts resulted in the retention of 25 publications from six countries, which were included in the synthesis. RESULTS: Studies consistently indicate that for people with cancer, 'work' forms a central basis for self-identity and self-esteem, provides financial security, forms and maintains social relationships, and represents an individual's abilities, talents and health. Work is therefore more than paid employment. Its importance to individuals rests on the relative value survivors place on these constituent functions. The desirability, importance and subsequent interpretation of individuals' experience of 'return to work' appears to be influenced by the ways in which cancer affects these functions or goals of 'work'. Our synthesis draws these complex elements into a heuristic model to help illustrate and communicate these inter-relationships. CONCLUSION: The concept of 'return to work' may be overly simplistic, and as a result, misleading. The proposed benefits previously ascribed to 'return to work' may only be achieved through consideration of the specific meaning and role of work to the individual. Interventions to address work-related issues need to be person-centred, acknowledging the work-related outcomes that are important to the individual. A conceptual and operational shift towards supporting survivors to identify and achieve their 'work-related goals' may be more appropriate.

Lifestyle issues for colorectal cancer survivors--perceived needs, beliefs and opportunities.

PURPOSE: As survival rates for patients treated with colorectal cancer (CRC) increase, it is important to consider the short- and long-term self-management needs. The current work aimed to explore perceived patient needs for advice on diet, activity and beliefs about the role of lifestyle for reducing disease recurrence. METHODS: Forty colorectal cancer survivors, aged between 27 and 84, participated in six focus groups in community locations in the UK. RESULTS: The findings suggest that CRC survivors would welcome guidance on diet in the immediate posttreatment period to alleviate symptoms and fears about food choices. Many participants actively sought lifestyle advice but experienced confusion, mixed messages, culturally inappropriate guidance and uncertainty about evidence of benefit. There was scepticism over the role of diet and physical activity as causes of cancer, in part because people believed their lifestyles had been healthy and could not see how reinstating healthy behaviours would reduce future disease risk. The sense of changing lifestyle to 'stack the odds in their favour' (against recurrence) appeared a more meaningful concept than prevention per se. Those people who had made or maintained dietary changes highlighted the importance of these to contributing to wellbeing and a sense of control in their life. CONCLUSIONS: A dogmatic approach to lifestyle change may lead to perceptions of victim blaming and stigmatisation. Personalised, evidence informed, guidance on lifestyle choices does appear to be a much needed part of care planning and should be built in to survivorship programmes.

A secondary qualitative analysis of stakeholder views about participant recruitment, retention, and adherence in decentralised clinical trials (DCTs).

BACKGROUND: Decentralised clinical trials (DCTs) are clinical trials where all or most trial activities occur in or near participants' homes instead of hospitals or research sites. While more convenient for participants, DCTs may offer limited opportunities to build trust with investigators and trial teams. This qualitative analysis explored DCT stakeholder views to inform strategies for maximising participant recruitment, retention, and adherence. METHODS: A secondary analysis of original interview transcripts focused on participant engagement: recruitment, retention, and adherence. Semi-structured interviews were conducted with a purposive sample of stakeholders, including trial managers and administrators, investigators, nurses, vendors, and patient representatives. Interview data were coded using a thematic approach to generate descriptive themes. RESULTS: Forty-eight stakeholders were interviewed. Three components of participant engagement in DCTs were identified: identifying and attracting potential participants, retaining participants and encouraging adherence, and involvement of patients and the public. Interviewees believed that a potential participant's beliefs about research value and their trust in the research team strongly influenced the likelihood of taking part in a DCT. Early involvement of patients was identified as one way to gauge participant priorities. However, perceived burden was seen as a barrier to recruitment. Factors influencing retention and adherence were related to the same underlying motivators that drove recruitment: personal values, circumstances, and burden. Being part of a DCT should not conflict with the original motivations to participate. CONCLUSION: Recruitment, retention, and adherence in DCTs are driven by factors that have previously been found to affect conventional clinical trials. Increasing patient and public involvement can address many of these factors. In contrast to conventional trials, DCTs are perceived as requiring greater emphasis on communication, and contact, to engender trust between participants and researchers despite a relative lack of in-person interaction.

Development of a model home health nurse internship program for new graduates: key lessons learned.

A nursing shortage, the aging baby boomer population, an escalating need for home health care, and limited availability of health care dollars are threatening to undermine the quality of health care in the United States. The National Center for Health Workforce Analysis projects a deficit of 275,000 full-time equivalents by 2010 (-12%) and a deficit of 800,000 by 2020 (-29%). This article focuses on one home health agency's strategy to support nurse graduates transitioning from student to professional nurse. Based on Benner's (1984) hallmark theory from novice to expert, the goals of this program are to enhance job satisfaction and social integration, facilitate autonomy, increase critical thinking and psychomotor skills, and develop additional competencies. Eleven key lessons learned are outlined.

High Throughput Screening to Identify Selective and Nonpeptidomimetic Proteasome Inhibitors As Antimalarials.

The Ubiquitin Proteasome System is the main proteolytic pathway in eukaryotic cells, playing a role in key cellular processes. The essentiality of the Plasmodium falciparum proteasome is well validated, underlying its potential as an antimalarial target, but selective compounds are required to avoid cytotoxic effects in humans. Almost 550000 compounds were tested for the inhibition of the chymotrypsin-like activity of the P. falciparum proteasome using a Proteasome-GLO luminescence assay. Hits were confirmed in an orthogonal enzyme assay using Rho110-labeled peptides, and selectivity was assessed against the human proteasome. Four nonpeptidomimetic chemical families with some selectivity for the P. falciparum proteasome were identified and characterized in assays of proteasome trypsin and caspase activities and in parasite growth inhibition assays. Target engagement studies were performed, validating our approach. Hits identified are good starting points for the development of new antimalarial drugs and as tools to better understand proteasome function in P. falciparum.

Process evaluation of a randomised pilot trial of home-based rehabilitation compared to usual care in patients with heart failure with preserved ejection fraction and their caregiver's.

BACKGROUND: Whilst almost 50% of heart failure (HF) patients have preserved ejection fraction (HFpEF), evidence-based treatment options for this patient group remain limited. However, there is growing evidence of the potential value of exercise-based cardiac rehabilitation. This study reports the process evaluation of the Rehabilitation Enablement in Chronic Heart Failure (REACH-HF) intervention for HFpEF patients and their caregivers conducted as part of the REACH-HFpEF pilot trial. METHODS: Process evaluation sub-study parallels to a single-centre (Tayside, Scotland) randomised controlled pilot trial with qualitative assessment of both intervention fidelity delivery and HFpEF patients' and caregivers' experiences. The REACH-HF intervention consisted of self-help manual for patients and caregivers, facilitated over 12 weeks by trained healthcare professionals. Interviews were conducted following completion of intervention in a purposeful sample of 15 HFpEF patients and seven caregivers. RESULTS: Qualitative information from the facilitator interactions and interviews identified three key themes for patients and caregivers: (1) understanding their condition, (2) emotional consequences of HF, and (3) responses to the REACH-HF intervention. Fidelity analysis found the interventions to be delivered adequately with scope for improvement in caregiver engagement. The differing professional backgrounds of REACH-HF facilitators in this study demonstrate the possibility of delivery of the intervention by healthcare staff with expertise in HF, cardiac rehabilitation, or both. CONCLUSIONS: The REACH-HF home-based facilitated intervention for HFpEF appears to be a feasible and a well-accepted model for the delivery of rehabilitation, with the potential to address key unmet needs of patients and their caregivers who are often excluded from HF and current cardiac rehabilitation programmes. Results of this study will inform a recently funded full multicentre randomised clinical trial. TRIAL REGISTRATION: ISRCTN78539530 (date of registration 7 July 2015).

I've never not had it so I don't really know what it's like not to: nondifference and biographical disruption among children and young people with cystic fibrosis.

The relevance of biographical disruption and loss of self for children and young people is unclear, particularly in cases of congenital illness such as cystic fibrosis, where no prior period of wellness, stability, or perceived normality might exist. We explored the meaning, importance, and forms of maintenance of ideas of normality among 32 children and young people with cystic fibrosis. We examine the ways in which normalcy is produced, maintained, and threatened, and discuss the implications for the applicability and relevance of these traditional sociological concepts. Analysis of children's and young people's accounts resulted in a conceptualization of four forms of normalcy based on personal and social definitions and audiences. Biographical disruption appeared relevant but in a more nuanced form than its usual conceptualization when applied to adult populations. Maintaining normality within the family resulted in continual biographical revision in anticipation of future illness trajectory and life course.

From child to adult: an exploration of shifting family roles and responsibilities in managing physiotherapy for cystic fibrosis.

Although chest physiotherapy is central to the management of cystic fibrosis many report problems with adherence. Research in other long-term conditions suggests that non-adherence may be exacerbated as the child grows older and self-care responsibilities are transferred to the young person. We explored the nature and variation in roles of family members, how responsibility was transferred from the parent/family to the child, and what factors aided or hindered this process. We conducted in-depth interviews with 32 children with a diagnosis of cystic fibrosis aged 7-17 years, and with 31 parents attending cystic fibrosis clinics in two Scottish regions. Family responsibilities were primarily focused on mothers. The level and nature of involvement varied along a continuum that separated into six parental and five child roles and changed over time. However, this movement was frequently reversed during periods of illness or mistrust. The day to day experience of such a transfer was not straightforward, linear or unproblematic for any of the family members. Three factors were identified as assisting the transfer of responsibility: parents' perceptions of the benefits of transferring responsibility, children's perceptions of the benefits, and the available physical, social and psychological resources to support such a transfer. The principles and lessons from "concordance" (a therapeutic alliance based on a negotiation between equals and which may lead to agreement on management or agreement to differ) may provide a foundation for newly developing relationships between parents and their children emerging into adulthood. Further research is required to develop more specifically the content and structure of required support, its effectiveness in achieving more concordant relationships, and the resulting impact on adherence, perceived health and well-being from the perspective of the young person and parent.

Problems and solutions: accounts by parents and children of adhering to chest physiotherapy for cystic fibrosis.

PURPOSE: Although chest physiotherapy is central to the management of cystic fibrosis (CF), adherence among children is problematic. This study explores accounts by parents and children of the difficulties of adhering to chest physiotherapy for cystic fibrosis, and identifies strategies used by families to overcome these. METHODS: A qualitative study based on in-depth interviews with 32 children with a diagnosis of cystic fibrosis aged 7 - 17 years, and with 31 parents. RESULTS: Physiotherapy was frequently described as restrictive, threatening to identity and boring, giving rise to feelings of unfairness, inequality, 'difference', and social stigma. Motivation to adhere was influenced by perceptions of effectiveness that depended on external signs evident during or after the physiotherapy. Motivation was enhanced where parents and children visualized the accumulation of mucus. Some parents had developed distraction techniques that improved the experience of chest physiotherapy but had few opportunities to share these with other parents. CONCLUSION: The experience of physiotherapy is problematic to some parents and children. Furthermore, motivation to overcome these problems may be undermined by perceptions of ineffectiveness. Distraction techniques that change the value that the child places on the time spent doing physiotherapy and that reduces their perception of its duration may improve experience and adherence. The potential of visualization techniques to promote adherence should be investigated further.

Raman Spectroscopy of Three Average-Valence Dicopper Cryptates: Evidence for Copper-Copper Bonding.

Comparison of the X-ray structures of two pairs of dicopper(I) and dicopper(1.5) cryptates provides evidence (over 0.5 Å contraction of the internuclear distance in one pair) for copper-copper bond formation. Although resonance Raman spectroscopy fails to identify a pure copper-copper stretching mode, because of extensive mixing of several low-frequency stretching and bending modes, isotopic substitution experiments indicate significant Cu-Cu character in a band around 250 cm(-)(1). A normal coordinate analysis broadly supports the spectroscopic findings. X-ray crystal structures are presented for the dicopper(1.5) complex Cu(2)imBT(ClO(4))(3), C(18)H(30)Cl(3)Cu(2)N(8)O(12), a = 9.140(4) Å, c = 30.35(3) Å, rhombohedral, R32, Z = 3, and the dicopper(I) Cu(2)imbistrpn(ClO(4))(2), C(24)H(42)Cl(2)Cu(2)N(8)O(8), a = 9.279(2) Å, c = 32.846(9) Å, rhombohedral, R32, Z = 3.

Intervention description is not enough: evidence from an in-depth multiple case study on the untold role and impact of context in randomised controlled trials of seven complex interventions.

BACKGROUND: A number of single case reports have suggested that the context within which intervention studies take place may challenge the assumptions that underpin randomised controlled trials (RCTs). However, the diverse ways in which context may challenge the central tenets of the RCT, and the degree to which this information is known to researchers or subsequently reported, has received much less attention. In this paper, we explore these issues by focusing on seven RCTs of interventions varying in type and degree of complexity, and across diverse contexts. METHODS: This in-depth multiple case study using interviews, focus groups and documentary analysis was conducted in two phases. In phase one, a RCT of a nurse-led intervention provided a single exploratory case and informed the design, sampling and data collection within the main study. Phase two consisted of a multiple explanatory case study covering a spectrum of trials of different types of complex intervention. A total of eighty-four data sources across the seven trials were accessed. RESULTS: We present consistent empirical evidence across all trials to indicate that four key elements of context (personal, organisational, trial and problem context) are crucial to understanding how a complex intervention works and to enable both assessments of internal validity and likely generalisability to other settings. The ways in which context challenged trial operation was often complex, idiosyncratic, and subtle; often falling outside of current trial reporting formats. However, information on such issues appeared to be available via first hand 'insider accounts' of each trial suggesting that improved reporting on the role of context is possible. CONCLUSIONS: Sufficient detail about context needs to be understood and reported in RCTs of complex interventions, in order for the transferability of complex interventions to be assessed. Improved reporting formats that require and encourage the clarification of both general and project-specific threats to the likely internal and external validity need to be developed. In addition, a cultural change is required in which the open and honest reporting of such issues is seen as an indicator of study strength and researcher integrity, rather than a symbol of a poor quality study or investigator ability.

Is the routine recording of primary care consultations possible and desirable? Lessons for researchers from a consultation with multiple stakeholders.

OBJECTIVE: To explore stakeholders' attitudes towards routine, longitudinal recording of primary care consultations for research purposes, and to identify legal, ethical, and practical barriers and facilitators. METHODS: 183 stakeholders (including patients, researchers and practice staff) were identified using a purposeful sampling strategy. Stakeholders participated in focus groups and interviews. The data was analysed thematically in an iterative manner with themes and questions from earlier discussions being raised with later participants. RESULTS: Most participants supported the creation of a database and believed it would benefit patient care. They suggested it could be used to train doctors, aid understanding of conditions, and feed information back to practices to improve performance. However, enthusiasm was tempered by concerns about the ownership security and access of the data; quality and limitations of the dataset; impact on behaviour; and workload. Safeguards were suggested that protected vulnerable individuals, enabled participation, gave control to participants, and clarified data use. CONCLUSION: The findings show that collecting such longitudinal data is possible, valuable and acceptable providing certain safeguards are in place. PRACTICE IMPLICATIONS: Future studies employing routine recordings of consultations should: Attend to confidentiality, access and governance of the archive. Collect quality data, and store it securely.

Low exercise among children with asthma: a culture of over protection? A qualitative study of experiences and beliefs.

BACKGROUND: Research shows that children are insufficiently active in most affluent societies. Although children with asthma may particularly benefit from physical activity, they are less active than their peers. AIM: To explore the reasons for low physical activity levels among children with asthma and to identify strategies to improve activity. DESIGN OF STUDY: A qualitative study using in-depth interviews and focus groups. SETTING: Six GP practices, a Paediatric Respiratory Unit, and four schools in Tayside, Scotland. METHOD: Purposive sampling identified 30 children with asthma, their parents (n = 38) and school staff (n = 28), who were interviewed or took part in focus groups. Data were examined using constant comparative analysis. RESULTS: The lower level of activity among children with asthma was supported by a climate of fear among parents and teachers about what was safe and possible for the child. Restrictions were imposed because of perceived dangers of exercising in the presence of 'triggers'. Physical activity was regarded as a threat to be managed rather than something beneficial. Teachers found it difficult to distinguish between children who were physically incapable of exercise due to asthma and those who were unmotivated. GPs were unknowingly drawn into the controversy by children and parents who cite medical advice to sanction exemption from exercise. CONCLUSION: GPs and asthma nurses need to provide clear management plans explaining what is appropriate and safe in terms of exercise on a child-by-child basis, to counter the considerable misunderstanding and disagreement among children, parents, and teachers.

Comparison of copper imine and amine podates: geometric consequences of podand size and donor type.

The imine podands tris[(2-nitrobenzylidene)aminoethyl]amine and tris[(2-nitrobenzylidene)aminopropyl]amine both stabilize copper(I), forming {tris[(2-nitrobenzylidene)aminoethyl]amine-kappa4N}copper(I) perchlorate acetonitrile disolvate, [Cu(C27H27N7O6)]ClO4.2CH3CN, (II), and {tris[(2-nitrobenzylidene)aminopropyl]amine-kappa4N}copper(I) perchlorate, [Cu(C30H33N7O6)]ClO4, (VI), respectively. The larger propyl-based ligand is a poorer fit for the CuI ion. The reduced amine podand tris[(2-nitrobenzyl)aminoethyl]amine binds CuII and the resulting compound, chloro{tris[(2-nitrobenzyl)aminoethyl]amine-kappa4N}copper(II) chloride ethanol solvate, [Cu(C27H33N7O6)Cl]Cl.C2H5OH, (IV), shows both intra- and intermolecular hydrogen bonding, which gives rise to RRS or SSR conformations in the podand strands rather than the expected pseudo-threefold symmetry.