Illness representations and psychological wellbeing in adults with cancer

Background: Research has shown that the emotional impact of cancer can be more difficult to cope with than practical or physical demands and a diagnosis can have significant short- and long-term psychological sequalae including depression, anxiety, difficulties in adjustment and coping and associated poor quality of life (Vachon, 2006). The common-sense model of illness representations has been widely cited as a useful theoretical framework to explain how individuals with chronic illnesses such as cancer think about and respond to their condition (Leventhal & Nerenz, 1985). Aims: Two systematic reviews were conducted to identify studies that had measured the prospective relationship between illness representations and the psychological health of cancer patients (Review 1) and to identify studies that had developed interventions to modify the illness perceptions of cancer patients to improve their psychological health (Review 2). Methods: Using best practice guidelines for systematic reviews (Centre for Reviews and Dissemination, 2009) two independent systematic reviews were conducted. Results: Review 1 identified seven studies that had measured the prospective relationship between illness perceptions and psychological health outcomes in cancer patients. The majority of these studies found that patients with the most negative illness perceptions had the poorest psychological health in the future. Review 2 identified thirteen studies that had developed interventions to either directly target illness perceptions or had hypothesised that other types of intervention would indirectly change patient’s cancer related illness perceptions. Findings revealed some interventions were more effective than others in improving the psychological health of cancer patients, largely depending on their design and content. Discussion: Illness perceptions were overall predictive of several psychological health outcomes in cancer patients although there was a lack of methodological consistency in the measurement of illness perceptions making synthesis challenging. Interventions were more likely to be effective if they did not specifically target illness perceptions and if they were comprised multiple ‘active’ components including increased access to social support, homework based activity, group discussion, skills based training and improving the expression of emotions. Relaxation training appeared to be a significant component useful in facilitating psychological improvements in this patient group. Conclusions: Future research would benefit from further exploration of the process of change in such complex interventions in order determine which ingredients or indeed combination of ingredients are necessary for interventions to be effective in improving psychological health

Anthropomorphism Is Not Always A Marketing Panacea: How Anthropomorphism Shapes Product Durability Perception.

This research examined anthropomorphism as a marketing tool in the new paradigms of green and online merchandising. Two experiments tested how product anthropomorphism affects consumers' product durability perception. Study 1 demonstrated that anthropomorphic design had a significant effect on reducing a product’s durability perception due to its greater perceived performance risk. Importantly, this research reveals an important boundary condition for the negative effect of anthropomorphism on perceived durability and performance risk. Study 2 demonstrated the moderating role of consumers' green consumption attitudes, where individuals with lower green consumption attitudes perceiving anthropomorphised products to have greater perceived performance risk and lesser durability than non-anthropomorphised products. These studies produced clear and significant outcomes that can be utilised in both theoretical and managerial implications. Therefore, although most extant research has shown that anthropomorphism enhances consumers' perceptions of a product, the current research demonstrates that anthropomorphising a product or its promotion can become a detrimental marketing strategy when aiming to project durability

A Comparative Survey of the Frequency and Distribution of Polymorphism in the Genome of Xenopus tropicalis

Naturally occurring DNA sequence variation within a species underlies evolutionary adaptation and can give rise to phenotypic changes that provide novel insight into biological questions. This variation exists in laboratory populations just as in wild populations and, in addition to being a source of useful alleles for genetic studies, can impact efforts to identify induced mutations in sequence-based genetic screens. The Western clawed frog Xenopus tropicalis (X. tropicalis) has been adopted as a model system for studying the genetic control of embryonic development and a variety of other areas of research. Its diploid genome has been extensively sequenced and efforts are underway to isolate mutants by phenotype- and genotype-based approaches. Here, we describe a study of genetic polymorphism in laboratory strains of X. tropicalis. Polymorphism was detected in the coding and non-coding regions of developmental genes distributed widely across the genome. Laboratory strains exhibit unexpectedly high frequencies of genetic polymorphism, with alleles carrying a variety of synonymous and non-synonymous codon substitutions and nucleotide insertions/deletions. Inter-strain comparisons of polymorphism uncover a high proportion of shared alleles between Nigerian and Ivory Coast strains, in spite of their distinct geographical origins. These observations will likely influence the design of future sequence-based mutation screens, particularly those using DNA mismatch-based detection methods which can be disrupted by the presence of naturally occurring sequence variants. The existence of a significant reservoir of alleles also suggests that existing laboratory stocks may be a useful source of novel alleles for mapping and functional studies

A systematic genome-wide analysis of zebrafish protein-coding gene function

Since the publication of the human reference genome, the identities of specific genes associated with human diseases are being discovered at a rapid rate. A central problem is that the biological activity of these genes is often unclear. Detailed investigations in model vertebrate organisms, typically mice, have been essential for understanding the activities of many orthologues of these disease-associated genes. Although gene-targeting approaches1, 2, 3 and phenotype analysis have led to a detailed understanding of nearly 6,000 protein-coding genes3, 4, this number falls considerably short of the more than 22,000 mouse protein-coding genes5. Similarly, in zebrafish genetics, one-by-one gene studies using positional cloning6, insertional mutagenesis7, 8, 9, antisense morpholino oligonucleotides10, targeted re-sequencing11, 12, 13, and zinc finger and TAL endonucleases14, 15, 16, 17 have made substantial contributions to our understanding of the biological activity of vertebrate genes, but again the number of genes studied falls well short of the more than 26,000 zebrafish protein-coding genes18. Importantly, for both mice and zebrafish, none of these strategies are particularly suited to the rapid generation of knockouts in thousands of genes and the assessment of their biological activity. Here we describe an active project that aims to identify and phenotype the disruptive mutations in every zebrafish protein-coding gene, using a well-annotated zebrafish reference genome sequence18, 19, high-throughput sequencing and efficient chemical mutagenesis. So far we have identified potentially disruptive mutations in more than 38% of all known zebrafish protein-coding genes. We have developed a multi-allelic phenotyping scheme to efficiently assess the effects of each allele during embryogenesis and have analysed the phenotypic consequences of over 1,000 alleles. All mutant alleles and data are available to the community and our phenotyping scheme is adaptable to phenotypic analysis beyond embryogenesis

Correlated Genetic and Ecological Diversification in a Widespread Southern African Horseshoe Bat

The analysis of molecular data within a historical biogeographical framework, coupled with ecological characteristics can provide insight into the processes driving diversification. Here we assess the genetic and ecological diversity within a widespread horseshoe bat Rhinolophus clivosus sensu lato with specific emphasis on the southern African representatives which, although not currently recognized, were previously described as a separate species R. geoffroyi comprising four subspecies. Sequence divergence estimates of the mtDNA control region show that the southern African representatives of R. clivosus s.l. are as distinct from samples further north in Africa than they are from R. ferrumequinum, the sister-species to R. clivosus. Within South Africa, five genetically supported geographic groups exist and these groups are corroborated by echolocation and wing morphology data. The groups loosely correspond to the distributions of the previously defined subspecies and Maxent modelling shows a strong correlation between the detected groups and ecoregions. Based on molecular clock calibrations, it is evident that climatic cycling and related vegetation changes during the Quaternary may have facilitated diversification both genetically and ecologically

Case Reports1. A Late Presentation of Loeys-Dietz Syndrome: Beware of TGFβ Receptor Mutations in Benign Joint Hypermobility

Background: Thoracic aortic aneurysms (TAA) and dissections are not uncommon causes of sudden death in young adults. Loeys-Dietz syndrome (LDS) is a rare, recently described, autosomal dominant, connective tissue disease characterized by aggressive arterial aneurysms, resulting from mutations in the transforming growth factor beta (TGFβ) receptor genes TGFBR1 and TGFBR2. Mean age at death is 26.1 years, most often due to aortic dissection. We report an unusually late presentation of LDS, diagnosed following elective surgery in a female with a long history of joint hypermobility. Methods: A 51-year-old Caucasian lady complained of chest pain and headache following a dural leak from spinal anaesthesia for an elective ankle arthroscopy. CT scan and echocardiography demonstrated a dilated aortic root and significant aortic regurgitation. MRA demonstrated aortic tortuosity, an infrarenal aortic aneurysm and aneurysms in the left renal and right internal mammary arteries. She underwent aortic root repair and aortic valve replacement. She had a background of long-standing joint pains secondary to hypermobility, easy bruising, unusual fracture susceptibility and mild bronchiectasis. She had one healthy child age 32, after which she suffered a uterine prolapse. Examination revealed mild Marfanoid features. Uvula, skin and ophthalmological examination was normal. Results: Fibrillin-1 testing for Marfan syndrome (MFS) was negative. Detection of a c.1270G > C (p.Gly424Arg) TGFBR2 mutation confirmed the diagnosis of LDS. Losartan was started for vascular protection. Conclusions: LDS is a severe inherited vasculopathy that usually presents in childhood. It is characterized by aortic root dilatation and ascending aneurysms. There is a higher risk of aortic dissection compared with MFS. Clinical features overlap with MFS and Ehlers Danlos syndrome Type IV, but differentiating dysmorphogenic features include ocular hypertelorism, bifid uvula and cleft palate. Echocardiography and MRA or CT scanning from head to pelvis is recommended to establish the extent of vascular involvement. Management involves early surgical intervention, including early valve-sparing aortic root replacement, genetic counselling and close monitoring in pregnancy. Despite being caused by loss of function mutations in either TGFβ receptor, paradoxical activation of TGFβ signalling is seen, suggesting that TGFβ antagonism may confer disease modifying effects similar to those observed in MFS. TGFβ antagonism can be achieved with angiotensin antagonists, such as Losartan, which is able to delay aortic aneurysm development in preclinical models and in patients with MFS. Our case emphasizes the importance of timely recognition of vasculopathy syndromes in patients with hypermobility and the need for early surgical intervention. It also highlights their heterogeneity and the potential for late presentation. Disclosures: The authors have declared no conflicts of interes

Effect of remote ischaemic conditioning on clinical outcomes in patients with acute myocardial infarction (CONDI-2/ERIC-PPCI): a single-blind randomised controlled trial.

BACKGROUND: Remote ischaemic conditioning with transient ischaemia and reperfusion applied to the arm has been shown to reduce myocardial infarct size in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI). We investigated whether remote ischaemic conditioning could reduce the incidence of cardiac death and hospitalisation for heart failure at 12 months. METHODS: We did an international investigator-initiated, prospective, single-blind, randomised controlled trial (CONDI-2/ERIC-PPCI) at 33 centres across the UK, Denmark, Spain, and Serbia. Patients (age >18 years) with suspected STEMI and who were eligible for PPCI were randomly allocated (1:1, stratified by centre with a permuted block method) to receive standard treatment (including a sham simulated remote ischaemic conditioning intervention at UK sites only) or remote ischaemic conditioning treatment (intermittent ischaemia and reperfusion applied to the arm through four cycles of 5-min inflation and 5-min deflation of an automated cuff device) before PPCI. Investigators responsible for data collection and outcome assessment were masked to treatment allocation. The primary combined endpoint was cardiac death or hospitalisation for heart failure at 12 months in the intention-to-treat population. This trial is registered with ClinicalTrials.gov (NCT02342522) and is completed. FINDINGS: Between Nov 6, 2013, and March 31, 2018, 5401 patients were randomly allocated to either the control group (n=2701) or the remote ischaemic conditioning group (n=2700). After exclusion of patients upon hospital arrival or loss to follow-up, 2569 patients in the control group and 2546 in the intervention group were included in the intention-to-treat analysis. At 12 months post-PPCI, the Kaplan-Meier-estimated frequencies of cardiac death or hospitalisation for heart failure (the primary endpoint) were 220 (8·6%) patients in the control group and 239 (9·4%) in the remote ischaemic conditioning group (hazard ratio 1·10 [95% CI 0·91-1·32], p=0·32 for intervention versus control). No important unexpected adverse events or side effects of remote ischaemic conditioning were observed. INTERPRETATION: Remote ischaemic conditioning does not improve clinical outcomes (cardiac death or hospitalisation for heart failure) at 12 months in patients with STEMI undergoing PPCI. FUNDING: British Heart Foundation, University College London Hospitals/University College London Biomedical Research Centre, Danish Innovation Foundation, Novo Nordisk Foundation, TrygFonden

Latent preconditions of medication administration errors: development of a proactive error-management tool

latrogenic injury has been found to occur in around 10% of UK hospital admissions, equating to the harm of approximately 850,000 patients each year. The Department of Health has made repeated calls for NHS research to learn from proactive error management techniques (EMTs) employed within other 'safety-critical' organisations (DOH 2000,2001). The aim of this research was to develop a valid and reliable proactive measure of latent organisational failures (EMT) for use in secondary care using a psychological theory of organisational accidents (Reason, 1990,1997). This theory purports that errors occur as a result of a complex interaction between unsafe acts and systemic organisational weaknesses known as latent failures. This tool will be used to measure and monitor organisational safety in health care and predict the likelihood of medication administration errors (MAEs). Twenty semi-structured interviews were conducted in study I with qualified nurses from several general medical wards and senior managers from Bradford Teaching Hospitals NHS Foundation Trust. Using error vignettes, participants were asked to discuss their perceptions of error causation. Additional qualitative data was collected using clinical observations and incident report review. Using thematic content analysis, ten latent workplace and organisational causes of MAEs were identified, consistent with psychological error theory and error causes evidenced within other safety-critical industries (Reason, 1997; Groeneweg, 1992; Helmreich, 2000; Colla et al., 2005), including team functioning, human resources, culture and training. In ternis of Reason's organisational accident model, combining three pools of independent qualitative data afforded an in-depth exploration of latent error causes at an individual (e. g. unsafe practices), workplace (e. g. team functioning) and organisational level (e. g. use of policies and protocols). Study 2 was conducted to conceptualize identified latent preconditions of MAE within a proactive questionnaire measure; the Organisational Safety Questionnaire (OSQ). Revisiting qualitative data collected in Study 1, this study explored the ways in which each latent organisational failure would manifest at a hospital ward level. One hundred and forty-five safety indicators were generated based on these manifestations of poor safety. Pilot studies to test the face validity of indicators and content analysis to remove less commonly endorsed items led to refinement of the tool to 82 items. Given several notable drawbacks to using NHS formal incident reporting systems as an outcome measure, study 3 was conducted to develop an independent measure of MAEs against which to test the predictive validity of the OSQ (the Drug Round Behaviour questionnaire; DRBQ). This study explored the types of MAEs which can arise in secondary care as a direct or indirect result of the ten latent preconditions. Using the qualitative data obtained in study 1, a 27-item measure of 10 types of MAE (NCC MERP, 1995) was developed which was not reliant upon adverse patient outcomes and intended to also capture near misses. After a pilot study was conducted to improve the construct and face validity of the tool, 13 items which reflected 7 types of MAE had good face validity and were retained for study 4. The final study was conducted to measure the validity and reliability of the OSQ. The 82-item OSQ was administered to qualified and unqualified nurses working in 54 clinical areas across 2 two Bradford hospitals. Analysis revealed that the OSQ was relevant for all qualified nurses working in 34 of these clinical areas. Although developed as 10 subscales representing 10 latent preconditions of MAE, factor analysis yielded only one overall construct from 28 items named 'organisational safety'. However, these items reflected 8 of the 10 proposed predictors of MAE which supports their role in the occurrence of MAE. The 28-item OSQ had good internal consistency and concurrent validity (with an independent 9-item measure of local safety culture; Vogus & Sutcliffe, 2007). While the OSQ was significantly predictive of MAEs measured by the DRBQ, it did not significantly predict formally reported incidents. However, this may have been an artefact of low statistical power which may have been improved with a larger sample. Finally, high safety risk wards said they were less likely to formally report their errors than lower risk wards, yet all wards reported a similar number of incidents. It is proposed that high risk wards report a comparatively smaller percentage of the errors which actually occur compared to lower risk wards due to poorer safety cultures. Interestingly, high safety risk wards admitted making significantly more MAEs on the DRBQ than 'safer' wards suggesting the DRBQ was a more sensitive measure of the actual number of drug administration errors occurring on wards. The Organisational Safety Questionnaire represents a novel, valid and reliable proactive measure of safety which is not currently available in health care which would be useful in measuring the effects on systems interventions and other organisational changes. This thesis has explored and identified latent organisational causes of medication administration errors in secondary care and used methodological techniques used in other safety-critical industries to develop a valid and reliable measure of organisational safety which was successful in predicting medication administration errors. Findings are discussed in terms of the benefit of rigorous qualitative methods in this type of research and the direction of future research which could examine the generaliseability of the tool to other health care professionals or fields of medicin