Positive state mindfulness: A multidimensional model of mindfulness in relation to positive experience

The present research tested Langer’s theory of mindfulness in the context of positive experiences: positive state mindfulness. In Study 1 (N1 = 586, N2 = 415) confirmatory factor analyses indicated that a three-factor model (Focused Attention, Novelty Appreciation, Open-Ended Expectations) fit the data well and explained responses better than a one-factor model. In support of construct validity, Study 2 (N3 = 239, N4 = 126) suggested that each dimension had a different pattern of associations with unidimensional trait measures of mindfulness, savoring beliefs, trait absorption, uncertainty tolerance, need for structure, and need for cognition. Study 3 (N5 = 46) revealed that each dimension correlated uniquely with the positive affect, self-esteem, interpersonal connectedness, and the overall rehearsal frequency associated with positive autobiographical events. In support of criterion validity in Study 4, in Experiment 1 (N6 = 46) a boredom task decreased Novelty Appreciation, and in Experiment 2 (N7 = 92) a problem-solving task increased Focused Attention. Our data suggest that positive mindfulness is more than the absence of mindlessness and that it includes three distinct dimensions. We discuss the utility of positive mindfulness in both research and practice

Ordering our world: the quest for traces of temporal organization in autobiographical memory

An experiment examined the idea, derived from the Self Memory System model (Conway & Pleydell-Pearce, 2000), that autobiographical events are sometimes tagged in memory with labels reflecting the life era in which an event occurred. The presence of such labels should affect the ease of judgments of the order in which life events occurred. Accordingly, 39 participants judged the order of two autobiographical events. Latency data consistently showed that between-era judgments were faster than within-era judgments, when the eras were defined in terms of either: (a) college versus high school, (b) academic quarter within year, or (c) academic year within school. The accuracy data similarly supported the presence of a between-era judgment effect for the college versus high school dichotomy

A study of National Health Service management of chronic osteoarthritis and low back pain

AIM: To describe treatment and referral patterns and National Health Service resource use in patients with chronic pain associated with low back pain or osteoarthritis, from a Primary Care perspective. BACKGROUND: Osteoarthritis and low back pain are the two commonest debilitating causes of chronic pain, with high health and social costs, and particularly important in primary care. Understanding current practice and resource use in their management will inform health service and educational requirements and the design and optimisation of future care. METHOD: Multi-centre, retrospective, descriptive study of adults (⩾18 years) with chronic pain arising from low back pain or osteoarthritis, identified through primary care records. Five general practices in Scotland, England (two), Northern Ireland and Wales. All patients with a diagnosis of low back pain or osteoarthritis made on or before 01/09/2006 who had received three or more prescriptions for pain medication were identified and a sub-sample randomly selected then consented to an in-depth review of their medical records (n=264). Data on management of chronic pain were collected retrospectively from patients’ records for three years from diagnosis (‘newly diagnosed’ patients) or for the most recent three years (‘established’ patients). FINDINGS: Patients received a wide variety of pain medications with no overall common prescribing pattern. GP visits represented the majority of the resource use and ‘newly diagnosed’ patients were significantly more likely to visit their GP for pain management than ‘established’ patients. Although ‘newly diagnosed’ patients had more referrals outside the GP practice, the number of visits to secondary care for pain management was similar for both groups. CONCLUSION: This retrospective study confirmed the complexity of managing these causes of chronic pain and the associated high resource use. It provides an in-depth picture of prescribing and referral patterns and of resource use

Does designation as a UNESCO World Heritage Site influence tourist evaluation of a local destination?

The purpose of this study is to explore whether the UNESCO World Heritage Site (WHS) designation affects tourists’ evaluation of the local destination hosting the site, building on a large sample of about 0.8 million tourists who visited Italy over the period 1997-2015. We find that the inscription onto the UNESCO World Heritage List exerts surprisingly a negative effect on the overall evaluation of the destination and also on the evaluation of its artistic assets though the magnitude of the latter is lower. The effect is heterogeneous across visitors, depending on evaluation levels, as well as origin/destinations and demographics. Nonetheless, the presence of multiple WHSs in the same destination tends to increase evaluation suggesting that destination stakeholders with previous experience in dealing with WHS designations are better equipped to manage the complicated relationship between tourism and preservation. Managerial and policy-making implications are discussed

Diverse Convergent Evidence in the Genetic Analysis of Complex Disease: Coordinating Omic, Informatic, and Experimental Evidence to Better Identify and Validate Risk Factors

In omic research, such as genome wide association studies, researchers seek to repeat their results in other datasets to reduce false positive findings and thus provide evidence for the existence of true associations. Unfortunately this standard validation approach cannot completely eliminate false positive conclusions, and it can also mask many true associations that might otherwise advance our understanding of pathology. These issues beg the question: How can we increase the amount of knowledge gained from high throughput genetic data? To address this challenge, we present an approach that complements standard statistical validation methods by drawing attention to both potential false negative and false positive conclusions, as well as providing broad information for directing future research. The Diverse Convergent Evidence approach (DiCE) we propose integrates information from multiple sources (omics, informatics, and laboratory experiments) to estimate the strength of the available corroborating evidence supporting a given association. This process is designed to yield an evidence metric that has utility when etiologic heterogeneity, variable risk factor frequencies, and a variety of observational data imperfections might lead to false conclusions. We provide proof of principle examples in which DiCE identified strong evidence for associations that have established biological importance, when standard validation methods alone did not provide support. If used as an adjunct to standard validation methods this approach can leverage multiple distinct data types to improve genetic risk factor discovery/validation, promote effective science communication, and guide future research directions

Modulation of the tumour promoting functions of cancer associated fibroblasts by phosphodiesterase type 5 inhibition increases the efficacy of chemotherapy in human preclinical models of esophageal adenocarcinoma

Background and aims: Esophageal adenocarcinoma (EAC) is chemoresistant in the majority of cases. The tumor-promoting biology of cancer associated fibroblasts (CAF) make them a target for novel therapies. Phosphodiesterase type 5 inhibitors (PDE5i) have been shown to regulate the activated fibroblast phenotype in benign disease. We investigated the potential for CAF modulation in EAC using PDE5i to enhance the efficacy of chemotherapy. Methods: EAC fibroblasts were treated with PDE5i and phenotypic effects examined using immunoblotting, immunohistochemistry, gel contraction, transwell invasion, organotypics, single cell RNAseq and shotgun proteomics. The combination of PDE5i with standard-of-care chemotherapy (Epirubicin, 5-Fluorouracil and Cisplatin) was tested for safety and efficacy in validated near-patient model systems (3D tumor growth assays (3D-TGAs) and patient derived xenograft (PDX) mouse models). Results: PDE5i treatment reduced alpha-SMA expression in CAFs by 50% (p<0.05), associated with a significant reduction in the ability of CAFs to contract collagen-1 gels and induce cancer cell invasion, (p<0.05). RNAseq and proteomic analysis of CAF and EAC cell lines revealed PDE5i specific regulation of pathways related to fibroblast activation and tumor promotion. 3D-TGA assays confirmed the importance of stromal cells to chemoresistance in EAC, which could be attenuated by PDE5i. Chemotherapy+PDE5i in PDX-bearing mice was safe and significantly reduced PDX tumor volume (p<0.05). Conclusion: PDE5 is a candidate for clinical trials to alter the fibroblast phenotype in esophageal cancer. We demonstrate the specificity of PDE5i for fibroblasts to prevent transdifferentiation and revert the CAF phenotype. Finally, we confirm the efficacy of PDE5i in combination with chemotherapy in close-to-patient in vitro and in vivo PDX-based model systems

The potential of Cittaslow for sustainable tourism development: enhancing local community’s empowerment

The slow movement has recently offered an alternative approach to sustainable tourism development, and this study aims to investigate the potential of Cittaslow philosophy and practices for enhancing local community involvement and empowerment in the tourism sector through which sustainable tourism is better implemented. Qualitative research was conducted on the case of Goolwa in South Australia, the first non-European Cittaslow. The results reveal that not only did Cittaslow accreditation and its accompanying practices encourage local community participation in decision making processes, but also revitalised the locality of Goolwa through promoting local specialities and products, in particular food and wine. A stronger and more effective collaboration among local communities, businesses and residents after the Cittaslow accreditation was noted in the context of psychological and social aspects of local community empowerment, especially for developing and managing tourism. This paper further discusses the implications of Cittaslow through which local community empowerment and sustainability in tourism can be more achievable

Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization.

The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (LQTS). Using a genome-wide association and replication study in up to 100,000 individuals, we identified 35 common variant loci associated with QT interval that collectively explain ∼8-10% of QT-interval variation and highlight the importance of calcium regulation in myocardial repolarization. Rare variant analysis of 6 new QT interval-associated loci in 298 unrelated probands with LQTS identified coding variants not found in controls but of uncertain causality and therefore requiring validation. Several newly identified loci encode proteins that physically interact with other recognized repolarization proteins. Our integration of common variant association, expression and orthogonal protein-protein interaction screens provides new insights into cardiac electrophysiology and identifies new candidate genes for ventricular arrhythmias, LQTS and SCD

Clique-Finding for Heterogeneity and Multidimensionality in Biomarker Epidemiology Research: The CHAMBER Algorithm

Commonly-occurring disease etiology may involve complex combinations of genes and exposures resulting in etiologic heterogeneity. We present a computational algorithm that employs clique-finding for heterogeneity and multidimensionality in biomedical and epidemiological research (the "CHAMBER" algorithm).This algorithm uses graph-building to (1) identify genetic variants that influence disease risk and (2) predict individuals at risk for disease based on inherited genotype. We use a set-covering algorithm to identify optimal cliques and a Boolean function that identifies etiologically heterogeneous groups of individuals. We evaluated this approach using simulated case-control genotype-disease associations involving two- and four-gene patterns. The CHAMBER algorithm correctly identified these simulated etiologies. We also used two population-based case-control studies of breast and endometrial cancer in African American and Caucasian women considering data on genotypes involved in steroid hormone metabolism. We identified novel patterns in both cancer sites that involved genes that sulfate or glucuronidate estrogens or catecholestrogens. These associations were consistent with the hypothesized biological functions of these genes. We also identified cliques representing the joint effect of multiple candidate genes in all groups, suggesting the existence of biologically plausible combinations of hormone metabolism genes in both breast and endometrial cancer in both races.The CHAMBER algorithm may have utility in exploring the multifactorial etiology and etiologic heterogeneity in complex disease