The Science of Behavior Change : The Road Ahead

Peer reviewe

Understanding symptom appraisal and help-seeking in people with symptoms suggestive of pancreatic cancer: a qualitative study

Objective: Pancreatic cancer has poor survival rates due to non-specific symptoms leading to later diagnosis. Understanding how patients interpret their symptoms could inform approaches to earlier diagnosis. This study sought to explore symptom appraisal and help-seeking among patients referred to secondary care for symptoms suggestive of pancreatic cancer. Design: Qualitative analysis of semistructured in-depth interviews. Data were analysed iteratively and thematically, informed by the Model of Pathways to Treatment. Participants and setting: Pancreatic cancer occurs rarely in younger adults, therefore patients aged ≥40 years were recruited from nine hospitals after being referred to hospital with symptoms suggestive of pancreatic cancer; all were participants in a cohort study. Interviews were conducted soon after referral, and where possible, before diagnosis. Results: Twenty-six interviews were conducted (cancer n=13 (pancreas n=9, other intra-abdominal n=4), non-cancer conditions n=13; age range 48–84 years; 14 women). Time from first symptoms to first presentation to healthcare ranged from 1 day to 270 days, median 21 days. We identified three main themes. Initial symptom appraisal usually began with intermittent, non-specific symptoms such as tiredness or appetite changes, attributed to diet and lifestyle, existing gastrointestinal conditions or side effects of medication. Responses to initial symptom appraisal included changes in meal type or frequency, or self-medication. Symptom changes such as alterations in appetite and enjoyment of food or weight loss usually prompted further appraisal. Triggers to seek help included a change or worsening of symptoms, particularly pain, which was often a ‘tipping point’. Help-seeking was often encouraged by others. We found no differences in symptom appraisal and help-seeking between people diagnosed with cancer and those with other conditions. Conclusions: Greater public and healthcare professional awareness of the combinations of subtle and intermittent symptoms, and their evolving nature, is needed to prompt timelier help-seeking and investigation among people with symptoms of pancreatic cancer

The impact of emotional well-being on long-term recovery and survival in physical illness: a meta-analysis

This meta-analysis synthesized studies on emotional well-being as predictor of the prognosis of physical illness, while in addition evaluating the impact of putative moderators, namely constructs of well-being, health-related outcome, year of publication, follow-up time and methodological quality of the included studies. The search in reference lists and electronic databases (Medline and PsycInfo) identified 17 eligible studies examining the impact of general well-being, positive affect and life satisfaction on recovery and survival in physically ill patients. Meta-analytically combining these studies revealed a Likelihood Ratio of 1.14, indicating a small but significant effect. Higher levels of emotional well-being are beneficial for recovery and survival in physically ill patients. The findings show that emotional well-being predicts long-term prognosis of physical illness. This suggests that enhancement of emotional well-being may improve the prognosis of physical illness, which should be investigated by future research

Predictive modeling for determination of microscopic residual disease at primary cytoreduction: An NRG Oncology/Gynecologic Oncology Group 182 Study

Microscopic residual disease following complete cytoreduction (R0) is associated with a significant survival benefit for patients with advanced epithelial ovarian cancer (EOC). Our objective was to develop a prediction model for R0 to support surgeons in their clinical care decisions.Demographic, pathologic, surgical, and CA125 data were collected from GOG 182 records. Patients enrolled prior to September 1, 2003 were used for the training model while those enrolled after constituted the validation data set. Univariate analysis was performed to identify significant predictors of R0 and these variables were subsequently analyzed using multivariable regression. The regression model was reduced using backward selection and predictive accuracy was quantified using area under the receiver operating characteristic area under the curve (AUC) in both the training and the validation data sets.Of the 3882 patients enrolled in GOG 182, 1480 had complete clinical data available for the analysis. The training data set consisted of 1007 patients (234 with R0) while the validation set was comprised of 473 patients (122 with R0). The reduced multivariable regression model demonstrated several variables predictive of R0 at cytoreduction: Disease Score (DS) ( < 0.001), stage ( = 0.009), CA125 ( < 0.001), ascites ( < 0.001), and stage-age interaction ( = 0.01). Applying the prediction model to the validation data resulted in an AUC of 0.73 (0.67 to 0.78, 95% CI). Inclusion of DS enhanced the model performance to an AUC of 0.83 (0.79 to 0.88, 95% CI).We developed and validated a prediction model for R0 that offers improved performance over previously reported models for prediction of residual disease. The performance of the prediction model suggests additional factors (i.e. imaging, molecular profiling, etc.) should be explored in the future for a more clinically actionable tool

Recruitment and follow-up of adolescent and young adult cancer survivors: the AYA HOPE Study

IntroductionCancer is rare in adolescents and young adults (AYA), but these patients have seen little improvement in survival in contrast to most other age groups. Furthermore, participation in research by AYAs is typically low. We conducted a study to examine the feasibility of recruiting a population-based sample of AYA survivors to examine issues of treatment and health outcomes.MethodsIndividuals diagnosed in 2007-08 and age 15-39 at the time of diagnosis with acute lymphocytic leukemia, Hodgkin lymphoma, non-Hodgkin lymphoma, germ cell cancer or sarcoma were identified by 7 Surveillance, Epidemiology, and End-Results (SEER) cancer registries, mailed surveys within 14 months after diagnosis and again a year later, and had medical records reviewed.Results525 (43%) of the eligible patients responded, 39% refused and 17% were lost to follow-up. Extensive efforts were required for most potential respondents (87%). 76% of respondents completed the paper rather than online survey version. In a multivariate model, age, cancer site, education and months from diagnosis to the first mailing of the survey were not associated with participation, although males (p  &lt;  0.01), Hispanics and non-Hispanic blacks (p  &lt;  0.001) were less likely to participate. 91% of survivors completing the initial survey completed the subsequent survey.DiscussionDespite the response rate, those who participated adequately reflected the population of AYA cancer survivors. The study demonstrates that cancer registries are valuable foundations for conducting observational, longitudinal population-based research on AYA cancer survivors.Implications for cancer survivorsAchieving a reasonable response rate in this population is possible, but requires extensive resources

Highly Volcanic Exoplanets, Lava Worlds, and Magma Ocean Worlds:An Emerging Class of Dynamic Exoplanets of Significant Scientific Priority

Highly volcanic exoplanets, which can be variously characterized as 'lava worlds', 'magma ocean worlds', or 'super-Ios' are high priority targets for investigation. The term 'lava world' may refer to any planet with extensive surface lava lakes, while the term 'magma ocean world' refers to planets with global or hemispherical magma oceans at their surface. 'Highly volcanic planets', including super-Ios, may simply have large, or large numbers of, active explosive or extrusive volcanoes of any form. They are plausibly highly diverse, with magmatic processes across a wide range of compositions, temperatures, activity rates, volcanic eruption styles, and background gravitational force magnitudes. Worlds in all these classes are likely to be the most characterizable rocky exoplanets in the near future due to observational advantages that stem from their preferential occurrence in short orbital periods and their bright day-side flux in the infrared. Transit techniques should enable a level of characterization of these worlds analogous to hot Jupiters. Understanding processes on highly volcanic worlds is critical to interpret imminent observations. The physical states of these worlds are likely to inform not just geodynamic processes, but also planet formation, and phenomena crucial to habitability. Volcanic and magmatic activity uniquely allows chemical investigation of otherwise spectroscopically inaccessible interior compositions. These worlds will be vital to assess the degree to which planetary interior element abundances compare to their stellar hosts, and may also offer pathways to study both the very young Earth, and the very early form of many silicate planets where magma oceans and surface lava lakes are expected to be more prevalent. We suggest that highly volcanic worlds may become second only to habitable worlds in terms of both scientific and public long-term interest.Comment: A white paper submitted in response to the National Academy of Sciences 2018 Exoplanet Science Strategy solicitation, from the NASA Sellers Exoplanet Environments Collaboration (SEEC) of the Goddard Space Flight Center. 6 pages, 0 figure

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

Delivering the WISE (Whole Systems Informing Self-Management Engagement) training package in primary care: learning from formative evaluation

Background: The WISE (Whole System Informing Self-management Engagement) approach encompasses creating, finding, and implementing appropriate self-care support for people with long-term conditions. A training package for primary care to introduce the approach was developed and underwent formative evaluation. This entailed exploring the acceptability of the WISE approach and its effectiveness in changing communication within consultations. The study aimed to refine the patient, practitioner, and patient level components of the WISE approach and translate the principles of WISE into an operational intervention deliverable through National Health Service training methods. Methods: Normalisation Process Theory provided a framework for development of the intervention. Practices were recruited from an inner city Primary Care Trust in NW England. All practice staff were expected to attend two afternoon training sessions. The training sessions were observed by members of the training team. Post-training audio recordings of consultations from each general practitioner and nurse in the practices were transcribed and read to provide a narrative overview of the incorporation of WISE skills and tools into consultations. Face-to-face semi-structured interviews were conducted with staff post-training. Results: Two practices out of 14 deemed eligible agreed to take part. Each practice attended two sessions, although a third session on consultation skills training was needed for one practice. Fifty-four post-training consultations were recorded from 15 clinicians. Two members of staff were interviewed at each practice. Significant elements of the training form and methods of delivery fitted contemporary practice. There were logistical problems in getting a whole practice to attend both sessions, and administrative staff founds some sections irrelevant. Clinicians reported problems incorporating some of the tools developed for WISE, and this was confirmed in the overview of consultations, with limited overt use of WISE tools and missed opportunities to address patients' self-management needs. Conclusions: The formative evaluation approach and attention to normalisation process theory allowed the training team to make adjustments to content and delivery and ensure appropriate staff attended each session. The content of the course was simplified and focussed more clearly on operationalising the WISE approach. The patient arm of the approach was strengthened by raising expectations of a change in approach to self-care support by their practice. <br/

Phenotype and immune function of lymph node and peripheral blood CLL cells are linked to transendothelial migration

everal lines of evidence suggest that homing of tumor cells to lymphoid tissue contributes to disease progression in chronic lymphocytic leukemia (CLL). Here, we demonstrate that lymph node (LN)-derived CLL cells possess a distinct phenotype, and exhibit enhanced capacity for T-cell activation and superior immune synapse formation when compared with paired peripheral blood (PB) samples. LN-derived CLL cells manifest a proliferative, CXCR4(dim)CD5(bright) phenotype compared with those in the PB and higher expression of T-cell activation molecules including CD80, CD86, and HLA-D-related (DR). In addition, LN-CLL cells have higher expression of α4β1 (CD49d) which, as well as being a co-stimulatory molecule, is required for CLL cells to undergo transendothelial migration (TEM) and enter the proliferation centers of the LNs. Using an in vitro system that models circulation and TEM, we showed that the small population of CLL cells that migrate are CXCR4(dim)CD5(bright) with higher CD49d, CD80, CD86, and HLA-DR compared with those that remain circulating; a phenotype strikingly similar to LN-derived CLL cells. Furthermore, sorted CD49d(hi) CLL cells showed an enhanced capacity to activate T cells compared with CD49d(lo) subpopulations from the same patient. Thus, although PB-CLL cells have a reduced capacity to form immune synapses and activate CD4(+) T cells, this was not the case for LN-CLL cells or those with the propensity to undergo TEM. Taken together, our study suggests that CLL cell immunologic function is not only modulated by microenvironmental interactions but is also a feature of a subpopulation of PB-CLL cells that are primed for lymphoid tissue homing and interaction with T cells

Thinking outside the channel : modeling nitrogen cycling in networked river ecosystems

Author Posting. © Ecological Society of America, 2011. This article is posted here by permission of Ecological Society of America for personal use, not for redistribution. The definitive version was published in Frontiers in Ecology and the Environment 9 (2011): 229–238, doi:10.1890/080211.Agricultural and urban development alters nitrogen and other biogeochemical cycles in rivers worldwide. Because such biogeochemical processes cannot be measured empirically across whole river networks, simulation models are critical tools for understanding river-network biogeochemistry. However, limitations inherent in current models restrict our ability to simulate biogeochemical dynamics among diverse river networks. We illustrate these limitations using a river-network model to scale up in situ measures of nitrogen cycling in eight catchments spanning various geophysical and land-use conditions. Our model results provide evidence that catchment characteristics typically excluded from models may control river-network biogeochemistry. Based on our findings, we identify important components of a revised strategy for simulating biogeochemical dynamics in river networks, including approaches to modeling terrestrial–aquatic linkages, hydrologic exchanges between the channel, floodplain/riparian complex, and subsurface waters, and interactions between coupled biogeochemical cycles.This research was supported by NSF (DEB-0111410). Additional support was provided by NSF for BJP and SMT (DEB-0614301), for WMW (OCE-9726921 and DEB-0614282), for WHM and JDP (DEB-0620919), for SKH (DEB-0423627), and by the Gordon and Betty Moore Foundation for AMH, GCP, ESB, and JAS, and by an EPA Star Fellowship for AMH