An experimental test of deviant modeling

Objectives: Test the effect of deviant peer modeling on theft as conditioned by verbal support for theft and number of deviant models. Methods: Two related randomized experiments in which participants were given a chance to steal a gift card (ostensibly worth $15) from the table in front of them. Each experiment had a control group, a verbal prompting group in which confederate(s) endorsed stealing, a behavioral modeling group in which confederate(s) committed theft, and a verbal prompting plus behavioral modeling group in which confederate(s) did both. The first experiment used one confederate; the second experiment used two. The pooled sample consisted of 335 undergraduate students. Results: Participants in the verbal prompting plus behavioral modeling group were most likely to steal followed by the behavioral modeling group. Interestingly, behavioral modeling was only influential when two confederates were present. There were no thefts in either the control or verbal prompting groups regardless of the number of confederates. Conclusions: Behavioral modeling appears to be the key mechanism, though verbal support can strengthen the effect of behavioral modeling.UW/SSHRC Seed Gran

Connecting the dots between breast cancer, obesity and alcohol consumption in middle-aged women: ecological and case control studies

This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.Abstract Background Breast cancer (BC) incidence in Australian women aged 45 to 64 years (‘middle-aged’) has tripled in the past 50 years, along with increasing alcohol consumption and obesity in middle-age women. Alcohol and obesity have been individually associated with BC but little is known about how these factors might interact. Chronic psychological stress has been associated with, but not causally linked to, BC. Here, alcohol could represent the ‘missing link’ – reflecting self-medication. Using an exploratory cross-sectional design, we investigated inter-correlations of alcohol intake and overweight/obesity and their association with BC incidence in middle-aged women. We also explored the role of stress and various lifestyle factors in these relationships. Methods We analysed population data on BC incidence, alcohol consumption, overweight/obesity, and psychological stress. A case control study was conducted using an online survey. Cases (n = 80) were diagnosed with BC and controls (n = 235) were women in the same age range with no BC history. Participants reported lifestyle data (including alcohol consumption, weight history) over consecutive 10-year life periods. Data were analysed using a range of bivariate and multivariate techniques including correlation matrices, multivariate binomial regressions and multilevel logistic regression. Results Ecological inter-correlations were found between BC and alcohol consumption and between BC and obesity but not between other variables in the matrix. Strong pairwise correlations were found between stress and alcohol and between stress and obesity. BMI tended to be higher in cases relative to controls across reported life history. Alcohol consumption was not associated with case-control status. Few correlations were found between lifestyle factors and stress, although smoking and alcohol consumption were correlated in some periods. Obesity occurring during the ages of 31 to 40 years emerged as an independent predictor of BC (OR 3.5 95% CI: 1.3–9.4). Conclusions This study provides ecological evidence correlating obesity and alcohol consumption with BC incidence. Case-control findings suggest lifetime BMI may be important with particular risk associated with obesity prior to 40 years of age. Stress was ecologically linked to alcohol and obesity but not to BC incidence and was differentially correlated with alcohol and smoking among cases and controls. Our findings support prevention efforts targeting weight in women below 40 years of age and, potentially, lifelong alcohol consumption to reduce BC risk in middle-aged women

Care Transitions From Patient and Caregiver Perspectives

PURPOSE: Despite concerted actions to streamline care transitions, the journey from hospital to home remains hazardous for patients and caregivers. Remarkably little is known about the patient and caregiver experience during care transitions, the services they need, or the outcomes they value. The aims of this study were to (1) describe patient and caregiver experiences during care transitions and (2) characterize patient and caregiver desired outcomes of care transitions and the health services associated with them. METHODS: We interviewed 138 patients and 110 family caregivers recruited from 6 health networks across the United States. We conducted 34 homogenous focus groups (103 patients, 65 caregivers) and 80 key informant interviews (35 patients, 45 caregivers). Audio recordings were transcribed and analyzed using principles of grounded theory to identify themes and the relationship between them. RESULTS: Patients and caregivers identified 3 desired outcomes of care transition services: (1) to feel cared for and cared about by medical providers, (2) to have unambiguous accountability from the health care system, and (3) to feel prepared and capable of implementing care plans. Five care transition services or provider behaviors were linked to achieving these outcomes: (1) using empathic language and gestures, (2) anticipating the patient\u27s needs to support self-care at home, (3) collaborative discharge planning, (4) providing actionable information, and (5) providing uninterrupted care with minimal handoffs. CONCLUSIONS: Clear accountability, care continuity, and caring attitudes across the care continuum are important outcomes for patients and caregivers. When these outcomes are achieved, care is perceived as excellent and trustworthy. Otherwise, the care transition is experienced as transactional and unsafe, and leaves patients and caregivers feeling abandoned by the health care system

Lung Megakaryocytes are Immune Modulatory Cells that Present Antigen to CD4+ T cells.

Although platelets are the cellular mediators of thrombosis, they are also immune cells. Platelets interact both directly and indirectly with immune cells, impacting their activation and differentiation, as well as all phases of the immune response. Megakaryocytes (Mks) are the cell source of circulating platelets, and until recently Mks were typically only considered bone marrow–resident (BM-resident) cells. However, platelet-producing Mks also reside in the lung, and lung Mks express greater levels of immune molecules compared with BM Mks. We therefore sought to define the immune functions of lung Mks. Using single-cell RNA sequencing of BM and lung myeloid-enriched cells, we found that lung Mks, which we term MkL, had gene expression patterns that are similar to antigen-presenting cells. This was confirmed using imaging and conventional flow cytometry. The immune phenotype of Mks was plastic and driven by the tissue immune environment, as evidenced by BM Mks having an MkL-like phenotype under the influence of pathogen receptor challenge and lung-associated immune molecules, such as IL-33. Our in vitro and in vivo assays demonstrated that MkL internalized and processed both antigenic proteins and bacterial pathogens. Furthermore, MkL induced CD4+ T cell activation in an MHC II–dependent manner both in vitro and in vivo. These data indicated that MkL had key immune regulatory roles dictated in part by the tissue environment.pre-print236 K

Activation-Induced Apoptosis of Autoreactive and Alloreactive T Lymphocytes in the Target Organ as a Major Mechanism of Tolerance

Normal individuals have mature T lymphocytes that are capable of reacting to self-antigens and can be activated by cross-reacting environmental antigens. The mechanism that maintains immune tolerance and prevents these activated autoreactive T cells from causing autoimmune disease is unclear. We have previously hypothesized that activation-induced apoptosis of previously activated autoreactive T cells in the target organ is a major mechanism for maintaining tolerance. Here I review the current evidence to support this hypothesis. It is proposed that when activated autoreactive T cells enter the target organ, they are reactivated mainly by non-professional antigen-presenting cells (APC) and deleted by activation-induced apoptosis through the Fas (CD95) pathway before producing significant target organ damage. This apoptosis occurs because the reactivated T cells do not receive sufficient costimulation from the non-professional APC to up-regulate their expression of Bcl-2-related anti-apoptotic proteins, which inhibit the CD95 pro-apoptotic pathway. This is in contrast to the situation in peripheral lymphoid organs, where reactivation of T cells by professional APC results in sufficient costimulation-induced up-regulation of Bcl-2-related proteins to inhibit the CD95 pathway and allow T cell proliferation and survival as memory T cells. Activation-induced apoptosis of alloreactive T cells in allografts can similarly account for spontaneous allograft acceptance, as occurs after MHC-mismatched liver transplantation

Body circumferences: clinical implications emerging from a new geometric model

<p>Abstract</p> <p>Background</p> <p>Body volume expands with the positive energy balance associated with the development of adult human obesity and this "growth" is captured by two widely used clinical metrics, waist circumference and body mass index (BMI). Empirical correlations between circumferences, BMI, and related body compartments are frequently reported but fail to provide an important common conceptual foundation that can be related to key clinical observations. A two-phase program was designed to fill this important gap: a geometric model linking body volume with circumferences and BMI was developed and validated in cross-sectional cohorts; and the model was applied to the evaluation of longitudinally monitored subjects during periods of voluntary weight loss. Concepts emerging from the developed model were then used to examine the relations between the evaluated clinical measures and body composition.</p> <p>Methods</p> <p>Two groups of healthy adults (n = 494 and 1499) were included in the cross-sectional model development/testing phase and subjects in two previous weight loss studies were included in the longitudinal model evaluation phase. Five circumferences (arm, waist, hip, thigh, and calf; average of sum, C), height (H), BMI, body volume (V; underwater weighing), and the volumes of major body compartments (whole-body magnetic resonance imaging) were measured.</p> <p>Results</p> <p>The evaluation of a humanoid geometric model based a cylinder confirmed that V derived from C and H was highly correlated with measured V [R²both males and females, 0.97; p < 0.001). Developed allometric models confirmed model predictions that C and BMI (represented as V/H) are directly linked as, C = (V/H)^0.5. The scaling of individual circumferences to V/H varied, with waist the highest (V/H^~0.6) and calf the lowest (V/H^~0.3), indicating that the largest and smallest between-subject "growth" with greater body volume occurs in the abdominal area and lower extremities, respectively. A stepwise linear regression model including all five circumferences²showed that each contributed independently to V/H. These cross-sectional observations were generally confirmed by analysis of the two longitudinal weight loss studies. The scaling of circumference ratios (e.g., waist/hip) to V/H conformed to models developed on the scaling of individual circumferences to V/H, indicating their relations to BMI are predictable <it>a priori</it>. Waist, hip, and arm/calf circumferences had the highest associations with whole-body visceral adipose tissue, subcutaneous adipose tissue, and skeletal muscle volumes, respectively.</p> <p>Conclusion</p> <p>These observations provide a simple geometric model relating circumferences with body size and composition, introduce a conceptual foundation explaining previous empirical observations, and reveal new clinical insights.</p

Metabolic and Behavioral Compensations in Response to Caloric Restriction: Implications for the Maintenance of Weight Loss

BackgroundMetabolic and behavioral adaptations to caloric restriction (CR) in free-living conditions have not yet been objectively measured.Methodology and principal findingsForty-eight (36.8+/-1.0 y), overweight (BMI 27.8+/-0.7 kg/m(2)) participants were randomized to four groups for 6-months;Controlenergy intake at 100% of energy requirements; CR: 25% calorie restriction; CR+EX: 12.5% CR plus 12.5% increase in energy expenditure by structured exercise; LCD: low calorie diet (890 kcal/d) until 15% weight reduction followed by weight maintenance. Body composition (DXA) and total daily energy expenditure (TDEE) over 14-days by doubly labeled water (DLW) and activity related energy activity (AREE) were measured after 3 (M3) and 6 (M6) months of intervention. Weight changes at M6 were -1.0+/-1.1% (CONTROL), -10.4+/-0.9% (CR), -10.0+/-0.8% (CR+EX) and -13.9+/-0.8% (LCD). At M3, absolute TDEE was significantly reduced in CR (-454+/-76 kcal/d) and LCD (-633+/-66 kcal/d) but not in CR+EX or controls. At M6 the reduction in TDEE remained lower than baseline in CR (-316+/-118 kcal/d) and LCD (-389+/-124 kcal/d) but reached significance only when CR and LCD were combined (-351+/-83 kcal/d). In response to caloric restriction (CR/LCD combined), TDEE adjusted for body composition, was significantly lower by -431+/-51 and -240+/-83 kcal/d at M3 and M6, respectively, indicating a metabolic adaptation. Likewise, physical activity (TDEE adjusted for sleeping metabolic rate) was significantly reduced from baseline at both time points. For control and CR+EX, adjusted TDEE (body composition or sleeping metabolic rate) was not changed at either M3 or M6.ConclusionsFor the first time we show that in free-living conditions, CR results in a metabolic adaptation and a behavioral adaptation with decreased physical activity levels. These data also suggest potential mechanisms by which CR causes large inter-individual variability in the rates of weight loss and how exercise may influence weight loss and weight loss maintenance.Trial registrationClinicalTrials.gov NCT00099151.Leanne M. Redman, Leonie K. Heilbronn, Corby K. Martin, Lilian de Jonge, Donald A. Williamson, James P. Delany, Eric Ravussin, for the Pennington CALERIE tea

Health-related Quality of Life Analysis from KEYNOTE-426: Pembrolizumab plus Axitinib Versus Sunitinib for Advanced Renal Cell Carcinoma

The first interim analysis of the KEYNOTE-426 study showed superior efficacy of pembrolizumab plus axitinib over sunitinib monotherapy in treatment-naive, advanced renal cell carcinoma. The exploratory analysis with extended follow-up reported here aims to assess long-term efficacy and safety of pembrolizumab plus axitinib versus sunitinib monotherapy in patients with advanced renal cell carcinoma

Measurement of the cosmic ray spectrum above 4×10184{\times}10^{18} eV using inclined events detected with the Pierre Auger Observatory

A measurement of the cosmic-ray spectrum for energies exceeding $4{\times}10^{18}$ eV is presented, which is based on the analysis of showers with zenith angles greater than $60^{\circ}$ detected with the Pierre Auger Observatory between 1 January 2004 and 31 December 2013. The measured spectrum confirms a flux suppression at the highest energies. Above $5.3{\times}10^{18}$ eV, the "ankle", the flux can be described by a power law $E^{-\gamma}$ with index $\gamma=2.70 \pm 0.02 \,\text{(stat)} \pm 0.1\,\text{(sys)}$ followed by a smooth suppression region. For the energy ($E_\text{s}$) at which the spectral flux has fallen to one-half of its extrapolated value in the absence of suppression, we find $E_\text{s}=(5.12\pm0.25\,\text{(stat)}^{+1.0}_{-1.2}\,\text{(sys)}){\times}10^{19}$ eV.Comment: Replaced with published version. Added journal reference and DO