Loyalty Program Effectiveness: An Examination of Mainstream and Niche Sport Fan-Team Relationships

The purpose of this study was to explore the efficacy of using loyalty programs on sport fans’ relationship quality and fan engagement toward sport organizations. This study also sought to explore which relationship quality and fan engagement factors potentially differed as a result of using loyalty programs. Since there are two major defined sport levels, differences were explored across niche and mainstream sport organizations. Using relationship marketing as the theoretical framework, participants (n = 678) were administered a 55-item instrument that included revised relationship quality and fan engagement scales. Quantitative data were used to run confirmatory factor analyses, analyses of covariance, and multivariate analyses of covariance. Results first showed that significant differences existed between mainstream sport fans that have access to a loyalty program and mainstream sport fans that do not have access to a loyalty program. Mainstream sport fans that have access to a loyalty program had higher identification and reciprocity. Mainstream sport fans that do not have access to a loyalty program were found to have higher overall fan engagement, commitment, intimacy, and performance tolerance. Results also showed differences between niche sport fans that have access to a loyalty program and mainstream sport fans that have access to a loyalty program. Mainstream sport fans that have access to a loyalty program were divided into two groups (simple or complex) based on the design of the loyalty programs. Niche sport fans that have access to a loyalty program were found to have higher overall relationship quality, trust, intimacy, management cooperation, and performance tolerance. The findings provide an introduction in to the possibility that loyalty programs could be effective for increasing relationship quality for both niche and mainstream sport organizations. Moreover, for niche sport organizations that have access to fewer resources, it is encouraging that the use of a loyalty program appears to have the capabilities to build stronger relationships and engagement. These results provide several implications for sport organizations and sport marketers and serve as a foundation for which future research on loyalty programs can build

Dissociation and symptom dimensions of obsessive-compulsive disorder: A replication study

Background: Obsessive-compulsive disorder (OCD) is a phenotypically very heterogeneous disease with high rates of comorbid psychiatric pathology. Previous studies have indicated that OCD is associated with higher levels of dissociation. The aims of the present study were to replicate and extend previous findings of a significant link between certain OCD symptom dimensions and dissociation. Methods: The study sample comprised 50 patients with OCD, as confirmed by the Mini International Neuropsychiatric Interview,who had a score of at least 16 on the Yale-Brown Obsessive-Compulsive Scale. All patients were assessed with the short version of the Hamburg Obsessive-Compulsive Inventory and the Dissociative Experience Scale (DES). Correlation analyses and multiple regression analyses were performed to evaluate the relationship between OCD symptom dimensions and dissociation. Results: The checking dimension was most strongly related to dissociation, followed by the symmetry/ordering and obsessive thoughts dimensions. In contrast, no significant relationship was found between dissociation and the washing/cleaning, counting/touching, and aggressive impulses/fantasies dimensions. Multiple regression analyses revealed that: (1) only the checking dimension showed an independent positive correlation with dissociation, and (2) only higher scores on the DES subscale "amnestic dissociation" were associated with higher scores for checking compulsions. Conclusions: Our results suggest that there might be a specific link between checking behavior and dissociation in OCD. Moreover, checking compulsions seem to be particularly associated with amnestic dissociation. Further studies focusing on amnestic dissociation as a potentially important determinant of checking compulsions are warrante

Pharmacological Analysis of Dopamine Modulation in the \u3cem\u3eDrosophila melanogaster\u3c/em\u3e Larval Heart

Dopamine (DA) and other neurotransmitters affect nonneuronal tissues in insects by circulating in the hemolymph. In several organisms, DA has been shown to modulate distinct aspects of cardiac function but the signal transduction pathways that mediate dopaminergic effects on the heart are not well characterized. Here, we used a semiintact Drosophila melanogaster larva preparation and drugs targeting DA receptors and canonical second messenger pathways to identify signaling cascades that mediate the effect of DA on a myogenic heart. DA has a positive chronotropic effect that is mimicked by SKF38393 (type‐1 DA receptor agonist) and quinpirole (type‐2 DA receptor agonist). SCH23390 and spiperone (type‐1 and type‐2 DA receptor antagonists) are moderately effective at inhibiting DA\u27s effect. An adenylate cyclase inhibitor (SQ,22536) is also effective at blocking the stimulatory effect of DA but the drug has its own dose‐dependent effect. Activation of protein kinase C with a diacylglycerol analog has a stimulatory effect on heart rate (HR). These results suggest that (1) both DA receptor subtypes are expressed in third instar larva cardiac myocytes to increase HR in response to rising levels of DA in the hemolymph, and (2) canonical second messenger pathways modulate HR in D. melanogaster larvae. Having these disparate signaling cascades converge toward a common modulatory function appears redundant, but in the context of multiple cardioactive chemicals this redundancy is likely to increase the fidelity of signal transduction

Simultaneous coexpression of memory-related and effector-related genes by individual human CD8 T cells depends on antigen specificity and differentiation.

Phenotypic and functional cell properties are usually analyzed at the level of defined cell populations but not single cells. Yet, large differences between individual cells may have important functional consequences. It is likely that T-cell-mediated immunity depends on the polyfunctionality of individual T cells, rather than the sum of functions of responding T-cell subpopulations. We performed highly sensitive single-cell gene expression profiling, allowing the direct ex vivo characterization of individual virus-specific and tumor-specific T cells from healthy donors and melanoma patients. We have previously shown that vaccination with the natural tumor peptide Melan-A-induced T cells with superior effector functions as compared with vaccination with the analog peptide optimized for enhanced HLA-A*0201 binding. Here we found that natural peptide vaccination induced tumor-reactive CD8 T cells with frequent coexpression of both memory/homing-associated genes (CD27, IL7R, EOMES, CXCR3, and CCR5) and effector-related genes (IFNG, KLRD1, PRF1, and GZMB), comparable with protective Epstein-Barr virus-specific and cytomegalovirus-specific T cells. In contrast, memory/homing-associated and effector-associated genes were less frequently coexpressed after vaccination with the analog peptide. Remarkably, these findings reveal a previously unknown level of gene expression diversity among vaccine-specific and virus-specific T cells with the simultaneous coexpression of multiple memory/homing-related and effector-related genes by the same cell. Such broad functional gene expression signatures within antigen-specific T cells may be critical for mounting efficient responses to pathogens or tumors. In summary, direct ex vivo high-resolution molecular characterization of individual T cells provides key insights into the processes shaping the functional properties of tumor-specific and virus-specific T cells

Long-term course and outcome of obsessive-compulsive patientsafter cognitive-behavioral therapy in combination with eitherfluvoxamine or placebo: A 7-year follow-up of a randomized double-blind trial

Longitudinal studies with very long follow-up periods of patients with obsessive-compulsive disorder (OCD) who have received adequate treatment are rare. In the current study, 30 of 37 inpatients (81%) with severe OCD were followed up 6-8 years after treatment with cognitive-behavioral therapy (CBT) in combination with either fluvoxamine or placebo in a randomized design. The significant improvements (with large effectsizes) in obsessive-compulsive symptoms from pre- to post-treatment (41% reduction on the Y-BOCS) remained stable at follow-up (45 %). Responder rates, defined as ≥35% reduction on the Y-BOCS, were 67% and 60%, respectively. Depressive symptoms decreased significantly not only from pre- to post-treatment but also during follow-up. Re-hospitalization, which occurred in 11 patients (37 %), was associated with more severe depressive symptoms at pre-treatment and living without a partner. Full symptom remission at follow-up, defined as both Y-BOCS total score ≤ 7 and no longer meeting diagnostic criteria for OCD, was achieved by 8 patients (27 %). Patients without full remission at follow-up had a significantly longer history of OCD, assessed at pretreatment, compared to remitted patients. The shortterm treatment outcome had no predictive value for the long-term course. Throughout the naturalistic follow-up, nearly all patients (29 patients) received additional psychotherapy and/or medication. This might indicate that such chronic OCD patients usually need additional therapeutic support after effective inpatient treatment to maintain their improvements over long period

Single cell analysis reveals similar functional competence of dominant and nondominant CD8 T-cell clonotypes.

Immune protection from infectious diseases and cancer is mediated by individual T cells of different clonal origin. Their functions are tightly regulated but not yet fully characterized. Understanding the contribution of each T cell will improve the prediction of immune protection based on laboratory assessment of T-cell responses. Here we developed techniques for simultaneous molecular and functional assessment of single CD8 T cells directly ex vivo. We studied two groups of patients with melanoma after vaccination with two closely related tumor antigenic peptides. Vaccination induced T cells with strong memory and effector functions, as found in virtually all T cells of the first patient group, and fractions of T cells in the second group. Interestingly, high functionality was not restricted to dominant clonotypes. Rather, dominant and nondominant clonotypes acquired equal functional competence. In parallel, this was also found for EBV- and CMV-specific T cells. Thus, the nondominant clonotypes may contribute similarly to immunity as their dominant counterparts

Adequacy of Maternal Iron Status Protects against Behavioral, Neuroanatomical, and Growth Deficits in Fetal Alcohol Spectrum Disorders

Fetal alcohol spectrum disorders (FASD) are the leading non-genetic cause of neurodevelopmental disability in children. Although alcohol is clearly teratogenic, environmental factors such as gravidity and socioeconomic status significantly modify individual FASD risk despite equivalent alcohol intake. An explanation for this variability could inform FASD prevention. Here we show that the most common nutritional deficiency of pregnancy, iron deficiency without anemia (ID), is a potent and synergistic modifier of FASD risk. Using an established rat model of third trimester-equivalent binge drinking, we show that ID significantly interacts with alcohol to impair postnatal somatic growth, associative learning, and white matter formation, as compared with either insult separately. For the associative learning and myelination deficits, the ID-alcohol interaction was synergistic and the deficits persisted even after the offsprings’ iron status had normalized. Importantly, the observed deficits in the ID-alcohol animals comprise key diagnostic criteria of FASD. Other neurobehaviors were normal, showing the ID-alcohol interaction was selective and did not reflect a generalized malnutrition. Importantly ID worsened FASD outcome even though the mothers lacked overt anemia; thus diagnostics that emphasize hematological markers will not identify pregnancies at-risk. This is the first direct demonstration that, as suggested by clinical studies, maternal iron status has a unique influence upon FASD outcome. While alcohol is unquestionably teratogenic, this ID-alcohol interaction likely represents a significant portion of FASD diagnoses because ID is more common in alcohol-abusing pregnancies than generally appreciated. Iron status may also underlie the associations between FASD and parity or socioeconomic status. We propose that increased attention to normalizing maternal iron status will substantially improve FASD outcome, even if maternal alcohol abuse continues. These findings offer novel insights into how alcohol damages the developing brain

Rapid and Continued T-Cell Differentiation into Long-term Effector and Memory Stem Cells in Vaccinated Melanoma Patients.

<b>Purpose:</b> Patients with cancer benefit increasingly from T-cell-based therapies, such as adoptive T-cell transfer, checkpoint blockade, or vaccination. We have previously shown that serial vaccinations with Melan-A <sup>MART-1</sup> <sub>26-35</sub> peptide, CpG-B, and incomplete Freund adjuvant (IFA) generated robust tumor-specific CD8 T-cell responses in patients with melanoma. Here, we describe the detailed kinetics of early- and long-term establishment of T-cell frequency, differentiation (into memory and effector cells), polyfunctionality, and clonotype repertoire induced by vaccination. <b>Experimental Design:</b> Twenty-nine patients with melanoma were treated with multiple monthly subcutaneous vaccinations consisting of CpG-B, and either the native/EAA ( <i>n</i> = 13) or the analogue/ELA ( <i>n</i> = 16) Melan-A <sup>MART-1</sup> <sub>26-35</sub> peptide emulsified in IFA. Phenotypes and functionality of circulating Melan-A-specific CD8 T cells were assessed directly <i>ex vivo</i> by multiparameter flow cytometry, and TCR clonotypes were determined <i>ex vivo</i> by mRNA transcript analyses of individually sorted cells. <b>Results:</b> Our results highlight the determining impact of the initial vaccine injections on the rapid and strong induction of differentiated effector T cells in both patient cohorts. Moreover, long-term polyfunctional effector T-cell responses were associated with expansion of stem cell-like memory T cells over time along vaccination. Dominant TCR clonotypes emerged early and persisted throughout the entire period of observation. Interestingly, one highly dominant clonotype was found shared between memory and effector subsets. <b>Conclusions:</b> Peptide/CpG-B/IFA vaccination induced powerful long-term T-cell responses with robust effector cells and stem cell-like memory cells. These results support the further development of CpG-B-based cancer vaccines, either alone or as specific component of combination therapies. <i>Clin Cancer Res; 23(13); 3285-96. ©2016 AACR</i>

Long-lasting stem cell-like memory CD8+ T cells with a naïve-like profile upon yellow fever vaccination.

Efficient and persisting immune memory is essential for long-term protection from infectious and malignant diseases. The yellow fever (YF) vaccine is a live attenuated virus that mediates lifelong protection, with recent studies showing that the CD8(+) T cell response is particularly robust. Yet, limited data exist regarding the long-term CD8(+) T cell response, with no studies beyond 5 years after vaccination. We investigated 41 vaccinees, spanning 0.27 to 35 years after vaccination. YF-specific CD8(+) T cells were readily detected in almost all donors (38 of 41), with frequencies decreasing with time. As previously described, effector cells dominated the response early after vaccination. We detected a population of naïve-like YF-specific CD8(+) T cells that was stably maintained for more than 25 years and was capable of self-renewal ex vivo. In-depth analyses of markers and genome-wide mRNA profiling showed that naïve-like YF-specific CD8(+) T cells in vaccinees (i) were distinct from genuine naïve cells in unvaccinated donors, (ii) resembled the recently described stem cell-like memory subset (Tscm), and (iii) among all differentiated subsets, had profiles closest to naïve cells. Our findings reveal that CD8(+) Tscm are efficiently induced by a vaccine in humans, persist for decades, and preserve a naïveness-like profile. These data support YF vaccination as an optimal mechanistic model for the study of long-lasting memory CD8(+) T cells in humans