ASU Scholarship Showcase

Background: Cancer diagnosis in both dogs and humans is complicated by the lack of a non-invasive diagnostic test. To meet this clinical need, we apply the recently developed immunosignature assay to spontaneous canine lymphoma as clinical proof-of-concept. Here we evaluate the immunosignature as a diagnostic for spontaneous canine lymphoma at both at initial diagnosis and evaluating the disease free interval following treatment.

Methods: Sera from dogs with confirmed lymphoma (B cell n = 38, T cell n = 11) and clinically normal dogs (n = 39) were analyzed. Serum antibody responses were characterized by analyzing the binding pattern, or immunosignature, of serum antibodies on a non-natural sequence peptide microarray. Peptides were selected and tested for the ability to distinguish healthy dogs from those with lymphoma and to distinguish lymphoma subtypes based on immunophenotype. The immunosignature of dogs with lymphoma were evaluated for individual signatures. Changes in the immunosignatures were evaluated following treatment and eventual relapse.

Results: Despite being a clonal disease, both an individual immunosignature and a generalized lymphoma immunosignature were observed in each dog. The general lymphoma immunosignature identified in the initial set of dogs (n = 32) was able to predict disease status in an independent set of dogs (n = 42, 97% accuracy). A separate immunosignature was able to distinguish the lymphoma based on immunophenotype (n = 25, 88% accuracy). The individual immunosignature was capable of confirming remission three months following diagnosis. Immunosignature at diagnosis was able to predict which dogs with B cell lymphoma would relapse in less than 120 days (n = 33, 97% accuracy).

Conclusion: We conclude that the immunosignature can serve as a multilevel diagnostic for canine, and potentially human, lymphoma.

Over the past couple of decades, quality has been an area of increased focus. Multiple models and approaches have been proposed to measure the quality in the construction industry. This paper focuses on determining the quality of one of the types of roofing systems used in the construction industry, i.e., sprayed polyurethane foam roofs (SPF roofs). Thirty-seven urethane-coated SPF roofs that were installed in 2005/2006 were visually inspected to measure the percentage of blisters and repairs three times over a period of four years, six years, and seven years. A repairing criteria was established after a six-year mark based on the data that were reported to contractors as vulnerable roofs. Furthermore, the relation between four possible contributing time-of-installation factors—contractor, demographics, season, and difficulty (number of penetrations and size of the roof in square feet) that could affect the quality of the roof was determined. Demographics and difficulty did not affect the quality of the roofs, whereas the contractor and the season when the roof was installed did affect the quality of the roofs.

Antigen-antibody complexes are central players in an effective immune response. However, finding those interactions relevant to a particular disease state can be arduous. Nonetheless many paths to discovery have been explored since deciphering these interactions can greatly facilitate the development of new diagnostics, therapeutics, and vaccines. In silico B cell epitope mapping approaches have been widely pursued, though success has not been consistent. Antibody mixtures in immune sera have been used as handles for biologically relevant antigens, but these and other experimental approaches have proven resource intensive and time consuming. In addition, these methods are often tailored to individual diseases or a specific proteome, rather than providing a universal platform. Most of these methods are not able to identify the specific antibody’s epitopes from unknown antigens, such as un-annotated neo antigens in cancer. Alternatively, a peptide library comprised of sequences unrestricted by naturally-found protein space provides for a universal search for mimotopes of an antibody’s epitope. Here we present the utility of such a non-natural random sequence library of 10,000 peptides physically addressed on a microarray for mimotope discovery without sequence information of the specific antigen. The peptide arrays were probed with serum from an antigen-immunized rabbit, or alternatively probed with serum pre-absorbed with the same immunizing antigen. With this positive and negative screening scheme, we identified the library-peptides as the mimotopes of the antigen. The unique library peptides were successfully used to isolate antigen-specific antibodies from complete immune serum. Sequence analysis of these peptides revealed the epitopes in the immunized antigen. We present this method as an inexpensive, efficient method for identifying mimotopes of any antibody’s targets. These mimotopes should be useful in defining both components of the antigen-antibody complex.

Background: Interaction in the form of cooperation, communication, and friendly competition theoretically precede the development of group cohesion, which often precedes adherence to health promotion programs. The purpose of this manuscript was to explore longitudinal relationships among dimensions of group cohesion and group-interaction variables to inform and improve group-based strategies within programs aimed at promoting physical activity.

Methods: Ethnic minority women completed a group dynamics-based physical activity promotion intervention (N = 103; 73% African American; 27% Hispanic/Latina; mage = 47.89 + 8.17 years; mBMI = 34.43+ 8.07 kg/m[superscript 2]) and assessments of group cohesion and group-interaction variables at baseline, 6 months (post-program), and 12 months (follow-up).

Results: All four dimensions of group cohesion had significant (ps < 0.01) relationships with the group-interaction variables. Competition was a consistently strong predictor of cohesion, while cooperation did not demonstrate consistent patterns of prediction.

Conclusions: Facilitating a sense of friendly competition may increase engagement in physical activity programs by bolstering group cohesion.

Background: Latino preschoolers (3-5 year old children) have among the highest rates of obesity. Low levels of physical activity (PA) are a risk factor for obesity. Characterizing what Latino parents do to encourage or discourage their preschooler to be physically active can help inform interventions to increase their PA. The objective was therefore to develop and assess the psychometrics of a new instrument: the Preschooler Physical Activity Parenting Practices (PPAPP) among a Latino sample, to assess parenting practices used to encourage or discourage PA among preschool-aged children.

Methods: Cross-sectional study of 240 Latino parents who reported the frequency of using PA parenting practices. 95% of respondents were mothers; 42% had more than a high school education. Child mean age was 4.5 (±0.9) years (52% male). Test-retest reliability was assessed in 20%, 2 weeks later. We assessed the fit of a priori models using Confirmatory factor analyses (CFA). In a separate sub-sample (35%), preschool-aged children wore accelerometers to assess associations with their PA and PPAPP subscales.

Results: The a-priori models showed poor fit to the data. A modified factor structure for encouraging PPAPP had one multiple-item scale: engagement (15 items), and two single-items (have outdoor toys; not enroll in sport-reverse coded). The final factor structure for discouraging PPAPP had 4 subscales: promote inactive transport (3 items), promote screen time (3 items), psychological control (4 items) and restricting for safety (4 items). Test-retest reliability (ICC) for the two scales ranged from 0.56-0.85. Cronbach’s alphas ranged from 0.5-0.9. Several sub-factors correlated in the expected direction with children’s objectively measured PA.

Conclusion: The final models for encouraging and discouraging PPAPP had moderate to good fit, with moderate to excellent test-retest reliabilities. The PPAPP should be further evaluated to better assess its associations with children’s PA and offers a new tool for measuring PPAPP among Latino families with preschool-aged children.

Background: To combat the disproportionately higher risk of childhood obesity in Latino preschool-aged children, multilevel interventions targeting physical (in) activity are needed. These require the identification of environmental and psychosocial determinants of physical (in) activity for this ethnic group. The objectives were to examine differences in objectively-measured physical activity and sedentary behavior across objectively-determined types of locations in Latino preschool-aged children; and determine whether the differences in physical activity by location were greater in children of parents with higher neighborhood-safety perceptions and physical activity-supportive parenting practices.

Methods: An observational field study was conducted in Houston (Texas, USA) from August 2011 to April 2012. A purposive sample of Latino children aged 3–5 years and one of their parents (n = 84) were recruited from Census block groups in Houston (Texas) stratified by objectively-assessed high vs. low traffic and crime safety. Seventy-three children provided valid data. Time spent outdoors/indoors tagged with geographic locations was coded into location types based on objective data collected using Global Positioning Systems units that children wore >8 hr/day for a week. Physical activity parenting practices, perceived neighborhood-safety, and demographics were reported by parents. Time spent in sedentary behavior and moderate-to-vigorous physical activity was measured based on objective data collected using accelerometers (motion sensors) that children wore >8 hr/day for a week.

Results: The odds of children engaging in moderate-to-vigorous physical activity were 43 % higher when outdoors than indoors (95 % confidence interval: 1.30, 1.58), and the odds of being sedentary were 14 % lower when outdoors compared to indoors (95 % confidence intervals: 0.81, 0.91). This difference depended on parental neighborhood-safety perceptions and parenting practices. Children were most active in parks/playgrounds (30 % of the time spent in moderate-to-vigorous physical activity) and least active in childcare/school settings (8 % of the time spent in moderate-to-vigorous physical activity).

Conclusions: Objectively-assessed time spent in specific locations is correlated with physical activity and sedentary behavior in Latino preschoolers. Interventions and policies should identify ways to engage Latino preschool-aged children in more physical activity and less sedentary behavior while in childcare, and encourage parents to spend more time with their young children in parks/playgrounds and other safe outdoor places.

The purpose of this review was to determine the degree to which physical activity interventions for Latin American populations reported on internal and external validity factors using the RE-AIM framework (reach & representativeness, effectiveness, adoption, implementation, maintenance). We systematically identified English (PubMed; EbscoHost) and Spanish (SCIELO; Biblioteca Virtual en Salud) language studies published between 2001 and 2012 that tested physical activity, exercise, or fitness promotion interventions in Latin American populations. Cross-sectional/descriptive studies, conducted in Brazil or Spain, published in Portuguese, not including a physical activity/fitness/exercise outcome, and with one time point assessment were excluded. We reviewed 192 abstracts and identified 46 studies that met the eligibility criteria (34 in English, 12 in Spanish). A validated 21-item RE-AIM abstraction tool was used to determine the quality of reporting across studies (0-7 = low, 8-14 = moderate, and 15-21 = high). The number of indicators reported ranged from 3–14 (mean = 8.1 ± 2.6), with the majority of studies falling in the moderate quality reporting category. English and Spanish language articles did not differ on the number of indicators reported (8.1 vs. 8.3, respectively). However, Spanish articles reported more across reach indicators (62% vs. 43% of indicators), while English articles reported more across effectiveness indicators (69% vs 62%). Across RE-AIM dimensions, indicators for reach (48%), efficacy/effectiveness (67%), and implementation (41%) were reported more often than indicators of adoption (25%) and maintenance (10%). Few studies reported on the representativeness of participants, staff that delivered interventions, or the settings where interventions were adopted. Only 13% of the studies reported on quality of life and/or potential negative outcomes, 20% reported on intervention fidelity, and 11% on cost of implementation. Outcomes measured after six months of intervention, information on continued delivery and institutionalization of interventions, were also seldom reported. Regardless of language of publication, physical activity intervention research for Latin Americans should increase attention to and measurement of external validity and cost factors that are critical in the decision making process in practice settings and can increase the likelihood of translation into community or clinical practice.

Background: The success of new sequencing technologies and informatic methods for identifying genes has made establishing gene product function a critical rate limiting step in progressing the molecular sciences. We present a method to functionally mine genomes for useful activities in vivo, using an unusual property of a member of the poxvirus family to demonstrate this screening approach.

Results: The genome of Parapoxvirus ovis (Orf virus) was sequenced, annotated, and then used to PCR-amplify its open-reading-frames. Employing a cloning-independent protocol, a viral expression-library was rapidly built and arrayed into sub-library pools. These were directly delivered into mice as expressible cassettes and assayed for an immune-modulating activity associated with parapoxvirus infection. The product of the B2L gene, a homolog of vaccinia F13L, was identified as the factor eliciting immune cell accumulation at sites of skin inoculation. Administration of purified B2 protein also elicited immune cell accumulation activity, and additionally was found to serve as an adjuvant for antigen-specific responses. Co-delivery of the B2L gene with an influenza gene-vaccine significantly improved protection in mice. Furthermore, delivery of the B2L expression construct, without antigen, non-specifically reduced tumor growth in murine models of cancer.

Conclusion: A streamlined, functional approach to genome-wide screening of a biological activity in vivo is presented. Its application to screening in mice for an immune activity elicited by the pathogen genome of Parapoxvirus ovis yielded a novel immunomodulator. In this inverted discovery method, it was possible to identify the adjuvant responsible for a function of interest prior to a mechanistic study of the adjuvant. The non-specific immune activity of this modulator, B2, is similar to that associated with administration of inactivated particles to a host or to a live viral infection. Administration of B2 may provide the opportunity to significantly impact host immunity while being itself only weakly recognized. The functional genomics method used to pinpoint B2 within an ORFeome may be more broadly applicable to screening for other biological activities in an animal.

Background: Physical activity (PA) public health programming has been widely used in Mexico; however, few studies have documented individual and organizational factors that might be used to evaluate their public health impact. The RE-AIM framework is an evaluation tool that examines individual and organizational factors of public health programs. The purpose of this study was to use the RE-AIM framework to determine the degree to which PA programs in Mexico reported individual and organizational factors and to investigate whether reporting differed by the program’s funding source.

Methods: Public health programs promoting PA were systematically identified during 2008–2013 and had to have an active program website. Initial searches produced 23 possible programs with 12 meeting inclusion criteria. A coding sheet was developed to capture behavioral, outcome and RE-AIM indicators from program websites.

Results: In addition to targeting PA, five (42%) programs also targeted dietary habits and the most commonly reported outcome was change in body composition (58%). Programs reported an average of 11.1 (±3.9) RE-AIM indicator items (out of 27 total). On average, 45% reported reach indicators, 34% reported efficacy/effectiveness indicators, 60% reported adoption indicators, 40% reported implementation indicators, and 35% reported maintenance indicators. The proportion of RE-AIM indicators reported did not differ significantly for programs that were government supported (M = 10, SD = 3.1) and programs that were partially or wholly privately or corporately supported (M = 12.0, SD = 4.4).

Conclusion: While reach and adoption of these programs were most commonly reported, there is a need for stronger evaluation of behavioral and health outcomes before the public health impact of these programs can be established.

Background: Immunosignaturing is a new peptide microarray based technology for profiling of humoral immune responses. Despite new challenges, immunosignaturing gives us the opportunity to explore new and fundamentally different research questions. In addition to classifying samples based on disease status, the complex patterns and latent factors underlying immunosignatures, which we attempt to model, may have a diverse range of applications.

Methods: We investigate the utility of a number of statistical methods to determine model performance and address challenges inherent in analyzing immunosignatures. Some of these methods include exploratory and confirmatory factor analyses, classical significance testing, structural equation and mixture modeling.

Results: We demonstrate an ability to classify samples based on disease status and show that immunosignaturing is a very promising technology for screening and presymptomatic screening of disease. In addition, we are able to model complex patterns and latent factors underlying immunosignatures. These latent factors may serve as biomarkers for disease and may play a key role in a bioinformatic method for antibody discovery.

Conclusion: Based on this research, we lay out an analytic framework illustrating how immunosignatures may be useful as a general method for screening and presymptomatic screening of disease as well as antibody discovery.