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AbstractChronic pain affects more than 50 million Americans. Treatments remain inadequate, in large part, because the pathophysiological mechanisms underlying the development of chronic pain remain poorly understood. Pain biomarkers could potentially identify and measure biological pathways and phenotypical expressions that are altered by pain, provide insight into biological treatment targets, and help identify at-risk patients who might benefit from early intervention. Biomarkers are used to diagnose, track, and treat other diseases, but no validated clinical biomarkers exist yet for chronic pain. To address this problem, the National Institutes of Health Common Fund launched the Acute to Chronic Pain Signatures (A2CPS) program to evaluate candidate biomarkers, develop them into biosignatures, and discover novel biomarkers for chronification of pain after surgery. This article discusses candidate biomarkers identified by A2CPS for evaluation, including genomic, proteomic, metabolomic, lipidomic, neuroimaging, psychophysical, psychological, and behavioral measures. Acute to Chronic Pain Signatures will provide the most comprehensive investigation of biomarkers for the transition to chronic postsurgical pain undertaken to date. Data and analytic resources generatedby A2CPS will be shared with the scientific community in hopes that other investigators will extract valuable insights beyond A2CPS's initial findings. This article will review the identified biomarkers and rationale for including them, the current state of the science on biomarkers of the transition from acute to chronic pain, gaps in the literature, and how A2CPS will address these gaps.

This design case presents an early career designer's reflection on the design and design narrative from an asynchronous video tutorial, reflecting on the unexpected obstacles of the process and unintended consequences of certain design decisions. The first author designed a tutorial for a non-academic department of a large southeastern university. The first author was an early career instructional designer at the time of this design. She shares insights that she gained through this design process, reflecting on developing communication strategies for working with the client and other stakeholders, as well as the critical moments where she might have avoided design failures. The second author mentored her and supported the design case's development. He has included reflection notes in the article in key locations where common challenges to writing the case appeared. This design case details how assumptions and infrequent communication, or communication that lacked vital details, impacted the design process. It offers readers pivotal discoveries that figured prominently in the final design and compelled the designer to reflect on how the design came to be as it was. The case aims to share the precedent embodied in the design (Howard et al., 2012). This case is presented not to generalize about all cases but rather to offer readers the opportunity to find their own utility in the narrative and reflections. We hope that sharing this experience of reflecting on design inspires creativity in overcoming challenges to communication and collaboration.

Systemic lupus erythematosus (SLE) is a multi-organ autoimmune disorder with a prominent genetic component. Individuals of Asian-Ancestry (AsA) disproportionately experience more severe SLE compared to individuals of European-Ancestry (EA), including increased renal involvement and tissue damage. However, the mechanisms underlying elevated severity in the AsA population remain unclear. Here, we utilized available gene expression data and genotype data based on all non-HLA SNP associations in EA and AsA SLE patients detected using the Immunochip genotyping array. We identified 2778 ancestry-specific and 327 trans-ancestry SLE-risk polymorphisms. Genetic associations were examined using connectivity mapping and gene signatures based on predicted biological pathways and were used to interrogate gene expression datasets. SLE-associated pathways in AsA patients included elevated oxidative stress, altered metabolism and mitochondrial dysfunction, whereas SLE-associated pathways in EA patients included a robust interferon response (type I and II) related to enhanced cytosolic nucleic acid sensing and signaling. An independent dataset derived from summary genome-wide association data in an AsA cohort was interrogated and identified similar molecular pathways. Finally, gene expression data from AsA SLE patients corroborated the molecular pathways predicted by SNP associations. Identifying ancestry-related molecular pathways predicted by genetic SLE risk may help to disentangle the population differences in clinical severity that impact AsA and EA individuals with SLE.

Harmful algal blooms (HABs) are on the rise worldwide. Known drivers for the proliferation and intensification of HAB events include increasing nutrient pollution, climate change, regulation and modification of hydrological flow, and the combined effect of climate drivers and nutrient pollution. The San Francisco Bay–Delta system has largely been immune to severe or acute HAB events, but there is both a potential and realized threat which has been underestimated and under-reported, in part because of the lack of coordinated sampling and data reporting. There is also increasing evidence that HABs must be considered in the context of a freshwater-to-marine continuum, and that the physical and political boundaries separating components of the Bay–Delta system are porous barriers to HABs and their toxins. Much remains to be learned about the ecology and physiology of HAB organisms in this system, but five primary environmental drivers can be identified: temperature, salinity, irradiance, nutrients, and stratification/residence time. All these drivers are responding rapidly to climate change, but nutrients are the primary variable that is largely under human control. Plans for the development of a comprehensive monitoring, prediction, and mitigation strategy across the freshwater-to-marine continuum have been documented; effectively following through on these plans provides a roadmap toward identifying the drivers and threats—and reducing the potential consequences now and in the future. While HABs alone are not a sufficient motivator for potentially costly and extensive mitigation efforts, there is strong evidence that decreasing nutrient loads, maintaining hydrological connectivity while minimizing stagnant regions, and managing the biota to maintain biodiversity of the Bay–Delta system will result in multiple co-benefits, including reduction of the HAB threat potential.

This article presents two similar design cases and a discussion of how like values resulted in dissimilar design moves. Both cases were gamified learning activities for graduate students in instructional design. Both interventions employed rapid prototyping and were delivered synchronously in an at-a-distance setting. This article compares the two designs, the two designs' similar development narratives, and the two designs' divergent features. We give special attention to the common values the designers brought to the act of designing. Contrasting crucial features in similar designs allowed us, as designers, to appreciate divergent design moves. A discussion of the two cases explains how designers arrived at different design decisions through similar rationale. The authors were both designers and instructors of the implementations; each presents their case in relation to the other. Our combined cases explore how designers might compare salient features of similar instructional interventions and appreciate design moves that one chose not to make.

Using data from the 2014 Community College Survey of Student Engagement (CCSSE), we examined traditional and nontraditional students' perceived preparation for job skills in terms of the "three ways of knowing" from a career capital perspective. Results showed that traditional and nontraditional students shared commonalities as well as differences in terms of "three ways of knowing." Multinomial regression showed that different sets of predicators were significant in predicting students' perceived preparation for job skills, depending on the outcome being considered. However, variables that are directly aligned to the work or job preparation -- updating job skills as a goal, work-based learning, and using job placement assistance, each representing one way of knowing -- had the largest odds ratios in explaining the perceived preparation for job skills. Discussions of findings and implications are provided.

In this essay, we discuss issues related to the integration of career exploration in our nation's middle schools. We discuss the theoretical and empirical basis for career exploration at the middle school level and identify selected barriers to its effective implementation, namely with regards to career advising and parent involvement. We also propose new directions for practice and research as we work to counteract these barriers.

Chronic pain has become a global health problem contributing to years lived with disability and reduced quality of life. Advances in the clinical management of chronic pain have been limited due to incomplete understanding of the multiple risk factors and molecular mechanisms that contribute to the development of chronic pain. The Acute to Chronic Pain Signatures (A2CPS) Program aims to characterize the predictive nature of biomarkers (brain imaging, high-throughput molecular screening techniques, or "omics," quantitative sensory testing, patient-reported outcome assessments and functional assessments) to identify individuals who will develop chronic pain following surgical intervention. The A2CPS is a multisite observational study investigating biomarkers and collective biosignatures (a combination of several individual biomarkers) that predict susceptibility or resilience to the development of chronic pain following knee arthroplasty and thoracic surgery. This manuscript provides an overview of data collection methods and procedures designed to standardize data collection across multiple clinical sites and institutions. Pain-related biomarkers are evaluated before surgery and up to 3 months after surgery for use as predictors of patient reported outcomes 6 months after surgery. The dataset from this prospective observational study will be available for researchers internal and external to the A2CPS Consortium to advance understanding of the transition from acute to chronic postsurgical pain.

In this case, we focus on two innovations in the design of competitive discussions for a high stakes learning context. The designer created the intervention to provide learners first-hand discussion experiences despite large class sizes. It was a business communication course, and the large class sizes and group dynamics previously had inhibited constructive feedback and limited learner participation; however, the combination of a (1) time-constrained asynchronous CMC activity, along with (2) strategically selected smaller groups, created an interactive space that matched the designer's values of equity and inclusion that he wanted to bring to the design. The case chronicles a number of unforeseen consequences of logical design moves, and presents a multimodal re-conception of what it means to discuss in the context of modern business school.

Although many loci have been associated with height in European ancestry populations, very few have been identified in African ancestry individuals. Furthermore, many of the known loci have yet to be generalized to and fine-mapped within a large-scale African ancestry sample. We performed sex-combined and sex-stratified meta-analyses in up to 52,764 individuals with height and genome-wide genotyping data from the African Ancestry Anthropometry Genetics Consortium (AAAGC). We additionally combined our African ancestry meta-analysis results with published European genome-wide association study (GWAS) data. In the African ancestry analyses, we identified three novel loci (SLC4A3, NCOA2, ECD/FAM149B1) in sex-combined results and two loci (CRB1, KLF6) in women only. In the African plus European sex-combined GWAS, we identified an additional three novel loci (RCCD1, G6PC3, CEP95) which were equally driven by AAAGC and European results. Among 39 genome-wide significant signals at known loci, conditioning index SNPs from European studies identified 20 secondary signals. Two of the 20 new secondary signals and none of the 8 novel loci had minor allele frequencies (MAF) < 5%. Of 802 known European height signals, 643 displayed directionally consistent associations with height, of which 205 were nominally significant (p < 0.05) in the African ancestry sex-combined sample. Furthermore, 148 of 241 loci contained ≤20 variants in the credible sets that jointly account for 99% of the posterior probability of driving the associations. In summary, trans-ethnic meta-analyses revealed novel signals and further improved fine-mapping of putative causal variants in loci shared between African and European ancestry populations.

Decline in insulin sensitivity due to dysfunction of adipose tissue (AT) is one of the earliest pathogenic events in type 2 diabetes. We hypothesize that differential DNA methylation (DNAm) controls insulin sensitivity and obesity by modulating transcript expression in AT. Integrating AT DNAm profiles with transcript profile data measured in a cohort of 230 African Americans (AAs) from the African American Genetics of Metabolism and Expression cohort, we performed cis-expression quantitative trait methylation (cis-eQTM) analysis to identify epigenetic regulatory loci for glucometabolic trait-associated transcripts. We identified significantly associated cytosine-guanine dinucleotide regions for 82 transcripts (false discovery rate [FDR]-P < 0.05). The strongest eQTM locus was observed for the proopiomelanocortin (POMC; ρ = -0.632, P = 4.70 × 10-27) gene. Epigenome-wide association studies (EWAS) further identified 155, 46, and 168 cytosine-guanine dinucleotide regions associated (FDR-P < 0.05) with the Matsuda index, SI, and BMI, respectively. Intersection of EWAS, transcript level to trait association, and eQTM results, followed by causal inference test identified significant eQTM loci for 23 genes that were also associated with Matsuda index, SI, and/or BMI in EWAS. These associated genes include FERMT3, ITGAM, ITGAX, and POMC In summary, applying an integrative multiomics approach, our study provides evidence for DNAm-mediated regulation of gene expression at both previously identified and novel loci for many key AT transcripts influencing insulin resistance and obesity.

Collaborative Video Annotation (CVA) is a kludge where learners annotate video together, experiencing both the video and each other's annotations in a dynamic discussion. Three scenes from small group CVA discussions were selected for analysis from 14 CVA discussions where 8-12 learners interacted via the annotation tool on top of a video. The twenty-second scenes were analyzed for semiotic meaning-making practices and this revealed a variety of participatory media literacy levels among these undergraduates. Topics of discussions were related but not identical, and the selected exemplars showed a range of attention to communicative features of the media. Discussions evolved in dramatically different ways due to the interplay of images, text, and learner choices. Results suggest that converged media require new literacies educators would be wise to explore and wiser still to educate our learners about.

Meta-analytic studies are syntheses of literature in which researchers use statistical means to summarize the findings presented across primary studies. They are of great interest in the fields of medicine and social sciences with numerous examples published in peer-reviewed journals. However, it appears that career and technical education (CTE) researchers are either not performing these research syntheses, or are not publishing their findings. Thus, there are three purposes to this manuscript. The first is to present CTE researchers and practitioners with a rationale as to why meta-analyses should be performed. The second is to provide guidelines that researchers and practitioners use to perform their own meta-analyses. The third is to provide suggestions that researchers and practitioners can use to disseminate the results of their meta-analyses. The manuscript concludes with a listing of suggested areas for future research.

The purpose of this study was to examine quality indicators currently guiding the rigor of secondary career and technical education (CTE) programs of study in the United States. Quality indicators are desirable characteristics or expectations for a comprehensive and effective CTE program of study. As of May 2017, we were able to locate publicly accessible secondary CTE quality program standards/guidelines for 38 states. A majority (n=24) updated their secondary CTE quality program standards/guidelines within the last five years (i.e., 2012-2017). Deductive content analysis was conducted to examine the 38 state profiles using the Association of Career and Technical Education (ACTE) Quality CTE Program of Study Framework 4.0 for coding purposes. Common quality elements and key quality indicators were identified from those state documents, which supplements the ACTE Framework. Implications and examples for practice are also discussed.

Although prior studies have examined the influence of career and technical education (CTE) on high school completion in the United States, few studies provided direct empirical evidence on how it worked. Using the High School Longitudinal Study of 2009 (HSLS:2009), this study examined public high school students' CTE experience from three integral aspects (coursework, career and technical student organizations, and work-based learning) and investigated whether these experiences influenced high school on-time completion through school engagement. Results indicated that CTE coursework had the strongest positive influence on on-time completion. Mediating effects of selected school engagement variables existed for most CTE activities. Directions for future research are provided.

As a result of a university partnership, elementary students at two midwest Catholic elementary schools have been provided with exploratory world language instruction (FLEX) from pre-service teachers. To investigate students' attitudes and learning of Spanish, researchers interviewed second and fourth graders. The students' parents and pre-service teachers answered open-ended questionnaires. The research questions for this qualitative study were: (a) How does exploratory world language instruction (FLEX) affect children's attitudes about learning world languages and cultures? (b) How does exploratory world language instruction (FLEX) affect children's learning of a world language? The results showed that students possessed positive attitudes about world language instruction, and they learned numbers, colors, cultural information, and food and animal vocabulary, as well as how to communicate at the novice level. Universities should consider engaging in service-learning partnerships with Catholic elementary schools so students learn to open their minds and hearts to diverse languages and cultures.

Participation in interactive games, especially those in immersive environments, is often employed in learning contexts to stochastically develop L2 learners' language ability. However, typical measures of language ability often do not reflect pragmatic competencies. This study juxtaposes two elementary school ESL learners' language ability, and facility with the media, with their politeness measures. Data was collected from out-of-school gameplay chat in a virtual environment designed for elementary school learners. Results suggest learners can express pragmatic miscues to interlocutors in the lean media of synchronous chat.

The purpose of this descriptive study was to explore staff members' perceptions of student-veterans college experiences at a 2-year and a 4-year institution. This study was guided by Schlossberg's Theory of Adult Transitions. Purposive sampling was used to identify 640 participants for the study. Respondents indicated that their campus should add more support services for student- veterans. Staff members rank the following as major problems that the Department of Veterans should be responsible for when helping student-veterans with selected problems: military- related physical injuries, PTSD, and talking about their military experiences. A majority of the respondents reported that they would be willing to participate in a seminar about student-veterans and military culture.

This study sought to explore faculty members' perceptions of student-veterans' transition at a two-year college compared to a four-year institution. The guiding framework for this study was provided by Schlossberg's (1984) Theory of Adult Transitions. A simple random sample was used to identify 557 academic faculty members for the study. Overall, there were several significant differences between twoyear and four-year faculty members' perceptions of student-veterans' transitions. [Paper presented at the Annual Meeting of the Northern Rocky Mountain Educational Research Association (NRMERA) (34th, 2016).]

In this design case, we present an instructional design project that resulted in a French language learning game development system. What we describe here is not the game itself, but rather the pedagogical intervention that created what the design team termed a mobile "application farm," which in turn produced the game. The term "farm" was used due to the perspective of the designers to create a sustainable system rather than a single design. This design case also has another purpose beyond presenting precedent in instructional design; we interrogate the interview process and the protocol we used while documenting this project. We present the outcome of our interrogation in reflection notes posted throughout this design case. We do this because we believe that there is a value and need for design cases created by someone outside of the design arena but with access to members of the design team, in order to elicit where precedents might be found within complex designs.

The authors present insights from the creation of an "Industry Liaison" (IL) role in a graduate program in Instructional Technology. An analysis of learner questions posed to practicing designers showed masters candidates' concerns fell into four areas: rejections and acceptance in the workplace, career logistics, technological skills, and application materials. Using these questions, the IL solicited practicing designers', design managers', and instructional design consultants' answers. Findings expose areas where instructional design learning can be improved, and areas where academic preparation can be better connected to the practice of instructional design.

Purpose: We previously demonstrated an association between decreased SMAD4 expression and cetuximab resistance in head and neck squamous cell carcinoma (HNSCC). The purpose of this study was to further elucidate the clinical relevance of SMAD4 loss in HNSCC.Experimental Design: SMAD4 expression was assessed by IHC in 130 newly diagnosed and 43 patients with recurrent HNSCC. Correlative statistical analysis with clinicopathologic data was also performed. OncoFinder, a bioinformatics tool, was used to analyze molecular signaling in TCGA tumors with low or high SMAD4 mRNA levels. The role of SMAD4 was investigated by shRNA knockdown and gene reconstitution of HPV-negative HNSCC cell lines in vitro and in vivoResults: Our analysis revealed that SMAD4 loss was associated with an aggressive, HPV-negative, cetuximab-resistant phenotype. We found a signature of prosurvival and antiapoptotic pathways that were commonly dysregulated in SMAD4-low cases derived from TCGA-HNSCC dataset and an independent oral cavity squamous cell carcinoma (OSCC) cohort obtained from GEO. We show that SMAD4 depletion in an HNSCC cell line induces cetuximab resistance and results in worse survival in an orthotopic mouse model in vivo We implicate JNK and MAPK activation as mediators of cetuximab resistance and provide the foundation for the concomitant EGFR and JNK/MAPK inhibition as a potential strategy for overcoming cetuximab resistance in HNSCCs with SMAD4 loss.Conclusions: Our study demonstrates that loss of SMAD4 expression is a signature characterizing the cetuximab-resistant phenotype and suggests that SMAD4 expression may be a determinant of sensitivity/resistance to EGFR/MAPK or EGFR/JNK inhibition in HPV-negative HNSCC tumors. Clin Cancer Res; 23(17); 5162-75. ©2017 AACR.

"Designerly Talk in Non-Pedagogical Social Spaces" (Gray and Howard, 2014) is a paper on a study that was conducted as an early attempt to understand the kinds of talk students engaged in outside of the formal curriculum in student-run communities that enhanced their design learning. While the paper has only been available for a relatively short time, there has been wide interest in the confluence of social media, design education, and learning opportunities that exist outside of the formal curriculum. This reflection discusses more recent work conducted by the authors, and explores the occurrence of designerly talk in a non-classroom studio space and the ways in which designerly talk arises without the initiation or management by academics. The paper, "Designerly Talk in Non-Pedagogical Social Spaces" (Gray and Howard, 2014) is included as it appeared in "Journal of Learning Design" v7 n1 2014, with minor edits. [For "Designerly Talk in Non-Pedagogical Social Spaces," see EJ1020704.]

Systemic lupus erythematosus (SLE) is an autoimmune disease with marked gender and ethnic disparities. We report a large transancestral association study of SLE using Immunochip genotype data from 27,574 individuals of European (EA), African (AA) and Hispanic Amerindian (HA) ancestry. We identify 58 distinct non-HLA regions in EA, 9 in AA and 16 in HA (∼50% of these regions have multiple independent associations); these include 24 novel SLE regions (P

Students live and work in worlds where virtual communities, such as those created via social network sites (e.g. Facebook) may interplay with their formal learning, but scholars of design pedagogy know little about how these spaces can support design learning. In this study, we describe how a set of informal communications, encapsulated in five student-created and managed Facebook groups, functioned as part of the overall pedagogy in an interaction design Master's program. We discuss ways in which students may learn in these spaces apart from the formal curriculum, and document instances where communication with other students and practitioners brought about instances of self-directed learning and sharing of expertise. Some of these learning experiences emerged as designerly talk through our investigation of extended comment threads in these Facebook groups. We present the conventions of the discourse and four types of design learning embodied in specific examples, noting implications for design pedagogy and the recognition of a student-generated hidden curriculum.