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1.  Systematic Dissection of Coding Exons at Single Nucleotide Resolution Supports an Additional Role in Cell-Specific Transcriptional Regulation 
PLoS Genetics  2014;10(10):e1004592.
In addition to their protein coding function, exons can also serve as transcriptional enhancers. Mutations in these exonic-enhancers (eExons) could alter both protein function and transcription. However, the functional consequence of eExon mutations is not well known. Here, using massively parallel reporter assays, we dissect the enhancer activity of three liver eExons (SORL1 exon 17, TRAF3IP2 exon 2, PPARG exon 6) at single nucleotide resolution in the mouse liver. We find that both synonymous and non-synonymous mutations have similar effects on enhancer activity and many of the deleterious mutation clusters overlap known liver-associated transcription factor binding sites. Carrying a similar massively parallel reporter assay in HeLa cells with these three eExons found differences in their mutation profiles compared to the liver, suggesting that enhancers could have distinct operating profiles in different tissues. Our results demonstrate that eExon mutations could lead to multiple phenotypes by disrupting both the protein sequence and enhancer activity and that enhancers can have distinct mutation profiles in different cell types.
Author Summary
Exons that code for protein can also have additional functions, such as regulating gene transcription through enhancer activity. Here, we changed every nucleotide in three different exons that also function as enhancers, and examined their enhancer activity to test whether nucleotide changes in these exons can affect both the protein sequence and enhancer function. We found that mutations with a significant effect on enhancer function can reside both in regions that change the protein sequence (non-synonymous) and regions that do not change it (synonymous). When we conducted a similar analysis in a different cell type, we observed a difference in the nucleotide changes that cause a significant effect on enhancer activity, suggesting that the enhancer functional units can differ between tissues.
PMCID: PMC4207465  PMID: 25340400
2.  The Development of a Community-Based, Pharmacist-Provided Falls Prevention MTM Intervention for Older Adults: Relationship Building, Methods, and Rationale 
Innovations in pharmacy  2014;5(1):140-.
The objectives of this article are to discuss the process of community engagement experienced to plan and implement a pilot study of a pharmacist-provided MTM intervention focused on reducing the use of medications associated with falling, and to present the research methods that emerged from the community engagement process to evaluate the feasibility, acceptance, and preliminary impact of the intervention. Key lessons learned from the community engagement process also are presented and discussed. The relationship building and planning process took twelve months. The RE-AIM framework broadly guided the planning process since an overarching goal for the community partners was developing a program that could be implemented and sustained in the future. The planning phase focused on identifying research questions that were of most interest to the community partners, the population to study, the capacity of partners to perform activities, process evaluation. Much of the planning phase was accomplished with face-to-face meetings. After all study processes, study materials, and data collection tools were developed, a focus group of older adults who represented the likely targets of the MTM intervention provided feedback related to the concept and process of the intervention. Nine key lessons were identified from the community engagement process. One key to successful community engagement is partners taking the time to educate each other about experiences, processes, and success and failures. Additionally, partners must actively listen to each other to better understand barriers and facilitators that likely will impact the planning and implementation process. Successful community engagement will be important to develop both formative and summative evaluation processes that will help to produce valid evidence about the effectiveness of pharmacists in modifying drug therapy and preventing falls as well as promote adoption and implementation of the intervention in other communities.
PMCID: PMC4190035  PMID: 25309809
Falls Prevention; Community Pharmacy; Medication Therapy Management; Community Engagement
3.  Impact and Application of Material Learned in a Pharmacy Residency Teaching Certificate Program 
Objective. To describe the impact and application of material learned in a pharmacy resident teaching certificate program on the career experiences of alumni 1 to 11 years after completion of the program.
Design. A teaching certificate program was established in 2001 that brought together residents from various training programs throughout Wisconsin to discuss essential educational skills in a dynamic learning environment. The purpose of the program was to teach participants the fundamental skills to continue to develop as a pharmacy educator throughout their career.
Assessment. An electronic survey instrument was sent to alumni of the program. Greater than 70% of respondents agreed that the teaching certificate program reinforced their desire to teach in practice and that the program helped qualify them for their current or previous practice position. Alumni in academic positions more strongly agreed that the program changed their career interest to include academia and qualified them for their position in academia.
Conclusions. A teaching certificate program can reinforce or stimulate interest among pharmacy residents in pursuing an academic career and prepare them for this role. Completion of the program led to a high level of confidence among the majority of alumni in their ability to precept students and residents and influenced some alumni involved in the hiring of pharmacists.
PMCID: PMC4140489  PMID: 25147395
teaching certificate program; pharmacy; residency training
4.  A Nontraditional Faculty Development Initiative Using a Social Media Platform 
Objective. To assess the outcomes from an 11-year nontraditional professional development activity implemented by female faculty members at several colleges and schools of pharmacy.
Design. Within the context of an online fantasy football league, faculty members practiced community-based faculty development strategies, including peer mentoring, skills development, constructive feedback and other supportive behaviors.
Assessment. Data were extracted from curriculum vitae to characterize the academic progress of participants and to quantify scholarly work collaborations among league members. Analyses were limited to members who had participated in the league for 10 or more consecutive years. Seventy-one collaborative scholarly works occurred among team managers, including presentation of 20 posters and 2 oral presentations at national or international meetings, publication of 29 peer-reviewed articles and 15 book chapters, and funding of 5 research projects.
Conclusion. Social media platforms can foster nontraditional faculty development and mentoring by enhancing connectivity between pharmacy educators who share similar interests.
PMCID: PMC4064482  PMID: 24954945
mentor; inservice training; faculty development; pharmacy faculty; social media
5.  The haplotype-resolved genome and epigenome of the aneuploid HeLa cancer cell line 
Nature  2013;500(7461):207-211.
The HeLa cell line was established in 1951 from cervical cancer cells taken from a patient, Henrietta Lacks, marking the first successful attempt to continually culture human-derived cells in vitro1. HeLa’s robust growth and unrestricted distribution resulted in its broad adoption – both intentionally and through widespread cross-contamination2 – and for the past sixty years it has served a role analogous to that of a model organism3. Its cumulative impact is illustrated by the fact that HeLa is named in >74,000 or ~0.3% of PubMed abstracts. The genomic architecture of HeLa remains largely unexplored beyond its karyotype4, in part because like many cancers, its extensive aneuploidy renders such analyses challenging. We performed haplotype-resolved whole genome sequencing5 of the HeLa CCL-2 strain, discovering point and indel variation, mapping copy-number and loss of heterozygosity (LOH), and phasing variants across full chromosome arms. We further investigated variation and copy-number profiles for HeLa S3 and eight additional strains. Surprisingly, HeLa is relatively stable with respect to point variation, accumulating few new mutations since early passaging. Haplotype resolution facilitated reconstruction of an amplified, highly rearranged region at chromosome 8q24.21 at which the HPV-18 viral genome integrated as the likely initial event underlying tumorigenesis. We combined these maps with RNA-Seq6 and ENCODE Project7 datasets to phase the HeLa epigenome, revealing strong, haplotype-specific activation of the proto-oncogene MYC by the integrated HPV-18 genome ~500 kilobases upstream, and permitting global analyses of the relationship between gene dosage and expression. These data provide an extensively phased, high-quality reference genome for past and future experiments relying on HeLa, and demonstrate the value of haplotype resolution for characterizing cancer genomes and epigenomes.
PMCID: PMC3740412  PMID: 23925245
6.  Educational Testing and Validity of Conclusions in the Scholarship of Teaching and Learning 
Validity and its integral evidence of reliability are fundamentals for educational and psychological measurement, and standards of educational testing. Herein, we describe these standards of educational testing, along with their subtypes including internal consistency, inter-rater reliability, and inter-rater agreement. Next, related issues of measurement error and effect size are discussed. This article concludes with a call for future authors to improve reporting of psychometrics and practical significance with educational testing in the pharmacy education literature. By increasing the scientific rigor of educational research and reporting, the overall quality and meaningfulness of SoTL will be improved.
PMCID: PMC3831397  PMID: 24249848
psychometrics; educational testing; scholarship of teaching and learning; reliability; validity
8.  Longitudinal Teaching of Evidence-Based Decision Making 
Objective. To determine whether longitudinal design and delivery of evidence-based decision making (EBDM) content was effective in increasing students’ knowledge, skills, and confidence as they progressed through a doctor of pharmacy (PharmD) curriculum.
Design. Three student cohorts were followed from 2005 to 2009 (n=367), as they learned about EBDM through lectures, actively researching case-based questions, and researching and writing answers to therapy-based questions generated in practice settings.
Assessment. Longitudinal evaluations included repeated multiple-choice examinations, confidence surveys, and written answers to practice-based questions (clinical inquiries). Students’ knowledge and perception of EBDM principles increased over each of the 3 years. Students’ self-efficacy (10-items, p<0.0001) and perceived skills (7-items, p<0.0001) in applying EBDM skills to answer practice-based questions also increased. Graded clinical inquiries verified that students performed satisfactorily in the final 2 years of the program.
Conclusions. This study demonstrated a successful integration of EBDM throughout the curriculum. EBDM can effectively be taught by repetition, use of real examples, and provision of feedback.
PMCID: PMC3530059  PMID: 23275662
evidence-based decision making; longitudinal evaluation; curriculum; evidence-based medicine
9.  A Model for Partnering First-Year Student Pharmacists With Community-Based Older Adults 
Objectives. To design, integrate, and assess the effectiveness of an introductory pharmacy practice experience intended to redefine first-year student pharmacists’ views on aging and medication use through their work with a healthy, community-based older-adult population.
Design. All students (N = 273) completed live skills training in an 8-hour boot camp provided during orientation week. Teams were assigned an independently living senior partner, completed 10 visits and reflections, and documented health-related information using an electronic portfolio (e-portfolio).
Assessment. As determined by pre- and post-experience survey instruments, students gained significant confidence in 7 skill areas related to communication, medication interviews, involving the partner in health care, and applying patient-care skills. Student reflections, in-class presentations, and e-portfolios documented that personal attitudes toward seniors changed over time. Senior partners enjoyed mentoring and interacting with students and many experienced health improvements as a result of the interaction.
Conclusions. The model for partnering first-year student pharmacists with community-based older adults improved students’ skills and fostered their connections to pharmacist roles and growth as person-centered providers.
PMCID: PMC3386036  PMID: 22761526
geriatrics; senior partner; senior mentor; introductory pharmacy practice experience
10.  Evaluating pharmacists' ability to counsel on tobacco cessation using two standardized patient scenarios 
Patient education and counseling  2011;83(3):319-324.
To evaluate the impact that role-playing two pre/post standardized patient scenarios within a tobacco cessation training program had on pharmacists' counseling skills. Second, to analyze the validity of the observation coding tool used to evaluate pharmacist's role-play performance.
Pharmacists performed two role-playing scenarios which incorporated national guidelines, the 5A's counseling process, and the “preparation” and “action” phases of the transtheoretical model. Pharmacists' performance was evaluated with an observation coding tool.
Pharmacists' (n=25) counseling performance improved significantly post-training (p<0.02: Action Scenario; p<0.004: Preparation Scenario). More than 50% of pharmacists provided patient-directed tobacco consultation services in the one year following training. The observation tool score for the “action phase” scenario was highly associated with pharmacists' subsequent delivery of tobacco cessation services in community practice.
Role-playing facilitated pharmacists' skill development. The evaluation tool and Action Scenario may be powerful for predicting pharmacists' delivery of tobacco cessation services.
Practice Implications
Incorporating role-playing and structured tools for performance evaluation can help enhance pharmacist performance during training and predict service delivery in community practice. Together they could facilitate tailored feedback to help pharmacists struggling with the difficult task of extending cognitive service roles in practice.
PMCID: PMC3110982  PMID: 21237610
Tobacco cessation counseling; transfer of learning; standardized patient; role-play; pharmacist
11.  Development of a Scale to Measure Pharmacists’ Self-Efficacy in Performing Medication Therapy Management Services 
Measuring community pharmacists’ self-efficacy in performing medication therapy management (MTM) services can be useful for tailoring interventions and predicting participation.
To identify relevant survey constructs related to the Wisconsin Pharmacy Quality Collaborative (WPQC) MTM program and to evaluate scale validity.
The 31-item MTM Self-efficacy Scale was developed using previous research, identifying critical program components, and beta-testing. After administration to pharmacists in the 53 WPQC pilot sites, summary statistics and exploratory factor analysis (EFA) were conducted. Parallel analysis was used to determine the optimal number of factors. Internal consistency reliabilities were calculated.
Baseline participation rate was 94% (N=76). The 11-point scale (0–10) item means ranged from 2.83±3.05 to 7.82±2.19. Parallel analysis produced a 3-factor solution, accounting for 56% of the variance. Low factor loadings or unacceptably high cross-loadings resulted in 17 item deletions. The final EFA on the remaining 14 items retained the original 3-factor solution and increased the proportion of explained variance (72%). The factors relate to MTM tasks (alpha = 0.92), personal interactions (alpha = 0.86), and goal setting (alpha = 0.84). Overall Cronbach’s alpha = 0.90.
Constructs for measuring self-efficacy were identified that may aid in future research predicting whether pharmacists engage in and persist in providing MTM services.
PMCID: PMC2904078  PMID: 20511114
Self-efficacy; Medication therapy management; Community pharmacy; Scale validation; Research methods
12.  Effect of a tobacco cessation continuing professional education program on pharmacists' confidence, skills, and practice-change behaviors 
To evaluate the impact of a tobacco cessation training program on pharmacists' confidence, skills, and practice-change behaviors.
Quasiexperimental study.
Wisconsin during 2002–2003.
25 community pharmacists.
A continuing education training program was developed and implemented using home and live training components consisting of the national tobacco cessation guidelines, including the 5A's counseling process. The home study component included lectures and readings in CD-ROM format. Consistent with self-efficacy theory, the live training was based on exercises that included modeling, rehearsal, and feedback to learners.
Main outcome measures
Knowledge assessment, pre- and postsurveys assessing confidence and skill levels, and service provision indicators.
Self-efficacy and perceived ability to counsel patients to quit using tobacco improved significantly after the combined program. No significant change in confidence or perceived skills occurred following home study alone, suggesting value in using a combination of teaching strategies (problem solving, modeling, rehearsal, and feedback). Of participants, 92% received a passing knowledge score and 75% attempted to implement a tobacco cessation service posttraining; more than 50% assisted patients up to 1 year posttraining. A relationship between self-efficacy and service provision was found when practice settings were considered.
This program increased pharmacists' knowledge and self-efficacy to counsel patients on tobacco use. Further, the majority of pharmacy participants attempted to implement a tobacco cessation service.
PMCID: PMC2863290  PMID: 20097634
Self-efficacy; continuing education; counseling (patient); tobacco cessation
13.  Risk for Osteoporosis in Elderly Nuns: Need for Better Recognition and Treatment 
Background: The risk for osteoporosis in Catholic sisters (nuns) may be even higher than that of the general female population given their longer life expectancy (82.0 to 89.0 years vs 79.6 years for the average white woman) and the use of a traditional habit as a young adult, resulting in limited sun exposure (ie, exposure to vitamin D).
Objectives: The aim of this study was to determine, in a group of elderly nuns attending an annual health screening day (Health Forum), how many met National Osteoporosis Foundation (NOF) treatment criteria using peripheral bone mineral density (BMD) measurements and risk factors; what proportion received adequate vitamin D; whether BMD was related to length of time that nuns wore a habit; and whether BMD measurement led to medical interventions. In addition, we compared the usefulness of calcaneal BMD with that of BMD at central sites for identification of those at risk for osteoporosis.
Methods: This cross-sectional study assessed BMD by calcaneal dual energy X-ray absorptiometry (DXA) and, for some participants, central DXA. A baseline questionnaire and follow-up mail survey also were included.
Results: Of the 230 nuns attending the Health Forum, 146 (63%) (mean age, 70 years; range, 48–90 years) participated in the study. Of these, 14% had calcaneal osteoporosis (T-score <−2.5) and 32% met NOF treatment criteria, indicating risk comparable to that of other postmenopausal American women. Sixty-four percent were receiving less than the recommended amount of vitamin D (≥400 IU/d for those aged <71 years and ≥600 IU/d for those aged ≥71 years). Calcaneal BMD was inversely related to the length of time nuns had worn a habit. Fifty-six women subsequently underwent central DXA. Using a calcaneal T-score of −1.2 to identify those with central osteoporosis, sensitivity and specificity of 78% and 76%, respectively, were obtained. According to the mail survey, 11 of 42 respondents who had met NOF treatment criteria started new medications for osteoporosis.
Conclusions: Elderly nuns are at substantial risk for osteoporosis. Most receive inadequate vitamin D. For nuns and others who may have limited access to central DXA measurement, peripheral measurements may help identify those in need of further intervention. Further efforts, in addition to BMD measurements, are necessary to ensure appropriate therapy for those who meet treatment criteria.
PMCID: PMC4053027  PMID: 24944357
postmenopausal osteoporosis; bone density; vitamin D; nuns

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