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The primary goals of the project were to improve rates of developmental screening and appropriate referral for atypical screens for children from birth to 3 years in participating practices and to integrate parent partners (PPs) into primary care.Parents' Place of Maryland, in collaboration with the Maryland Department of Health, developed a quality improvement project to improve rates of developmental screening, referral, and follow-up. Nine practices from across the state completed the project. Participating practices received training and technical assistance for screening, referral, and data collection as well as a paid part-time PP to assist with care coordination. Families of children with atypical developmental screening results were offered a referral to receive support in following through with referrals, including needed social services to address health care barriers.Developmental screening rates across practices increased from 65% to 95% during the 9-month project, and autism-specific screening increased from 75% to 94%. Appropriate referral rates tripled from 6% to 20% of children. After an initial learning curve, practices gradually increased referrals to PPs, and they served 292 individual families (total of 544 contacts) over 9 months. PPs helped families identify a variety of community services to meet their needs.While developmental screening rates can be improved using quality improvement processes, supporting families to connect to services requires additional resources. Integrating trained PPs into pediatric practices improves access to community-based services in a cost-efficient manner. More research is needed to identify the most efficient models for providing this service on a broader scale.

Purpose: Despite potential benefits of intravenous (i.v.) administration of acetaminophen (APAP), consistent outcome data are lacking. This, combined with the higher acquisition cost of the drug, has led to variation in i.v. APAP management strategies. This project evaluated the contemporary formulary status and restrictions of i.v. APAP in the perioperative setting. Methods: A survey focusing on i.v. APAP formulary restriction in the perioperative setting was developed by the Vizient Pharmacy Research Committee and distributed to Vizient Pharmacy Program participant listservs for Pharmacy Directors or Drug Information Pharmacists. The four survey domains included hospital characteristics, perioperative i.v. APAP formulary status and prescribing restrictions, perioperative i.v. APAP use, and perioperative i.v. APAP medication use evaluation (MUE) results. Responses were collected and summarized, and primary outcomes were evaluated using Fisher’s exact test. Results: A total of 1195 surveys were distributed with a response rate of 19%. Respondents were equally distributed between academic medical centers (AMC) and non-academic medical centers (non-AMC). Two cohorts were examined: those with i.v. APAP on formulary and those without. The non-AMCs showed a larger proportion of hospitals with the medication on formulary ( P = .041). Regarding formulary decision-making, the AMCs were more considerate of value. Several different practices were employed to limit or restrict i.v. APAP. Conclusion: A survey of directors of pharmacy and drug information specialists revealed that the majority of hospitals have i.v. APAP on formulary for perioperative use, but use is restricted. Differences in i.v. APAP formulary practices between AMCs and non-AMCs warrant further consideration.

Objective: Autonomy-support and quality feedback have been shown to significantly impact student learning. Unfortunately, quality feedback is often very time consuming. The goal of this study was to examine the autonomy-supportive potential from feedback provided via technology, specifically the ExamSoft Strength and Opportunities report. Methods: Students were divided into two groups: one received enhanced performance feedback via the ExamSoft Strength and Opportunities report, the other received traditional grade-only feedback in the form of grades and course averages, via ExamSoft. The Learning Self-Regulation Survey (SRQ-L) was administered to 139 third-year doctor of pharmacy students. The survey contained 14 statements asking students to rate their reasons (relative autonomy) for reviewing ExamSoft feedback, three items related to use of the ExamSoft technology, and five demographic items. Results: A statistical difference, t(52) = -2.07, p =0.043; d = .577, was reported between the two groups indicating enhanced feedback via ExamSoft had a moderate impact on students’ autonomy. Conclusions: Students who received enhanced ExamSoft feedback reported significantly higher relative autonomy index (RAI) for feedback review than students who did not receive the feedback. This suggests that the enhanced ExamSoft feedback was autonomy-supportive. Conflict of Interest: None Treatment of Human Subjects: IRB review/approval required and obtained Type: Original Research

Objective. To assess the impact of the COVID-19 pandemic on pharmacy residency application/interview processes, match rate, and factors influencing match rankings at a single college of pharmacy Methods. In spring of 2020 and 2021, an anonymous survey of fourth-year pharmacy school (P4) residency applicants at one college of pharmacy was administered. Survey responses were compared to explore trends in showcase participation, number/type/geographic dispersion of applications submitted, interview invitations, grade point average (GPA), research experience, and match rate. A thematic analysis evaluated common factors influencing match rankings. Results. Responses were collected from 75 of 99 (75.8% response rate) residency-seeking students in 2020 and 79 of 94 (84.0% response rate) in 2021. Students in 2021 reported applying to a higher median number of programs, with no significant differences in mean reported number of interview invitations or match rate. The virtual American Society of Health-System Pharmacists (ASHP) Midyear Showcase led to a median reported savings of $1000 with no significant impact on perceived value. Virtual interviews led to a median reported savings of $430. Thematic analysis revealed feel/culture, location, and learning experience options as the most prevalent deciding factors for match rankings in both years. Conclusion. The pandemic led to an increase in the number of residency applications per student and yielded a net cost savings. There were no differences in number of interviews offered, match rate, or in deciding factors influencing match rankings. As the pandemic evolves, schools should maintain a flexible and dynamic approach to support students.

Background and purpose The University of Kentucky College of Pharmacy piloted a novel longitudinal introductory experiential program to provide second (P2) and third (P3) year professional students early exposure to pharmacist-provided direct patient care, opportunity to develop professionally expected behaviors, and ability to explore contemporary pharmacy career options. This paper describes the influence of the pilot on pre-advanced pharmacy practice experiences (APPEs) career interests and professional development. Educational activity and setting Forty P2 and P3 students participated in the longitudinal experiential pilot course. Students were assigned to 32 pharmacist preceptors in a variety of direct patient care practices. Students completed 16 onsite hours over the fall semester. Influence of the pilot experience on APPE plans and future career interests was assessed by an end of experience reflective assignment and survey. Findings The pilot course served as the initial exposure for the majority of students to both direct patient care and specialized areas of pharmacy practice. Nearly half of students indicated the experience advanced their knowledge of pharmacists' scope of practice and potential career opportunities. Most students (85%) reported the experience influenced future career plans, with half indicating increased interest in their specific practice specialty. Over 75% planned to pursue an APPE in that practice area. Nearly all students reported making professional contacts through this experience. Summary Early exposure to direct patient care and specialized pharmacy practice areas through this IPPE provided students opportunity to inform career interest and develop professional contacts with preceptors in specialized practice areas.

Background Accreditation Council for Pharmacy Education (ACPE) Standards 2016 established a new standard on interprofessional education (IPE) to place specific emphasis on developing interprofessional competence among pharmacy graduates. Interprofessional education activity Interprofessional Collaboration And Team Skills (iCATS) serves as the core interprofessional curriculum for nearly 700 first-year students in seven participating health professional programs. The curriculum was developed around the four Interprofessional Education Collaborative (IPEC) Competencies to develop foundational interprofessional knowledge, skills, and attitudes. Pharmacy students build preliminary competence in interprofessional roles and responsibilities, team dynamics, values and ethics, communication, and conflict resolution (ACPE Standard 11.1) and have an opportunity to learn about, from, and with other interprofessional students (ACPE Standard 11.2). Discussion Refinement of the iCATS curriculum has been an iterative process over the past four years. For iCATS 2016–2017, all Interprofessional Collaborative Competency Attainment Scale (ICCAS) evaluation items indicated significant changes in pre- and posttest indicating targeted IPEC Competencies were addressed through the iCATS curriculum. Implications The 2016–2017 revision of iCATS resulted in the most effective iteration of this core interprofessional curriculum to date. Clearer course objectives, a compressed schedule, employment of a variety of teaching/learning methods, and greater schedule cooperation among the colleges have contributed to the success and delivery of an IPE curriculum. Additionally, iCATS provides a unique opportunity for pharmacy students to interact with health professions students from six other programs while making significant progress toward competence in ACPE Standards 11.1 and 11.2 on interprofessional education (IPE).

Inspired by learning communities, an evidence-based solution to combat faculty burnout, the University of Kentucky (UK) Center for Interprofessional Health Education's Faculty Fellows and Associates Program offers a novel approach to contemporary faculty development. The Program utilizes minimal financial resources and modest staff support to accomplish its main objectives: identify and recognize IPE champions, promote and support faculty interprofessional education (IPE) contributions, and demonstrate ongoing institutional commitment to faculty development, engagement, and support. This model simultaneously honors faculty IPE contributions and offers robust professional development, while effectively promoting IPE broadly. To date, members from thirteen different colleges and departments have leveraged the program to create numerous scholarly presentations and publications as well as a broad variety of other creative work. The benefits of the Fellows and Associates Program extend to the next generation of health care providers, the students ultimately inspired by these IPE champions.

The International Classification of Func¬tioning (ICF) model is recommended for interprofessional use to define, measure, and create health and disability policy. Our goal was to expand a uniprofessional student learning experience into an interprofessional experiential clinical learning experience focused on the ICF model.An experiential interprofessional education program was developed for Physical Therapy (PT), Physician Assistant (PA), and Pharmacy students. Student teams interviewed a community mentor from a senior living community outside of class to explore their mentor's health journey, assess quality of life, and perform an environmental safety assessment. In this pilot study, students completed an anonymous, unique-identifier electronic survey with open response items pre- and post-experience. Data were coded using inductive thematic analysis.Four themes emerged: learning about other professions (scope of practice), mentor's experiences with health care, treating the whole person, and improving team effectiveness. All four Interprofessional Education Collaborative (IPEC) competencies mapped to the data broadly indicating this learning experience meets interprofessional educational requirements.Student teams deepened their understanding of their community mentor's health and valued the interprofessional knowledge gained. Using the common lens of the ICF, students' understanding and appreciation of other disciplines emerged and students began to see their mentors from a more holistic perspective.

Background Quality facility-based care, amongst other factors has been linked to improved patient outcomes and has been used as an indicator of wider health system strengthening in low- and middle-income countries (LMICs). In an effort to continue supporting quality improvement (QI) initiatives, healthcare providers from both LMICs and high-income countries are partnering to develop clinical training, knowledge transfer and mentoring initiatives. Aim This paper aims to explore the ‘lessons learned’ by international mentors during their experiences assisting with QI initiatives in LMICs, reflecting purposefully on mentor’s perceptions of factors that affected ‘small successes’ during implementation of QI initiatives in district hospitals. Methods Over a five-month period, eight bi-monthly reports written by the researches whilst working as international mentors were collected and analysed using constant comparative thematic analysis. NVivo 12 software was used to compare and analyze codes and emerging themes. Results Four thematic areas emerge as important points of experience and observation: Assessment of needs and project planning; Importance of initial observation period, by international and local clinicians, to identify and agree needs and plan QI strategy; Importance of ‘soft skills’ alongside clinical acumen, to model critical processes in teamwork, effective communication, critical thinking and problem solving; Project partnership; continuous understanding by international and local clinical counterparts, of meaning of partnership, roles and expectations – with regular opportunity to assess partnership progress and address misunderstandings; Critical importance of identifying, agreeing and gathering data on QI processes and outcomes, for key clinical and administrative players to monitor and evaluate facilities’ progress. Conclusions Sustainable QI initiatives require continuous and frequent evaluation and adjustment. Identifying, sharing and understanding ‘small successes’ maintains momentum and creates a shared sense of positive change. ‘Small successes’ were frequently associated with multifaceted approaches to QI such as combining knowledge transfer with practical mentorship or leadership skills with teamwork. Beyond conventional models of training and continuing medical education, future research into facility-based QI and international partnership should focus more on understanding LMICs healthcare provider motivation, and how combined approaches to knowledge transfer and ‘soft skills’ development may improve the quality of provider performance.

Introduction In low-resource settings untrained ‘workers’ may substitute for trained nurses and without appropriate basic skills, may contribute to sub-standard care. RCPCH Global Links Mentors (GLMs) partner with local teams, developing quality improvement (QI) initiatives in low-income district hospitals. Faced with widespread workforce capacity constraints, GLMs have explored upskilling ‘workers’ as a viable option. Clinical checklists provide structure and routine, supporting basic patient observations, and are correlated with improved care quality. However, their potential for upskilling untrained staff is not understood. Aim We proposed a QI initiative whereby a clinical checklist could be instituted, improving communication and adherence to routine observations – critically at night, when trained staff were unavailable – and increasing patient safety awareness. Method An ‘essential clinical duties checklist’ was developed prioritising common safety themes. Staff received training covering vital-signs (VS) recording, cannula and orogastric-tube assessment and essential equipment checks. Neonatal records were scrutinised for accuracy and completeness. A Likert-scale scoring for NICU staff (3 nurses, 4 workers) was used to assess capabilities in communication, confidence with neonatal assessment and understanding of patient safety. Results Data were collected at baseline, two and eight-weeks post intervention; twenty-four and thirty-six twelve-hourly shifts were analysed. All 60 episodes had complete documentation of clinical duties. Potential risks identified included cannula patency, jaundice and nasogastric tube misplacement. There was notable improvement in VS documentation, from ad-hoc documentation pre-intervention to 100% having 6-hourly VS recorded. All staff strongly agreed that team communication improved. Staff reported improved understanding of safety issues (57% strongly agree). Unanticipated benefits were noted; staff unanimously reported increased confidence with neonatal assessment, interest in learning about neonatal care and improved confidence with teaching parents’ danger signs (100% strongly agreed). Conclusions Despite small sample size, introduction of a clinical checklist accompanied by relevant training was associated with improved documentation and communication in a low-resource NICU. Unanticipated benefits to untrained workers were noted suggesting that simple initiatives to upskill workers could be a cost-effective approach to managing poor workforce capacity. This critical observation is pertinent to widespread skilled staff shortages, and the search for appropriate QI strategies. Further research is needed to understand impact on patient outcomes and wider applicability of this initiative.

In an important and provocative paper Christopher Freiman recently has defended the view that vote-buying should be legal in democratic societies. Freiman offers four arguments in support of this claim: that vote buying would be ex ante beneficial to both the buyers and sellers of votes; that voters enjoy wide discretion in how they use their votes, and so this should extend to selling them; that vote markets would lead to electoral outcomes that better reflect voters’ preferences; and that vote-buying is relevantly similar to other democratic practices that are currently legal, such as logrolling and earmarking. In this paper I will address the last of Freiman’s arguments. I will argue that there are significant disanalogies between vote buying and both logrolling and earmarking, and that these differences justify the legal prohibition of the former practice while legally permitting the latter two.

Objectives To describe the impact of a faculty development program on faculty's confidence and ability to facilitate interprofessional learning. Methods Faculty members from the Colleges of Pharmacy and Health Sciences (n = 12) participated in a training program for interprofessional education (IPE). Students evaluated faculty learners using the interprofessional facilitation skills (IPFS) survey by Sargeant, Hill, and Breau (2010). Faculty completed the IPFS survey pre and post intervention for self-assessment of interprofessional facilitation efficacy. Results Most faculty (78%) had limited prior IPE experience; 55% went on to facilitate the University's year-long interprofessional core curriculum. Faculty IPFS self-assessment scores improved following program completion ( p p Conclusions This program effectively prepared faculty to facilitate IPE and positively impacted their desire to participate in future activities.

Objective. To determine the ability of first-year Doctor of Pharmacy (PharmD) students to describe patient care activities performed by pharmacists and accurately associate those activities with the five core steps of the Pharmacists’ Patient Care Process (PPCP). Methods. First-year student pharmacists completed introductory practice experiences at ambulatory and institutional pharmacies. Students’ ability to describe activities that occurred in these settings and align them with the five core steps (collect, assess, plan, implement, and follow-up) of the PPCP were assessed. Results. The students were more adept in describing patient care activities and aligning them to the appropriate PPCP steps in an ambulatory pharmacy setting than in an institutional pharmacy setting. Students achieved higher scores when describing and aligning patient care activities associated with the collect and implement steps in an ambulatory pharmacy setting and for the assess step in an institutional pharmacy setting. Conclusion. As institutions strive to adopt the PPCP in all areas of the curriculum, this application serves as an example of successful PPCP integration early in the introductory experiential curriculum. Our results challenge faculty to provide early opportunities for students to apply the PPCP in a variety of practice settings, including settings focused on the medication distribution system.

Aims To assess the impact of a national programme in paediatric secondary care, to introduce ETAT protocols and train nursing staff to lead emergency management. Methods Within a wider strategy to reduce child mortality, the Sierra Leone Ministry of Health and Sanitation engaged WHO and RCPCH to introduce WHO Emergency Triage Assessment and Treatment (ETAT) protocols to all district hospitals. Two clinical mentors (one Sierra Leonean, one UK/international) were placed at each hospital for six months, and delivered a three-month teaching programme with a written and practical examination, as well as hands-on clinical mentorship. Upon passing the examination, nurses were awarded the right to assess, prescribe for, and treat emergency paediatric cases. The mentors collected treatment data each day on children admitted the previous day, and followed each child to record their discharge outcome. This programme monitoring data was analysed to identify compliance with clinical protocols, and to calculate mortality rates. The programme delivery period was split into seven four-week blocks, and compliance rates and mortality rates were calculated for each four-week period. Results We analysed monitoring data from three regional hospitals in the first phase of roll-out (table 1). The combined mortality rate across the three hospitals fell from 15% in the first four-week period, to 4% in the final period. This fall was accompanied by improvements in key areas of compliance with WHO ETAT standards. Conclusion This study suggests that implementation of ETAT protocols and delivery of improved quality of care and decreased mortality may be achievable with an effective and cost-efficient nurse-led model for emergency paediatric care in low-resource settings.

Introduction State pharmacy association membership levels have remained stagnant in recent years despite active student organization involvement among student pharmacists and an increased number of pharmacy schools producing new pharmacy graduates in the United States. The objective of this project was to examine factors considered by recent pharmacy graduates when deciding to join state pharmacy associations. Methods A 16-item cross sectional survey of recent pharmacy graduates collected respondents’ demographic profile, professional student organization involvement, association memberships, and membership decision factors. Results The most influential factors in membership decisions included continuing education (62.8%), opportunity to advance pharmacy practice (51.1%), email updates (39.4%), and networking opportunities (37.2%). State pharmacy association meeting attendance (p = 0.004 and p = 0.028 for the Kentucky Society of Health-System Pharmacists and the Kentucky Pharmacists Association respectively), student organization membership (p = 0.038), committee service (p = 0.025), and state association board participation (p = 0.021) during pharmacy education increases the likelihood of membership in state associations. Conclusions Early engagement in state pharmacy associations during pharmacy school improves the likelihood of new practitioner membership. Pharmacy schools should engage with state association leaders to promote student committee participation, association board participation, and attendance at state meetings to ensure the continued success of state pharmacy associations.

Despite recent advances in the understanding of ethanol's biological action, many of the molecular targets of ethanol and mechanisms behind ethanol's effect on behavior remain poorly understood. In an effort to identify novel genes, the products of which regulate behavioral responses to ethanol, we recently identified a mutation in the dtao gene that confers resistance to the locomotor stimulating effect of ethanol in Drosophila. dtao encodes a member of the Ste20 family of serine/threonine kinases implicated in MAP kinase signaling pathways. In this study, we report that conditional ablation of the mouse dtao homolog, Taok2, constitutively and specifically in the nervous system, results in strain-specific and overlapping alterations in ethanol-dependent behaviors. These data suggest a functional conservation of dtao and Taok2 in mediating ethanol's biological action and identify Taok2 as a putative candidate gene for ethanol use disorders in humans.

Purpose Many classroom educational assistants (EAs) have a significant amount of responsibility in carrying out educational plans for children who use augmentative and alternative communication (AAC), but they receive little instruction on how to do so (Kent-Walsh & Light, 2003). This study investigates the impact of using a communication partner instructional program to teach EAs how to teach their students to produce symbol combinations on their speech-generating devices. Method A single-subject multiple-probe-across-participants design was used to evaluate the effectiveness of the instructional program on (a) the EAs' implementation of an interaction strategy with their students who used AAC and (b) the rates of multisymbol message productions for the students who used AAC. Results All 3 participating EAs learned to use the interaction strategy appropriately, and all 3 participating students who used AAC increased their multisymbol message production rates. Conclusions Results provide further evidence (a) of the viability of using a communication partner instructional program for teaching partners how to facilitate the communication skills of children who use AAC and (b) that the interaction strategy can be an effective tool for increasing expressive multisymbol message rates for children who use AAC.

A preferred format to deliver interprofessional education (IPE) has not been described. The aim of this study was to compare students' (N = 150) perceived value and improvement in communication between an IPE activity delivered using a comprehensive versus an abbreviated format. Although both formats were perceived by students to improve their communication skills and add value to their education, students indicated the abbreviated format was more effective than the comprehensive format.

Few interprofessional education (IPE) models include patients and caregivers. To address this, we developed a novel model for teaching IP communication which included patients and caregivers as team members. We describe the model and our use of it in several health professions education curricula. We report preliminary data from learners regarding their experiences learning and utilizing the model as part of their IPE. Overall the model was positively viewed by students, although the perceived value of learning activities involving the model varied by discipline. Physical therapy, nursing, and pharmacy students valued the IPE model most, whereas medical students valued it the least. Received: 05/04/2015 Accepted: 08/21/2015 Published: 10/01/2015 © 2015 Conigliaro et al. This open access article is distributed under a Creative Commons Attribution License, which allows unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. H IP & Application and Student Perceptions of the PEEER© Model EDUCATIONAL STRATEGY 2(3):eP1079 | 2 Introduction In their report Crossing the Quality Chasm, the Institute of Medicine (Institute of Medicine Committee on Quality Health Care in America, 2001) identified the development of effective patient-centered teams as one of the re-design imperatives to achieve safe, effective, efficient, personalized, timely, and equitable care. The Core Competencies for Interprofessional Collaborative Practice sponsored by the Interprofessional Educational Collaborative (Interprofessional Education Collaborative Expert Panel, 2011) has refocused healthcare education’s attention on interprofessional education (IPE) and practice. As a result, many health professional training programs are developing curricula to improve the quantity and quality of interprofessional (IP) experiences (Aston et al., 2012; McNair, 2005), including training in IP communication and teamwork. Healthcare teams are complex, with multiple shared responsibilities in the provision of patient care, including creating team structure, ensuring professionalism, practicing flexibility, achieving conflict management, promoting trust and respect, and ensuring interand intra-team communication (Firth-Cozens, 2001; Hobgood et al., 2010). IP healthcare teams, which include members of different healthcare professions, must have shared goals focused on patients’ needs to provide effective health care. Accomplishing these goals may be particularly challenging when IP healthcare teams are composed of professionals with little prior experience working with team members from different disciplines (Barr, Hammick, Koppel & Reeves, 1999), as is often the case. Functioning effectively within an IP healthcare team may require individuals to develop skills beyond their traditional specialty training and education (Nembhard & Edmondson, 2006; Wanzer, Wojtaszczyk & Kelly, 2009). Effective communication among these IP team members is critical to the realization of team goals for safe, high-quality patient care. Our early experiences with IPE activities involving IP teams of students interacting with standardized patients revealed that students’ ability to form functional teams and communicate with each other was not intuitive. To address this and improve our educational process we identified existing models for communication among healthcare professionals (Apker, Propp, Zabava Ford, & Hofmeister, 2006; Boaro, Fancott, Baker, Velji & Andreoli, 2010; Ellingson, 2003; Wanzer et al., 2009), yet found little guidance for models of communication among IP healthcare teams which included patients as team members. Given the increasing emphasis on patient-centered care in many aspects of health care delivery, we believe that IPE should specifically address the inclusion of patients as part of the IP team. We therefore developed a schematic for IP team communication that stressed purposefully working together with each other as well as with the patient and their caregiver(s). In this context, “team” denotes the patient, caregiver, and all healthcare providers; caregiver is defined as anyone, family member or otherwise, who provides care and assistance, either personal or other care such as emotional or logistical support. Through literature review and iterative discussion, we identified five key skills essential for effective communication: 1) use of Plain Language understood by all team participants; 2) Engagement of all team members; 3) Empathy to convey an awareness of the experience of all team members; 4) Empowerment of each team member to actively participate; and 5) Respect for the experiences contributed by each team member. We named this the PEEER© model to allow easy recall of each skill and identified exemplar behaviors which demonstrate each skill (Conigliaro et al., 2013). The schematic representation of the PEEER© model (Figure 1, following page) includes all healthcare providers, patients, and caregivers and intentionally places all members as equal participants in the healthcare team communication process. It is built upon the foundational concept that all team members bring essential knowledge and skills to successful patient outcomes, stressing that effective team communication is both expressive and receptive. Of critical importance in the schematic is the non-hierarchical approach to valuing the contributions of each member of the team. Of additional importance is the flexibility of the model to be utilized with various pedagogical approaches. We present the PEEER© model’s use in health professions education, and report our preliminary results describing students experiences utilizing it.

Some clinicians advocate using metered-dose inhaler (MDI) spacers prepared from common household bottles. We evaluated the in vitro aerosol characteristics of fluticasone from the MDI alone and through spacers fashioned from 237-, 500-, 1000-, and 1500-mL polyethylene terephlate plastic cold drink bottles using a cascade impactor. Ten 110-microg actuations of fluticasone were sampled into the impactor during each of five runs with each configuration. The primary outcomes were the respirable dose (i.e., quantity aerosol 1.1-4.7 microm in size) and the quantity trapped in the oropharynx. The mean fluticasone respirable dose from the MDI alone (46.2 microg/actuation) was no different (p0.05) compared with the same MDI mated to any of the bottle spacers, regardless of volume. The mean quantity of fluticasone trapped in the oropharynx from the MDI alone (39.2 microg/actuation) was greater (p0.001) than the same MDI mated with any bottle spacer (range 1.5-3.5 microg/actuation). These data suggest that any of the bottle spacers tested would be an acceptable method to decrease the quantity of fluticasone that would deposit onto the oropharynx and thereby diminish the risk of topical adverse effects. Among the range of volumes tested, there was no relationship between spacer volume and respirable dose of fluticasone.

The assembly of lipoprotein(a) (Lp(a)) involves an initial noncovalent interaction between apolipoprotein (apo) B100 and apo(a), followed by the formation of a disulfide bond between apoB100 cysteine 4326 and apo(a) cysteine 4057. The structural features of apoB100 that are required for its noncovalent interaction with apo(a) have not been fully defined. To analyze that initial interaction, we tested whether apo(a) could bind noncovalently to two apoB proteins that lack cysteine 4326: mouse apoB100 and human apoB100-C4326G. Our experiments demonstrated that both mouse apoB and the human apoB100-C4326G bind noncovalently to apo(a). We next sought to gain insights into the apoB amino acid sequences required for the interaction between apoB100 and apo(a). Previous studies of truncated human apoB proteins indicated that the carboxyl terminus of human apoB100 (amino acids 4330-4397) is important for Lp(a) assembly. To determine whether the carboxyl terminus of mouse apoB100 can interact with apo(a), transgenic mice were produced with a mutant human apoB gene construct in which human apoB100 amino acids 4279-4536 were replaced with the corresponding mouse apoB100 sequences and tyrosine 4326 was changed to a cysteine. The mutant apoB100 bound to apo(a) and formed bona fide disulfide-linked Lp(a), but Lp(a) assembly was less efficient than with wild-type human apoB100. The fact that Lp(a) assembly was less efficient with the mouse apoB sequences provides additional support for the notion that sequences in the carboxyl terminus of apoB100 are important for Lp(a) assembly.

Prior studies have established that the expression of the human apolipoprotein B (apoB) gene in the intestine is dependent on DNA sequences located a great distance from the structural gene. To identify the location of those sequences, we usedrecA-assisted restriction endonuclease (RARE) cleavage to truncate the 5′- or 3′-flanking sequences from a 145-kilobase (kb) bacterial artificial chromosome spanning the entire human apoB gene. Seven RARE cleavage– modified bacterial artificial chromosomes with different lengths of flanking sequences were used to generate transgenic mice. An analysis of those mice revealed that as little as 1.5 kb of 3′ sequences or 5 kb of 5′ sequences were sufficient to confer apoB expression in the liver. In contrast, apoB gene expression in the intestine required DNA sequences 54–62 kb 5′ to the structural gene. Those sequences retained their ability to direct apoB expression in the intestine when they were moved closer to the gene. These studies demonstrate that the intestinal expression of the apoB gene is dependent on DNA sequences located an extraordinary distance from the structural gene and that the RARE cleavage/transgenic expression strategy is a powerful approach for analyzing distant gene-regulatory sequences.

We show that the liver-specific expression of all four genes in the human apolipoprotein (apo) E/C-I/C-IV/C-II gene cluster in transgenic mice is determined by the coordinate action of two distinct hepatic control regions (HCR). These enhancers are positioned 15 kilobases (kb) (HCR.1) and 26 kb (HCR.2) downstream of the apoE gene. To investigate the action of each HCR, transgenic mice were generated with a 70-kb human genomic fragment that contained the complete apoE gene cluster or with this fragment modified by the specific deletion of HCR.1, HCR.2, or both HCR domains. Hepatic expression of all four apolipoprotein genes was observed in transgenic mice in which either HCR.1 or HCR.2 was deleted, but no transgene expression was found in the liver in the absence of both HCR domains. The overall patterns of transgene expression suggested that HCR.2 was the dominant element for apoC-IV and apoC-II expression and that HCR.1 was dominant for the apoE/C-I expression. No liver-specific transcriptional activity was identified for the proximal promoter of any gene in the cluster; all liver-specific activity was associated with HCR.1 and HCR.2. Thus, the HCRs of the apoE gene cluster constitute unique regulatory domains for determining the requirements for apolipoprotein gene expression in the liver.

The structural features of apolipoprotein (apo) B that are important for its covalent linkage to apo(a) to form lipoprotein(a) (Lp(a)) are incompletely understood. Although apoB100 cysteine 4326 is required for the disulfide linkage with apo(a), other structural features, aside from a single free cysteine residue, must be important for apoB’s initial interaction with apo(a) and for facilitating the formation of the disulfide bond. To determine if sequences carboxyl-terminal to cysteine 4326 affect the efficiency of Lp(a) formation, we used “pop-in, pop-out” gene targeting in a human apoB yeast artificial chromosome to introduce nonsense mutations into exon 29 of the apoB gene. The mutant yeast artificial chromosomes, which coded for the truncated versions of human apoB, apoB95, and apoB97, were then used to express these mutant forms of apoB in transgenic mice. As judged by in vitro assays of Lp(a) formation, apoB95 (4330 amino acids) formed a small amount of Lp(a) but did so slowly. In contrast, apoB97 (4397 amino acids) formed Lp(a) rapidly, although not quite as rapidly as the full-length apoB100 (4536 amino acids). These results were supported by an analysis of double-transgenic mice expressing both human apo(a) and either apoB95 or apoB97. In mice expressing both apoB95 and apo(a), there was only a trace amount of Lp(a) in the plasma, and most of the apo(a) was free, whereas in mice expressing both apoB97 and apo(a), virtually all of the apo(a) was bound to apoB97 in the form of Lp(a). These results show that sequences carboxyl-terminal to apoB95 (amino acids 4331–4536) are not absolutely required for Lp(a) formation, but this segment of the apoB molecule, particularly residues 4331–4397, is necessary for the efficient assembly of Lp(a).

Introduction This resource exposes learners to the challenges involved in effectively communicating within interprofessional teams and between teams, patients and caregivers, and provides learners with a template for overcoming these challenges and optimizing communication. The PEEER (Plain Language, Engagement, Empathy, Empowerment, Respect) model is a new model, grounded in communication and patient safety literature, to teach interprofessional (IP) communication to professionals who will be working in IP teams, and in IP teams with patients and caregivers. Methods The resource contains three sets of video clips demonstrating good and bad IP communication skills between health professionals and between health professionals and patients/caregivers. Accompanying these videos are worksheets for learners to critique the videos, and facilitator worksheets with prompts to help lead discussion about the good and bad communication skills demonstrated. Finally, the resource contains a learner postassessment which reflects how well they grasped the model components and concepts, and an evaluation of the process. Additional readings with extensive references are also provided. Results The PEEER model was incorporated into an existing interprofessional education (IPE) activity with health profession students in either their second year of the doctor of medicine (MD) program, third year of the doctor of pharmacy (PharmD) program, or fourth year of the bachelor of science in nursing (BSN) program. The evaluation of the IPE activity was sent to all student participants (119 MD, 124 PharmD, 78 BSN students) and completed surveys were received from 273 of 321 participants (91% MD student response rate, 94% PharmD response rate, 62% BSN response rate). Over 70% of the BSN and PharmD students, and 58% of MD, students agreed or strongly agreed that the PEEER model activity was a valuable education activity. Discussion The PEEER model can be tailored to complement any curriculum for all levels of learners in any of the health care disciplines. In addition, the PEEER model utilizes communication concepts familiar to most learners and educators, is grounded in the communications literature, and applies those concepts for use in a clinical setting where teams commonly function. The model is easily integrated into either simulated practice (such as in a course) or actual clinical experiences (either inpatient or outpatient situations) and can provide opportunities for the practice and improvement of interprofessional team skills.

The specificity of expression in the liver of the human apolipoprotein (apo) E/C-I gene locus is determined by a hepatic control region (HCR) that is located 15 kilobases downstream of the apoE gene. DNase I footprint studies of this sequence using nuclear extracts identified a region of the HCR that is enriched in nuclear protein-binding sites. Nuclease analysis of chromatin revealed liver-specific DNase I-hypersensitive sites that were associated with this region, and additional liver-specific nuclease-sensitive sites associated with the apoE gene were identified. The HCR domain has a limited binding affinity for the nuclear scaffold. The specific domain required for liver expression was tested by ligating subfragments of the HCR to the apoE gene and examining their activity in transgenic mice. A segment of 319 nucleotides that contained several potential regulatory sequences was required for full activity of liver-specific transcription with shorter segments yielding much lower levels of expression in the liver. All constructs that contained a fully active HCR were expressed in approximately a copy-dependent manner, suggesting that transgene expression was independent of integration position. Taken together, the properties of the HCR are consistent with its function as a locus control region for the liver-specific expression of the apoE gene.

Rat hepatoma McA-RH7777 cell lines transfected with full-length human apolipoprotein (apo) B constructs produce mostly human apoB48 and only small amounts of apoB100, as a result of mRNA editing at codon 2153 (C to U conversion at nucleotide 6666). To abolish the formation of apoB48 and increase the yield of apoB100 and other forms of apoB longer than apoB48, site-specific mutations were introduced at or near the site of apoB mRNA editing. Among four mutations examined, only that in which codon 2153 was converted from CAA (Gln) to CTA (Leu) effectively precluded the formation of apoB48. In this mutant, a stop codon would not be generated even if the C to U conversion occurred. The three other mutations were introduced to disrupt the proposed stem-loop structure encompassing the editing site. Changes made in the third positions of five codons on the 5' side of the edited base or of four codons 3' of the edited base failed to eliminate the production of a protein with the approximate size of apoB48. A construct in which codon 2153 was changed from CAA to GAT (Asp) also failed to eliminate the production of a protein the size of apoB48. Analysis of the region between nucleotides 6200 and 6900 of the cDNA did not detect any prevalent alternate editing sites. Immunoblot analysis using polyclonal antibodies raised against synthetic peptides of human apoB100 indicated that the carboxyl terminus of the apoB48-like proteins probably resides between amino acid residues 2068 and 2129 of apoB100. These results provide some insight into the mechanism of apoB mRNA editing and will facilitate further studies on apoB-containing lipoproteins.

Precise regulation of Wnt signaling is important in many contexts, as in development of the vertebrate forebrain, where excessive or ectopic Wnt signaling leads to severe brain defects. Mutation of the widely expressed oto gene causes loss of the anterior forebrain during mouse embryogenesis. Here we report that oto is the mouse ortholog of the gpi deacylase gene pgap1, and that the endoplasmic reticulum (ER)-resident Oto protein has a novel and deacylase-independent function during Wnt maturation. Oto increases the hydrophobicities of Wnt3a and Wnt1 by promoting the addition of glycophosphatidylinositol (gpi)-like anchors to these Wnts, which results in their retention in the ER. We also report that oto-deficient embryos exhibit prematurely robust Wnt activity in the Wnt1 domain of the early neural plate. We examine the effect of low oto expression on Wnt1 in vitro by knocking down endogenous oto expression in 293 and M14 melanoma cells using shRNA. Knockdown of oto results in increased Wnt1 secretion which is correlated with greatly enhanced canonical Wnt activity. These data indicate that oto deficiency increases Wnt signaling in vivo and in vitro. Finally, we address the mechanism of Oto-mediated Wnt retention under oto-abundant conditions, by cotransfecting Wnt1 with gpi-specific phospholipase D (GPI-PLD). The presence of GPI-PLD in the secretory pathway results in increased secretion of soluble Wnt1, suggesting that the gpi-like anchor lipids on Wnt1 mediate its retention in the ER. These data now provide a mechanistic framework for understanding the forebrain defects in oto mice, and support a role for Oto-mediated Wnt regulation during early brain development. Our work highlights a critical role for ER retention in regulating Wnt signaling in the mouse embryo, and gives insight into the notoriously inefficient secretion of Wnts.

We examined the relationship between the size of human apolipoprotein (apo) B and the formation and secretion of apoB-containing lipoprotein particles. Stable transformants of the rat hepatoma cell line McA-RH7777 harboring a variety of human apoB cDNA constructs were established, and these produced carboxyl-terminally truncated apoB proteins (apoB18, -B23, -B28, -B31, -B48, and -B53). Immunoblotting of apoB proteins secreted into the culture medium and fractionated by equilibrium density ultracentrifugation revealed that each of the truncated apoB species was secreted from the cells. The peak densities of the apoB-containing particles decreased as the length of the apoB proteins increased. Apolipoproteins B18 and B23 appeared at the bottom of the salt gradient (d = 1.23 g/ml), whereas particles containing apoB28, -B31, -B37, -B48, and -B53 exhibited progressive decreases in density. The density distribution of secreted apolipoproteins was not affected by the expression or secretion of these recombinant apoB species. As determined by nondenaturing gel electrophoresis, apoB28, -B31, -B37, -B48, and -B53 formed their own discrete particles, and there was a direct correlation between the size of the particles and the length of the apoB species. The efficiency and rate of secretion of these truncated forms of apoB were studied by measuring the decrease of immunoprecipitated 35S-labeled apoB proteins in the cells and their accumulation in the medium. Proteins corresponding to apoB28 or larger were rapidly and efficiently secreted, whereas apoB18 and apoB23 were secreted much more slowly. These data imply that the size of these truncated apoB forms governs the lipid content of the apoB-containing lipoproteins formed as well as the kinetics of secretion.

Augmentative and alternative communication (AAC) service provision can be time-consuming, and it is important to ensure that the time invested in aided AAC interventions is worth the costs. As children who use AAC are multimodal communicators, it is important to understand the effects that aided AAC interventions may have not only on AAC use but also on other communication modes, including speech and symbolic gestures. Toward these ends, this article contains a review of commonly used AAC intervention techniques, a discussion of how use of these techniques affects aided AAC use, and an examination of the effect that AAC interventions have on other communication modes, including speech and various types of gestures. Overall, current research findings indicate that aided AAC interventions can be highly effective for teaching students who use AAC to become more effective communicators and that such interventions do not have a negative effect on speech-and may, in some cases, have a positive effect on speech.

Dispersal can influence population dynamics, species distributions, and community assembly, but few studies have attempted to determine the factors that affect dispersal of insects in natural populations. Consequently, little is known about how proximate factors affect the dispersal behavior of individuals or populations, or how an organism's behavior may change in light of such factors. Adult predaceous diving beetles are active dispersers and are important predators in isolated aquatic habitats. We conducted interrelated studies to determine how several factors affected dispersal in two common pond-inhabiting species in southern Alberta, Canada: Graphoderus occidentalis and Rhantus sericans. Specifically, we (1) experimentally tested the effect of plant and beetle densities on dispersal probabilities in ponds; (2) surveyed ponds and determined the relationships among beetle densities and plant densities and water depth; and (3) conducted laboratory trials to determine how beetle behavior changed in response to variation in plant densities, conspecific densities, food, and water depth. Our field experiment determined that both species exhibited density dependence, with higher beetle densities leading to higher dispersal probabilities. Low plant density also appeared to increase beetle dispersal. Consistent with our experimental results, densities of R. sericans in ponds were significantly related to plant density and varied also with water depth; G. occidentalis densities did not vary with either factor. In the laboratory, behavior varied with plant density only for R. sericans, which swam at low density but were sedentary at high density. Both species responded to depth, with high beetle densities eliciting beetles to spend more time in deeper water. The presence of food caused opposite responses for G. occidentalis between experiments. Behavioral changes in response to patch-level heterogeneity likely influence dispersal in natural populations and are expected to be important for observed patterns of individuals in nature.

Over-the-counter herbal and alternative medicines are classified as dietary supplements and, unlike drugs, are not rigorously regulated by the United States Food and Drug Administration. Their potential adverse effects are often poorly characterized. Red clover, dong quai, and Siberian ginseng are herbal compounds used for treatment of perimenopausal symptoms such as hot flashes. These compounds are known to contain coumarins, and thus carry the potential for hemorrhagic complications; however, no cases of intracranial hemorrhage have been reported. We report a 53-year-old woman with spontaneous subarachnoid hemorrhage due to the use of an herbal supplement containing red clover, dong quai, and Siberian ginseng.

Lipoprotein(a) [Lp(a)] is a lipoprotein formed by the disulfide linkage of apolipoprotein (apo) B100 of a low density lipoprotein particle to apolipoprotein(a). Prior studies have suggested that one of the C-terminal Cys residues of apo-B100 is involved in the disulfide linkage of apo-B100 to apo(a). To identify the apo-B100 Cys residue involved in the formation of Lp(a), we constructed a yeast artificial chromosome (YAC) spanning the human apo-B gene and used gene-targeting techniques to change Cys-4326 to Gly. The mutated YAC DNA was used to generate transgenic mice expressing the mutant human apo-B100 (Cys4326Gly). Unlike the wild-type human apo-B100, the mutant human apo-B100 completely lacked the ability to bind to apo(a) and form Lp(a). This study demonstrates that apo-B100 Cys-4326 is required for the assembly of Lp(a) and shows that gene targeting in YACs, followed by the generation of transgenic mice, is a useful approach for analyzing the structure of large proteins coded for by large genes.

Apolipoprotein (apo-) B mRNA editing is the deamination of cytidine that creates a new termination codon and produces a truncated version of apo-B (apo-B48). The cytidine deaminase catalytic subunit [apo-B mRNA-editing enzyme catalytic polypeptide 1 (APOBEC-1)] of the multiprotein editing complex has been identified. We generated transgenic rabbits and mice expressing rabbit APOBEC-1 in their livers to determine whether hepatic expression would lower low density lipoprotein cholesterol concentrations. The apo-B mRNA from the livers of the transgenic mice and rabbit was extensively edited, and the transgenic animals had reduced concentrations of apo-B100 and low density lipoproteins compared with control animals. Unexpectedly, all of the transgenic mice and a transgenic rabbit had liver dysplasia, and many transgenic mice developed hepatocellular carcinomas. Many of the mouse livers were hyperplastic and filled with lipid. Other hepatic mRNAs with sequence motifs similar to apo-B mRNA were examined for this type of editing (i.e., cytidine deamination). One of these, tyrosine kinase, was edited in livers of transgenic mice but not of controls. This result demonstrates that other mRNAs can be edited by the overexpressed editing enzyme and suggests that aberrant editing of hepatic mRNAs involved in cell growth and regulation is the cause of the tumorigenesis. Finally, these findings compromise the potential use of APOBEC-1 for gene therapy to lower plasma levels of low density lipoproteins.

Transgenic mice that express human apolipoprotein (apo)B have been developed by microinjecting fertilized mouse oocytes with an 80 kb genomic DNA fragment that encompasses the entire human APOB gene. In the transgenic mice expressing the largest amounts of human apoB, the concentration of human apoB100 in the plasma is nearly as high as the levels observed in normolipidemic humans (50 mg/dl). Virtually all of the human apoB100 in the transgenic plasma is located in the LDL fraction, resulting in substantially increased levels of LDL cholesterol. These human apoB-transgenic mice should be useful animal models for understanding various aspects of lipoprotein metabolism and for further delineating the role of LDL in atherogenesis.

Chronic pain remains one of the most widespread and under treated medical conditions. Opioid drugs, such as morphine, are some of the most effective analgesics available. However, their utility for the treatment of chronic pain are limited by side effects including tolerance and dependence. Morphine induces its biological actions primarily through the G-protein coupled mu-opioid peptide receptor (MOP-R) [1], which is also the target of the endogenous opioids. However, unlike endogenous MOP-R ligands, morphine fails to promote substantial endocytosis of the MOP-R both in vitro [2–5] and in vivo [6–11]. Endocytosis of the MOP-R serves at least two important functions in regulating signal transduction. First, desensitization and endocytosis act as an “OFF” switch by uncoupling receptors from their cognate G protein. Second, endocytosis and receptor recycling serve as an “ON” switch, resensitizing receptors by recycling them to the plasma membrane where agonist can regain access to the receptors. Thus, due to poor endocytosis, both the OFF and ON function of the MOP-R are altered in response to morphine compared to endogenous ligands. To examine whether poor endocytosis contributes to morphine tolerance and dependence, we generated a knock-in mouse that expresses a mutant MOP-R that undergoes rapid endocytosis in response to morphine. Morphine remains an excellent antinociceptive agent in these mice. In addition, the mutant mice display substantially reduced antinociceptive tolerance and attenuated physical dependence. These data suggest that opioid drugs with pharmacological profile of morphine and the ability to promote endocytosis of the receptor could provide analgesia while having a reduced liability for the side effects of tolerance and dependence.