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1.  Therapeutic targeting of regulatory T cells enhances tumor-specific CD8+ T cell responses in Epstein–Barr virus associated nasopharyngeal carcinoma 
Virology  2013;441(2):107-113.
Epstein–Barr virus (EBV) is associated with multiple malignancies including nasopharyngeal carcinoma (NPC). In nasopharynx cancer, CD8+ T cells specific for EBV Nuclear Antigen-1 (EBNA-1) and Latent Membrane Protein 2 (LMP2) are important components of anti-tumor immunity since both are consistently expressed in NPC. We have previously shown that EBNA-1-specific CD8+ T cell responses were suppressed in NPC patients compared to healthy controls. We now find that CD8+ T cell responses specific for LMP2 are also abnormal in NPC patients, and both EBNA-1- and LMP2-specific responses are suppressed by regulatory T cells (Treg). EBNA-1 and LMP2-specific CD8+ T cell responses, as well as immune control of EBV-infected cells in vitro, could be restored by the depletion of Tregs and by use of a clinically approved drug targeting Tregs. Thus, in vivo modulation of Tregs may be an effective means of enhancing these anti-tumor immune responses in NPC patients.
doi:10.1016/j.virol.2013.03.016
PMCID: PMC3782090  PMID: 23601786
Epstein–Barr virus; Nasopharyngeal carcinoma; CD8+ T cells; T regulatory cells; Ontak
2.  Understanding the Etiology of Prescription Opioid Abuse: Implications for Prevention and Treatment 
Qualitative health research  2013;23(7):963-975.
Although studies on the initiation of substance abuse abound, the body of literature on prescription opioid abuse (POA) etiology is small. Little is known about why and how the onset of POA occurs, especially among high-risk populations. In this study we aimed to fill this important knowledge gap by exploring the POA initiation experiences of 90 prescription opioid abusers currently in treatment and their narrative accounts of the circumstances surrounding their POA onset. This research was conducted within a storyline framework, which operates on the premise that the path to drug abuse represents a biography or a process rather than a static condition. Audiotapes of in-depth interviews were transcribed, coded, and thematically analyzed. Analyses revealed the presence of four trajectories leading to POA. This study adds to the limited research on POA etiology by not only illuminating the psychosocial factors that contribute to POA onset, but also by situating initiation experiences within broader life processes. The study findings provide crucial insights to policymakers and interventionists in identifying who is at risk for POA, and more important, when and how to intervene most efficaciously.
doi:10.1177/1049732313488837
PMCID: PMC3680787  PMID: 23656723
addiction/substance use; illness and disease, prevention; interviews, semistructured; mental health and illness; psychosocial issues; social constructionism; sociology
3.  Synthesis of Antioxidants for Prevention of Age-related Macular Degeneration.# 
Journal of natural products  2013;76(3):450-454.
Photooxidation of A2E may be involved in diseases of the macula and antioxidants could serve as therapeutic agents for these diseases. Inhibitors of A2E photooxidation were prepared by Mannich reaction of the antioxidants quercetin and sesamol. These compounds contain water-solubilizing amine groups and several were more potent inhibitors of A2E photooxidation than quercetin.
doi:10.1021/np300769c
PMCID: PMC4069254  PMID: 23346866
4.  Epidemiology of injuries in hurling: a prospective study 2007–2011 
BMJ Open  2014;4(6):e005059.
Objectives
Hurling is a stick handling game which, although native to Ireland, has international reach and presence. The aim of this study was to report incidence and type of injuries incurred by elite male hurling players over five consecutive playing seasons.
Design
Prospective cohort study.
Setting
Male intercounty elite sports teams participating in the National GAA Injury Database, 2007–2011.
Participants
A total of 856 players in 25 county teams were enrolled.
Primary and secondary outcomes
Incidence, nature and mechanism of injury were recorded by team physicians or physiotherapists to a secure online data collection portal. Time-loss injury rates per 1000 training and match play hours were calculated and injury proportions were expressed.
Results
In total 1030 injuries were registered, giving a rate of 1.2 injuries per player. These were sustained by 71% (n=608) of players. Injury incidence rate was 2.99 (95% CI 2.68 to 3.30) per 1000 training hours and 61.75 (56.75 to 66.75) per 1000 match hours. Direct player-to-player contact was recorded in 38.6% injuries, with sprinting (24.5%) and landing (13.7%) the next most commonly reported injury mechanisms. Median duration of time absent from training or games, where the player was able to return in the same season, was 12 days (range 2–127 days). The majority (68.3%) of injuries occurred in the lower limbs, with 18.6% in the upper limbs. The trunk and head/neck regions accounted for 8.6% and 4.1% injuries, respectively. The distribution of injury type was significantly different (p<0.001) between upper and lower extremities: fractures (upper 36.1%, lower 1.5%), muscle strain (upper 5.2%, lower 45.8%).
Conclusions
These data provide stable, multiannual data on injury patterns in hurling, identifying the most common injury problems. This is the first step in applying a systematic, theory-driven injury prevention model in the sport.
doi:10.1136/bmjopen-2014-005059
PMCID: PMC4067887  PMID: 24948748
Athletic Injuries; Sports Medicine; Epidemiology; Incidence
5.  GRP78(BiP) facilitates the cytosolic delivery of anthrax lethal factor (LF) in vivo and functions as an unfoldase in vitro 
Molecular microbiology  2011;81(5):1390-1401.
Summary
Anthrax toxin is an A/B bacterial protein toxin which is composed of the enzymatically active Lethal Factor (LF) and/or Oedema Factor (EF) bound to Protective Antigen 63 (PA63) which functions as both the receptor binding and transmembrane domains. Once the toxin binds to its cell surface receptors it is internalized into the cell and traffics through Rab5- and Rab7-associated endosomal vesicles. Following acidification of the vesicle lumen, PA63 undergoes a dynamic change forming a beta-barrel that inserts into and forms a pore through the endosomal membrane. It is widely recognized that LF, and the related fusion protein LFnDTA, must be completely denatured in order to transit through the PA63 formed pore and enter the eukaryotic cell cytosol. We demonstrate by protease protection assays that the molecular chaperone GRP78 mediates the unfolding of LFnDTA and LF at neutral pH and thereby converts these proteins from a trypsin resistant to sensitive conformation. We have used immuno-electron microscopy and gold-labeled antibodies to demonstrate that both GRP78 and GRP94 chaperones are present in the lumen of endosomal vesicles. Finally, we have used siRNA to demonstrate that knock down of GRP78 results in the emergence of resistance to anthrax lethal toxin and edema toxin action.
doi:10.1111/j.1365-2958.2011.07770.x
PMCID: PMC4041151  PMID: 21797942
unfoldase; anthrax toxin; siRNA; anthrax toxin entry
6.  Treerunners, cryptic lizards of the Plica plica group (Squamata, Sauria, Tropiduridae) of northern South America 
ZooKeys  2013;49-77.
The arboreal, Neotropical lizard Plica plica (Linnaeus, 1758) has been long considered a widespread species with a distribution east of the Andes. A preliminary examination of 101 specimens from about 28 locations mostly north of the Amazon suggests that Plica plica is a cryptic species complex with taxa that can be distinguished on the basis of the number of scale rows at mid-body; the arrangement, shape and ornamentation of scales on the snout; the number of lamellae on the fourth toe; the number of subocular plates; as well as other commonly used external morphological traits. The allopatric species discussed here are concordant with northern South American geography. Plica plica (Linnaeus, 1758) is associated with the Guiana Shield (Suriname, Guyana and Venezuela). A second species, P. caribeana sp. n. is associated with the Caribbean Coastal Range of Venezuela including Trinidad and Tobago. A third, distinctive species, P. rayi sp. n. is associated with the middle Orinoco at the eastern edge of the Guiana Shield. Two other species, P. kathleenae sp. n. and P. medemi sp. n., each based upon a single specimen, one from the Sierra Acarai Mountains of Guyana, and the other from southern Meta, Colombia are described. In addition to morphological analyses, we sequenced 12S and 16S rDNA gene fragments from one Plica plica from Trinidad to assess its relationship and taxonomy to other mainland Plica cf. plica. The results suggest Plica caribeana sp. n. likely diverged prior to the separation of Trinidad from northern Venezuela. Isolation in the Caribbean Coastal Range during its rapid uplift in the late Miocene, combined with a marine incursion into northern Venezuela may have contributed to their genetic divergence from other populations.
doi:10.3897/zookeys.355.5868
PMCID: PMC3867189  PMID: 24363569
Arboreal lizards; Iguania; Neotropics; new species; systematics
7.  Global Substrate Profiling of Proteases in Human Neutrophil Extracellular Traps Reveals Consensus Motif Predominantly Contributed by Elastase 
PLoS ONE  2013;8(9):e75141.
Neutrophil extracellular traps (NETs) consist of antimicrobial molecules embedded in a web of extracellular DNA. Formation of NETs is considered to be a defense mechanism utilized by neutrophils to ensnare and kill invading pathogens, and has been recently termed NETosis. Neutrophils can be stimulated to undergo NETosis ex vivo, and are predicted to contain high levels of serine proteases, such as neutrophil elastase (NE), cathepsin G (CG) and proteinase 3 (PR3). Serine proteases are important effectors of neutrophil-mediated immunity, which function directly by degrading pathogenic virulent factors and indirectly via proteolytic activation or deactivation of cytokines, chemokines and receptors. In this study, we utilized a diverse and unbiased peptide library to detect and profile protease activity associated with NETs induced by phorbol-12-myristate-13-acetate (PMA). We obtained a “proteolytic signature” from NETs derived from healthy donor neutrophils and used proteomics to assist in the identification of the source of this proteolytic activity. In addition, we profiled each neutrophil serine protease and included the newly identified enzyme, neutrophil serine protease 4 (NSP4). Each enzyme had overlapping yet distinct endopeptidase activities and often cleaved at unique sites within the same peptide substrate. The dominant proteolytic activity in NETs was attributed to NE; however, cleavage sites corresponding to CG and PR3 activity were evident. When NE was immunodepleted, the remaining activity was attributed to CG and to a lesser extent PR3 and NSP4. Our results suggest that blocking NE activity would abrogate the major protease activity associated with NETs. In addition, the newly identified substrate specificity signatures will guide the design of more specific probes and inhibitors that target NET-associated proteases.
doi:10.1371/journal.pone.0075141
PMCID: PMC3779220  PMID: 24073241
8.  Overturning Established Chemoselectivities: Selective Reduction of Arenes over Malonates and Cyanoacetates by Photoactivated Organic Electron Donors 
Journal of the American Chemical Society  2013;135(30):10934-10937.
The prevalence of metal-based reducing reagents, including metals, metal complexes, and metal salts, has produced an empirical order of reactivity that governs our approach to chemical synthesis. However, this reactivity may be influenced by stabilization of transition states, intermediates, and products through substrate–metal bonding. This article reports that in the absence of such stabilizing interactions, established chemoselectivities can be overthrown. Thus, photoactivation of the recently developed neutral organic superelectron donor 5 selectively reduces alkyl-substituted benzene rings in the presence of activated esters and nitriles, in direct contrast to metal-based reductions, opening a new perspective on reactivity. The altered outcomes arising from the organic electron donors are attributed to selective interactions between the neutral organic donors and the arene rings of the substrates.
doi:10.1021/ja4050168
PMCID: PMC3755536  PMID: 23859883
9.  ZFP36L1 Negatively Regulates Plasmacytoid Differentiation of BCL1 Cells by Targeting BLIMP1 mRNA 
PLoS ONE  2012;7(12):e52187.
The ZFP36/Tis11 family of zinc-finger proteins regulate cellular processes by binding to adenine uridine rich elements in the 3′ untranslated regions of various mRNAs and promoting their degradation. We show here that ZFP36L1 expression is largely extinguished during the transition from B cells to plasma cells, in a reciprocal pattern to that of ZFP36 and the plasma cell transcription factor, BLIMP1. Enforced expression of ZFP36L1 in the mouse BCL1 cell line blocked cytokine-induced differentiation while shRNA-mediated knock-down enhanced differentiation. Reconstruction of regulatory networks from microarray gene expression data using the ARACNe algorithm identified candidate mRNA targets for ZFP36L1 including BLIMP1. Genes that displayed down-regulation in plasma cells were significantly over-represented (P = <0.0001) in a set of previously validated ZFP36 targets suggesting that ZFP36L1 and ZFP36 target distinct sets of mRNAs during plasmacytoid differentiation. ShRNA-mediated knock-down of ZFP36L1 in BCL1 cells led to an increase in levels of BLIMP1 mRNA and protein, but not for mRNAs of other transcription factors that regulate plasmacytoid differentiation (xbp1, irf4, bcl6). Finally, ZFP36L1 significantly reduced the activity of a BLIMP1 3′ untranslated region-driven luciferase reporter. Taken together, these findings suggest that ZFP36L1 negatively regulates plasmacytoid differentiation, at least in part, by targeting the expression of BLIMP1.
doi:10.1371/journal.pone.0052187
PMCID: PMC3527407  PMID: 23284928
11.  Adhesive Performance of Biomimetic Adhesive-Coated Biologic Scaffolds 
Biomacromolecules  2010;11(11):2976-2984.
Surgical repair of a discontinuity in traumatized or degenerated soft tissues is traditionally accomplished using sutures. A current trend is to reinforce this primary repair with surgical grafts, meshes, or patches secured with perforating mechanical devices (i.e., sutures, staples, or tacks). These fixation methods frequently lead to chronic pain and mesh detachment. We developed a series of biodegradable adhesive polymers that are synthetic mimics of mussel adhesive proteins (MAPs), composed of 3,4-dihydroxyphenylalanine (DOPA)-derivatives, polyethylene glycol (PEG), and polycaprolactone (PCL). These polymers can be cast into films, and their mechanical properties, extent of swelling, and degradation rate can be tailored through the composition of the polymers as well as blending with additives. When coated onto a biologic mesh used for hernia repair, these adhesive constructs demonstrated adhesive strengths significantly higher than fibrin glue. With further development, a pre-coated bioadhesive mesh may represent a new surgical option for soft tissue repair.
doi:10.1021/bm1007794
PMCID: PMC3027843  PMID: 20919699
biomimetic material; tissue adhesive; surgical mesh; multiblock copolymer; DOPA
12.  Bilateral atypical insufficiency fractures of the proximal tibia and a unilateral distal femoral fracture associated with long-term intravenous bisphosphonate therapy: a case report 
Introduction
Atypical insufficiency fractures of the femur in patients on long-term bisphosphonate therapy have been well described in recent literature. The majority of cases are associated with minimal or no trauma and occur in the subtrochanteric or diaphyseal region.
Case presentation
We describe the case of a 76-year-old British Caucasian woman who presented initially to an emergency department and then to her primary care physician with a long-standing history of bilateral knee pain after minor trauma. Plain radiographs showed subtle linear areas of sclerosis bilaterally in her proximal tibiae. Magnetic resonance imaging confirmed the presence of insufficiency fractures in these areas along with her left distal femur. There are very few reports of atypical insufficiency fractures involving the tibia in patients on long-term bisphosphonate therapy and this appears to be the only documented bilateral case involving the metaphyseal regions of the proximal tibia and distal femur.
Conclusion
In addition to existing literature describing atypical fractures in the proximal femur and femoral shaft, there is a need for increased awareness that these fractures can also occur in other weight-bearing areas of the skeleton. All clinicians involved in the care of patients taking long-term bisphosphonates need to be aware of the growing association between new onset lower limb pain and atypical insufficiency fractures.
doi:10.1186/1752-1947-6-50
PMCID: PMC3292822  PMID: 22309438
13.  Biomechanical properties of Achilles tendon repair augmented with a bioadhesive-coated scaffold 
The Achilles tendon is the most frequently ruptured tendon. Both acute and chronic (neglected) tendon ruptures can dramatically affect a patient’s quality of life, and require a prolonged period of recovery before return to pre-injury activity levels. This paper describes the use of an adhesive-coated biologic scaffold to augment primary suture repair of transected Achilles tendons. The adhesive portion consisted of a synthetic mimic of mussel adhesive proteins that can adhere to various surfaces in a wet environment, including biologic tissues. When combined with biologic scaffolds such as bovine pericardium or porcine dermal tissues, these adhesive constructs demonstrated lap shear adhesive strengths significantly greater than that of fibrin glue, while reaching up to 60% of the strength of a cyanoacrylate-based adhesive. These adhesive constructs were wrapped around transected cadaveric porcine Achilles tendons repaired with a combination of parallel and three-loop suture patterns. Tensile mechanical testing of the augmented repairs exhibited significantly higher stiffness (22–34%), failure load (24–44%), and energy to failure (27–63%) when compared to control tendons with suture repair alone. Potential clinical implications of this novel adhesive biomaterial are discussed.
doi:10.1088/1748-6041/6/1/015014
PMCID: PMC3046464  PMID: 21266745
14.  Reflections on the Knife Edge 
The Oncologist  2011;16(2):257-259.
Introduction
The accompanying article, written by John Murphy, a retired lawyer and lifelong outdoorsman from his beloved Colorado Rockies, draws the striking parallel between his experiences as a mountain climber and as a patient with metastatic melanoma facing the hope and uncertainty of experimental therapy. Both are life-threatening circumstances, demanding courage and hope, and challenging our soul in a way almost unique to human experience. Both involve a conscious choice to move forward into dangerous and uncertain territory, and require a determination to look death (John's “Reaper”) in the eye. Many remarkable books and films have been written about such experiences. I recall in particular the 2003 documentary film Touching the Void, about the incredible survival of a mountaineer who returned from a perilous fall in Peru. I highly recommend it to the reader. Another is Laura Hillenbrand's Unbroken: A World War II Story of Survival, Resilience, and Redemption (Random House, 2010), about the survival of a prisoner of war, the celebrated miler Louis Zamperini. Again, unbridled courage and undeniable hope turned futility into future.
John Murphy's reflections remind us of the daily heroism of our patients who are holding tight to the lifeline offered by clinical research. Good climbing, John. All of us are with you on that Knife Edge, waiting for our turn to ascend... and hoping to be as courageous as you were then on Capitol Peak and are again now on the Knife Edge of a clinical trial. For our turn will come.
doi:10.1634/theoncologist.2011-0021
PMCID: PMC3228094  PMID: 21349953
15.  Nasu-Hakola Syndrome: An Unusual Cause of Pathological Fractures 
Case Reports in Orthopedics  2012;2012:817189.
Nasu-Hakola syndrome is a hereditary cause of pathological fractures. Uniquely, patients also develop neuropsychiatric symptoms and signs. The disease is ultimately fatal. We propose a management strategy for pathological fractures in sufferers based on the stage of the disease.
doi:10.1155/2012/817189
PMCID: PMC3505912  PMID: 23227394
16.  Marine Reptiles 
PLoS ONE  2011;6(11):e27373.
doi:10.1371/journal.pone.0027373
PMCID: PMC3210815  PMID: 22087300
17.  Characterisation and Deposition Studies of Recrystallised Lactose from Binary Mixtures of Ethanol/Butanol for Improved Drug Delivery from Dry Powder Inhalers 
The AAPS Journal  2010;13(1):30-43.
Dry powder inhaler formulations comprising commercial lactose–drug blends can show restricted detachment of drug from lactose during aerosolisation, which can lead to poor fine particle fractions (FPFs) which are suboptimal. The aim of the present study was to investigate whether the crystallisation of lactose from different ethanol/butanol co-solvent mixtures could be employed as a method of altering the FPF of salbutamol sulphate from powder blends. Lactose particles were prepared by an anti-solvent recrystallisation process using various ratios of the two solvents. Crystallised lactose or commercial lactose was mixed with salbutamol sulphate and in vitro deposition studies were performed using a multistage liquid impinger. Solid-state characterisation results showed that commercial lactose was primarily composed of the α-anomer whilst the crystallised lactose samples comprised a α/β mixture containing a lower number of moles of water per mole of lactose compared to the commercial lactose. The crystallised lactose particles were also less elongated and more irregular in shape with rougher surfaces. Formulation blends containing crystallised lactose showed better aerosolisation performance and dose uniformity when compared to commercial lactose. The highest FPF of salbutamol sulphate (38.0 ± 2.5%) was obtained for the lactose samples that were crystallised from a mixture of ethanol/butanol (20:60) compared to a FPF of 19.7 ± 1.9% obtained for commercial lactose. Engineered lactose carriers with modified anomer content and physicochemical properties, when compared to the commercial grade, produced formulations which generated a high FPF.
Electronic supplementary material
The online version of this article (doi:10.1208/s12248-010-9241-x) contains supplementary material, which is available to authorized users.
doi:10.1208/s12248-010-9241-x
PMCID: PMC3032097  PMID: 21057906
deposition study; dry powder inhaler; lactose; particle engineering; salbutamol sulphate
18.  Phylogeography of the Mekong mud snake (Enhydris subtaeniata): the biogeographic importance of dynamic river drainages and fluctuating sea levels for semiaquatic taxa in Indochina 
Ecology and Evolution  2011;1(3):330-342.
During the Cenozoic, Southeast Asia was profoundly affected by plate tectonic events, dynamic river systems, fluctuating sea levels, shifting coastlines, and climatic variation, which have influenced the ecological and evolutionary trajectories of the Southeast Asian flora and fauna. We examined the role of these paleogeographic factors on shaping phylogeographic patterns focusing on a species of semiaquatic snake, Enhydris subtaeniata (Serpentes: Homalopsidae) using sequence data from three mitochondrial fragments (cytochrome b, ND4, and ATPase—2785 bp). We sampled E. subtaeniata from seven locations in three river drainage basins that encompassed most of this species’ range. Genetic diversities were typically low within locations but high across locations. Moreover, each location had a unique suite of haplotypes not shared among locations, and pairwise φST values (0.713–0.998) were highly significant between all location pairs. Relationships among phylogroups were well resolved and analysis of molecular variance (AMOVA) revealed strong geographical partitioning of genetic variance among the three river drainage basins surveyed. The genetic differences observed among the populations of E. subtaeniata were likely shaped by the Quaternary landscapes of Indochina and the Sunda Shelf. Historically, the middle and lower Mekong consisted of strongly dissected river valleys separated by low mountain ranges and much of the Sunda Shelf consisted of lowland river valleys that served to connect faunas associated with major regional rivers. It is thus likely that the contemporary genetic patterns observed among populations of E. subtaeniata are the result of their histories in a complex terrain that created abundant opportunities for genetic isolation and divergence yet also provided lowland connections across now drowned river valleys.
doi:10.1002/ece3.29
PMCID: PMC3287308  PMID: 22393504
Freshwater snake; Homalopsidae; Khorat basin; Mekong River; Pleistocene; Sea levels; Sundaland
19.  Short course pre-operative ferrous sulphate supplementation – is it worthwhile in patients with colorectal cancer? 
INTRODUCTION
Pre-operative anaemia is well recognised in patients presenting with colorectal cancer (CRC). While the benefits of long-term FeSO4 supplementation on Fe deficiency anaemia are well established, it is not known if short-course supplementation (2–3 weeks) impacts significantly on pre-operative haemoglobin (Hb) levels. This study examines the impact of short-term, oral FeSO4 supplementation on patients undergoing surgery for CRC.
PATIENTS AND METHODS
All patients with CRC presenting to a single surgeon were included. At diagnosis, baseline Hb and blood film were checked on all patients who then received 200 mg tds of FeSO4. Haemoglobin was rechecked pre-operatively and daily postoperatively. Patients requiring pre-operative blood transfusions were excluded from analysis.
RESULTS
Between 1 January 2004 and 31 December 2006, 117 patients were identified, 14 of whom were excluded. Patients received a median of 39 days’ treatment with FeSO4. Fifty-eight (56.3%) patients were anaemic at presentation gaining a mean of 1.73 g/dl (P < 0.001) from short-course FeSO4 supplementation. Right-sided tumours (lower mean Hb at presentation; P = 0.008) responded more to FeSO4 when compared to left-sided tumours (P < 0.017). Increase in Hb was unrelated to pathological stage. The transfusion rate for all curative resections was 0.69 units/patient. For the historical cohort (patients undergoing curative resection between 1 January 2001 and 31 December 2003), the mean transfusion rate fell from 1.69 units/patient.
CONCLUSIONS
Routine short-course supplementation with iron offers improved pre-operative Hb prior to surgery in CRC, especially in right-sided lesions and those with presenting anaemia.
doi:10.1308/003588410X12699663904277
PMCID: PMC3229346  PMID: 20573311
Colorectal cancer; FeSO4 supplementation; Anaemia; Haemoglobin
20.  The Science of Safety Curriculum in US Colleges and Schools of Pharmacy 
Objective. To describe the integration of science of safety (SoS) topics in doctor of pharmacy (PharmD) curricula of US colleges and schools of pharmacy.
Methods. A questionnaire that contained items pertaining to what and how SoS topics are taught in PharmD curricula was e-mailed to representatives at 107 US colleges and schools of pharmacy.
Results. The majority of the colleges and schools responding indicated that they had integrated SoS topics into their curriculum, however, some gaps (eg, teaching students about communicating risk, Food and Drug Administration [FDA] Sentinel Initiative, utilizing patient databases) were identified that need to be addressed.
Conclusions. The FDA and the American Association of Colleges of Pharmacy (AACP) should continue to collaborate to develop resources needed to ensure that topics proposed by the FDA in their SoS framework are taught at all colleges and schools of pharmacy.
doi:10.5688/ajpe757141
PMCID: PMC3175655  PMID: 21969727
medication safety; pharmacy education; curriculum; science of safety
21.  Student Evaluations of the Portfolio Process 
Objective. To evaluate pharmacy students’ perceived benefits of the portfolio process and to gather suggestions for improving the process.
Methods. A questionnaire was designed and administered to 250 first-, second-, and third-year pharmacy students at the University of Arizona College of Pharmacy.
Results. Although the objectives of the portfolio process were for students to understand the expected outcomes, understand the impact of extracurricular activities on attaining competencies, identify what should be learned, identify their strengths and weaknesses, and modify their approach to learning, overall students perceived the portfolio process as having less than moderate benefit. First-year students wanted more examples of portfolios while second- and third-year students suggested that more time with their advisor would be beneficial.
Conclusions. The portfolio process will continue to be refined and efforts made to improve students’ perceptions of the process as it is intended to develop the self-assessments skills they will need to improve their knowledge and professional skills throughout their pharmacy careers.
doi:10.5688/ajpe757132
PMCID: PMC3175659  PMID: 21969718
survey; portfolio; questionnaire; expected outcomes; assessment
22.  Perspectives on Educating Pharmacy Students About the Science of Safety 
Objective. To identify opinions about pharmacy graduates’ science of safety (SoS) educational needs.
Methods. Semi-structured interviews were performed with 25 educators and researchers at US pharmacy colleges and schools and 5 individuals from associations engaged in drug safety-related issues.
Results. Themes that emerged from the 30 interviews with key informants included: pharmacists should meet minimum SoS requirements; medication safety education is inconsistent; and barriers exist to improving SoS curricula. Student deficiencies noted included the lack of: student acceptance of a “culture of safety”: ability to effectively communicate verbally about medication safety; knowledge of the drug development process; and quality improvement skills. Key informants did not agree on how to address these gaps.
Conclusions. While educators, researchers, and other leaders in drug safety-related issues thought that US colleges and schools of pharmacy covered portions of SoS well, there were perceived deficiencies. Minimum standards should be set to assist with curricular adoption of SoS.
doi:10.5688/ajpe757142
PMCID: PMC3175660  PMID: 21969728
medication safety; patient safety pharmacy education; science of safety; education
23.  Pharmacy Students’ Retention of Knowledge of Drug-Drug Interactions 
Objectives. To evaluate pharmacy students' drug-drug interaction (DDI) knowledge retention over 1 year and to determine whether presenting DDI vignettes increased knowledge retention.
Methods. A knowledge assessment tool was distributed to fourth-year pharmacy students before and after completing a DDI educational session. The questionnaire was re-administered after 1 year to assess knowledge retention. During the intervening year, students had the option of presenting DDI case vignettes to preceptors and other health professionals as part of their advanced pharmacy practice experiences (APPEs).
Results. Thirty-four of 78 pharmacy students completed both the post-intervention and 1-year follow-up assessments. Students’ knowledge of 4 DDI pairs improved, knowledge of 3 DDI pairs did not change, and knowledge of the remainder of DDI pairs decreased. Average scores of the 18 students who completed all tests and presented at least 1 vignette during their APPEs were higher on the 1-year follow-up assessment than students who did not, suggesting greater DDI knowledge retention (p = 0.04).
Conclusion. Although pharmacy students’ overall DDI knowledge decreased in the year following an educational session, those who presented vignettes to health professionals retained more DDI knowledge, particularly on those DDIs for which they gave presentations. Other methods to enhance pharmacy students’ retention of DDI knowledge of clinically important DDIs are needed.
doi:10.5688/ajpe756110
PMCID: PMC3175677  PMID: 21931448
drug-drug interaction; assessment
24.  Teaching the Science of Safety in US Colleges and Schools of Pharmacy 
This paper provides baseline information on integrating the science of safety into the professional degree curriculum at colleges and schools of pharmacy. A multi-method examination was conducted that included a literature review, key informant interviews of 30 individuals, and in-depth case studies of 5 colleges and schools of pharmacy. Educators believe that they are devoting adequate time to science of safety topics and doing a good job teaching students to identify, understand, report, manage, and communicate medication risk. Areas perceived to be in need of improvement include educating pharmacy students about the Food and Drug Administration's (FDA's) role in product safety, how to work with the FDA in post-marketing surveillance and other FDA safety initiatives, teaching students methods to improve safety, and educating students to practice in interprofessional teams. The report makes 10 recommendations to help pharmacy school graduates be more effective in protecting patients from preventable drug-related problems.
PMCID: PMC3138345  PMID: 21769153
safety; curriculum; pharmacy education; FDA; quality
25.  Spatial hearing of normally hearing and cochlear implanted children 
Objective
Spatial hearing uses both monaural and binaural mechanisms that require sensitive hearing for normal function. Deaf children using either bilateral (BCI) or unilateral (UCI) cochlear implants would thus be expected to have poorer spatial hearing than normally hearing (NH) children. However, the relationship between spatial hearing in these various listener groups has not previously been extensively tested under ecologically valid conditions using a homogeneous group of children who are UCI users. We predicted that NH listeners would outperform BCI listeners who would, in turn, outperform UCI listeners.
Methods
We tested two methods of spatial hearing to provide norms for NH and UCI using children and preliminary data for BCI users. NH children (n = 40) were age matched (6–15 years) to UCI (n = 12) and BCI (n = 6) listeners. Testing used a horizontal ring of loudspeakers within a booth in a hospital outpatient clinic. In a ‘lateral release’ task, single nouns were presented frontally, and masking noises were presented frontally, or 90° left or right. In a ‘localization’ task, allowing head movements, nouns were presented from loudspeakers separated by 30°, 60° or 120° about the midline.
Results
Normally hearing children improved with age in speech detection in noise, but not in quiet or in lateral release. Implant users performed more poorly on all tasks. For frontal signals and noise, UCI and BCI listeners did not differ. For lateral noise, BCI listeners performed better on both sides (within ∼2 dB of NH), whereas UCI listeners benefited only when the noise was opposite the unimplanted ear. Both the BCI and, surprisingly, the UCI listeners performed better than chance at all loudspeaker separations on the ecologically valid, localization task. However, the BCI listeners performed about twice as well and, in two cases, approached the performance of NH children.
Conclusion
Children using either UCI or BCI have useful spatial hearing. BCI listeners gain benefits on both sides, and localize better, but not as well as NH listeners.
doi:10.1016/j.ijporl.2011.01.002
PMCID: PMC3069302  PMID: 21295863
Unilateral cochlear implants; Bilateral cochlear implants; Lateral release; Sound localization; Head movements

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