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Benjamin Q Duong,1 Meghan J Arwood,2 J Kevin Hicks,3 Amber L Beitelshees,4 Francesco Franchi,5 John T Houder,2 Nita A Limdi,6 Kelsey J Cook,7,8 Aniwaa Owusu Obeng,9 Natasha Petry,10 Sony Tuteja,11 Amanda R Elsey,2 Larisa H Cavallari,2 Kristin Wiisanen2 on behalf of the IGNITE Network1Department of Precision Medicine, Nemours/Alfred I. DuPont Hospital for Children, Wilmington, DE, USA; 2Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics & Precision Medicine, University of Florida College of Pharmacy, Gainesville, FL, USA; 3Department of Individualized Cancer Management, Moffitt Cancer Center, Tampa, FL, USA; 4Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, USA; 5Department of Cardiology, University of Florida College of Medicine, Jacksonville, FL, USA; 6University of Alabama School at Birmingham, Birmingham, AL, USA; 7Department of Pharmacotherapy and Translational Research, University of Florida College of Pharmacy, Jacksonville, FL, USA; 8Department of Precision Medicine, Nemours Children’s Specialty Care, Jacksonville, FL, USA; 9The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA; 10Department of Pharmacy Practice, North Dakota State University College of Health Professions, Fargo, ND, USA; 11Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USACorrespondence: Kristin WiisanenDepartment of Pharmacotherapy and Translational Research and Center for Pharmacogenomics & Precision Medicine, University of Florida College of Pharmacy, P.O. Box 100486, Gainesville, FL 32610-0486, USATel +1 352-273-5114Email kwiisanen@cop.ufl.eduIntroduction: Clinical adoption of genomic medicine has lagged behind the pace of scientific discovery. Practice-based resources can help overcome implementation challenges.Methods: In 2015, the IGNITE (Implementing GeNomics In pracTicE) Network created an online genomic medicine implementation resource toolbox that was expanded in 2017 to incorporate the ability for users to create targeted implementation guides. This expansion was led by a multidisciplinary team that developed an evidence-based, structured framework for the guides, oversaw the technical process/build, and pilot tested the first guide, CYP2C19-Clopidogrel Testing Implementation.Results: Sixty-five resources were collected from 12 institutions and categorized according to a seven-step implementation framework for the pilot CYP2C19-Clopidogrel Testing Implementation Guide. Five months after its launch, 96 CYP2C19-Clopidogrel Testing Implementation Guides had been created. Eighty percent of the resources most frequently selected by users were created by IGNITE to fill an identified resource gap. Resources most often included in guides were from the test reimbursement (22%), Implementation support gathering (22%), EHR integration (17%), and genetic testing workflow steps (17%).Conclusion: Lessons learned from this implementation guide development process provide insight for prioritizing development of future resources and support the value of collaborative efforts to create resources for genomic medicine implementation.Keywords: pharmacogenomics, CYP2C19, clopidogrel, implementation, precision medicine, personalized medicine, clinical pharmacogenomics, CYP2D6

Pharmacogenetics promises to optimize treatment-related outcomes by informing optimal drug selection and dosing based on an individual's genotype in conjunction with other important clinical factors. Despite significant evidence of genetic associations with drug response, pharmacogenetic testing has not been widely implemented into clinical practice. Among the barriers to broad implementation are limited guidance for how to successfully integrate testing into clinical workflows and limited data on outcomes with pharmacogenetic implementation in clinical practice. The Pharmacogenomics Global Research Network Implementation Working Group seeks to engage institutions globally that have implemented pharmacogenetic testing into clinical practice or are in the process or planning stages of implementing testing to collectively disseminate data on implementation strategies, metrics, and health-related outcomes with the use of genotype-guided drug therapy to ultimately help advance pharmacogenetic implementation. This paper describes the goals, structure, and initial projects of the group in addition to implementation priorities across sites and future collaborative opportunities., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: Engaging in reflective practice (RP) and demonstrating reflective abilities is an essential graduate skill for speech-language pathologists (SLPs), yet limited studies have examined the perspectives of practicing SLPs and how and why they engage in RP. This qualitative study aimed to examine SLPs' experiences and perspectives of RP in diverse workplaces., Method: Individual semi-structured interviews were conducted with 30 SLPs working in health, education, or private practice sectors. Interviews were analysed using thematic analysis., Result: Three themes were developed from the data, describing what SLPs use RP for, what SLPs perceive as important in order to engage in RP in the workplace, as well as the barriers they have identified, and how SLPs have observed a change in engaging in RP as they have progressed in their careers., Conclusion: SLPs described that RP is valued in the workplace for supporting client focused care, problem-solving, and lifelong learning. SLPs wanted time to be protected for RP at all stages of their career and valued the relationships with others as contributing positively to RP. Perceptions of and engagement in RP changed in relation to SLPs' clinical experience. Implications for clinical practice are discussed.

Introduction: Treatment intensity for people with aphasia (PWA) is a significant factor in enhancing recovery. Personal factors such as fatigue, physical endurance, and motivation as well as clinician availability have been described as barriers to increased intensity. The use of student therapists has been shown to assist with addressing service gaps., Methods: The aim of the study was to explore the experiences of PWA who received enhanced community-based treatment delivered by speech-language pathology (SLP) students. Enhanced community-based treatment was defined as three or more treatment sessions per week targeting communication. Semi-structured interviews were conducted with 10 PWA living in New Zealand. Interview data were analysed with reflexive thematic analysis., Results: Two themes and six sub-themes were developed. Theme 1 related to intensity and included more treatment is better than less (sub-theme 1), there's a "right time" for more intensive treatment (sub-theme 2), the hard work is worth the effort (sub-theme 3). Theme 2 related to working with SLP students; it didn't feel like they were students (sub-theme 4), we just got on so well (sub-theme 5), and they listened to what I wanted (sub-theme 6)., Conclusions: The findings confirm that PWA value access to more intensive treatment and desire involvement in decisions about flexible treatment schedules. PWA have positive experiences when treatment is provided by SLP students. Implications for clinical practice and future research directions are discussed., (© 2024 S. Karger AG, Basel.)

Purpose: While communication changes associated with Parkinson's disease (PD) have been documented, research on the impact of these changes on family members is just beginning to emerge. With this new focus on family, questions arise as to how well speech-language pathology services address their needs communicating with their loved one with PD. The purpose of this study was to explore the experiences of family members of people with PD (PwPD) and their recommendations for speech-language pathology services that incorporated their needs., Method: Seventeen spouses/partners of PwPD participated in focus groups that were recorded, transcribed, and analyzed using thematic analyses., Results: Three themes emerged, all focusing around the central tenet that the experiences of family members, and hence their need for speech-language pathology support, transitioned through the stages of PD progression. Theme 1 summarized increasing burdens on family to manage communication as PD progressed beyond a brief period of independent strategy use by PwPD. Theme 2 highlighted multifactorial contributors to communication burdens on families, with cognitive impairments being the most underrecognized. Theme 3 illustrated how families wanted more intervention options from speech-language pathologists (SLPs) that included them, but with a tailored approach for PD stages and personal preferences., Conclusions: When SLPs provide families with either generic communication strategies or strategies that do not fit the individualized needs of PwPD and their families, we may inadvertently be increasing the burden on families. There is a need for systematic, evidence-based, family-centered interventions that include, but go beyond, current speech-focused interventions to meet the shared communication needs of PwPD and their families.

The properties of superheavy elements probe extremes of physics and chemistry. They are synthesised at accelerator laboratories using nuclear fusion, where two atomic nuclei collide, stick together (capture), then with low probability evolve to a compact superheavy nucleus. The fundamental microscopic mechanisms controlling fusion are not fully understood, limiting predictive capability. Even capture, considered to be the simplest stage of fusion, is not matched by models. Here we show that collisions of 40 Ca with 208 Pb, experience an 'explosion' of mass and charge transfers between the nuclei before capture, with unexpectedly high probability and complexity. Ninety different partitions of the protons and neutrons between the projectile-like and target-like nuclei are observed. Since each is expected to have a different probability of fusion, the early stages of collisions may be crucial in superheavy element synthesis. Our interpretation challenges the current view of fusion, explains both the successes and failures of current capture models, and provides a framework for improved models., (© 2023. The Author(s).)

The risk of severe adverse events related to thiopurine therapy can be reduced by personalizing dosing based on TPMT and NUDT15 genetic polymorphisms. However, the optimal genetic testing platform has not yet been established. In this study, we report on the TPMT and NUDT15 genotypes and phenotypes generated from 320 patients from a multicenter pediatric healthcare system using both Sanger sequencing and polymerase chain reaction genotyping (hereafter: genotyping) methods to determine the appropriateness of genotyping in our patient population. Sanger sequencing identified variant TPMT alleles including *3A (8, 3.2% of alleles), *3C (4, 1.6%), and *2 (1, 0.4%), and NUDT15 alleles including *2 (5, 3.6%) and *3 (1, 0.7%). For genotyped patients, variants identified in TPMT included *3A (12, 3.1%), *3C (4, 1%), *2 (2, 0.5%), and *8 (1, 0.25%), whereas NUDT15 included *4 (2, 1.9%) and *2 or *3 (1, 1%). Between Sanger sequencing and genotyping, no significant difference in allele, genotype, or phenotype frequency was identified for either TPMT or NUDT15. All patients who were tested using Sanger sequencing would have been accurately phenotyped for either TPMT (124/124), NUDT15 (69/69), or both genes (68/68) if they were assayed using the genotyping method. Considering 193 total TPMT and NUDT15 Sanger Sequencing tests reviewed, all tests would have resulted in an appropriate clinical recommendation if the test had instead been conducted using the comparison genotyping platforms. These results suggest that, in this study population, genotyping would be sufficient to provide accurate phenotype calls and clinical recommendations., (© 2023 The Authors. Clinical and Translational Science published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Background: Written reflective practice (WRP) is a teaching tool used across speech-language therapy (SLT) clinical education programmes. The process aims to support the development of reflective skills required for the workplace (e.g., problem-solving and self-evaluation)., Aims: This cross-sectional and repeated-measures study design investigated students' demonstration of breadth of WRP across the clinical education programme., Methods & Procedures: The participants were 77 undergraduate SLT students in their first, second or final professional year of the clinical programme. Participants wrote critical reflections following an interaction with a client/s as part of their clinical education experiences. Formative feedback was provided after each written reflection (WR). In total four WRs per participant were coded for breadth of WRP using a modification of Plack et al.'s coding schema from 2005. This was completed for each of the four time points across the academic year for each professional year., Outcomes & Results: There was a statistically significant association between time (i.e., professional year of the programme) and likelihood of demonstration of breadth of reflection for the lower level reflective element of 'attend' and higher level reflective element of 're-evaluate'. A positive trend between time and likelihood of demonstration of breadth of reflection was seen for the lower level element of 'reflection-for-action'. Final-professional-year students exhibited significant enhancements in the higher level elements (e.g., 'premise') compared with first- and second-professional-year students., Conclusions & Implications: This group of SLT students exhibited significant change in breadth of WRP across the degree programme. This finding has positive implications for facilitating WRP with students and using the current coding framework in clinical programmes., What This Paper Adds: What is already known on this subject WRP is one form of reflective practice (RP) used in SLT, allied health, medical and nursing clinical education programmes. Researchers have suggested that RP skills develop over time for students. Previously, studies examining WRP have focused on one off assessment of skill or over a timeframe of 6-10 weeks. Here, we examine SLT students' WRP skills across the degree programme. What this paper adds to existing knowledge SLT students exhibited significant positive change in breadth of WRP across the degree programme as their clinical experience increased. Our results provide quantitative information in support of using RP as a learning tool throughout clinical education programmes for SLT. What are the potential or actual clinical implications of this work? This study offers support for educators of SLT students; for example, how educators can assess WRP, and how educators can foster SLT student skill development with formative feedback and reflective questioning. This study also offers support for student SLT, for example, describing how WRP can be part of their individualized learning approach and provide a purposeful examination of self and clinical skill development., (© 2022 The Authors. International Journal of Language & Communication Disorders published by John Wiley & Sons Ltd on behalf of Royal College of Speech and Language Therapists.)

Essential cellular processes such as metabolism, protein synthesis, and autophagy require the intracellular transport of membrane-bound vesicles. The importance of the cytoskeleton and associated molecular motors for transport is well documented. Recent research has suggested that the endoplasmic reticulum (ER) may also play a role in vesicle transport through a tethering of vesicles to the ER. We use single-particle tracking fluorescence microscopy and a Bayesian change-point algorithm to characterize vesicle motility in response to the disruption of the ER, actin, and microtubules. This high-throughput change-point algorithm allows us to efficiently analyze thousands of trajectory segments. We find that palmitate-mediated disruption of the ER leads to a significant decrease in vesicle motility. A comparison with the disruption of actin and microtubules shows that disruption of the ER has a significant impact on vesicle motility, greater than the disruption of actin. Vesicle motility was dependent on cellular region, with greater motility in the cell periphery than the perinuclear region, possibly due to regional differences in actin and the ER. Overall, these results suggest that the ER is an important factor in vesicle transport., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 Biophysical Society. Published by Elsevier Inc. All rights reserved.)

The beneficial effects of sodium butyrate (NaB) and sodium propionate (NaP) on fatty acid oxidation (FAO) genes and production of proinflammatory cytokines related to nonalcoholic fatty liver disease (NAFLD) were evaluated using HepG2 human liver hepatocellular carcinoma cells exposed to palmitate/oleate or lipopolysaccharides (LPSs) as a model. The results showed that NaP or NaB was able to promote FAO, regulate lipolysis, and reduce reactive oxygen species production by significantly increasing the mRNA expression of peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1 α ), peroxisome proliferator-activated receptor alpha (PPAR α ), adipose triglyceride lipase (ATGL), carnitine palmitoyltransferase 1 alpha (CPT1 α ), fibroblast growth factor 21 (FGF21), and uncoupling protein 2 (UCP2) in HepG2 cells. Together, NaP and NaB may produce greater effects by increasing CPT1 α , PPAR α , and UCP2 mRNA expression in LPS-treated HepG2 cells and by increasing CPT1 α and ATGL mRNA expression in palmitate-/oleate-treated HepG2 cells. Only NaP treatment significantly increased FGF21 mRNA expression in palmitate-/oleate-treated HepG2 cells. The enzyme-linked immunosorbent assay results revealed that only pretreatment with LPSs and not palmitate/oleate significantly increased tumor necrosis factor alpha (TNF- α ) expression in HepG2 cells. NaP alone or in combination with NaB significantly decreased TNF- α expression in LPS-induced HepG2 cells. The expression of interleukin-8 in both models showed no significant differences in all treatments. NaP and NaB show potential for in vivo studies on NAFLD.

The dynamics of a nuclear open quantum system could be revealed in the correlations between the breakup fragments of halo nuclei. The breakup mechanism of a proton halo nuclear system is of particular interest as the Coulomb polarization may play an important role, which, however, remains an open question. Here we use a highly efficient silicon detector array and measure the correlations between the breakup fragments of 8 B incident on 120 Sn at near-barrier energies. The energy and angular correlations can be explained by a fully quantum mechanical method based on the state-of-the-art continuum discretized coupled channel calculations. The results indicate that, compared to the neutron halo nucleus 6 He, 8 B presents distinctive reaction dynamics: the dominance of the elastic breakup. This breakup occurs mainly via the short-lived continuum states, almost exhausts the 7 Be yield, indicating the effect of Coulomb polarization on the proton halo state. The correlation information reveals that the prompt breakup mechanism dominates, occurring predominantly on the outgoing trajectory. We also show that, as a large environment, the continuum of 8 B breakup may not significantly influence elastic scattering and complete fusion., (© 2022. The Author(s).)

Opioid prescribing for postoperative pain management is challenging because of inter-patient variability in opioid response and concern about opioid addiction. Tramadol, hydrocodone, and codeine depend on the cytochrome P450 2D6 (CYP2D6) enzyme for formation of highly potent metabolites. Individuals with reduced or absent CYP2D6 activity (i.e., intermediate metabolizers [IMs] or poor metabolizers [PMs], respectively) have lower concentrations of potent opioid metabolites and potentially inadequate pain control. The primary objective of this prospective, multicenter, randomized pragmatic trial is to determine the effect of postoperative CYP2D6-guided opioid prescribing on pain control and opioid usage. Up to 2020 participants, age ≥8 years, scheduled to undergo a surgical procedure will be enrolled and randomized to immediate pharmacogenetic testing with clinical decision support (CDS) for CYP2D6 phenotype-guided postoperative pain management (intervention arm) or delayed testing without CDS (control arm). CDS is provided through medical record alerts and/or a pharmacist consult note. For IMs and PM in the intervention arm, CDS includes recommendations to avoid hydrocodone, tramadol, and codeine. Patient-reported pain-related outcomes are collected 10 days and 1, 3, and 6 months after surgery. The primary outcome, a composite of pain intensity and opioid usage at 10 days postsurgery, will be compared in the subgroup of IMs and PMs in the intervention (n = 152) versus the control (n = 152) arm. Secondary end points include prescription pain medication misuse scores and opioid persistence at 6 months. This trial will provide data on the clinical utility of CYP2D6 phenotype-guided opioid selection for improving postoperative pain control and reducing opioid-related risks., (© 2022 The Authors. Clinical and Translational Science published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Community service serves as a major aspect of pharmacy education; however, coronavirus disease 2019 (COVID-19) represented a significant disruption to student involvement. The College of Pharmacy student council, which serves as the local student government organization for the University of Florida College of Pharmacy, Jacksonville campus, developed a community service initiative to offer more consistent opportunities for students to participate in community service events, while adapting to COVID-19 restrictions. A retrospective, qualitative review of this initiative demonstrates the potential value of this model. Prior to this initiative, students relied on individual student organizations to provide service opportunities to their members. This excluded portions of the student body and led to sparse and inconsistent events, with limited variation in the types of service events available. Furthermore, de-centralized planning of service opportunities increased the difficulty of ensuring that COVID-19 safety restrictions were followed appropriately. This initiative resulted in 39 students logging over 200 service hours through nine events in the first seven months after its development. Despite the challenges presented by the COVID-19 pandemic, our centralized initiative serves as a model for improving community service involvement.

Lysosomes are membrane-bound organelles that serve as the endpoint for endocytosis, phagocytosis, and autophagy, degrading the molecules, pathogens, and organelles localized within them. These cellular functions require intracellular transport. We use fluorescence microscopy to characterize the motion of lysosomes as a function of intracellular region, perinuclear or periphery, and lysosome diameter. Single-particle tracking data are complemented by changepoint identification and analysis of a mathematical model for state switching. We first classify lysosomal motion as motile or stationary. We then study how lysosome location and diameter affects the proportion of time spent in each state and quantify the speed during motile periods. We find that the proportion of time spent stationary is strongly region dependent, with significantly decreased motility in the perinuclear region. Increased lysosome diameter only slightly decreases speed. Overall, these results demonstrate the importance of decomposing particle trajectories into qualitatively different behaviors before conducting population-wide statistical analysis. Our results suggest that intracellular region is an important factor to consider in studies of intracellular transport., (Copyright © 2022 Biophysical Society. Published by Elsevier Inc. All rights reserved.)

A challenge preventing successful inverse kinematics measurements with heavy nuclei that are not fully stripped is identifying and tagging the beam particles. For this purpose, the HEavy ISotope Tagger (HEIST) has been developed. HEIST utilizes two micro-channel plate timing detectors to measure the time-of-flight, a multi-sampling ion chamber to measure energy loss, and a high-purity germanium detector to identify isomer decays and calibrate the isotope identification system. HEIST has successfully identified 198 Pb and other nearby nuclei at energies of about 75 MeV/A. In the experiment discussed, a typical cut containing 89% of all 198 Pb 80+ in the beam had a purity of 86%. We examine the issues of charge state contamination. The observed charge state populations of these ions are presented and, using an adjusted beam energy, are well described by the charge state model GLOBAL.

Mass and angle distributions for the ^{52}Cr+^{198}Pt and ^{54}Cr+^{196}Pt reactions (both forming ^{250}No) were measured and subtracted, giving new information on fast quasifission mass evolution, and the first direct determination of the dependence of sticking times on angular momentum. TDHF calculations showed good agreement with average experimental values, but experimental mass distributions unexpectedly extended to symmetric splits while the peak yield remained close to the initial masses. This implies a strong role of fluctuations in mass division early in the collision, giving insights into the transition from fast energy dissipative deep-inelastic collisions to quasifission.

CYP2D6 genotype is increasingly being integrated into practice to guide prescribing of certain medications. The CYP2D6 drug metabolizing enzyme is susceptible to inhibition by concomitant drugs, which can lead to a clinical phenotype that is different from the genotype-based phenotype, a process referred to as phenoconversion. Phenoconversion is highly prevalent but not widely integrated into practice because of either limited experience on how to integrate or lack of knowledge that it has occurred. We built a calculator tool to help clinicians integrate a standardized method of assessing CYP2D6 phenoconversion into practice. During tool-building, we identified several clinical factors that need to be considered when implementing CYP2D6 phenoconversion into clinical practice. This tutorial shares the steps that the University of Florida Health Precision Medicine Program took to build the calculator tool and identified clinical factors to consider when implementing CYP2D6 phenoconversion in clinical practice., (© 2021 The Authors. Clinical Pharmacology & Therapeutics © 2021 American Society for Clinical Pharmacology and Therapeutics.)

In this study, we design and use a mathematical model to primarily address the question of who are the main drivers of COVID-19 - the symptomatic infectious or the pre-symptomatic and asymptomatic infectious in the state of Wisconsin and the entire United States. To set the stage, we first briefly simulate and illustrate the benefit of lockdown. With these lockdown scenarios, and in general, the more dominant influence of the the pre-symptomatic and asymptomatic infectious over the symptomatic infectious, is shown in various ways. Numerical simulations for the U.S. show that an increase in testing and isolating for the pre-symptomatic and asymptomatic infectious group has up to 4 times more impact than an increase in testing for the symptomatic infectious in terms of cumulative deaths. An increase in testing for the pre-symptomatic and asymptomatic infectious group also has significantly more impact (on the order of twice as much) on reducing the control reproduction number than testing for symptomatic infectious. Lastly, we use our model to simulate an implementation of a natural herd immunity strategy for the entire U.S. and for the state of Wisconsin (once an epicenter for COVID-19). These simulations provide specific examples confirming that such a strategy requires a significant number of deaths before immunity is achieved, and as such, this strategy is certainly questionable in terms of success.

Genotyping for CYP2C19 no function alleles to guide antiplatelet therapy after percutaneous coronary intervention (PCI) improves clinical outcomes. Although results for the increased function CYP2C19*17 allele are also reported, its clinical relevance in this setting remains unclear. A collaboration across nine sites examined antiplatelet therapy prescribing and clinical outcomes in 3,342 patients after implementation of CYP2C19-guided antiplatelet therapy. Risk of major atherothrombotic and bleeding events over 12 months after PCI were compared across cytochrome P450 2C19 isozyme (CYP2C19) metabolizer phenotype and antiplatelet therapy groups by proportional hazards regression. Clopidogrel was prescribed to a similar proportion of CYP2C19 normal (84.5%), rapid (82.9%), and ultrarapid metabolizers (80.6%) (P = 0.360). Clopidogrel-treated normal metabolizers (20.4 events/100 patient-years; adjusted hazard ratio (HR) 1.00, 95% confidence interval (CI), 0.75-1.33, P = 0.993) and clopidogrel-treated rapid or ultrarapid metabolizers (19.1 events/100 patient-years; adjusted HR 0.95, 95% CI, 0.69-1.30, P = 0.734) exhibited no difference in major atherothrombotic events compared with patients treated with prasugrel or ticagrelor (17.6 events/100 patient-years). In contrast, clopidogrel-treated intermediate and poor metabolizers exhibited significantly higher atherothrombotic event risk compared with prasugrel/ticagrelor-treated patients (adjusted HR 1.56, 95% CI, 1.12-2.16, P = 0.008). When comparing clopidogrel-treated rapid or ultrarapid metabolizers to normal metabolizers, no difference in atherothrombotic (adjusted HR 0.97, 95% CI, 0.73-1.29, P = 0.808) or bleeding events (adjusted HR 1.34, 95% CI, 0.83-2.17, P = 0.224) were observed. In a real-world setting of genotype-guided antiplatelet therapy, the CYP2C19*17 allele did not significantly impact post-PCI prescribing decisions or clinical outcomes. These results suggest the CYP2C19 *1/*17 and *17/*17 genotypes have limited clinical utility to guide antiplatelet therapy after PCI., (© 2020 The Authors Clinical Pharmacology & Therapeutics © 2020 American Society for Clinical Pharmacology and Therapeutics.)

Atypical Aeromonas salmonicida causes furunculosis infections of non-salmonid fish, which requires antibiotic therapy. However, antibiotics may induce biofilm in some bacteria, which protects them against hostile conditions while allowing them to persist on surfaces, thus forming a reservoir for infection. The aim of this study was to determine whether atypical isolates of A. salmonicida increased biofilm in the presence of two antibiotics, florfenicol and oxytetracycline. A microtitre plate assay was used to quantify biofilm in the presence and absence of each antibiotic. Fifteen of 28 isolates formed biofilms under control conditions, while 23 of 28 isolates increased biofilm formation in the presence of at least one concentration of at least one antibiotic. For oxytetracycline, the most effective concentration causing biofilm to increase was one-quarter of that preventing visible bacterial growth, whereas for florfenicol it was one-half of this value. This is the first study to demonstrate that a bacterial pathogen of fish increases biofilm in response to antibiotics. Biofilm formation may increase the risk of re-infection in culture systems and this lifestyle favours the transmission of genetic material, which has implications for the dissemination of antibiotic-resistance genes and demonstrates the need for enhanced disease prevention measures against atypical A. salmonicida., (© 2020 The Authors. Journal of Fish Diseases published by John Wiley & Sons Ltd.)

Background and Purpose: Globally, five million women are affected by opioid use disorder (OUD). Women with OUD are less likely to breastfeed than the general population, increasing risk of neonatal withdrawal. Theoretical frameworks related to breastfeeding did not address women with OUD. The purpose of this study was to develop a conceptual model to better understand breastfeeding disparities among this vulnerable population., Methods: A grounded theory study was conducted from August 2018 to March 2019 to investigate concepts likely to influence breastfeeding decisions in women with OUD. In-depth interviews were conducted in North Carolina with 10 women in recovery who breastfed, and their six identified support persons. Data were analyzed through iterative coding. This article focuses on maternal perspectives of breastfeeding informed by support persons., Results: The overarching theme was breastfeeding decision-making in an addiction trajectory. Two antecedent pathways led to the recovery-relapse cycle. This cycle involved seeking, initiating, and maintaining recovery with episodic relapse. Perceived stigma linked the recovery-relapse cycle with breastworks. Breastworks, an emergent concept, was characterized by learning and knowing, good intentions, and health-care provider sensitivity., Implications for Practice: This grounded theory model may inform clinicians in caring for women with OUD and support breastfeeding and newborn well-being. Strategies to address research and practice may include the development of a mobile application, having women in recovery on the health-care team, and incorporation of breastfeeding guidelines., (© Copyright 2020 Springer Publishing Company, LLC.)

There have been significant advancements in precision medicine and approaches to medication selection based on pharmacogenetic results. With the availability of direct-to-consumer genetic testing and growing awareness of genetic interindividual variability, patient demand for more precise, individually tailored drug regimens is increasing. The University of Florida (UF) Health Precision Medicine Program (PMP) was established in 2011 to improve integration of genomic data into clinical practice. In the ensuing years, the UF Health PMP has successfully implemented several single-gene tests to optimize the precision of medication prescribing across a variety of clinical settings. Most recently, the UF Health PMP launched a custom-designed pharmacogenetic panel, including pharmacogenes relevant to supportive care medications commonly prescribed to patients undergoing chemotherapy treatment, referred to as "GatorPGx." This tutorial provides guidance and information to institutions on how to transition from the implementation of single-gene pharmacogenetic testing to a preemptive panel-based testing approach. Here, we demonstrate application of the preemptive panel in the setting of an adult solid tumor oncology clinic. Importantly, the information included herein can be applied to other clinical practice settings., (© 2020 The Authors Clinical Pharmacology & Therapeutics © 2020 American Society for Clinical Pharmacology and Therapeutics.)

The heaviest bound isotope of boron ^{19}B has been investigated using exclusive measurements of its Coulomb dissociation, into ^{17}B and two neutrons, in collisions with Pb at 220  MeV/nucleon. Enhanced electric dipole (E1) strength is observed just above the two-neutron decay threshold with an integrated E1 strength of B(E1)=1.64±0.06(stat)±0.12(sys)  e^{2} fm^{2} for relative energies below 6 MeV. This feature, known as a soft E1 excitation, provides the first firm evidence that ^{19}B has a prominent two-neutron halo. Three-body calculations that reproduce the energy spectrum indicate that the valence neutrons have a significant s-wave configuration and exhibit a dineutronlike correlation.

In isolated or declining populations, viability may be compromised further by loss of genetic diversity. Therefore, it is important to understand the relationship between long-term ecological trajectories and population genetic structure. However, opportunities to combine these types of data are rare, especially in natural systems. Using an existing panel of 15 microsatellites, we estimated allelic diversity in seagrass, Zostera marina, at five sites around the Isles of Scilly Special Area of Conservation, UK, in 2010 and compared this to 23 years of annual ecological monitoring (1996-2018). We found low diversity and long-term declines in abundance in this relatively pristine but isolated location. Inclusion of the snapshot of genotypic, but less-so genetic, diversity improved prediction of abundance trajectories; however, this was spatial scale-dependent. Selection of the appropriate level of genetic organization and spatial scale for monitoring is, therefore, important to identify drivers of eco-evolutionary dynamics. This has implications for the use of population genetic information in conservation, management, and spatial planning.

Superheavy elements are formed in fusion reactions which are hindered by fast nonequilibrium processes. To quantify these, mass-angle distributions and cross sections have been measured, at beam energies from below-barrier to 25% above, for the reactions of ^{48}Ca, ^{50}Ti, and ^{54}Cr with ^{208}Pb. Moving from ^{48}Ca to ^{54}Cr leads to a drastic fall in the symmetric fission yield, which is reflected in the measured mass-angle distribution by the presence of competing fast nonequilibrium deep inelastic and quasifission processes. These are responsible for reduction of the compound nucleus formation probablity P_{CN} (as measured by the symmetric-peaked fission cross section), by a factor of 2.5 for ^{50}Ti and 15 for ^{54}Cr in comparison to ^{48}Ca. The energy dependence of P_{CN} indicates that cold fusion reactions (involving ^{208}Pb) are not driven by a diffusion process.

Above-barrier complete fusion involving nuclides with low binding energy is typically suppressed by 30%. The mechanism that causes this suppression, and produces the associated incomplete fusion products, is controversial. We have developed a new experimental approach to investigate the mechanisms that produce incomplete fusion products, combining singles and coincidence measurements of light fragments and heavy residues in ^{7}Li+^{209}Bi reactions. For polonium isotopes, the dominant incomplete fusion product, only a small fraction can be explained by projectile breakup followed by capture: the dominant mechanism is triton cluster transfer. Suppression of complete fusion is therefore primarily a consequence of clustering in weakly bound nuclei rather than their breakup prior to reaching the fusion barrier. This implies that suppression of complete fusion will occur in reactions of nuclides where strong clustering is present.

Objective: This study compares and contrasts new graduate nurse attributes and perceptions using findings from a 2010 study and a recent analysis of new graduate nurses participating in the same residency program., Background: As millennials saturate the healthcare work environment, their unique views and needs will influence the evolution of new graduate nurse residencies., Methods: This study used previously reported data on new graduate nurses between 1999 and 2009 and compared it with a secondary analysis of data collected on new graduate nurses between 2011 and 2016., Results: This study provides evidence that millennial new graduate nurses' levels of commitment and satisfaction do not moderate turnover intentions in the 1st 2 years of practice as they did in the previous group of new graduate nurses., Conclusions: Job embeddedness, a construct that measures the likelihood of whether a person is going to stay, may be a better measurement among new graduate nurses than commitment or satisfaction because millennials, a generation that is predominant in current new graduate nurses, are more engaged than loyal.

Energy dissipative processes play a key role in how quantum many-body systems dynamically evolve toward equilibrium. In closed quantum systems, such processes are attributed to the transfer of energy from collective motion to single-particle degrees of freedom; however, the quantum many-body dynamics of this evolutionary process is poorly understood. To explore energy dissipative phenomena and equilibration dynamics in one such system, an experimental investigation of deep-inelastic and fusion-fission outcomes in the ^{58}Ni+^{60}Ni reaction has been carried out. Experimental outcomes have been compared to theoretical predictions using time dependent Hartree-Fock and time dependent random phase approximation approaches, which, respectively, incorporate one-body energy dissipation and fluctuations. Excellent quantitative agreement has been found between experiment and calculations, indicating that microscopic models incorporating one-body dissipation and fluctuations provide a potential tool for exploring dissipation in low-energy heavy ion collisions.

The atomic numbers and the masses of fragments formed in quasifission reactions are simultaneously measured at scission in ^{48}Ti+^{238}U reactions at a laboratory energy of 286 MeV. The atomic numbers are determined from measured characteristic fluorescence x rays, whereas the masses are obtained from the emission angles and times of flight of the two emerging fragments. For the first time, thanks to this full identification of the quasifission fragments on a broad angular range, the important role of the proton shell closure at Z=82 is evidenced by the associated maximum production yield, a maximum predicted by time-dependent Hartree-Fock calculations. This new experimental approach gives now access to precise studies of the time dependence of the N/Z (neutron over proton ratios of the fragments) evolution in quasifission reactions.

Measurement of population persistence is a long-standing problem in ecology; in particular, whether it is possible to gain insights into persistence without long time-series. Fractal measurements of spatial patterns, such as the Korcak exponent or boundary dimension, have been proposed as indicators of the persistence of underlying dynamics. Here we explore under what conditions a predictive relationship between fractal measures and persistence exists. We combine theoretical arguments with an aerial snapshot and time series from a long-term study of seagrass. For this form of vegetative growth, we find that the expected relationship between the Korcak exponent and persistence is evident at survey sites where the population return rate can be measured. This highlights a limitation of the use of power-law patch-size distributions and other indicators based on spatial snapshots. Moreover, our numeric simulations show that for a single species and a range of environmental conditions that the Korcak-persistence relationship provides a link between temporal dynamics and spatial pattern; however, this relationship is specific to demographic factors, so we cannot use this methodology to compare between species.

Interaction between biotic and abiotic drivers of dynamics is an important topic in ecology. Despite numerous short-term studies, there is a paucity of evidence about how environmental structure modifies dynamics in marine systems. We quantified Zostera marina flowering and non-flowering shoot density annually from 1996 to 2012 around the Isles of Scilly, UK, parameterizing a population dynamic model. Flowering is structured in time and space, with temperature and flowering positively associated at some locations only. We found no evidence that flower production contributes to seagrass density but 'patchiness' was positively associated with flowering in the previous year. With evidence of substantial overwinter survival, findings support the hypothesis that local populations are maintained largely through vegetative reproduction but sexual reproduction may contribute to colonisation of vacant habitat. This long-term study (1) tests validity of shorter-term investigations, (2) quantifies interaction between biotic and abiotic factors and (3) promotes seagrass as a model ecosystem., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Epidermal downgrowth, commonly associated with long-term percutaneous implants, weakens the skin-implant seal and greatly increases the vulnerability of the site to infection. To improve the skin attachment and early tissue integration with porous metal percutaneous implants, we evaluated the effect of bone marrow-derived mesenchymal stem cells (BMMSCs) to provide wound healing cues and vascularization to the dermal and epidermal tissues in establishing a barrier with the implant. Two porous metal percutaneous implants, one treated with BMMSCs and one untreated, were placed subdermally on the dorsum of Lewis rats. Implants were evaluated at 0, 3, 7, 28, and 56 days after implantation. Histological analyses evaluated cellular infiltrates, vascularization, quantity and quality of tissue ingrowth, epidermal downgrowth, and fibrous encapsulation. The amount of collagen infiltrating the porous coating was significantly greater for the BMMSC-treated implants at 3 and 28 days post implantation compared to untreated implants. There was an early influx and resolution of cellular inflammatory infiltrates in the treated implants compared to the untreated, though not statistically significant. Vascularization increased over time in both treated and untreated implants, with no statistical significance. Epidermal downgrowth was minimally observed in all implants with or without the BMMSC treatment. Our results suggest that BMMSCs can influence an early and rapid resolution of acute and chronic inflammation in wound healing, and can stimulate early collagen deposition and granulation tissue associated with later stages of wound repair. These findings provide evidence that BMMSCs can stimulate a more rapid and improved barrier between the skin and porous metal percutaneous implant., (Published by Elsevier Ltd.)

It is well known that ecological processes such as population regulation and natural enemy interactions potentially occur over a range of spatial scales, and there is a substantial body of literature developing theoretical understanding of the interplay between these processes. However, there are comparatively few studies quantifying the long-term effects of spatial scaling in natural ecosystems. A key challenge is that trophic complexity in real-world biological communities quickly obscures the signal from a focal process. Seagrass meadows provide an excellent opportunity in this respect: in many instances, seagrasses effectively form extensive natural monocultures, in which hypotheses about endogenous dynamics can be formulated and tested. We present amongst the longest unbroken, spatially explict time series of seagrass abundance published to date. Data include annual measures of shoot density, total above-ground abundance, and associated epiphyte cover from five Zostera marina meadows distributed around the Isles of Scilly, UK, from 1996 to 2011. We explore empirical patterns at the local and metapopulation scale using standard time series analysis and develop a simple population dynamic model, testing the hypothesis that both local and metapopulation scale feedback processes are important. We find little evidence of an interaction between scales in seagrass dynamics but that both scales contribute approximately equally to observed local epiphyte abundance. By quantifying the long-term dynamics of seagrass-epiphyte interactions we show how measures of density and extent are both important in establishing baseline information relevant to predicting responses to environmental change and developing management plans. We hope that this study complements existing mechanistic studies of physiology, genetics and productivity in seagrass, whilst highlighting the potential of seagrass as a model ecosystem. More generally, this study provides a rare opportunity to test some of the predictions of ecological theory in a natural ecosystem of global conservation and economic value.

The role of disease in the long-term dynamics of threatened species is poorly quantified, as well as being under-represented in ecology and conservation management. To understand persistent host-pathogen interaction operating in a vulnerable habitat, we quantified dynamics driving patterns of seagrass density using a longitudinal study in a relatively pristine site (Isles of Scilly, UK). Replicated samples of eelgrass (Zostera marina) density and wasting disease prevalence, presumably caused by Labyrinthula zosterae, were taken from five meadows at the height of the growing season, over the years 1997-2010. Data were used to parameterise a population dynamic model, incorporating density-dependent factors and sea temperature records. We found that direct density and disease-mediated feedback operate within a network of local populations. Furthermore, our results indicate that the strength of limitation to seagrass growth by disease was increased at higher temperatures. This modification of the coupled host-pathogen dynamics forms a novel hypothesis to account for dramatic die-backs of Z. marina widely reported elsewhere. Our findings highlight the importance of disease in structuring distributions of vulnerable species, as well as the application of population modelling in order to reveal ecological processes and prioritize future mechanistic investigation.

White privilege is a system of benefits, advantages, and opportunities experienced by White persons in our society simply because of their skin color. In this article, the authors present the results of a descriptive, exploratory study of White privilege in battered women's shelters in the Deep South. Based on a qualitative analysis, the authors show how White privilege is intricately connected to executive directors' claims of color blindness, the othering of women of color, and viewing White as the norm. The authors conclude the article with implications for service provision to battered women and directions for future research.

A multiple cannulated rat model was utilized to investigate the relative contribution of the gut and liver as sites of first-pass metabolism of orally administered U-54494A, an anticonvulsant drug candidate. Each rat received a dose of U-54494A by oral, intraportal, and intravenous routes on three separate occasions. Intraportal and intravenous doses were administered through chronic cannulas surgically implanted in the portal vein and superior vena cava, respectively. Blood samples were collected over a 6-hr period from the superior vena cava cannula. The mean (n = 3) bioavailability of orally dosed U-54494A was 4.5 +/- 1.1%, while that dosed intraportally was 19.1 +/- 3.0%. The relative contribution of the gut and liver as sites of first-pass extraction and/or metabolism of orally administered drug was 69.9 +/- 14.0% and 24.5 +/- 12.2%, respectively. Approximately 35 to 40% of the total plasma clearance was attributeds to the liver. The plasma concentrations of the four known metabolites of U-54494A were apparently higher for the oral and intraportal routes compared to that after intravenous administration. This investigation confirms that the low oral bioavailability of U-54494A in the rat can be primarily attributed to both extensive intestinal and hepatic first-pass metabolism.

A sensitive activity assay for high volume evaluation of human renin inhibitory peptides (RIPs) in rat sera (range 2-80 ng/ml) was developed based on the low affinity of RIPs to rat renin and their high affinity to human renin. The utility of this activity assay was tested by measuring concentrations of a human RIP, U-71,038 (BOC-Pro-Phe-N-MeHis-Leu psi [CHOHCH2]Val-Ile-Amp), in rat sera, determined by the activity assay, by a sensitive radioimmunoassay (RIA), and by tracking tritiated drug. Rats were given radiolabeled drug as an intravenous bolus, and blood samples were collected at various times after dosing. The serum level of U-71,038 equivalents was determined by the three techniques. Whole blood was also counted for total radioactivity to evaluate the potential for U-71,038 incorporation into red blood cells. Results from the three serum assays indicate good agreement between the calculated U-71,038 equivalents for the 30 min and 1 hr collection times. The 2 and 4 hr collection times show excellent agreement for the activity assay and RIA; [3H]-U-71,038 determinations gave substantially higher values. Serum levels for U-71,038 determined 30 min after dosing averaged less than 300 ng equivalents/ml suggesting that less than 1% of the administered dose was in the systemic circulation at that time. Thus, U-71,038 was rapidly cleared. At the 4 hr collection time, the level of U-71,038 equivalents, as determined by activity assay and RIA, was ten times the in vitro IC50 for the renin inhibitory activity of U-71,038.(ABSTRACT TRUNCATED AT 250 WORDS)

A new topological index, the largest eigenvalue of the distance matrix (DI), is presented as a measure of molecular branching. The DI and Balaban's J index are used to predict the densities of a series of alkanes. The statistical correlations obtained are excellent and give a correlation coefficient of 0.961.

The in vivo fate of U-71038 (Boc-Pro-Phe-N-MeHis-Leu psi [CHOHCH2] Val-Ile-(aminomethyl)pyridine), a potent renin inhibitor, was investigated in rats by single iv administration of tritium-labeled drug at a dose level of 5 mg/kg. The plasma concentrations of drug-related radioactivity diminished very rapidly during the first hour after dosing, with the initial concentrations measured at 2 min falling by more than 95% during the first 30 min. Estimates of the approximate half-life of this earliest phase of the plasma concentration-time curve gave an average value of 4 min. The residual amount of radioactivity after 30 min was cleared from the plasma more slowly, with trace levels still detected 48 hr after dosing. The radioactivity was recovered chiefly (91% of the dose) in feces, indicating biliary clearance as the primary route of elimination from systemic circulation. Urinary recoveries averaged 4% of the dose. Radio-HPLC profiling of plasma, urine, and bile extracts detected only a single radioactive drug-related component in these samples. Preparative HPLC was used to isolate this component from bile; mass spectral comparison to U-71038 confirmed its identity as the unchanged drug. Therefore, U-71038 does not undergo significant systemic metabolism in this species and is eliminated in bile and urine in intact form. Distribution of drug-related radioactivity was very rapid to most of the organs and tissues that were sampled, with the exception of very limited penetration into the central nervous system. Highest tissue levels of tritium were generally found in organs associated with elimination (liver, intestine, kidney) and in thyroid.