Simulated cardiopulmonary bypass: a high fidelity model for developing and accessing clinical perfusion skills.

BACKGROUND: Traditionally, novice perfusionists learn and practice clinical skills, during live surgical procedures. The profession's accrediting body is directing schools to implement simulated cardiopulmonary bypass (CPB) into the curriculum. Unfortunately, no CPB simulation models have been validated. Here we describe the design and application of a CPB simulation model. METHODS: A CPB patient simulator was integrated into a representative operative theater and interfaced with a simple manikin, a heart-lung machine (HLM), clinical perfusion circuitry, and equipment. Participants completed a simulation scenario designed to represent a typical CPB procedure before completing an exit survey to assess the fidelity and validity of the experience. Questions were scored using a 5-point Likert scale. RESULTS: Participants (n = 81) contributed 953 opinions on 40 questions. The participants reported that the model of simulated CPB (1) realistically presented both the physiologic and technical parameters seen during CPB (n = 347, mean 4.37, SD 0.86), (2) accurately represented the psychological constructs and cognitive mechanisms of the clinical CPB (n = 139, mean 4.24, SD 1.08), (3) requires real clinical skills and reproduces realistic surgical case progression (n = 167, mean 4.38, SD 0.86), and (4) would be effective for teaching, practicing, and assessing the fundamental skills of CPB (n = 300, mean 4.54, SD 0.9). Participants agreed that their performance in the simulation scenario accurately predicted their performance in a real clinical setting (n = 43, mean 4.07, SD 1.03) CONCLUSION: This novel simulation model of CPB reproduces the salient aspects of clinical CPB and may be useful for teaching, practicing, and assessing fundamental skills.

Route of drug administration in out-of-hospital cardiac arrest: A protocol for a randomised controlled trial (PARAMEDIC-3).

Aims: The PARAMEDIC-3 trial evaluates the clinical and cost-effectiveness of an intraosseous first strategy, compared with an intravenous first strategy, for drug administration in adults who have sustained an out-of-hospital cardiac arrest. Methods: PARAMEDIC-3 is a pragmatic, allocation concealed, open-label, multi-centre, superiority randomised controlled trial. It will recruit 15,000 patients across English and Welsh ambulance services. Adults who have sustained an out-of-hospital cardiac arrest are individually randomised to an intraosseous access first strategy or intravenous access first strategy in a 1:1 ratio through an opaque, sealed envelope system. The randomised allocation determines the route used for the first two attempts at vascular access. Participants are initially enrolled under a deferred consent model.The primary clinical-effectiveness outcome is survival at 30-days. Secondary outcomes include return of spontaneous circulation, neurological functional outcome, and health-related quality of life. Participants are followed-up to six-months following cardiac arrest. The primary health economic outcome is incremental cost per quality-adjusted life year gained. Conclusion: The PARAMEDIC-3 trial will provide key information on the clinical and cost-effectiveness of drug route in out-of-hospital cardiac arrest.Trial registration: ISRCTN14223494, registered 16/08/2021, prospectively registered.

Peer-led team learning in an undergraduate biology course: Impacts on recruitment, retention, and imposter phenomenon.

OBJECTIVES: The data presented in this note were collected during a multi-year project conducted in the context of large-enrollment introductory biology course at a large private R-1 research institution in the Northeastern United States. The project aimed to examine the impact of Peer-Led Team Learning (PLTL) on the recruitment and retention of marginalized groups in Science, Technology, Engineering, and Mathematics (STEM) majors. While several results from the project have been published, additional data of interest have yet to be reported. This data note reports on additional associations between PLTL participation and improved outcomes for students from groups that have historically been excluded in STEM. Additional data reported herein were collected to determine if students in the course experienced imposter phenomenon, and whether PLTL may be associated with reduced levels of imposter feelings. DATA DESCRIPTION: The data in this note includes academic information such as final course grades and academic level; socio-demographic information such as gender identity, minority status, and first-generation status; and information on student recruitment, retention, imposter feelings, and participation in Peer-Led Team Learning (PLTL). These data might be useful and of value to education researchers and undergraduate STEM instructors who are interested in improving equity in STEM education.

Danicopan, an Oral Complement Factor D Inhibitor, Exhibits High and Sustained Exposure in Ocular Tissues in Preclinical Studies.

Purpose: Complement alternative pathway (AP) dysregulation has been implicated in geographic atrophy, an advanced form of age-related macular degeneration. Danicopan is an investigational, first-in-class inhibitor of factor D, an essential AP activation enzyme. We assessed danicopan distribution to the posterior segment of the eye after oral dosing. Methods: Tissue distribution of drug-derived radioactivity was evaluated using whole-body autoradiography following oral administration of [14C]-danicopan to pigmented and albino rats. Pharmacokinetics and ocular tissue distribution were studied in pigmented and albino rabbits following single and multiple oral dosing of danicopan. The melanin binding property was characterized in vitro. Results: Radioactivity was distributed widely in rats and became nonquantifiable in most tissues 24 hours postdose except in the pigmented rat uvea (quantifiable 672 hours postdose). Danicopan binding to melanin was established in vitro. After single dosing, the maximum concentration (Cmax) and area under the curve (AUC) in neural retina and plasma were similar in both rabbit types. After multiple dosing, AUC in neural retina was 3.4-fold higher versus plasma in pigmented rabbits. Drug levels in choroid/Bruch's membrane (BrM)/retinal pigment epithelium (RPE) were similar to plasma in albino rabbits but higher in pigmented rabbits: Cmax and AUC were 2.9- and 23.8-fold higher versus plasma after single dosing and 5.8- and 62.7-fold higher after multiple dosing. In pigmented rabbits, ocular tissue exposures slowly declined over time but remained quantifiable 240 hours postdose. Conclusions: The results demonstrate that danicopan crosses the blood-retina barrier and binds melanin reversibly, leading to a higher and more sustained exposure in melanin-containing ocular tissues (choroid/BrM/RPE) and in the neural retina as compared to in plasma after repeated oral dosing in pigmented animals. Translational Relevance: These findings suggest that oral danicopan possesses potential for treating geographic atrophy because AP dysregulation in the posterior segment of the eye is reported to be involved in the disease pathogenesis.

A comparison study of human examples vs. non-human examples in an evolution lesson leads to differential impacts on student learning experiences in an introductory biology course.

BACKGROUND: Instructors can teach evolution using any number of species contexts. However, not all species contexts are equal, and taxa choice can alter both cognitive and affective elements of learning. This is particularly true when teaching evolution using human examples, a promising method for evolution instruction that nevertheless comes with unique challenges. In this study, we tested how an evolution lesson focused on a human example may impact students' engagement, perceived content relevance, learning gains, and level of discomfort, when compared to the same lesson using a non-human mammal example. We use this isomorphic lesson and a pre-post study design administered in a split-section introductory biology classroom to isolate the importance of the species context. RESULTS: For two of the four measurements of interest, the effect of using human examples could not be understood without accounting for student background. For learning gains, students with greater pre-class content knowledge benefited more from the human examples, while those with low levels of knowledge benefited from the non-human example. For perceived relevance, students who were more accepting of human evolution indicated greater content relevance from the human example. Regardless of condition, students with lower evolution acceptance reported greater levels of discomfort with the lesson. CONCLUSIONS: Our results illustrate the complexities of using human examples to teach evolution. While these examples were beneficial for many students, they resulted in worse outcomes for students that were less accepting of evolution and those who entered the course with less content knowledge. These findings demonstrate the need to consider diverse student backgrounds when establishing best practices for using human examples to teach evolution. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12052-021-00148-w.

Lessons learned through listening to biology students during a transition to online learning in the wake of the COVID-19 pandemic.

During the Spring Semester of 2020, an outbreak of a novel coronavirus (SARS-CoV-2) and the illnesses it caused (COVID-19) led to widespread cancelling of on-campus instruction at colleges and universities in the United States and other countries around the world. Response to the pandemic in university settings included a rapid and unexpected shift to online learning for faculty and students. The transition to teaching and learning online posed many challenges, and the experiences of students during this crisis may inform future planning for distance learning experiences during the ongoing pandemic and beyond. Herein, we discuss the experiences of first- and second-year university students enrolled in a biology seminar course as their classes migrated to online environments. Drawing on reported student experiences and prior research and resources, we discuss the ways we will adjust our own teaching for future iterations of the course while offering recommendations for instructors tasked with teaching in online environments.

Objective Content Validation of the Hemodynamic and Technical Parameters of the OrpheusTM Cardiopulmonary Bypass Simulator.

The utilization of simulators for training is increasing in the professions associated with cardiac surgery. Before applying these simulators to high-stakes assessment, the simulator's output data must be validated. The aim of this study is to validate a Cardiopulmonary Bypass (CPB) simulator by comparing the simulated hemodynamic and technical outputs to published clinical norms. Three Orpheus™ CPB simulators were studied and compared to a published reference of physiologic and technical metrics that are managed during clinical CPB procedures. The limits of the simulators user modifiable variables were interrogated across their full range and the results were plotted against the published clinical norms. The data generated with the simulator conforms to validated clinical parameters for patients between 50 and 110 kg. For the pre- and post-CPB periods, the independent variables of central venous pressure (CVP), heart rate (HR), contractility, and systemic vascular resistance (SVR) must be operated between the limits of 7 and 12 mmHg, 65 and 110 beats/min, 28% and 65%, and 6 and 32 units respectively. During full CPB the arterial pump flows should be maintained between 3.5 and 5.5 LPM and SVR between 18 and 38 units. Validated technical parameters during cardioplegia delivery are expected at solution flow rates between 250 and 400 mL/min and 100 and 225 mL/min for antegrade and retrograde delivery routes, respectively. We have identified the limits for user-modifiable settings that produce data conforming to the physiologic and technical parameter limits reported in the peer reviewed literature. These results can inform the development of simulation scenarios used for high stakes assessments of personnel, equipment, and technical protocols.

Survey of the Routine Practice Limits for Physiologic and Technical Parameters Managed by Clinical Perfusionists during Adult Cardiopulmonary Bypass.

Cardiopulmonary bypass (CPB) is a highly technical clinical discipline with a recognized variability in practice. Professional standards and guidelines documents help direct clinical practice and reduce variability, but these guidelines are necessarily vague and fall short of providing specific objective recommendations of clinical practice metrics. If clinical practice metrics were known, they would be informative when writing departmental policy manuals, structuring quality improvement initiatives, describing product R&D specifications, and designing educational assessment rubrics. Therefore, to address this gap, we conducted a national survey of clinical practice with the purpose of producing a benchmark of the typical variability of specific technical parameters that are commonly managed during adult CPB procedures. A pool of expert clinical perfusionists collaborated to compile a data set of normal ranges for 41 individual physiologic and technical parameters (pressures, flows, saturation, times, solutions, and temperatures) that are commonly managed during adult CPB procedures. Results were collected using an online survey application. Respondent demographics and measures of central tendency with descriptive quartile statistics and confidence intervals for each parameter are presented. Of the 335 people who participated in the survey, 315 met the inclusion criteria. The geographic demographics of the respondents were representative of the American Board of Cardiovascular Perfusion's distribution of certified clinical perfusionists. Of the 41 parameters investigated, there were 13 hemodynamic parameters, 13 normal flow rates and technical circuit parameters, 10 blood gasses and hematocrit parameters, and five parameters of patient temperatures. The data presented here are informative and provide a consensus-based objective assessment of the standard practice for adult CPB as reported by practicing clinical perfusionists. Based on these survey data, we have identified the typical clinical limits for the 41 parameters that are managed during adult CPB. This information may be incorporated into guiding documents to support the work of clinicians, researchers, and educators.

Communicating the consensus on climate change to college biology majors: The importance of preaching to the choir.

College and university biology majors who are not climate change deniers may yet be unaware of the degree of scientific consensus on climate change and unprepared to communicate about climate science to others. This study reports on a population of climate change accepting biology majors at a large, private research university in the American northeast. Our students tended to greatly underestimate the degree of scientific consensus around climate change, to be only moderately worried about climate change, and to be unconfident in their ability to communicate about the state of the scientific consensus around climate change. After an introduction to the scholarly literature that substantiates and quantifies the scientific consensus on climate change in the context of a course on biological research literature, our students showed significant increases in their estimates of the consensus on climate change, and their estimates were more accurate. Additionally, they became more worried about climate change as well as more confident in their ability to communicate about the scientific consensus to others. These results are in line with the Gateway Belief Model, which positions perception of scientific agreement on climate change as an important driver of acceptance and motivation toward action.

Exploratory Activities for Understanding Evolutionary Relationships Depicted by Phylogenetic Trees: United but Diverse.

Evolution explains both the unity and the diversity of all organisms, and developing students' ability to represent and communicate evolutionary relationships is an important component of a complete biology education. We present a series of student-centered, exploratory activities to help students develop their tree-thinking skills. In these activities, students use complementary phenotypic and molecular data to explore how to build phylogenetic trees and interpret the evolutionary relationships they represent. This learning module is designed to engage students in the process of science, provide them with active learning experiences using online bioinformatics tools, and foster their appreciation for the evolutionary connections across the tree of life.

Discovery and Development of the Oral Complement Factor D Inhibitor Danicopan (ACH-4471).

Complement plays a vital role in our innate immune defense against invasive microorganisms. Excessive complement activation or insufficient control of activation on host cells, however, is associated with several chronic disorders. Essential to the activation and amplification of the Alternative Pathway (AP) of complement, Complement Factor D (CFD) is a specific serine protease that cleaves its unique substrate, Complement Factor B (CFB) in complex with an activated form of complement component 3 (C3), to generate the AP C3 convertases C3(H2O)Bb and C3bBb. These convertases comprise a central component in eliciting effector responses following AP activation, and they also enable a powerful amplification loop for both the Classical Pathway (CP) and Lectin Pathway (LP) of complement. Because CFD is not required for the activation of either the CP or LP, selective CFD inhibition presents a favorable therapeutic approach to modulating complement activity that leaves intact the effector functions following CP and LP activation and thus poses a lower risk of bacterial infection than other complement-directed approaches. This review provides an update on inhibitors of CFD, which have evolved from irreversible small molecules that demonstrate poor selectivity to reversible small molecules and monoclonal antibodies that demonstrate exceptional selectivity and potency. The reversible small-molecule inhibitor danicopan.

Utilizing Pediatric Physiologically Based Pharmacokinetic Models to Examine Factors That Contribute to Methadone Pharmacokinetic Variability in Neonatal Abstinence Syndrome Patients.

Chronic intrauterine exposure to psychoactive drugs often results in neonatal abstinence syndrome (NAS). NAS is the symptomatic drug withdrawal in newborns that generally occurs after in utero chronic opioid exposure. Methadone is an opioid analgesic commonly prescribed for pharmacologic management of NAS. It exhibits high pharmacokinetic (PK) variability. The current study used physiologically based PK modeling to predict the PK profile of methadone in 20 newborns treated for NAS. The physiologically based PK simulations adequately predicted the PK profile of the clinical data for 45% of the patients. Sensitivity analyses were conducted to explore contributing factors to methadone PK variability. The data suggest that P450 enzymatic activity impacts the clearance of methadone in virtual adults and neonates, while the contribution of cardiac output may be negligible. Understanding maturational and/or pharmacogenetic changes in cytochrome P450 enzymatic activity may further explain the large PK variability of methadone in newborns with NAS and will help individualized treatment.

Fundamental clinical skills of adult cardiopulmonary bypass: results of the 2017 national survey.

INTRODUCTION: Training students to become entry-level perfusionists requires evaluation and assessment of their clinical skills. While our professional organizations have compiled resources which identify the profession's knowledge base and categorical skills applied to clinical practice, these resources are lacking the necessary detail to develop validated clinical assessment rubrics. Therefore, the purpose of this project is to identify, through expert opinion, the detailed fundamental skills necessary to perform adult cardiopulmonary bypass (CPB). METHODS: We define a fundamental skill based upon frequency of use and risk of harm. A skill that experts report is conducted in >50% of their CPB cases - and, if not properly conducted, can cause harm, is deemed a fundamental skill. To identify these skills, a 73-question survey was developed and posted on PerfList and PerfMail from May 2017 to July 2017. RESULTS: The results from 261 respondents were analyzed. The demographics of the participants were representative of the workforce. Twenty skills were surveyed and all 20 met the criteria to be identified as a fundamental skill. Data regarding the actions, assessments and behaviors that may be associated with fundamental skills were also identified. CONCLUSIONS: Based upon this survey data, we have identified that there is consensus within our profession regarding the fundamental skills of adult CPB and a core body of actions, assessments and behaviors that experts perform when conducting these skills. This information may be incorporated into the entry-level educational process to inform curricula and design valid assessment rubrics.

Ferrocene-based inhibitors of hepatitis C virus replication that target NS5A with low picomolar in vitro antiviral activity.

An unprecedented series of organometallic HCV (hepatitis C virus) NS5A (nonstructural 5A protein) replication complex inhibitors that incorporates a 1,1'-ferrocenediyl scaffold was explored. This scaffold introduces the elements of linear flexibility and non-planar topology that are unconventional for this class of inhibitors. Data from 2-D NMR spectroscopic analyses of these complexes in solution support an anti (unstacked) arrangement of the pharmacophoric groups. Several complexes demonstrate single-digit picomolar in vitro activity in an HCV genotype-1b replicon system. One complex to arise from this investigation (10a) exhibits exceptional picomolar activity against HCV genotype 1a and 1b replicons, low hepatocellular cytotoxicity, and good pharmacokinetic properties in rat.

Concern About Hunger May Increase Receptivity to GMOs.

Due to a phenomenon known as the 'backfire effect', intuition-based opinions can be inadvertently strengthened by evidence-based counterarguments. Students' views on genetically modified organisms (GMOs) may be subject to this effect. We explored the impact of an empathetically accessible topic, world hunger, on receptivity to GMO technology as an alternative to direct evidence-based approaches.

Peer-Led Team Learning Helps Minority Students Succeed.

Active learning methods have been shown to be superior to traditional lecture in terms of student achievement, and our findings on the use of Peer-Led Team Learning (PLTL) concur. Students in our introductory biology course performed significantly better if they engaged in PLTL. There was also a drastic reduction in the failure rate for underrepresented minority (URM) students with PLTL, which further resulted in closing the achievement gap between URM and non-URM students. With such compelling findings, we strongly encourage the adoption of Peer-Led Team Learning in undergraduate Science, Technology, Engineering, and Mathematics (STEM) courses.

A Cohort Comparison of Buprenorphine versus Methadone Treatment for Neonatal Abstinence Syndrome.

OBJECTIVES: To compare the duration of opioid treatment and length of stay among infants treated for neonatal abstinence syndrome (NAS) by using a pilot buprenorphine vs conventional methadone treatment protocol. STUDY DESIGN: This retrospective cohort analysis evaluated infants who received pharmacotherapy for NAS at 6 hospitals in Southwest Ohio from January 2012 through August 2014. A single neonatology provider group used a standardized methadone protocol across all 6 hospitals. However, at one of the sites, infants were managed with a buprenorphine protocol unless they had experienced chronic in utero exposure to methadone. Linear mixed models were used to calculate adjusted mean duration of opioid treatment and length of inpatient hospitalization with 95% CIs in infants treated with oral methadone compared with sublingual buprenorphine. The use of adjunct therapy was examined as a secondary outcome. RESULTS: A total of 201 infants with NAS were treated with either buprenorphine (n = 38) or methadone (n = 163) after intrauterine exposure to short-acting opioids or buprenorphine. Buprenorphine therapy was associated with a shorter course of opioid treatment of 9.4 (CI 7.1-11.7) vs 14.0 (12.6-15.4) days (P < .001) and decreased hospital stay of 16.3 (13.7-18.9) vs 20.7 (19.1-22.2) days (P < .001) compared with methadone therapy. No difference was detected in the use of adjunct therapy (23.7% vs 25.8%, P = .79) between treatment groups. CONCLUSION: The choice of pharmacotherapeutic agent is an important determinant of hospital outcomes in infants with NAS. Sublingual buprenorphine may be superior to methadone for management of NAS in infants with select intrauterine opioid exposures.

Pharmacokinetics of Oral Methadone in the Treatment of Neonatal Abstinence Syndrome: A Pilot Study.

OBJECTIVE: To characterize the population pharmacokinetics of oral methadone in neonates requiring pharmacologic treatment of neonatal abstinence syndrome and to develop a pharmacokinetic (PK) model toward an evidence-based treatment protocol. STUDY DESIGN: Based on a methadone dosing protocol, serum concentrations of methadone and its metabolites were assessed by high performance liquid chromatography-tandem mass spectrometry from dried blood spots. Population PK analysis was performed to determine the volume of distribution and clearance of oral methadone. Methadone plasma concentration-time profiles were simulated from the deduced PK model to optimize the dosing regimen. RESULTS: There was substantial interindividual variability in methadone concentrations. Blood concentrations of methadone were best described by a 1-compartment model with first-order absorption. The population mean estimates (coefficient of variation percentage) for oral clearance and volume of distribution were 8.94 (103%) L/h/70 kg and 177 (133%) L/70 kg, respectively. Optimized dosing strategies were developed based on the simulated PK profiles. We suggest a starting dose of 0.1 mg/kg per dose every 6 hours for most patients requiring pharmacologic treatment of neonatal abstinence syndrome followed by an expedited weaning phase. CONCLUSIONS: The proposed dosing regimen may reduce the cumulative dose of opioid and shorten the length of hospitalization. Future studies should aim to validate the simulated dosing schemes with clinical data and expand our understanding of the between-patient PK variability. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01754324.

Implementation of the peer-led team-learning instructional model as a stopgap measure improves student achievement for students opting out of laboratory.

In entry-level university courses in science, technology, engineering, and mathematics fields, students participating in associated laboratory sessions generally do better than those who have no related lab classes. This is a problem when, for various reasons, not enough lab sections can be offered for students and/or when students opt out of optional available lab courses. Faced with such a situation, this study evaluated the efficacy of the peer-led team-learning (PLTL) instructional model as a potential method for narrowing the achievement gap among undergraduate students electing not to enroll in an optional laboratory component of an introductory biology course. In peer-led workshops, small groups of students participated in solving problems and other activities that encouraged active learning. Students led by peer leaders attained significantly higher exam and final course grades in introductory biology than comparable students not participating in PLTL. Among the introductory biology students who opted not to enroll in the optional lab course, those who participated in PLTL averaged more than a letter grade higher than those who did not. This difference was statistically significant, and the PLTL workshops almost entirely closed the achievement gap in lecture exam and final grades for students who did not take the lab.