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Efferent muscle sympathetic nerve activity (MSNA) is under tonic baroreflex control. The arterial baroreflex exerts the strongest influence over medium-sized sympathetic action potential (AP) subpopulations in efferent MSNA recordings. Prior work from multiunit MSNA recordings has shown baroreflex loading selectively abolishes the sympathetic response to hypoxia. The purpose of the study was to examine baroreflex control over different-sized AP clusters and characterize the neural recruitment strategies of sympathetic AP subpopulations with baroreflex and combined baroreflex/chemoreflex (i.e., hypoxia) activation. We loaded the arterial baroreceptors [intravenous phenylephrine (PE)] alone and in combination with systemic hypoxia (S p O 2 80%) in nine healthy young men. We extracted sympathetic APs using the wavelet-based methodology and quantified baroreflex gain for individual AP clusters. AP baroreflex threshold gain was measured as the slope of the linear relationship between AP probability versus diastolic blood pressure for 10 normalized clusters. Baroreflex loading with phenylephrine decreased MSNA and AP firing compared with baseline (all P < 0.05). However, the phenylephrine-mediated decrease in AP firing was lost with concurrent hypoxia (P = 0.384). Compared with baseline, baroreflex loading reduced medium-sized AP cluster baroreflex threshold slope (condition P = 0.005) and discharge probability (condition P < 0.0001); these reductions from baseline were maintained during simultaneous hypoxia (both P < 0.05). Present findings indicate a key modulatory role of the baroreceptors on medium-sized APs in blood pressure regulation that withstands competing signals from peripheral chemoreflex activation. NEW & NOTEWORTHY: This study provides a novel understanding on baroreflex control of efferent sympathetic nervous system activity during competing stressors: baroreflex loading and peripheral chemoreflex activation. We show chemoreflex activation buffers baroreflex-mediated reductions in sympathetic nervous system activity. More importantly, baroreflex loading reduced baroreflex threshold gain of sympathetic action potential clusters and this reduction withstood chemoreflex activation. These data suggest the arterial baroreflex holds a primary regulatory role over medium-sized sympathetic neurons despite competing chemoreflex signals. [ABSTRACT FROM AUTHOR]

The aim of this study was to determine the effect of posture changes on vascular compliance in intracranial (brain) versus extracranial vascular beds (forearm). Eighteen young adults (nine females) performed a supine-to-seated-to-standing protocol involving 5 min of rest in each position. Continuous blood pressure, middle cerebral artery (MCA) blood velocity, and brachial artery blood velocity were recorded at each posture. Three to five consecutive steady-state cardiac cycles at each posture were analyzed by a four-element lumped parameter modified Windkessel model to calculate vascular compliance. Mean arterial pressure (MAP) increased from supine to seated (76(9) vs. 81(12) mmHg; P = 0.006) and from supine to standing (76(9) vs. 82(13) mmHg; P = 0.034). Mean blood flow was greater in the MCA relative to the forearm (forearm: 40(5) mL·min−1, MCA: 224(17) mL·min−1; main effect P < 0.001). Conversely, vascular resistance (forearm: 3.25(0.50) mmHg−1·mL·min−1, brain: 0.36(0.04) mmHg−1·mL·min−1; main effect P < 0.001) and compliance (forearm: 0.010(0.001) mL·min−1·mmHg−1, brain: 0.005(0.001) mL·min−1·mmHg−1; main effect P = 0.001) were greater in the forearm compared to the brain. Significant main effects of posture were observed with decreasing values in upright positions for mean blood flow (P = 0.001) in both vascular beds, but not for resistance (P = 0.163) or compliance (P = 0.385). There were no significant interaction effects between vascular bed and posture for mean flow (P = 0.057), resistance (P = 0.258), or compliance (P = 0.329). This study provides evidence that under steady-state conditions, posture does not affect cerebrovascular compliance. [ABSTRACT FROM AUTHOR]

The present study investigated the impact of central α2‐adrenergic mechanisms on sympathetic action potential (AP) discharge, recruitment and latency strategies. We used the microneurographic technique to record muscle sympathetic nerve activity and a continuous wavelet transform to investigate postganglionic sympathetic AP firing during a baseline condition and an infusion of a α2‐adrenergic receptor agonist, dexmedetomidine (10 min loading infusion of 0.225 µg kg−1; maintenance infusion of 0.1–0.5 µg kg h−1) in eight healthy individuals (28 ± 7 years, five females). Dexmedetomidine reduced mean pressure (92 ± 7 to 80 ± 8 mmHg, P < 0.001) but did not alter heart rate (61 ± 13 to 60 ± 14 bpm; P = 0.748). Dexmedetomidine reduced sympathetic AP discharge (126 ± 73 to 27 ± 24 AP 100 beats−1, P = 0.003) most strongly for medium‐sized APs (normalized cluster 2: 21 ± 10 to 5 ± 5 AP 100 beats−1; P < 0.001). Dexmedetomidine progressively de‐recruited sympathetic APs beginning with the largest AP clusters (12 ± 3 to 7 ± 2 clusters, P = 0.002). Despite de‐recruiting large AP clusters with shorter latencies, dexmedetomidine reduced AP latency across remaining clusters (1.18 ± 0.12 to 1.13 ± 0.13 s, P = 0.002). A subset of six participants performed a Valsalva manoeuvre (20 s, 40 mmHg) during baseline and the dexmedetomidine infusion. Compared to baseline, AP discharge (Δ 361 ± 292 to Δ 113 ± 155 AP 100 beats−1, P = 0.011) and AP cluster recruitment elicited by the Valsalva manoeuvre were lower during dexmedetomidine (Δ 2 ± 1 to Δ 0 ± 2 AP clusters, P = 0.041). The reduction in sympathetic AP latency elicited by the Valsalva manoeuvre was not affected by dexmedetomidine (Δ –0.09 ± 0.07 to Δ –0.07 ± 0.14 s, P = 0.606). Dexmedetomidine reduced baroreflex gain, most strongly for medium‐sized APs (normalized cluster 2: –6.0 ± 5 to –1.6 ± 2 % mmHg−1; P = 0.008). These data suggest that α2‐adrenergic mechanisms within the central nervous system modulate sympathetic postganglionic neuronal discharge, recruitment and latency strategies in humans. Key points: Sympathetic postganglionic neuronal subpopulations innervating the human circulation exhibit complex patterns of discharge, recruitment and latency. However, the central neural mechanisms governing sympathetic postganglionic discharge remain unclear.This microneurographic study investigated the impact of a dexmedetomidine infusion (α2‐adrenergic receptor agonist) on muscle sympathetic postganglionic action potential (AP) discharge, recruitment and latency patterns.Dexmedetomidine infusion inhibited the recruitment of large and fast conducting sympathetic APs and attenuated the discharge of medium sized sympathetic APs that fired during resting conditions and the Valsalva manoeuvre.Dexmedetomidine infusion elicited shorter sympathetic AP latencies during resting conditions but did not affect the reductions in latency that occurred during the Valsalva manoeuvre.These data suggest that α2‐adrenergic mechanisms within the central nervous system modulate sympathetic postganglionic neuronal discharge, recruitment and latency strategies in humans. [ABSTRACT FROM AUTHOR]

BACKGROUND. Convalescent plasma is the only antibody-based therapy currently available for patients with coronavlrus disease 2019 (COVID-19). It has robust historical precedence and sound biological plausibility. Although promising, convalescent plasma has not yet been shown to be safe as a treatment for COVID-19. METHODS. Thus, we analyzed key safety metrics after transfusion of ABO-compatible human COVID-19 convalescent plasma in 5000 hospitalized adults with severe or life-threatening COVID-19, with 66% in the intensive care unit, as part of the US FDA expanded access program for COVID-19 convalescent plasma. RESULTS. The incidence of all serious adverse events (SAEs), including mortality rate (0.3%), in the first 4 hours after transfusion was CONCLUSION. Given the deadly nature of COVID-19 and the large population of critically ill patients included in these analyses, the mortality rate does not appear excessive. These early indicators suggest that transfusion of convalescent plasma is safe in hospitalized patients with COVID-19. TRIAL REGISTRATION. ClinicalTrials.gov NCT04338360. FUNDING. Mayo Clinic, Biomedical Advanced Research and Development Authority (75A50120C00096), National Center for Advancing Translational Sciences (UL1TR002377), National Heart, Lung, and Blood Institute (5R35HL139854 and R01 HL059842), National Institute of Diabetes and Digestive and Kidney Diseases (5T32DK07352), Natural Sciences and Engineering Research Council of Canada (PDF-532926-2019), National Institute of Allergy and Infectious Disease (R21 AI145356, R21 AI152318, and AI152078), Schwab Charitable Fund, United Health Group, National Basketball Association, Millennium Pharmaceuticals, and Octapharma USA Inc., Introduction The number of confirmed cases of coronavirus disease 2019 (COVID-19) and the number of deaths attributed to COVID-19 in the US exceed that of any other country in the [...]

Background The United States (US) Expanded Access Program (EAP) to coronavirus disease 2019 (COVID-19) convalescent plasma was initiated in response to the rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19. While randomized clinical trials were in various stages of development and enrollment, there was an urgent need for widespread access to potential therapeutic agents. The objective of this study is to report on the demographic, geographical, and chronological characteristics of patients in the EAP, and key safety metrics following transfusion of COVID-19 convalescent plasma. Methods and findings Mayo Clinic served as the central institutional review board for all participating facilities, and any US physician could participate as a local physician-principal investigator. Eligible patients were hospitalized, were aged 18 years or older, and had-or were at risk of progression to-severe or life-threatening COVID-19; eligible patients were enrolled through the EAP central website. Blood collection facilities rapidly implemented programs to collect convalescent plasma for hospitalized patients with COVID-19. Demographic and clinical characteristics of all enrolled patients in the EAP were summarized. Temporal patterns in access to COVID-19 convalescent plasma were investigated by comparing daily and weekly changes in EAP enrollment in response to changes in infection rate at the state level. Geographical analyses on access to convalescent plasma included assessing EAP enrollment in all national hospital referral regions, as well as assessing enrollment in metropolitan areas and less populated areas that did not have access to COVID-19 clinical trials. From April 3 to August 23, 2020, 105,717 hospitalized patients with severe or life-threatening COVID-19 were enrolled in the EAP. The majority of patients were 60 years of age or older (57.8%), were male (58.4%), and had overweight or obesity (83.8%). There was substantial inclusion of minorities and underserved populations: 46.4% of patients were of a race other than white, and 37.2% of patients were of Hispanic ethnicity. Chronologically and geographically, increases in the number of both enrollments and transfusions in the EAP closely followed confirmed infections across all 50 states. Nearly all national hospital referral regions enrolled and transfused patients in the EAP, including both in metropolitan and in less populated areas. The incidence of serious adverse events was objectively low ( Conclusions These results suggest that the EAP provided widespread access to COVID-19 convalescent plasma in all 50 states, including for underserved racial and ethnic minority populations. The study design of the EAP may serve as a model for future efforts when broad access to a treatment is needed in response to an emerging infectious disease. Trial registration ClinicalTrials.gov NCT#: NCT04338360., Author(s): Jonathon W. Senefeld 1, Patrick W. Johnson 2, Katie L. Kunze 3, Evan M. Bloch 4, Noud van Helmond 1,5, Michael A. Golafshar 3, Stephen A. Klassen 1, Allan [...]

A major aspect of the power of a historically based science story derives from its ability to cultivate interest in the reader or listener. In this paper, we review the research on interest originating from diverse scholarly areas and apply it to the understanding, construction, and effective use of science stories in both formal and informal learning environments. Significantly, the raising of interest in science addresses the vital concern of declining engagement with school science, which might be thought of as a decline in interest. Prototype stories and methods to incorporate them are included.

The purpose of this paper is to discuss and apply the notion of romantic understanding by outlining its features and its potential role in science education, to identify its features in the story of Nikola Tesla, and to describe an empirical study conducted to determine the effect of telling such a story to Grade 9 students. Elaborated features of the story are the humanization of meaning, an association with heroes and heroic qualities, the limits of reality and extremes of experience, a sense of wonder, and a contesting of conventions and conventional ideas. The study demonstrates the learning benefits of encouraging a romantic understanding through a story that is structured explicitly around the identified features, in this instance in the context of the production and transmission of alternating current electricity. Quantitative and qualitative analyses of journal entries showed that the group of students who were encouraged to understand the concept of alternating current romantically (the experimental group) became more involved with both the content and the context of the story than a comparison group of students who were taught the concept explicitly, without a context (the control group). The students in the experimental group also performed statistically better on a science-content test taken 1 week and again 8 weeks after the indicated teaching intervention. This finding, along with the content analyses of students' journals, provided evidence of romantic understanding of the science content for those students who listened to the Tesla story.

The literature on the pedagogical aspects of the photoelectric effect as used in the undergraduate student laboratory shows that little research has been done in this area. Our current study is an analysis of the instructions in 38, electronically published laboratory manuals for the photoelectric effect. The analyses were based on history and philosophy of science criteria that we had developed for evaluating the presentation of the photoelectric effect in introductory, university-physics textbooks. The results show that writers of laboratory instructions do not pay sufficient attention to the relevant background for the photoelectric effect. In our study, none of the instructions achieved a score of excellent, only 5% were scored as satisfactory, and only 7% mentioned the various aspects contained in our criteria. These results for our analysis of laboratory instructions are significantly less favorable than those achieved for physics textbooks in our previous study. Based on our work, we recommend that several historical aspects be included in all laboratory instructions for the photoelectric effect.

History of science can be used to bring scientific concepts to school science in a way that humanizes the protagonists and provides an appropriate context. The authors have researched the 1909 meeting of the British Association for the Advancement of Science (BAAS) in Winnipeg, a significant event in the city's history that has remained largely unexplored until now, despite the existence of the original documents. The Mathematics and Physical Science Division of the BAAS met in Wesley College, which is now the University of Winnipeg. The meeting took place with much fanfare and public attention, especially with the attendance of the prominent scientists Rutherford, Thomson, Hahn, and Millikan, all of whom were or would become Nobel Laureates. Prominent themes relating to this meeting will be discussed in this paper.

The photoelectric effect is an important part of general physics textbooks. To study the presentation of this phenomenon, we have reconstructed six essential, history and philosophy of science (HPS)-related aspects of the events that culminated in Einstein proposing his hypothesis of lightquanta and the ensuing controversy within the scientific community. These aspects are (1) Lenard's trigger hypothesis to explain the photoelectric effect, (2) Einstein's quantum hypothesis to explain the photoelectric effect, (3) lack of acceptance of Einstein's quantum hypothesis in the scientific community, (4) Millikan's experimental determination of the Einstein photoelectric equation and Planck's constant, h, (5) Millikan's presuppositions about the nature of light, and (6) the historical presentation and its interpretation within a history and philosophy of science perspective. Using these aspects as criteria, we analyzed 103 university general physics textbooks. Results obtained reveal that these historical elements are largely ignored or distorted in the textbooks, with only three of the texts obtaining a score of satisfactory and none a score of excellent. It is concluded that inclusion of HPS-related aspects in general physics textbooks can facilitate a better understanding of the dynamics associated with the initial controversy and final acceptance of Einstein's explanation of the photoelectric effect by the scientific community. (Contains 3 tables and 1 figure.)

Millikan's oil-drop experiment is one of the classic experiments from the history of physics. Due to its content (the determination of the elementary charge) it is also among those experiments that are frequently used and discussed in teaching situations. Disappointingly, a review of the educational literature on this experiment reveals that its implementation in teaching situations is not especially successful. Using a collaborative approach, we have attempted to develop an understanding of the difficulties that students encounter with this experiment. In our approach, apart from evaluating students' lab reports, we used questionnaires and semi-structured interviews. Additionally, we have used the historical development of the oil-drop experiment as a resource for restructuring the educational use of the experiment, and we have attempted to develop a more thorough understanding of the experiment through an analysis of the data generated in the experiment and its mathematical treatment. As a result, we suggest a different use of the apparatus that appears to result in less frustration of the students as well as a better understanding of the experiment and its difficulties by the students. (Contains 7 figures and 5 footnotes.)

Although various reasons have been proposed to explain the potential effectiveness of science stories to promote learning, no explicit relationship of stories to learning theory in science has been propounded. In this paper, two structurally analogous models are developed and compared: a structural model of stories and a temporal conceptual change model of learning. On the basis of the similarity of the models, as elaborated, it is proposed that the structure of science stories may promote a re-enactment of the learning process, and, thereby, such stories serve to encourage active learning through the generation of hypotheses and explanations. The practical implications of this theoretical analogy can be applied to the classroom in that the utilization of stories provides the opportunity for a type of re-enactment of the learning process that may encourage both engagement with the material and the development of long-term memory structures.

The authors of this paper portray the perspective of Professor Leon Cooper, a theoretical physicist, Nobel laureate, active researcher, and physics textbook author, on teaching science and on the nature of science (NOS). The views presented emerged from an interview prepared by the authors and responded to in writing by Professor Cooper. Based on the gathered data and the subsequent interpretation of it, the authors identified several educational implications and drew the following conclusions: (a) science should be taught within an historical perspective; (b) textbook authors generally have an empiricist epistemology which makes their presentation of science difficult to understand; (c) an historical perspective inevitably involves comparing, contrasting, and scrutinizing different historical accounts of the same events; (d) varying interpretations of observations do not undermine the objective nature of science; (e) new ideas in physics comprise an imposed vision of the world, and these ideas are then slowly accepted by the scientific community; (f) the current view in any science is almost always a mixture of data, hypotheses, theoretical ideas, and conjectures; (g) since experiments are difficult to perform and understand, scientists rely on their presuppositions to guide the integration of data, theory, and conjectures; (h) inconsistencies in the construction of theories can facilitate new theoretical ideas; and (i) case studies based on various experiments show that scientists use intuition which is guided by facts, conjectures, and speculations.

The Millikan oil drop experiment has been characterized as one of the "most beautiful" physics experiments of all time and, certainly, as one of the most frustrating of all the exercises in the undergraduate physics laboratory. A literature review reveals that work done on addressing student difficulties in performing the oil drop experiment has, to date, not achieved a significant measure of success. The historical background of the oil drop experiment is well established in the literature from the perspective of historians of science, but not so from the perspective of teachers and students of science. A summary of historical details surrounding the original experiment suitable for use in revising the instructional approach is presented. Both Millikan and his graduate student, Fletcher, are featured with the view to emphasizing details that humanize the protagonists and that are likely to raise student interest. The issue of the necessary reliance on presuppositions in doing speculative research is raised, both from the historical account and from the insights of university physics students who heard the historical account and performed the experiment. Difficulties current students have in performing the experiment are discussed from the perspective of Hodson ("Stud Sci Educ" 22:85-142, 1993) framework and the students' own observations. Last, further historical materials are outlined that may be used to encourage student insight into the fundamental nature of electricity. It is proposed that these aspects are essential as a basis for identifying and addressing student difficulties with the Millikan oil drop experiment.

Science educators are beginning to establish a theoretical and methodological foundation for constructing and using stories in science teaching. At the same time, it is not clear to what degree science stories that have recently been written adhere to the guidelines that are being proposed. The author has written a story about Louis Slotin, which deals with the beginnings of radiation protection, to serve as a case study. In this paper, the story is dissected and evaluated with the view to begin to establish a method of literary criticism for science stories. In addition, student responses to the story are investigated and interpreted.

The use of historically based stories to teach science has both theoretical and practical support. This paper outlines how the historically based story may be utilized effectively in the classroom and, as an illustration of this, presents the story of Lord Kelvin's role in the laying of the first trans-Atlantic communications cable during the period from 1857 to 1866. Expected and observed classroom benefits that accrue from this approach are summarized. The paper concludes with an outline of a program of research which incorporates the development of historically based stories.

Many educators today advocate the use of historical narratives as one of a number of possible contexts for teaching science. However, several pedagogical and epistemological issues arise when implementing narratives in the classroom. In this paper, we are interested in expanding our view of narrative, specific to integrating the history of science and science teaching, and we extend our argument beyond simple anecdotal references to recognise the benefits of the historical narrative in a variety of ways. At the same time, we address pedagogical concerns by broadening perceptions of the manner and contexts in which narratives can be developed so as to include imaginative and manipulative elements that provide interactive experiences for students that are more conducive to implementation by science teachers. Several practical examples are presented as illustrations of historical narratives with imaginative and manipulative elements that by design facilitate a more meaningful implementation in the science classroom.

It is well established that thought experiments are both scientifically and philosophically significant, and even that they are pedagogically significant. However, the basis and methodology for their pedagogical use is not as well established. Pedagogical thought experiments are defined as mental simulations with special features to isolate certain conceptual elements. It is argued that thought experiments are made pedagogically effective through the process of re-enactment of the thought-experimental process. The process of re-enactment is best captured by rewriting thought experiments as stories. Several examples of thought experiments are analysed for their narrative content and an example is given of a pedagogical thought experiment re-written as a story. Recommendations are made as to how such thought experimental stories can be used effectively.

The contextual approach to teaching is generally recognized as a reasonable and desirable strategy to enhance student learning in science. Using several cognitive and learning theories together with various philosophical considerations, I identify five distinct contexts that are important in engaging learners: the theoretical, practical, social, historical, and affective. Based on these five contexts, I construct a model for teaching and learning, named the Story-Driven Contextual Approach (SDCA), in which the story assumes a major role in engaging the learner affectively. The teacher introduces the SDCA to students by means of a story, encouraging students to engage actively with the five contexts. In the SDCA, students function as novice researchers and the teacher as a research director.