bluuebunny/crossref_metadata_2025 huggingface dataset:
Plutarch
Authors: Erler Michael
Published: August 2020

Plutarch, a priest at Delphi and an enthusiastic adherent of “divine” Plato, found himself diametrically opposed to Epicurus’s teachings, yet granted considerable space to discussions of his propositions. He devoted a considerable number of his writings entirely to discussions of Epicurean doctrines. In these texts, he points out significant discrepancies between the theory and practice of Epicurean teachings. He discusses Epicurus’s deistic theology, criticizes Epicurus’s seemingly apolitical stance and in one treatise discusses a work by the Epicurean Colotes, who posited that it is impossible to live according to the precepts of other philosophers. Other works touch on Epicurean subjects, but are known only by title. All of this indicates that Plutarch engaged deeply with the entire breadth of Epicurean doctrine. After all, even those of Plutarch’s writings that do not deal directly or exclusively with the subject do frequently bring up Epicurean teachings and, more often than not, refute them. In doing so, Plutarch was apparently less concerned with a systematic refutation of Epicurus. Rather, it seems that Plutarch used Epicurus as a welcome foil to highlight his own, Platonist positions and to justify and underline his loyalty to Plato’s teachings. But his writings testify to the importance of Epicurean teachings at his time.
Philodemus and the Herculaneum Papyri
Authors: Capasso Mario
Published: August 2020

The article is divided into three parts: in the first part the most important phases of Philodemus of Gadara’s life are reconstructed through his works and his epigrams: his cultural trip to Alexandria; his educational stay in Athens, where he joined the Epicurean philosophy, by attending Zeno Sidonius’s lectures; his transfer to Rome, where he embarked on the difficult undertaking of popularizing the Philosophy of the Garden; his meeting and his relationship with Lucius Calpurnius Piso Caesoninus, who was his most important patronus; the place where he lived, his presence in the Villa dei Papiri with the group of Augustan intellectuals including Lucius Varius Rufus, Quinctilius Varus, Plotius Tucca, and Vergil, whom Philodemus addressed in certain books of the work On Vices and Their Opposite Virtues, sharing reflections on ethical topics, developed in the important treatise. The second part is devoted to the Villa dei Papiri: when it was built, who lived there, how it was furnished. The third part outlines the contents of the works of Philodemus recovered from papyri in the Villa and it reaches three relevant conclusions: he collected most of the Greek books in the Villa; he was, at least to a certain extent, an original philosophical writer; and he did not address his teaching to a small circle of learned men associated with the Villa.
Early Christianity
Authors: Ramelli Ilaria
Published: August 2020

Many fragments and testimonies in Usener’s collection, Epicurea, come from ancient Christian sources. This essay explores Patristic interest in Epicureanism, which is often critical, and sometimes imprecise or distorted, but tangible. It shows how the fading away of the availability and use of good sources on Epicureanism, along with the disappearance of the Epicurean school itself, brought about a progressive impoverishment and hostility among Christian authors with respect to Epicurus and Epicureanism. A comparison between the representation of Epicureanism in Acts or Clement, or still in Nazianzen or Ambrose, on one side, and, on the other, authors like Jerome or even Isidore of Seville is telling. Not only did appreciation for at least some sides of Epicureanism (clearly present in the author of Acts, Clement, Bardaisan, and Nazianzen) disappear, but even anti-Epicurean polemic became more and more stereotyped, crass hedonism and atheism being its main focuses, with scarce ground in Epicurean theory in both cases. The distortions surrounding the charge of hedonism were still clear to Nazianzen; as for the falsity of the charge of atheism, which was alive already in pre-Christian philosophical debate, the certainly Hellenized author of Acts was arguably aware of it, as is suggested by Paul’s Areopagus speech, which is here carefully analyzed. It is suggested that both Paul’s Athenian speech in Acts and Seneca may have referred to the same tenets of Epicurean theology.
Thomas Jefferson
Authors: Richard Carl J.
Published: August 2020

“Thomas Jefferson” demonstrates that Jefferson combined elements of Epicureanism with components of Stoicism and Christianity to form a unique philosophy. Jefferson derived from the Stoics and from Cicero the belief in an innate moral sense. Like these forebears, Jefferson envisioned the moral sense as a mere instinct for good that required training (reason acting on experience) to develop into full-blown virtue, rather than as a collection of Platonic innate ideas. Christianity furnished him with the concepts of a creator, a resurrection, and an afterlife. It also provided a system of ethics based on positive benevolence. He preferred the warmth and benevolence of Christianity to the cold obligations of classical philosophy, which centered on the mere avoidance of injury to oneself and others. Epicureanism provided other essential features of Jefferson’s philosophy, such as a materialist metaphysics and consequent rejection of miracles. Although Jefferson’s Epicureanism did not lead him to reject the doctrine of divine providence commonly held in his day, it contributed greatly to his belief that God worked solely through natural causes to achieve his ends. The Epicurean emphasis on the role played by reason (logic) acting on experience in uncovering truth and its concept of free will also influenced the Virginian.
Hedonism
Authors: Tsouna Voula
Published: August 2020

This chapter aims to give a fairly comprehensive account of Epicurean hedonism, highlighting its philosophical interest and its complex relation to rival doctrines. Evidence is used from relatively unexplored sources, in particular Philodemus and Diogenes of Oenoanda, as well as from Epicurus, his early associates, and Lucretius. The discussion will bring out the distinctive nature of Epicurean hedonism, its originality and sophistication, and its enduring core as well as its peripheral developments over time. The topics discussed include the following: Epicurus’s conception of the moral end and his theory of motivation; Epicurus’s conceptual amplification and defense of his hedonism (especially the controversial distinction between kinetic and katastematic pleasure, the claim that the removal of pain is the highest pleasure, and the respective roles of the body and the mind in the achievement of the supreme good); the Epicurean classification of desires and its ethical implications; and the unique importance of virtue in the rational pursuit of pleasure. Finally, the chapter considers some of the criticisms rehearsed by Cicero against Epicurean hedonism and discusses whether the Epicureans have sufficient resources to respond to them.
Cicero
Authors: Lévy Carlos
Published: August 2020

Epicurus confronted Cicero with a singular situation: a philosopher whom he thought had managed, despite professing erroneous doctrines, to live a philosophical life and thus overcome the incoherence of his doctrines. Schooled in Epicureanism in his youth and surrounded by Epicurean friends, Cicero nonetheless retained a strong aversion to Epicurean doctrines. Too many of the basic assumptions of Epicurus’s philosophy ran at cross-purposes with the deepest currents of his personality. Accepting Epicureanism would have required him to admit that society and ethics were grounded in the unstable vagaries of individuals’ desires for pleasure. So too, the Epicurean tendency to build everything upon self-interest appeared to deprive traditional Roman axiology of any true foundation. What is more, for him who had placed such importance on the concept of free will as a self-generated cause, the connection fashioned by Epicureans between voluntary action and the swerve of atoms governed by chance failed to provide a plausible rational explanation and, he thought, would inevitably act to dilute individual responsibility. Epicureanism, which counted immediate sense perceptions as necessarily true; rejected a philosophical language inaccessible to the masses; made its gods distant and indifferent yet all-too-visible; built an ethics so easy to grasp—and caricature; claimed to illuminate everything with a shining light; advertised its distrust for social and political hierarchies—all this was ultimately too distant, both intellectually and emotionally, from the conception of the world that was Cicero’s own.
Western Europe, the Second Front in the War of Algerian Independence
Authors: Amiri Linda
Published: August 2020

The Algerian War of Independence took place on two main fronts: Algeria and metropolitan France. In both cases, the National Liberation Front (Front de libération nationale [FLN]) paid little heed to national borders as they sought to internationalize their cause. Serving as the linchpin of Algerian nationalism, immigration was instrumental in the emergence and development of a clandestine organization with totalitarian aspirations: the French Federation of the FLN. Manned by a politico-administrative organization coupled with a military organization, the Federation sought both to combat Algerian opponents in Europe and to bring the struggle for independence to metropolitan France. Algerian immigration thus came under the purvey of the FLN’s general strategy and further spread the conflict to metropolitan France and, by extension, to Western Europe. Although the human costs of the war are still difficult to establish, this does nothing to diminish the long-standing stigma that it continues to bear on French postcolonial society.
CyberterrorismUnderstandings, Debates, and Representations
Authors: Whiting Andrew , Macdonald Stuart , Jarvis Lee
Published: August 2020

This chapter focuses on understandings and debates around cyberterrorism as well as the effect particular representations of this phenomenon have upon assessing its threat. The chapter begins by introducing various understandings of cyberterrorism and differentiates between narrow and broad conceptions as well as effects and intent based definitions. Moving on to consider the threat of cyberterrorism the chapter identifies an ongoing debate between “concerned” and “sceptical” voices as well as those that contest whether cyberterrorism has ever taken place. The chapter then introduces a range of broadly constructivist studies which question the orthodox approach to cyberterrorism as an ontological reality and highlight the importance of media representations of this threat. To illustrate this, the chapter concludes by highlighting findings from a recent study of global news media coverage. It shows that this media is frequently apprehensive in tone, despite the existence of diverse understandings of cyberterrorism and cybersecurity.
Terrorism as an Artifact of Transition in Post–Cold War Latin America
Authors: McAllister Carlota
Published: August 2020

This chapter surveys accounts of the nature and causes of violence in four Latin American truth commission reports produced from 1984 to 2003 for the purpose of examining when and how the terms “terrorist” and “terrorism” are used to describe the continent’s cold war revolutionary actors. It argues that these terms acquired explanatory value only gradually, in a context marked by the defeat of the armed Left, the emergence of a new global order legitimated by appeals to universal human rights, and the marginalization of other potential descriptors for violence. Invocations of “terrorism” can thus be understood as both indexing and foreclosing social and political tensions left unresolved by the application of transitional justice in Latin America, suggesting that one of the spoils of the cold war was the power to determine what counts as violence and why.
Photometric classification of Hyper Suprime-Cam transients using machine learning
Authors: Takahashi Ichiro , Suzuki Nao , Yasuda Naoki , Kimura Akisato , Ueda Naonori , Tanaka Masaomi , Tominaga Nozomu , Yoshida Naoki
Published: August 2020

The advancement of technology has resulted in a rapid increase in supernova (SN) discoveries. The Subaru/Hyper Suprime-Cam (HSC) transient survey, conducted from fall 2016 through spring 2017, yielded 1824 SN candidates. This gave rise to the need for fast type classification for spectroscopic follow-up and prompted us to develop a machine learning algorithm using a deep neural network with highway layers. This algorithm is trained by actual observed cadence and filter combinations such that we can directly input the observed data array without any interpretation. We tested our model with a dataset from the LSST classification challenge (Deep Drilling Field). Our classifier scores an area under the curve (AUC) of 0.996 for binary classification (SN Ia or non-SN Ia) and 95.3% accuracy for three-class classification (SN Ia, SN Ibc, or SN II). Application of our binary classification to HSC transient data yields an AUC score of 0.925. With two weeks of HSC data since the first detection, this classifier achieves 78.1% accuracy for binary classification, and the accuracy increases to 84.2% with the full dataset. This paper discusses the potential use of machine learning for SN type classification purposes.
On Bourgain’s Counterexample for the Schrödinger Maximal Function
Authors: Pierce Lillian B
Published: August 2020

This paper provides a rigorous derivation of a counterexample of Bourgain, related to a well-known question of pointwise a.e. convergence for the solution of the linear Schrödinger equation, for initial data in a Sobolev space. This counterexample combines ideas from analysis and number theory, and the present paper demonstrates how to build such counterexamples from first principles, and then optimize them.
JNR monopoles
Authors: Murray Michael K , Norbury Paul
Published: August 2020

We review the theory of JNR, mass $\frac{1}{2}$ hyperbolic monopoles in particular their spectral curves and rational maps. These are used to establish conditions for a spectral curve to be the spectral curve of a JNR monopole and to show that the rational map of a JNR monopole arises by scattering using results of Atiyah. We show that for JNR monopoles the holomorphic sphere has a remarkably simple form and show that this can be used to give a formula for the energy density at infinity. In conclusion, we illustrate some examples of the energy density at infinity of JNR monopoles.
Volumes And Random Matrices
Authors: Witten Edward
Published: August 2020

This article is an introduction to newly discovered relations between volumes of moduli spaces of Riemann surfaces or super Riemann surfaces, simple models of gravity or supergravity in two dimensions, and random matrix ensembles. (The article is based on a lecture at the conference on the Mathematics of Gauge Theory and String Theory, University of Auckland, January 2020)
Carbon Taxes and Climate Commitment with Non-constant Time Preference
Authors: Iverson Terrence , Karp Larry
Published: August 2020

We study the Markov perfect equilibrium in a dynamic game where agents have non-constant time preference, decentralized households determine aggregate savings, and a planner chooses climate policy. The article is the first to solve this problem with general discounting and general functional forms. With time-inconsistent preferences, a commitment device that allows a planner to choose climate policy for multiple periods is potentially very valuable. Nevertheless, our quantitative results show that while a permanent commitment device would be very valuable, the ability to commit policy for “only” 100 years adds less than 2% to the value of climate policy without commitment. We solve a log-linear version of the model analytically, generating a formula for the optimal carbon tax that includes the formula in Golosov et al. (2014, Econometrica, 82, 41–88) as a special case. More importantly, we develop new algorithms to solve the general game numerically. Convex damages lead to strategic interactions across generations of planners that lower the optimal carbon tax by 45% relative to the scenario without strategic interactions.
Insurance-Associated Disparities in Opioid Use and Misuse Among Patients Undergoing Gynecologic Surgery for Benign Indications
Authors: Huang Yongmei , Jacobson Judith S. , Tergas Ana I. , Ananth Cande V. , Neugut Alfred I. , Hershman Dawn L. , Wright Jason D.
Published: August 2020

OBJECTIVE:

To compare perioperative use and persistent postoperative opioid use among Medicaid-insured women and commercially insured women who underwent gynecologic surgery for benign indications.

METHODS:

The Truven Health MarketScan database, a nationwide data source collecting commercial insurance claims across all states and Medicaid insurance claims from 12 states, was used to identify opioid-naïve women without cancer aged 18–64 years who underwent common gynecologic surgeries from 2012 to 2016 and filled a prescription for an opioid perioperatively. Persistent opioid use was defined as filling an opioid prescription 90–180 days after the surgery. Opioid use disorder (OUD) was defined as hospitalizations or emergency department visits for opioid dependence, misuse, or overdose. Multivariable models were developed to examine the insurance-associated disparity in persistent opioid use and OUD.

RESULTS:

A total of 31,155 Medicaid-insured women and 270,716 commercially insured women were identified. Medicaid-insured women received greater quantities of opioids and for longer durations than did commercially insured women. Persistent postoperative opioid use was identified in 14.1% of Medicaid-insured women and 5.8% of commercially insured women (P<.001). More opioid prescriptions filled, longer days supplied, and higher total doses perioperatively contributed most to the prediction of persistent opioid use. Medicaid-insured patients who persistently used opioids were two times more likely to develop OUD than commercially insured patients (16.8% vs 5.1% adjusted relative risk 1.99; 99% CI 1.26–3.15).

CONCLUSION:

Medicaid-insured women received larger quantities of opioids perioperatively, were more likely to use them persistently, and were more likely to develop OUD than commercially insured women.
Re-examining the Meis Trial for Evidence of False-Positive Results
Authors: Sibai Baha , Saade George R. , Das Anita F.
Published: August 2020

U.S. Food and Drug Administration (FDA)–approved 17α-hydroxyprogesterone caproate therapy is currently available to reduce recurrent preterm birth in the United States. This commentary reviews the original landmark Meis trial (“Prevention of Recurrent Preterm Delivery by 17 Alpha-Hydroxyprogesterone Caproate”), which led to conditional approval of 17α-hydroxyprogesterone caproate by the FDA in 2011. The recent PROLONG (Progestin's Role in Optimizing Neonatal Gestation) trial failed to confirm the original findings. The Meis trial was rigorously designed and conducted, with highly statistically significant results that should not be undermined by the negative results of PROLONG. Given that the United States has among the highest preterm birth rates in the world and that the predominant enrollment in PROLONG was outside the United States, the results of the “old” Meis trial should not be summarily dismissed. It would be detrimental to high-risk pregnant patients to inappropriately prioritize results of PROLONG over the Maternal-Fetal Medicine Units Network’s Meis trial (funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development). We assert PROLONG was underpowered, based on substantially lower observed preterm birth rates than anticipated, and therefore was a false-negative study, rather than the Meis trial being a false-positive study. Careful assessment of these two trials is critical as removal of 17α-hydroxyprogesterone caproate from the U.S. marketplace may have substantial effects on public health.
Care for Incarcerated Pregnant People With Opioid Use Disorder
Authors: Ahlbach Chris , Sufrin Carolyn , Shlafer Rebecca
Published: August 2020

With the simultaneous rise in maternal opioid use disorder (OUD) and the incarceration of pregnant people in the United States, we must ensure that prisons and jails adequately address the health and well-being of incarcerated pregnant people with OUD. Despite long-established, clear, and evidence-based recommendations regarding the treatment of OUD during pregnancy, incarcerated pregnant people with OUD do not consistently receive medication treatment and are instead forced into opioid withdrawal. This inadequate care raises multiple concerns, including issues of justice and equity, considerations regarding the legal and ethical obligations of the provision of health care, and violations of the medical and legal rights of incarcerated people. We offer recommendations for improving care for this often-ignored group.
Place-Pitch Interval Perception With a Cochlear Implant
Authors: Stupak Natalia , Todd Ann E. , Landsberger David M.
Published: August 2020

Objectives:

Pitch is poorly perceived by cochlear implant (CI) users. However, as it is not well understood how pitch is encoded with electric stimulation, improving pitch representation with a CI is challenging. Changes in place of stimulation along the cochlea have been described as changes in pitch and can be accurately ranked by CI users. However, it remains unknown if place-pitch can be used to encode musical intervals, which are a necessary attribute of pitch. The objective of these experiments is to determine if place-pitch coding can be used to represent musical intervals with a CI.

Design:

In the first experiment, 10 CI users and 10 normal hearing (NH) controls were tested on their sensitivity to changes in the semitone spacing between each of the notes in the melody “Happy Birthday.” The changes were implemented by uniformly expanding or compressing the frequency differences between each note in the melody. The participant’s task was to scale how “out-of-tune” the melody was for various semitone spacing distortions. The notes were represented by pure-tones ≥440 Hz to minimize potential useful temporal information from the stimuli. A second experiment replicated the first experiment using single-sided deafened CI users allowing for a within-subject control. A third experiment verified that the CI users who participated in Experiment 1 were each able to determine pitch direction reliably.

Results:

Unlike NH listeners, CI listeners often ranked all distortions of interval spacing similarly in both the first and second experiment, and no effect of interval spacing was detected across CI users. Some participants found distorted interval spacings to be less out-of-tune than the nominally correct interval spacings. However, these patterns were inconsistent across listeners. Although performance was better for the NH listeners, the third experiment demonstrated that the CI listeners were able to reliably identify changes in pitch direction from place-pitch coding.

Conclusions:

The data suggest that place-pitch intervals are not properly represented through a CI sound processor. Some limited support is found for place-pitch being useful for interval encoding as some participants demonstrated improved ratings for certain interval distortions. Presumably the interval representation for these participants could be improved by a change to the frequencies represented by each electrode. However, as these patterns vary across listeners, there is not a universal correction to frequency representation that will solve this issue. As results are similar for single-sided deafened CI users, the limitations in ratings are likely not limited by an eroded representation of the melody caused by an extended duration of deafness.
Covid-19 Lockdown Affects Hearing Disability and Handicap in Diverse Ways: A Rapid Online Survey Study
Authors: Naylor Graham , Burke Louise A. , Holman Jack A.
Published: August 2020

Objectives:

The aim of this study was to explore the perceived effects of coronavirus disease 2019 (Covid-19) social distancing restrictions and safety measures on people with hearing loss.

Design:

Participants were 129 adults (48.1% female, mean age 64.4 years) with an audiometric hearing loss, living in Glasgow, Scotland. A rapidly deployed 24-item online questionnaire asked about the effects of certain aspects of lockdown, including face masks, social distancing, and video calling, on participants' behavior, emotions, hearing performance, practical issues, and tinnitus. Data were analyzed descriptively across the entire sample, and with Chi-squared tests for differences between subgroups self-reporting relatively good and relatively poor unaided hearing, respectively. Additional free-text responses provided further perspectives.

Results:

Behavior: Video calls are used more frequently than prelockdown. The better-hearing group use their hearing aids less. Emotions: There is increased anxiety (especially among the worse hearing group) concerning verbal communication situations and access to audiology services, and greater rumination about one’s own hearing loss. Enjoyment of group video calls is mixed. The worse hearing group shows substantial relief at not being obliged to attend challenging social gatherings. Across both groups, a majority would like to see all key workers equipped with transparent face masks. Hearing performance: A large majority finds it hard to converse with people in face masks due to muffled sound and lack of speechreading cues, but conversing at a safe distance is not universally problematic. In the worse hearing group, performance in video calls is generally inferior to face-to-face, but similar to telephone calls. Those who use live subtitling in video calls appreciate their value. TV and radio updates about Covid-19 are easy to follow for most respondents. There is only weak evidence of face mask fixtures interfering with hearing aids on the ear, and of tinnitus having worsened during lockdown.

Conclusions:

With due regard for the limitations of this rapid study, we find that there are many negative—and a few positive—effects of Covid-19 restrictions and safety measures on people with hearing loss. From a societal perspective, the widespread adoption of clear face masks may alleviate some of the difficulties and anxieties this population experience. From an individual perspective, one may consider using live subtitles on video calls. Manufacturers of hearing devices should consider developing processing modes and accessories specifically designed for video calls. Finally, repair and maintenance services should be resumed as soon as it is safe to do so.
Skeletal Muscle Composition Predicts Outcome in Critically Ill Patients
Authors: Loosen Sven H. , Schulze-Hagen Maximilian , Püngel Tobias , Bündgens Lukas , Wirtz Theresa , Kather Jakob N. , Vucur Mihael , Paffenholz Pia , Demir Münevver , Bruners Philipp , Kuhl Christiane , Trautwein Christian , Tacke Frank , Luedde Tom , Koch Alexander , Roderburg Christoph
Published: August 2020

Objectives:

Parameters of patients’ body composition have been suggested as prognostic markers in several clinical conditions including cancer and liver transplantation, but only limited data on its value in critical illness exist to date. In this study, we aimed at evaluating a potential prognostic value of the skeletal muscle mass and skeletal muscle myosteatosis of critically ill patients at admission to the ICU.

Design:

Exploratory observational cohort study.

Setting:

An urban, academic medical institution.

Patients:

One-hundred fifty-five patients treated for critical illness on a medical ICU.

Interventions:

None.

Measurements and Main Results:

We used routine CT scans to assess the patients’ individual body composition. The skeletal muscle index as a surrogate for sarcopenia was defined as the total skeletal muscle area at the level of the third lumbar vertebra on axial CT scan, normalized for the patient’s height. Myosteatosis was evaluated by assessing the mean skeletal muscle attenuation measured in Hounsfield unit at the same sectional plane. The skeletal muscle index and mean skeletal muscle attenuation at admission to the ICU were significantly higher in patients with long-term survival (180-day or 1-year mortality), while both parameters were comparable between short-term survivors and nonsurvivors (ICU mortality or 30-d mortality). Patients with a skeletal muscle index or mean skeletal muscle attenuation below our established ideal cutoff values (74.95 mm2/cm and 29 Hounsfield unit) showed a significantly reduced overall survival. These findings were confirmed in univariate and multivariate Cox regression analyses. Furthermore, myosteatosis significantly correlated with the time of mechanical ventilation, the duration of hospital stay, and the presence of sepsis.

Conclusions:

Our data suggest that sarcopenia and myosteatosis represent important prognostic factors in critically ill patients that can be easily obtained from routine CT scans. Both parameters at admission to the ICU yield important information on the patients’ long-term outcome and might be used for early clinical decision-making in these patients.
Preclinical Device Thrombogenicity Assessments: Key Messages From the 2018 FDA, Industry, and Academia Forum
Authors: jamiolkowski megan a. , snyder trevor a. , perkins ina laura , malinauskas richard a. , lu qijin
Published: August 2020

Device-related thrombosis and thromboembolic complications remain a major clinical concern and often impact patient morbidity and mortality. Thus, improved preclinical thrombogenicity assessment methods that better predict clinical outcomes and enhance patient safety are needed. However, there are several challenges and limitations associated with developing and performing preclinical thrombogenicity assessments on the bench and in animals (e.g., the clinical relevance of most in vitro tests has not been established, animal studies may not accurately predict clinical thrombotic events). To facilitate a discussion on how to overcome some of these challenges and to promote collaboration between the Food and Drug Administration (FDA), industry, and academia for the development of more reliable test methods, a scientific forum was organized by FDA and held in Washington, DC, on June 15, 2018 at the ASAIO 64th Annual Conference. Three subject matter experts from the medical device industry and FDA presented their perspectives at this forum, and several audience experts provided input during the open dialogue session. This article summarizes the key messages from the forum regarding the current status and challenges of preclinical thrombogenicity testing, important areas of needed research, and mechanisms for working with FDA to further improve thrombogenicity evaluations of medical devices.
Activated Partial Thromboplastin Time Versus Anti-Factor Xa Monitoring of Heparin Anticoagulation in Adult Venoarterial Extracorporeal Membrane Oxygenation Patients
Authors: Kulig Caitlin E. , Schomer Kendra J. , Black Hugh B. , Dager William E.
Published: August 2020

The preferred assay for measuring and adjusting unfractionated heparin (UFH) infusion to achieve optimal outcomes during extracorporeal membrane oxygenation (ECMO) is not well established. This retrospective cohort study explored safety and efficacy outcome differences between anti-factor Xa (anti-Xa) and activated partial thromboplastin time (aPTT) for UFH in adult venoarterial ECMO. Forty-one patients were included and analyzed. The UFH rate at first goal and time to goal were both higher in the aPTT versus anti-Xa cohort but did not achieve statistical significance (12.14 vs. 9.58 unit/kg/hour (p = 0.29), 20.22 vs. 12.05 hours (p = 0.11)). The aPTT cohort was in target goals 35.0% of the time versus 47.7% in the anti-Xa cohort (p = 0.13), above goal 41.0% vs. 17.3% (p = 0.02), and below-goal 24.0% versus 35.0% of the time (p = 0.34). Minimum heparin rates in the aPTT cohort were 6.28 vs. 3.33 unit/kg/hour in the anti-Xa cohort (p = 0.07), and the maximum UFH rate was 18.77 unit/kg/hour vs. 15.48 unit/kg/hour (p = 0.10). Our findings suggest that aPTT monitoring may result in a delay to target attainment, higher UFH rates, and overall exposure.
Thrombophilia in Pediatric Patients with Multisystem Inflammatory Syndrome in Children Secondary to Coronavirus Disease 2019 Supported on Extracorporeal Membrane Oxygenation
Authors: Minen Federico , Hands Christopher , Mustafa Muhammad R , Pienaar Alison , Lillie Jon
Published: August 2020

Coronavirus disease 2019 (COVID-19) in adults has been associated with thrombosis. Multisystem inflammatory syndrome in children (MIS-C) with COVID-19 case series have reported high fibrinogen levels, but it is not known whether this causes thrombophilia. We report two patients needing extracorporeal membrane oxygenation (ECMO) who both suffered thrombotic complications. We retrospectively reviewed patients with MIS-C needing ECMO support admitted to a single Paediatric and Cardiac Intensive Care Unit within a regional center for MIS-C in South East England. Two children required ECMO for cardiovascular support. Both developed thrombotic events despite receiving heparin infusions at dosing higher than the interquartile range for our ECMO population. Case 1 developed a right anterior and middle cerebral artery infarct, which led to his death. Case 2 had a right atrial thrombus, which resolved without complication. When compared with patients undergoing ECMO in the same institution in pre-MIS-C era, fibrinogen levels were consistently higher before and during ECMO therapy. MIS-C patients presenting with hyperfibrinogenemia are likely to have a propensity toward thrombotic complications; this must be considered when optimizing the anticoagulation strategy on ECMO.
Genetic and morphological estimates of androgen exposure predict social deficits in multiple neurodevelopmental disorder cohorts
Authors: McKenna Brooke G. , Huang Yongchao , Vervier Kévin , Hofamman Dabney , Cafferata Mary , Al-Momani Seima , Lowenthal Florencia , Zhang Angela , Koh Jin-Young , Thenuwara Savantha , Brueggeman Leo , Bahl Ethan , Koomar Tanner , Pottschmidt Natalie , Kalmus Taylor , Casten Lucas , Thomas Taylor R. , Michaelson Jacob J.
Published: August 2020

Background

Neurodevelopmental disorders (NDDs) such as autism spectrum disorder (ASD) display a strong male bias. Androgen exposure is profoundly increased in typical male development, but it also varies within the sexes, and previous work has sought to connect morphological proxies of androgen exposure, including digit ratio and facial morphology, to neurodevelopmental outcomes. The results of these studies have been mixed and the relationships between androgen exposure and behavior remain unclear.

Methods

Here, we measured both digit ratio masculinity (DRM) and facial landmark masculinity (FLM) in the same neurodevelopmental cohort (N=763) and compared these proxies of androgen exposure to clinical and parent-reported features as well as polygenic risk scores.

Results

We found that FLM was significantly associated with NDD diagnosis (ASD, ADHD, ID; allp< 0.05), while DRM was not. When testing for association with parent-reported problems, we found that both FLM and DRM were positively associated with concerns about social behavior (ρ= 0.19,p= 0.004;ρ= 0.2,p= 0.004, respectively). Furthermore, we found evidence via polygenic risk scores (PRS) that DRM indexes masculinity via testosterone levels (t= 4.0,p= 8.8 × 10−5), while FLM indexes masculinity through a negative relationship with sex hormone binding globulin (SHBG) levels (t= −3.3,p= 0.001). Finally, using the SPARK cohort (N=9,419) we replicated the observed relationship between polygenic estimates of testosterone, SHBG, and social functioning (t= −2.3,p= 0.02, andt= 4.2,p= 3.2 × 10−5for testosterone and SHBG, respectively). Remarkably, when considered over the extremes of each variable, these quantitative sex effects on social functioning were comparable to the effect of binary sex itself (binary male: −0.22 ± 0.05; testosterone: −0.35 ± 0.15 from 0.1%-ile to 99.9%-ile; SHBG: 0.64 ± 0.15 from 0.1%-ile to 99.9%-ile).

Conclusions

These findings and their replication in the large SPARK cohort lend support to the hypothesis that increasing net androgen exposure diminishes capacity for social functioning in both males and females.
Comparative Evaluation of Three Serologic Assays for the Identification of SARS-CoV-2 Antibodies
Authors: Hogan Keenan O. , Klippel Dave , Plapp Fred V. , Liesman Rachael M.
Published: August 2020

Background and aims

Serologic assays for the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies are being developed and approved rapidly with limited external validation. Accurate diagnostics are an essential component to pandemic management and public health.

Materials and methods

Residual serum samples (N=113) from patients who were evaluated for SARS-CoV-2 infection status by polymerase chain reaction (PCR) were retrospectively tested in parallel across three automated SARS-CoV-2 serologic assays: Liaison SARS-CoV-2 S1/S2 IgG, Elecsys anti-SARS-CoV-2 total antibody, and Access SARS-CoV-2 IgG.

Results

Testing of 51 PCR-positive and 62 PCR-negative patients demonstrated qualitative inter-test agreement of 96% overall, 100% in PCR-negative patients, 88% in early positive samples (0-13 days post positive PCR), and 100% in convalescent samples (14+ days post positive PCR).

Calculated kappa values for paired inter-test agreement ranged 0.93-0.96. Compared to PCR, overall percent positive agreement ranged from 82-86% (100% for convalescent samples) and percent negative agreement was 100% for each assay.

Conclusion

This study demonstrates high diagnostic accuracy and inter-test agreement for three automated SARS-CoV-2 serologic assays. External validation of serologic assays is critical to ensure diagnostic accuracy and appropriate utilization of critical resources.
Seroprevalence of SARS-CoV-2-Specific IgG Antibodies Among Adults Living in Connecticut: Post-Infection Prevalence (PIP) Study
Authors: Mahajan Shiwani , Srinivasan Rajesh , Redlich Carrie A. , Huston Sara K. , Anastasio Kelly M. , Cashman Lisa , Massey Dorothy S. , Dugan Andrew , Witters Dan , Marlar Jenny , Li Shu-Xia , Lin Zhenqiu , Hodge Domonique , Chattopadhyay Manas , Adams Mark D. , Lee Charles , Rao Lokinendi V. , Stewart Chris , Kuppusamy Karthik , Ko Albert I. , Krumholz Harlan M.
Published: August 2020

Background

A seroprevalence study can estimate the percentage of people with SARS-CoV-2 antibodies in the general population, however, most existing reports have used a convenience sample, which may bias their estimates.

Methods

We sought a representative sample of Connecticut residents, aged ≥18 years and residing in non-congregate settings, who completed a survey between June 4 and June 23, 2020 and underwent serology testing for SARS-CoV-2-specific IgG antibodies between June 10 and July 29, 2020. We also oversampled non-Hispanic Black and Hispanic subpopulations. We estimated the seroprevalence of SARS-CoV-2-specific IgG antibodies and the prevalence of symptomatic illness and self-reported adherence to risk mitigation behaviors among this population.

Results

Of the 567 respondents (mean age 50 [±17] years; 53% women; 75% non-Hispanic White individuals) included at the state-level, 23 respondents tested positive for SARS-CoV-2-specific antibodies, resulting in weighted seroprevalence of 4.0 (90% confidence interval [CI] 2.0–6.0). The weighted seroprevalence for the oversampled non-Hispanic Black and Hispanic populations was 6.4% (90% CI 0.9–11.9) and 19.9% (90% CI 13.2–26.6), respectively. The majority of respondents at the state-level reported following risk mitigation behaviors: 73% avoided public places, 75% avoided gatherings of families or friends, and 97% wore a facemask, at least part of the time.

Conclusions

These estimates indicate that the vast majority of people in Connecticut lack antibodies against SARS-CoV-2 and there is variation by race/ethnicity. There is a need for continued adherence to risk mitigation behaviors among Connecticut residents to prevent resurgence of COVID-19 in this region.
Prevalence of Hepatitis B, Hepatitis C and HIV infection among patients undergoing hemodialysis in Argentina
Authors: Pereson Matías J. , Martínez Alfredo P. , Isaac Katia , Laham Gustavo , Ridruejo Ezequiel , Garcia Gabriel H. , Flichman Diego M. , Di Lello Federico A.
Published: August 2020

Background and Aim

Blood-borne infections are a major cause of damage in individuals on hemodialysis (HD). In particular, knowledge about the viral status of hepatitis B (HBV), hepatitis C (HCV) and human immunodeficiency virus (HIV) in HD patients is gold data to face medical challenges. Related information is scarce in Argentina. The aim of this study was to determine the prevalence of HBV, HCV and HIV infections in HD patients from Buenos Aires, Argentina.

Methods

Seven hundred and forty-eight HD patients were included in a retrospective cross-sectional study. Laboratories assays were performed to determine virological status. HCV genotyping was carried out by phylogenetic analysis of NS5B partial gene.

Results

Infection with one of the viruses was detected in 31.1% of patients [HBV in 82 (11.0%), HCV in 179 (23.9%), and HIV in 6 (0.8%)]. Thirty-two (4.3%) patients had two virus markers [27 (3.6%) with HCV/HBV, 4 (0.5%) with HCV/HIV and 1 (0.13%) with HBV/HIV]. Finally, one single patient (0.13%) presented all three markers. Time on dialysis was correlated with HCV infection but no with HBV. Distribution of HCV subtypes was inverted respect to the observed in general population [HCV-1a (73.2%) and HCV-1b (26.8%) in HD vs. HCV-1a (26.5%) and HCV-1b (73.5%) in general population, p<0.001].

Conclusions

These infections, mainly HCV, continue to occur at a very high rate in HD patients. Results emphasize the need to consider a priority the HCV infected patients in dialysis treatment and to vaccine against HBV in order to decrease its morbidity and mortality.
COVID-19: Beliefs in misinformation in the Australian community
Authors: Pickles K , Cvejic E , Nickel B , Copp T , Bonner C , Leask J , Ayre J , Batcup C , Cornell S , Dakin T , Dodd RH , Isautier JMJ , McCaffery KJ
Published: August 2020

Objectives

To investigate prevalence of beliefs in COVID-19 misinformation and examine whether demographic, psychosocial and cognitive factors are associated with these beliefs, and how they change over time.

Study design

Prospective national longitudinal community online survey.

Setting

Australian general public.

Participants

Adults aged over 18 years (n=4362 baseline/Wave 1; n=1882 Wave 2; n=1369 Wave 3).

Main outcome measure

COVID-19 misinformation beliefs.

Results

Stronger agreement with misinformation beliefs was significantly associated with younger age, male gender, lower education, and primarily speaking a language other than English at home (all p<0.01). After controlling for these variables, misinformation beliefs were significantly associated (p<0.001) with lower digital health literacy, lower perceived threat of COVID-19, lower confidence in government, and lower trust in scientific institutions. The belief that the threat of COVID-19 is “greatly exaggerated” increased between Wave 1-2 (p=0.002), while belief that herd immunity benefits were being covered up decreased (p<0.001). Greatest support from a list of Australian Government identified myths was for those regarding ‘hot temperatures killing the virus’ (22%) and ‘Ibuprofen exacerbates COVID-19’ (13%). Lower institutional trust and greater rejection of official government accounts were associated with greater support for COVID-19 myths after controlling for sociodemographic variables.

Conclusion

These findings highlight important gaps in communication effectiveness. Stronger endorsement of misinformation was associated with male gender, younger age, lower education and language other than English spoken at home. Misinformation can undermine public health efforts. Public health authorities must urgently target groups identified in this study when countering misinformation and seek ways to enhance public trust of experts, governments, and institutions.
Rapid, reliable, and cheap point-of-care bulk testing for SARS-CoV-2 by combining hybridization capture with improved colorimetric LAMP (Cap-iLAMP)
Authors: Bokelmann Lukas , Nickel Olaf , Maricic Tomislav , Pääbo Svante , Meyer Matthias , Borte Stephan , Riesenberg Stephan
Published: August 2020

Efforts to contain the spread of SARS-CoV-2 have spurred the need for reliable, rapid, and cost-effective diagnostic methods which can easily be applied to large numbers of people. However, current standard protocols for the detection of viral nucleic acids while sensitive, require a high level of automation, sophisticated laboratory equipment and trained personnel to achieve throughputs that allow whole communities to be tested on a regular basis. Here we present Cap-iLAMP (capture and improved loop-mediated isothermal amplification). This method combines a hybridization capture-based RNA extraction of non-invasive gargle lavage samples to concentrate samples and remove inhibitors with an improved colorimetric RT-LAMP assay and smartphone-based color scoring. Cap-iLAMP is compatible with point-of-care testing and enables the detection of SARS-CoV-2 positive samples in less than one hour. In contrast to direct addition of the sample to improved LAMP (iLAMP), Cap-iLAMP does not result in false positives and single infected samples can be detected in a pool among 25 uninfected samples, thus reducing the technical cost per test to ~1 Euro per individual.
Low Quantity single strand CAGE (LQ-ssCAGE) maps regulatory enhancers and promoters
Authors: Takahashi Hazuki , Nishiyori-Sueki Hiromi , Ramilowski Jordan A. , Itoh Masayoshi , Carninci Piero
Published: August 2020

The Cap Analysis of Gene Expression (CAGE) is a powerful method to identify the Transcription Start Sites (TSSs) of capped RNAs while simultaneously measuring transcripts expression level. CAGE allows mapping at single nucleotide resolution at all active promoters and enhancers. Large CAGE datasets have been produced over the years from individual laboratories and consortia, including the Encyclopedia of DNA Elements (ENCODE) and Functional Annotation Of the Mammalian Genome (FANTOM). These datasets constitute open resource for TSS annotations and gene expression analysis. Here we provide an experimental protocol for the most recent CAGE method called Low Quantity (LQ) single strand (ss) CAGE “LQ-ssCAGE”, which enables cost-effective profiling of low quantity RNA samples. LQ-ssCAGE is especially useful for samples derived from cells cultured in small volumes, cellular compartments such as nuclear RNAs or for samples from developmental stages. We demonstrate the reproducibility and effectiveness of the method by constructing 240 LQ-ssCAGE libraries from 50 ng of THP-1 cell extracted RNAs and discover lowly expressed novel enhancer and promoter-derived lncRNAs.