bluuebunny/crossref_metadata_2025 huggingface dataset:
Son of the Heartland
Authors: Zangwill Andrew
Published: January 2021

Anderson’s parents come from academic families in Indiana. Phil and his sister Grace grew up in Urbana, Illinois because their father was a plant pathologist at the University of Illinois (UI). Mother Elsie demanded academic excellence and respect for others. Father Harry was a model of integrity, a fact displayed during the so-called Krebiozen affair. The Depression affected the family relatively little and Phil acquired his lifelong liberal politics from a UI social group called the Saturday Hikers. At age twelve, he accompanies his family to Europe (a sabbatical for his father) where they observe the rise of Nazism. Phil attends and excels at the University High School where he enjoys math, tennis, and speed skating, but not physics. He wins a National Scholarship to attend Harvard University with a plan to major in mathematics.
Making Waves
Authors: Zangwill Andrew
Published: January 2021

Sixteen-year-old Phil Anderson does not fit in well with the prep school boys at Harvard, but he finds a congenial study group (including future historian of science Thomas Kuhn) and does well academically. The beginning of World War II causes him to change his major to Electronic Physics. His class graduates in three years so they can contribute to the war effort. Anderson does his service as a radar (microwave) engineer at the Naval Research Laboratory where he learns quantum mechanics, learns he is probably not suited for experimental work, and grows up socially. John Van Vleck visits NRL and helps convince Anderson to return to Harvard for graduate school.
First Fruits
Authors: Zangwill Andrew
Published: January 2021

Anderson thrives in graduate school where he begins a career-long friendly rivalry with Walter Kohn. He consciously chooses not to work with superstar theorist Julian Schwinger and pursues a PhD supervised by John Van Vleck. His thesis problem is a quantum mechanical calculation of the microwave absorption spectrum of small molecules. His social time is spent almost exclusively with non-physics graduate students, including the mathematician-comedic songwriter Tom Lehrer. He meets Joyce Gothwaite during a vacation trip home and only a short time passes before they marry in Boston and she becomes pregnant. Daughter Susan is born and Anderson completes his thesis work quickly. Money is tight.
The Pope of Condensed Matter Physics
Authors: Zangwill Andrew
Published: January 2021

This chapter gives an overview of Anderson’s life at the top of the theoretical condensed matter world. He became very influential at Bell Labs and retired as a Consulting Director of the Physical Science Laboratory. He moved his half-time professorship from Cambridge to Princeton in 1975, but it took a decade to break down the resistance there to condensed matter physics. He was heavily involved with the Aspen Center and turned down an offer of the Directorship of the Institute for Theoretical Physics in Santa Barbara. He wrote the magisterial “Basic Notions of Condensed Matter Physics” but was widely regarded as a poor classroom instructor. His Nobel Prize gave him a platform to oppose the ABM and Star Wars ballistic missile systems, and the Superconducting Super Collider.
The Problem of a Lifetime
Authors: Zangwill Andrew
Published: January 2021

Anderson is the only theorist who answers questions at a news conference at the 1987 March Meeting of the American Physical Society (the “Woodstock of Physics”) where most physicists learned details about the newly discovered high-temperature cuprate superconductors, which lose all resistance at temperatures not very far below room temperature. He had just proposed a radical non-BCS theory which attributed superconductivity in these materials to a “resonating valence bond” description of a doped Mott insulator using a model first proposed by John Hubbard. He spent the next twenty years trying to convince his colleagues of the correctness of this theory, with only limited success.
Four Facts About Science
Authors: Zangwill Andrew
Published: January 2021

This chapter is an exploration of Anderson’s philosophy of science based on the contents of his article in a British newspaper, “Four Facts Everyone Ought to Know about Science.” These are: (1) science is not democratic; (2) computers will not replace scientists; (3) statistical methods are missed and often misunderstood; and (4) good science has aesthetic qualities. Anderson aimed to alert the public about the inaccurate and misleading information they were constantly subjected to by uncritical journalists, agenda-driven political pundits, social critics of science, religious fundamentalists, and publicity-seeking professional scientists. He describes science as an interconnected web and discusses Bayesian statistics.
Conclusion
Authors: Zangwill Andrew
Published: January 2021

Anderson’s activities after age 85 are changed fundamentally by a stroke suffered by his wife Joyce. This brings him close to his daughter Susan for the first time. John Maynard Keynes is offered as a similar figure in intellectual history. A career summary leads to the conclusion that Anderson was one of the world’s greatest scientists.
Temporality, Aspect, and Narrative
Authors: Blattner William
Published: January 2021

This chapter examines the phenomenological conditions of the possibility of our experience of narrated process. It begins with Husserl’s account of retention and protention, which are the capacities by which we retain the immediate past and anticipate the immediate future. This allows us to experience processes. The chapter then turns to Heidegger, according to whom the experience of process depends on a sense of what is relevant to the process. Here a different axis of temporal analysis comes into view: temporal aspect. Temporal aspect expresses the internal temporal structure of what we understand. Heidegger analyzes temporal aspects as part of his account of what he calls “originary temporality.” His analysis can be used to shed light on narrative understanding, and so, of how we understand ourselves and what we are up to.
Studying Organization from the Perspective of the Ontology of Temporality
Authors: Hussenot Anthony , Hernes Tor , Bouty Isabelle
Published: January 2021

This chapter suggests an events-based approach that can be used to understand organization as a temporal phenomenon. To date, the ontology of time sees the present, the past, and the future as different and discrete temporal epochs and thus prevents us from understanding activities as a creative process in which the past, the present, and the future are constantly redefined to give meaning and sense to actors. Conversely, an ontology of temporality enables us to grasp the situated nature of organizational phenomena. We argue that an events-based approach provides a better understanding of how past, present, and future events are constantly co-defined and configured, thereby enabling actors to gain a sense of continuity, i.e. a sense about their history, the present moment, and an expected future. Following a discussion of the nature of an events-based approach, we discuss the contributions and implications of such an approach by showing how it redefines the very subject of organization and brings insights to the study of contemporary organizational phenomena.
Ethnicity, Religion, and Diversity at the International Criminal Court
Authors: Bossa Solomy Balungi , Dossan Gilles Landry
Published: January 2021

The legal framework of the International Criminal Court (ICC) provides for several criteria designed to ensure a level of diversity on the Court’s bench. The drafters of the Court’s legal instruments did not provide for these criteria ex nihilo, they built on previous long-standing practices of international courts and tribunals, such as the International Court of Justice. Reflecting on the diversity of the ICC’s bench raises the question whether additional criteria could be imposed to strengthen the existing framework. This chapter explores whether ethnicity and religion may fall in that category, by revisiting the existing rules and questioning the implications of adding these concepts as criteria to reinforce diversity on the ICC’s bench. Even though a deeper understanding of the ethnic and religious dimensions of a conflict could potentially improve judicial decision-making, this chapter concludes that ethnicity and religion should not form part of the appointment criteria for the judges of the Court.
The Many Ages of the Court of Justice of the European Union
Authors: Arnull Anthony
Published: January 2021

From its origins in the Schuman Declaration of 9 May 1950, the Court of Justice of the European Union has developed into a legal leviathan, exercising a profound influence on the Union through its widely studied case law. That case law has been lauded and criticized in equal measure. Some see it as bold and ingenious, while others consider it the product of a rogue court. Who were the individuals who made the early Court tick? What were the obstacles the Court had to overcome in order to achieve its current status? Why were the Member States slow to grasp the significance of the Court’s work? What is the relationship between the Court and the General Court, created by the Council in 1988 to alleviate the pressure imposed on the Court itself by its growing case load? This chapter addresses these questions in their temporal, political, and geopolitical context.
Judicial Legitimacy in the European Union
Authors: Komárek Jan
Published: January 2021

The chapter begins with some reflections on the concept of legitimacy, as it is used in the debates on the EU and its judicial system, particularly the ECJ. In the following section, it seeks to present a framework for studying the ECJ’s legitimacy, which does justice to its dual role: to decide particular cases and at the same time to fulfil much wider functions in the EU political system. The third section then focuses on the perennial problem of judicial legitimacy in the Western legal tradition: how to legitimize creative moments of judicial interpretation of law, which are at the same time unavoidable and deeply problematic for what is sometimes called the liberal doctrine of politics. The fourth section looks in some detail at the recent turn to semantic pragmatism and its relationship to the democratic theory and discusses some of its shortcomings.
Invisibility, Social Exclusion, Survival
Authors: Pati Biswamoy
Published: January 2021

This chapter lays out the canvas of the book, highlighting the destructive impact of colonialism on the socially excluded sections of Orissan society. Colonial agrarian interventions, the emergence of private property, and commercialization of agriculture further impoverished the marginalized sections. Colonization also consolidated upper caste/class dominance in areas where they had been fluid earlier. Critiquing trends in historiography, this chapter argues that till very recently an obsessive focus on the coastal tract and on Jagannath and Puri had continued to shape our understanding of the region. This, combined with the nationalist and imperialist narratives, had a strong impact even on relatively sophisticated, historical works on the region. The chapter concludes that there appear to be distinct continuities between the colonial and post-colonial perspectives on the socially excluded continuing to this day.
Alternative Visions
Authors: Pati Biswamoy
Published: January 2021

This chapter explores an area that is usually missing in narratives related to the Indian national movement, even though it involves alternative possibilities and visions and perhaps even ways of writing alternative histories. It does this by focusing on the State People’s Movement in the princely state of Nilgiri in colonial Orissa, which was led by the communists. However, it does not look at this movement as being organized ‘from above’, but as one that was guided and shaped by the tribals and peasants themselves. The chapter places these struggles against broader regional and national developments, thus challenging the idea that adivasis and untouchables/dalits were ‘unreflexive’/‘spontaneous’ people who merely fought against their immediate oppressors and had no conception of the wider social and political context.
Renovation
Authors: Hotson Howard
Published: January 2021

The rapid assimilation of Cartesianism into the young Dutch universities is often regarded as evidence of the unique open-mindedness of Dutch society and culture during the Golden Age. Absent from such accounts is the fact that a disproportionate share of the earliest and most avid ‘Dutch Cartestians’ were in fact first- or second-generation refugees, displaced from the heartland of the Ramist and post-Ramist tradition in Reformed Germany during the course of the Thirty Years War (section 5.i). Particularly instructive is a group of early defenders of Cartesianism—Tobias Andreae, Johannes Clauberg, and Christoph Wittich—educated in the Reformed academy in Bremen under the little-known figure of Gerhard de Neufville (section 5.ii). To this group can be added the Bremen-born Johannes Coccejus, whose variety of covenant theology was combined with Cartesianism to generate a tradition characteristic of the early Dutch moderate Enlightenment (section 5.iii). Placing the advent of academic Cartesianism within the intellectual diaspora of the Thirty Years War therefore opens fresh perspective on the Dutch Golden Age of the mid-seventeenth century and the intellectual fertility of Holy Roman Empire during the previous period (section 5.iv).
Cicero
Authors: Schofield Malcolm
Published: January 2021

This engagingly written book offers an innovative account of Cicero’s treatment of key political ideas: liberty and equality, government, law, cosmopolitanism and imperialism, republican virtues, and ethical decision-making in politics. Cicero (106–43 BC) is well known as a major participant in the turbulent politics of the last three decades of the Roman Republic. But he was a political thinker, too, influential for many centuries on the Western intellectual and cultural tradition. His theoretical writings stand as the first surviving attempt to articulate a philosophical rationale for republicanism. They were not written in isolation either from the stances he took in his political oratory of the period, or from his discussions in his voluminous correspondence with friends and acquaintances of immediate political issues or questions of character or behaviour. The book situates the intimate interrelationships between Cicero’s writings in all these modes within the historical context of a fracturing traditional Roman political order, while exhibiting the continuing attractions of his conceptual landscape, as well as some of its limitations as a response to the crisis that was engulfing Rome.
An exploration of referees’ comments published in open peer review journals: The characteristics of review language and the association between review scrutiny and citations
Authors: Wolfram Dietmar , Wang Peiling , Abuzahra Fuad
Published: January 2021

Journals that adopt open peer review (OPR), where review reports of published articles are publicly available, provide an opportunity to study both review content characteristics and quantitative aspects of the overall review process. This study investigates two areas relevant to the quality assessment of manuscript reviews. First, do journal policies for reviewers to identify themselves influence how reviewers evaluate the merits of a manuscript based on the relative frequency of hedging terms and research-related terms appearing in their reviews? Second, is there an association between the number of reviews/reviewers and the manuscript’s research impact once published as measured by citations? We selected reviews for articles published in 17 OPR journals from 2017 to 2018 to examine the incidence of reviewers’ uses of hedging terms and research-related terms. The results suggest that there was little difference in the relative use of hedging term usage regardless of whether reviewers were required to identify themselves or if this was optional, indicating that the use of hedging in review contents was not influenced by journal requirements for reviewers to identify themselves. There was a larger difference observed for research-related terminology. We compared the total number of reviews for a manuscript, rounds of revisions, and the number of reviewers with the number of Web of Science citations the article received since publication. The findings reveal that scrutiny by more reviewers or conducting more reviews or rounds of review do not result in more impactful papers for most of the journals studied. Implications for peer review practice are discussed.
Simulated Participants as Health Care Providers: An Innovative Approach to Interprofessional Simulation
Authors: Ross Jennifer Gunberg , Meakim Colleen H. , Hohenleitner Stacy Grant , Prieto Patricia , Solnick Arlene , Yates Kathleen Williams , Qi Bing Bing
Published: January 2021

With the increased attention to patient safety and quality care in health care, it is imperative that prelicensure health care provider students are taught to collaborate effectively to decrease medical errors. For this project, simulated participants were utilized as health care providers for a simulation in a stand-alone nursing school without affiliation to a medical or allied health school. Both simulated participants and students reacted positively to the experience. This project demonstrated that utilizing simulated participants to portray health care providers in simulation scenarios is a feasible and well-received method of providing learning experiences that emphasize the importance of collaboration.
Untethered Lecture Capture: Stimulating Educational Affordances Through Technology-Enhanced Teaching
Authors: Krautscheid Lorretta
Published: January 2021

Untethered Lecture Capture (ULC) permits faculty to be freely mobile in the classroom (untethered) and synchronously create reusable learning media assets (lecture capture) through mobile technology resources. Integrating the cognitive theory of multimedia instruction with ULC creates affordances that facilitate learning. Anecdotal student comments indicate ULC supports accessibility, enhances personalized self-paced learning, and creates opportunities for academic success. Untethered faculty teach among students, enhancing in-class focus, time-on-task, and student-faculty engagement. Although all students may benefit from ULC teaching strategies, first-generation students and students whose first language is not English reported increased confidence, coupled with decreased stress.
Full-Time Faculty in Clinical and Basic Science Departments by Sex and Underrepresented in Medicine Status: A 40-Year Review
Authors: Xierali Imam M. , Nivet Marc A. , Rayburn William F.
Published: January 2021

Purpose

To assess the changing diversity of faculty in specific clinical and basic science departments, stratified by sex and underrepresented in medicine (URM) status, at all Liaison Committee on Medical Education (LCME)-accredited medical schools.

Method

In this retrospective, cross-sectional, observational study, the authors used data from the Association of American Medical Colleges Faculty Roster (data pulled in October 2019) to identify trends in clinical department faculty and in basic science department faculty by sex and URM status. They included full-time faculty at all LCME-accredited medical schools from 1979 to 2018. They compared the proportions of faculty across separate departments according to sex and URM status, and they used 2-independent-sample t test and simple linear regressions for statistical comparisons.

Results

The number of full-time faculty increased from 49,909 in 1979 to 175,326 in 2018. The largest increase occurred in clinical departments, where the number of faculty increased from 38,726 to 155,677 (a fourfold increase). The number of faculty in basic science departments increased from 11,183 to 19,649 (a 1.8-fold increase). The proportions of faculty who were non-URM females (compared with non-URM males, URM females, and URM males) increased the most—from 14.4% (5,595 of 38,726) to 37.6% (58,478 of 155,677) for clinical departments, and from 14.9% (1,669 of 11,183) to 33.0% (6,485 of 19,649) for basic science departments. Growth was steady but slow among URM faculty, especially for Black males; the absolute number of male URM faculty remained low in both basic science and clinical departments. The proportions of females and URM faculty were highest in the departments of obstetrics and gynecology, pediatrics, and family medicine.

Conclusions

The substantial increase in faculty, especially in clinical departments, has led to greater diversity, but mostly among non-URM females. The rise of URM male and URM female faculty has been minimal.
The Effect of Adjuvant Pelvic Radiotherapy on Distant Metastasis for Uterine Carcinosarcoma
Authors: Eng Nina L. , Rana Shushan R. , Hall Kevin L. , Eng Tony Y.
Published: January 2021

Background:

Uterine carcinosarcomas (UCS) are rare tumors that carry a poor prognosis and high recurrence rate. Standard treatment consists of surgical resection and chemotherapy, though the benefit of adjuvant radiotherapy (RT) has yet to be determined. This study assessed survival rates between patients with UCS who underwent surgical resection alone and patients who underwent combinations of surgery, chemotherapy, and RT.

Materials and Methods:

We conducted a retrospective review of all patients who underwent surgical resection for UCS between 1993 and 2011 at a single institution. We assessed 3-year disease-free survival, locoregional recurrence-free survival, distant metastases-free survival (DMFS), and overall survival rates and utilized Kaplan-Meier modeling to analyze differences between UCS treatment modalities.

Results:

Twenty-four patients underwent UCS surgical resection between 1993 and 2011. The mean age was 61 (range: 39 to 75 y). Of these patients, 100% (n=24) underwent surgical resection, 25% (n=6) underwent surgery and adjuvant chemotherapy, 29% (n=7) underwent surgery and adjuvant RT, and 33% (n=8) underwent surgery and adjuvant chemotherapy and RT. At 3 years median follow, there was no significant difference in overall survival between treatment modalities. The addition of radiation therapy conferred increased DMFS in patients undergoing surgery irrespective of adjuvant chemotherapy (44% vs. 83%, P=0.0211).

In patients receiving adjuvant chemotherapy, the significant increase in DMFS persisted with the addition of RT (P=0.0310). Lymph node involvement (n=8) was associated with a lower locoregional recurrence-free survival (38% vs. 92%, P=0.0029).

Conclusions:

RT may offer a potential benefit in reducing the rate of distant metastases, though there were no statistically significant improvements in survival metrics.
Use of an Ultrasonic Aspirator in Removal of an Orbital Rim Hemangioma
Authors: Donegan Patrick , Law James , Schauwecker Suzanne M. , Mawn Louise A.
Published: January 2021

Intraosseous hemangiomas are rare bony neoplasms that infrequently develop in the calvarium or facial bones. Due to their highly vascular nature, biopsy or resection of these tumors can present a surgical challenge, with reports of significant blood loss during tumor resection. Traditional surgical resection of intraosseous hemangiomas often includes the use of high speed oscillating or sagittal saws. Ultrasonic aspirators, which spare adjacent soft-tissue structures and minimize blood loss, have been successfully used in resection of firm soft tissue masses of the orbit; however, this technology has not been demonstrated in the treatment of a vascular tumor in the orbit. The authors present the case of a 37-year-old woman who presented with an intraosseous hemangioma at the left inferior orbital rim and maxilla; the mass was successfully resected with the aid of a Sonopet Ultrasonic Aspirator bone knife. The knife allowed for simultaneous emulsification and cautery of the bone encasing the mass with low risk to sensitive surrounding tissue.
Management of interface irregularity due to high energy after uneventful SMILE
Authors: Ganesh Sri , Brar Sheetal
Published: January 2021

A 48-year-old man was referred for the management of suboptimal vision after an uneventful bilateral small-incision lenticule extraction (SMILE) procedure, performed 6 weeks previously. His corrected distance visual acuity (CDVA) was 6/9p and 6/12 in the right eye and the left eye, respectively. Corneal topography was regular, and higher-order aberrations were within the acceptable range. Clinical photographs in retroillumination revealed rough and irregular interface in both eyes, probably because of the use of a relatively high-energy cut index of 40 (200 nJ) to perform SMILE. The case was managed by CIRCLE software–enabled flap creation with phototherapeutic keratectomy (PTK), followed by enhancement with flap relift and topography-guided LASIK 3 months later in both eyes, which resulted in improvement in the CDVA to 6/4.5 in the right eye and 6/9p in the left eye. CIRCLE software–enabled flap creation and PTK might result in satisfactory visual outcomes in cases of interface irregularity after SMILE.
Pituitary adenylate cyclase-activating polypeptide/vasoactive intestinal peptide (Part 2): biology and clinical importance in central nervous system and inflammatory disorders
Authors: Moody Terry W. , Jensen Robert T.
Published: January 2021

Purpose of review

To discuss recent advances of vasoactive intestinal peptide/pituitary adenylate cyclase-activating polypeptide (VIP/PACAP) receptors in the selected central nervous system (CNS) and inflammatory disorders.

Recent findings

Recent studies provide evidence that PACAP plays an important role in a number of CNS disorders, particularly the pathogenesis of headaches (migraine, etc.) as well as posttraumatic stress disorder and drug/alcohol/smoking addiction. VIP has important therapeutic effects in a number of autoimmune/inflammatory disorder such as rheumatoid arthritis. In some cases, these insights have advanced to therapeutic trials.

Recent insights from studies of VIP/PACAP and their receptors in both CNS disorders (migraine, posttraumatic stress disorder, addiction [drugs, alcohol, smoking]) and inflammatory disorders [such as rheumatoid arthritis] are suggesting new treatment approaches. The elucidation of the importance of VIP/PACAP system in these disorders combined recent development of specific drugs acting on this system (i.e., monoclonal VIP/PACAP antibodies) will likely lead to importance novel treatment approaches in these diseases.
Radiologic and clinicopathologic characteristics of thyroid nodules with focal 68Ga-DOTATATE PET activity
Authors: Kohlenberg Jacob D. , Panda Ananya , Johnson Geoffrey B. , Castro M. Regina
Published: January 2021

Objective

Our aim was to determine the radiologic and clinicopathologic characteristics of thyroid nodules with focal 68Ga-DOTATATE activity.

Methods

In this retrospective study of 1927 consecutive 68Ga-DOTATATE PET scans, 85 patients with incidental and nonincidental focal 68Ga-DOTATATE avid thyroid nodules were identified, of which 31 patients with 33 thyroid nodules underwent fine-needle aspiration (FNA) or surgery. These 33 nodules were reviewed for Krenning score and SUVmax of the thyroid nodule, contralateral thyroid lobe and left atrium.

Results

Cytology/histopathology included 58% (19/33) with benign findings, 18% (6/33) medullary thyroid carcinoma (MTC), 9% (3/33) atypia or follicular lesion of undetermined significance (AUS/FLUS), 9% (3/33) suspicious for follicular neoplasm and Hurthle cell adenoma (SFN/HCA) and 6% (2/33) nondiagnostic cytology. Median serum calcitonin was 1156 pg/mL (range, 460–1828) in MTC and was <5.0 pg/mL (<5.0–12.5) in patients with benign nodules. Nodules had Krenning score of 1, 2 and 3 in 46% (15/33), 27% (9/33) and 27% (9/33). The majority of MTC and AUS/FLUS nodules had a Krenning score of 3, and there was substantial intragroup variation in Krenning score among the benign nodules. The mean SUVmax for the entire cohort was 5.5 ± 2.9 (mean ± SD), and the range was 2.0–13.0. There was overlap in the nodule/contralateral thyroid SUVmax ratios between groups. The MTC and AUS/FLUS nodules tended to have a higher nodule/blood pool SUVmax ratio than the other pathologic groups.

Conclusion

There was considerable variation in radiologic characteristics among benign thyroid nodules. The ratio of thyroid nodule SUVmax/blood pool SUVmax may be useful to differentiate pathologic groups, but larger studies are needed to investigate this further. Given the potential for malignancy in thyroid nodules with focal 68Ga-DOTATATE activity, further evaluation with serum calcitonin and FNA may be considered.

Video Abstract: http://links.lww.com/NMC/A186
Timing of Intravenous Epinephrine Administration During Out-of-Hospital Cardiac Arrest
Authors: Fukuda Tatsuma , Ohashi-Fukuda Naoko , Inokuchi Ryota , Kondo Yutaka , Taira Takayuki , Kukita Ichiro
Published: January 2021

Background:

Current guidelines for cardiopulmonary resuscitation recommend that standard dose of epinephrine be administered every 3 to 5 min during cardiac arrest. However, there is controversy about the association between timing of epinephrine administration and outcomes after out-of-hospital cardiac arrest (OHCA). This study aimed to determine whether the timing of intravenous epinephrine administration is associated with outcomes after OHCA.

Methods:

We analyzed Japanese government-led nationwide population-based registry data for OHCA. Adult OHCA patients who received intravenous epinephrine by emergency medical service personnel in the prehospital setting from 2011 to 2017 were included. Multivariable logistic regression models were used to assess the associations between time to first epinephrine administration and outcomes after OHCA. Subsequently, associations between early (≤20 min) versus delayed (>20 min) epinephrine administration and outcomes after OHCA were examined using propensity score-matched analyses. The primary outcome was 1-month neurologically favorable survival.

Results:

A total of 119,946 patients (mean [SD] age, 75.2 [14.8] years; 61.4% male) were included. The median time to epinephrine was 23 min (interquartile range, 19–29). Longer time to epinephrine was significantly associated with a decreased chance of 1-month neurologically favorable survival (multivariable adjusted OR per minute delay, 0.91 [95% CI, 0.90–0.92]). In the propensity score-matched cohort, when compared with early (≤20 min) epinephrine, delayed (>20 min) epinephrine was associated with a decreased chance of 1-month neurologically favorable survival (959/42,804 [2.2%] vs. 330/42,804 [0.8%]; RR, 0.34; 95% CI, 0.30–0.39; NNT, 69).

Conclusions:

Delay in epinephrine administration was associated with a decreased chance of 1-month neurologically favorable survival among patients with OHCA.
Long-term Persistence of Allosensitization After Islet Allograft Failure
Authors: Rios Paola , Baidal David , Lemos Joana , Camhi Stephanie S. , Infante Marco , Padilla Nathalia , Alvarez Gil Ana M. , Fuenmayor Virginia , Ambut Jonathan , Qasmi Fatima A. , Mantero Alejandro M. , Cayetano Shari Messinger , Ruiz Phillip , Ricordi Camillo , Alejandro Rodolfo
Published: January 2021

Background.

Allosensitization has been reported after discontinuation of immunosuppression following graft failure in islet transplantation (ITx) recipients, though duration of its persistence is unknown.

Methods.

We evaluated 35 patients with type 1 diabetes who received ITx, including 17 who developed graft failure (ITx alone, n = 13; ITx plus bone marrow-derived hematopoietic stem cells, n = 4) and 18 with persistent graft function. Panel-reactive antibody (PRA) was measured yearly for the duration of graft function within 1 y after graft failure at enrollment and yearly thereafter.

Results.

In ITx alone graft failure patients, 61% (8/13) were PRA-positive at 6 y postgraft failure, and 46% (6/13) developed donor-specific anti-HLA antibodies (DSA to 2 ± 1 donors) during follow-up. The degree of sensitization was variable (cPRA ranging between 22% and 100% after graft failure). Allosensitization persisted for 7–15 y. Three subjects (3/13) were not allosensitized. In ITx plus bone marrow-derived hematopoietic stem cell recipients, cPRA-positivity (88%–98%) and DSA positivity persisted for 15 y in 75% (3/4) of subjects.

Conclusions.

Allosensitization was minimal while subjects remained on immunosuppression, but after discontinuation of immunosuppressive therapy, the majority of subjects (77%) became allosensitized with persistence of PRA positivity for up to 15 y. Persistence of allosensitization in this patient population is of clinical importance as it may result in longer transplant waiting list times for identification of a suitable donor in the case of requiring a subsequent transplant.
A large food-borne outbreak of campylobacteriosis in kindergartens and primary schools in Pescara, Italy, May–June 2018
Authors: Sorgentone Simona , Busani Luca , Calistri Paolo , Robuffo Giorgio , Bellino Stefania , Acciari Vicdalia , Ferri Maurizio , Graziani Caterina , Antoci Salvatore , Lodi Fabrizio , Alfonsi Valeria , Cammà Cesare , Fazii Paolo , Andrianou Xanthi , Cito Francesca , Lombardi Giuliano , Centorotola Gabriella , D’Amario Massimo , D’Alterio Nicola , Savini Vincenzo , De Massis Fabrizio , Pelatti Anna , Di Domenico Marco , Di Donato Guido , Di Giannatale Elisabetta , Di Marcantonio Lisa , Di Marzio Violeta , Di Serafino Gabriella , Janowicz Anna , Marfoglia Cristina , Marotta Francesca , Morelli Daniela , Migliorati Giacomo , Neri Diana , Pomilio Francesco , Scattolini Silvia , Rezza Giovanni , Caponetti Antonio , Pezzotti Patrizio , Garofolo Giuliano
Published: January 2021

Introduction. In May–June 2018, an outbreak of campylobacteriosis involved students and school staff from kindergartens and primary schools in Pescara, southern Italy.

Aim. We present details of the epidemiological and microbiological investigation, and the findings of the analytical study, as well as the implemented control measures.

Methodology. To identify possible risk factors associated with the observed outbreak, a case control study was conducted using a questionnaire to collect information on the date of symptoms onset, type and duration of symptoms, type of healthcare contact, school attendance, and food items consumed at school lunches during the presumed days of exposure. Attack rates were calculated for each date and school. Logistic regression models were used to estimate the odds ratios of being a case and the odds of illness by food items consumed, respectively. Moreover, we carried out a comparative genomic analysis using whole genome multilocus sequence typing (wgMLST) of

Campylobacter jejuni

strains isolated during the outbreak investigation to identify the source of the outbreak.

Results. Overall, 222 probable cases from 21 schools were identified, and

C. jejuni

was successfully isolated from 60 patients. The meals in the schools involved were provided by two cooking centres managed by a joint venture between two food companies. Environmental and food sampling, epidemiological and microbiological analyses, as well as a case control study with 176 cases and 62 controls from the same schools were performed to identify the source of the outbreak. The highest attack rate was recorded among those having lunch at school on 29 May (7.8 %), and the most likely exposure was ‘caciotta’ cheese (odds ratio 2.40, 95 % confidence interval 1.10–5.26, P=0.028).

C. jejuni

was isolated from the cheese, and wgMLST showed that the human and cheese isolates belonged to the same genomic cluster, confirming that the cheese was the vehicle of the infection.

Conclusion. It is plausible that a failure of the pasteurization process contributed to the contamination of the cheese batches. Timely suspension of the catering service and summer closure of the schools prevented further spread.
Modeling hepatitis C virus kinetics during liver transplantation highlights the role of the liver in virus clearance
Authors: Shekhtman Louis , Navasa Miquel , Sansone Natasha , Crespo Gonzalo , Subramanya Gitanjali , Chung Tje Lin , Pérez-del-Pulgar Sofía , Perelson Alan S. , Cotler Scott J. , Uprichard Susan L. , Dahari Harel , Forns Xavier
Published: January 2021

While the liver, specifically hepatocytes, are widely accepted as the main source for hepatitis C virus (HCV) production, the role of the liver/hepatocytes in the clearance of circulating HCV remains largely unknown. Here we evaluated the function of the liver/hepatocytes in clearing virus from the circulation by investigating viral clearance during liver transplantation and from culture medium in vitro. Frequent HCV kinetic data during liver transplantation were recorded from 5 individuals throughout the anhepatic (AH) phase and for 4 hours after reperfusion (RP), along with recordings of fluid balances. Using mathematical modeling, the serum viral clearance rate, c, was estimated. Analogously, we monitored the clearance rate of HCV at 37°C from culture medium in vitro in the absence and presence of chronically infected Huh7 human hepatoma cells. During the AH phase, in 3 transplant cases viral levels remained at pre-AH levels, while in the other 2 cases HCV declined (half-life, t1/2~1h). Immediately post-RP, virus declined in a biphasic manner in Cases 1-4 consisting of an extremely rapid (median t1/2=5min) decline followed by a slower decline (HCV t1/2=67min). In Case 5, HCV remained at the same level post-RP as at the end of AH. Declines in virus level were not explained by adjusting for dilution from IV fluid and blood products. Consistent with what was observed in the majority of patients in the anhepatic phase, the t1/2 of HCV in cell culture was much longer in the absence of chronically HCV-infected Huh7 cells. Therefore, kinetic and modeling results from both in vivo liver transplantation cases and in vitro cell culture studies suggest that the liver plays a major role in clearing HCV from the circulation.
A Whole-Brain Functional Connectivity Model of Alzheimer’s Disease Pathology
Authors: Prakash Ruchika S. , McKenna Michael R. , Gbadeyan Oyetunde , Shankar Anita R. , Andridge Rebecca , Scharre Douglas W.
Published: January 2021

Early detection of Alzheimer’s disease (AD) is a necessity as prognosis is poor upon symptom onset. Although previous work diagnosing AD from protein-based biomarkers has been encouraging, cerebrospinal (CSF) biomarker measurement of AD proteins requires invasive lumbar puncture, whereas assessment of direct accumulation requires radioactive substance exposure in positron emission tomography (PET) imaging. Functional magnetic resonance imaging (fMRI)-based neuromarkers, offers an alternative, especially those built by capitalizing on variance distributed across the entire human connectome. In this study, we employed connectome-based predictive modeling (CPM) to build a model of functional connections that would predict CSF p-tau/Aβ42 (PATH-fc model) in individuals diagnosed with Mild Cognitive Impairment (MCI) and AD dementia. fMRI, CSF-based biomarker data, and longitudinal data from neuropsychological testing from the Alzheimer’s Disease NeuroImaging Initiative (ADNI) were utilized to build the PATH-fc model. Our results provide support for successful in-sample fit of the PATH-fc model in predicting AD pathology in MCI and AD dementia individuals. The PATH-fc model, distributed across all ten canonical networks, additionally predicted cognitive decline on composite measures of global cognition and executive functioning. Our highly distributed pathology-based model of functional connectivity disruptions had a striking overlap with the spatial affinities of amyloid and tau pathology, and included the default mode network as the hub of such network-based disruptions in AD. Future work validating this model in other external datasets, and to midlife adults and older adults with no known diagnosis, will critically extend this neuromarker development work using fMRI.

Significance Statement

Alzheimer’s disease (AD) is clinical-pathological syndrome with multi-domain amnestic symptoms considered the hallmark feature of the disease. However, accumulating evidence from autopsy studies evince support for the onset of pathophysiological processes well before the onset of symptoms. Although CSF- and PET-based biomarkers provide indirect and direct estimates of AD pathology, both methodologies are invasive. In here, we implemented a supervised machine learning algorithm – connectome-based predictive modeling – on fMRI data and found support for a whole-brain model of functional connectivity to predict AD pathology and decline in cognitive functioning over a two-year period. Our study provides support for AD pathology dependent functional connectivity disturbances in large-scale functional networks to influence the trajectory of key cognitive domains in MCI and AD patients.
Using numerical modeling and simulation to assess the ethical burden in clinical trials and how it relates to the proportion of responders in a trial sample
Authors: Boissel Jean-Pierre , Pérol David , Décousus Hervé , Klingmann Ingrid , Hommel Marc
Published: January 2021

In order to propose a more precise definition and explore how to reduce ethical losses in randomized controlled clinical trials (RCTs), we set out to identify trial participants who do not contribute to demonstrating that the treatment in the experimental arm is superior to that in the control arm. RCTs emerged mid-last century as the gold standard for assessing efficacy, becoming the cornerstone of the value of new therapies, yet their ethical grounds are a matter of debate. We introduce the concept of unnecessary participants in RCTs, the sum of non-informative participants and non-responders. The non-informative participants are considered not informative with respect to the efficacy measured in the trial in contrast to responders who carry all the information required to conclude on the treatment’s efficacy. The non-responders present the event whether or not they are treated with the experimental treatment. The unnecessary participants carry the burden of having to participate in a clinical trial without benefiting from it, which might include experiencing side effects. Thus, these unnecessary participants carry the ethical loss that is inherent to the RCT methodology. On the contrary, responders to the experimental treatment bear its entire efficacy in the RCT. Starting from the proportions observed in a real placebo-controlled trial from the literature, we carried out simulations of RCTs progressively increasing the proportion of responders up to 100%. We show that the number of unnecessary participants decreases steadily until the RCT’s ethical loss reaches a minimum. In parallel, the trial sample size decreases (presumably its cost as well), although the trial’s statistical power increases as shown by the increase of the chi-square comparing the event rates between the two arms. Thus, we expect that increasing the proportion of responders in RCTs would contribute to making them more ethically acceptable, with less false negative outcomes.
External Validations of Cardiovascular Clinical Prediction Models: A Large-scale Review of the Literature
Authors: Wessler Benjamin S. , Nelson Jason , Park Jinny G. , McGinnes Hannah , Gulati Gaurav , Brazil Riley , Van Calster Ben , van Klaveren D. , Venema Esmee , Steyerberg Ewout , Paulus Jessica K. , Kent David M.
Published: January 2021

Background

There are many clinical prediction models (CPMs) available to inform treatment decisions for patients with cardiovascular disease. However, the extent to which they have been externally tested and how well they generally perform has not been broadly evaluated.

Methods

A SCOPUS citation search was run on March 22, 2017 to identify external validations of cardiovascular CPMs in the Tufts PACE CPM Registry. We assessed the extent of external validation, performance heterogeneity across databases, and explored factors associated with model performance, including a global assessment of the clinical relatedness between the derivation and validation data.

Results

2030 external validations of 1382 CPMs were identified. 807 (58%) of the CPMs in the Registry have never been externally validated. On average there were 1.5 validations per CPM (range 0-94). The median external validation AUC was 0.73 (25th−75thpercentile [IQR] 0.66, 0.79), representing a median percent decrease in discrimination of −11.1% (IQR −32.4%, +2.7%) compared to performance on derivation data. 81% (n = 1333) of validations reporting AUC showed discrimination below that reported in the derivation dataset. 53% (n = 983) of the validations report some measure of CPM calibration. For CPMs evaluated more than once, there was typically a large range of performance. Of 1702 validations classified by relatedness, the percent change in discrimination was −3.7% (IQR −13.2, 3.1) for ‘closely related’ validations (n=123), −9.0 (IQR −27.6, 3.9) for ‘related validations’ (n=862) and −17.2% (IQR −42.3, 0) for ‘distantly related’ validations (n=717) (p<0.001).

Conclusion

Many published cardiovascular CPMs have never been externally validated and for those that have, apparent performance during development is often overly optimistic. A single external validation appears insufficient to broadly understand the performance heterogeneity across different settings.
Pre-stimulus alpha activities predict the confidence in subjective judgment by modulating post-stimulus theta oscillation
Authors: Qian Haoyue , Lu Yang , Liu Zhiyuan , Weng Xue , Guo Xiuyan , Li Lin , Zheng Li , Xu Min , Cai Xiaohan , Men Weiwei , Gao Jiahong , Gao Xiangping
Published: January 2021

Even when making arbitrary decisions, people tend to feel varying levels of confidence, which is associated with the pre-stimulus neural oscillation of the brain. We investigated varying confidence in a pure subjective judgment task, and how this confidence was predicted by pre-stimulus alpha oscillations. Participants made pure subjective judgments where their prior experience seems to be helpful but actually useless, and their fluctuating confidence was related to the choice boundary process rather than the evidence accumulation process, suggesting participants underwent varying confidence resulting from the internal signals. With EEG and MEG analyses, we not only revealed the linkage between confidence and pre-stimulus alpha activities, but also successfully located this linkage onto decision-making relevant brain areas, i.e. MCC/PCC and SMA. Moreover, we unveiled a specific pathway underlying such linkage, that is, the influence of pre-stimulus alpha activities on decision confidence was fulfilled through modulating post-stimulus theta activities of SMA.
How the Easter Egg Weevils Got Their Spots: Phylogenomics reveals Müllerian Mimicry inPachyrhynchus(Coleoptera, Curculionidae)
Authors: Van Dam Matthew H. , Cabras Analyn Anzano , Lam Athena W.
Published: January 2021

The evolutionary origins of mimicry in the Easter Egg weevil,Pachyrhynchus,have fascinated researchers since first noted more than a century ago by Alfred Russel Wallace. Müllerian mimicry, or mimicry in which two or more distasteful species look similar, is widespread throughout the animal kingdom. Given the varied but discrete color patterns inPachyrhynchus,this genus presents one of the best opportunities to study the evolution of both perfect and imperfect mimicry. We analyzed more than 10,000 UCE loci using a novel partitioning strategy to resolve the relationships of closely related species in the genus. Our results indicate that many of the mimetic color patterns observed in sympatric species are due to convergent evolution. We suggest that this convergence is driven by frequency-dependent selection.