bluuebunny/crossref_metadata_2025 huggingface dataset:
Cytochrome b Drug Resistance Mutation Decreases Babesia Fitness in the Tick Stages But Not the Mammalian Erythrocytic Cycle
Authors: Chiu Joy E , Renard Isaline , George Santosh , Pal Anasuya C , Alday P Holland , Narasimhan Sukanya , Riscoe Michael K , Doggett J Stone , Ben Mamoun Choukri
Published: June 2021

Human babesiosis is an emerging tick-borne malaria-like illness caused by Babesia parasites following their development in erythrocytes. Here, we show that a mutation in the Babesia microti mitochondrial cytochrome b (Cytb) that confers resistance to the antibabesial drug ELQ-502 decreases parasite fitness in the arthropod vector. Interestingly, whereas the mutant allele does not affect B. microti fitness during the mammalian blood phase of the parasite life cycle and is genetically stable as parasite burden increases, ELQ-502–resistant mutant parasites developing in the tick vector are genetically unstable with a high rate of the wild-type allele emerging during the nymphal stage. Furthermore, we show that B. microti parasites with this mutation are transmitted from the tick to the host, raising the possibility that the frequency of Cytb resistance mutations may be decreased by passage through the tick vector, but could persist in the environment if present when ticks feed.
Large-Scale Identification of T-Cell Epitopes Derived From Severe Acute Respiratory Syndrome Coronavirus 2 for the Development of Peptide Vaccines Against Coronavirus Disease 2019
Authors: Ma Yipeng , Liu Fenglan , Lin Tong , Chen Lei , Jiang Aixin , Tian Geng , Nielsen Morten , Wang Mingjun
Published: June 2021

Background

Coronavirus disease 2019 (COVID-19) continues to be a major public health challenge globally. The identification of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-derived T-cell epitopes is of critical importance for peptide vaccines or diagnostic tools of COVID-19.

Methods

In this study, several SARS-CoV-2-derived human leukocyte antigen (HLA)-I binding peptides were predicted by NetMHCpan-4.1 and selected by Popcover to achieve pancoverage of the Chinese population. The top 5 ranked peptides derived from each protein of SARS-CoV-2 were then evaluated using peripheral blood mononuclear cells from unexposed individuals (negative for SARS-CoV-2 immunoglobulin G).

Results

Seven epitopes derived from 4 SARS-CoV-2 proteins were identified. It is interesting to note that most (5 of 7) of the SARS-CoV-2-derived peptides with predicted affinities for HLA-I molecules were identified as HLA-II-restricted epitopes and induced CD4+ T cell-dependent responses. These results complete missing pieces of pre-existing SARS-CoV-2-specific T cells and suggest that pre-existing T cells targeting all SARS-CoV-2-encoded proteins can be discovered in unexposed populations.

Conclusions

In summary, in the current study, we present an alternative and effective strategy for the identification of T-cell epitopes of SARS-CoV-2 in healthy subjects, which may indicate an important role in the development of peptide vaccines for COVID-19.
An open source tool to compute measures of inpatient glycemic control: translating from healthcare analytics research to clinical quality improvement
Authors: Chen Ying , Ning Yilin , Thomas Prem , Salloway Mark , Tan Maudrene Luor Shyuan , Tai E-Shyong , Kao Shih Ling , Tan Chuen Seng
Published: June 2021

Objectives

The objective of this study is to facilitate monitoring of the quality of inpatient glycemic control by providing an open-source tool to compute glucometrics. To allay regulatory and privacy concerns, the tool is usable locally; no data are uploaded to the internet.

Materials and Methods

We extended code, initially developed for healthcare analytics research, to serve the clinical need for quality monitoring of diabetes. We built an application, with a graphical interface, which can be run locally without any internet connection.

Results

We verified that our code produced results identical to prior work in glucometrics. We extended the prior work by including additional metrics and by providing user customizability. The software has been used at an academic healthcare institution.

Conclusion

We successfully translated code used for research methods into an open source, user-friendly tool which hospitals may use to expedite quality measure computation for the management of inpatients with diabetes.
Team Science: A Practical Approach to Starting Collaborative Projects
Authors: Patel Miral M , Moseley Tanya W , Nia Emily S , Perez Frances , Kapoor Megha M , Whitman Gary J
Published: June 2021

A collaborative approach to treating patients is well taught in medical training. However, collaboration and team building in clinical and laboratory research may have been given less emphasis. More scientific discoveries are now being made with multidisciplinary teams, requiring a thoughtful approach in order to achieve research goals while mitigating potential conflicts. Specific steps for a successful team science project include building the team, assigning roles and responsibilities, allocating rules, and discussing authorship guidelines. Building a team involves bringing individuals together and developing a common research goal while establishing psychological safety for all members of the team. Clear assignment of roles and responsibilities avoids confusion and allows each member’s contributions to be acknowledged. Allocating rules involves discussing how decisions in the team will be made, how data and knowledge sharing will occur, and how potential conflicts will be resolved. Discussing authorship at the start of the project ensures that the entire team knows what work must be completed for authorship to be obtained.
Cost-Effectiveness of Magnetic Resonance Imaging Screening for Women With Extremely Dense Breast Tissue
Authors: Geuzinge H Amarens , Bakker Marije F , Heijnsdijk Eveline A M , van Ravesteyn Nicolien T , Veldhuis Wouter B , Pijnappel Ruud M , de Lange Stéphanie V , Emaus Marleen J , Mann Ritse M , Monninkhof Evelyn M , de Koekkoek-Doll Petra K , van Gils Carla H , de Koning Harry J ,   the DENSE trial study group
Published: June 2021

Background

Extremely dense breast tissue is associated with increased breast cancer risk and limited sensitivity of mammography. The DENSE trial showed that additional magnetic resonance imaging (MRI) screening in women with extremely dense breasts resulted in a substantial reduction in interval cancers. The cost-effectiveness of MRI screening for these women is unknown.

Methods

We used the MISCAN-breast microsimulation model to simulate several screening protocols containing mammography and/or MRI to estimate long-term effects and costs. The model was calibrated using results of the DENSE trial and adjusted to incorporate decreases in breast density with increasing age. Screening strategies varied in the number of MRIs and mammograms offered to women ages 50-75 years. Outcomes were numbers of breast cancers, life-years, quality-adjusted life-years (QALYs), breast cancer deaths, and overdiagnosis. Incremental cost-effectiveness ratios (ICERs) were calculated (3% discounting), with a willingness-to-pay threshold of €22 000.

Results

Calibration resulted in a conservative fit of the model regarding MRI detection. Both strategies of the DENSE trial were dominated (biennial mammography; biennial mammography plus MRI). MRI alone every 4 years was cost-effective with €15 620 per QALY. Screening every 3 years with MRI alone resulted in an incremental cost-effectiveness ratio of €37 181 per QALY. All strategies with mammography and/or a 2-year interval were dominated because other strategies resulted in more additional QALYs per additional euro. Alternating mammography and MRI every 2 years was close to the efficiency frontier.

Conclusions

MRI screening is cost-effective for women with extremely dense breasts, when applied at a 4-year interval. For a willingness to pay more than €22 000 per QALY gained, MRI at a 3-year interval is cost-effective as well.
Stress, Burnout, and Coping Strategies
Authors: Merlo Gia
Published: June 2021

Excessive and prolonged stress can result in physician burnout. Burnout can compromise a physician’s ability to effectively meet the needs of patients, while also having adverse effects on personal health and well-being. Physicians are exposed to a tremendous number of stressors that arise from factors such as time and resource constraints, the complex hierarchy among medical professionals, malpractice claims, and “difficult” patients and treatments. Although burnout is currently considered to be mostly due to external causes, protective mechanisms that physicians can employ to shield themselves are explored. Hans Selye’s model of the general adaptation syndrome is one means that individuals cope with stress, along with Richard Lazarus’s transactional model of stress. Other coping strategies include problem-based coping, the ABC technique, and meditation and mindfulness. Several maladaptive responses may temporarily offer relief but can in the long run prove to be damaging. Finally, online and other digital stress-reduction programs are explored.
Isavuconazole for treatment of refractory coccidioidal meningitis with concomitant cerebrospinal fluid and plasma therapeutic drug monitoring
Authors: Davis Matthew R , Chang Sandy , Gaynor Pryce , McCreary Erin K , Allyn Paul
Published: June 2021

Coccidioidal meningitis (CM) is a life-threatening infection with limited treatment options. Small series have reported success with isavuconazole; however, limited data exist on cerebrospinal fluid (CSF) penetration. Paired plasma and CSF isavuconazole concentrations were measured. Eleven CSF levels were tested, (7 ventricular, 4 lumbar) in three CM patients. Ventricular CSF levels were undetectable despite detectable plasma levels. All lumbar CSF levels were detectable (mean 1.00 µg/ml). Three pairs of lumbar CSF/plasma concentrations taken within 1 h of each other yielded a mean CSF/plasma ratio of 0.31. Isavuconazole was detectable in lumbar but not ventricular CSF in three patients treated for refractory CM.

Lay Summary

Isavuconazole is a triazole antifungal that has been used as salvage therapy in the treatment of coccidioidal meningitis (CM). Few data exist characterizing its concentration in the cerebrospinal fluid (CSF). We report tandem plasma and CSF concentrations of isavuconazole in three patients with CM.
H2 molecular gas absorption-selected systems trace CO molecular gas-rich galaxy overdensities
Authors: Klitsch Anne , Péroux Céline , Zwaan Martin A , De Cia Annalisa , Ledoux Cédric , Lopez Sebastian
Published: June 2021

Absorption-selected galaxies offer an effective way to study low-mass galaxies at high redshift. However, the physical properties of the underlying galaxy population remain uncertain. In particular, the multiphase circumgalactic medium is thought to hold key information on gas flows into and out of galaxies that are vital for galaxy evolution models. Here, we present ALMA observations of CO molecular gas in host galaxies of H2-bearing absorbers. In our sample of six absorbers, we detect molecular gas-rich galaxies in five absorber fields, although we did not target high-metallicity (>50 per cent solar) systems for which previous studies reported the highest detection rate. Surprisingly, we find that the majority of the absorbers are associated with multiple galaxies rather than single haloes. Together with the large impact parameters, these results suggest that the H2-bearing gas seen in absorption is not part of an extended disc, but resides in dense gas pockets in the circumgalactic and intragroup medium.
Locus-specific transcription silencing at the FHIT gene suppresses replication stress-induced copy number variant formation and associated replication delay
Authors: Park So Hae , Bennett-Baker Pamela , Ahmed Samreen , Arlt Martin F , Ljungman Mats , Glover Thomas W , Wilson Thomas E
Published: June 2021

Impaired replication progression leads to de novo copy number variant (CNV) formation at common fragile sites (CFSs). We previously showed that these hotspots for genome instability reside in late-replicating domains associated with large transcribed genes and provided indirect evidence that transcription is a factor in their instability. Here, we compared aphidicolin (APH)-induced CNV and CFS frequency between wild-type and isogenic cells in which FHIT gene transcription was ablated by promoter deletion. Two promoter-deletion cell lines showed reduced or absent CNV formation and CFS expression at FHIT despite continued instability at the NLGN1 control locus. APH treatment led to critical replication delays that remained unresolved in G2/M in the body of many, but not all, large transcribed genes, an effect that was reversed at FHIT by the promoter deletion. Altering RNase H1 expression did not change CNV induction frequency and DRIP-seq showed a paucity of R-loop formation in the central regions of large genes, suggesting that R-loops are not the primary mediator of the transcription effect. These results demonstrate that large gene transcription is a determining factor in replication stress-induced genomic instability and support models that CNV hotspots mainly result from the transcription-dependent passage of unreplicated DNA into mitosis.
Ceftolozane/Tazobactam and Imipenem/Relebactam Cross-Susceptibility Among Clinical Isolates of Pseudomonas aeruginosa From Patients With Respiratory Tract Infections in ICU and Non-ICU Wards—SMART United States 2017–2019
Authors: Lob Sibylle H , DePestel Daryl D , DeRyke C Andrew , Kazmierczak Krystyna M , Young Katherine , Motyl Mary R , Sahm Daniel F
Published: June 2021

Background

Carbapenem-nonsusceptible and multidrug-resistant (MDR) P. aeruginosa, which are more common in patients with lower respiratory tract infections (LRTIs) and in patients in intensive care units (ICUs), pose difficult treatment challenges and may require new therapeutic options. Two β-lactam/β-lactamase inhibitor combinations, ceftolozane/tazobactam (C/T) and imipenem/relebactam (IMI/REL), are approved for treatment of hospital-acquired/ventilator-associated bacterial pneumonia.

Methods

The Clinical and Laboratory Standards Institute–defined broth microdilution methodology was used to determine minimum inhibitory concentrations (MICs) against P. aeruginosa isolates collected from patients with LRTIs in ICUs (n = 720) and non-ICU wards (n = 914) at 26 US hospitals in 2017–2019 as part of the Study for Monitoring Antimicrobial Resistance Trends (SMART) surveillance program.

Results

Susceptibility to commonly used β-lactams including carbapenems was 5–9 percentage points lower and MDR rates 7 percentage points higher among isolates from patients in ICUs than those in non-ICU wards (P < .05). C/T and IMI/REL maintained activity against 94.0% and 90.8% of ICU isolates, respectively, while susceptibility to all comparators except amikacin (96.0%) was 63%–76%. C/T and IMI/REL inhibited 83.1% and 68.1% of meropenem-nonsusceptible (n = 207) and 71.4% and 65.7% of MDR ICU isolates (n = 140), respectively. Among all ICU isolates, only 2.5% were nonsusceptible to both C/T and IMI/REL, while 6.7% were susceptible to C/T but not to IMI/REL and 3.5% were susceptible to IMI/REL but not to C/T.

Conclusions

These data suggest that susceptibility to both C/T and IMI/REL should be considered for testing at hospitals, as both agents could provide important new options for treating patients with LRTIs, especially in ICUs where collected isolates show substantially reduced susceptibility to commonly used β-lactams.
Robot-Assisted Stereoelectroencephalography: 2-Dimensional Operative Video
Authors: Kondylis Efstathios , Whiting Alexander C , Harasimchuk Stephen P , Bulacio Juan , Bingaman William
Published: June 2021

Invasive neuromonitoring is an important component of presurgical workup and seizure onset zone localization in patients with epilepsy being considered for surgical resection. In the United States, intraparenchymal stereoelectroencephalography (SEEG) electrodes have been replacing subdural grid electrodes for most cases, following a trend that has already matured in Europe. The use of robotic assistance has been shown to improve operative times and accuracy in SEEG electrode placement, as users benefit from the embedded planning software as well as the efficiency and accuracy of the robotic arm. The greatest barriers to implementation of this technology are the upfront cost and learning curve. This case-based surgeon's perspective operative video could benefit those considering incorporating robotic assistance for SEEG electrode placement. Those considering robotic assistance for pedicle screw placement and other budding applications may also benefit, as well as innovators looking for new applications.

The patient consented for the procedure, video recording, and inclusion in subsequent publications.
The Secular Bias and the Study of Religious Politics
Authors: Hashemi Nader
Published: June 2021

This chapter focuses on the problem of misunderstanding religious politics in the Arab-Islamic world. The goal is to advance an objective historical and comparative framework for interpreting this subject. Two key themes that have been central to John Esposito’s scholarship are examined: the secular bias in modernization theory and the need for a historical and contextual understanding of the many faces of political Islam. To advance this argument, Michael Walzer’s The Paradox of Liberation: Secular Revolutions and Religious Counterrevolutions will be utilized, focusing on his discussion of Algeria and political Islam. It is argued that Walzer offers a typical liberal reading of this topic that upon examination is ideologically biased and analytically distorting. Ironically, his earlier writings on religion and politics provide a more useful interpretive framework for understanding the rise of religious politics in our contemporary world.
Crimes and Punishments of Imperial Women
Authors: Boatwright Mary T.
Published: June 2021

Discussion of Domitia Longina, who survived allegations of adultery, Domitian’s divorce and (re)marriage, and his assassination, opens this chapter on imperial women and Roman law. Moving from Ulpian’s statement about legal rights and privileges of emperors and the Augusta, it covers norms and regulations for imperial women’s sexuality, particularly marriage and divorce, as well as crimes and punishments of imperial women, including the adultery cases and sentences of Julia the Elder in 2 BCE and Julia the Younger in 8 CE that Tacitus obliquely ties to treason. Reviewing finally imperial women’s fates at the deaths of their husband or other relative as emperor, the chapter concludes that inclusion in the imperial family brought women greater liability, but no immunity or impunity.
The Forgiven
Authors: Shoemaker David
Published: June 2021

For most theorists, paradigm cases of direct blame consist in the feeling and expression of resentment. It has thus seemed natural for these theorists to begin by presenting, and leaning on, an analysis of resentment. But it turns out there are numerous conflicting analyses of it, and these disagreements ramify when theorists use resentment to tell us about the nature of both blame and its resolution in forgiveness. Resentment cannot bear such theoretical weight. So instead of starting at the front end of the blaming exchange with an analysis of resentment, this chapter starts at the back end with an account of what it takes to be successfully forgiven. This approach promises to yield several more determinate conclusions about (a) when the withdrawal of blame and forgiveness are appropriate and why; (b) the nature of the hard feelings that paradigm forgiveness withdraws; (c) why judgment is superfluous to this blaming and forgiving exchange; and (d) why resentment has been the wrong core blaming component to lean on all along.
Forgiveness as Renunciation of Moral Protest
Authors: Pereboom Derk
Published: June 2021

In this chapter, Derk Pereboom defends the claim that forgiveness is essentially the renunciation of a stance of moral protest. Forgiveness need not be preceded by actual resentment or by any angry emotion. Rather, by virtue of regarding wrongdoers as blameworthy for past wrongdoing, forgivers regard the stance of moral protest against them as having been appropriate. In forgiving, they then renounce this stance. This renunciation is norm-changing, first of all because it involves moral protest changing from being appropriate to being inappropriate. Other alterations in norms may also accompany this change: earlier the wronged party perhaps legitimately demanded apology and amends, while upon forgiving, the request for new apologies and additional amends becomes inappropriate.
Forgiving Evil
Authors: Garrard Eve , McNaughton David
Published: June 2021

Are evil acts forgivable? This question lies at the intersection of theories about the nature of evil and theories about the nature of forgiveness. Since evil acts seem to be the most plausible candidates for unforgivability, we start with a brief defense of the secular deployment of the idea of evil, and then move to an overview of various theories of evil. After providing an outline of what forgiveness involves, we consider what being unforgivable might actually amount to. Four possible accounts of being unforgivable are canvassed—psychological impossibility, psychological difficulty, lack of reasons for forgiveness, and a moral prohibition on forgiveness—and their implications for the opening question are considered. We conclude that nothing so far considered rules out the moral permissibility of forgiveness for evil acts. Finally, the question of whether forgiveness would enable the evildoer’s slate to be wiped clean at last is briefly considered.
Larinum in Cicero’sPro Cluentio
Authors: Robinson Elizabeth C.
Published: June 2021

This chapter analyzes the social history that can be gleaned from a close reading of Cicero’s Pro Cluentio. After presenting the case against Cluentius, it discusses the chief elements of the social history of Larinum that appear in the oration. These include intermarriage between the domi nobiles of the town, links between Larinum and other Italian communities, links with Rome, travel and road networks, the effects of the Social War, and the patronage and wealth of the domi nobiles. Although Cicero’s speech is a work of rhetoric, the historical details that he includes can be considered largely accurate. This information cannot be obtained from any other source. The Pro Cluentio provides information about the leading families of the town that complements the prosopographical information found in the epigraphic record. When combined with the other evidence discussed in the rest of the book, it shows the ways that the citizens of Larinum were interacting with Rome and the effects of the town’s transition into the Roman state that could be seen in the middle of the first century bce.
Messaging and Branding to Engage Veterans as Employees
Authors: Gudmundsson Peter A.
Published: June 2021

This chapter offers suggestions on the two essential foundations of any veteran hiring initiative—branding (making the case for why a veteran would want to work for your organization) and engagement (ways to effectively connect with the veterans and attract them to work for your organization). Effective corporate branding to veterans includes a focus on the organization’s mission or higher purpose, a sense that the organization will provide veterans with momentum in their career as they transition into civilian employment, and mentorship to help veterans develop in their civilian careers. Recommendations are offered for effective messaging to veterans, including targeted emails, digital advertising, having a presence at veteran events, and corporate involvement in veteran philanthropy. Suggestions are offered on how to develop the metrics to measure the success of these initiatives are also presented.
Employer Misconceptions of Veterans and Veteran Misconceptions of Employers
Authors: Eversole Eric
Published: June 2021

This chapter outlines the misconceptions that employers may have about hiring military veterans and the misconceptions that veterans might have about civilian employers and offers recommendations on how to overcome the misconceptions. Employer misconceptions are countered in this chapter by presenting data on veteran socioeconomic status, geography, income, and education to give employers a better understanding of the groups they are trying to hire. Recommendations are offered to employers on how they can address veteran misconceptions with examples of how to market and sell their company and industry, properly train recruiters and other employees on military culture, create networking and mentoring opportunities, and establish accurate expectations to veterans, recruiters, and other employees within the company.
Supporting the National Guard and Reservists as Civilian Employees
Authors: Kirchner Michael , Herd Ann M.
Published: June 2021

Members of the military’s National Guard and Reserves acquire numerous competencies and technical skills through their training that could be valuable to civilian organizations. For employers seeking to hire and retain National Guardsmen and Reservists, understanding the challenges faced while managing dual employment can aid organizations that are striving to become or improve their support of employees also serving in a Reserve component. This chapter reviews distinctions between the National Guard, Reserves, and active duty before outlining legal rights of employers and service members who work for nonmilitary organizations. The chapter then provides a business case for employing National Guardsmen and Reservists while describing prominent corresponding challenges experienced by all stakeholders. It concludes with best practices for organizations striving to be military friendly to National Guardsmen and Reservists.
Retention of Veteran Employees
Authors: Goulart Mark
Published: June 2021

Instead of viewing veteran employment as simply the state of having a job, this chapter posits thinking about the issue more holistically by examining the employment life cycle, including recruiting, hiring/onboarding, and retention. As military veteran unemployment numbers remain low, this chapter argues that the primary question has now shifted from whether or not veterans have a job to whether they have the right job and how long they remain in that job (i.e., retention or attrition). It next examines why veteran employees in civilian organizations leave their jobs; the reasons for their dissatisfaction; differences between veteran and nonveteran employees; how this impacts attraction; the difference between positive and negative veteran attrition; and how underemployment is defined and addressed. Best practices for retaining veteran employees are offered.
Defending Representation Realism
Authors: Ramsey William
Published: June 2021

The representations that are invoked by theorists and researchers in cognitive science allow for a variety of different ontological interpretations. Along with both straightforward realist and eliminativist positions, there are various forms of deflationism. Deflationist accounts deny that the explanatory value or even accuracy of representational theories depends upon the existence of objectively real structures or states that play a representational role in the brain. Alternatively, many deny the existence of any sort of representational content that is objectively real and independent of our explanatory goals or interpretative activities. This chapter argues that this sort of representational deflationism doesn’t really work. After spelling out what a robust sort of realism does or does not entail, the chapter offers some general reasons for thinking realism is preferable to deflationism. Then it looks at three versions of deflationism and argues that all three either fail to capture our scientific practice, or collapse into a more straightforward sort of realism or eliminativism.
Representing as Coordinating with Absence
Authors: Orlandi Nico
Published: June 2021

This chapter offers an account of mental representation that spells out the conditions for representational status. I argue that we should draw a distinction between issues concerning content and issues concerning representational role, and that the challenge of understanding representational role is at least as pressing as the more familiar challenge of giving an account of content. I then argue that we should understand representational role in terms of serving as a stand-in, and use the idea of structural isomorphism, with examples from animal cognition and from the literature on analog representation, to capture standing-in.
Situated Mental Representations
Authors: Newen Albert , Vosgerau Gottfried
Published: June 2021

If we want to account for mental representations (MRs) as being used in scientific explanations and realized by neural correlates in biological systems, then we have to give up the traditional Fodorian view of rigid symbolic MRs. However, we do not have to throw out the baby with the bathwater and accept anti-representationalism. Instead this chapter offers a new account of mental representations as real, nonstable, use-dependent, and situated. As such, they can be pivotal constituents of scientific explanations. The chapter demonstrates the empirical adequacy of this account by discussing cases of birds and rats relying on what-where-when memory. It argues that we need to involve nonlinguistic MRs to adequately account for their abilities. In this way, the alternative theory presented here provides a detailed description of situated mental representations: it combines a functionalist account of MR with a relational dimension that can vary with the situation type and that allows for nonstatic constructions of MRs in specific contexts.
Nonnatural Mental Representation
Authors: Piccinini Gualtiero
Published: June 2021

This chapter distinguishes between two types of representation, natural and nonnatural. It argues that nonnatural representation is necessary to explain intentionality. It also argues that traditional accounts of the semantic content of mental representations are insufficient to explain nonnatural representation and, therefore, intentionality. To remedy this, the chapter sketches an account of nonnatural representation in terms of natural representation plus offline simulation of nonactual environments plus tracking the ways in which a simulation departs from the actual environment. To represent nonnaturally, a system must be able to decouple internal simulations from sensory information by activating representational resources offline. The system must be able to represent things that are not in the actual environment and to track that it’s doing so; i.e., there must be an internal signal or state that can indicate whether what is represented departs from the actual environment. In addition, the system must be able to manipulate a representation independently of what happens in the actual environment and keep track that it’s doing so. In short, nonnatural representations are offline simulations whose departure from the actual environment the system has the function to keep track of. This is a step toward a naturalistic, mechanistic, neurocomputational account of intentionality.
The Baroque Violin & Viola
Authors: Reiter Walter S.
Published: June 2021

The Early Music revival has had far-reaching consequences on how music of the past is performed, both by specialists and non-specialists. This timely book is a practical step-by-step course of lessons for violinists and violists in both these categories, covering the interpretation, technique, culture, and historical background of the Baroque violin repertoire. Written by a violinist and teacher specializing in Baroque music over many years, it guides readers from the basics (how to hold the violin) to Bach, via music from a wide variety of styles. Avoiding obscure musicological jargon, it is eminently readable and accessible. Packed with information, detailed observations on the music under discussion, and relevant quotations from historical and contemporary sources, it covers everything the Baroque violin student should know and may be considered the equivalent of two to three years of individual lessons. The book contains over 100 exercises devised for and tested on students over the years. The author’s holistic approach is evident through the exercises aimed at bringing out the individual voice of each student, and his insistence that what happens within, the identification and manipulation of affects, is a vital part of successful performance. Imitating the voice, both spoken and sung, is a constant theme, beginning with the simple device of playing words. There are fifty lessons, including five Ornamentation Modules and ones on specific topics: temperament, rhetoric, the affects, and so on. All the music, transcribed for both violin and viola, is downloadable from the website, where there is also a series of videos.
Bringing Fast Notes to Life
Authors: Reiter Walter S.
Published: June 2021

This lesson uses a fast movement from an Albinoni sonata to investigate various devices that are essential for bringing Baroque music to life. The main focus is on how to play a line of equal notes in an interesting way: three flexibilities are identified: rhythm, dynamics, and articulation, with special exercises devised to maximize the uses of each one. The question of sequences is explored in detail (there are eleven in the movement) along with the issue of adding (or not) slurs where the composer writes none.
The Starting-Point of Interpretation: Learning to Observe
Authors: Reiter Walter S.
Published: June 2021

This lesson begins with a detailed investigation into a complete Corelli sonata. After a brief introduction to Corelli’s work and significance, there are crucial basic questions: what is meant by interpretation and what does the process of interpretation actually involve? Subjectivity and objectivity are discussed, the conclusion being that as a performer’s mission is not to express the performer but to reveal the music, the guiding mantra should be “The Starting-point of Interpretation Is Observation.” Baroque music depends for its effectiveness on the observation of minutiae, for every stroke of the composer’s pen is there for a purpose; it is the performer’s task to observe these minutiae, understand them, and bring them to life. The detailed “Observations” section of each lesson reflects this. Also discussed are ways of transforming these observations into sound, how to choose a tempo, whether the tempi of the movements are related, and the meaning of syncopation.
Rhetoric
Authors: Reiter Walter S.
Published: June 2021

The origin and purpose of rhetoric is explained and the strong links between rhetoric and music, mentioned by writers from the ancient world to modern times, detailed. Much Baroque music is not melodic, multiple sources tell us, but is written “in the manner of a discourse,” the aim being to influence the emotions of the listener through the many purposeful details of which it is formed. To be effective, music composed in this way must be played with this in mind: seeking to impose a lyrical way of playing appropriate to later musical styles will be ineffective. Readers are encouraged to examine the devices orators use to persuade their audiences and apply those skills to develop a more rhetorical way of playing; one exercise teaches students to “speak music.” Rhetorical devices such as punctuation, tessitura, abruptio, tirata, and parenthesis are listed, explained, and illustrated with corresponding literary and musical examples.
We the Gamers
Authors: Schrier Karen
Published: June 2021

The world is in crisis. The people of the world are all connected, and rely on one another to make ethical decisions and to solve civic problems together. Ethics and civics have always mattered, but it is becoming more evident how much they matter. Teaching ethics and civics is essential to the future. This book argues that games can encourage the practice of ethics and civics. They can help people to connect, deliberate, reflect, and flourish. They can help people to reimagine systems and solve problems. Games are communities and public spheres. Like all communities, they may encourage care, connection, and respect. They may also be used for hate, disinformation, and exclusion. Games reveal humanity’s compassion as well as its cruelty. We the Gamers provides research-based perspectives related to why and how people should play, make, and use games in ethics, civics, character, and social studies education. The book also shows how people are already engaging in ethics and civics through games. It systematically evaluates how to use games in classrooms, remote learning environments, and other educational settings, with consideration to different audiences and standards. This book also provides tips and guidelines, as well as resources, activities, and case studies. It includes examples of all different types of games—virtual reality, mobile, computer, and card games, and big-budget commercial games, indie games, and more. How can people play and design a new world, together?
How Do We Read and Evaluate Information?
Authors: Schrier Karen
Published: June 2021

Chapter 10 describes how games may help people practice critical literacy skills such as reading, evaluating, and interpreting information. How is it determined which evidence and data are valid and reliable, and how might games support this? How might games help people to engage with news and current events, or to counter fake news? The chapter includes an overview of why reading and interpreting information matters in civics and ethics, and why games may support this. It also includes the limitations of using games to explore evidence and information, and how to minimize those limitations. Finally, it reviews strategies that teachers can take to use games to practice literacy and information evaluation skills. It opens with the example of the game Factitious, and also shares three examples-in-action: Executive Command, Thoughts and Prayers, and Bad News.
On the Idea of and Necessity for a Metaphysics of Morals
Authors: Timmons Mark
Published: June 2021

This chapter focuses on Section I of the general introduction to The Metaphysics of Morals in which Kant explains what a metaphysics of morals is, and why there must be one. To properly understand Kant’s views on these matters requires explaining Kant’s conception of philosophy and the place of metaphysics as a branch of philosophy. In spelling this out, the chapter discusses key distinctions between theoretical and practical cognition, empirical (a posteriori) versus rational (a priori) sources of cognition, and the analytic/synthetic distinction as Kant understood it. For Kant, a metaphysics of morals is that branch of philosophy concerned with those synthetic a priori propositions and principles fundamental to morality. The chapter also explains the role of anthropology in a metaphysics of morals.
Vascularization
Authors: Douglas Kenneth
Published: June 2021

Abstract: This chapter gives an account of the vascularization of bioprinted constructs—that is, how scientists have found ways of providing a hierarchical network of blood vessels for bioprinted cells to supply the cells with oxygen and nutrients. The chapter calls attention to the particular obstacle of vascularizing so-called thick tissue. The dilemma is that cells must be within approximately 100–200 millionths of a meter (the so-called diffusion limit) of a source of blood or else they will die. So for tissue many millimeters thick, bioprinting researchers must build an extensive vasculature. One way in which the issue has been addressed is with an innovative fugitive ink that melts when cooled. The reason this ink is so critical is that other fugitive materials require high temperatures or other treatments for removal that would kill the cells nearby.
What’s in the Offing?
Authors: Douglas Kenneth
Published: June 2021

Abstract: This chapter attempts to peer into the possible future of bioprinting to consider two conceivable directions that bioprinting might take while also contemplating what we may be able to learn about bioprinting’s trajectory by reflecting on another biomedical quest—the twentieth-century’s attempt to conquer polio. In one study that might offer a route for bioprinting, a team created bioconstructs with cell densities approaching that of native tissue (about 108 cells/gram). The group used embedded 3D printing to create a branched, hierarchical network of vascular channels within a large, high cell density bioconstruct and perfused media through the channels that they created using fugitive ink. This was to provide nutrient support for the cells. They also built a high-density cardiac construct in which the cells beat synchronously and showed functional contractility. They quantitatively measured the deformation of the cardiac tissue during contraction.
Bullshit, Post-truth, and Propaganda
Authors: Cassam Quassim
Published: June 2021

The question addressed in this chapter is whether the concepts of post-truth and bullshit are useful tools of politico-epistemological analysis in relation to political events in the U.S. and U.K. since 2016. Bullshitters are understood as knowingly ignorant individuals who conceal their ignorance by pretending to know what they do not know or understand what they do not understand. This account is compared to other accounts of bullshit, including Frankfurt’s. Three notions of post-truth are distinguished. The concepts of post-truth and bullshit are shown not to provide for an adequate conceptualization of the political tactics that have come to the fore in recent years. An emphasis on bullshit and post-truth trivializes and misdescribes these tactics, which are more adequately conceptualized in terms of notions such as propaganda and hate speech.
Special Concern and Personal Identity
Authors: Brink David O.
Published: June 2021

As discussed by John Locke, Joseph Butler, and Thomas Reid, prudence involves a special concern for the agent’s own personal good that she does not have for others. This should be a concern for the agent’s overall good that is temporally neutral and involves an equal concern for all parts of her life. In this way, prudence involves a combination of agent relativity and temporal neutrality. This asymmetrical treatment of matters of interpersonal and intertemporal distribution might seem arbitrary. Henry Sidgwick raised this worry, and Thomas Nagel and Derek Parfit have endorsed it as reflecting the instability of prudence and related doctrines such as egoism and the self-interest theory. However, Sidgwick thought that the worry was unanswerable only for skeptics about personal identity, such as David Hume. Sidgwick thought that one could defend prudence by appeal to realism about personal identity and a compensation principle. This is one way in which special concern and prudence presuppose personal identity. However, as Jennifer Whiting has argued, special concern displayed in positive affective regard for one’s future and personal planning and investment is arguably partly constitutive of personal identity, at least on a plausible psychological reductionist conception of personal identity. After explaining both conceptions of the relation between special concern and personal identity, the chapter concludes by exploring what might seem to be the paradoxical character of conjoining them, suggesting that there may be no explanatory priority between the concepts of special concern and personal identity.
Separating Persons
Authors: Goodrich James
Published: June 2021

In Reasons and Persons, Derek Parfit argues for a reductionist view of persons and that our ethical thinking should become more impersonal. While doing so, he argues that we may need to give up some widely shared intuitions about the Separateness of Persons and all of those views which crucially hinge upon it. However, this chapter argues that Parfit was mistaken. His reductionist views of persons and his more general claim that our ethical thinking should become more impersonal are in fact compatible with several plausible interpretations of the Separateness of Persons. Parfit’s project in Reasons and Persons should thus be understood not as undermining the Separateness of Persons, but as transforming our understanding of it. The chapter closes by considering the degree to which Parfit had reason by his own lights to accept some version of the Separateness of Persons.
Individualist Utilitarianism and Converging Theories of Rights
Authors: Ashford Elizabeth
Published: June 2021

The paper develops two core themes of Derek Parfit’s philosophy. The first is his goal of unifying the two main rival impartial moral theories, Kantian deontology and consequentialism, therefore reinforcing their claim to pertain to objective moral truths. The second is his focus on the moral significance of the combined effects of many agents’ behaviour, and on the challenges this poses to ordinary moral thinking. This is a theme that runs throughout his work, that he returns to at the very end of volume iii of On What Matters. Kantianism and consequentialism have been thought to fundamentally diverge on the issue of rights and trade-offs. The chapter first outlines the version of consequentialism taken to be most plausible, calling it ‘individualist utilitarianism’, which differs from so-called ‘classical utilitarianism’ in taking the moral importance of well-being to be grounded on the moral importance of the persons whose well-being it is. This paves the way for a pluralist Kantian and utilitarian account of human rights, grounded on the moral significance both of persons’ well-being and their dignity as rational autonomous agents. The chapter then turns to the topic of the threat to access to the means of subsistence, both for the current poor and future generations, posed by global as well as domestic socio-economic structures and anthropogenic climate change. This harm is the combined effect of the ongoing patterns of behaviour of a vast number of agents. The chapter argues that individualist utilitarianism and Kantianism converge on the conclusion that the duty to avoid harms of this kind should be analysed as a shared duty of basic justice, non-fulfilment of which constitutes a structural human rights violation.
Parfit’s Reorientation
Authors: Persson Ingmar
Published: June 2021

This paper aims to show that between Reasons and Persons and On What Matters the orientation of Derek Parfit’s philosophy underwent a significant change. The approach of Reasons and Persons is largely revisionist, which is exemplified by his reductionist account of personal identity. This account is omitted in On What Matters apparently because it does not fit in with the conciliationist project of this work. The aim of the first two volumes of that work is to show that, on the basis of a non-naturalist theory of normative reasons, three supposedly irreconcilable moral theories—rule-consequentialism, Kantian and Scanlonian contractualism—could converge to form a single Triple Theory. In the third volume, the conciliationist approach is carried further by Parfit’s attempt to show both that his metaethical position is in essential agreement with rivals, such as Gibbard’s expressivism, and to reconcile parts of common-sense morality and consequentialism in order to bring them together in the Triple Theory. This chapter argues that the failure of these attempts as well as the fact that the most controversial revisionist claims in Reasons and Persons are left out throw doubt on the feasibility of Parfit’s conciliationalist undertaking.