bluuebunny/crossref_metadata_2025 huggingface dataset:
Narcissus or Literary Illusion
Authors: Rosati Gianpiero
Published: December 2021

It was almost certainly Ovid who joined together the narratives of frustrated desire of Echo (in love with Narcissus) and Narcissus (in love with his own mirror image). This he did by exploiting the Latin word imago, which defines both the visual reflection and the acoustic one. The illusion produced by the reflection is the central theme in Ovid’s story, and it is also the principle on which the two stories are closely intertwined, replicating the theme of reflection in both structure and language, and offering a reading of reality as a space dominated by ambiguities and deceptions. Narcissus’ ‘tragicomedy of errors’ implies at the same time a discourse on the fictitious nature of all literary texts, but his figure is also an emblem of the poet bent over in admiration of his own virtuosity, and in particular of Ovid himself, who was said by Quintilian to have been ‘too in love with his own brilliance’.
The Spectacle of Appearances
Authors: Rosati Gianpiero
Published: December 2021

Ovid thematizes the gap between appearance and reality, which also is represented on the linguistic level through an insistent, systematic discordance between the literal meaning of the language and the figurative one. The metamorphic and spectacular nature of language therefore becomes a mirror of the whole reality, which is subject to the law of continuous change, and gives rise to the game of illusions and deceptions in which humans are involved and often overwhelmed. Ovid’s verbal pyrotechnics, long dismissed as a fatuous rhetorical exercise, is actually a highly conscious key to representing reality with its paradoxes; and the distinctive visual, ekphrastic style of his poem (destined to become the ‘Bible of painters’) is the mark of Ovid’s continuous intense reflection on his own representational strategies.
Marriage
Authors: Toulmin Camilla
Published: December 2021

Marriage can be viewed in economic terms as an investment, an outlay of capital by the man’s family before and at the time of the wedding which yields returns over the subsequent period. Returns take a variety of forms, depending on the rights and obligations associated with marriage in a given society. Bambara society in Kala is patriarchal, and lineage-based, in which bride-wealth is paid by the man’s family to that of the woman’s family. Control over childbearing is one of several rights which pass on marriage, along with a woman’s labour power, in the millet-field and in domestic arenas. A woman’s income and resources, and the links of support between her and her natal households, are also valuable elements which come with marriage. Being married is seen as a fundamental and necessary state, very few women remain unmarried for long, polygamy and widow inheritance are practiced, and rates of remarriage are very high. The chapter compares the costs of and returns from marriage. These costs and returns have been changing over time and do patterns of marriage. Marriage also faces certain risks, from mortality, illness, sterility, and marital breakdown.
The Role of the Directors
Authors: Micheler Eva
Published: December 2021

This chapter describes the role of the directors. The duties of the directors are owed to the company and while the shareholders are the primary indirect beneficiaries of those duties, the law integrates the interests of creditors and also of wider society. The law is primarily focused on ensuring compliance with the Companies Act and the constitution rather than with the enhancement of economic interests. The Company Directors Disqualification Act 1986 serves as a mechanism through which the public interest is integrated into company law, while the UK Corporate Governance Code adds a further procedural dimension to the operation of the board of directors. The chapter then looks at how the idea of designing remuneration in a way that guides the directors to act either for the benefit of the shareholder or for the benefit of the company is flawed and has served as a motor justifying increasing rewards without bringing about commensurate increases in performance. It also analyses the duties of the directors to keep accounting records and to produce financial reports.
The Role of the Shareholders
Authors: Micheler Eva
Published: December 2021

This chapter explores the role of the shareholders, who have substantial influence over the company. UK company law is shareholder-centred, but it would be wrong to conclude that shareholders are the principals of the directors or of the company. Shareholders normally appoint the directors and auditors, and they have a mandatory power to remove them. The shareholders are also responsible for approving certain transactions, including share issues, takeover defences, political donations, provisions made for employees on the cessation of business, and (under the Listing Rules) certain large transactions. Taken together, these powers give the shareholders significant influence over the management of the company. The rights of shareholders are, however, also subject to constraints. These constraints operate for the benefit of minority shareholders and creditors. The chapter then examines the UK Stewardship Code, through which the government attempts to exercise pressure on institutional shareholders to refrain from requesting short-term return. It also analyses the reflective loss principle, which restricts shareholders in pursuing damages claims against third parties in circumstances where the company has a competing claim.
Conclusions
Authors: Micheler Eva
Published: December 2021

This concluding chapter summarizes how the previous chapters explained company law through a real entity theory. According to this theory, the law does not create organizations but finds them as a real social phenomenon. When human beings interact, habits, routines, processes, and procedures form. These affect the way participants of an organization act and so are real in their consequences. Organizations are characterized by this social structure. There also exists individual agency, which enables participants to deviate from the social structure and over time also to modify it. At a positive level, company law can be explained as making it easier for organizations to act autonomously and also as supplying a decision-making process that assigns roles to directors, shareholders, auditors, and a company secretary. Not all organizations are companies and not every company operates as an organization. Company law is nevertheless designed with a view to facilitating autonomous organizational action.
The Social and Political Nature of Spirit
Authors: Wilburn Josh
Published: December 2021

Chapter 3 explores two aspects of spirit’s social and political nature—its role in the process of absorbing social influences that shape a person’s values, and its responsibility for a person’s emotional reactions to those they consider either part of, or outside of, their social groups or communities—as well as two related problems that arise in corrupt political circumstances. According to Plato’s critique of contemporary Greek society, popular education and politics fail because they reflect a value system informed primarily by human appetite and pleonexia that prioritizes bodily, external, and material goods. When citizens absorb these values through thumos, their resulting moral corruption leads to civic discord as their aggressive spirited desires become directed against one another in their competition for limited appetitive goods. This establishes two challenges for Plato that involve attention to human spirit: making people virtuous through social education and making cities unified and stable.
The Spirited Part of the Soul in the Timaeus
Authors: Wilburn Josh
Published: December 2021

Chapter 8 examines Plato’s account of intrapsychic “communication” in the Timaeus and defends an imagistic account according to which the various activities of the spirited part of the soul—the motivations it generates, its training through musical and gymnastic education, its responsiveness to rational judgment, and its resistance to offensive appetites—can all be explained at the cognitive level by appealing only to the resources of sense-perception, memory, and imagination. On this view, it is not necessary to attribute to spirit the capacity either to understand the “logistic” (i.e. linguistic or propositional) content of rational judgments themselves, or to issue judgments with such content of its own. This chapter also examines how Plato adapts the Homeric and poetic association of thumos with the heart and circulatory system (as well as with the lungs and respiratory system) to provide a biological foundation for the dialogue’s theory of spirited cognition.
Hedging Bets with BITS
Authors: Dreyfuss Rochelle C
Published: December 2021

This chapter argues that bilateral investment treaties (BITS) and free trade agreements (FTAs) erect a high hedge around intellectual property rights, protecting them from the impact of state regulation. Two investor-state dispute settlements (ISDS) involving IP have been resolved by final award. In both cases, the state prevailed, suggesting that the hedge may not be as impenetrable as had originally been feared. However, the chapter contends that this view is mistaken. While the awards in the decided disputes may close the door on specific contentions, they invite further challenges and maintain the heavy shadow that the hedge provided by ISDS casts on state action. In order to trim that hedge, it will be necessary for the drafters of investment obligations and the tribunals that hear ISDS disputes to take into account the intangibility of IP rights in determining when IP is sufficiently localized in a host state that it should be considered protectable by that state's investment obligations. The chapter then explores ways to trim ISDS, including the possibility of using ISDS as a mechanism for building counter-norms—hedges that protect the public and its regulatory interest.
Emotion and the arts
Authors: Brown Steven
Published: December 2021

While many historical approaches equate the arts with aesthetics, I see the arts far more broadly than that. In addition, aesthetic emotions themselves need to be grounded in a general theory of human emotion. Along these lines, this chapter presents a communication model of emotion that covers the full gamut of processes from the production to the perception of emotion in the arts. The production side includes compositional processes for imbuing an artwork with emotions, as well as performance processes for conveying the emotions contained in an artwork. The perceptual mechanisms include recognition of the emotional content of an artwork, as well as the experience of felt emotions by people in response to such a work. The latter is where aesthetic emotions are situated in the model.
Italianating the Boy
Authors: Brown Pamela Allen
Published: December 2021

In the 1580s John Lyly and other writers for children’s companies created novel plays featuring a keen-witted, hot-blooded, virtuosic innamorata, relying on the beauty and skills of the cross-dressed boy player. Plays aimed at a worldly elite audience exoticize and eroticize the “boy actress,” painting him as extravagantly Italianate in ways that shadow the foreign diva, evidence of her transnational impact on plays and playing. Lyly’s Gallathea, Sapho and Phao, and The Woman in the Moone; Peele’s Arraignment of Paris; and Marlowe’s Dido, Queen of Carthage show how the English contained the threat of the actress by appropriating and adapting her trademark playing and star scenes, such as solo song and madness. As a result, the skilled labor of both divas and boys left its mark on these innovative works.
“Let all the dukes and all the devils roar!” Mad Skills and Madwomen
Authors: Brown Pamela Allen
Published: December 2021

The wildly popular star scene of female derangement enriched the stock of theatergrams deployed by playwrights across the map. Isabella Andreini’s triumph playing La Pazzia (“Madness”), featuring her skills in singing, impersonation, languages, and improvisation, spurred many imitations. On the English stage female madness took several forms. Bereaved madwomen leap from deep mourning to subversive songs and jokes, as with Ophelia in Hamlet and Cornelia in Webster’s The White Devil. Others express furious grief cut off by showy suicides (Isabella in Kyd’s The Spanish Tragedy, and Zabina in Marlowe’s Tamburlaine). Sapho in Lyly’s Sapho and Phao and Dido in Marlowe’s The Tragedie of Dido, Queen of Carthage suffer comic and tragic erotomania. Most distinctive are the comic virtuosas: Pandora in Lyly’s The Woman in the Moone and the Jailer’s Daughter in Shakespeare and Fletcher’s The Two Noble Kinsmen amuse and astonish with multiple prolonged pazzie and prodigious displays of skill.
Introduction
Authors: Kumojima Tomoe
Published: December 2021

The introductory chapter provides the historical and cultural contexts to situate the discussions on Victorian women’s travel writing on Meiji Japan in the wider academic debate on the British Empire, Victorian literature, and female travel writing. It provides an overview of Anglo–Japanese relations between 1854 and 1912 to trace shifts in the bilateral relationship and foreground its singularity in a multitude of East–West encounters. It then examines travel writings by both male and female travellers to Meiji Japan and fictional representations of the country in Victorian literature and theatre. It surveys travelogues by a group of female travellers alongside those by diplomats and journalists like Kipling, Japan-related writings by Wilde and Stevenson, and theatrical pieces such as The Mikado. The chapter considers the literary invention of Japan and analyses how women travellers negotiated discursive constraints due to gender and colonialism and challenged mainstream representations of Japan and Japanese people.
Explaining Membership Eligibility
Authors: Thomas Daniel C.
Published: December 2021

This chapter elaborates the book’s argument on the nature of regional communities, the contestation and evolution of membership norms, how these norms shape a regional community’s decision-making on which non-member states are eligible to join, and what happens when membership norms break down. It compares this argument to alternative hypotheses with observable implications derived from existing theories of regional integration.
The Evolution of EU Membership Norms
Authors: Thomas Daniel C.
Published: December 2021

This chapter traces the emergence, contestation, and evolution of membership norms within the European Union and its institutional precursors from the 1950s to the present. The genealogy demonstrates that these norms have changed significantly over time, contrary to the assumptions of many scholars and the claims of many EU pronouncements in recent decades. EU norms limited membership to non-Communist states (1957–1961), parliamentary democracies (1962–1969), and liberal democracies (1970–2005), but consensus then broke down and has not been re-established. The chapter thus establishes an empirical basis for investigating in later chapters how prevailing membership norms have shaped the community’s decision-making on the eligibility of particular aspirant and candidate states.
EU Membership Eligibility in Statistical and Comparative Perspective
Authors: Statsch Patrick D.
Published: December 2021

This chapter offers various empirical tests of competing arguments regarding the factors that shape a regional community’s decision-making on the membership eligibility of non-member states. It introduces a new dataset of 48 cases where the EU made a decision on the membership eligibility of a non-member state between 1957 and 2017. It then tests the explanatory power of the various theories introduced in the previous chapter using three, complementary analytical methods—cross tabulation, logistic regression, and qualitative comparative analysis. All three methods support the conclusion that membership norms have a more consistent impact on EU decision-making than familiar explanatory factors such as the commercial and security interests of member states.
Ritual’s Evolutionary Landscapes
Authors: Whitehouse Harvey
Published: December 2021

Understanding the role of ritual in the evolution of social complexity requires attention to many complex, interacting processes operating at different levels. This chapter attempts to sort these out into a coherent overarching framework by building on the ideas of British biologist, philosopher, and polymath C. H. Waddington, who put forward the idea of an ‘epigenetic landscape’ to explain how organisms develop. Waddington’s basic model can be extended to explain how cognitive-developmental and social-historical landscapes unfold and how all three kinds of landscapes interact. Adopting this overarching perspective on cultural evolution helps bridge the unnecessary divisions among branches of evolutionary theory and psychology that emphasize distinct but potentially complementary aspects of social learning and cultural transmission.
‘The Kinge and His Cubbs’ in Peril
Authors: Akkerman Nadine
Published: December 2021

This chapter considers several thwarted plots against the Stuarts, which had a particular affect on Elizabeth’s relationship with her brother Henry. First, the Main and Bye plots - a pair of overlapping plots whose combined intention was to overthrow King James in favour of his first cousin, the English-born Lady Arbella Stuart, and install Thomas Grey, 15th Baron Grey of Hilton, as de facto king, to secure greater religious toleration for Catholics in England – which would have seen Elizabeth killed. The plotters included Sir Walter Raleigh and, more importantly, Lord Cobham, husband of Elizabeth’s governess Lady Kildare. Though the plots failed, they resulted in Lady Kildare’s removal from office and Elizabeth and Henry being separated for their own safety – the court at Oatlands was dissolved and Elizabeth moved to Coombe Abbey near Coventry, the residence of the Haringtons. The second plot was the notorious Gunpowder Plot which would have had Elizabeth crowned queen: the confession of Guy Fawkes showed beyond doubt that although the primary aim had been to blow up parliament with James and Henry in attendance, this was merely a clearing of the way, as ‘they intended that the king’s daughter the Lady Elizabeth should have succeeded’. The plot showed that having Elizabeth in the country was not safe either, and so she was moved closer to the court, to Kew. This enabled her and Henry to visit each other regularly and even share their education. They behaved and were in many ways treated as if they were twins.
Heidelberg
Authors: Akkerman Nadine
Published: December 2021

After the wedding, Elizabeth and Frederick began the journey to his ancestral home, Heidelberg, and were entertained royally in the United Provinces. After persuading the States General to join the Protestant Union, Frederick left Elizabeth in the United Provinces to prepare Heidelberg Castle for her arrival. Heidelberg had accommodated two, complementary, households since the death of Elector Friedrich IV in 1610: that of the Administrator of the Lower Palatinate, the Duke of Zweibrücken-Veldenz, who would govern until Frederick came of age, and that of Frederick’s mother, the Electress-Dowager Louise Juliana. The arrival of Frederick and Elizabeth in 1613 introduced two new households into the equation – to make matters more confusing, Elizabeth’s own household was riven along factional lines; the majority of her ladies-in-waiting were English, while most of her gentlemen were Scots. The couple failed to agree on matters of precedence, as Elizabeth believed that her status as a royal-born princess accorded her a higher status than anyone else at court, including Frederick. There were also financial problems, and Hans Meinhard Schomberg, the head of Elizabeth’s household, tried hard to solve both the financial and precedence issues. Elizabeth soon delivered the Palatinate a male heir while Frederick’s first decision on reaching his majority was whether or not to go to war. Elizabeth became increasingly reliant on Schomberg, and his being called away to fight at the newly reignited Jülich-Berg & Cleves crisis, along with her husband falling prey to fits of melancholy, left her at the mercy of her mother-in-law.
In the Service of the Electress
Authors: Akkerman Nadine
Published: December 2021

Elizabeth had to negotiate complex networks of honour and obligation with little money, and gives her jewellery away to servants to force James to reward them by buying the pieces back. Another way for Elizabeth to assert her authority was through the hiring of Salomon de Caus, designer of the famous Hortus Palatinus and several masques. Elizabeth’s position was further enhanced by the Dowager Electress retiring to her dower. As relations within the court improved, Elizabeth went against her father’s wishes by approving the marriage of Schomberg with Anne Dudley, her chief lady-in-waiting. Dudley, however, died shortly afterwards and Elizabeth was grief-stricken. The conflicts over precedence returned during a disastrous state visit to Stuttgart, and Elizabeth, homesick, spent increasing amounts of time at the hunt. After a report by Sir Henry Wotton on morale at Heidelberg, Lady Harington was sent to raise Elizabeth’s spirits. Elizabeth gave birth to a second son, Charles Louis, on 1 January 1618, but was still desperate to return to England, and soon received permission to undertake the journey from her father. Carleton, afraid that she would not be received warmly by the Stuart court, sent her a gift of monkeys. He need not have worried, as Frederick banned her from travelling as she was once more pregnant – this time with Elisabeth. Elizabeth attempted to hide her next pregnancy, with Rupert, in order that she might undertake the journey but was unsuccessful, and would not try to leave Heidelberg again.
Losing Champions
Authors: Akkerman Nadine
Published: December 2021

1626 was a dangerous year for those wedded to Elizabeth’s cause. The first major loss was Christian of Brunswick, who succumbed to illness aged 26. Elizabeth bore this badly, lapsing into a melancholy exacerbated by the ill-health of her most recent child, Henriette. Having lost one champion, another, Bethlen Gabor of Transylvania, made peace with the Emperor. To make matters worse, Mansfeld’s battered body also gave up the fight. When Christian IV was defeated at Lütter, everyone blamed Buckingham for diverting resources from The Hague Alliance. Buckingham had compounded the Cadiz debacle, supporting the Huguenots under siege at Isle de Rhé. Intending to forge a coalition with the French, he merely precipitated a Franco-Stuart war. While Charles I tried to bolster Danish forces, Buckingham’s subsequent assassination surprised nobody. Elizabeth employed Miereveldt and Honthorst to help charm Charles with politically motivated portraiture. Charles opened peace talks with the French and the Spanish; his wife Henrietta Maria finally produced a male heir. Frederick took his firstborn Frederick Henry to view a Spanish treasure ship recently captured by the Dutch, but his barge capsized and Frederick Henry drowned. But as the Franco-Stuart war was ended by treaty and the Swedish king Gustavus Adolphus opened a new phase in the Thirty Years War, landing at Usedom and winning a string of dramatic victories against Imperial forces, the Palatinate was within touching distance. Frederick joined Gustavus in battle, but as his inferior. Just as Elizabeth opened new negotiations to recover her dower Frankenthal, Gustavus died.
Dwindling Influence
Authors: Akkerman Nadine
Published: December 2021

Her ally the Landgravine of Hesse died, but Elizabeth could not afford mourning clothes. The Hague had become a centre of elite entertainment under Elizabeth's influence, with masques (Ballet de la Carmesse, with soldiers of the Dutch Army dancing) and literary salons (such as L'Ordre de l'union de la Joye, with Huygens and Johan de Witt). Many of the Stuart contingent nevertheless left The Hague, feeling less than welcome following the outbreak of the First Anglo-Dutch War. Rupert and Maurice were surprised by a hurricane close to the Virgin Islands - Maurice drowned; Elizabeth hung onto her hope that he had survived for years. Elizabeth believed she could return to Germany, if not to Frankenthal than to Heidelberg Castle, where rooms were being prepared for her. In 1653 she informed the States of Holland of her plans, and 164 creditors presented their accounts. Another embassy was sent to parliament with the request to clear her debts. In 1654, the States of Holland finally granted her a pension. Elizabeth did not want to leave without settling her debts, or retrieving her jewels from the pawnshops. Charles Louis wanted to empty Rhenen yet further. Louise Hollandine converted to Catholicism. Cromwell died. Elizabeth abandoned plans to return to Germany as Charles Louis had so many domestic troubles (he was asking for a divorce to marry below his station). After spending a week with her nephews in Brussels, she wanted to return to England, now that the stage for the Restoration had been set.
Abundances of phosphorus in bright F-G type main-sequence stars
Authors: Sadakane Kozo , Nishimura Masayoshi
Published: December 2021

Abundances of phosphorus (P) in 45 main sequence F-G type stars (including the Sun by using reflected light from the minor planet Vesta) in the metallicity range [Fe/H] from −0.4 to +0.3 have been determined. The effective temperatures of target stars range from 5500 to 6600 K. Two lines of P i at 9750.75 Å and at 9796.83 Å (multiplet No. 2) are analysed by using a profile fitting method. Significant star-to-star scatters up to 0.4 dex have been found at all metallicities. We find three stars (HD 9826, HD 20010, and HD 82328) in which values of [P/Fe] are lower than −0.20, showing that P is deficient with respect to Fe in these stars. Such objects have never been reported in the past and may have an impact on the theoretical studies of origin and evolution of P. The sample contains 18 stars with confirmed planets (not including the Sun) and no significant difference in abundance of P has been found between stars with planets and those with no confirmed planet.
Firm Organization with Multiple Establishments
Authors: Gumpert Anna , Steimer Henrike , Antoni Manfred
Published: December 2021

We show theoretically and empirically that the managerial organization of multiestablishment firms is interdependent across establishments. To derive our result, we study the effect of geographic frictions on firm organization. In our model, we assume that a CEO’s time is a resource in limited supply, shared across headquarters and establishments. Geographic frictions increase the costs of accessing the CEO. Hiring middle managers at one establishment substitutes for CEO time, which is reallocated across all establishments. Consequently, geographic frictions between the headquarters and one establishment affect the organization of all establishments of a firm. Our model is consistent with novel facts about multiestablishment firm organization that we document using administrative data from Germany. We exploit the opening of high-speed railway routes to show that not only the establishments directly affected by faster travel times but also the other establishments of the firm adjust their organization. Our findings imply that local conditions propagate across space through firm organization.
Informal Risk Sharing with Local Information
Authors: Ambrus Attila , Gao Wayne , Milán Pau
Published: December 2021

This article considers the effect of contracting limitations in risk-sharing networks, arising for example from observability, verifiability, complexity, or cultural constraints. We derive necessary and sufficient conditions for Pareto efficiency under these constraints in a general setting, and we provide an explicit characterization of Pareto efficient bilateral transfer profiles under CARA utility and normally distributed endowments. Our model predicts that network centrality is positively correlated with consumption volatility, as more central agents become quasi-insurance providers to more peripheral agents. The proposed framework has important implications for the empirical specification of risk-sharing tests, allowing for local risk-sharing groups that overlap within the village network.
Intelligence, Errors, and Cooperation in Repeated Interactions
Authors: Proto Eugenio , Rustichini Aldo , Sofianos Andis
Published: December 2021

We study how strategic interaction and cooperation are affected by the heterogeneity of cognitive skills of groups of players, over consecutive plays of repeated games with randomly matched opponents using Prisoner’s Dilemma as stage game. We observe overall higher cooperation rates and average final payoffs in integrated treatment groups—where subjects of different IQ levels interact together—than in separated treatment groups. Lower IQ subjects are better off and higher IQ subjects are worse off in integrated groups than in separated groups. Higher IQ subjects adopt harsher strategies when they are pooled with lower IQ subjects than when they play separately. We demonstrate that this outcome should be expected in learning and evolutionary models where higher intelligence subjects exhibit lower frequency of errors in the implementation of strategies. Estimations of errors and strategies in our experimental data are consistent with the model’s assumptions and predictions.
Portfolios for Long-Term Investors
Authors: Cochrane John H
Published: December 2021

How should long-term investors form portfolios in our time-varying, multi-factor and friction-filled world? Two conceptual frameworks may help: first, look directly at the stream of payments that a portfolio and payout policy can produce. Second, include a general equilibrium view of the markets’ economic purpose, and the nature of investors’ different preferences, risk-taking ability, and function in that equilibrium. These perspectives can rationalize some of investors’ behaviors, suggest substantial revisions to standard portfolio theory, and help us to apply portfolio theory in a way that is useful in practice.
Harnessing dendritic cells for innovative therapeutic cancer vaccines
Authors: Plumas Joël
Published: December 2021

Purpose of review

The clinical activity of new immunotherapies in cancer, such as anti-Programmed cell death 1 (PD-1)/Programmed death-ligand 1, has revealed the importance of the patient's immune system in controlling tumor development. As in infectious diseases, dendritic cells (DCs) are critical for inducing immune responses in cancer. Unfortunately, autologous DC-based vaccines have not yet demonstrated their clinical benefit. Here, we review recent research using allogeneic DCs as alternatives to autologous DCs to develop innovative therapeutic cancer vaccines.

Recent findings

A novel approach using an allogeneic plasmacytoid dendritic cell (PDC) line as an antigen presentation platform showed great potency when used to prime and expand antitumor-specific CD8+ T cells in vitro and in vivo in a humanized mouse model. This PDC platform, named PDC∗vac, was first evaluated in the treatment of melanoma with encouraging results and is currently being evaluated in the treatment of lung cancer in combination with anti-PD-1 immunotherapy.

Therapeutic cancer vaccines are of particular interest because they aim to help patients, to mount effective antitumor responses, especially those who insufficiently respond to immune checkpoint inhibitors. The use of an allogeneic plasmacytoid DC-based platform such as PDC∗vac could greatly potentiate the efficacy of these new immunotherapies.
Histopathological Analysis of Decellularized Porcine Small Intestinal Submucosa after Treatment of Skin Ulcer
Authors: Kobayashi Hisashi , Imai Yasuo , Hirao Takayuki , Nakao Ko , Kajinaka Hayato , Kishi Kazuo
Published: December 2021

Background:

Decellularized porcine small intestinal submucosa (SIS), commercialized as an extracellular matrix rich in cell-inducing substrates and factors, has been clinically applied to treat intractable skin ulcers and has shown therapeutic effects. The SIS reportedly induces cell infiltration and integrates with the ulcer bed after 3–7 days of application. The attached SIS degenerates over time, and the remaining mass appears as slough, below which is granulation tissue that is essential for healing. This study aimed to determine whether the slough should be removed in clinical settings.

Methods:

Five patients with intractable skin ulcers were included in this case series. Seven days after applying a two-layer fenestrated-type SIS to the ulcer, the removed slough was histopathologically examined.

Results:

The collagen fibers of the SIS somewhat degenerated, and inflammatory cell infiltration was observed from the ulcer side to the surface side of the SIS. Neovascularization was similarly observed on the ulcer side. The degree of inflammatory cell infiltration decreased from the ulcer side to the surface side, whereas pus (ie, aggregates of neutrophils) was observed on the surface and ulcer edges. Additionally, the removed slough contained regenerative epithelium on the ulcer side of the remaining collagen fibers.

Conclusions:

After treating intractable skin ulcers using SIS, we recommend removal of the upper surface and ulcer edge of the degenerated SIS or slough to prevent infection and preservation of the lower side of the degenerated SIS to maintain the granulation tissue and regenerative epithelium.
A Feasibility Study to Measure Protection Offered by a Coronavirus Disease 2019 Intubation Enclosure
Authors: Diaz Maria Carmen G. , Rahman Tariq , Hossain Jobayer , Dawson Kimberly , Madaus Stacy , Lim Doyle
Published: December 2021

This study assessed the feasibility of quantifying an intubation enclosure's ability to limit spread of aerosolized particles during simulated pediatric endotracheal intubation. Aerosolized particle counts were measured at the airway provider and around the room using the enclosure without suction, with suction, and no enclosure. The enclosure with suction had the least overall mean of 0.3-μ particles at the airway provider at 30 seconds (1,396.0), followed by enclosure without suction (26,308.3) and no enclosure (103,517.3), P = .064. This study's intubation enclosure limited the spread of aerosolized particles. Additional studies are needed to ensure this model translates to actual patient care.
Patient Monitoring Replacement Forecast
Authors: Crisafulli Jacob
Published: December 2021

Patient monitors and monitoring systems are a staple for all healthcare facilities and healthcare delivery organizations. The continuous monitoring of patient parameters such as heart rate, heart electrical activity, oxygen saturation (Spo
2), blood pressure, temperature, and other specialty measurements is a common feature for the care and safety of patients. Patient monitoring systems must record, collect, and display physiological data accurately and in real time to support clinical decision making during treatment. Patient monitoring can be rigorously defined as “repeated or continuous observations or measurements of the patient, his or her physiological function, and the function of life support equipment, for the purpose of guiding management decisions, including when to make therapeutic interventions, and assessment of those interventions [Michael SM, Gardner RM. Decision Support Systems in Critical Care. Springer; 1994].” The data provided by patient monitors are used for a multitude of applications: it directly affects the diagnostic and therapeutic treatment plans for a patient, alerts care providers to potential life-threatening incidents, and provides insight on the control of connected life-support medical devices. Physiological monitors can be found everywhere within a hospital. Depending on the acuity of a department or their intended application, the complexity of the device can vary as to how many parameters are monitored, whether it is bedside (fixed), portable, or telemetry, and what other medical equipment directly communicate with the monitor. The most commonly known application of physiological monitoring is for unstable/critically ill patients in intensive care units and medical/surgical units. Monitoring is needed on patients in these areas who have compromised homeostatic systems, are suspected to have a life-threatening condition, or are at a high risk of developing a life-threatening condition. Outside the more common environments where patient monitors reside, they are also used during more specialized practices including labor and delivery, operating room procedures, and interhospital and intrahospital patient transport.
Drug-induced bile duct injury: new agents, new mechanisms
Authors: Scoazec Jean-Yves
Published: December 2021

Purpose of review

Drug-induced bile duct injury can be caused by a long list of agents. In most cases, damage is because of T-cell-mediated idiosyncratic reactions. Recently, a number of new agents, including not only drugs but also herbal supplements, have been incriminated and new mechanisms of bile duct injury have emerged. This review will focus on these new data.

Recent findings

New members of drug families already known to be responsible for bile duct injury have been incriminated. New players have been identified, such as herbal supplements, like kratom, and recreational drugs, such as ketamine used outside the medical setting. Anticytokine monoclonal antibodies are rarely involved. In contrast, antineoplastic treatments are of growing concern, especially immune checkpoint inhibitors, which induce immune-related adverse effects because of the excessive stimulation of the immune system and its lack of regulation.

Two patterns of bile duct injury are recognized. Drug-induced small-duct cholangiopathies target the smaller bile ducts; acute injuries eventually progress to chronic disease in the form of the vanishing bile duct syndrome. Drug-induced sclerosing cholangitis target large bile ducts, with a protracted chronic course; the onset of symptoms may be delayed after drug discontinuation; potentially severe, life-threatening complications can occur.
Lobular Carcinoma of the Breast Metastatic to the Ovary
Authors: Chuang Ai-Ying , Watkins Jaclyn C. , Young Robert H. , Lerwill Melinda F.
Published: December 2021

We evaluated the clinicopathologic features of 38 cases of metastatic lobular (n=33) or predominantly lobular (n=5) carcinoma involving the ovary. The patients were from 39 to 91 years of age (mean: 53 y). In 2 cases, the breast primary and ovarian metastasis were diagnosed synchronously, and in 5, the breast primary was only discovered after the metastatic carcinoma in the ovary was found. In the majority of cases (79%), both ovaries were involved; the mean ovarian tumor size was 5.9 cm. The ovarian tumors demonstrated a range of architectural patterns including macronodular (71%), diffuse/solid growth (87%), single-cell infiltration (87%), cords (74%), and small nests/clusters (50%). Nine cases demonstrated focal signet ring cell morphology. The associated stromal reaction ranged from none to marked, with almost half of cases demonstrating a marked stromal response, largely prominent sclerosis. A variety of neoplasms, most typically sex cord-stromal tumors, lymphoma/leukemia, and desmoplastic small round cell tumor, may enter the differential. In addition to the obvious help afforded in most cases by the clinical history, a combination of judicious sampling, particularly to unearth the delicate cords or single-cell growth of lobular carcinoma, appropriate consideration of the cytologic features of the neoplastic cells, and immunohistochemistry can resolve the diverse issues in differential diagnosis that may arise.
EURO-MUSCULUS/USPRM Dynamic Ultrasound Protocols for Elbow
Authors: Ricci Vincenzo , Güvener Orhan , Chang Ke-Vin , Wu Wei-Ting , Mezian Kamal , Kara Murat , Leblebicioğlu Gürsel , Pirri Carmelo , Ata Ayşe Merve , Dughbaj Muhammad , Jain Nitin B. , Stecco Carla , Özçakar Levent
Published: December 2021

In this dynamic protocol, ultrasound examination of the elbow using different maneuvers is described for several/relevant elbow problems. Scanning videos are coupled with real-time patient examination videos for better understanding. The authors believe that this practical guide—prepared by an international consensus of several experts (EURO-MUSCULUS: European Musculoskeletal Ultrasound Study Group and USPRM: Ultrasound Study Group of ISPRM [International Society of Physical and Rehabilitation Medicine])—will help musculoskeletal physicians perform a better and uniform/standard approach.
Reliability and validity of 3D limb scanning for ankle-foot orthosis fitting
Authors: Powers Olivia A. , Palmer Jeff R. , Wilken Jason M.
Published: December 2021

Background:

Recent decreases in the cost of 3D scanners and improved functionality have resulted in increased adoption for ankle-foot orthosis (AFO) fittings, despite limited supporting data. For 3D limb scanning to be a feasible alternative to traditional casting methods, a consistent and accurate representation of limb geometry must be produced at a reasonable cost.

Objectives:

To evaluate the repeatability and validity of multiple lower limb measurements obtained using low-cost 3D limb scanning technology.

Study design:

Prospective, randomized, crossover-controlled, cross-sectional, reliability, and validity study.

Methods:

Physical measurements and 3D limb scans were completed for 30 participants. 11 measurements were selected for comparison based on their relevance to AFO fittings. Validity was assessed by comparison of physical and scan-based measures using Pearson's correlation coefficients and root mean square differences. Reliability was assessed using intraclass correlation coefficients and minimal detectable change (MDC) values. Bland–Altman plots were generated for data visualization.

Results:

All correlation values were above or equal to 0.80. Most intraclass correlation coefficient values were above 0.95. MDC values for physical and scan-based measurements differed by less than 2.0 mm. Scan MDC values were around or below 4 mm for foot and ankle measures and under 6 mm for circumference and length measures.

Conclusions:

The results of this study demonstrate that low-cost 3D limb scanning can be used to obtain valid and reliable measurements of 3D limb geometry for the purpose of AFO fitting, when collected using the clinically relevant standardized conditions presented here.
Impact of the COVID-19 restrictions on physical activity and quality of life in adults with lower limb amputation
Authors: Mellema Mirjam , Risnes Martha , Mirtaheri Peyman , Gjøvaag Terje
Published: December 2021

Background:

This study investigated the impact of COVID-19 restrictions on ambulatory activity and health-related quality of life (HR-QoL) in people with a lower limb amputation (LLA) in Norway. We hypothesized that the restrictions would negatively affect HR-QoL and decrease prosthetic wear time and ambulatory activity in participants with already limited mobility.

Methods:

Twenty individuals with LLA (age and time since amputation 56.2 ± 11.9 and 22.3 ± 20.1 years, respectively) participated. Ambulatory activity (stepwatch: prosthetic wear time; steps per day; minutes of low-intensity (1–15 steps min-1), moderate-intensity (16–40 steps min-1), and high-intensity ambulation (>40 steps min-1)) and HR-QoL (EQ-5D-5L) data were collected prepandemic and 8–12 months later during pandemic restrictions. Semistructured interviews identified personal experiences of coping with restrictions.

Results:

Prosthetic wear time decreased significantly (−1.0 ± 1.5 hours day-1
, p < 0.05). Steps per day (440 ± 1481), moderate-intensity and high-intensity ambulation (3.7 ± 23.4, and 4.8 ± 13.9 minutes day-1, respectively), and EQ-5D-5L index (.02 ± .10) increased, whereas low-intensity ambulation decreased (−1.5 ± 16.1 minutes day-1), all nonsignificant changes. Qualitative analysis identified three themes related to coping with restrictions: (1) personal situation, (2) a prosthetic user’s perspective, and (3) mindset.

Conclusions:

Increased time spent at home might explain the decreased prosthetic wear time. Contrary to the hypothesis, participants did not decrease their physical activity, and the declined low-intensity ambulation was offset by increased moderate-intensity and high-intensity ambulation. A positive mindset, intrinsic motivation, and health awareness may be important factors for maintaining ambulatory activity and HR-QoL in people with LLA.
Toward improving residual limb climate within prostheses for persons with lower limb loss: a technical note
Authors: Knight Ashley D , Hendershot Brad D , Sleeman Todd J , Dearth Christopher L , Starker Felix , Schneider Urs , Koehler-McNicholas Sara R , Barrons Kyle , Nickel Eric , Mion Spencer , Ferguson John , Slater Billie Savvas , Voss Gregory O , Koester Karl , Hansen Andrew H
Published: December 2021

Background:

Individuals with lower limb loss often wear a gel liner and enclosed socket for connecting to a terminal prosthetic device. Historically, a significant limitation to traditional liners and sockets is that they are thermal insulators, thereby trapping heat and moisture within, which can lead to numerous deleterious issues, including loss of suspension and residual limb skin problems, and, in turn, reductions in mobility, function, and overall quality of life. To mitigate these issues, new approaches are therefore needed to enhance the residual limb climate (e.g. breathability and air permeability), allowing the dispersal of heat and moisture from within the liner and socket.

Methods:

In this study, a multidisciplinary team sought to establish the feasibility of an innovative prosthetic liner-socket system, designed to improve residual limb climate by capitalizing on passive (i.e. nonpowered) ventilation to reduce temperature/moisture and improve socket comfort for persons with transtibial amputations. Focus group meetings, along with an iterative design approach, were implemented to establish innovative design and development concepts that led to a passively ventilated liner-socket system.

Conclusions:

Ex vivo design has supported the feasibility of developing a passively ventilated liner-socket. To build on these successes, future development and human subjects testing are needed to finalize a commercially viable system. Implementing a passively ventilated liner-socket system that improves residual limb health and comfort, without compromising function or mobility of the user, into standard clinical care may encourage a more active lifestyle and enhance the quality of life for individuals after lower limb loss.