bluuebunny/crossref_metadata_2025 huggingface dataset:
Warriors and Ruins
Authors: Mottram Stewart
Published: March 2019

This chapter explores Shakespeare’s response to the ‘bare ruined choirs’ of dissolved churches and monasteries, focusing on Cymbeline (c.1610) and showing how this play’s language of ruin works to remind Shakespeare’s contemporaries of the potential for anti-catholic intolerance to incite further acts of religious violence in early Stuart England and Wales. Cymbeline conveys a double vision of Wales, the site of Britain’s heroic victory over Rome, but also the scene for Welsh acts of savagery and rebellion that coalesce around the image of Cloten’s headless corpse, described by Lucius in the play as a ‘ruin … that sometime | … was a worthy building’ (4.2.353–4). The chapter shows how Shakespeare uses this language of ruin to reflect anxieties over the role of Welsh catholics in the Essex rising (1601) and Gunpowder Plot (1605), in which demands for greater toleration of catholics were a recurrent concern. Cymbeline condemns these acts of catholic rebellion, but the chapter argues that it also questions the merits of England’s Jacobean culture of intolerance towards catholics—an intolerance that, as Shakespeare hints, must also take some measure of responsibility for catholic acts of rebellion in the early seventeenth century. Shakespeare’s emphasis on the need for toleration of catholic loyalism need not, however, imply Shakespeare’s own sympathies for catholic beliefs and practices. The chapter shows how Shakespeare remembers the monastic ruinations under Henry VIII in order to reflect on the continuing cycles of religious violence that this originary moment of reformation iconoclasm unleashed.
Introduction
Authors: Mottram Stewart
Published: March 2019

This chapter introduces the book as a whole, tracing the history of protestant iconoclasm and ruin creation across the long reformation, from the dissolution of the monasteries in the 1530s to the disestablishment of the English protestant church in the 1650s. It focuses attention on the poet George Herbert, whose poems, in The Temple (1633), on aspects of church interiors bear witness to the sanctioned iconoclasm of successive Tudor governments—iconoclasm that had broken altars, upended statues, and whitewashed church walls. Herbert was a protestant minister whose poetry celebrates the church established under Elizabeth I, defining its reformed appearance as a middle ground—‘Neither too mean, nor yet too gay’—between Genevan Calvinism and Roman catholicism. But Herbert’s poetry also reveals anxieties about the future of English protestantism—besieged not only by catholic plots but also by puritan and presbyterian clamours for further church reform. Herbert’s anxieties over this twofold threat to the English church are at once anti-catholic and anti-iconoclastic. Although Herbert celebrates the protestant reforms that had dissolved monasteries and destroyed catholic shrines, his poetry also attacks puritans, whose dissatisfaction with the half-hearted reforms of the Elizabethan settlement sought in Herbert’s eyes to ruin the church from within. Herbert’s paranoid poetry provides a keynote for this study’s exploration of the ruined churches and monasteries represented in early modern English literature—ruins, the study argues, that betray similar anxieties about the consequences of catholic plots and puritan iconoclasm for the fate of the English church in its formative century.
The Prologue as a Paschal Hymn
Authors: Behr John
Published: March 2019

On the basis of the analysis of the Gospel of John given so far, and in particular the celebration of Pascha that began with him, this chapter offers a radically new interpretation of the Prologue to the Gospel of John. Rather than a pre-existing hymn to the Word adopted and modified by the Evangelist, or a Prologue to the Gospel written by the Evangelist himself, explaining how the Word became flesh as the prelude to the narrative that follows, it is argued that the Prologue is best understood as a Paschal hymn in three parts. The first verse celebrates the one who is in first place, the crucified and exalted Jesus Christ, on his way to God, and as himself God. Verses 1:2—5 speak not of creation and the presence of the Word in creation before his sojourn on earth, but of how everything that occurs throughout the Gospel happens at his will, specifically the life that comes to be in him, a light which enlightens human beings, that is, those who receive and follow him. The third part, verses 1:6—18, are a chiastically structured celebration of what has come to be in Christ, where 1:14, ‘the Word became flesh and dwelt in us’ refers to the Eucharist, the flesh that he now offers to those who receive him and so become his body, following on from baptism in verses 1:12–13; the chiastic center of this section is 1:10–11, his rejection by the world but reception by his own, and the beginning and end of this section is the witness provided by John the Baptist.
The UN Core: Micromanaging Principals and Segmented Budgets
Authors: Patz Ronny , Goetz Klaus H.
Published: March 2019

In this first case study focused on (core) UN budgeting, the authors trace the evolution and setup of the extremely complex budget arrangements in the UN; the multiplication of budget procedures including regular budgeting, peacekeeping budgeting, special political missions’ budgeting, and budgeting in the many Funds and Programmes; and the resulting complex budgeting administration needed to navigate a highly complex principal–agent constellation. The analysis finds an extremely high degree of micro-management by member states as principals in the core UN budget process and an increasing segmentation of UN budgets and funds in recent decades that seem to be the direct result of complex principal constellations, but also, as in the case of peacekeeping budgeting, related to the UN bureaucracy’s interest in achieving a high degree of budgeting routinization.
UNESCO: Between Sectoral Fragmentation and Budget Crisis
Authors: Patz Ronny , Goetz Klaus H.
Published: March 2019

Chapter 7 examines the case of UNESCO and the effects of the sectoral and vertical fragmentation of the organization. The case is particularly pertinent since the US stopped its contributions after Palestine was admitted as a member in 2011, resulting in a major financial crisis for the organization. Despite the need for rigorous cutback management, budgeting procedures and budgeting administration have remained highly routinized. While this highlights the important procedural role of international bureaucrats and their ability to ensure the continued functioning of IOs, these solutions also show the limits to the substantive influence of international bureaucracies in budgeting. In essence, UNESCO remains an organization that is highly fragmented along policy lines, horizontally and vertically, and both among member states as well as inside its own bureaucracy. This results in budgetary segmentation and increased proceduralization well beyond the core budgeting stages regulated by formal rules.
Your Sister in the Gospel
Authors: Newell Quincy D.
Published: March 2019

In this biography of Jane Elizabeth Manning James, Quincy D. Newell traces the life of a free African American woman who converted to Mormonism in the early 1840s and remained a member of the Church of Jesus Christ of Latter-day Saints (the LDS, or Mormon, Church) for the rest of her life. James worked as a servant for LDS founder Joseph Smith and his successor Brigham Young. She traveled to the Salt Lake Valley with the church and lived there until her death in 1908. In the last decades of her life, James persistently requested permission to perform the temple rituals that would ensure that she reached the highest degree of glory after death, but church leaders denied her requests because she was black. Nevertheless, they created a ritual just for her: a master–servant sealing that allowed her to be a servant in Joseph Smith’s household for eternity. James’s life provides a different angle on the development of the LDS Church than the experiences of white, male Mormons, whose perspective dominates the narrative of Mormon history. Her story is an important addition to the history of African American religion, American women’s history, the history of the American West, and the history of the LDS Church.
Introduction
Authors: Newell Quincy D.
Published: March 2019

African American Biddy Mason’s story is relatively common in texts on American history, whereas Jane James’s story is all but absent from the same literatures. James’s story appears to follow a very different trajectory than Mason’s that makes it fit less well in the grand narratives of American history. The stories of both these women are necessary to understand American history. James’s experience enhances our understanding of African American history, the history of American women, and the history of the American West. It also reveals a form of Mormonism that de-centers priesthood and temple rituals and focuses instead on supernatural religious experiences and a sense of divine favor.
Is There No Blessing for Me?
Authors: Newell Quincy D.
Published: March 2019

By the 1880s, Jane James began a campaign to get permission to perform the temple rituals she believed were necessary to reach the highest degree of glory after death. She wanted to be sealed to Joseph Smith as a child and to receive her endowment, requests that church leaders denied. In 1888, James received a temple recommend to do baptisms for the dead in the Logan Temple. James’s children, meanwhile, made their ways out of the church. She received a second patriarchal blessing in 1889, which may have encouraged her to persist despite her disappointments. Her ex-husband Isaac James returned to Salt Lake in 1890 and lived with Jane James until his death in 1891. The following year, Jane James’s brother Isaac Manning came to live with her. In 1894, church leaders created a temple ceremony to seal Jane James to Joseph Smith as a servant rather than a child.
US–India Nuclear Relations Post 2008
Authors: Ravi Chaitanya
Published: March 2019

Chapter 6 focuses on debate over the crucial issue of liability in India and the emergence of liability legislation that has prevented the operationalization of the nuclear deal and negated euphoric predictions by US businesses that the deal would create thousands of hi-tech jobs in the US through the sale of nuclear reactors to India. The memories of the Bhopal disaster and residual suspicions of the US amongst the Indian polity gave rise to liability legislation that channelled liability to the suppliers of nuclear reactors, in variance with the prevailing norm of holding reactor operators responsible for accidents. The loud protests of American corporations that the liability law exposes them to unsustainable amounts of liability and the attempts of the Modi government to find a ‘workaround’ at the bureaucratic level have borne little fruit.
The Prime Minister’s Legacy and Traditions of Public Speech in India
Authors: Bajpai Anandita
Published: March 2019

The office of the Prime Minister and tradition(s) of public oratory have a distinct legacy. The chapter illustrates how Jawaharlal Nehru re-engineered the role and powers of the office in the newly constituted postcolonial state and how his oratorical legacy continues to impact the expectations accorded to speeches of the successive Prime Ministers. The first section traces how Nehru negotiated the executive powers of the office to make it the most powerful one in the Cabinet, a higher ‘First Among Equals’. It then shows how his persona was used to give the office an irrefutable status. The second section tracks the gravity of the spoken word in India by embedding it in its longstanding cultural history of orality and aurality. A concluding part brings the two themes of the Prime Minister’s Office and public speech in India together, grounding the importance of the Prime Ministers’ speeches as material to be studied in its own right.
‘The World Is Changing…’
Authors: Bajpai Anandita
Published: March 2019

This chapter shows what the PMs speak and how they speak is highly dependent on the spatial context, i.e. the audience for which the speech is intended. For the perceived internal audiences, the first three PMs naturalize the reforms by signaling them as a change made necessary by the transitions the world faces at large. These ‘global’ changes necessitate that India adapts to transformations as well. However, this is accompanied by a simultaneous assurance: India’s adaptation to that change is cautious and calculated. The sense of assurance is produced in two distinct ways: Firstly, by giving people the re-assurance that opening up of the economy will not jeopardize India’s economic sovereignty and secondly, by stating that in spite of change, India’s cultural core is fundamentally secure. For external audiences, however, India is presented as an Investment Destination, ready to embrace the world markets and celebrating change. The chapter concludes by analysing Modi’s spatializing strategies in light of continuities/discontinuities with the former PMs.
Everyday Policing and Legality
Authors: Khanikar Santana
Published: March 2019

How does a police force in the capital city of a democracy operate at an everyday level? Ethnographic fieldwork of policing practices inside police stations and outside in the policed territories and interpreting them in the light of police manuals and laws, help develop in this chapter a background to understand the place of the police as an institution and the police personnel as performers of the state, in the self-imaginations of police personnel as well as in the imaginations of those in the margins. Looking at methods of crime investigation and categories such as ‘Bad Character’, the chapter further comments on constructions of crime and criminality. The chapter also briefly engages with the question of the positionality of the researcher and how the identity of an intersectional ‘outsider’ in the space of a police station evokes complex responses.
Money in Elections
Authors: Sircar Neelanjan
Published: March 2019

This chapter investigates the role of personal wealth and self-financing candidates in Indian elections, namely, why financial capacity of the candidate is an important feature of Indian electoral politics and how it structures the incentives of political parties. Using detailed data on candidates’ assets, this chapter demonstrates that a candidate’s personal wealth, measured in terms of moveable assets, has a significant positive impact on her electoral fortunes. It further shows that wealthy candidates directly filter into competitive parties. But even among these wealthy candidates from competitive parties, the wealthiest candidate has a greater probability of winning the constituency. The empirical results strongly support the view that there are structural and institutional reasons for the outward display of wealth in Indian electoral campaigns.
Uttarakhand
Authors: Balls Jonathan
Published: March 2019

Uttarakhand was created out of Uttar Pradesh and endowed with a substantial benefit: sole access to cheap hydro power. Low-cost power allowed the state to attract industry by cutting tariffs, providing a stable financial base, and enabling a well-functioning sector. With low tariffs, the power sector has not become an arena for populist policies despite frequent electoral shifts. However, this comfortable situation also limited the pressure to use the breathing room created by low cost power coupled with high share of industrial consumption to address long-standing loss levels in other parts of the state. As the limits of low-cost power are reached, the threat to Uttarakhand’s high-level equilibrium comes from having to turn to high-cost thermal power and stagnating industrial consumption.
The Rise of Hindu Nationalism and the Competitive Politics of Offence-Taking
Authors: Maheshwari Malvika
Published: March 2019

The chapter explores the profound strengthening of communal conflicts and ethno-religious politics, particularly in the shape of Hindu nationalism. It is divided into two parts: The first, part explores the evolution of attacks on artists, beginning with the early ones by Hindu nationalists. However, instead of showing this as an unruptured sequence of instances leading to their imminent rise, it underlines their early setbacks and strategic manoeuvres. These initial attempts led to the refinement of the Hindu nationalist techniques for attacking artists, and highlight the relevance of the media’s expansion in the enterprise. Also, the rise in the attacks on artists was not just a sign of the Sangh Parivar’s prowess, but at least partially due to the encouragement provided by the Congress-led government, not just to the Hindu nationalists to continue imposing their rules, but also to similarly self-assigned spokesmen of the Muslim community in India. The second, shorter part of the chapter covers the second half of the 1990s, after the BJP formed its government at the Centre for the first time, and in coalition with the Shiv Sena in Maharashtra. Here we observe the normalization of the influence wielded by non-state actors, and the consolidation of these attacks from lone random instances into sustained campaigns, but also the limits of such an exercise.
The Anatomy of an Attack and Inspirations of Attackers
Authors: Maheshwari Malvika
Published: March 2019

Chapter 6 explores the dynamics of this form of collective action, which might be best characterized as the violence of offence-taking, along with exploring the role and motivations of individuals at the forefront of these attacks—to bring out the inconsistencies of what is otherwise passed off as an all-encompassing chronicle of communal and ethno-religious tensions or as party politics. The chapter presents narratives of three attackers with special emphasis on the micro-political make-up of this violence, underlined by a common thread—namely, the search for glory, recognition, and dignity through the interiorization and creative appropriation of a cult of the hero and role model. Reiterating the central argument of the book, the language of the Indian Constitution—assuring its citizens dignity, respect, and equality—emerges here as an enabling technique for attackers to indulge their violent rage, taking on a particularly perverse form in a state that already suffers from weak enforcement of the law.
Performing Representation
Authors: Rai Shirin M. , Spary Carole
Published: March 2019

Breaking new ground in scholarship on gender and politics, Performing Representation is the first comprehensive analysis of women in the Indian Parliament. It explores the possibilities and limits of parliamentary democracy and the participation of women in its institutional performances. Performing Representation offers a new, multi-method analysis of the gendered nature of India’s Parliament. Through an examination of electoral data, media reports, and life stories of women MPs it sheds light on the performance, aesthetics, and norms of parliamentary life. It explores how the gendered axis of power underpins the performance of Parliament and its members as well as the political economy in which they are embedded. The book makes a strong case for taking parliamentary politics seriously in these times of populism, without either a utopian framing of women MPs as challengers of masculinized institutional politics or seeing them simply as docile actors in a gendered institution. Performing Representation raises critical questions about the politics of difference, claim-making, representation, and intersectionality. It addresses these questions as part of global feminist debates on the importance of women’s representation in political institutions.
Contesting Elections
Authors: Rai Shirin M. , Spary Carole
Published: March 2019

The chapter argues that although women’s representation has increased in numerical terms over the last 20 years, this increase has been marginal. It traces this argument through an analysis of the role of political parties as gatekeepers to parliamentary politics. Using both quantitative and qualitative methodologies, this chapter explores women’s participation as candidates in general elections for the Lok Sabha over the last two decades to understand the role that elections and the election process have on opportunities for women to enter Parliament. By analysing trends in the nomination of women by political parties and across states and regions it contests notions of incrementalism, which are often used to counter proposals for quotas, and which argue that women’s presence in elected bodies will increase over time.
Women Members of Parliament
Authors: Rai Shirin M. , Spary Carole
Published: March 2019

This chapter explores women’s contribution to parliamentary debates—how women access participatory time to contribute to debates through party mechanisms, which concerns they are likely to prioritize (for example party, constituency, issue-based), the extent to which they participate, whether if at all they foreground their identity as women (or other aspects of identity), and the ways in which their contributions are received and interpreted (promoted, lauded, acknowledged, prevented, ignored, silenced, or delegitimized) by others form the substance of this chapter. We argue that we should be concerned about the consequences of reproducing a gendered division of labour where only women MPs, and not men, are tasked to represent ‘women’s issues’, or where women MPs are only tasked to represent ‘women’s issues’ and not other issues.
Science of Uncertainty
Authors: Gurukkal Rajan
Published: March 2019

This chapter virtually illuminates the invisible universe of subatomic dynamics through mathematical formalism and probability theory rather than empiricism based on instrumentation. A series of strange discoveries go into the making of the New Science and a discussion of the process constitutes the core of this chapter. Max Planck’s proposition of the Quanta, Niels Bohr’s discovery of objects’ non-observable and immeasurable complementary properties, Erwin Schrodinger’s interpretation of the object-subject split as a figment of imagination, Werner Karl Heisenberg’s enunciation of the Uncertainty Principle precluding the possibility of precision about certain pairs of physical properties of a particle, Kurt Friedrich Godel’s thesis of Undecidability based on his incompleteness theorems demonstrating certain inherent limits of provability about formal axiomatic theories, Murray Gell-Mann’s theory of Complexity in particle physics, Richard Feynman’s thesis on quantum mechanics, and Einstein’s theories of relativity, literally shook Newtonian physics of certainty with problems of uncertainty and subjectivity. At the end, the chapter makes a review of speculative thoughts and imagination about the dynamics of subatomic micro-universe as well as the mechanics of the galactic macro-universe.
The Qur’an and History
Authors: Neuwirth Angelika
Published: March 2019

This chapter examines the notions of “history” as they are presented and developed in the Qur’an. It critically reviews the notion that the Qur’an is ahistorical—that the Prophet stories and other narrative elements in the text do not show an understanding of or interest in history as such. Rather, it is argued, the text reveals a relationship to history that is quite varied, presenting vital and interesting reinterpretations of earlier narratives, both pagan and biblical, and a constant “conversation” with the notion of history at work in earlier traditions. This conversation reflects the formation of the community and the process of its development.
Biblical-Qur’anic Figures
Authors: Neuwirth Angelika
Published: March 2019

In this chapter, a detailed depiction is offered of the development of specific biblical figures and narratives in the Qur’an. Each figure reflects the Qur’anic reframing of the role of prophecy in general and the biblical figuration of prophecy and Prophets in specific. The depictions of these figures are set against the background of their evidence in the preceding Late Antique religious and literary traditions, including Alexander legends, Christian homilies, and the Jewish accounts of Josephus.
The Qur’an and Poetry
Authors: Neuwirth Angelika
Published: March 2019

This chapter discusses the relationship of the Qur’an to poetry, both in terms of poetry as a broader interpretive category and, in specific, in relation to pre-Islamic Arabic poetry, in which poetry is associated with prophecy. Specific Qur’anic statements in relation to poetry are discussed, but the broader relevance of the function of poetry in the pre-Islamic Arabian context is also brought to bear on the historical interpretation of the function of the Qur’an in the lives of its first recipients. The Qur’anic text actively counters negative associations with poets and seers in pre-Islamic Arabic culture, distancing the proclaimer from charges of ecstatic possession.
Effect of Preoperative Opioid Use on Adverse Outcomes, Medical Spending, and Persistent Opioid Use Following Elective Total Joint Arthroplasty in the United States: A Large Retrospective Cohort Study of Administrative Claims Data
Authors: Blevins Peratikos Meridith , Weeks Hannah L , Pisansky Andrew J B , Yong R Jason , Stringer Elizabeth Ann
Published: March 2019

Objective

Between 17% and 40% of patients undergoing elective arthroplasty are preoperative opioid users. This US study analyzed patients in this population to illustrate the relationship between preoperative opioid use and adverse surgical outcomes.

Design

Retrospective study of administrative medical and pharmaceutical claims data.

Subjects

Adults (aged 18+) who received elective total knee, hip, or shoulder replacement in 2014–2015.

Methods

A patient was a preoperative opioid user if opioid prescription fills occurred in two periods: 1–30 and 31–90 days presurgery. Zero-truncated Poisson (incidence rate ratio [IRR]), logistic (odds ratio [OR]), Cox (hazard ratio [HR]), and quantile regressions modeled the effects of preoperative opioid use and opioid dose, adjusted for demographics, comorbidities, and utilization.

Results

Among 34,792 patients (38% hip, 58% knee, 4% shoulder), 6,043 (17.4%) were preoperative opioid users with a median morphine equivalent daily dose of 32 mg. Preoperative opioid users had increased length of stay (IRR = 1.03, 95% CI = 1.02 to 1.05), nonhome discharge (OR = 1.10, 95% CI = 1.00 to 1.21), and 30-day unplanned readmission (OR = 1.43, 95% CI = 1.17 to 1.74); experienced 35% higher surgical site infection (HR = 1.35, 95% CI = 1.14 to 1.59) and 44% higher surgical revision (HR = 1.44, 95% CI = 1.21 to 1.71); had a median $1,084 (95% CI = $833 to $1334) increase in medical spend during the 365 days after discharge; and had a 64% lower rate of opioid cessation (HR = 0.34, 95% CI = 0.33 to 0.35) compared with patients not filling two or more prescriptions across periods.

Conclusions

Preoperative opioid users had longer length of stay, increased revision rates, higher spend, and persistent opioid use, which worsened with dose. Adverse outcomes after elective joint replacement may be reduced if preoperative opioid risk is managed through increased monitoring or opioid cessation.
Cost–risk–benefit analysis in diagnostic radiology with special reference to the application of referral guidelines
Authors: Moores B Michael
Published: March 2019

Cost–risk–benefit analysis has been applied to protection of the patient in diagnostic radiology with special reference to the application of referral guidelines. The analysis presented has extended previous work in this field to provide a theoretical framework that encompasses key factors that need to be considered in the optimisation of patient protection from both diagnostic and radiation risks. The fraction of patients whose symptoms do not meet criteria contained in the referral guidelines and, therefore, for whom an X-ray examination is not indicated has been termed the selectivity of the guidelines. Also included are the detriments arising from rejected or repeated examinations as well as the levels of patient dose employed in order to achieve given levels of true and false diagnostic outcomes. A comprehensive framework for optimisation is outlined and its relationship to justification discussed.
Clinical Level of Evidence Presented at the Lumbar Spine Research Society (LSRS) Annual Meeting Over 10 Years (2008–2017)
Authors: Eyrich Nicholas W. , Rodoni Bridger M. , Patel Rakesh , Aleem Ilyas S.
Published: March 2019

Study Design.

A systematic review.

Objective.

The Lumbar Spine Research Society (LSRS) is dedicated to advancing knowledge of the lumbar spine to promote evidence-based care. We sought to systematically review the level of clinical evidence presented at LSRS annual meetings from 2008 through 2017.

Summary of Background Data.

Improvements in clinical evidence have been reported at similar bone and joint scientific meetings.

Methods.

A total of 458 paper abstracts presented at LSRS annual meetings were independently assessed by two reviewers. Only clinical studies being included for analysis. Reviewers designated a clinical level of evidence (LOE) to each included abstract from level I to level IV based on criteria set forth by the Oxford Centre for Evidence-Based Medicine. Reviewer agreement was assessed using Cohens Kappa coefficient (k). Student t test was used to assess for differences in mean LOE grades. Chi-squared testing was used to assess nonrandom changes in LOE.

Results.

A total of 299 abstracts met inclusion criteria. Over the last 10 LSRS meetings, 2.68% of the presentations were level I, 22.4% were level II, 37.1% were level III, and 37.8% were level IV. We found the average LOE from 2008 to 2017 to be 3.10 (median = 3). In addition, 63.9% presentations were Therapeutic Studies, 30.1% were Prognostic Studies, and 6.02% were Diagnostic studies. When comparing the first 5 years (2008–2012) to the last 5 years (2013–2017), we observed a significant increase in Level II (P < 0.05) and Level III (P < 0.05) evidence along with a corresponding decrease in level IV evidence (P < 0.01). The average LOE improved significantly from 3.28 (2008–2012) to 2.88 (2013–2017) (P < 0.001).

Conclusion.

Emphasis on evidence-based medicine within spine surgery, specifically pertaining to the lumbar spine, has positively influenced the clinical LOE disseminated at LSRS annual meetings between 2008 and 2017.

Level of Evidence: 4
Cardiac Arrest and Subsequent Hospitalization–Induced Posttraumatic Stress Is Associated With 1-Year Risk of Major Adverse Cardiovascular Events and All-Cause Mortality
Authors: Agarwal Sachin , Presciutti Alex , Cornelius Talea , Birk Jeffrey , Roh David J. , Park Soojin , Claassen Jan , Elkind Mitchell S. V. , Edmondson Donald
Published: March 2019

Objectives:

To compare 1-year all-cause mortality and major adverse cardiovascular events in cardiac arrest survivors with and without posttraumatic stress disorder symptomatology at hospital discharge.

Design:

Prospective, observational cohort.

Setting:

ICUs at a tertiary-care center.

Patients:

Adults with return of spontaneous circulation after in-hospital or out-of-hospital cardiac arrest between September 2015 and September 2017. A consecutive sample of survivors with sufficient mental status to self-report cardiac arrest and subsequent hospitalization–induced posttraumatic stress disorder symptoms (cardiac arrest–induced posttraumatic stress symptomatology) at hospital discharge were included.

Interventions:

None.

Measurements and Main Results:

The combined primary endpoint was all-cause mortality or major adverse cardiovascular event—hospitalization for nonfatal myocardial infarction, unstable angina, congestive heart failure, emergency coronary revascularization, or urgent implantable cardio-defibrillators/permanent pacemaker placements within 12 months of discharge. An in-person posttraumatic stress disorder symptomatology was assessed at hospital discharge via the Posttraumatic Stress Disorder Checklist-Specific scale; a suggested diagnostic cutoff of 36 for specialized medical settings was adopted. Outcomes for patients meeting (vs not meeting) this cutoff were compared using Cox-hazard regression models. Of 114 included patients, 36 (31.6%) screened positive for cardiac arrest–induced posttraumatic stress symptomatology at discharge (median 21 d post cardiac arrest; interquartile range, 11–36). During the follow-up period (median = 12.4 mo; interquartile range, 10.2–13.5 mo), 10 (8.8%) died and 29 (25.4%) experienced a recurrent major adverse cardiovascular event: rehospitalizations due to myocardial infarction (n = 4; 13.8%), unstable angina (n = 8; 27.6%), congestive heart failure exacerbations (n = 4; 13.8%), emergency revascularizations (n = 5, 17.2%), and urgent implantable cardio-defibrillator/permanent pacemaker placements (n = 8; 27.6%). Cardiac arrest–induced posttraumatic stress symptomatology was associated with all-cause mortality/major adverse cardiovascular event in univariate (hazard ratio, 3.19; 95% CI, 1.7–6.0) and in models adjusted for age, sex, comorbidities, preexisting psychiatric condition, and nonshockable initial rhythm (hazard ratio, 3.1; 95% CI, 1.6–6.0).

Conclusions:

Posttraumatic stress disorder symptomatology is common after cardiac arrest, and cardiac arrest–induced posttraumatic stress symptomatology was associated with significantly higher risk of death and cardiovascular events. Further studies are needed to better understand the underlying mechanisms.
Center Effects in Hospital Mortality of Critically Ill Patients With Hematologic Malignancies*
Authors: Biard Lucie , Darmon Michaël , Lemiale Virginie , Mokart Djamel , Chevret Sylvie , Azoulay Elie , Resche-Rigon Matthieu
Published: March 2019

Objectives:

We aimed to investigate center effects on hospital mortality of ICU patients with hematologic malignancies and to explore interactions between center and patients characteristics.

Design:

Multicenter prospective cohort.

Setting:

Seventeen ICUs across France and Belgium.

Patients:

One-thousand eleven patients with hematologic malignancies hospitalized in ICUs.

Interventions:

Reanalysis of the original data using state-of-the-art statistical methods with permutation procedures for testing multiple random effects.

Measurements and Main Results:

Average crude mortality was 39% and varied from 11% to 58% across centers. There was a significant center effect on the mean hospital mortality, after adjustment on individual prognostic factors (p < 0.001; median adjusted odds ratio for center effect 1.57 [interquartile range, 1.24–2.18]). There was also a quantitative interaction between center and the effect of the Sequential Organ Failure Assessment score: higher scores were associated with higher mortality (odds ratio for 1 point = 1.24 on average; 95% CI, 1.15–1.33) but with a magnitude that depended on center (p = 0.028).

Conclusions:

Between-center heterogeneity in hospital mortality was confirmed after adjustment for individual prognostic factors. It was partially explained by center experience in treating oncology patients. Interestingly, center effect was similar in magnitude to that of known mortality risk factors.
Outcomes of Cancer Patients Discharged From ICU After a Decision to Forgo Life-Sustaining Therapies
Authors: Praça Ana P. A. , Nassar Antonio P. , Caruso Pedro
Published: March 2019

Objectives:

Many cancer patients are admitted to an ICU and decisions to forgo life-sustaining therapies are frequent during ICU stay. A significant proportion of these patients are subsequently discharged from ICU, but their outcomes are unknown.

Design:

Retrospective.

Setting:

ICU of oncological hospital.

Patients:

Adult cancer patients admitted to ICU, then with a decision to forgo life-sustaining therapies and that were discharged from ICU.

Interventions:

None.

Measurements and Main Results:

Hospital mortality, long-term survival, recommencement of cancer treatment, and ICU readmission were recorded. Hospital mortality predictors were evaluated. The propensity score method was used to test the hypothesis that decision to forgo life-sustaining therapies was independently associated with hospital mortality. Among the 16,998 patients that were admitted to ICU, in 1,369 patients (8.1%) a decision to forgo life-sustaining therapies was made during ICU stay. Among the latter group, 507 were discharged from ICU and were examined in this study. The hospital mortality of this group was 80.1% and was independently predicted according to the occurrence of delirium or acute kidney injury during their ICU stay. Six-month and 12-month survival rates were 3.6% and 0.6%. Sixty-four patients (12.6%) resumed cancer treatment and had a longer survival (p < 0.01). Fifty-two patients (10.3%) were readmitted to ICU and had a longer survival (p < 0.01). The decision to forgo life-sustaining therapies was associated with higher hospital mortality (80.0% vs 26.3%, respectively; p < 0.01) and lower rates of survival (p < 0.01).

Conclusions:

Approximately 20% of cancer patients discharged from our ICU after a decision to forgo life-sustaining therapies were discharged from hospital. Delirium and acute kidney injury during ICU stay were predictors of hospital mortality. The decision to forgo life-sustaining therapies was independently associated with hospital mortality. Patients readmitted to the ICU and those that resumed cancer treatment had longer survival. Knowledge of these outcomes is important for providing proper therapeutic planning and counseling for patients and their relatives.
Trigeminal Nerve Stimulation: A Novel Method of Resuscitation for Hemorrhagic Shock*
Authors: Li Chunyan , Chiluwal Amrit , Afridi Adil , Chaung Wayne , Powell Keren , Yang Weng-Lang , Wang Ping , Narayan Raj K.
Published: March 2019

Objectives:

To determine if trigeminal nerve stimulation can ameliorate the consequences of acute blood loss and improve survival after severe hemorrhagic shock.

Design:

Animal study.

Setting:

University research laboratory.

Subjects:

Male Sprague-Dawley rats.

Interventions:

Severe hemorrhagic shock was induced in rats by withdrawing blood until the mean arterial blood pressure reached 27 ± 1 mm Hg for the first 5 minutes and then maintained at 27 ± 2 mm Hg for 30 minutes. The rats were randomly assigned to either control, vehicle, or trigeminal nerve stimulation treatment groups. The effects of trigeminal nerve stimulation on survival rate, autonomic nervous system activity, hemodynamics, brain perfusion, catecholamine release, and systemic inflammation after severe hemorrhagic shock in the absence of fluid resuscitation were analyzed.

Measurements and Main Results:

Trigeminal nerve stimulation significantly increased the short-term survival of rats following severe hemorrhagic shock in the absence of fluid resuscitation. The survival rate at 60 minutes was 90% in trigeminal nerve stimulation treatment group whereas 0% in control group (p < 0.001). Trigeminal nerve stimulation elicited strong synergistic coactivation of the sympathetic and parasympathetic nervous system as measured by heart rate variability. Without volume expansion with fluid resuscitation, trigeminal nerve stimulation significantly attenuated sympathetic hyperactivity paralleled by increase in parasympathetic tone, delayed hemodynamic decompensation, and improved brain perfusion following severe hemorrhagic shock. Furthermore, trigeminal nerve stimulation generated sympathetically mediated low-frequency oscillatory patterns of systemic blood pressure associated with an increased tolerance to central hypovolemia and increased levels of circulating norepinephrine levels. Trigeminal nerve stimulation also decreased systemic inflammation compared with the vehicle.

Conclusions:

Trigeminal nerve stimulation was explored as a novel resuscitation strategy in an animal model of hemorrhagic shock. The results of this study showed that the stimulation of trigeminal nerve modulates both sympathetic and parasympathetic nervous system activity to activate an endogenous pressor response, improve cerebral perfusion, and decrease inflammation, thereby improving survival.
Immunotherapy in recurrent and or metastatic squamous cell carcinoma of the head and neck
Authors: Saada-Bouzid Esma , Peyrade Frederic , Guigay Joël
Published: March 2019

Purpose of review

Checkpoint inhibitors (CPI) are revolutionizing the treatment of advanced cancers including recurrent and or metastatic squamous cell carcinoma of the head and neck (RM-SCCHN).

Recent findings

In this review, we will summarize the results of prospective trials evaluating CPI and particularly antiprogrammed death 1 (PD-1)/antiprogrammed death-ligand 1 (PD-L1) in RM-SCCHN.

Nivolumab and Pembrolizumab, two anti-PD-1 CPI, were associated with longer overall survival than standard chemotherapy in pretreated RM-SCCHN in two randomized phase 3 trials (respectively CHECKMATE-141 and KEYNOTE-040). Both are now approved in this setting. In the KEYNOTE-048 trial, the pembrolizumab was also associated with a longer survival when compared with the EXTREME regimen in first-line RM-SCCHN patients whose tumors overexpressed PD-L1 (combined positive score ≥20%). This trial also showed a superiority of platinum-based chemotherapy and pembrolizumab vs. EXTREME regimen in unselected first-line RM-SCCHN. Pembrolizumab will probably be the next standard of care for first-line RM-SCCHN with high expression of PD-L1. Further evaluation of CPI combined with other antitumoral agents is ongoing in advanced and locally advanced SCCHN.
Fertility, sexuality and cancer in young adult women
Authors: Condorelli Margherita , Lambertini Matteo , Del Mastro Lucia , Boccardo Francesco , Demeestere Isabelle , Bober Sharon L.
Published: March 2019

Purpose of review

To provide an up-to-date overview on indications, efficacy and safety of the existing fertility preservation strategies as well as on the features and management of sexual dysfunction in young adult women with newly diagnosed cancer.

Recent findings

Because of the improved life expectancy of cancer survivors, a growing attention should be given to the side effects of anticancer treatments. Among young cancer patients, risk of infertility and sexual dysfunction are of great concern.

As advocated by guidelines, patients need to be thoroughly informed of potential side effects of treatment before starting them. On this regard, efforts should be made to improve the counseling of young adult patients around fertility and sexuality. Fertility preservation strategies should be properly and extensively explained to all young patients, weighting the pros and cons to choose the more appropriate options for each situation. In addition, discussing sexual dysfunction and delivering sexual rehabilitation for cancer survivors not only allows for renewal of sexual function but can also promote increased quality of life and help women create a new and satisfying chapter in their life for many years after cancer.
Polymorphisms in DNA repair genes in lung cancer patients living in a coal-mining region
Authors: Minina Varvara I. , Bakanova Marina L. , Soboleva Olga A. , Ryzhkova Anastasia V. , Titov Ruslan A. , Savchenko Yana A. , Sinitsky Maxim Yu. , Voronina Elena N. , Titov Victor A. , Glushkov Andrey N.
Published: March 2019

Air pollutants and ionizing radiation are well-known carcinogens involved in the pathogenesis of lung cancer, and residents of coal-mining regions are exposed routinely to these agents. Polymorphisms in DNA repair genes may be associated with an increased risk of malignant transformation. We investigated associations between the risk of lung cancer in residents of the coal-mining region and polymorphisms in the genes APEX1 (rs1130409), hOGG1 (rs1052133), XRCC1 (rs25489, rs25487), XRCC2 (rs3218536), XRCC3 (rs861539), ADPRT/PARP1 (rs1136410), XPD/ERCC2 (rs13181), XPG/ERCC5 (rs17655), XPC (rs2228001), ATM (rs1801516), and NBS1 (rs1805794). Three hundred and forty residents of the Kemerovo Region (a coal-mining region of western Siberia) were lung cancer patients exposed to air pollutants and ionizing radiation (case) and 335 were healthy donors (control). Genotyping was performed by real-time PCR and allele-specific PCR. We discovered that polymorphisms in the XPD gene in men [log-additive model: odds ratio (OR) = 1.64, 95% confidence interval (CI): 1.17–2.31], the ATM gene in women and nonsmokers (codominant model: OR = 0.11, 95% CI: 0.02–0.49 and OR = 0.25, 95% CI: 0.08–0.72, respectively), the APEX1 gene for smokers (recessive model: OR = 2.55, 95% CI: 1.34–4.85), and the NBS1 gene for those who work in the coal industry (overdominant model: OR = 0.40, 95% CI: 0.21–0.75) are associated with an increased risk of lung cancer. Using the multifactor dimensionality reduction method, we found a model of gene–gene interactions associated with the risk of lung cancer: NBS1 (rs1805794)–XRCC1 (rs25487)–hOGG1 (rs1052133)–XPG (rs17655). These results indicate an association between combinations of polymorphisms in the studied genes and the risk of lung cancer in residents of a coal-mining region.
Two cases of pneumonitis induced by targeted therapy
Authors: Lafabregue Eva , Arnault Jean-Philippe , Auquier Marianne , Magois Eline , Chaby Guillaume , Lok Catherine
Published: March 2019

Interstitial pneumonitis is a rare drug adverse effect. We report two cases of cobimetinib-induced and vemurafenib-induced reversible interstitial pneumonitis. Two patients presenting a BRAF-mutated metastatic melanoma were treated with cobimetinib and vemurafenib. After 3 months, they developed severe feverish dyspnea. Thoracic imaging showed a pattern of organizing pneumonia in one case and a pattern of hypersensitivity pneumonitis in the other case. Infectious and cardiogenic causes were eliminated. An improvement was noted after discontinuation of cobimetinib, vemurafenib, and introducing steroids. Treatment was switched to dabrafenib (a BRAF inhibitor) with no recurrence of drug pneumonitis. To the best of our knowledge, it appears that cases of targeted-therapy-induced pneumonitis are predominantly an MEK-inhibitor effect. We, therefore, propose a management strategy of discontinuing targeted therapy, introducing steroid treatment and switching to dabrafenib.
Hyalinized Neurofibromas: Not Just Rare Variants in Skin of the Female Breast
Authors: McHugh Kelsey E. , Sturgis Charles D. , Bergfeld Wilma F.
Published: March 2019

Although classical neurofibromas are commonly encountered skin lesions, histologic variants are infrequent. We report a greater than 15-year retrospective review of a single institution's experience with the histopathologic diagnosis of neurofibroma of the female breast with a focus on the hyalinized variant. An electronic histopathology record review (CoPathPlus; Cerner Corp, North Kansas City, MO) was conducted from January 1, 2000, to October 16, 2015, for all “neurofibroma” diagnoses rendered in “females” at the anatomical site “breast”. All cases were microscopically revisited and subclassified into 1 of 10 histopathologic categories. Immunohistochemistry (IHC) for S100, tryptase, and CD117 were performed on 19 hyalinized and 19 age-matched classical neurofibromas. During the study period, 62,021 breast specimens were reviewed at our institution. Of these, 86 (0.14%) were diagnosed as neurofibromas. Subclassification was as follows: 50 classical (58%), 19 hyalinized (22%), 6 diffuse (7%), 5 cellular (6%), 3 myxoid (4%), 2 epithelioid (2%), and 1 plexiform (1%). All hyalinized and age-matched classical neurofibromas were S100 positive. The mean number of IHC-positive mast cells per high-power field (hpf) was 34.5 by tryptase and 26.8 by CD117 for the hyalinized subset and 22.5 by tryptase and 19.3 by CD117 for the classical cohort. Published literature reports a 2.6% incidence of hyalinized neurofibromas at nonspecial cutaneous sites. Our series details a 22% incidence in the breast. Regarding pathophysiology, there is a statistically significant increase in the average number of IHC-positive mast cells per hpf in hyalinized variants when compared with classical neurofibromas of the breast both by tryptase (P = 0.00157) and CD117 (P = 0.00901).