bluuebunny/crossref_metadata_2025 huggingface dataset:
The Structure of Single Networks
Authors: Bianconi Ginestra
Published: July 2018

Chapters 2–3 constitute Part II of the book, ‘Single Networks’, and provide a reference point for the rest of the book devoted exclusively to Multilayer Networks, making the book self-contained. This chapter provides the relevant background on the network structure of complex networks formed by just one layer (single networks). Here the basic definitions of network structure are given, the major network universalities are presented and methods to extract relevant information from network structure including centrality measures and community detection methods are discussed. Finally, modelling frameworks are introduced including random graphs, growing network models (including notably the Barabasi–Albert Model) and network ensembles.
Basic Structural Properties
Authors: Bianconi Ginestra
Published: July 2018

In this chapter the basic structural properties of multilayer networks are given. This chapter reveals that on multilayer networks the most basic structural properties of a network such as the degree or the clustering coefficient are also significantly modified. Therefore, it is necessary to define the multiplex degree and the multiplex degree distribution, the multilayer degree and the multilayer degree distribution, and the multilayer clustering coefficients. The chapter also discusses the relation between the properties of multiplex and multi-slice networks and the corresponding properties of their aggregated network. Finally, the chapter introduces multilayer distance-dependent measures, including generalization of the betweenness centrality (interdependence, cross-betweenness) and of the closeness centrality.
‘Pluck’t from the Pit’
Authors: Newton Hannah
Published: July 2018

Recovery was often experienced as a narrow escape from death. ‘I was snatch’d out of the very Jaws of Death!’, exclaimed Thomas Steward from Suffolk in 1699. While historians have examined emotional responses to the prospect of death, little has been said about reactions to not dying; this new angle sheds fresh light on attitudes to both life and death. Patients usually expressed great joy, and gave three reasons for doing so: the relief of the body and soul not to have to part; the desire to remain in the ‘land of the living’; and the opportunity to ‘improve’ one’s salvation. Occasionally, however, owing to beliefs in the superiority of heaven over earth, patients felt disappointed not to die! This chapter also discusses families’ reactions, showing that their feelings varied according to their relationship with the patient, and the timing and means through which they heard of the survival.
Developmental Systems Theory as a Process Theory
Authors: Griffiths Paul , Stotz Karola
Published: July 2018

Paul Griffiths and Russell D. Gray have argued that the fundamental unit of analysis in developmental systems theory should be a process—the life cycle—and not a set of developmental resources and interactions between those resources. The key concepts of developmental systems theory, epigenesis and developmental dynamics, also suggest a process view of the units of development. This chapter explores in greater depth the features of developmental systems theory that favour treating processes as fundamental in biology and examines the continuity between developmental systems theory and ideas about process in the work of several major figures in early twentieth-century biology, most notably C. H. Waddington.
Capturing Processes
Authors: Rosa Laura Nuño de la
Published: July 2018

While a processual view of biological entities might be said to be congenial to embryologists, the intractability and speed of developmental processes traditionally led to an epistemological abandon of processes in favour of the advantages of discretizing ontogenies in arrays of patterns. It is not until the turn of the twenty-first century that the digital embryos obtained from in vivo microscopy have started to replace developmental series as the reference representations of development. This chapter looks at how new microscopy, molecular, and computer technologies for reconstructing biological processes are contributing to a processual understanding of development. First it investigates how time-lapse imaging has brought with it a radical dynamization, not only of the images, but also of the theories of development themselves. Next it explores the role that imaging technologies have played in the return of organicism in developmental biology. Finally, it focuses on how quantitative imaging contributes to the explanatory modelling of developmental processes.
Intersecting Processes Are Necessary Explanantia for Evolutionary Biology, but Challenge Retrodiction
Authors: Bapteste Eric , Anderson Gemma
Published: July 2018

Processes are ubiquitous in biology and play a key explanatory role in evolutionary biology, where they are frequently depicted by patterns. In particular, phylogenetic trees represent divergence from a last common ancestor with a branching pattern. However, the increasingly recognized underdetermination of phylogenetic trees limits the accuracy of tree-based retrodiction. Even phylogenetic networks, which include additional processes intersecting with vertical descent, still provide incomplete descriptions of evolutionary processes, as they usually miss processes that impact unrelated lineages. Interaction networks highlight the intersection of processes that sustain biological diversity. The complex topology of all these networks further challenges retrodiction. Remarkably, when intersecting processes are involved in evolutionary transitions, they introduce new biological processes on Earth. Processes, and hence the explanantia of evolutionary biology, evolve, which challenges uniformitarian approaches to retrodiction. Despite these difficulties, a yet to be introduced typology of processes would help to analyse the (big) processual picture of life.
Germany
Authors: Kraft Ina
Published: July 2018

This chapter provides an analysis of the changes that German defence has undergone since 1990. Two developments shaped German defence after the end of the cold war: First, the German armed forces changed owing to a radical downsizing, the end of conscription, and the modernization of equipment. Secondly, the style of German defence policy changed from reactive and norm-based in the 1990s to assertive, interest-based, and executive in the 2010s. The culture of military restraint—for decades a characteristic trait of German defence—waned. German military deployments abroad became more frequent and more serious. The leadership position Germany had taken in Europe during the Euro crisis and during the Ukraine conflict, as well as a domestic window of opportunity stemming from a favourable majority for the government parties in the parliament, serve as explanations for a more assured formulation of national security interests.
Poland
Authors: Michta Andrew A.
Published: July 2018

This chapter analyses the adaptation of Poland’s defence policy and armed forces to the rapidly changing security environment along NATO’s north-eastern flank. First, it examines the impact of a resurgent Russia on Poland’s security calculus, especially since Russia’s seizure of Crimea and the war in eastern Ukraine. Next, it addresses the evolution of Warsaw’s views on the relative utility of NATO and the European Union and its efforts to return NATO to its traditional territorial defence role. It then focuses on the modernization of Poland’s armed forces, with a special emphasis on doctrinal change, the reform of the command and control system, and the creation of the Territorial Defence units. It also reviews the t state of key hardware purchases as of mid-2017. The chapter concludes with an overall assessment of the level of capabilities and the readiness of the armed forces in the changing threat environment along NATO’s north-eastern flank.
The Common Security and Defence Policy
Authors: Hyde-Price Adrian
Published: July 2018

Since the late 1990s, EU member states have committed themselves to deeper and more structured military cooperation, within the framework of the ESDP/CSDP. At the same time, European defence budgets have shrunk and military capabilities reduced. This chapter analyses the evolution of European military cooperation and identifies its key drivers and the changing strategic context to Europe’s east and south. The chapter argues that the emergence of a credible EU military capability will depend both on developing new defence synergies and on investment in critical military capabilities and infrastructure. Above all, however, it requires greater political cohesion and a common European strategic culture. Elements of a shared strategic culture have emerged, but substantial differences remain among EU member states. The chapter concludes by highlighting the crucial role of Europe’s major states in fostering defence and security cooperation, particularly the UK, France, and Germany.
Cyber Defence
Authors: Kello Lucas
Published: July 2018

Europe confronts an enormous cyber threat. The continent hosted the first international cyber crisis—the 2007 attacks by Russian political activists that crashed computer infrastructures in Estonia. Large European nations such as the UK and France focus their defensive efforts on proactive measures, which seek to neutralize threats before they materialize. Another tool of large powers is deterrence by punishment, an attempt to prevent hostile action with the pledge of severe reprisal. Smaller powers, by contrast, lack the resources necessary to implement proactive measures or deterrence. They focus instead on reactive methods such as resiliency and redundancy, which seek to absorb the damage of attack. They strive to prevent major cyberattacks by participating in regional organizations such as NATO. Whatever their differences in doctrinal approach, European nations small and large confront a common challenge: how to defeat a novel threat in the absence of conclusive experience on which to revise strategy.
Defence Industrial Cooperation
Authors: Weiss Moritz , Biermann Felix
Published: July 2018

This chapter examines to what extent Europe’s governments and defence contractors cooperate to provide European Armed Forces with military capabilities. Defence industrial cooperation has evolved as almost the default policy option for European powers to develop large military platforms. Yet, there is no uniform trend, but large variation across countries (for example, France versus Germany), across sectors (land versus air versus sea), and with regards to the sources of cooperation (for example, government induced versus investment driven). The chapter shows that, while the major powers dominate defence industrial cooperation both at the government and at the corporate level, the lesser powers and smaller defence firms follow the trend and participate in the supply chains of large weaponry. Finally, the chapter addresses the question whether cooperation or competition represents the most promising strategy towards a capable European Defence Technological and Industrial Base.
Nuclear, Chemical, and Biological Weapons
Authors: Kühn Ulrich
Published: July 2018

This chapter discusses the military- and defence-related capabilities and policies of Western Europe’s major powers (Germany, France, United Kingdom), of the NATO alliance, the Russian Federation, and Austria in the realm of nuclear, biological, and chemical weapons (weapons of mass destruction (WMD)). It focuses on the differing roles, positions, and security policy outlooks of these actors, with a special emphasis on their respective policies towards nuclear weapons. Particularly in the realm of nuclear weapons, the situation on the European continent is extremely diverse and complex, with officially recognized nuclear-weapons states, non-nuclear-weapons states under NATO’s ‘nuclear umbrella’, and staunch supporters of a world free from nuclear weapons. Highlighting converging and diverging international policy trends, the chapter concludes that European security policies on WMD continue to have a significant impact on related global security and defence matters.
European Involvement in United Nations Peacekeeping
Authors: Gowan Richard
Published: July 2018

European soldiers played a major part in United Nations peacekeeping during the cold war, and were heavily involved in missions in the Balkans and Africa in the early 1990s. The disasters of Rwanda and Srebrenica led most European states, with exceptions such as Ireland and Sweden, to limit their role in blue-helmet peacekeeping missions. European multinational forces and EU-flagged missions have, however, backed up UN missions in cases such as Sierra Leone, and Europeans returned to UN peacekeeping in cases including Lebanon and Mali. Officers used to NATO and EU standards remain wary of UN command and control, medical evacuation, and intelligence gathering. When Europeans deploy in UN missions, they often find their non-Western comrades ‘exotic’. Nonetheless, since the end of major operations in Afghanistan, a number of European countries have taken UN operations more seriously, especially as a tool to handle threats of terrorism and uncontrolled migration from Africa.
CSDP Military Operations
Authors: Krotz Ulrich , Wright Katerina
Published: July 2018

Common Security and Defence Policy (CSDP) operations, while still novel, are rapidly becoming a vital means through which Europe projects physical power and influence beyond its borders. This chapter analyses the EU’s multilateral, intergovernmental military operations, examining where and how the EU has pursued its emerging strategic interests around the globe. It first surveys the history and politics of the thirteen CSDP mweilitary operations launched since 2003. It then dissects the nature and diversity of military missions. While the EU has deployed, on average, some 3,000 military troops around the world each day, operations have varied widely in their mandate, the number of troops involved, the number of participating member states, and the symmetry with which states support and staff these missions. The analysis underscores that CSDP operations will remain an integral part of European politics and Europe’s search for its role and place in twenty-first-century world politics.
The Limits of Emotion in Moral Judgment
Authors: May Joshua
Published: July 2018

This chapter argues that our best science supports the rationalist idea that, independent of reasoning, emotions are not integral to moral judgment. There is ample evidence that ordinary moral cognition often involves conscious and unconscious reasoning about an action’s outcomes and the agent’s role in bringing them about. Emotions can aid in moral reasoning by, for example, drawing one’s attention to such information. However, there is no compelling evidence for the decidedly sentimentalist claim that mere feelings are causally necessary or sufficient for making a moral judgment or for treating norms as distinctively moral. The chapter concludes that, even if moral cognition is largely driven by automatic intuitions, these should not be mistaken for emotions or their non-cognitive components. Non-cognitive elements in our psychology may be required for normal moral development and motivation but not necessarily for mature moral judgment.
One of Ten Billion Earths
Authors: Schrijver Karel
Published: July 2018

Illustrated with breathtaking images of the Solar System and of the Universe around it, this book explores how the discoveries within the Solar System and of distant exoplanets come together to aid understanding of the habitability of Earth, and how this guides the search for exoplanets that could support life. The author recounts how, within two decades of the discovery of the first planets outside the Solar System in the 1990s, scientists concluded that planets are so common that most stars are orbited by them. The twelve chapters highlight what we have learned about exoplanets and how the lives of exoplanets and their stars are inextricably interwoven. Stars are the seeds around which planetary systems form. Stars provide their planets with light and warmth for as long as they shine. At the end of their lives, stars expel massive amounts of newly forged elements into deep space. That ejected material is incorporated into subsequent generations of planets. How do we learn about these distant worlds? What does the exploration of other planets tell us about the history of Earth? Can we find out what the distant future may have in store for us? What do we know about exoworlds and starbirth, and where do migrating hot Jupiters, polluted white dwarfs, and free-roaming nomad planets fit in? What does all that have to do with the habitability of Earth and the possibility of finding extraterrestrial life? And how did the globe-spanning network of the sciences begin to answer all these questions?
Hobbes and the Future of Religion
Authors: Parkin Jon
Published: July 2018

Hobbes gives only ambiguous hints about the future of religion under a Hobbesian scheme. The chapter argues that consideration of that ambiguity might tell us something important about the nature of Hobbes’s intervention in debates over religion. Far from being committed (overtly or covertly) to particular ecclesiological options, Hobbes sought instead to make his basic ideas available to a range of religious readers. Those readers were thus invited to interpret their doctrines in accordance with Hobbesian principles. Evidence from Hobbes’s reception suggests that his readers did accept this invitation, leading to a range of possible Hobbesian ‘futures’. The fact that commentators have been able to identify so many different modes of Hobbesian religion may in fact capture a crucial feature of his project, but perhaps not in the way that many of them have previously thought.
All the Wars of Christendom
Authors: Collins Jeffrey
Published: July 2018

This chapter considers Thomas Hobbes’s account of religious warfare, and his position within modern historical memory of the European ‘wars of religion’ as an era. From an interdisciplinary perspective, it critically interrogates the concept of religious war as a modern observer’s category. It then measures Hobbes’s specific account of European religious conflict against both rival contemporary accounts and this modern theoretical construct. Hobbes’s account, it is argued, emerged from a specific and sectarian perspective. In another register, however, Leviathan offered a psychologized account of religious violence, which anticipated generic modern theories that often obscure that specificity. This tension in Hobbes’s account suggests features of the political project that the concept of religious war has sought to advance.
Taking Stock
Authors: Dancy Jonathan
Published: July 2018

This chapter considers some general issues about the nature of the account that is emerging. It asks whether moral reasoning should have been treated as it was in Chapter 5. It also askes whether an explanation of practical reasons by appeal to value could be mirrored by a similar explanation of theoretical reasoning if one thinks of truth as a value. One might also think of the probability of a belief as a respect in which it is of value. The chapter ends by introducing the idea of a focalist account, and maintains that the account offered of practical reasoning is focalist.
Are Perceptual Reasons the Objects of Perception?
Authors: Cunningham J.J.
Published: July 2018

This paper begins with a Davidsonian puzzle in the epistemology of perception and introduces two solutions to that puzzle: the Truth-Maker View (TMV) and the Content Model. The paper goes on to elaborate TMV, elements of which can be found in the work of Kalderon (2011) and Brewer (2011). The central tenant of TMV is the claim that one’s reason for one’s perceptual belief should, in all cases, be identified with some item one perceives which makes the proposition believed true. I defend an argument against TMV which appeals to (a) the claim that the reason for which one believes should always to be identified with the explanans of the rationalizing explanation to which one’s belief is subject and (b) the claim that the explanantia of rationalizing explanations must be identified with truths. I finish by replying to two objections to the argument.
Queen Boudica and Historical Culture in Britain
Authors: Vandrei Martha
Published: July 2018

This innovative and distinctive book takes a long chronological view and a wide-ranging, interdisciplinary approach. It is the definitive work on the posthumous reputation of the ever-popular warrior queen of the Iceni, Queen Boadicea/Boudica. It explores her presence in British historical discourse, from the early modern rediscovery of the works of Tacitus to the first historical films of the early twentieth century. In doing so, the book seeks to demonstrate the continuity and persistence of historical ideas across time and throughout a variety of media. This focus on continuity leads into an examination of the nature of history as a cultural phenomenon and the implications this has for our own conceptions of history and its role in culture more generally. While providing contemporary contextual readings of Boudica’s representations, this book also explores the unique nature of historical ideas as durable cultural phenomena, articulated by very different individuals over time, all of whom were nevertheless engaged in the creative process of making history. Thus this book presents a challenge to the axioms of cultural history, new historicism, and other mainstays of twentieth- and twenty-first-century historical scholarship. It shows how, long before professional historians sought to monopolize historical practice, audiences encountered visions of past ages created by antiquaries, playwrights, poets, novelists, and artists, all of whom engaged with, articulated, and even defined the meaning of ‘historical truth’. This book argues that these individual depictions, variable audience reactions, and the abiding notion of history as truth constitute the substance of historical culture.
Governing Extractive Industries
Authors: Bebbington Anthony , Abdulai Abdul-Gafaru , Humphreys Bebbington Denise , Hinfelaar Marja , Sanborn Cynthia
Published: July 2018

Proposals for more effective natural resource governance emphasize the importance of institutions and governance, but say less about the political conditions under which institutional change occurs. This book synthesizes findings regarding the political drivers of institutional change in extractive industry governance. The authors analyse resource governance from the late nineteenth century to the present in Bolivia, Ghana, Peru, and Zambia. They focus on the ways in which resource governance and national political settlements interact. Special attention is paid to the nature of elite politics, the emergence of new political actors, forms of political contention, changing ideas regarding natural resources and development, the geography of natural resource deposits, and the influence of the transnational political economy of global commodity production. National elites and subnational actors are in continuous contention over extractive industry governance. Resource rents are used by elites to manage this contention and incorporate actors into governing coalitions and overall political settlements. Periodically, new resource frontiers are opened, and new political actors emerge with the power to redefine how extractive industries are governed and used as instruments for development. Colonial and post-colonial histories of resource extraction continue to give political valence to ideas of resource nationalism that mobilize actors who challenge existing institutional arrangements. The book is innovative in its focus on the political longue durée, and the use of in-depth, comparative, country-level analysis in Africa and Latin America, to build a theoretical argument that accounts for both similarity and divergence between these regions.
Problems of Evil
Authors: Oppy Graham
Published: July 2018

The chapter begins with a discussion of the nature and diversity of worldviews, and the proper ways to go about comparing and evaluating worldviews. Three stages of worldview assessment are delineated: articulation, internal evaluation, and comparative evaluation, with the latter stage consisting in the weighting of theoretical virtues. There follows a comparison of theistic worldviews with naturalistic worldviews. It is contended that naturalism is simpler than theism, and that, while considerations about evil may not lead to the internal defeat of either theism or naturalism, naturalism has an advantage over theism in that the distribution of suffering and flourishing in the universe is more difficult to account for on theism than on naturalism, at least if theistic explanations of evil incur no additional theoretical commitments.
God and Evil without Theodicy
Authors: Gleeson Andrew
Published: July 2018

Against traditional theodicies, which conceive of God tolerating evils as necessary costs of higher goods, this chapter presents God on the model of a loving parent who refuses to countenance the sacrifice of his children for the sake of greater goods. The theodicists’ anthropomorphic image of God as a disembodied Cartesian consciousness producing effects in the physical world is then challenged. In rejecting this view of God, the contention is made that it is a conceptual confusion to draw conclusions about God from the nature of the world, the way we may do for agents in the world from the consequences of their actions. The standard academic problem of evil thus collapses. But this does not put an end to the problem of evil simpliciter. There remains an ‘existential’ problem of evil arising from basic human reactions to the conditions of life.
A Guide to Old Spanish
Authors: Dworkin Steven N.
Published: July 2018

This book describes the linguistic structures that constitute Medieval or Old Spanish as preserved in texts written prior to the beginning of the sixteenth century. It emphasizes those structures that contrast with the modern standard language. Chapter 1 presents methodological issues raised by the study of a language preserved only in written sources. Chapter 2 examines questions involved in reconstructing the sound system of Old Spanish before discussing relevant phonetic and phonological details. The chapter ends with an overview of Old Spanish spelling practices. Chapter 3 presents in some detail the nominal, verbal, and pronominal morphology of the language, with attention to regional variants. Chapter 4 describes selected syntactic structures, with emphasis on the noun phrase, verb phrase, object pronoun placement, subject-verb-object word order, verb tense, aspect, and mood. Chapter 5 begins with an extensive list of Old Spanish nouns, adjectives, verbs, and function words that have not survived into the modern standard language. It then presents examples of coexisting variants (doublets) and changes of meaning, and finishes with an overview of the creation of neologisms in the medieval language through derivational morphology (prefixation, suffixation, compounding). The book concludes with an anthology composed of three extracts from Spanish prose texts, one each from the thirteenth, fourteenth, and fifteenth centuries. The extracts contain footnotes that highlight relevant morphological, syntactic, and lexical features, with cross references to the relevant sections in the body of the book.
Anthology of texts
Authors: Dworkin Steven N.
Published: July 2018

This short anthology contains extracts from three Castilian prose texts, one from the second half of the thirteenth century (General estoria IV of Alfonso X the Wise), one from the first half of the fourteenth century (El conde Lucanor of don Juan Manuel), and one from near the mid-point of the fifteenth century (Atalaya de las corónicas of Alfonso Martínez de Toledo, Arcipreste de Talavera). These passages illustrate in context many of the phonological, orthographic, morphological, syntactic, and lexical features of medieval Hispano-Romance described in the body of this book. A linguistic commentary discussing relevant forms and constructions, as well as the meaning of lexical items no longer used or employed with different meanings in modern Spanish, with cross references to the appropriate sections in the five main chapters, accompanies each selection.
Nogo‐A promotes inflammatory heat hyperalgesia by maintaining TRPV‐1 function in the rat dorsal root ganglion neuron
Authors: Hu Fang , Liu Huai-Cun , Su Dong-Qiang , Chen Hai-Jing , Chan Sun-On , Wang Yun , Wang Jun
Published: July 2018

Nogo‐A is a key inhibitory molecule of axon regeneration in oligodendrocytes. However, little is known about its role in adult neurons. In this study, we showed an important function of Nogo‐A on regulation of inflammatory pain in dorsal root ganglion (DRG) neurons. In adult rats with complete Freund's adjuvant (CFA) hind paw inflammation, DRG neurons showed a significant increase in Nogo‐A expression. Disruption of Nogo‐A signaling with Nogo‐66 receptor antagonist peptide, Nogo‐A blocking antibody, Nogo‐A short hairpin RNA, or Nogo‐A gene knockout attenuated CFA‐induced inflammatory heat hyperalgesia. Moreover, disruption of Nogo‐A signaling suppressed the function and expression in DRG neurons of the transient receptor potential vanilloid subfamily member (TRPV)‐1 channel, which is known to be the endogenous transducer of noxious heat during inflammation. These effects were accompanied with a reduction in LIM domain kinase (LIMK)/cofilin phosphorylation and actin polymerization. Similar disruption of actin filament architecture by direct action of Latrunculin A reduced the TRPV‐1 activity and up‐regulation of TRPV‐1 protein caused by CFA. We conclude that Nogo‐A plays an essential role in the development of inflammatory heat hyperalgesia, partly through maintaining TRPV‐1 function via activation of the LIMK/cofilin pathway, which regulates actin filament dynamics. These findings support a therapeutic potential of modulating Nogo‐A signaling in pain management.—Hu, F., Liu, H.‐C., Su, D.‐Q., Chen, H.‐J., Chan, S.‐O., Wang, Y., Wang, J. Nogo‐A promotes inflammatory heat hyperalgesia by maintaining TRPV‐1 function in the rat dorsal root ganglion neuron. FASEB J. 33, 668–682 (2019). www.fasebj.org
Globalization and anaphylaxis
Authors: Kase Tanno Luciana , Ansotegui Ignacio , Demoly Pascal
Published: July 2018

Purpose of review

To understand the impact of globalization in the management of anaphylaxis and identify potential strategies to improve patients’ care and prevention.

Recent findings

Developments in the field of anaphylaxis have been consistently following these globalization trends offering possibilities of collaborations of the allergy community and integrated international initiatives to reach quality care of allergic patients worldwide.

Globalization is the process of interaction and integration between people, companies, and governments worldwide. Developments in the field of anaphylaxis have been following these globalization trends offering possibilities of collaborations and integrated international initiatives to reach quality care of allergic patients worldwide. Complex disorders, such as anaphylaxis, have called for complex integrative strategies, leading to a new acceptance of outside traditions. Allergy is encouraging us to accept holistic and integrative medical practices as viable options. With the dissolution of multinational boundaries and the universal free access to information, the notion of holistic and global-based care is emerging as the new reality of the medicine. We strongly believe that the integrated action plan to the management and prevention of anaphylaxis, just possible through the globalization, is a key health, political and economical move that advocates for the best practice of allergology.
Mini Screws for Improving Accuracy in Navigation-assisted Spine Surgery
Authors: Ahmadi Sebastian A. , Hashemi Amin , Harms Jürgen , Orakcioglu Berk
Published: July 2018

Study Design:

Presentation of a surgical technique with accompanying video (Supplemental Digital Content 1, http://links.lww.com/CLINSPINE/A67) of an illustrative case.

Objective:

The objective of this study was to present a helpful and easy-to-implement technique for improving initial referencing accuracy, as well as rereferencing accuracy in cases of multilevel instrumentation or in cases of dislocation of the reference array.

Summary of Background Data:

Navigation-assisted spine surgery has become standard of care in most hospitals performing complex spine interventions. Although short-segment instrumentations are fairly straight-forward with current hardware and software solutions, obtaining ideal accuracies and troubleshooting reference array disruptions remain challenging.

Methods:

A surgical technique is presented as a step-by-step guide using intraoperative videos and photographs as well as imaging data in an illustrative case of thoracic hemivertebra resection and dorsal instrumentation.

Technique/Results:

After skin incision is performed at the index level, posterior soft tissue preparation is performed. Before firmly attaching the reference array to a spinous process we then insert a minimum of four 5 mm mini screws at any bony structure within the exposure. Then an intraoperative navigation scan (3-dimensional computed tomography or x-ray) is obtained, and initial referencing is performed using the previously inserted mini screws as landmarks. This yields mean accuracies of 1 mm or lower and is easily verifiable by placing the navigation probe on a mini screw head. This action can be swiftly repeated at any time to prevent reduced accuracy because of insertion forces applied during pedicle screw placement. In addition, this allows for easy rereferencing in cases of disruption or complete removal of the navigation array, eliminating the need to perform additional computed tomography or x-ray scans during the procedure.

Conclusions:

The technique presented allows for rapid and highly accurate initial referencing and can be used in all cases of navigation-assisted spine surgery. It also allows for hassle-free rereferencing in cases of disruption or accidental removal of the reference array.
Reappraisal of eligibility criteria in cancer clinical trials
Authors: Penel Nicolas , Lebellec Loïc , Vanseymortier Marie
Published: July 2018

Purpose of review

We aimed to summarize the recent reflections and collaborative initiatives pertaining to the definition of more appropriate eligibility criteria in cancer clinical trials.

Recent findings

There is an intrinsic tension between two opposite purposes when it comes to defining eligibility criteria: on the one hand, participants must be protected, and on the other, the study population must be defined as accurately as possible. However, stringent eligibility criteria jeopardize the feasibility of trials, and, consequently, the generalizability of trial results. Therefore, interdisciplinary working groups under the auspices of the American Society of Clinical Oncology and Friends of Cancer Research propose to adapt/relax some of the classical eligibility criteria.

In-depth reflection of the existing eligibility criteria, and implementation of recent recommendations are needed.
The role of allogeneic stem cell transplantation in T-cell lymphoma
Authors: Friedrichs Birte , Stelljes Matthias , Schmitz Norbert
Published: July 2018

Purpose of review

T – and natural killer (NK) cell neoplasms are a heterogeneous group of rare diseases with often inferior outcome. Only few studies exist, clarifying the role of allogeneic transplantation in different clinical scenarios. Larger prospective randomized studies are largely missing even for the more frequent entities. Mostly retrospective analysis and anecdotal reports of patients with advanced disease are available, hampering direct conclusions on the significance of allogeneic stem cell transplantation (alloSCT).

Recent findings

Looking at recent data for T and NK cell neoplasm, it becomes evident that advances in donor search and availability of alternative stem cell sources as haploidentical or mismatched donors in addition to substantial improvements in graft-versus-host-disease prophylaxis reduce treatment-related mortality in alloSCT. The time point of transplantation has been described in a number of studies to be critically impacting outcome results as patients with advanced, chemorefractory disease often profit much less from alloSCT.

Allogeneic transplantation offers a treatment option that can induce long-term remissions even in the relapsed setting. Many patients do not reach transplantation though because of chemorefractory disease and efforts should be made to bring more patients to transplantation earlier in the course of disease.
AGE-RELATED MACULAR DEGENERATION–ASSOCIATED PERIPAPILLARY CHOROIDAL NEOVASCULARIZATION IN THE ERA OF ANTI–VASCULAR ENDOTHELIAL GROWTH FACTOR THERAPY
Authors: Lin Tiezhu , Dans Kunny , Meshi Amit , Muftuoglu Ilkay Kilic , Amador-Patarroyo Manuel J. , Chen Kevin C. , Cheng Lingyun , Freeman William R.
Published: July 2018

Purpose:

To characterize the natural history and response of age-related macular degeneration–associated peripapillary choroidal neovascularization to anti–vascular endothelial growth factor therapy.

Methods:

This was a retrospective case series of patients with peripapillary choroidal neovascularization secondary to neovascular age-related macular degeneration. All patients underwent complete ophthalmologic examination and retinal imaging including fluorescein angiography and spectral domain optical coherence tomography at each visit. Eyes with subretinal or intraretinal macular fluid were treated with anti–vascular endothelial growth factor monotherapy using a modified as-needed treatment algorithm.

Results:

Thirty-three eyes of 27 patients were included. The median age was 82 years (range, 62–94), and the median duration of follow-up was 65 months (range, 6–165). Fourteen eyes (58%) without fovea-involving fluid at baseline subsequently developed exudation after a median observation period of 16 months (range, 4–107). Ten of 24 eyes (42%) without initial macular fluid remained dry during the entire follow-up. The median number of injections required until complete fluid reabsorption was 3 (range, 1–21) during the first treatment cycle. The median time to fluid recurrence was 6 months (range, 3–74).

Conclusion:

Peripapillary choroidal neovascularization secondary to wet age-related macular degeneration has a slow progression, may not require treatment for a prolonged period, and responds rapidly to anti–vascular endothelial growth factor treatment with good visual outcomes.
Human Otopathologic Findings in Cases of Folded Cochlear Implant Electrodes
Authors: Trakimas Danielle R. , Kozin Elliott D. , Ghanad Iman , Nadol Joseph B. , Remenschneider Aaron K.
Published: July 2018

Hypothesis:

We hypothesize that human cases of cochlear implantation (CI) with folding of the electrode array will demonstrate greater degrees of intracochlear ossification, lower spiral ganglion neuron (SGN) counts, and poorer audiometric outcomes.

Background:

CI electrode array folding, such folding of the proximal array, is a relatively common surgical complication that can occur with forceful electrode insertion and may be an important and avoidable factor affecting implant outcomes. However, otopathologic findings and audiologic outcomes of human cases where folding of the implant electrode array is observed remain undefined.

Methods:

Specimens from a human temporal bone repository having undergone CI during life were evaluated. Specimens with folding of the electrode array on histological analysis constituted study cases. Electrode-matched specimens without array folding constituted controls. All specimens were examined by light microscopy and histopathologically described. Intracochlear fibrosis and osseous tissue, and SGN counts were measured. Pre- and postoperative word recognition scores were also compared.

Results:

Cases with folded electrodes showed greater volumes of intracochlear osseous tissue than controls, which was most prominent in areas adjacent to array folding. Both cases and controls demonstrated similar amounts of fibrous tissue. Folded cases showed decreased SGNs when compared with the contralateral ear, whereas controls showed stable SGN populations between ears. In this small cohort, postoperative hearing outcomes were similar between groups.

Conclusion:

Atypical fibro-osseous changes and lower SGN counts are observed in cases of CI electrode folding. Future studies are necessary to determine if recognition and correction of folding can prevent long-term intracochlear changes.
Evolution and current status of United States Food and Drug Administration and European Medicines Agency regulatory guidance for studies of nosocomial pneumonia
Authors: Talbot George H.
Published: July 2018

Purpose of review

Regulatory guidance for design, conduct and analysis of studies of nosocomial pneumonia, including ventilator-associated pneumonia, has undergone substantial evolution over the past three decades. This review summarizes this evolutionary process and the current status of guidance.

Recent findings

The US Food and Drug Administration and the European Medicines Agency have taken different approaches to defining endpoints for studies of nosocomial pneumonia, especially with regard to the primary endpoint. Both agencies accept a noninferiority design. Independent efforts to develop new endpoints and bridge existing discordances have been fruitful.

Transatlantic differences in the approach to study of nosocomial pneumonia complicate study design and analysis, but they will hopefully be resolved in future iterations of regulatory agency guidance.
Risk factors for anastomotic recurrence after primary ileocaecal resection in Crohn’s disease
Authors: Aaltonen Gisele , Keränen Ilona , Carpelan-Holmström Monika , Lepistö Anna
Published: July 2018

Objective

Ileocaecal resection is the most common operation performed in Crohn’s disease. Our study aimed to identify the risk factors for anastomotic recurrence following primary ileocaecal resection.

Patients and methods

We retrospectively analysed data from all Crohn’s disease surgical patients in a single colorectal unit between 2006 and 2016, including all patients who underwent primary ileocaecal resection. We defined anastomotic recurrence as the postoperative need for endoscopic dilatation of the ileocolic anastomosis or neoterminal ileal resection, and used Cox regression to determine the risk factors for such recurrence.

Results

In total, 101 patients underwent primary ileocaecal resection during the study period. Nine (8.9%) patients were excluded because of follow-up less than 1 year and 12 (13.0%) patients had anastomotic recurrence. The median follow-up was 4.7 (1.3–10.8) years. At 3 years, 93.1% of patients required no neoterminal ileal resection or dilatation of the ileocolic anastomosis. Urgent primary ileocaecal resection [hazard ratio (HR)=4.98, 95% confidence interval (CI)=1.45–17.11, P=0.011], stapled anastomosis (HR=20.34, 95% CI=5.06–81.77, P<0.001) and need for postoperative corticosteroid treatment after the primary ileocaecal resection (HR=3.58, 95% CI=1.03–12.40, P=0.044) emerged as significant risk factors for anastomotic recurrence.

Conclusion

Urgent surgery and postoperative corticosteroid need represented risk factors for anastomotic recurrence. Hand-sewn anastomosis with an opening of the bowel’s antimesenteric border seems to be a safe choice for ileocaecal resection.
Insulin resistance does not impair response of chronic hepatitis C virus to direct-acting antivirals, and improves with the treatment
Authors: Elhelbawy Mostafa , Abdel-Razek Wael , Alsebaey Ayman , Hashim Mohamed , Elshenawy Hassan , Waked Imam
Published: July 2018

Background

Insulin resistance (IR) is a common complication in chronic hepatitis C virus (HCV) patients. The impact of IR on outcome of therapy with direct antivirals has not been studied.

Aim

The aim was to assess the impact of direct-acting antiviral (DAA) therapy on IR status in chronic HCV patients.

Patients and methods

A total of 511 patients [mean age: 50.7±10.4 years, 29.7% pegylated interferon and ribavirin (RBV) experienced] were enrolled. Patients with uncontrolled diabetes, decompensated liver disease, or previous nonresponse to DAAs were excluded. Homeostatic model assessment (HOMA) was calculated before and 12 weeks after treatment, and IR was defined as HOMA greater than 1.9. Patients were treated according to the treating physician’s choice, and received 12 weeks of either ombitasvir/ritonavir/paritaprevir/RBV (n=28); sofosbuvir (SOF)/simeprevir (n=36); SOF/ravidasvir (n=101); SOF/pegylated interferon/RBV (n=192); or 24 weeks of SOF/RBV (n=154).

Results

Most patients received IR pretreatment (80.6%); 51.3% had fibrosis stage F4 and 24.7% had diabetes. A sustained virological response (SVR) at 12 weeks after treatment (SVR12) was achieved in 465 (91%) patients. SVR12 was achieved in 90.5% of patients with IR and in 92.9% of patients without IR (P=0.560), and pretreatment HOMA was not different in responders and nonresponders (P=0.098). The number of patients with IR decreased significantly in patients who achieved an SVR much more than in nonresponders (P<0.0001) and HOMA improved significantly more in patients with SVR than in nonresponders (P=0.001). All treatment protocols were associated with a comparable improvement in HOMA (P=0.101). Predictors of SVR12 included age, platelets, and liver stiffness, but not pretreatment IR.

Conclusion

IR does not impair the response of patients with HCV treated with DAAs, and improves significantly in patients who achieve an SVR.
Apoptotic cell-based therapies for promoting transplantation tolerance
Authors: Dangi Anil , Yu Shuangjin , Luo Xunrong
Published: July 2018

Purpose of review

This article is aimed to provide readers with an updated review on the applicability, efficacy, and challenges of employing donor apoptotic cell-based therapies to promote transplantation tolerance in various experimental and clinical settings.

Recent findings

Recently, donor apoptotic cell-based therapies have been employed in various models of cell (including pancreatic islets and bone marrow hematopoietic stem cells) and solid organ (heart and kidney) transplantation to promote donor-specific tolerance. Published data, thus far, have revealed a high potential of this approach in inducing robust transplantation tolerance. Recent clinical trials have also underscored the safety and potential efficacy of this approach in alleviating graft-versus-host disease (GVHD) in bone marrow transplantation (BMT). Host factors including prior allo-sensitization and opportunistic infections pose major obstacles in establishing transplantation tolerance employing this strategy. However, emerging data provide strategies for overcoming such obstacles in these clinically relevant settings.

Donor apoptotic cell therapy is an emerging strategy in promoting transplantation tolerance, with recent data emphasizing its efficacy and applicability for transplantation tolerance in the clinic.