bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparative Succession Law
Authors: De Waal Marius J.
Published: May 2019

It cannot be denied that the law of succession often projects a static image. One possible explanation for this is the fact that certain areas of the law of succession are indeed somewhat technical. However, this article examines comparative research, private international law, examples of trust and the transfer of estate to argue that there are changes that have been detected and explained principally through comparative scholarship in the field of the law of succession. The first is the significance of common social and economic changes and their impact on aspects of the law of succession. The article stresses the intimate relationship between the law of succession and family law. The identification and analysis of these changes have also been the stimulus for a new ‘mission’ for comparative researchers in the field of the law of succession—the quest for greater harmonization, especially in the European context.
Comparative Family Law
Authors: Scherpe Jens M.
Published: May 2019

This chapter discusses family law in relation to comparative law. It first considers whether family law can be a subject fit for comparative study in a constantly changing world before describing various efforts aimed at introducing comparative perspectives into family law, both by individuals as well as by several key groups and institutions. It then examines ‘organic’ and ‘institutional’ harmonization of family law, along with the ‘great debates’ and future challenges with respect to comparative family law. In particular, it explores issues relating to horizontal family law (marriage, divorce, and property division; registered partnerships; cohabitation/de facto relationships) and vertical family law (parentage; paternity and maternity; parenthood; parental responsibility). The chapter also analyzes individual family law and concludes with an overview of family law’s move away from form towards function.
Comparative Competition Law
Authors: Gerber David J.
Published: May 2019

This article examines comparative competition law. It looks first at the current state of the literature. It envisions a path for comparative antitrust law scholarship that may allow it to realize more fully its potential value and respond more effectively to the challenges of economic globalization. Three main themes run through this article. One is that US law dominates the world of comparative competition law scholarship. A second is that the centrality of US law and experience divides the writing in the area and often distorts it. The third thread that runs through this article identifies the potential impact of economic globalization on the agenda of comparative competition law and the opportunities it creates for writers in the area to contribute to creating a sounder policy framework for transnational markets.
Development of Comparative Law in Italy
Authors: Grande Elisabetta
Published: May 2019

Since Italy’s unification in 1861, Italian law has mainly been a ‘context of reception’. In contrast to contexts of production, where legal scholarship tends to unfold in a self-centred mode, contexts of reception tend to search for legal innovation abroad. Italian legal culture has often copied legal ideas, norms, and institutions from foreign countries but only rarely produced original work of its own. The article begins the story of comparative law in Italy in the early part of the twentieth century. It distinguishes three fundamental layers: a commercial law branch, a reformist tradition, and a mainstream, ‘scientific’, approach. It discusses the current state of Italian comparative law resulting from the academic and cultural influence of these three layers. It also attempts to assess the impact of the more significant and original contributions of Italian comparative law at the European and global levels.
Comparative Criminal Law
Authors: Dubber Markus D.
Published: May 2019

Criminal law occupies an odd position in the field of comparative jurisprudence. Historically speaking, one can occasionally read that comparative law as a serious academic discipline began as comparative criminal law, either in Germany or in France, or both. And yet, introductions to comparative law tend to assume that comparative law means comparative civil law first and foremost. The first section of this chapter describes criminal law’s parochialism. The second section discusses the histories and functions of comparative criminal law. The third section discusses selected topics in comparative law, such as punishment theory, victims, jurisdiction, the principle of legality, the an analysis of criminal liability, and general principles of criminal liability. The last section discusses comparative criminal law in context, arguing that comparative criminal law is best seen as a mode of critical analysis of law, that is, as one way to gain critical distance from a given legal system by placing it within a larger context.
Comparative Civil Procedure
Authors: Zekoll Joachim
Published: May 2019

This essay will first examine the attempts to categorize and label procedural systems, an impulse that many comparatists cannot, but should, resist because the very exercise of creating categories invites undue generalizations. The focus will then shift to procedural harmonization, a term that encompasses a number of topics of increasing importance to proceduralists. This section forms the centrepiece of the essay because it is here that most opportunities to benefit from comparative scholarship present themselves—and are still being missed. After illustrating the dynamics and results of regional, particularly European, and supra-regional harmonization initiatives, this section identifies trends towards harmonization through private rule making and examines principles that determine the scope of, and limits to, procedural harmonization. The final section addresses the growing concern about access to justice, specifically cost considerations and claim aggregation techniques, which prompt the somewhat related questions of whether and to what extent one legal system can borrow procedural rules from another one.
Comparative Law in Legal Education
Authors: Demleitner Nora V.
Published: May 2019

This chapter discusses comparative law within the framework of legal education in North America and Europe. It first considers some of the key debates surrounding the teaching of comparative law before providing a historical overview of major developments on both sides of the Atlantic since the nineteenth century. It then examines the post-World War II resurgence of comparative law in US legal education and the ascent of comparative law teaching in Europe, as well as the place of comparative law in legal education today. It also analyzes the present role of comparative law teaching in the European Union, the impact of international and transnational law on comparative legal education in the United States, and comparative law in Australia and Canada. The chapter concludes with a review of some of the current challenges to comparative law as a subject of teaching and scholarship and how comparative law fits into legal education more generally.
New Directions in Comparative Law
Authors: Siems Mathias
Published: May 2019

This chapter discusses new directions in comparative law. It shows that the field of comparative law has become more diverse, both in its methods and by turning its attention to new topics. These changes have occurred, first, as traditional comparative law has increasingly allowed modifications to functionalism and has expanded its reach beyond ‘just’ Western-based state laws. Second, comparative law has also ventured into new terrain, for example, by more readily accepting quantitative methods and by turning its attention to the comparison of regional, international, and transnational law. Third, there is an increase in interdisciplinary research on topics of comparative law, for example, as it incorporates research from economics and political science that aims to establish causal relationships and to assess new forms of global governance.Thus, the overall trend is that comparative law has broadened both its methodological tool box and its substantive perspective. One can regard this as a kind of centrifugal effect: apparently, there is much interest in comparative law but also considerable dissatisfaction with the established core, and in combination, these elements drive the exploration of new methods and themes. Yet, there are also centripetal forces at work, reaffirming the traditional status quo of a more confined core of comparative law.
Development of Comparative Law in the United States
Authors: Clark David S.
Published: May 2019

This chapter examines the origins of comparative law activities during the colonial British American period and the formative era of the United States. During the eighteenth and nineteenth centuries, knowledge of Enlightenment philosophy and Roman and continental European legal systems acted as a filter for the importation of rules and structures to serve a culturally diverse people and to construct an emerging nation in the new world. Nevertheless, the first 125 years of United States history saw some exportation of American laws and legal institutions, primarily to the newly independent Latin American nations in the 1820s. These included concepts from the Constitution of 1789, the 1791 Bill of Rights, and public law structures such as federalism, a presidential executive, and judicial review of legislative and executive action. By the twentieth century, American comparative law began to form as an organized activity, with its own institution, journal, and annual meetings. This process was uneven, but steady. When the Comparative Law Bureau folded into a more comprehensive ABA section, the American Foreign Law Association kept the flame alive. Comparatists dealt with more complex methods and issues, some debated in international meetings. After World War II, law school professors established American comparative law on a firmer institutional basis with a new association, journal, and scholarly meetings.
Comparative Law in Central and Eastern Europe
Authors: Kühn Zdeněk
Published: May 2019

The region of Central and Eastern Europe covers many of the European nations east of Germany. The dominant nation of the region is Russia. Between Russia and Germany there are, first, a number of small nations composing the region known as Central Europe (Poland, Hungary, the Czech Republic, and Slovakia); second, the nations which formed the western part of the Soviet Union; and, third, the states on the Balkan peninsula. This article shows the rich history of comparative law before the installment of communist regimes, such as the era of Stalin, and then discusses comparative law under communism and the role and status of comparative law after the fall of communist rule.
Personal Narratives, Expressive Writing and Wellbeing
Authors: Tarragona Margarita
Published: May 2019

This chapter discusses the importance that stories have in our lives and how the creation of coherent personal narratives is important for well-being and a relevant topic for positive psychology. There is solid research evidence about the benefits of expressive writing on mental health, particularly for people who have experienced trauma, and analyses of people´s choice of words in their writing can be useful in predicting depression and suicidal risk. Studies also show how writing can help us deal with adversity in the present and dream of better futures. Expressive writing can have beneficial effects on physical health, as it has an impact on immune function and cardiovascular health; writing is also associated with higher subjective well-being in patients with a variety of chronic diseases. Expressive writing has also been found to improve interpersonal relationships in schools and in work settings, and it can be helpful for couples who are struggling with their relationship and for individuals who have gone through a break-up. In the final section, the chapter presents a list of positive psychology interventions that are use writing to increase well-being.
Paul and Theological Interpretation
Authors: Fowl Stephen E.
Published: May 2019

This article examines theological interpretations of Scripture, with a focus on Paul. It discusses the presumption that Christians interpret Scripture theologically to improve their prospects of living and worshipping faithfully before the Triune God, and links this presumption to arguments about the doctrine of Scripture and the place of Scripture in God’s drama of salvation. It also looks at the role of Scripture in God’s economy of salvation and considers letters attributed to Paul. After providing an overview of Pauline theology and theological interpretation of Paul, the article talks about Paul as interpreter of Scripture as well as his trinitarianism. It also comments on Paul’s particular theological and ecclesiological concerns over relationships between Jews and Gentiles in Christ, and how such concerns shape and are shaped by his convictions about God, Christ, and the Spirit.
Paul and Ethnicity
Authors: Johnson Hodge Caroline
Published: May 2019

This chapter argues that a theorized and historically contextual approach to ethnicity and race allows us to look critically at these concepts in Paul’s letters and challenges the traditional reading of Paul. After reviewing race and ethnicity in Pauline scholarship, this essay applies these approaches to the Pauline texts. Arguing for an understanding of racial and ethnic identity as both ‘natural’ and malleable, of identity as multiple, and of religion as central to ethnic identity construction, this chapter shows that these discourses, rather than being peripheral or rejected by Paul, are central to his thinking. We see that Paul conceives of central theological issues—such as Paul’s identity as a Jew, Israel’s standing before God, and the invitation to faithful Gentiles-in-Christ—in terms of ethnic reasoning. This approach contributes not only to a more historically situated reading of Paul, but also to modern understandings of racial and religious identity.
Introduction
Authors: Truswell Robert
Published: May 2019

This introduction summarizes the major pieces of research that laid the foundations for the current field of event structure. It discusses three leading ideas from the 1950s and 1960s: (1) many sentences have a covert event argument (Davidson); (2) event descriptions can be divided into classes according to their aspectual properties (Vendler); (3) apparently lexical meaning is partly a product of compositional processes involving operators like CAUSE and BECOME (Lakoff, McCawley). These ideas became intertwined during the 1970s–90s, laying out the terrain for today’s event-structural research. This chapter also summarizes the contents of the handbook, and relationships between the chapters.
The Semantic Representation of Causation and Agentivity
Authors: Thomason Richmond H.
Published: May 2019

In accounting for causativity and related constructions, it was popular at first to avoid appealing to events and event structure. But internal problems with this conservative approach motivate the introduction of eventualities into the semantic apparatus. Terence Parsons gets the credit for seeing this. His ideas can serve as the basis of a theory that begins to do justice to how causal notions are incorporated in natural language morphology. But work remains to be done in refining Parsons’ logical primitives, in relating the semantic picture to work in the metaphysics of causation, and in developing the causal picture in relation to other ideas about eventualities, such as the work discussed in this volume.
Event Structure and Syntax
Authors: Siloni Tal
Published: May 2019

This chapter examines the syntactic decompositional view of event structure. On this view, the event is composed of distinct syntactic heads that correspond to its meaning ingredients. The chapter critically reviews the various arguments presented in the literature for a decompositional analysis of pairs of verbs that differ roughly in that one of them has one more argument than the other. It focuses on the inchoative alternation, comparing it to the Japanese and Hungarian causative alternations. The chapter shows that these alternations differ from one another in important respects, and only the Japanese causative alternation deserves a syntactic decompositional treatment. The chapter thus contributes a critical evaluation of the scope and limitations of syntactic representations of lexical decomposition.
Event Kinds
Authors: Gehrke Berit
Published: May 2019

This chapter provides an overview of different empirical domains for which it has been argued to be useful to add event kinds (or types) to the ontology, in addition to event tokens. Direct parallels are drawn to the motivation that have led to positing kinds in the nominal domain, such as the idea that elements like so (English such) is a kind anaphora and that modification derives subkinds, which is related to the general hierarchical organization of kinds found in both domains, or the observation that modified event kinds have to be well-established, a constraint that is also found with kind reference by singular definite noun phrases.
Thematic Roles and Events
Authors: Gisborne Nikolas , Donaldson James
Published: May 2019

Thematic roles have been put to various uses, including the definition of events. But there is another way of understanding this relationship: it might be the events that define the thematic roles they are associated with. We argue in favour of this approach with the complication that Talmy’s force dynamic roles should be seen as prior to both events and traditional roles. Force dynamic roles differ from traditional roles in that their number is limited to two, they are not found only within word meanings, and they can link to participants outside the sentence. We examine evidence that they play a role in both causation and modality, and provide an argument that while ditransitives involve a result or purpose relation, they should not be analysed as prototypically causative, as they involve variable force-dynamic transfer. The conclusion is that not only do events cause events, but also participants act on participants.
Semantic Domains for Syntactic Word-Building
Authors: Levinson Lisa
Published: May 2019

Event structure often appears to co-vary with verbal morphology and VP syntax. Thus theories of event structure interact with theories of the organization of the grammar. Some theories have posited that syntactic heads associated with the introduction of events are responsible for ‘closing off’ a domain of idiomatic interpretation, both below and above the word level. The traditional boundary between ‘idiosyncratic’ words and ‘generated’ sentences breaks down when one considers idiosyncrasy at the phrasal level such as idioms, on the one hand, and structure and compositional meaning within words, such as derivational morphology, on the other. This chapter introduces several current approaches to syntactic word-building, and then reviews different proposals for the semantic interpretation of syntactically-composed words. This background will be used to explore the different domains that have been put forth as delimiting the site for special interpretations, within which it is predicted we will find Apparent Compositionality Exceptions.
Aspectual Classes
Authors: Mittwoch Anita
Published: May 2019

This chapter deals with meaning elements of the predicate that are mainly connected with temporal characteristics other than those, like tense, that are directly connected to the speech act. These are sometimes referred to as inner aspect, in contrast to outer aspect, which deals with temporal operators like Progressive, Perfect and Habitual. The chapter focuses in particular on the division of predicates into aspectual classes, such as states, activities, accomplishments, achievements, and semelfactives, and criteria for such classifications. There is also some discussion of the stage level/individual level distinction, and the theory introduced by the philosopher Donald Davidson that all predicates have an event argument. Most of the data are from English but there are examples from Slavonic languages and a number of other languages.
Event Structure without naïve Physics
Authors: Verkuyl Henk J.
Published: May 2019

What is the real nature of the aspectual division between perfective and imperfective as revealed by the well-known in/for-test? The answer is founded on the idea that this division between completion and incompletion mirrors our cognitive capacity to shift between discreteness and continuity as expressed in the number systems N and R. To get at the real contribution of a verb to aspectual information, the first step is to determine the basic atemporal building block making a tenseless verb stative or non-stative. For this, verbhood is to be understood aspectually in a very strict way abstracting from the contribution of arguments. It follows that one has to get ‘below’ event structure in order to see why the in/for-test works as it turns out to do (or in some cases not).
Introduction
Authors: Haselgrove Colin , Rebay-Salisbury Katharina , Wells Peter S.
Published: May 2019

This chapter provides an overview of the origins and development of Iron Age studies in Europe and outlines the main research themes explored in this book. The period is understood to begin when iron first came into general use, between 1000 and 600 BC in different regions. It is the final recognized period of prehistory, continuing in lands outside the Roman Empire until the arrival of Christianity in the later first millennium AD. The archaeology of the Iron Age shows intensification of subsistence production, manufacturing, and trading, as iron came to be applied to many economically important tasks, populations increased, and interactions between communities grew. Larger settlements of the period are thought to indicate the beginnings of urbanism. Settlement sites, cemeteries, and deposits of different kinds are abundantly represented, their material remains generating a rich picture of lifeways, social organization, economic activities, and ritual practices across the continent.
The rs75862629 minor allele in the endoplasmic reticulum aminopeptidases intergenic region affects human leucocyte antigen B27 expression and protects from ankylosing spondylitis in Sardinia
Authors: Paladini Fabiana , Fiorillo Maria Teresa , Tedeschi Valentina , D’Otolo Viviana , Piga Matteo , Cauli Alberto , Mathieu Alessandro , Sorrentino Rosa
Published: May 2019

Objectives

HLA-B27 and the endoplasmic reticulum aminopeptidase 1 (ERAP1) and ERAP2 genes are predisposing factors for AS. A single nucleotide polymorphism (SNP) in the ERAP2 promoter (rs75862629) coordinates the transcription of both ERAP genes. We investigated whether this SNP associates with AS and whether it affects the expression of the two major HLA-B27 alleles present in Sardinia, the AS-associated B*2705 and the non-AS-associated B*2709.

Methods

Four SNPs in the ERAP region were genotyped in HLA-B*2705-positive patients with AS (n = 145), B27-positive healthy subjects (n = 126) and B27-negative controls (n = 250) and the allele and haplotype frequencies were derived. The expression of ERAP1 and ERAP2 mRNAs in 36 HLA-B27-positive B lymphoblastoid cell lines was measured by quantitative PCR. An electrophoretic mobility shift assay was performed to search for a nuclear factor binding the DNA sequence encompassing rs75862629. The expression of HLA-B27 molecules related to the SNP at rs75862629 was determined by flow cytometry.

Results

The minor allele G at rs75862629 was found significantly increased in B27 healthy individuals, both B*2705 and B*2709, compared with B*2705-positive patients with AS and B27-negative controls. The electrophoretic mobility shift assay indicated the lack of binding of a transcription factor as the cause of the observed reduction in the ERAP2 concomitant with a higher ERAP1 expression. Of note, this occurs with a different cell surface expression of the HLA-B*2705 and HLA-B*2709 molecules.

Conclusion

SNP rs75862629, by modulating simultaneously the expression of ERAP1 and ERAP2, provides protection from AS in HLA-B27-positive subjects in Sardinia. This has a functional impact on HLA-B27 expression and likely on disease onset.
CAPTURE-JIA: a consensus-derived core dataset to improve clinical care for children and young people with juvenile idiopathic arthritis
Authors: McErlane Flora , Armitt Gillian , Cobb Joanna , Bailey Kathryn , Cleary Gavin , Douglas Sharon , Lunt Laura , Rashid Amir , Sampath Sunil , Shoop-Worrall Stephanie , Smith Nicola , Foster Helen , Thomson Wendy
Published: May 2019

Objectives

Data collected during routine clinic visits are key to driving successful quality improvement in clinical services and enabling integration of research into routine care. The purpose of this study was to develop a standardized core dataset for juvenile idiopathic arthritis (JIA) (termed CAPTURE-JIA), enabling routine clinical collection of research-quality patient data useful to all relevant stakeholder groups (clinicians, service-providers, researchers, health service planners and patients/families) and including outcomes of relevance to patients/families.

Methods

Collaborative consensus-based approaches (including Delphi and World Café methodologies) were employed. The study was divided into discrete phases, including collaborative working with other groups developing relevant core datasets and a two-stage Delphi process, with the aim of rationalizing the initially long data item list to a clinically feasible size.

Results

The initial stage of the process identified collection of 297 discrete data items by one or more of fifteen NHS paediatric rheumatology centres. Following the two-stage Delphi process, culminating in a consensus workshop (May 2015), the final approved CAPTURE-JIA dataset consists of 62 discrete and defined clinical data items including novel JIA-specific patient-reported outcome and experience measures.

Conclusions

CAPTURE-JIA is the first ‘JIA core dataset’ to include data items considered essential by key stakeholder groups engaged with leading and improving the clinical care of children and young people with JIA. Collecting essential patient information in a standard way is a major step towards improving the quality and consistency of clinical services, facilitating collaborative and effective working, benchmarking clinical services against quality indicators and aligning treatment strategies and clinical research opportunities.
Depressive symptoms, sleep patterns, and physical activity in adolescents with narcolepsy
Authors: Parmar Arpita , Yeh E Ann , Korczak Daphne J , Weiss Shelly K , Lu Zihang , Zweerink Allison , Toulany Alene , Murray Brian J , Narang Indra
Published: May 2019

Study Objectives

To evaluate the association between depressive symptoms, sleep patterns (duration and quality), excessive daytime sleepiness (EDS), and physical activity (PA) in adolescents with narcolepsy.

Methods

This cross-sectional study included adolescents (ages 10–18 years) with narcolepsy attending a tertiary care facility (The Hospital for Sick Children, Toronto, Canada). Adolescents with narcolepsy completed questionnaires evaluating depressive symptoms (Children’s Depression Inventory-2nd edition [CDI-2]), sleep quality (Pittsburgh Sleep Quality Index), EDS (Epworth Sleepiness Scale), and PA (Godin Leisure-Time Exercise Questionnaire). Wrist-based actigraphy was worn by adolescents for 1 week to measure total sleep time (over 24 hr) and sleep efficiency percentage.

Results

Thirty adolescents with narcolepsy (mean age = 13.8 ± 2.2 years, 76.7% male) participated. In this cohort of adolescents with narcolepsy, 23.3% had CDI-2 total scores in the elevated range. Greater CDI-2 total scores were associated with poor sleep quality (ρ = 0.571; p = 0.02), EDS (ρ = 0.360; p = 0.05), and lower self-reported PA levels (ρ = −0.512; p < 0.01).

Conclusions

Adolescents with narcolepsy report experiencing depressive symptoms, which are associated with poor sleep quality, EDS, and low PA levels. Strategies to improve nocturnal sleep quality and symptoms of EDS as well as promoting increased PA levels in adolescents with narcolepsy may provide an opportunity to improve depressive symptoms in this population. Multidisciplinary care with mental health and sleep specialists for adolescents with narcolepsy is needed.
The energy distribution of a train impact process based on the active–passive energy-absorption method
Authors: Guangjun Gao
Published: May 2019

This paper examines the energy-absorption characteristics of trains for active–passive safety protection. A one-dimensional collision-simulation model of traditional subway vehicles and active–passive safety vehicles was developed based on the multibody dynamics theory using MATLAB simulation software. The effectiveness of the simulation model was verified by scaled-collision tests. Then, the energy-absorption characteristics of traditional trains and the active–passive safety trains under different marshalling conditions were studied. The results showed that as the number of marshalling vehicles increased from 5 to 8, the energy absorption of interface 1 for the active–passive safety trains during the collision was 681 kJ, 775 kJ, 840 kJ and 901 kJ, and the physical compression of the interface of the head car of the active–passive safety trains was 619 mm, 704 mm, 764 mm and 816 mm, which was far below the maximum value of 1773 mm. The head car of the active–passive safety subway vehicles therefore had sufficient energy-absorption capacity. Finally, to find the maximum safe impact velocity of the active–passive safety trains, the energy distribution of the active–passive safety subway vehicles with 8-car marshalling at different impact velocities was studied. It was found that the safe impact velocity of an active–passive safety subway vehicle conforming to the requirements of the EN15227 collision standard reached 32 km/h, far exceeding the safe impact velocity of 25 km/h allowed by traditional trains, and representing an increase in the safe impact velocity of 28%. The total collision-energy absorption of the interface of the head car of the active–passive trains was 89.1% higher than that of the traditional trains at the safe impact velocity. The active–passive energy absorption method was therefore effective at improving the crashworthiness of the subway trains.
Joint contributions of cortical morphometry and white matter microstructure in healthy brain aging: A partial least squares correlation analysis
Authors: Hoagey David A. , Rieck Jenny R. , Rodrigue Karen M. , Kennedy Kristen M.
Published: May 2019

Cortical atrophy and degraded axonal health have been shown to coincide during normal aging; however, few studies have examined these measures together. To lend insight into both the regional specificity and the relative timecourse of structural degradation of these tissue compartments across the lifespan, we analyzed grey matter (GM) morphometry (cortical thickness, surface area, volume) and estimates of white matter (WM) microstructure (fractional anisotropy, mean diffusivity) using traditional univariate and more robust multivariate techniques to examine age associations in 186 healthy adults aged 20-94 years old. Univariate analysis of each tissue type revealed that negative age associations were largest in frontal grey and white matter tissue and weaker in temporal, cingulate, and occipital regions, representative of not only an anterior-to-posterior gradient, but also a medial-to-lateral gradient. Multivariate partial least squares correlation (PLSC) found the greatest covariance between GM and WM was driven by the relationship between WM metrics in the anterior corpus callosum and projections of the genu, anterior cingulum, and fornix; and with GM thickness in parietal and frontal regions. Surface area was far less susceptible to age effects and displayed less covariance with WM metrics, while regional volume covariance patterns largely mirrored those of cortical thickness. Results support a retrogenesis-like model of aging, revealing a coupled relationship between frontal and parietal GM and the underlying WM, which evidence the most protracted development and the most vulnerability during healthy aging.
Non-autonomous induction of epithelial lineage infidelity and hyperplasia by DNA damage
Authors: Seldin Lindsey , Macara Ian G.
Published: May 2019

Several epithelial tissues contain stem cell reserves to replenish cells lost during normal homeostasis or upon injury. However, how epithelial tissues respond to distinct types of damage, and how stem cell plasticity and proliferation are regulated in these contexts, remain poorly understood. Here, we reveal that genotoxic agents, but not mechanical damage, induce hyperplasia and lineage infidelity in three related epithelial tissues: the mammary gland, interfollicular epidermis and hair follicle. Furthermore, DNA damage also promotes stromal proliferation. In the mammary gland, we find that DNA damage activates multipotency within the myoepithelial population and hyper-proliferation of their luminal progeny, resulting in tissue disorganization. Additionally, in epidermal and hair follicle epithelia, DNA damage induces basal cell hyperplasia with the formation of abnormal, multi-layered K14+/K10+ cells. This behavior does not involve apoptosis or immunity, and is epithelial cell non-autonomous; stromal fibroblasts are both necessary and sufficient to induce the epithelial response. Thus, genotoxic agents that are used chemotherapeutically to promote cancer cell death can have the opposite effect on wild-type epithelial tissue, paradoxically promoting hyperplasia and inducing both stemness and lineage infidelity.
Electrocardiographic characterization of non-selective His bundle pacing. Validation of novel diagnostic criteria
Authors: Jastrzębski Marek , Moskal Paweł , Curila Karol , Fijorek Kamil , Kukla Piotr , Bednarek Agnieszka , Kiełbasa Grzegorz , Bednarski Adam , Baranchuk Adrian , Czarnecka Danuta
Published: May 2019

Aims

Permanent His bundle (HB) pacing is usually accompanied by simultaneous capture of the adjacent right ventricular (RV) myocardium - this is described as a non-selective (ns)-HB pacing. Our aim was to identify ECG criteria for loss of HB capture during ns-HB pacing.

Methods

Consecutive patients with permanent HB pacing were recruited. Surface 12-lead ECGs during ns-HB pacing and loss of HB capture (RV-only capture) were obtained. ECG criteria for loss/presence of HB capture were identified. In the validation phase these criteria and the “HB ECG algorithm” were tested by two blinded observers using a separate, sizable set of ECGs.

Results

A total of 353 ECG (226 ns-HB and 128 RV-only) were obtained from 226 patients with permanent HB pacing devices. QRS notch/slur in left ventricular leads and R-wave peak time in lead V6 were identified as the best features for differentiation. The 2-step HB ECG algorithm based on these features correctly classified 87.1% of cases with sensitivity and specificity of 93.2% and 83.9%, respectively. Moreover, the proposed criteria for definitive diagnosis of ns-HB capture (no QRS slur/notch in leads I, V1, V4-V6andthe R-wave peak time in V6 ≤ 100 ms) presented 100% specificity.

Conclusion

A novel ECG algorithm for the diagnosis of loss of HB capture and novel criteria for definitive confirmation of HB capture were formulated and validated. Practical application of these criteria during implant and follow-up of patients with HB pacing devices is feasible.

Condensed Abstract

The 2-step ECG algorithm for loss of His bundle capture based on surface ECG analysis is proposed and validated. This method correctly classified 87.1% of cases with a sensitivity and specificity of 93.2% and 83.9%, respectively.

What’s New

This is the first study that analyzes QRS characteristics during non-selective His bundle pacing in a sizable cohort of patients.

Precise criteria and a novel algorithm for electrocardiographic diagnosis of loss of HB capture during presumed non-selective HB pacing were validated.

QRS notch/slur in left ventricular leads was identified as a simple and reproducible feature indicating loss of HB capture or lack/loss of correction of intraventricular conduction disturbances.

Assessment of R-wave peak time in lead V6 rather than QRS duration for diagnosis of ns-HB pacing was validated.
An investigation of PS-b-PEO polymersomes for the oral treatment and diagnosis of hyperammonemia
Authors: Matoori Simon , Bao Yinyin , Schmidt Aaron , Fischer Eric J. , Ochoa-Sanchez Rafael , Tremblay Mélanie , Oliveira Mariana , Rose Christopher F. , Leroux Jean-Christophe
Published: May 2019

Ammonia-scavenging transmembrane pH-gradient poly(styrene)-b-poly(ethylene oxide) polymersomes were investigated for the oral treatment and diagnosis of hyperammonemia, a condition associated with serious neurologic complications in patients with liver disease as well as in infants with urea cycle disorders. While these polymersomes were highly stable in simulated intestinal fluids at extreme bile salt and osmolality conditions, they unexpectedly did not reduce plasmatic ammonia levels in cirrhotic rats after oral dosing. Incubation in dietary fiber hydrogels mimicking the colonic environment suggested that the vesicles were probably destabilized during the dehydration of the intestinal chyme. Our findings question the relevance of commonly used simulated intestinal fluids for studying vesicular stability. With the encapsulation of a pH-sensitive dye in the polymersome core, the local pH increase upon ammonia influx could be exploited to assess the ammonia concentration in the plasma of healthy and cirrhotic rats as well as in other fluids. Due to its high sensitivity and selectivity, this novel polymersome-based assay could prove useful in the monitoring of hyperammonemic patients and in other applications such as drug screening tests.

Graphical abstract
Membrane-type 1 matrix metalloproteinase (MMP-14) modulates tissue homeostasis by a non-proteolytic mechanism
Authors: Attur Mukundan , Lu Cuijie , Zhang Xiaodong , Han Tianzhen , Alexandre Cassidy , Valacca Cristina , Zheng Shuai , Meikle Sarina , Dabovic Branka Brukner , Tassone Evelyne , Yang Qing , Kolupaeva Victoria , Yakar Shoshana , Abramson Steven , Mignatti Paolo
Published: May 2019

Membrane-type 1 matrix metalloproteinase (MT1-MMP, MMP-14), a transmembrane proteinase with a short cytoplasmic tail, is a major effector of extracellular matrix (ECM) remodeling. Genetic silencing of MT1-MMP in mouse (Mmp14−/−) and man causes dwarfism, osteopenia, arthritis and lipodystrophy, abnormalities ascribed to defective collagen turnover. We have previously shown non-proteolytic functions of MT1-MMP mediated by its cytoplasmic tail, where the unique tyrosine (Y573) controls intracellular signaling. The Y573D mutation blocks TIMP2/MT1-MMP-induced Erk1/2 and Akt signaling without affecting proteolytic activity. Here we report that a mouse with the MT1-MMP Y573D mutation (Mmp14Y573D/Y573D) shows abnormalities similar to, but also different from those ofMmp14−/−mice. Skeletal stem cells (SSC) ofMmp14Y573D/Y573Dmice show defective differentiation consistent with the mouse phenotype, which is rescued by wild-type SSC transplant. These results provide the firstin vivodemonstration that MT1-MMP modulates bone, cartilage and fat homeostasis by controlling SSC differentiation through a mechanism independent of proteolysis.
Tropomyosin 1 genetically constrains in vitro hematopoiesis
Authors: Thom CS , Jobaliya CD , Lorenz K , Maguire JA , Gagne A , Gadue P , French DL , Voight BF
Published: May 2019

Identifying causal variants and genes from human genetics studies of hematopoietic traits are important to enumerate basic regulatory mechanisms underlying these traits, and could ultimately augment translational efforts to generate platelets and/or red blood cells in vitro. To identify putative causal genes from these data, we performed computational modelling using available genome-wide association data sets for platelet traits. Our model identified a joint collection of genomic features enriched at established platelet trait associations and plausible candidate variants. Additional studies associating variation at these loci with change in gene expression highlighted the Tropomyosin 1 (TPM1) among our top-ranked candidate genes. CRISPR/Cas9-mediated TPM1 knockout in human induced pluripotent stem cells (iPSCs) enhanced hematopoietic progenitor development, increasing total megakaryocyte as well as erythroid cell yields. Our findings may help explain human genetics associations and identify a novel genetic strategy to enhance in vitro hematopoiesis.
Zinc finger RNA binding protein Zn72D regulates ADAR-mediated RNA editing in neurons
Authors: Sapiro Anne L. , Freund Emily C. , Restrepo Lucas , Qiao Huan-Huan , Bhate Amruta , Li Qin , Ni Jian-Quan , Mosca Timothy J. , Li Jin Billy
Published: May 2019

Adenosine-to-inosine RNA editing, catalyzed by ADAR enzymes, alters RNA sequences from those encoded by DNA. These editing events are dynamically regulated, but few trans regulators of ADARs are known in vivo. Here, we screen RNA binding proteins for roles in editing regulation using in vivo knockdown experiments in the Drosophila brain. We identify Zinc-Finger Protein at 72D (Zn72D) as a regulator of editing levels at a majority of editing sites in the brain. Zn72D both regulates ADAR protein levels and interacts with ADAR in an RNA-dependent fashion, and similar to ADAR, Zn72D is necessary to maintain proper neuromuscular junction architecture and motility in the fly. Furthermore, the mammalian homolog of Zn72D, Zfr, regulates editing in mouse primary neurons, demonstrating the conservation of this regulatory role. The broad and conserved regulation of ADAR editing by Zn72D in neurons represents a novel mechanism by which critically important editing events are sustained.
Understanding the basis of CYP26 mediated regulation of lens regeneration usingex vivoeye cultures and 4-oxo-RA
Authors: Thomas Alvin G , Adil Mohd Tayyab , Henry Jonathan J
Published: May 2019

PURPOSE

Xenopushas the remarkable ability to regenerate a lens from the basal cornea epithelial cells in response to signals from the retina. Previous work demonstrated that the Retinoic Acid (RA) metabolizing enzyme CYP26 is expressed in the cornea, and that its activity is required for lens regeneration. Gaps remain in our knowledge as to whether CYP26 is needed only to attenuate RA signaling via RA elimination, or whether it also acts to generate retinoid metabolites, such as 4-oxo-RA, to act as signaling ligands. Other key questions are why CYP26 antagonism, but not exogenous retinoids, can reduce cell division in the cornea, and when during regeneration CYP26 is important.

MATERIALS AND METHODS

Ex vivocultures supplemented with RA, 4-oxo-RA, or the CYP26 inhibitor Liarozole were used to assay the effects of these compounds on lens regeneration. Similarly, corneas were explanted, cultured in the presence of these compounds, and assayed for mitotic changes by counting anti-Histone H3 positive nuclei. qPCRs validated responsiveness to these compounds.

RESULTS

Ex vivocultures showed that when the media was supplemented with the RA metabolite 4-oxo-RA in addition to Liarozole, lens regeneration was still inhibited. 4-oxo-RA also does not rescue the loss of cell division in the cornea that is observed upon CYP26 antagonism. Liarozole inhibited regeneration when added 12 hours after lentectomy, but not when added 48 hours after.

CONCLUSIONS

These data show that the necessity of CYP26 is not explained as a generator of 4-oxo-RA for regeneration. Moreover, Liarozole-induced mitotic reduction is not explained by 4-oxo-RA deficiency. These results support a model of RA-independent mitotic regulation by CYP26, though other retinoid metabolites may be active. Finally, CYP26 activity is only needed between 12 and 48 hours post-surgery, showing that its action is required only during the earliest stages of lens regeneration.

Financial interests

The authors declare no competing financial interests.
Risk factors for postoperative meningitis after microsurgery for vestibular schwannoma
Authors: Huang Bowen , Ren Yanming , Wang Chenghong , Lan Zhigang , Hui Xuhui , Liu Wenke , Zhang Yuekang
Published: May 2019

OBJECTIVE

Meningitis after microsurgery for vestibular schwannoma (VS) is a severe complication and result in high morbidity. But few studies have focused on meningitis after VS surgery alone. The purpose of this study was to identify the risk factors for meningitis after VS surgery.

METHODS

We undertook a retrospective analysis of all VS patients, who underwent microsurgery of VS and at least live for 7 days after surgery, between 1st June 2015 and 30st November 2018 at West China Hospital of Sichuan University. Univariate and multivariate analyses were performed to identify the risk factors for postoperative meningitis (POM).

RESULTS

We collected 410 patients, 27 of whom had POM. Through univariate analysis, hydrocephalus (p=0. 018), Koos grade IV (p=0.04), The operative duration (> 3 hours p=0.03) and intraoperative bleeding volume (≥ 400ml p=0. 02) were significantly correlated to POM. Multivariate analysis showed that Koos grade IV (p=0.04; OR=3.19; 95% CI 1.032-3.190), operation duration (> 3 hours p=0.03 OR= 7.927; 95% CI 1.043-60.265), and intraoperative bleeding volume (≥ 400ml p=0.02; OR=2.551; 95% CI 1.112-5.850) are the independent influencing factors of POM.

CONCLUSIONS

Koos grade IV, the duration of operation, and the amount of bleeding were identified as independent risk factors for POM after microsurgery of VS. POM caused a prolonged hospital stay.
Capillary hemoglobin electrophoresis of healthy and anemic dogs: quantification, validation, and reference intervals of hemoglobin fractions
Authors: Oikonomidis Ioannis L. , Tsouloufi Theodora K. , Mylonakis Mathios E. , Kritsepi-Konstantinou Maria
Published: May 2019

Despite the advances in canine medicine and the rapid gaining of attention of canine models in biomedical field and particularly in hemoglobin genes research, the studies on canine hemoglobin composition are sparse with ambiguous findings. Our aim was: i) to investigate the electrophoretic pattern of canine hemoglobin and the possible effect of age, sex, and anemia using a capillary electrophoresis assay, and ii) to validate this assay and calculate reference intervals (RIs) for canine hemoglobin fractions. Blood samples were collected from 53 healthy and 42 dogs with regenerative and non-regenerative anemias. The Sebia Capillarys 2 flex-piercing was used for hemoglobin analysis and it was validated using canine blood samples. R statistical language was employed for the statistical analyses. A major hemoglobin fraction (named HbA0) and a minor one (named HbA2) were identified in 100% and 47.4% of samples, respectively. The within-run and between-run CV was 0.1% for HbA0and 9.1% and 11.2% for HbA2, respectively. The extremely narrow range of HbA0and HbA2values hampered a linearity study using canine blood samples. The RIs for HbA0and HbA2were 98.9-100% and 0-1.1%, respectively. HbA0and HbA2values were not correlated with age (P=0.866). No differences were observed in the median HbA0and HbA2between the two sexes (P=0.823), and healthy and anemic dogs (P=0.805). In conclusion, the capillary electrophoresis revealed a major hemoglobin fraction and an inconsistently present minor fraction. No effect of age, sex, or anemia was detected. The assay used was validated and RIs were generated, so as to be suitable for use in future investigations.