bluuebunny/crossref_metadata_2025 huggingface dataset:
Intrinsic polarization of elongated porous dust grains
Authors: Kirchschlager Florian , Bertrang Gesa H-M , Flock Mario
Published: June 2019

Observations of the Atacama Large Millimeter Array (ALMA) revealed recently polarized radiation of several protoplanetary discs in the (sub)millimetre wavelength range. Besides self-scattering of large particles, thermal emission by elongated grains is a potential source for the detected polarization signal. We calculate the wavelength dependent absorption and intrinsic polarization of spheroidally shaped, micrometre, and submillimetre sized dust grains using the discrete dipole approximation. In particular, we analyse the impact of dust grain porosity that appears to be present in discs when small grains coagulate to form larger aggregates. For the first time, our results show that (a) the intrinsic polarization decreases for increasing grain porosity and (b) the polarization orientation flips by 90 deg for certain ratios of wavelength to grain size. We present a new method to constrain grain porosity and the grain size in protoplanetary discs using multiwavelength polarization observations in the far-infrared to millimetre wavelengths. Finally, we find that moderate grain porosities ($\mathcal {P}\lesssim 0.7$) potentially explain the observed polarization fraction in the system HD 142527 while highly porous grains ($\mathcal {P}\gt 0.7$) fail unless the grain’s axis ratio is extraordinarily large.
DNA damage tolerance in stem cells, ageing, mutagenesis, disease and cancer therapy
Authors: Pilzecker Bas , Buoninfante Olimpia Alessandra , Jacobs Heinz
Published: June 2019

The DNA damage response network guards the stability of the genome from a plethora of exogenous and endogenous insults. An essential feature of the DNA damage response network is its capacity to tolerate DNA damage and structural impediments during DNA synthesis. This capacity, referred to as DNA damage tolerance (DDT), contributes to replication fork progression and stability in the presence of blocking structures or DNA lesions. Defective DDT can lead to a prolonged fork arrest and eventually cumulate in a fork collapse that involves the formation of DNA double strand breaks. Four principal modes of DDT have been distinguished: translesion synthesis, fork reversal, template switching and repriming. All DDT modes warrant continuation of replication through bypassing the fork stalling impediment or repriming downstream of the impediment in combination with filling of the single-stranded DNA gaps. In this way, DDT prevents secondary DNA damage and critically contributes to genome stability and cellular fitness. DDT plays a key role in mutagenesis, stem cell maintenance, ageing and the prevention of cancer. This review provides an overview of the role of DDT in these aspects.
From general base to general acid catalysis in a sodium-specific DNAzyme by a guanine-to-adenine mutation
Authors: Ma Lingzi , Kartik Sanjana , Liu Biwu , Liu Juewen
Published: June 2019

Recently, a few Na+-specific RNA-cleaving DNAzymes were reported, where nucleobases are likely to play critical roles in catalysis. The NaA43 and NaH1 DNAzymes share the same 16-nt Na+-binding motif, but differ in one or two nucleotides in a small catalytic loop. Nevertheless, they display an opposite pH-dependency, implicating distinct catalytic mechanisms. In this work, rational mutation studies locate a catalytic adenine residue, A22, in NaH1, while previous studies found a guanine (G23) to be important for the catalysis of NaA43. Mutation with pKa-perturbed analogs, such as 2-aminopurine (∼3.8), 2,6-diaminopurine (∼5.6) and hypoxanthine (∼8.7) affected the overall reaction rate. Therefore, we propose that the N1 position of G23 (pKa ∼6.6) in NaA43 functions as a general base, while that of A22 (pKa ∼6.3) in NaH1 as a general acid. Further experiments with base analogs and a phosphorothioate-modified substrate suggest that the exocyclic amine in A22 and both of the non-bridging oxygens at the scissile phosphate are important for catalysis for NaH1. This is an interesting example where single point mutations can change the mechanism of cleavage from general base to general acid, and it can also explain this Na+-dependent DNAzyme scaffold being sensitive to a broad range of metal ions and molecules.
The role of ZAP and OAS3/RNAseL pathways in the attenuation of an RNA virus with elevated frequencies of CpG and UpA dinucleotides
Authors: Odon Valerie , Fros Jelke J , Goonawardane Niluka , Dietrich Isabelle , Ibrahim Ahmad , Alshaikhahmed Kinda , Nguyen Dung , Simmonds Peter
Published: June 2019

Zinc finger antiviral protein (ZAP) is a powerful restriction factor for viruses with elevated CpG dinucleotide frequencies. We report that ZAP similarly mediates antiviral restriction against echovirus 7 (E7) mutants with elevated frequencies of UpA dinucleotides. Attenuation of both CpG- and UpA-high viruses and replicon mutants was reversed in ZAP k/o cell lines, and restored by plasmid-derived reconstitution of expression in k/o cells. In pull-down assays, ZAP bound to viral RNA transcripts with either CpG- and UpA-high sequences inserted in the R2 region. We found no evidence that attenuation of CpG- or UpA-high mutants was mediated through either translation inhibition or accelerated RNA degradation. Reversal of the attenuation of CpG-high, and UpA-high E7 viruses and replicons was also achieved through knockout of RNAseL and oligodenylate synthetase 3 (OAS3), but not OAS1. WT levels of replication of CpG- and UpA-high mutants were observed in OAS3 k/o cells despite abundant expression of ZAP, indicative of synergy or complementation of these hitherto unconnected pathways. The dependence on expression of ZAP, OAS3 and RNAseL for CpG/UpA-mediated attenuation and the variable and often low level expression of these pathway proteins in certain cell types, such as those of the central nervous system, has implications for the use of CpG-elevated mutants as attenuated live vaccines against neurotropic viruses.
Pharmacogenomics of Nicotine Metabolism: Novel CYP2A6 and CYP2B6 Genetic Variation Patterns in Alaska Native and American Indian Populations
Authors: Claw Katrina G , Beans Julie A , Lee Seung-Been , Avey Jaedon P , Stapleton Patricia A , Scherer Steven E , El-Boraie Ahmed , Tyndale Rachel F , Nickerson Deborah A , Dillard Denise A , Thummel Kenneth E , Robinson Renee F
Published: June 2019

Introduction

Alaska Native and American Indian (AN/AI) populations have higher tobacco use prevalence than other ethnic/racial groups. Pharmacogenetic testing to tailor tobacco cessation treatment may improve cessation rates. This study characterized polymorphic variations among AN/AI people in genes associated with metabolism of nicotine and drugs used for tobacco cessation.

Methods

Recruitment of AN/AI individuals represented six subgroups, five geographic subgroups throughout Alaska and a subgroup comprised of AIs from the lower 48 states living in Alaska. We sequenced the CYP2A6 and CYP2B6 genes to identify known and novel gain, reduced, and loss-of-function alleles, including structural variation (eg, gene deletions, duplications, and hybridizations).

Results

Variant allele frequencies differed substantially between AN/AI subgroups. The gene deletion CYP2A6*4 and reduced function CYP2A6*9 alleles were found at high frequency in Northern/Western subgroups and in Lower 48/Interior subgroups, respectively. The reduced function CYP2B6*6 allele was observed in all subgroups and a novel, predicted reduced function CYP2B6 variant was found at relatively high frequency in the Southeastern subgroup.

Conclusions

Diverse CYP2A6 and CYP2B6 variation among the subgroups highlight the need for comprehensive pharmacogenetic testing to guide tobacco cessation therapy for AN/AI populations.

Implications

Nicotine metabolism is largely determined by CYP2A6 genotype, and variation in CYP2A6 activity has altered the treatment success in other populations. These findings suggest pharmacogenetic-guided smoking cessation drug treatment could provide benefit to this unique population seeking tobacco cessation therapy.
Nicolò de’ Rossi
Authors: Sangiovanni Fabio
Published: June 2019

Nicolò de’ Rossi (c. 1295–c. post-1348) was born in Treviso, Italy, toward the end of the 13th century and died in Venice after 1348. Beyond a preeminent legal activity that allowed him to take part as a Guelph to the unstable political events of those years, he was one of the most important literary personalities of his age in northern Italy. His cultural renown within the Trevisan area is confirmed by the fact that after the completion of his law studies in Bologna in 1318, he was preferred over Cino da Pistoia as professor of civil law at the academic Studium of Treviso, and he was often chosen as one of the members of diplomatic missions in several troublesome circumstances (in particular during the war against Cangrande della Scala). However, his name is primarily remembered because of his fervent literary activity: his poetic production includes more than 400 poems (sonnets and four canzoni, one associated to a Latin commentary) written between 1317 and 1329, collected, almost as a lyric canzoniere, in the manuscript Colombino 7.1.32 preserved at the Biblioteca Capitular in Seville. These poems mainly deal with love subjects (he experienced all the possibilities offered by the coeval tradition, from Guittone’s style to Stilnovo styles), as well as with political, moral, realistic, and religious themes. Furthermore, thanks to the testimony of this manuscript, we are able to recognize him as the author of the first vernacular examples of figurative poetry: by renewing the model of the Latin carmina figurata, he integrated the phonic element into the graphic one through the elaboration of complex visual architectures for four poems. His importance in the Veneto region is also due to his activity as a veritable editor of the Italian lyric tradition, as witnessed by another manuscript (Barberiniano lat. 3953 of the Vatican Library), collecting a wide series of Tuscan texts (by Dante, Cavalcanti, Cino da Pistoia, Cecco Angiolieri, etc.) that constitute a remarkable anthology based on particular criteria of selection and inner order.
Pandharpur and Vitthal
Authors: Reenberg Sand Erik
Published: June 2019

Pandharpur, with its main deity, Viṭṭhala (hereafter Vitthal), alias Viṭhobā or Pāṇḍuraṅga, is the most popular pilgrimage site in Maharashtra. Every year it is visited by hundreds of thousands of pilgrims, first of all in connection with the Āṣāḍha and Kārttika festivals of the Vārakarī (hereafter Varkari) Sampradāya. Vitthal is a manifestation of Viṣṇu in his Krishna incarnation (avatāra). According to local tradition Vitthal arrived in Pandharpur attracted by the filial devotion of the seer Puṇḍalīka, or, according to another, later tradition, while looking for his wife Rukmiṇī. Since then he has established himself there for the favor of his devotees while Puṇḍalīka is considered to be the founder of the devotional cult known as Varkaris. The real explanation of Vitthal’s arrival in Pandharpur is another matter. Although many scholars have taken the myth about Puṇḍalīka to reflect a story about an actual person credited with bringing the worship of Vitthal to Pandharpur, some modern scholars believe that the myth is inspired by Purāṇic traditions legitimizing the establishment of Śaiva liṅgas. In fact, the idol of the Puṇḍalīka samādhi, one of the oldest temples in Pandharpur, contains a Śiva-liṅga. This, taken together with the fact that some of the oldest temples in the town are devoted to Śiva, suggests that Pandharpur was originally a Śaiva place that was later Vaiṣṇavized with the introduction of Vitthal, who may have been of pastoral origin and come from Karnataka to the south. When exactly this Vaiṣṇavization took place is not sure but it seems to have more or less coincided with the earliest historical inscription mentioning Pandharpur and Vitthal dating from the end of the 12th century when a temple of Vitthal was founded. At the end of the 13th century the cult was attracting support from the northern Marathi-speaking area when it was probably visited by the Yadava king Rāmacandra and his chief minister Hemādri as well as by Jñāneśvara, the “founder” of the Varkari Sampradāya. Literary sources for the study of Pandharpur either belong to the devotional Varkari tradition and are in the vernacular Marathi or they belong to the local Brahmanic tradition in the form of Sanskrit māhātmyas. Since the latter have either been unedited or are difficult to access, a characteristic of the research on Pandharpur until the 1980s is that it has mainly been based on literature in the Marathi language.
Historical Land Uses and Their Changes in the European Alps
Authors: Tappeiner Ulrike , Tasser Erich
Published: June 2019

The Alps are the highest and largest mountain range in Europe. They extend from the Ligurian Sea to the Pannonian Basin in an arc 744 miles (1,200 km) long and between 93 and 155 miles (150–250 km) wide. The settlement history of this large European landscape is closely linked to the settlement of Europe as a whole, whereby the inner Alpine region was not permanently settled until around 4500 bce because of topographical and climatic disadvantages. Dense forest cover initially made it difficult to use large grazing areas, but transhumance gradually developed in the Alpine region when the animals spent their summers high up in the mountains and their winters in the valleys. At about the same time, the Alpine self-sufficiency economy of arable farming and livestock breeding was added, which made permanent settlement possible. However, the most intensive settlement and land reclamation advance took place in the Middle Ages. In the 19th century, industrialization reached the Alpine region a little delayed, and globalization in the middle of the 20th century. This also led to a fundamental change in society. The previous agricultural society was replaced by the service society of the 20th century. Developments since the late 1950s have taken place against the background of developments in the European Union (EU) as a whole, above all the Common Agricultural Policy and the European Spatial Development Perspective (ESDP), but these developments were and still are influenced by additional agreements specific to the Alps, such as the Alpine Convention, the Alpine Protection Commission (CIPRA), and the Alpine Working Community (Arge Alp). All these factors mean that historical and current development of land use in the Alpine region has been and is always linked to developments in Europe. Many studies on land use in the Alpine region should therefore be seen in this context. Moreover, past land use often has long-lasting legacy effects on ecosystems and their development. Therefore, in this article we deal not only with historical land use but also with current and future developments and their impacts on ecosystem functions and services.
The Growth of Effective Mental Health Services in Schools in the United States
Authors: Weist Mark , Riddle David , Quell Ashley , Massey Cameron , McWhirter Crystal
Published: June 2019

This chapter provides a review of the movement toward more comprehensive mental health systems in schools through mental health-education system partnerships. We review factors contributing to the growth of this field including experiences in school nursing, school-based health centers, regulations regarding special education, and progressively expanding federal support. We then discuss integration of these expanded school mental health (SMH) programs with multitiered systems of support (MTSS) in schools, such as Positive Behavioral Interventions and Supports (PBIS). Specifically, the Interconnected Systems Framework (ISF) for SMH and PBIS represents a platform for effective programs and services at Tier 1, involving promotion/prevention; Tier 2, involving early intervention; and Tier 3, more intensive intervention. Key strategies associated with the ISF and effective practices at each of these tiers are reviewed, including emphases on effective team and culturally responsive and evidence-based practices. The chapter concludes with a review of future directions for SMH.
Intercultural Conflict Mediation
Authors: Busch Dominic
Published: June 2019

Conflict mediation refers to the dialogue-based process by which a third person supports two or more parties, constructively managing their conflict. In North America and Europe, the term “conflict mediation” is usually associated with procedural principles that originate from the US-based “alternative dispute resolution” (ADR) movement. Originally, conflict mediation in the United States had been introduced as an alternative to court-based conflict resolution. Mediation was meant to produce results that were more sustainable and more satisfying for all concerned parties. From the 1980s onward, conflict mediation has increasingly been considered to be particularly suitable for the management of conflicts in intercultural settings; its inherent high procedural flexibility may help in adapting the concept to other cultural contexts, as well as taking cultural aspects of the parties concerned into consideration. The dialogue orientation of the tool was expected to give equal voices to all participants, balancing hidden power inequalities resulting from different cultural affiliations. This general and basic assumption has laid a very fruitful groundwork for the emergence of a highly diverse landscape of approaches to the idea of intercultural conflict mediation since the late 20th century. Researchers on intercultural communication (see also the separate Oxford Bibliographies in Communication article “Intercultural Communication”) and intercultural competence took mediation as a long-expected hands-on tool to finally manage problems resulting from interculturality. This transfer from an alternative to courts to a tool promoting intercultural understanding, however, will leave some gaps open for research, since the tool does not match perfectly: research on intercultural communication and intercultural competence has so far seen its main challenges in rather subtle irritations and everyday interactions instead of focusing on escalated disputes. Parallel to this, although numerous different notions of culture have existed in research for ages, academia concerning interculturality has started to include a wider variety of paradigms since the late 20th century, resulting in widely different notions of culture and its effects. Depending on what paradigm authors adhere to, they will produce widely different understandings on what intercultural conflict mediation is supposed to be. This article will illuminate the range of these understandings. It will also focus on concepts of mediation, taking single individuals into consideration and leaving aside the mediation of large ethnic groups as a different scenario to be located in international politics.
Rap/Hip-Hop
Authors: Keyes Cheryl L.
Published: June 2019

Rap evolved as a vernacular term used among African Americans to define a stylized way of speaking. Over the years, black radio disc jockeys, musicians, literary figures, and 1960s political figures incorporated rap into their performances or way of speaking to appeal to black audiences. By the early 1970s, rap continued its development in the urban streets among “rhymin’ emcees” (MCs) accompanied by pre-recorded music, provided by a disc jockey on two turntables. This concept became associated with a youth arts movement driven and populated by black and Latino youth in New York City called hip-hop. Comprised of four elements—breakdancing (b-boying/b-girling), graffiti (writing), disc jockeying (DJing), and emceeing (MCing)—hip-hop also distinguishes a distinct form of dress, gesture, and language that embodies an urban street consciousness. By the late 1970s, the rhymin’ MC/DJ combination attracted music entrepreneurs who recognized the commercial potential with the release of the recording “Rapper’s Delight” by the Sugarhill Gang. Subsequently, music trade magazines such as Billboard contributed to popularizing the MC/DJ concept as rap music. Additionally, the production of hip-hop arts via the silver screen, advertising, and fashion industries further contributed to its rise to global prominence. Realizing its viability to a growing youth constituency, entrepreneurs placed significant value on certain elements of hip-hop believed to be more marketable to youth consumers in the popular music mainstream. For example, MCing and DJing became primary markets while breakdancing and graffiti served as hip-hop’s secondary markets. As such, rap music eventually eclipsed in popularity breakdancing and graffiti, thus solidifying this music category. Occasionally, critics and aficionados use rap music interchangeably with hip-hop. The sources herein will be used interchangeably as rap music/hip-hop along with their associates (breakdance and graffiti), and allied traditions. Similar to the burgeoning success of hip-hop culture in the mainstream popular culture, rap garnered the attention of academicians during the late 1980s, who perceived it as fertile ground for the study of popular youth culture. This is evident with a flurry of theses, articles, books, journalistic writings, and photo-essays leading to the establishment of hip-hop studies. Today, there are thousands of written sources on hip-hop. Rather than attempting to present all of these written sources, which would be beyond the scope of this bibliography, this article instead offers a survey of book sources and seminal journal articles that reflect the erudition, scholarly depth, and interdisciplinary scope of hip-hop studies.
Problem Solving and Decision Making
Authors: Nielsen Emily G. , Minda John Paul
Published: June 2019

Problem solving and decision making are both examples of complex, higher-order thinking. Both involve the assessment of the environment, the involvement of working memory or short-term memory, reliance on long term memory, effects of knowledge, and the application of heuristics to complete a behavior. A problem can be defined as an impasse or gap between a current state and a desired goal state. Problem solving is the set of cognitive operations that a person engages in to change the current state, to go beyond the impasse, and achieve a desired outcome. Problem solving involves the mental representation of the problem state and the manipulation of this representation in order to move closer to the goal. Problems can vary in complexity, abstraction, and how well defined (or not) the initial state and the goal state are. Research has generally approached problem solving by examining the behaviors and cognitive processes involved, and some work has examined problem solving using computational processes as well. Decision making is the process of selecting and choosing one action or behavior out of several alternatives. Like problem solving, decision making involves the coordination of memories and executive resources. Research on decision making has paid particular attention to the cognitive biases that account for suboptimal decisions and decisions that deviate from rationality. The current bibliography first outlines some general resources on the psychology of problem solving and decision making before examining each of these topics in detail. Specifically, this review covers cognitive, neuroscientific, and computational approaches to problem solving, as well as decision making models and cognitive heuristics and biases.
Multiple Stable States and Catastrophic Shifts in Ecosystems
Authors: Kéfi Sonia
Published: June 2019

The idea that ecosystems may have multiple alternative stable states dates back to the late 1960s–early 1970s, when ecologists realized that this type of behavior could arise in simple mathematical models. A direct consequence is that such ecosystems can suddenly switch (or “tip”) between their alternative stable states rather than gradually responding to changes. In other terms, in these ecosystems, a small environmental perturbation can cause large, discontinuous, and irreversible changes, referred to as catastrophic shifts. This idea has attracted increasing interest in the literature over the years, and has become even more relevant in the current context of global change. Examples of catastrophic shifts in ecosystems include the eutrophication of shallow lakes, the desertification of drylands, and the degradation of coral reefs. Theoretical models have investigated the conditions under which alternative stable states and catastrophic shifts occur. A well-recognized cause of alternative stable states is the presence of strong positive—or self-reinforcing—feedback processes that maintain each of the stable ecosystem states. Understanding the mechanisms underlying the emergence of alternative stable states can help design management as well as restoration strategies for ecosystems. Because catastrophic shifts can have dramatic ecological and economic consequences, approaches have been proposed to detect possible alternative stable states in natural systems, and indicators of approaching ecosystem transitions have been identified (so-called early warning signals of critical slowing down).
Thomas Hardy
Authors: Koehler Karin
Published: June 2019

Thomas Hardy was born in Lower Bockhampton, Dorset, in 1840 and, with brief interruptions, continued to live in and around Dorchester until his death in 1928. His work was intimately linked to the “half-real, half-dream country” of Wessex, a fictionalized version of England’s rural South West. Hardy trained and practiced as an architect but went on to publish fourteen novels, over forty short stories, roughly a thousand poems, several essays, an epic verse drama about the Napoleonic War, and a shorter verse play with Arthurian themes. Given the volume and diversity of this output, and the fact that his writing career spanned from the mid-Victorian years to the heyday of literary Modernism, Hardy’s work resists easy categorization. It is, moreover, marked by profound tensions: between a rural upbringing, a modern education, and an international literary career; between a commitment to preserving local tradition, dialect, and folklore and an ongoing, thorough engagement with contemporary cultural debate; and between the commercial profitability of fiction and the desire to be remembered as a poet. Correspondingly, critical responses to Hardy’s work, especially from the 1980s onward, have been richly diverse and shaped by a broad range of critical concerns and methodologies, including—but not limited to—Marxism, feminism, poststructuralism, psychoanalysis, deconstruction, New Historicism, ecocriticism, animal studies, and postcolonial theory. During the 19th century, several of Hardy’s novels became objects of critical controversy, given his frank treatment of sexual matters, his critique of marriage, and his religious skepticism. Numerous scholars have explored the creative repercussions of Hardy’s fraught negotiations with literary and social conventions. In the first half of the 20th century, though, critical discussions paid particular attention to Hardy’s philosophy, his tragic outlook, and his humanist ethics, while focusing primarily on the poetry and so-called major novels. More recent studies have provided a more nuanced picture of Hardy’s oeuvre, by accounting for works, formal features, and thematic elements that disrupt the image of a liberal-humanist chronicler of rural life. Since the 1970s, Hardy’s writings have provided a fertile ground Hardy saw the beginning of feminist, psychoanalytic, poststructuralist, Marxist, and New Historicist revaluations. Recent criticism has gained particular impetus from a growing awareness that, though firmly associated with rural “Wessex” life, Hardy’s work is shaped by an ongoing engagement with nationwide and international cultural debates, political issues, technological developments, scientific discoveries, and aesthetic trends.
Stephen Fry, the Meaning of Life, and the Problem with Irish Blasphemy Law
Authors: Cox Neville
Published: June 2019

In May 2017, news broke that comedian Stephen Fry was, briefly, under investigation in Ireland, for blasphemy, leading to a reaction of outrage that a blasphemy law existed in Ireland in 2017. This mirrored the equivalent reaction in 2009 when Ireland, in fulfilment of a constitutional obligation, defined the crime in a piece of legislation. A blasphemy law must, by definition, be predicated on a religious public morality that regards certain kinds of irreverence as being ‘unsayable’ and, because Irish public morality is now secular in nature, the law, even though it can have no substantive impact, carried an embarrassingly erroneous message about the nature of modern Ireland. The impact of the law was, therefore, symbolic, and the reaction was against what was seen as an embarrassing and inaccurate symbolic message about the nature of modern Ireland. The disconnect between Irish public morality and the existence of a blasphemy law is the strongest reason why the law should be abolished, and is also the reason why it is unjustifiable as a matter of International Human Rights Law.
Damage accrual and mortality over long-term follow-up in 300 patients with systemic lupus erythematosus in a multi-ethnic British cohort
Authors: Segura Beatriz Tejera , Bernstein Brett Sydney , McDonnell Thomas , Wincup Chris , Ripoll Vera M , Giles Ian , Isenberg David , Rahman Anisur
Published: June 2019

Objective

Damage in patients with systemic lupus erythematosus is irreversible change in organs due to disease activity, concomitant disease or medication side-effects. It is measured using the Systemic Lupus International Collaborative Clinics Damage Index (SDI) and is associated with increased mortality. Previous reports have suggested associations between damage accrual and various ethnic, disease and treatment factors, but there is a dearth of long-term follow-up data from large multi-ethnic cohorts. We describe a study of damage and mortality in 300 patients from London, UK followed for up to 40 years.

Methods

We carried out retrospective analysis of medical records and SDI scores of 300 patients followed for up to 40 years (median 13.3 years). Characteristics of the groups who did and did not develop damage and those who died or survived to the end of follow-up were compared using univariable and multivariable analysis. Kaplan-Meier analysis was used to analyse factors affecting mortality and accrual of damage.

Results

Damage developed in 231/300 (77%) of patients. There was a linear accrual of damage over 40 years follow-up. Factors associated with damage were African/Caribbean ethnicity, renal and cerebral involvement, early use of high-dose corticosteroids or immunosuppressants, anti-RNP and antiphospholipid antibodies. Damage was strongly associated with mortality. Of 87 patients who died, 93% had damage compared with 70% of survivors (P < 0.001).

Conclusion

Development of damage is strongly associated with increased mortality. We identified groups at increased risk of developing damage, including those treated with high-dose steroids and immunosuppressants within the first two years.
What I have heard: conference summary and thoughts for the future1
Authors: Galyean Michael L
Published: June 2019

Twenty-nine presentations by 28 speakers at the California Net Energy System (CNES) 50th Anniversary Symposium provided an informative overview of the past, present, and future of the CNES. The Symposium was divided into eight sessions, with each one or two sessions followed by a lively discussion period. This article provides a summary of key points made by the speakers in each session as provided at the conclusion of the Symposium. Additional thoughts about future directions for research related to the CNES are offered.
Assessment of nociception and related quality-of-life measures in a porcine model of neurofibromatosis type 1
Authors: Khanna Rajesh , Moutal Aubin , White Katherine A. , Chefdeville Aude , Negrao de Assis Pedro , Cai Song , Swier Vicki J. , Bellampalli Shreya S. , Giunta Marissa D. , Darbro Benjamin W. , Quelle Dawn E. , Sieren Jessica C. , Wallace Margaret R. , Rogers Christopher S. , Meyerholz David K. , Weimer Jill M.
Published: June 2019

Neurofibromatosis type 1 (NF1) is an autosomal dominant genetic disorder resulting from germline mutations in the NF1 gene, which encodes neurofibromin. Patients experience a variety of symptoms, but pain in the context of NF1 remains largely underrecognized. Here, we characterize nociceptive signaling and pain behaviors in a miniswine harboring a disruptive NF1 mutation (exon 42 deletion). We present the first characterization of pain-related behaviors in a pig model of NF1, identifying unchanged agitation scores, lower tactile thresholds (allodynia), and decreased response latencies to thermal laser stimulation (hyperalgesia) in NF1

+/ex42del
(females only) pigs. Male NF1

+/ex42del
pigs with tumors showed reduced sleep quality and increased resting, 2 health-related quality-of-life symptoms found to be comorbid in people with NF1 pain. We explore these phenotypes in relationship to suppression of the increased activity of the N-type voltage-gated calcium (CaV2.2) channel by pharmacological antagonism of phosphorylation of a regulatory protein—the collapsin response mediator protein 2 (CRMP2), a known interactor of neurofibromin, and by targeting the interface between the α subunit of CaV2.2 and the accessory β-subunits with small molecules. Our data support the use of NF1

+/ex42del
pigs as a large animal model for studying NF1-associated pain and for understanding the pathophysiology of NF1. Our findings demonstrate the translational potential of 2 small molecules in reversing ion channel remodeling seen in NF1. Interfering with CaV2.2, a clinically validated target for pain management, might also be a promising therapeutic strategy for NF1-related pain management.
Incidence and Prevalence of Borrelia burgdorferi Antibodies in Male Professional Football Players
Authors: Breitbart Philipp , Meister Steffen , Meyer Tim , Gärtner Barbara C.
Published: June 2019

Objective:

Infections with Borrelia burgdorferi can cause Lyme disease with multiorganic involvement such as (myo)carditis or joint manifestations. Musculoskeletal complaints possibly mimicking some of these symptoms are common among elite athletes. This study aimed to determine seroprevalence and incidence of B. burgdorferi antibodies in professional football players.

Design:

Prospective observational study.

Setting:

Healthy professional football players.

Participants:

Five hundred thirty-five men in the first and second German league.

Interventions:

Two screening assays were used to examine immunoglobulin M (IgM) and immunoglobulin G (IgG) against B. burgdorferi: an enzyme immunoassay (EIA) and a chemiluminescence assay (CLIA). In case of a positive or equivocal result, an immunoblot including in vivo antigens was performed.

Main Outcome Measures:

Course of IgM and IgG against B. burgdorferi in overall 1529 blood samples.

Results:

A total of 96.4% of all results were concordant between EIA and CLIA. Considering only samples with identical results in both assays, prevalence was 1.6%. A positive IgM was detected in 2.3%. No player showed any symptoms of Lyme disease. A seroconversion to IgG was not found. Three players developed a positive IgM corresponding to an incidence of 1032/100 000 person-years. Depending on the assay, 49% to 75% of positive or equivocal screening results could not be confirmed by immunoblot.

Conclusions:

Seroprevalence and incidence of B. burgdorferi among healthy male professional football players are low. Therefore, infections with B. burgdorferi have to be regarded a rare differential diagnosis in professional football in Central Europe. The low confirmation rate of positive screening assays points to an unspecific immune activation.
Myeloid Sarcoma of the Testis in Children: Clinicopathologic and Immunohistochemical Characteristics With KMT2A (MLL) Gene Rearrangement Correlation
Authors: El Jamal Siraj M. , Salama Abeer , Marcellino Bridget K. , Abulsayen Hend A. , Zhou Xinchun , Hassan Mohamed , Firpo-Betancourt Adolfo , Saad Ali G.
Published: June 2019

Myeloid sarcoma (MS) is defined as an extramedullary mass-forming lesion composed of immature myeloid cells. It is a rare but well-known manifestation of acute myeloid leukemia. Pediatrics testicular MS may pose a possible diagnostic challenge, an issue that is underscored in the few testicular pediatric MS cases reported in the literature. Herein, we report a series of 5 cases of pediatric testicular MS that are evaluated at the morphologic and immunohistochemical levels with correlation with the KMT2A (MLL) rearrangement status. Three patients presented with no prior history of acute myeloid leukemia. All 5 cases showed monoblastic morphology; positive for CD33, CD43, CD68, CD163, CD4 (dim), and lysozyme; and negative for CD10, CD34, CD117, and myeloperoxidase. KMT2A (MLL) rearrangement was detected in 4 of the 5 cases. In the literature, 8 more cases of pediatric testicular lymphoma were reported. Most of them showed monocytic differentiation and KMT2A (MLL) rearrangement was reported in 3 of the cases. In conclusions, testicular MS in pediatric patients shows monoblastic differentiation which may be attributed to the KMT2A (MLL) rearrangement. We also highlight the importance of using an extended immunohistochemistry panel in the diagnosis of MS.
Exploring the lower thermal limits for development of the human malaria parasite,
Plasmodium falciparum
Authors: Waite Jessica L. , Suh Eunho , Lynch Penelope A. , Thomas Matthew B.
Published: June 2019

The rate of malaria transmission is strongly determined by parasite development time in the mosquito, known as the extrinsic incubation period (EIP), since the quicker parasites develop, the greater the chance that the vector will survive long enough for the parasite to complete development and be transmitted. EIP is known to be temperature-dependent but this relationship is surprisingly poorly characterized. There is a single degree-day model for EIP of
Plasmodium falciparum
that derives from a limited number of poorly controlled studies conducted almost a century ago. Here, we show that the established degree-day model greatly underestimates the rate of development of
P. falciparum
in both
Anopheles stephensi
and
An. gambiae
mosquitoes at temperatures in the range of 17–20°C. We also show that realistic daily temperature fluctuation further speeds parasite development. These novel results challenge one of the longest standing models in malaria biology and have potentially important implications for understanding the impacts of future climate change.
MARK2/Par1b kinase present at centrosomes and retraction fibres corrects spindle off-centring induced by actin disassembly
Authors: Hart Madeleine , Zulkipli Ihsan , Shrestha Roshan Lal , Dang David , Conti Duccio , Gul Parveen , Kujawiak Izabela , Draviam Viji M.
Published: June 2019

Tissue maintenance and development requires a directed plane of cell division. While it is clear that the division plane can be determined by retraction fibres that guide spindle movements, the precise molecular components of retraction fibres that control spindle movements remain unclear. We report MARK2/Par1b kinase as a novel component of actin-rich retraction fibres. A kinase-dead mutant of MARK2 reveals MARK2's ability to monitor subcellular actin status during interphase. During mitosis, MARK2's localization at actin-rich retraction fibres, but not the rest of the cortical membrane or centrosome, is dependent on its activity, highlighting a specialized spatial regulation of MARK2. By subtly perturbing the actin cytoskeleton, we reveal MARK2's role in correcting mitotic spindle off-centring induced by actin disassembly. We propose that MARK2 provides a molecular framework to integrate cortical signals and cytoskeletal changes in mitosis and interphase.
Crohn’s disease and ulcerative colitis patient perspectives on clinical trials and participation
Authors: Ehrlich Orna , Testaverde James , Heller Caren , Daman Stuart , Anderson Annick , Higgins Peter D.R.
Published: June 2019

Background

Clinical trial recruitment is often the rate-limiting step in the development of new treatments reaching patients across all disease states. With more than 1500 currently available clinical trials for inflammatory bowel diseases (IBD) patients, it is important to understand patient perceptions of clinical trial participation to improve recruitment and retention. This study aimed to examine the specific challenges and barriers that might be reducing IBD patient enrollment and potential methods to overcome these barriers.

Methods

Five in-person patient focus groups were conducted from February through May 2016 using two facilitation guides. Participants self-reported a diagnosis of Crohn’s disease or ulcerative colitis.

Results

The five focus groups included a total of 34 participants. Participants discussed several barriers, including fears, disease severity at trial onset, potential adverse effects, time constraints, and the influence of both their primary IBD provider and support network. Methods to improve participation included better communication to prospective patients, reduced length of trial and time commitment, lower placebo rates, the option of open label extension, and support of the patient’s primary IBD provider.

Conclusions

This is the first study to examine patient perceptions for IBD clinical trial enrollment, including barriers to participation and methods to improve participation. Fear and misunderstanding of clinical trials, engagement with providers, limiting time demands, and limiting the impact on work and family were found to be barriers to participation. Creative solutions to these problems could lead to greater participation in trials and more rapid advancement of new therapies to clinical approval and use.
Formation of synthetic RNA protein granules using engineered phage-coat-protein -RNA complexes
Authors: Granik Naor , Katz Noa , Willinger Or , Goldberg Sarah , Amit Roee
Published: June 2019

Liquid-solid transition, also known as gelation, is a specific form of phase separation in which molecules cross-link to form a highly interconnected compartment with solid – like dynamical properties. Here, we utilize RNA hairpin coat-protein binding sites to form synthetic RNA based gel-like granules via liquid-solid phase transition. We show bothin-vitroandin-vivothat hairpin containing synthetic long non-coding RNA (slncRNA) molecules granulate into bright localized puncta. We further demonstrate that upon introduction of the coat-proteins, less-condensed gel-like granules form with the RNA creating an outer shell with the proteins mostly present inside the granule. Moreover, by tracking puncta fluorescence signals over time, we detected addition or shedding events of slncRNA-CP nucleoprotein complexes. Consequently, our granules constitute a genetically encoded storage compartment for protein and RNA with a programmable controlled release profile that is determined by the number of hairpins encoded into the RNA. Our findings have important implications for the potential regulatory role of naturally occurring granules and for the broader biotechnology field.
Thirty years of Doi Moi in the museum
Authors: Were Graeme
Published: June 2019

Purpose

The purpose of this paper is to describe an exhibition that celebrated 30 years of reform in the Vietnamese National Museum of History, which opened in 2016. It contributes to anthropological understandings of the way exhibitions create new forms of cultural heritage, and so operate as a kind of technology of governance for legitimising state transformations that seek to celebrate neoliberal ideologies and the rise of the individual.

Design/methodology/approach

Using an ethnographic methodology, it explores some of the behind-the-scenes decisions involved in producing a narrative of national development since the Doi Moi reforms of 1986.

Findings

In analysing how imported memory approaches were innovatively employed alongside conventional historical facts, this paper reveals ways in which old revolutionary narratives make way for expansive and more acceptable concepts of development that embrace well-being and quality of life as well as national achievements.

Originality/value

This research is based on original ethnographic research conducted by the author and contributes to an emerging field of museum and heritage studies in East and South-East Asia.
Assessing consumer attitudes and perceptions towards food authenticity
Authors: Chousou Charoula , Mattas Konstadinos
Published: June 2019

Purpose

The purpose of this paper is to identify and assess the factors that consumers evaluate significant in the assessment of food authenticity and guide them to make safe food choices.

Design/methodology/approach

In this respect, a mixture model for consumer preferences, namely CUB, was employed due to the ability of discriminate features that are rated similarly allowing the detection of significant similarities and differences in consumers’ judgments. Moreover, introducing covariates in CUB models allow studying the influence that consumers’ socio-demographic characteristics have on the importance of the attributes used in the assessment of food authenticity.

Findings

The results demonstrate that organic certificate, traditional and homemade production practices, origin certificate as well as information about product’s origin country and raw materials production region are significant quality cues enable consumers to judge food authenticity. In addition, consumers further segmentation according to socio-demographic characteristics indicate that country of origin information are mainly used by middle-aged consumers, highly educated and paid, whereas production techniques and organic certification constitute the most effective indicators for judging food authenticity by older consumers.

Originality/value

The paper confirms that consumers can use extrinsic and intrinsic quality cues to judge food’s authenticity.
Sustainability and human competences: a systematic literature review
Authors: Galleli Barbara , Hourneaux Jr Flavio , Munck Luciano
Published: June 2019

Purpose

The purpose of this paper is to identify and discuss human competences required for sustainability management in organisations.

Design/methodology/approach

The research is based on a systematic review of the literature, through qualitative thematic analysis.

Findings

The research covered 15 years of scientific publications and was summarised in 43 articles. It revealed that education, more than management, was the field of knowledge with more references in human competences, through exploratory methodological approaches. The competences found were plenty, but there is still some misunderstanding regarding their conceptual and theoretical bases.

Research limitations/implications

This research provides evidence that the academic knowledge on the subject is still at its initial stage, and it exposes the debility of the management area in addressing the subject.

Practical implications

The authors intend to indicate to managers some fundamentals for the adoption of human competences for sustainability aiming at a more sustainable performance in organisations.

Social implications

The results may instigate studies concerning the fit of sustainability competences developed on higher education institutions and the job market. From it, curricula and pedagogical projects can be proposed and revised with better alignment to the organisational context.

Originality/value

This paper presents a theoretical contribution by building bridges among different perspectives and fields of knowledge on the topic. The paper also offers a managerial contribution by stimulating practical discussions to develop sustainability in organisations through individuals.