bluuebunny/crossref_metadata_2025 huggingface dataset:
Methods of Teaching or Discovery? Analysis and Synthesis from Zabarella to Spinoza
Authors: Hattab Helen
Published: December 2020

This contribution looks directly at the so-called novatores and their own appropriation and reworking of the traditional methodological and pedagogic approaches. It shows how academic approaches and established tradition worked not only as a polemical target but also as a crucial resource that nourished the growth of alternatives to academic and Aristotelian approaches. This point is developed by discussing in detail the problem of method in Spinoza, and by connecting it with its scholastic background. By the mid-seventeenth century proponents of controversial philosophies appropriated more familiar didactic genres to convey their radical doctrines. For instance, the first book of Thomas Hobbes’s De Corpore follows the familiar order of standard Scholastic Aristotelian logic textbooks, and Baruch Spinoza’s Ethics emulates Euclid’s Elements, by presenting astounding conclusions about nature and extension more geometrico. There is a long-standing debate regarding whether Spinoza’s geometrical method is a method of discovery or merely a method of presentation. This contribution examines Spinoza’s reflections on method in the Treatise on the Emendation of the Intellect in the context of contemporaneous conceptions of analysis and synthesis found in the works of Zabarella, Burgersdijk, Descartes, and Hobbes to identify the most plausible readings of his method in the Ethics.
Broken Hebrewist Vessels
Authors: Shelleg Assaf
Published: December 2020

Whereas the music Mordecai Seter wrote in 1966 embodies a clash between his unsignified semiotic procedures and the national redemptive trajectories that animated them, Andre Hajdu’s music in 1970 knowingly staged unwanted sonic adjacencies of the Jewish Eastern European soundscape alongside Christian music from late medieval Europe. Both composers sought de-signification—either by eschewing ethnographic imports in the form of folk or liturgical music (Seter), or through violent deconstructions of seemingly opposing musical markers of Jews and Christians (Hajdu). The works of both therefore disclose meaningful disharmonie: both manifest the disabling of Zionist tropes and the concomitant reclaiming of the ethnic specificity of diasporic Ashkenazi culture. This chapter also reads the late music of Seter and Ben-Haim against the background of their notebooks and diaries, in addition to two seminal literary works—Past Continuous (1977) by Yaakov Shabtai and Unto Death (1969) by Amos Oz—that record admixtures of diasporic Jewish subcultures and the fallouts of a post-ideological age.
Conclusion
Authors: Nethercut Jason S.
Published: December 2020

LET ME END where I began: this has not been a book about Ennius’ Annales, but about Lucretius’ reconstruction of Ennius’ Annales. I have expanded our understanding of Lucretius’ relationship to Ennius well beyond what has been argued traditionally. On my analysis, Lucretius’ engagement with Ennius is dynamic and thoroughgoing. Lucretius’ ubiquitous Ennian style serves, on the one hand, to signal to the reader that a passage should be read with Ennius in mind and, on the other, to announce a sort of stylistic reflexive annotation of actual allusions to the content of the ...
The Ins and Outs of Measuring Income Inequality in the United States
Authors: Rose Stephen
Published: December 2020

Although measuring income inequality seems straightforward and uncontroversial, methodological issues greatly affect findings. This chapter shows that changes in real median income between 1979 and 2014 across six studies varied from negative 8 percent to positive 51 percent. Furthermore, the share of growth going to the top ten percent during these years in four studies ranged from 31 percent to 100 percent. The first choice that researchers make is choosing a dataset or linked datasets. This choice affects the income sharing unit, be it households, families, individuals, or tax units. The next choice is the definition of income, with the starting point being cash market income only—earnings, dividends, rents, interest payments, or business profits. This total can be expanded by including government cash benefits, employer benefits, the rental value of home ownership, and government and financial services that people don’t pay for. Even after the income concept is chosen, income can be presented as adjusted for family size and either before or after taxes. Finally, adjusting for inflation to change nominal incomes into inflation-adjusted incomes can be performed in a variety of ways.
Introduction
Authors: Porter Ethan
Published: December 2020

This chapter blends insights from political science, behavioral economics, history and psychology to lay out the theoretical proposition of the book. The consumer citizen approach has implications for attitudes toward government and government spending, levels of political knowledge, and even whether people sign up for government-sponsored health insurance. Empirical evidence about the incidence of consumer and political decisions is offered. The comparative ubiquity of consumer decisions, I argue, explains why consumer decision-making tools come to be used in political contexts. Ultimately, viewing citizens as consumer citizens means viewing their political behaviors and attitudes as they are, not as some might wish them to be.
The Consumer Citizen and Consumer Fairness
Authors: Porter Ethan
Published: December 2020

Consumer fairness matters for public opinion. Taxpayer receipts, despite the hopes of those who championed them, do not improve trust in government nor affect attitudes toward taxing and spending. Instead, consumer fairness can be used to change attitudes toward government. This chapter introduces the idea of “alignability”; this idea proposes that people want either (a) the amount they pay government, in the form of taxes, to roughly align with the value of the benefits they receive in return (cost-benefit alignability), or (b) the use of their tax money to align with the source of its collection (source-use alignability). Multiple experiments, conducted online and once in person, make clear how alignability can affect attitudes toward taxation. Alignability can affect attitudes toward taxes in general, as well as attitudes toward earmarked taxes specifically.
Human Rights Advocacy in Global Health
Authors: Amon Joseph J. , Friedman Eric
Published: December 2020

This chapter presents an overview of health and human rights advocacy and describes a broad framework and the diverse strategies used by human rights advocates to advance their goals. Based upon documenting abuses, raising awareness, building coalitions, and engaging communities, human rights advocacy seeks to ensure that government laws, policies, and practices respect, protect, and fulfill the right to health of all. These rights arguments and advocacy strategies, first developed in response to the HIV epidemic, have become the basis for broader right to health campaigns. Health-related human rights advocacy, beyond specific strategies, seeks to elevate the voices of people affected by human rights violations, analyze structural barriers, and identify obligations and responsibilities. Focusing on the strategies and tools that human rights advocates use in documenting rights abuses, raising awareness, and seeking change, it is necessary to examine new advocacy partnerships and approaches for evaluating advocacy efforts.
Divisibility or Indivisibility
Authors: Sattler Barbara M.
Published: December 2020

This chapter aims to show that the earliest discussion about continuity in Western thought is a debate within metaphysics and natural philosophy about homogeneity and divisibility. All parties to this dispute – the main proponents are Parmenides, Zeno, and Aristotle – agree that magnitudes which are continuous (suneches) are homogenous and without any gaps. They disagree, however, on which inferences to draw from this for the possibility of divisibility – whether it implies indivisibility, as Parmenides and Zeno assumed, or divisibility, as Aristotle claimed, building on a mathematical understanding of extended magnitudes. Furthermore, while a modern understanding of continuity may seem to be essentially anti-Aristotelian, Aristotle is shown to prepare many of the crucial features of a modern account of continuity in this debate.
Regulating Digital Platforms
Authors: Baldwin Robert , Cave Martin
Published: December 2020

One of the most pressing regulatory challenges of recent years has been what to do about the hugely successful digital platform and related companies which now bestride the world. Their emergence provides a brutal and urgent test for positive regulation: Can legislators and regulators maintain the benefits generated by such influential new actors, but also control the adverse effects? This chapter focuses on the challenges posed by the platforms’ abuses of their market power. It starts with an exposition of the special features of two-sided platforms which may create a heightened or special need for regulation. It then considers how these features might play out, and focuses on the risk of markets ‘tipping’ into monopolies. It then discusses how general competition law might be strengthened to keep up with the new dynamics of digital platforms and how competition law can be supplemented by additional regulatory interventions. The concluding section discusses prospects for positive regulation meeting these new challenges.
Guido Guinizzelli
Authors: Bowe David
Published: December 2020

Chapter 2 introduces the poetry of Guido Guinizzelli in the context of thirteenth-century literary networks and exchange, especially the tenzone tradition. The chapter focusses on Guinizzelli’s outward-looking version of dialogic subjectivity, through which he refines his poetic voice in relation to, and response to, external forces and others’ voices, including Guittone and Bonagiunta. The analysis of Guinizzelli’s poems, including ‘Al cor gentil’ shows how his subjectivity and poetics develop through the statement and restatement of poetic positions in the dialogic interactions of tenzoni with other poets and in dialogue with the voice of God.
Contractual Interpretation and Protection against Unfair Terms in Indonesia
Authors: Bell Gary F
Published: December 2020

This chapter examines the Indonesian law on contractual interpretation and the regulation of unfair terms. With regard to the former, it discusses two closely connected issues in defining the contents of contracts: the approaches adopted in interpreting the meaning of agreed contractual terms, as well as to what extent additional terms are implied to supplement the express terms. It discusses the underlying philosophy of interpretation with regard to the dichotomy of ‘objective’ and ‘subjective’ approaches; it details the various interpretative aids, such as customs, usages, the commercial background, good faith, and the negotiations of the parties; and it shows how Indonesian law resolves the tension between literalist and contextualist approaches to interpretation. With regard to the latter, the chapter shows that Indonesian contract law has only limited responses available to tackle extremely one-sided, onerous, or otherwise unfair terms, such as exclusions or limitations of liability, penalty clauses, or restraint of trade clauses. It discusses the overt judicial control of such terms under specific legislation, targeted exclusively at standard terms in consumer contracts. Attention is also paid to the enforcement mechanisms for measures of consumer protection. The chapter further analyses how the Indonesian courts have exercised a control by employing traditional general contract law doctrines such as good faith and equity, including the rules on interpretation, in order to protect parties against the imposition of unfair terms. A number of hypothetical scenarios illustrate how the courts in Indonesia deal with issues of contractual interpretation and gap-filling and how they regulate unfair terms in practice.
Werewolves and Projected Souls
Authors: Ogden Daniel
Published: December 2020

This chapter argues that the ideas of soul-projection so strongly associated with werewolfism in the medieval and early modern periods were already associated with it in the ancient world. This notion is more or less explicitly articulated by Augustine, but long before him there obtained a striking parallel between werewolf narratives (in which the werewolf off on his adventures leaves behind the human shell constituted by his clothes and must keep them secure, so that he can don them again to retrieve his human form), and the ‘Greek shaman’ narratives (in which the soul-projector must keep his catatonic human body secure as he sends his soul off on his adventures, so that the soul can reanimate it again and he can continue his physical life in the world). Petronius’ intriguingly complex werewolf narrative, when taken with other evidence, presupposes the existence already in antiquity of other werewolf narratives broadly along the lines of Marie de France’s Bisclavret in which a werewolf, perhaps an innkeeper, is stranded in lupine form when his clothes are stolen by his unfaithful wife.
Bundle Prolongations and Connections
Authors: Canarutto Daniel
Published: December 2020

A synthetic introduction to the fundamental notions of differential geometry, including tangent, vertical and jet prolongations of fibered manifolds; the Frölicher-Nijenhuis bracket; connections of fibered manifolds and, in particular, linear connections of vector bundles and tangent bundles; the covariant differential of vector-valued forms as a generalisation of the standard covariant derivative.
Bundles of Quantum States
Authors: Canarutto Daniel
Published: December 2020

A brief introduction to Frölicher's notion of smoothness (F-smoothness) leads to a natural definition of a distributional bundle, that is a bundle whose fibers are distributional spaces constituted of generalised sections of 2-fibered classical bundles. Indeed the essential notions of finite-dimensional differential geometry can be seamlessly extended to such bundles. The case when the underlying classical bundle is a vector bundle over a mass-shell bundle yields the bundle of quantum states of a multi-particle system.
Mathematical Knowledge and Sentential vs. Subsentential Priority
Authors: Weiner Joan
Published: December 2020

In this chapter, as in Chapter 7, an example is given that shows how Frege’s lessons can be put to work on contemporary issues. The focus here is on two papers, written by Paul Benacerraf in 1965 and 1973, that are still of concern to many philosophers today. In the first, Benacerraf argues that, although it seems obvious that numbers are objects, in fact numbers cannot be objects. In the second, Benacerraf presents an epistemological puzzle that seems to undermine our claims to have mathematical knowledge—even knowledge of elementary facts about numbers. These puzzles challenge our everyday understanding both of the nature of numbers and of our knowledge about them. In this chapter, it is argued that both puzzles depend on our presupposing the subsentential priority view. And both puzzles, it is argued, vanish once we accept Frege’s sentential priority view.
Space and Power in the Syro-Anatolian Culture Complex
Authors: Osborne James F.
Published: December 2020

This chapter develops insights from recent social theory in space and place that emphasizes the socially contingent nature of the built environment and its perception by those who dwell within it. Spatial analysis of settlement patterns within the Syro-Anatolian Culture Complex illustrates that rather than being evenly distributed across the landscape, as per the vision of territoriality in the modern nation-state, power at the regional scale was highly variable and swift to change, a phenomenon referred to as malleable territoriality. Each kingdom’s capital city was a tightly coordinated nexus of symbols that celebrated royal authority to pedestrians in such a way that no matter where one turned, as one moved through the city, the legitimacy of the royal figure was constantly being reinforced. Yet as soon as one moved into a settlement lower on the settlement hierarchy, one sees that the political is far less evident, even absent. And even in the capital cities themselves, those indicators of royal power are frequently found smashed into pieces. Spatial analysis therefore indicates that not only was power expressed and experienced differently depending on one’s location in the built environment, it was also something that could be contested.
Conclusion
Authors: Osborne James F.
Published: December 2020

This chapter provides a summary of the preceding chapters’ two primary arguments: first, that the Syro-Anatolian Culture Complex (SACC) was a critical player in the political and cultural world of the Iron Age; and, second, that a new model needs to be used to describe it, one that celebrates diversity, mobility, fluidity, and hybridity. A preliminary list of attributes that characterizes SACC is offered. Finally, the chapter closes with a consideration of those aspects of SACC that require additional research, especially its Late Bronze Age antecedents and its interaction with other neighbors and contemporaries.
Banks and Brokers, 2007–20
Authors: Michie Ranald C.
Published: December 2020

Before the crisis the megabanks had established themselves at the centre of the world’s financial system, transcending national boundaries and time zones as they extended their operations around the globe. These banks also spread themselves over a growing diversity of activities that destroyed the compartmentalized structures of the past.Such was their size, scale, and spread, and the structure of the business they conducted, that these banks were regarded as too-big-to-fail not only by those who worked for them, used them, and traded with them but also by the regulators responsible for supervising financial systems and the central banks tasked with preserving financial and monetary stability. It was this world that appeared to evaporate with the Global Financial Crisis. That turned out not to be the case. Though curbs were placed on the megabanks they turned out to be indispensible in an age of globalization and the only available mechanism through which regulators and central banks could exercise a degree of control over the financial system. What remained after the crisis was a small number of even more powerful US-based megabanks along with an equivalent group of US-based megafunds.
Commodities and Derivatives, 2007–20
Authors: Michie Ranald C.
Published: December 2020

By the beginning of the twenty-first century the role of commodity exchanges was to set reference prices for both commodities and financial products. Actual trading took place directly between producers and consumers or buyers and sellers. The exchanges provided heavily traded standardized contracts that were highly liquid, but charged for the service they provided and imposed strict rules and regulations. In contrast, direct trading between buyers and sellers was conducted free of charge and customized to suit the interests of particular buyers and sellers. It was those contracts traded away from the exchanges that many blamed for the crisis because of their contribution to increased risk taking. As a result there were moves to ban such contracts and to bring all derivatives trading onto regulated exchanges. However, derivatives proved to be essential features of volatile markets and exchanges were unable to provide the ease and flexibility that users found in the OTC market. As a result the derivatives market recovered from the crisis as the products it provided remained indispensable.
Iran
Authors: Axworthy Michael
Published: December 2020

Since the beginning of recorded history, Iran/Persia has been one of the most important world civilizations. Iran remains a distinct civilization today despite its status as a major Islamic state with broad regional influence and its deep integration into the global economy through its vast energy reserves. Yet the close attention paid to Iran in recent decades stems from the impact of the 1979 revolution, which unleashed ideological shock waves throughout the Middle East that reverberate to this day. Many observers look at Iran through the prism of the Islamic Republic's adversarial relationship with the US, Israel, and Sunni nations in its region, yet as Michael Axworthy shows in Iran: What Everyone Needs to Know, there is much more to contemporary Iran than its fraught and complicated foreign relations. He begins with a concise account of Iranian history from ancient times to the late twentieth century, following that with sharp summaries of the key events since the1979 revolution. The final section of the book focuses on Iran today--its culture, economy, politics, and people--and assesses the challenges that the nation will face in coming years. Iran will be an essential overview of a complex and important nation that has occupied world headlines for nearly four decades.
Artificial Intelligence
Authors: Kaplan Jerry
Published: December 2020

Over the coming decades, Artificial Intelligence will profoundly impact the way we live, work, wage war, play, seek a mate, educate our young, and care for our elderly. It is likely to greatly increase our aggregate wealth, but it will also upend our labor markets, reshuffle our social order, and strain our private and public institutions. Eventually it may alter how we see our place in the universe, as machines pursue goals independent of their creators and outperform us in domains previously believed to be the sole dominion of humans. Whether we regard them as conscious or unwitting, revere them as a new form of life or dismiss them as mere clever appliances, is beside the point. They are likely to play an increasingly critical and intimate role in many aspects of our lives. The emergence of systems capable of independent reasoning and action raises serious questions about just whose interests they are permitted to serve, and what limits our society should place on their creation and use. Deep ethical questions that have bedeviled philosophers for ages will suddenly arrive on the steps of our courthouses. Can a machine be held accountable for its actions? Should intelligent systems enjoy independent rights and responsibilities, or are they simple property? Who should be held responsible when a self-driving car kills a pedestrian? Can your personal robot hold your place in line, or be compelled to testify against you? If it turns out to be possible to upload your mind into a machine, is that still you? The answers may surprise you.
North Korea
Authors: McEachern Patrick
Published: December 2020

After a year of trading colorful barbs with the American president and significant achievements in North Korea’s decades-long nuclear and missile development programs, North Korean leader Kim Jong Un declared mission accomplished in November 2017. Though Kim's pronouncement appears premature, North Korea is on the verge of being able to strike the United States with nuclear weapons. South Korea has long been in the North Korean crosshairs but worries whether the United States would defend it if North Korea holds the American homeland at risk. The largely ceremonial summit between US president Donald Trump and Kim Jong Un, and the unpredictability of both parties, has not quelled these concerns and leaves more questions than answers for the two sides' negotiators to work out. The Korean Peninsula’s security situation is an intractable conflict, raising the question, “How did we get here?” In this book, former North Korea lead foreign service officer at the US embassy in Seoul Patrick McEachern unpacks the contentious and tangled relationship between the Koreas in an approachable question-and-answer format. While North Korea is famous for its militarism and nuclear program, South Korea is best known for its economic miracle, familiar to consumers as the producer of Samsung smartphones, Hyundai cars, and even K-pop music and K-beauty. Why have the two Koreas developed politically and economically in such radically different ways? What are the origins of a divided Korean Peninsula? Who rules the two Koreas? How have three generations of the authoritarian Kim dictatorship shaped North Korea? What is the history of North-South relations? Why does the North Korean government develop nuclear weapons? How do powers such as Japan, China, and Russia fit into the mix? What is it like to live in North and South Korea? This book tackles these broad topics and many more to explain what everyone needs to know about South and North Korea.
Violence against Women
Authors: True Jacqui
Published: December 2020

Violence against women and girls (VAWG) is a longstanding problem that has increasingly come to the forefront of international and national policy debates and news: from the US reauthorization of the Violence against Women Act and a United Nations declaration to end sexual violence in war, to coverage of gang rapes in India, cyberstalking and "revenge porn", honor killings, female genital mutilation, and international trafficking. Yet, while we frequently read or learn about particular experiences or incidents of VAWG, we are often unaware of the full picture. Jacqui True, an internationally renowned scholar of globalization and gender, provides an expansive frame for understanding VAWG in this book. Among the questions she addresses include: What are we talking about when we discuss VAWG? What kinds of violence does it encompass? Who does it affect most and why? What are the risk factors for victims and perpetrators? Does VAWG occur at the same level in all societies? Are there cultural explanations for it? What types of legal redress do victims have? How reliable are the statistics that we have? Are men and boys victims of gender-based violence? What is the role of the media in exacerbating VAWG? And, what sorts of policy and advocacy routes exist to end VAWG? This volume addresses the current state of knowledge and research on these questions. True surveys our best understanding of the causes and consequences of violence against women in the home, local community, workplace, public, and transnationally. In so doing, she brings together multidisciplinary perspectives on the problem of violence against women and girls, and sets out the most promising policy and advocacy frameworks to end this violence.
Russia
Authors: Colton Timothy J.
Published: December 2020

Today’s Russia, also known as the Russian Federation, is often viewed as less powerful than the Soviet Union of the past. When stacked against other major nations in the present, however, the new Russia is a formidable if flawed player. Russia: What Everyone Needs to Know® provides fundamental information about the origins, evolution, and current affairs of the Russian state and society. The story begins with Russia’s geographic endowment, proceeds through its experiences as a kingdom and empire, and continues through the USSR’s three-quarters of a century, and finally the shocking breakup of that regime a generation ago. Chapters on the failed attempt to reform Communism under Mikhail Gorbachev, the halting steps toward democratization under Boris Yeltsin, and the entrenchment of central controls under Vladimir Putin bring the reader into the contemporary scene and to headline-grabbing events such as Russia’s annexation of the Crimean Peninsula from Ukraine and its military intervention in Syria. Drawing on trends within Russia and on ratings and rankings compiled by international organizations, Colton discusses the challenges facing the country--ranging from economic recession to demographic stress, political stagnation, and overextension in foreign policy--and to the realistic options for coping with them. The book shows that, although Russia is not imprisoned by its history, it is heavily influenced by it. Colton illustrates Russia’s greatest strength and, ironically, its greatest weakness: the ability of its people to adapt themselves to difficult circumstances beyond their immediate control. Russia, as Putin has asserted, will not soon be a second edition of the United States or Britain. But, Colton shows, there are ways in which it could become a better version of itself.
Spine Metastasis in Elderly
Authors: Beaufort Quentin , Terrier Louis-Marie , Dubory Arnaud , Le Nail Louis-Romée , Cook Ann-Rose , Cristini Joseph , Buffenoir Kévin , Pascal-Moussellard Hugues , Carpentier Alexandre , Mathon Bertrand , Amelot Aymeric
Published: December 2020

Mini

The incidence of spinal metastasis (SpM) is increasing, and life expectancy for patients with malignancy is also rising. The “elderly" represent a population with steady growth in SpM proportion. Bracing is associated with lower survival. We believe that surgery should be considered, regardless of the patient's age.

Study Design.

Multicentric prospective study.

Objective.

Through this study, we aimed to clarify and update the prognostic assessment of elderly with spine metastasis (SpM).

Summary of Background Data.

The incidence SpM is rising, in parallel life expectancy is getting longer and the number of elderly patients presenting malignancy is increasing. Elderly patients with SpM constitute a growing heterogeneous population

Methods.

The patient data used in this study were obtained from a French national multicenter database of patients treated for SpM between 2014 and 2017. Two hundred and forty-three consecutive patients >70 years’ old were diagnosed.

Results.

Median overall survival (OS) time for elderly patients following the event of SpM was 16.3 months. First, we identified significantly worse survival prognostic factors for elderly patients with SpM: poor WHO status 3/4: (hazard ratio [HR]: 2.245, 95% confidence interval [CI] 1.899–2.655; P < 0.0001), >80 years (HR: 1.758, 95% CI 1.117–2.765; P = 0.015) no-ambulatory neurological status (Franckel A/B status [HR: 3.219, 95% CI 1.621–6.390; P < 0.0001)], gastrointestinal cancer (HR: 3.530, 95% CI 1.75–7.1; P < 0.0001), lung cancer (HR: 3.452, 95% CI 1.784–6.680; P < 0.0001), orthopedic brace treatment (HR: 1.329; 95% CI 1.050–1.683; P = 0.018), and epiduritis (HR: 1.52, 95% CI 1.041–2.22; P = 0.03) were independently poor prognostic factors of survival. The only good prognosis factor identified was thyroid cancer (HR: 0.257, 95% CI 0.07–0.952; P = 0.04).

Conclusion.

Prognosis factors concerning the survival of elderly patients seem to be the same as those for the general population such as primary cancer histology, neurological status, WHO status, and epiduritis. Age >80 years also appears to be an independently poor prognosis factor. Our data suggest that orthopedic brace treatment is also associated with lower survival.

Level of Evidence: 2
Pseudoexfoliation syndrome and glaucoma: from genes to disease mechanisms
Authors: Schlötzer-Schrehardt Ursula , Khor Chiea Chuen
Published: December 2020

Purpose of review

The genetic basis of pseudoexfoliation (PEX) syndrome, the most common identifiable cause of open-angle glaucoma, is steadily being elucidated. This review summarizes the recent advances on genetic risk factors for PEX syndrome/glaucoma and their potential functional implications in PEX pathophysiology.

Recent findings

As of today, seven loci associated with the risk of PEX surpassing genome-wide significance have been identified by well-powered genome-wide association studies and sequencing efforts. LOXL1 (lysyl oxidase-like 1) represents the major genetic effect locus, although the biological role of common risk variants and their reversed effect in different ethnicities remain an unresolved problem. Rare protein-coding variants at LOXL1 and a single noncoding variant downstream of LOXL1 showed no allele effect reversal and suggested potential roles for elastin homeostasis and vitamin A metabolism in PEX pathogenesis. Other PEX-associated genetic variants provided biological insights into additional disease processes and pathways, including ubiquitin-proteasome function, calcium signaling, and lipid biosynthesis. Gene-environment interactions, epigenetic alterations, and integration of multiomics data have further contributed to our knowledge of the complex etiology underlying PEX syndrome and glaucoma.

PEX-associated genes are beginning to reveal relevant biological pathways and processes involved in disease development. To understand the functional consequences and molecular mechanisms of these loci and to translate them into novel therapeutic approaches are the major challenges for the future.
Beta-blockers in chronic obstructive pulmonary disease: the good, the bad and the ugly
Authors: Leitao Filho Fernando Sergio , Choi Lauren , Sin Don D.
Published: December 2020

Purpose of review

Several observational studies have suggested that β-blockers, especially cardioselective ones, are well tolerated and associated with a lower risk of acute exacerbations and death in patients with chronic obstructive pulmonary disease (COPD). However, there are dissenting studies. This review provides an update on the use of β-blockers in COPD, focusing on results of recent prospective studies and randomized controlled trials.

Recent findings

In totality, cohort studies indicate that β-blockers are generally well tolerated and effective in COPD patients who also have a clear cardiovascular indication for these medications. Although β-blockers on average reduce lung function acutely in COPD patients, the absolute decrease is relatively small, especially if cardioselective β-blockers are used. The results of two large randomized controlled trials suggest that β-blocker use does not reduce the therapeutic benefits of inhaled bronchodilators in COPD patients. The use of β-blockers in COPD patients, who do not have overt cardiovascular disease, does not prevent COPD exacerbations and may paradoxically increase the risk of COPD-related hospitalization and mortality.

The use of β-blockers is generally well tolerated and effective in COPD patients, who also have a clear cardiovascular indication for these drugs. However, they should not be used in patients who do not have overt cardiovascular disease as β-blockers can reduce lung function, worsen health status and increase the risk of COPD-related hospitalization.
Genetically increased circulating 25(OH)D level reduces the risk of type 2 diabetes in subjects with deficiency of vitamin D
Authors: Xu Yingying , Zhou Yuan , Liu Jingjing , Wang Chenfang , Qu Zhongjie , Wei Zhili , Zhou Dan
Published: December 2020

Observational studies have reported that Vitamin D deficiency and the risk type 2 diabetes are associated, but the causation is unclear. Mendelian randomization (MR) involving genetic variants as instrument variables (IVs) overcomes the reverse-casualty and unmeasured confounding. However, with limited sample size and IVs, previous MR studies showed inconsistent results. Leveraging by a largely increased sample size for both stages, we aim to provide an updated and precise estimate for the causality between Vitamin D and type 2 diabetes.

A 2-sample multi-IVs MR was performed. IVs for circulating 25-hydroxyvitamin D (25(OH)D) were obtained from a genome-wide association study from UK biobank involving 329,247 subjects of European ancestry. The causal effect of 25(OH)D and type 2 diabetes was estimated using traditional inverse variance weighting and MR pleiotropy residual sum and outlier (MR-PRESSO) framework which provides a robust estimate by systematically filtering out IVs identified with potential pleiotropy effects.

A higher genetically instrumented 25(OH)D was causally linked to reduced risk of type 2 diabetes risk by MR-PRESSO [odds ratio (OR) per standard deviation (SD) = 0.950, 95% confidence interval (CI) = 0.913–0.988, P = .010] after removing 13 (13/193) invalid IVs. In addition, we confirmed the causal role Vitamin D using 2 synthesis-related single-nucleotide polymorphisms (SNPs) which are consistent with previous MR studies [OR per SD = 0.894, 95% CI = 0.816–0.979, P = .016].

With a largely improved sample size, our results confirmed that genetically increased 25(OH)D concentration reduced the risk of type 2 diabetes and provided a more precise estimate for the effect size. The updated result empowers the role of Vitamin D and provides nontrivial evidence for interventional studies.
Effect of acupuncture treatment on post-stroke cognitive impairment
Authors: Du Yuzheng , Zhang Lili , Liu Wei , Rao Chang , Li Boxuan , Nan Xi , Li Zefang , Jiang Hailun
Published: December 2020

Introduction:

Post-stroke cognitive impairment (PSCI), which has a high morbidity, is closely associated with the recurrence and rehabilitation of ischemic stroke. There are 2 different stages of PSCI, including post-stroke cognitive impairment with no dementia (PSCIND) and post-stroke dementia (PSD). The latter has a significantly higher mortality rate than the previous one. Therefore, preventing the onset of PSD is of vital importance. However, there is no unequivocally effective prevention or treatment for PSCI, except intensive secondary prevention of stroke. The primary aim of this protocol is to explore whether acupuncture can improve cognitive function of patients with PSCIND and reduce the chances of developing PSD. On this bias, we also want to explore its possible mechanisms.

Methods and analysis:

A prospective, multicenter, large sample, randomized controlled trial will be conducted. A total of 360 eligible patients will be recruited from 5 different hospitals and randomly allocated into the acupuncture group (AG), sham acupuncture group (NAG), and waiting-list group (WLG) in a 1:1:1 ratio. The intervention period of NAG and AG will last 3 months (30 minutes per day, 3 times per week). Primary and secondary outcomes will be measured at baseline, 12 weeks (at the end of the intervention), 24 weeks (after the 12-week follow-up period), and 36 weeks (after the 24-week follow-up period). Resting-state and task-state functional MRI will be conducted at baseline and 12 weeks.

Ethics and dissemination:

The ethic committee of First Teaching Hospital of University of Traditional Chinese Medicine approved the study. Study results will be first informed to each participant and later disseminated to researchers, and the general public through courses, presentations and the internet, regardless of the magnitude or direction of effect. The results will also be documented in a published peer-reviewed academic journal.

Registration:

We have registered at ClinicalTrials.gov(ChiCTR2000033801).
Outcomes of dissolution therapy and monitoring for stone disease: should we do better?
Authors: Tzelves Lazaros , Mourmouris Panagiotis , Skolarikos Andreas
Published: December 2020

Purpose of review

Surgical management is the cornerstone of urolithiasis treatment, but high recurrence rates and associated complications necessitate the existence of medical treatment options, aiming at dissolution of kidney stones and prevention of recurrence. The purpose of this review is to present the most recent knowledge existing in scientific literature, regarding dissolution therapy and ways of monitoring nephrolithiasis patients.

Recent findings

A number of laboratory studies have been performed testing experimental treatments (tolvaptan, chlorthalidone, atorvastatin, a-lipoic acid, glucosaminoglycans, plant extracts), to reduce kidney stone formation and cellular damage and showed encouraging results. Uric acid stones is the main target of dissolution therapy, but until last years, existing level of evidence was low. A number of prospective and randomized studies, proved the efficacy and safety of oral chemolysis for radiolucent stones and associated prognostic features of success. Tolvaptan and a-Lipoic acid were also tested in patients with cystinuria and resulted in reduction of recurrence. Finally, some new diagnostic markers are suggested as tests for the monitoring of urolithiasis patients, with satisfying accuracy and discriminative ability.

Medical dissolution therapy for nephrolithiasis is an effective option, especially for patients with radiolucent/uric acid stones. In the future, we need clinical trials to confirm the encouraging results of pilot studies testing several agents for patients with cystinuria.
Uterine-Artery Embolization or Myomectomy for Uterine Fibroids
Authors: Manyonda Isaac , Belli Anna-Maria , Lumsden Mary-Ann , Moss Jonathan , McKinnon William , Middleton Lee J. , Cheed Versha , Wu Olivia , Sirkeci Fusun , Daniels Jane P. , McPherson Klim
Published: December 2020

(Abstracted from N Engl J Med 2020;383:440–451)

The most common type of tumor among women of reproductive age is uterine fibroids. The prevalence of these tumors increases with age.
Micronized Vaginal Progesterone to Prevent Miscarriage: A Critical Evaluation of Randomized Evidence
Authors: Coomarasamy Arri , Devall Adam J. , Brosens Jan J. , Quenby Siobhan , Stephenson Mary D. , Sierra Sony , Christiansen Ole B. , Small Rachel , Brewin Jane , Roberts Tracy E. , Dhillon-Smith Rima , Harb Hoda , Noordali Hannah , Papadopoulou Argyro , Eapen Abey , Prior Matt , Di Renzo Gian Carlo , Hinshaw Kim , Mol Ben W. , Lumsden Mary Ann , Khalaf Yacoub , Shennan Andrew , Goddijn Mariette , van Wely Madelon , Al-Memar Maya , Bennett Phil , Bourne Tom , Rai Raj , Regan Lesley , Gallos Ioannis D.
Published: December 2020

(Abstracted from Am J Obstet Gynecol 2020;223(2):167–176)

Historically, a lack of methodologically strong and generalizable studies has limited policy makers from recommending the use of progesterone supplementation to improve outcomes in women at high risk of miscarriage. The PROMISE and PRISM trials were carried out to rectify this and generate robust evidence on the role of progesterone supplementation to prevent miscarriage.
Smartphone-Based Financial Incentives to Promote Smoking Cessation During Pregnancy: A Pilot Study
Authors: Kurti Allison N. , Tang Katherine , Bolivar Hypatia A. , Evemy Carolyn , Medina Norman , Skelly Joan , Nighbor Tyler , Higgins Stephen T.
Published: December 2020

(Abstracted from Prev Med 2020;9:106201)

Smoking during pregnancy is a leading cause of preventable perinatal complications. Yet, its prevalence among pregnant women in the United States has remained about the same over the last decade—approximately 13%.
Adhaeribacter radiodurans sp. nov., isolated from the rhizospheric soil of Elymus tsukushiensis, a plant native to the Dokdo Islands, Republic of Korea
Authors: Hwang Ye-Ji , Son Jin-Soo , Lee Soo-Yeong , Kim Min-Ji , Park Jong Myong , Shin Jae-Ho , Ghim Sa-Youl
Published: December 2020

KUDC8001T was isolated from the rhizosperic soil of Elymus tsukushiensis in the Dokdo Islands, Republic of Korea. Strain KUDC8001T was Gram-stain-negative, non-motile and rod-shaped. KUDC8001T was catalase- and oxidase-positive. This strain is capable of growing at 4–37 °C and pH 7.0–8.0 and exhibited optimal growth at 25 °C and pH 7.0. It could be grown in R2A, nutrient agar and ISP2 agar plates. The cell width ranged from 0.7 to 1.0 µm, and length ranged from 2.5 to 5.5 µm. The genomic G+C content was 40.8 mol%. Phylogenetic analysis, based on 16S rRNA gene sequences, revealed that the strain KUDC8001T belongs to the genus

Adhaeribacter

, which is most closely related to the strain

A. pallidiroseus

HMF7616T (97.5%). The DNA relatedness of KUDC8001T with the type strains of

A. pallidiroseus

HMF7616T,

A. swui

17 mud1-7T and

A. arboris

HMF7605T was ≤80.3 % based on average nucleotide identity calculations and ≤86.9 % based on average amino acid identity calculations. In silico DNA–DNA hybridization values of the strain KUDC8001T with the most closely related strains were 22.1, 24.0 and 24.4 %. Based on its phenotypic, phylogenetic, genetic and chemotaxonomic features, the strain KUDC8001T should be considered as a novel species in the genus

Adhaeribacter

, for which we have proposed the name Adhaeribacter radiodurans sp. nov. The type strain is KUDC8001T (=KCTC 82078T=CGMCC 1.18475T).
Read trimming has minimal effect on bacterial SNP-calling accuracy
Authors: Bush Stephen J.
Published: December 2020

Read alignment is the central step of many analytic pipelines that perform variant calling. To reduce error, it is common practice to pre-process raw sequencing reads to remove low-quality bases and residual adapter contamination, a procedure collectively known as ‘trimming’. Trimming is widely assumed to increase the accuracy of variant calling, although there are relatively few systematic evaluations of its effects and no clear consensus on its efficacy. As sequencing datasets increase both in number and size, it is worthwhile reappraising computational operations of ambiguous benefit, particularly when the scope of many analyses now routinely incorporates thousands of samples, increasing the time and cost required. Using a curated set of 17 Gram-negative bacterial genomes, this study initially evaluated the impact of four read-trimming utilities (Atropos, fastp, Trim Galore and Trimmomatic), each used with a range of stringencies, on the accuracy and completeness of three bacterial SNP-calling pipelines. It was found that read trimming made only small, and statistically insignificant, increases in SNP-calling accuracy even when using the highest-performing pre-processor in this study, fastp. To extend these findings, >6500 publicly archived sequencing datasets from

Escherichia coli

,

Mycobacterium tuberculosis

and

Staphylococcus aureus

were re-analysed using a common analytic pipeline. Of the approximately 125 million SNPs and 1.25 million indels called across all samples, the same bases were called in 98.8 and 91.9 % of cases, respectively, irrespective of whether raw reads or trimmed reads were used. Nevertheless, the proportion of mixed calls (i.e. calls where <100 % of the reads support the variant allele; considered a proxy of false positives) was significantly reduced after trimming, which suggests that while trimming rarely alters the set of variant bases, it can affect the proportion of reads supporting each call. It was concluded that read quality- and adapter-trimming add relatively little value to a SNP-calling pipeline and may only be necessary if small differences in the absolute number of SNP calls, or the false call rate, are critical. Broadly similar conclusions can be drawn about the utility of trimming to an indel-calling pipeline. Read trimming remains routinely performed prior to variant calling likely out of concern that doing otherwise would typically have negative consequences. While historically this may have been the case, the data in this study suggests that read trimming is not always a practical necessity.