bluuebunny/crossref_metadata_2025 huggingface dataset:
Integration Theory
Authors: Boules Adel N.
Published: May 2021

The Lebesgue measure on ?n (presented in section 8.4) is a pivotal component of this chapter. The approach in the chapter is to extend the positive linear functional provided by the Riemann integral on the space of continuous, compactly supported functions on ?n (presented in section 8.1). An excursion on Radon measures is included at the end of section 8.4. The rest of the sections are largely independent of sections 8.1 and 8.4 and constitute a deep introduction to general measure and integration theories. Topics include measurable spaces and measurable functions, Carathéodory’s theorem, abstract integration and convergence theorems, complex measures and the Radon-Nikodym theorem, Lp spaces, product measures and Fubini’s theorem, and a good collection of approximation theorems. The closing section of the book provides a glimpse of Fourier analysis and gives a nice conclusion to the discussion of Fourier series and orthogonal polynomials started in section 4.10.
Substances and Cycles
Authors: Mallet Sarah , Stansbie Dan
Published: May 2021

This chapter looks at two sets of evidence for food: first, we consider the archaeological evidence of bones, plant remains, and pottery, each a direct indication of the food consumed; we also gather together and synthesize information on isotopes from human and animal bones for periods from the Iron Age to the early medieval period. Isotope data shows changes over time and space, reinforcing the idea that the Roman rural economy was more intensive than that of other periods. We are able to identify a series of regional food cultures and changes through time, looking also at the influence of towns from the late Iron Age onwards. We integrate the evidence through a consideration of the thought of Deleuze and De Landa.
Identity, Naming, and Division
Authors: Harkel Letty ten , Gosden Chris
Published: May 2021

We focus on evidence of naming the landscape in the medieval period starting with evidence from Domesday Book (1086 AD) and then moving backwards. We make links between names, the use of the landscape, and issues of identity. Landscapes would have been named in all periods. We consider what can be said of earlier landscapes for which evidence is scant or non-existent. Enclosure and naming were probably linked, in that when smaller parcels of land, such as fields, were created the are likely to have been given names in order to refer to them. We think about boundaries as evidence of sacred landscapes and end with conclusions on long-term continuities and differences. The landscapes of the early medeieval period stand out from those earlier, especially after the divisions, such as parishes, imposed by the church.
Subordinate clauses filling an argument position
Authors: Pinkster Harm
Published: May 2021

Chapter 15 deals with subordinate clauses, both finite and non-finite, which function as argument of their governing verb (traditionally called complement clauses). A distinction is made between declarative, interrogative, and imperative subordinate clauses. They are discussed according to the various subordinating devices: subordinators (e.g. quod, ut), question particles, infinitives (including accusative and infinitive clauses), gerunds, gerundives, and nominal clauses.
Subordinate clauses filling a satellite position
Authors: Pinkster Harm
Published: May 2021

Chapter 16 deals with subordinate clauses, both finite and non-finite, which function as satellites in their sentence (traditionally called adverbial clauses). The finite clauses with a subordinator are discussed according to their semantic function, e.g. reason, purpose, and condition. The non-finite clauses are discussed according to morphological type: infinitives, participles (including ablative absolute clauses), gerunds, gerundives, supines, and nominal clauses.
Coordination
Authors: Pinkster Harm
Published: May 2021

Chapter 19 deals with coordination, both syndetic (with an overt coordinator) and asyndetic. Three semantic types are distinguished: conjunctive, disjunctive, and adversative coordination. The conjoins that are coordinated may be clauses and noun, adjective, or adverb phrases. Conjoins can share a coordinator or have multiple coordinators. In addition there is epitactic coordination.
Comparison
Authors: Pinkster Harm
Published: May 2021

Chapter 20 deals with comparison. A distinction is made between expressions of comparison (equivalence and non-equivalence) and of similarity and dissimilarity. The former typically uses the comparative expression quam, the latter a coordinator. Attention is given to the ablative of comparison and the ablative of measure of difference. Comparative clauses of quality with ut are dealt with separately and so are proportional comparative expressions. Finally there is the absolute use of the comparative and the elative use of the superlative.
Secondary predicates
Authors: Pinkster Harm
Published: May 2021

Chapter 21 deals with secondary predicates (also called ‘praedicativa’), with quantifiers, and with the pronouns ipse and idem. The function of secondary predicate can be fulfilled by various categories of nominal expressions, such as adjectives, nouns, and participles which agree with the constituent to which they belong in case, number, and/or gender, but also by noun phrases in multiple case forms and prepositional phrases. The semantic relationship between the secondary predicate and the constituent it belongs to is usually implicit. A clause can contain more than one secondary predicate.
Discourse
Authors: Pinkster Harm
Published: May 2021

Chapter 24 deals with discourse, the way sentences form a coherent text. Coherence of a text is created by various means, apart from the internal semantic coherence. Forms of anaphora and various types of connectors create coherence between sentences. A distinction is made between conjunctive, adversative, and explanatory connectors, all syndetic connectors. However, asyndetic connection plays an important role as well. Some connectors are also used to connect paragraphs.
Introduction
Authors: Gottlieb Michah
Published: May 2021

The Introduction lays out the subject matter, problem, and plan of the book. A central theme is the emergence of middle-class German Judaism and the fraught dynamics of German Jews’ quest for legal and social equality. The connection between Bible translation and a “Jewish Reformation” and the importance of Protestant categories of religion are investigated. Three forms of bourgeois, middle-class German Judaism are explored: Moses Mendelssohn’s Haskalah, Leopold Zunz’s moderate Reform, and Samson Raphael Hirsch’s Neo-Orthodoxy. It is argued that bourgeois German Judaism is best understood as a spiritual enterprise where social and economic advancement are means to religious development and ethical responsibility.
Biblical Education and the Power of Conversation
Authors: Gottlieb Michah
Published: May 2021

This chapter covers the role of Bible translation in Mendelssohn’s endeavor to effect a reformation Jewish society by reimagining Jewish education. It explores Mendelssohn’s childhood education and his critique of the prevailing system of German Jewish education for males. Mendelssohn’s conception of the goal of education, his view of Yiddish, his understanding of biblical aesthetics, and his account of the roles of the Bible and rabbinic teachings in Jewish education is analyzed. The place of gender and class in Mendelssohn’s approach to Jewish education is investigated. The connection between Mendelssohn’s efforts to reform Jewish education, his attempt to restructure the hierarchy of German Jewish society and his argument for Jewish civil rights are explored. It is argued that Mendelssohn uses Protestantism and Catholicism as conceptual categories to elaborate his enlightened, bourgeois concept of Judaism.
Bible translation and the centrality of the synagogue
Authors: Gottlieb Michah
Published: May 2021

This chapter analyzes Zunz’s Bible translation, situating it within the context of Zunz’s critique of the traditional Ashkenazic system of Jewish education that he experienced personally. Zunz’s assessment of Moses Mendelssohn and his vision for Jewish education that steers a middle path between the “sham Enlightenment“ of Jewish youth and the “blind faith” of older Jewish traditionalists are presented. The role of gender in Jewish education and the centrality of the synagogue in Zunz’s Bible translation project are explored. Zunz’s Bible translation is set in relation to that of his teacher, the Bible critic Wilhelm De Wette as a way of comparing liberal German Protestantism and liberal German Judaism in the second quarter of the nineteenth century. It is shown how Zunz uses Protestantism and Catholicism as exemplary categories aligning his vision of Judaism with Protestantism while rejecting forms of Judaism that he deems “Catholic.”
The Innovative Orthodoxy of Hirsch’s Pentateuch
Authors: Gottlieb Michah
Published: May 2021

This chapter covers Hirsch’s translation and commentary on the Pentateuch exploring the anti-historicist premise on which it is founded. It is shown that Hirsch develops an entirely novel account of the relationship between the Bible and rabbinic literature to defend this premise, drawing on the scholarship of his opponent Zacharias Frankel to develop his view. Hirsch’s Pentateuch and Psalms translations and commentaries are compared. This chapter also presents Hirsch’s views on the cultural value of translation, impediments to translation, Hebrew, and Yiddish. The aims and methods of Hirsch’s Bible are analyzed and compared with Luther’s, Mendelssohn’s, and Zunz’s Bibles.
The Fracturing of German Judaism
Authors: Gottlieb Michah
Published: May 2021

This chapter explores the sectarian Orthodoxy of Hirsch’s Pentateuch. It is argued that the immediate context for Hirsch publishing his Pentateuch was the stunning success of the moderate Reformer Ludwig Philippson’s Israelite Bible (Israelitische Bibel). Philippson presented his Bible as an inclusive work to unite all German Jews including the Orthodox. It is shown that an important motivation for Hirsch’s Pentateuch was to prevent Orthodox communities from accepting Philippson’s Bible. Hirsch’s and Philippson’s Bibles are compared and connected to their opposing stances on the “Secession Controversy” of the 1870s that centered on the right of Orthodox congregations to withdraw from the governmentally-recognized official Jewish community. It is demonstrated that while Hirsch came to embrace the moniker “Orthodox” in 1854, during the “Secession Controversy” he distinguished his Neo-Orthodoxy from Ultra-Orthodoxy through a biting attack on the leading Ultra-Orthodox rabbinical authority in Germany at the time, Rabbi Seligmann Bamberger. While the early Hirsch presented a new, inclusive vision of German Judaism through his reading of the Bible in the Nineteen Letters, it is argued that the later Hirsch’s sectarian Neo-Orthodoxy which he grounded through his Pentateuch translation and commentary became emblematic of the irreparable fragmentation of German Judaism.
Conclusion
Authors: Gottlieb Michah
Published: May 2021

This chapter assesses the achievement of the Jewish Reformation by exploring Martin Buber’s and Franz Rosenzweig’s Jewish Counter-Reformation critique of it. Buber’s and Rosenzweig’s claim that the Jewish Reformation embodies a spiritually vacuous, craven account of Judaism whose final goal is social acceptance and economic advancement is rejected. It is argued that the Jewish Reformation Bible translations show security in a Judaism continuous with rabbinic tradition while Buber’s and Rosenzweig’s attempt to leap over rabbinic tradition to return to a “naked encounter” with the Bible evinces deep insecurity about their Judaism and their attempt to Germanicize the Bible reflects anxiety about the Jews’ place in German society. The dramatic, emotionally intense “archaic modernism” of Buber’s and Rosenzweig’s radical return to tradition is contrasted with the steady, learned spirituality of Mendelssohn’s, Zunz’s, and Hirsch’s middle-class Judaism.
The Fiery Test of Critique
Authors: Proops Ian
Published: May 2021

The book aims to provide a comprehensive study of the ‘Transcendental Dialectic’ of Kant’s first Critique. It argues that Kant conceives of ‘critique’ as a kind of winnowing exercise, aimed to separate the wheat of good metaphysics from the chaff of bad. However, he uses a less familiar metaphor to make this point, namely, that of ‘the fiery test of critique’. This turns out to be, not a medieval ordeal (a trial by fire), but rather a metallurgical assay: so-called ‘cupellation’—a procedure in which ore samples are tested for their precious-metal content. The upshot is that critique has a positive, investigatory side: it seeks not merely to eliminate the dross of bad ‘dogmatic’ metaphysics but also to uncover any hidden nuggets of value that might be contained in traditional speculative metaphysics. There are both gold and silver to be found. The gold is the indirect proof of Transcendental Idealism afforded by the resolution of the Antinomies, the silver Kant’s defence of theoretically grounded ‘doctrinal beliefs’ in a wise and great originator and in an afterlife. In the course of making these points, the book engages with Kant’s views on a number of central problems in philosophy and meta-philosophy, including: the explanation of the enduring human impulse towards metaphysics, correct philosophical method, the limits of self-knowledge, the possibility of human freedom, the resolution of metaphysical paradox (‘Antinomy’), the justification of faith, the nature of scepticism, and the role of ‘as if’ reasoning in natural science.
Introduction
Authors: Proops Ian
Published: May 2021

This chapter presents the main themes of the book, including, most importantly, a re-interpretation of Kant’s guiding metaphor for critique, namely, the ‘fiery test’ of the title. The image to which Kant is appealing is not that of an ordeal (a trial by fire) but rather a metallurgical test in which ore samples are checked for their precious metal content. The upshot is that critique is not a pass–fail affair, but has variegated results; moreover, it is in part optimistic: the test, in addition to burning. off the dross, seeks to uncover nuggets of value in traditional speculative metaphysics. Other topics examined in the chapter include: dogmatism and scepticism, method and experiment as guiding metaphors; Kant’s idiosyncratic take on Pyrrhonism; his practice of this idiosyncratic Pyrrhonism; Kantian charity; denying knowledge in order to make room for faith; the nature of speculation; the pre-eminence of the Antinomies; and Kant’s methodological influences.
The B-Edition First Paralogism
Authors: Proops Ian
Published: May 2021

This chapter analyses the second-edition first paralogism. It argues that Kant offers a plausible account of how a philosopher in the grip of transcendental illusion might be led to commit a fallacy of equivocation of the kind Kant discerns in the first paralogism (when its premises are taken to be true), namely, a sophisma figurae dictionis. (The paralogism Kant states is actually an abridged polysyllogism.) The chapter explains how Kant can, by the lights of his own epistemology, regard the premises of the argument as true. The chapter criticizes an interpretation of the Paralogism offered by Michelle Grier and responds to a textual worry raised by Patricia Kitcher. It defends the author’s interpretation against the recent criticisms of Julian Wuerth and Béatrice Longuenesse. Finally, the chapter explains the ways in which the author’s account diverges from that of the (to his mind) close-to-correct interpretation of Karl Ameriks.
The A-edition First Paralogism
Authors: Proops Ian
Published: May 2021

This chapter opens with an account of the A-edition first Paralogism. After refining the account of Transcendental Illusion given in Chapter 1, it proceeds to examine Julian Wuerth’s rival interpretation of the first Paralogism and, in connection with that interpretation, Kant’s notion of the ‘substantiale’. The chapter discusses a problem with Kant’s characterization of a paralogism in terms of ‘transcendental’ and ‘empirical’ uses of a category. Finally, it considers the three ways in which a paralogism can be diagnosed, namely, either as an invalid argument with known premises or as a valid argument with at least one unknown premise (a ‘paralogism’ now only by courtesy) or, finally, as a valid argument with known premises which is ‘false with respect to form’ because its proponent commits the fallacy of overestimating the significance of what has been proved. This last, it argues, is the diagnosis Kant offers of the A-edition first paralogism.
The Fourth Paralogism
Authors: Proops Ian
Published: May 2021

This chapter examines Kant’s diagnosis of the fourth paralogism. This paralogism argues for the differential certainty of our knowledge of external objects, on the one hand, and our knowledge of our own existence, on the other. The chapter argues that the paralogism does not wear its equivocal middle term, ‘existence outside us’, on its sleeve. An effort is made to reformulate the paralogism so that this phrase can be seen to be the true locus of the equivocation. The chapter then goes on to discuss a range of related issues, including: anti-materialism, monism, Kant’s rejection of external-world scepticism, and the role played by transcendental illusion in encouraging the paralogism. The chapter closes with some reflections on architectonic and method as these topics relate to the Paralogisms.
The Third Antinomy Presented
Authors: Proops Ian
Published: May 2021

This chapter presents Kant’s arguments for the thesis and antithesis of the third antinomy. It argues that Kant regards these claims as having a status that might be described as: ‘non-conflicting-when-correctly-construed’ (i.e., when construed as they ought to be construed on the assumption that Transcendental Idealism is true). The antinomy-resolving construal involves recognizing that, if Transcendental Idealism is assumed, an action can be free—in the sense of the product of a spontaneous ‘causality of freedom’—without failing to be event caused. Defending this interpretation requires discussion of Kant’s conception of ‘causality’ as well as of the plethora of meanings he bestows upon the term ‘freedom’. It also requires resolving an ambiguity in the meaning of ‘libertarianism’ that has crept into discussions of Kant’s views on free will. With these matters clarified, Kant—surprising as it may sound—emerges as a soft determinist—albeit one of a highly unusual stripe.
The Fourth Antinomy
Authors: Proops Ian
Published: May 2021

This chapter examines the thesis and antithesis of the fourth antinomy—along with their supporting arguments. It argues that Kant seeks to resolve this antinomy by a strategy paralleling the one he employs in the third Antinomy: namely, attempting to show that if Transcendental Idealism is true, the thesis and antithesis can be so understood that the truth of neither one excludes the truth of the other. The resolution further mirrors that of the third antinomy insofar as it does not purport to show on theoretical grounds that the concept of a necessary being is internally consistent. The chapter closes by examining the relevance to the fourth antinomy of Kant’s discussion of the example of De Mairan and the moon. This is a case in which one and the same body of evidence strikes each of two rival theorists as exclusively supporting their own position, thus inducing an antinomial dispute.
The Cosmological Argument
Authors: Proops Ian
Published: May 2021

This chapter argues, controversially, that all three of Kant’s announced criticisms are working parts of his critique of the cosmological argument. To see this point we need to appreciate that for Kant the assumption from which the argument begins is the fact that something existent is contingent—not in the sense that it might not have existed at all, but only in the sense that it might have existed in some other way. Consequently, the argument (even if it were not otherwise flawed) could hope to establish at most the existence of a being that can exist in only one way. Realizing this, Kant’s cosmological arguer attempts to strengthen the argument’s conclusion through reasoning that relies on the ontological argument. Recognizing this reliance, Kant sees the cosmological argument as merely an attempt to clothe the ontological argument in fashionably empirical garb—and thus to pass it off as something new.
ERAD-related E2 and E3 enzymes modulate the drought response by regulating the stability of PIP2 aquaporins
Authors: Chen Qian , Liu Ruijun , Wu Yaorong , Wei Shaowei , Wang Qian , Zheng Yunna , Xia Ran , Shang Xiaoling , Yu Feifei , Yang Xiaoyuan , Liu Lijing , Huang Xiahe , Wang Yingchun , Xie Qi
Published: May 2021

Endoplasmic reticulum-associated degradation (ERAD) is known to regulate plant responses to diverse stresses, yet its underlying molecular mechanisms and links to various stress signaling pathways are poorly understood. Here, we show that the ERAD component ubiquitin-conjugating enzyme UBC32 positively regulates drought tolerance in Arabidopsis thaliana by targeting the aquaporins PIP2;1 and PIP2;2 for degradation. Furthermore, we demonstrate that the RING-type ligase Rma1 acts together with UBC32 and that the E2 activity of UBC32 is essential for the ubiquitination of Rma1. This complex ubiquitinates a phosphorylated form of PIP2;1 at Lys276 to promote its degradation, thereby enhancing plant drought tolerance. Extending these molecular insights into crops, we show that overexpression of Arabidopsis UBC32 also improves drought tolerance in rice (Oryza sativa). Thus, beyond uncovering the molecular basis of an ERAD-regulated stress response, our study suggests multiple potential strategies for engineering crops with improved drought tolerance.
Disruption of mitochondrial open reading frame 352 partially restores pollen development in cytoplasmic male sterile rice
Authors: Omukai Shiho , Arimura Shin-ich , Toriyama Kinya , Kazama Tomohiko
Published: May 2021

Plant mitochondrial genomes sometimes carry cytoplasmic male sterility (CMS)-associated genes. These genes have been harnessed in various crops to produce high-yielding F1 hybrid seeds. The gene open reading frame 352 (orf352) was reported to be an RT102-type CMS gene in rice (Oryza sativa), although the mechanism underlying its role in CMS is unknown. Here, we employed mitochondrion-targeted transcription activator-like effector nucleases (mitoTALENs) to knockout orf352 from the mitochondrial genome in the CMS rice RT102A. We isolated 18 independent transformation events in RT102A that resulted in genome editing of orf352, including its complete removal from the mitochondrial genome in several plants. Sequence analysis around the mitoTALEN target sites revealed their induced double-strand breaks were repaired via homologous recombination. Near the 5ʹ-target site, repair involved sequences identical to orf284, while repair of the 3ʹ-target site yielded various new sequences that generated chimeric genes consisting of orf352 fragments. Plants with a chimeric mitochondrial gene encoding amino acids 179–352 of ORF352 exhibited the same shrunken pollen grain phenotype as RT102A, whereas plants either lacking orf352 or harboring a chimeric gene encoding amino acids 211–352 of ORF352 exhibited partial rescue of pollen viability and germination, although these plants failed to set seed. These results demonstrated that disruption of orf352 partially restored pollen development, indicating that amino acids 179–210 from ORF352 may contribute to pollen abortion.
Recognition of Collective Victimhood and Outgroup Prejudice
Authors: Dinas Elias , Fouka Vasiliki , Schläpfer Alain
Published: May 2021

Groups that have experienced collective suffering are sometimes more sympathetic toward outgroups, while other times they display higher outgroup prejudice. What can account for these contradictory observations? This study uses a unique historical episode of forced displacement to examine how perceptions of recognition of the ingroup’s victimhood affect views toward outgroups. We collect data on descendants of ethnic Germans ousted from Central and Eastern Europe after the end of World War II, and examine their attitudes toward Syrian refugees today. Both observational data and an experiment are used to test the role of victimhood recognition. When they learn that their suffering is acknowledged by more Germans than they expected, descendants of expellees become more positive toward refugees. Interestingly, this effect is not symmetric. When recognition of suffering is revealed to be lower than respondents’ expectations, their sympathy toward refugees does not decrease. This effect is not present among respondents without a family background of forced expulsion. Additional evidence documents the underlying mechanism at work.
A Cognitive Functional Therapy+ Pathway Versus an Interdisciplinary Pain Management Pathway for Patients With Severe Chronic Low Back Pain (CONFeTTI Trial): Protocol for a Pragmatic Randomized Controlled Trial
Authors: Vaegter Henrik Bjarke , Johansen Jannick Vaaben , Sopina Liza , Smith Anne , Kent Peter , Fuglsang Kira Søndberg , Pedersen Jesper Fredslund , Schutze Rob , O’Sullivan Peter , Handberg Gitte , Fatoye Francis , Ussing Kasper , Stegemejer Irene , Thorlund Jonas Bloch
Published: May 2021

Objective

Chronic low back pain (cLBP) is the leading cause of disability. Interdisciplinary pain management is recommended for patients with severe/high-impact cLBP. Such programs are expensive, not easily accessible, and have limited effect; therefore, new cost-effective strategies are warranted. Cognitive functional therapy (CFT) has shown promising results but has not been compared with an interdisciplinary pain management approach. The primary aim of this randomized controlled trial is to investigate if a pathway starting with CFT including psychologist support (CFT+) with the option of additional usual care (if needed) is superior in improving disability and more cost-effective at 12 months compared with an interdisciplinary pain management pathway (usual care).

Methods

This pragmatic, 2-arm, parallel-group randomized controlled trial will randomly allocate patients (n = 176) aged 18 to 75 years referred to an interdisciplinary pain center due to severe cLBP to 1 of 2 groups (1:1 ratio). Participants randomized to CFT+ will participate in a 3-month functional rehabilitation pathway with the option of additional usual care (if needed), and participants randomized to the interdisciplinary pain management pathway will participate in an individualized program of longer duration designed to best suit the individual’s situation, needs, and resources. The primary outcome is the proportion of participants with an 8-point improvement in the Oswestry Disability Index score at 12 months. Exploratory outcomes are change in Oswestry Disability Index scores over time and an economic analysis of quality-adjusted life years using the 3-level version of the EuroQol EQ-5D.

Impact

The study evaluates the cost-effectiveness of CFT+ with the option of additional usual care (if needed) for individuals with severe cLBP. Findings can potentially improve future care pathways and reduce cost for the health care system.
Fiscal Cyclicality and Currency Risk Premia
Authors: Jiang Zhengyang
Published: May 2021

I develop a model of real exchange rate determination that attributes a central role to the intertemporal government budget condition, which equates the market value of government debt to the present value of government surpluses. To enforce this equilibrium condition in the presence of nominal rigidities, the real exchange rate has to adjust in response to shocks to government surpluses. The model predicts that fiscal shocks account for real exchange rate movements, and the factor structure in fiscal shocks aligns with the factor structure in currency returns. Both predictions are confirmed in the sample of developed countries.
Corporate Bond Liquidity during the COVID-19 Crisis
Authors: Kargar Mahyar , Lester Benjamin , Lindsay David , Liu Shuo , Weill Pierre-Olivier , Zúñiga Diego
Published: May 2021

We study liquidity conditions in the corporate bond market during the COVID-19 pandemic. We document that the cost of trading immediately via risky-principal trades dramatically increased at the height of the sell-off, forcing customers to shift toward slower agency trades. Exploiting eligibility requirements, we show that the Federal Reserve’s corporate credit facilities have had a positive effect on market liquidity. A structural estimation reveals that customers’ willingness to pay for immediacy increased by about 200 bps per dollar of transaction, but quickly subsided after the Fed announced its interventions. Dealers’ marginal cost also increased substantially but did not fully subside.
Diagnostic accuracy of high-resolution peripheral quantitative computed tomography and X-ray for classifying erosive rheumatoid arthritis
Authors: Klose-Jensen Rasmus , Therkildsen Josephine , Blavnsfeldt Anne-Birgitte Garm , Langdahl Bente L , Zejden Anna , Thygesen Jesper , Keller Kresten Krarup , Hauge Ellen-Margrethe
Published: May 2021

Objective

To investigate whether high-resolution peripheral quantitative CT (HR-pQCT) of two metacarpophalangeal (MCP) joints can more accurately classify patients as having erosive RA compared with conventional radiography (CR) of 44 joints in the hands, wrists and feet.

Methods

In this single-centre cross-sectional study, patients with established RA (disease duration ≥5 years) were investigated by HR-pQCT and CR. The second and third MCP joints of the dominant hand were assessed for erosions by HR-pQCT. CR of the hands, wrists and feet were scored according to the Sharp–van der Heijde (SHS) method.

Results

In total, 353 patients were included; 66 (18.7%) patients were classified as having non-erosive RA, and 287 (81.3%) had erosive RA by CR. The sensitivity and specificity (95% CI) of HR-pQCT for classifying patients as having erosive RA when standard CR of hands, wrists and feet was used as the reference was 89% (84, 92%) and 30% (20, 43%), respectively. Using HR-pQCT as the reference, the sensitivity and specificity of CR for classifying patients having erosive RA were 85% (80, 89%) and 38% (25, 52%), respectively. McNemar’s χ2 test showed no significant difference between the sensitivities of patients classified as having erosive RA by HR-pQCT or by CR (2.14, P = 0.177).

Conclusion

The diagnostic accuracy of HR-pQCT scanning of only two MCP joints and CR of 44 joints suggests the two modalities were comparable for classifying patients with established RA as having erosive disease.

Clinical trial registration

ClinicalTrials.gov (NCT03429426).
Liver Toxicity Observed With Lorlatinib When Combined With Strong CYP3A Inducers: Evaluation of Cynomolgus Monkey as a Nonclinical Model for Assessing the Mechanism of Combinational Toxicity
Authors: Hu Wenyue , Lettiere Daniel , Tse Susanna , Johnson Theodore R , Biddle Kathleen E , Thibault Stephane , Palazzi Xavier , Chen Joseph , Pithavala Yazdi K , Finkelstein Martin
Published: May 2021

Lorlatinib is a potent small-molecule anaplastic lymphoma kinase inhibitor approved for the treatment of patients with nonsmall cell lung cancer. In a drug-drug interaction study in healthy human participants, liver enzyme elevations were observed when a single 100 mg dose of lorlatinib was administered after multiple doses of rifampin, a strong cytochrome P450 (CYP) 3A inducer and a pregnane X receptor (PXR) agonist. A series of in vitro and in vivo studies were conducted to evaluate potential mechanisms for the observed clinical toxicity. To investigate the involvement of CYP3A and/or PXR in the observed liver toxicity, studies were conducted in cynomolgus monkeys administered lorlatinib alone or with coadministration of multiple doses of known CYP3A inducers that are predominantly PXR agonists (rifampin, St. John’s wort) or predominantly constitutive androstane receptor agonists (carbamazepine, phenytoin) and a net CYP3A inhibitory PXR agonist (ritonavir). Results from the investigative studies identified cynomolgus monkeys as a pharmacologically relevant nonclinical model, which recapitulated the elevated liver function test results observed in humans. Furthermore, liver toxicity was only observed in this model when lorlatinib was coadministered with strong CYP3A inducers, and the effects were not restricted to, or exclusively dependent upon, a PXR activation mechanism. These results generated mechanistic insights on the liver enzyme elevations observed in the clinical drug-drug interaction study and provided guidance on appropriate product safety label for lorlatinib.
Molecular Characterization of All-Stage and Adult-Plant Resistance Loci Against Powdery Mildew in Winter Wheat Cultivar Liangxing 99 Using BSR-Seq Technology
Authors: Shi Xiaohan , Wu Peipei , Hu Jinghuang , Qiu Dan , Qu Yunfeng , Li Yahui , Liu Yi , Gebremariam Tesfay Gebrekirstos , Xie Jingzhong , Wu Qiuhong , Zhang Hongjun , Liu Hongwei , Yang Li , Sun Guozhong , Zhou Yang , Liu Zhiyong , Li Hongjie
Published: May 2021

Winter wheat cultivar Liangxing 99, which carries gene Pm52, is resistant to powdery mildew at both seedling and adult-plant stages. An F2:6 recombinant inbred line population from cross Liangxing 99 × Zhongzuo 9504 was phenotyped with Blumeria graminis f. sp. tritici isolate Bgt27 at the adult-plant stage in four field tests and the seedling stage in a greenhouse test. The analysis of bulk segregant RNA sequencing (BSR-Seq) identified a single-nucleotide polymorphism-enriched locus, Qaprpm.caas.2B, on chromosome 2BL in the same genomic interval of Pm52 associated with the all-stage resistance (ASR) and Qaprpm.caas.7A on chromosome 7AL associated with the adult-plant resistance (APR) against the disease. Qaprpm.caas.2B was detected in a 1.3 cM genetic interval between markers Xicscl726 and XicsK128 in which Pm52 was placed with a range of logarithm of odds (LOD) values from 28.1 to 34.6, and the phenotype variations explained in terms of maximum disease severity (MDS) ranged from 45 to 52%. The LOD peak of Qaprpm.caas.7A was localized in a 4.6 cM interval between markers XicsK7A8 and XicsK7A26 and explained the phenotypic variation of MDS ranging from 13 to 16%. The results of this study confirmed Pm52 for ASR and identified Qaprpm.caas.7A for APR to powdery mildew in Liangxing 99.
Origin and Dynamics of Rwt6, a Wheat Gene for Resistance to Nonadapted Pathotypes of Pyricularia oryzae
Authors: Asuke Soichiro , Umehara Yuta , Inoue Yoshihiro , Vy Trinh Thi Phuong , Iwakawa Mizuki , Matsuoka Yoshihiro , Kato Kenji , Tosa Yukio
Published: May 2021

Avirulence of Eleusine isolates of Pyricularia oryzae on common wheat is conditioned by at least five avirulence genes. One is PWT3 corresponding to resistance gene Rwt3 located on chromosome 1D. We identified a resistance gene corresponding to a second avirulence gene, PWT6, and named it Rmg9 (Rwt6). Rwt6 was closely linked to Rwt3. A survey of the population of Aegilops tauschii, the D genome donor to common wheat, revealed that some accessions from the southern coastal region of the Caspian Sea, the birthplace of common wheat, carried both genes. Rwt6 and Rwt3 carriers accounted for 65 and 80%, respectively, of accessions in a common wheat landrace collection. The most likely explanation of our results is that both resistance genes were simultaneously introduced into common wheat at the time of hybridization of Triticum turgidum and A. tauschii. However, a prominent difference was recognized in their geographical distributions in modern wheat; Rwt3 and Rwt6 co-occurred at high frequencies in regions to the east of the Caspian Sea, whereas Rwt6 occurred at a lower frequency than Rwt3 in regions to the west. This difference was considered to be associated with range of pathotypes to which these genes were effective. A. tauschii accessions carrying Rwt3 and Rwt6 also carried Rwt4, another resistance gene involved in the species specificity. We suggest that the gain of the D genome should have given an adaptive advantage to the genus Triticum by conferring disease resistance.
Logistic Models Derived via LASSO Methods for Quantifying the Risk of Natural Contamination of Maize Grain with Deoxynivalenol
Authors: Dalla Lana Felipe , Madden Laurence V. , Paul Pierce A.
Published: May 2021

Models were developed to quantify the risk of deoxynivalenol (DON) contamination of maize grain based on weather, cultural practices, hybrid resistance, and Gibberella ear rot (GER) intensity. Data on natural DON contamination of 15 to 16 hybrids and weather were collected from 10 Ohio locations over 4 years. Logistic regression with 10-fold cross-validation was used to develop models to predict the risk of DON ≥1 ppm. The presence and severity of GER predicted DON risk with an accuracy of 0.81 and 0.87, respectively. Temperature, relative humidity, surface wetness, and rainfall were used to generate 37 weather-based predictor variables summarized over each of six 15-day windows relative to maize silking (R1). With these variables, least absolute shrinkage and selection operator (LASSO) followed by all-subsets variable selection and logistic regression with 10-fold cross-validation were used to build single-window weather-based models, from which 11 with one or two predictors were selected based on performance metrics and simplicity. LASSO logistic regression was also used to build more complex multiwindow models with up to 22 predictors. The performance of the best single-window models was comparable to that of the best multiwindow models, with accuracy ranging from 0.81 to 0.83 for the former and 0.83 to 0.87 for the latter group of models. These results indicated that the risk of DON ≥1 ppm can be accurately predicted with simple models built using temperature- and moisture-based predictors from a single window. These models will be the foundation for developing tools to predict the risk of DON contamination of maize grain.
Moving Forward Together
Authors: Kennedy Maureen Shawn
Published: May 2021

Advances against COVID-19 offer hope, but work remains before we can fully move on.
New Treatment for Relapsed or Refractory Large B-cell lymphoma
Authors: Aschenbrenner Diane S.
Published: May 2021

Lisocabtagene maraleucel (Breyanzi), a personalized cell-based gene therapy, has been approved to treat adults with various relapsed or refractory large B-cell lymphomas.
Implementing a Multidisciplinary Prone Positioning Team
Authors: Elpern Ellen H. , Nedved Patricia , Weiss Tyler , Patel Ankeet D. , Cerda Flor
Published: May 2021

The coronavirus disease 2019 pandemic has escalated clinical needs while interrupting regular processes and straining resources. Striving to deliver optimal care to infected patients with respiratory failure, Rush University Medical Center in Chicago created a multidisciplinary team to provide manual prone positioning safely and efficiently. Team members' experiences, which they shared through a survey, help to illustrate the advantages of a multidisciplinary approach and suggest opportunities to enhance the effectiveness of such a team.
Fish Consumption Lowers CVD Risk in Patients with Vascular Disease
Authors: Rosenberg Karen
Published: May 2021

According to this study:

An intake of at least two servings of fish per week was associated with a lower risk of major cardiovascular disease events and total mortality in people with existing vascular disease, but not in the general population.
Lessons Learned: Implementation of a Concept-Based Curriculum in the Development of a New Prelicensure Nursing Program
Authors: Pyatt Amber
Published: May 2021

Nursing programs throughout the United States are making changes to curricula to decrease content overload, increase critical thinking and clinical reasoning skills of graduates, and prepare students to care for the complex needs of today’s health care consumer. In a student-centered approach, students are no longer passive recipients in the classroom but active learners. A concept-based curriculum is a design focused on a student-centered learning approach. This article provides lessons learned throughout the development and implementation of a concept-based curriculum in a new prelicensure nursing program.
Fetal Heart Rate Pattern in Term or Near-Term Cerebral Palsy: A Nationwide Cohort Study
Authors: Nakao Masahiro , Okumura Asumi , Hasegawa Junichi , Toyokawa Satoshi , Ichizuka Kiyotake , Kanayama Naohiro , Satoh Shoji , Tamiya Nanako , Nakai Akihito , Fujimori Keiya , Maeda Tsugio , Suzuki Hideaki , Iwashita Mitsutoshi , Ikeda Tomoaki
Published: May 2021

(Abstracted from Am J Obstet Gynecol 2020;223:907.e1–907.e13)

Among the major causes of cerebral palsy (CP) are hypoxic events that occur during labor. Therefore, fetal heart rate (FHR) monitoring to prevent brain injury associated with these events is an integral part of intrapartum management.
Does a Recent Urinary Tract Infection Increase the Risk of Postprocedure Urinary Tract Infection After Onabotulinum Toxin A?
Authors: Bickhaus Jennifer A. , Bradley Megan S. , Amundsen Cindy L. , Visco Anthony G. , Truong Tracy , Li Yi-Ju , Siddiqui Nazema Y.
Published: May 2021

(Abstracted from Female Pelvic Med Reconstr Surg 2021;27(2):121–125)

Onabotulinum toxin A (BTX-A) is commonly used as treatment for refractory overactive bladder (OAB) but is associated with postprocedural urinary tract infection (UTI) in up to 35% of cases despite antibiotic prophylaxis. In women with recent UTI, it is unclear whether there should be a prolonged waiting period prior to BTX-A.
Small for Gestational Age-Cognitive Performance From Infancy to Adulthood: An Observational Study
Authors: Eves R. , Mendonça M. , Bartmann P. , Wolke D.
Published: May 2021

(Abstracted from BJOG 2020;127(13):1598–1606)

Understanding the impact of being born small for gestational age (SGA) on cognitive performance is complicated. While SGA has been associated with lower developmental and intelligence test scores (IQ) in childhood, studies on its effects into adulthood are unclear.
Payments by Industry to Residency Program Directors in the United States: A Cross-Sectional Study
Authors: Janssen Stein J. , Langerhuizen David W.G. , Kerkhoffs Gino M.M.J. , Ring David
Published: May 2021

Purpose

To assess the proportion, nature, and extent of financial payments from industry to residency program directors in the United States.

Method

This cross-sectional study used open-source data from Doximity and the Centers for Medicare and Medicaid (CMS) open payments database. Profiles of 4,686 residency program directors from 28 different specialties were identified using Doximity and matched to records in the CMS database. All payments received per residency program director over the years 2014 to 2018 were extracted, including amount in U.S. dollars, payment year, and nature of payment (research versus general payments). Total payments (research plus general payments) received over the 5 years were added up per residency program director. Only personal payments were included.

Results

Overall, 74% (3,465/4,686) of all residency program directors received 1 or more personal payments, totaling $77,058,139, with a median of $216 (interquartile range, $0–$2,150) and a mean of $16,444 (standard deviation, $183,061) per residency program director over the 5 years. Ninety-five percent of total payment value were general payments, and 5% were personal research payments. About 11% (536/4,686) of residency program directors received more than $10,000, while 3% (133/4,686) received more than $100,000 in the study years. There was a substantial difference in the proportion (P < .001), nature (P < .001), and amount (P < .001) of payments of residency program directors between specialties. Almost all residency program directors of interventional radiology (96% [74/77]), vascular surgery (96% [53/55]), and orthopedic surgery (92% [184/201]) received payments, while only one-third to one-half of those in preventive medicine (29% [18/62]), pediatrics (43% [90/211]), and pathology (51% [73/143]) received payments.

Conclusions

Industry payments to residency program directors are common, although large variation exists between specialties. The majority of direct payments to residency program directors are for non–research-related activities.
Effect of Test Realism on Speech-in-noise Outcomes in Bilateral Cochlear Implant Users
Authors: Badajoz-Davila Javier , Buchholz Jörg M.
Published: May 2021

Objectives:

First, to evaluate the effect of laboratory-based test realism on speech intelligibility outcomes of cochlear implant users. Second, to conduct an exploratory investigation of speech intelligibility of cochlear implant users, including bilateral benefit, under realistic laboratory conditions.

Design:

For the first goal, the authors measured speech intelligibility scores of 15 bilateral cochlear implant recipients under three different test realism levels at two different signal-to-noise ratios (SNRs). The levels included (1) standard Bamford-Kowal-Bench-like sentences with spatially separated standard babble noise; (2) standard Bamford-Kowal-Bench-like sentences with three-dimensional recordings of actual situations; and (3) a variation of the second realism level where the sentences were obtained from natural effortful conversations. For the second goal, speech intelligibility of the realistic speech material was measured in six different acoustic scenes with realistic signal-to-noise ratios ranging from −5.8 dB to 3.2 dB.

Results:

Speech intelligibility was consistently highest in the most artificial (standard) test and lowest in the most realistic test. The effect of the realistic noise and that of the realistic speech material resulted in distinct SNR-dependent performance shifts with respect to their baselines. Speech intelligibility in realistic laboratory conditions was in general low, with mean scores around 60% at the highest SNR. Bilateral benefit provided on average a 7% benefit over unilateral speech understanding in the better-performing ear.

Conclusions:

The results obtained here suggest that standard speech-in-noise tests overestimate the performance of cochlear implant recipients in the real world. To address this limitation, future assessments need to improve the realism over current tests by considering the realism of both, the speech and the noise materials. Likewise, speech intelligibility data under realistic conditions suggest that, insofar as these results can be considered representative of real-life performance, conversational speech and noise levels common to cochlear implant recipients are challenging in terms of speech intelligibility, with average scores around 60%. The findings and limitations are discussed alongside the factors affecting speech intelligibility.