bluuebunny/crossref_metadata_2025 huggingface dataset:
Semantics and syntax in Old English mood selection
Authors: Jones Howard , Macleod Morgan
Published: April 2020

A principled model of mood selection in Old English (OE) has long proved elusive. We analyse the distribution of the indicative and subjunctive in the OE Bede in light of the Latin original, the syntactic construction, and a semantic model of modality which classifies clauses according to whether the situation is represented as holding in the actual world or in a possible world. The choice of mood in the Latin and OE Bede differs enough to rule out slavish imitation. In certain clauses, such as result and purpose clauses, the construction type, modality, and grammatical mood all match; however, in other clauses, such as concessives, the OE subjunctive is systematically used whether the situation is represented as actual or possible. Where the grammatical mood of OE forms is ambiguous, modal verbs are often seemingly used as a substitute for the subjunctive. Our results show that while the choice of mood in the OE Bede largely correlates with the syntactic construction, the subjunctive is close to being semantically redundant. This growing redundancy may have been one of the factors in the diminishing role of inflectional mood in the later history of English.
In the eye of the beholder: Employee sexual orientation, perceived supervisory support for life beyond work and job satisfaction
Authors: Stavrou Eleni , Solea Eftychia
Published: April 2020

We adopt congruence theory to compare perceptions of lesbian, gay and bisexual (LGB) and heterosexual employees between perceived supervisory support on life beyond work (LBW) and job satisfaction and the effect of life‐to‐work conflict (LWC). Using the 2011 UK WERS data and applying multilevel modelling, we find no incongruence between the two groups of employees on job satisfaction. We find a significant perceptual incongruence in the relation between supervisory support on LBW and job satisfaction. While the relation was positive for both groups, it was stronger for heterosexual than LGB employees. We also find significant perceptual incongruence when we add LWC. Specifically, as LWC increases, the positive relation between supervisory support on LBW and job satisfaction becomes stronger for LGB than heterosexual employees. This last finding may be the most interesting as it may place the concept of identity‐based conflict primarily in the life‐to‐work domain of LGB employees.
A pilot study of adjuvant chemotherapy with carboplatin and oral S‐1 for patients with completely resected stage II to IIIA non‐small cell lung cancer
Authors: Tanaka Hisashi , Tabe Chiori , Okumura Fumihiko , Shiratori Toshihiro , Ishioka Yoshiko , Itoga Masamichi , Taima Kageaki , Morimoto Takeshi , Kimura Daisuke , Tsushima Takao , Tasaka Sadatomo
Published: April 2020

Background

Adjuvant chemotherapy with platinum‐based regimens for completely resected early‐stage non‐small cell lung cancer (NSCLC) provides overall survival benefit in several clinical trials.

Objectives

We conducted this prospective study to evaluate the efficacy and safety of adjuvant chemotherapy with carboplatin and S‐1 for patients with completely resected stage II to IIIA NSCLC.

Methods

Patients with completely resected stage IIA to IIIA NSCLC were treated with four cycles of carboplatin with area under the concentration time curve of 5 mg/mL/min on day 1 plus S‐1 at 80–120 mg/bodyweight per day for two weeks, followed by one‐week rest as adjuvant chemotherapy. The primary endpoint was the completion rate of three cycles of the treatment. The secondary endpoints were safety and two‐year survival rate.

Results

A total of 19 patients were enrolled, until the study was terminated prematurely because of fatal pulmonary embolism in two patients. The median number of treatment cycles was three (range: 1–4). The completion rate of three cycles was 78.9% (95% confidence interval [CI]: 56.6–91.4%). Two‐year disease‐free survival rate was 57.8%. Grade 3 or 4 hematological toxicities included neutropenia (26.2%), anemia (5.2%), and thrombocytopenia (15.7%). Grade 3 or 4 nonhematological toxicities were anorexia (10.5%) and nausea (10.5%). Febrile neutropenia developed in 5.2%. In two patients (10.5%), grade five pulmonary embolism was observed, and the causal relationship with treatment could not be denied.

Conclusions

Carboplatin and oral S‐1 had modest survival benefit, but this regimen was not tolerable in an adjuvant setting because fatal pulmonary embolism occurred in two patients.

Key points

Carboplatin and oral S‐1 had modest survival benefit but this regimen was not tolerable.

Fatal pulmonary embolism occurred in this regimen.
Timeliness of Care for High‐acuity Conditions at Hospital‐affiliated Freestanding Emergency Departments
Authors: Baehr Avi , Ledbetter Caroline , Bookman Kelly J. , Wang Yang , Ginde Adit A. , Wiler Jennifer L.
Published: April 2020

Background

Hospital‐affiliated freestanding emergency departments (FREDs) are rapidly proliferating in some states and have been the subject of recent policy debate. As FREDs' role in acute care delivery is expanding in certain regions, little is known about the quality of care that they provide for their sickest patients. Our aim was to compare timeliness of emergent care at FREDs and hospital‐based EDs (HEDs) for patient visits with selected high‐acuity and time‐sensitive conditions.

Methods

We performed a retrospective observational analysis of adult patient visit data from 19 FREDs and five HEDs from one health system over a 1‐year period. Median times to events and hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated via Cox regression.

Results

The median time to electrocardiogram for visits with chest pain was 10 minutes at FREDs and 9 minutes at HEDs (HR = 0.91 [CI = 0.87 to 0.96]). Time to cardiac catheterization lab for visits with ST‐segment elevation myocardial infarction (STEMI) was 78 minutes at FREDs, inclusive of transfer time, and 31 minutes at HEDs (HR = 0.41 [CI = 0.24 to 0.71]). Time to computed tomography for visits with stroke was 37 minutes at FREDs and 29 minutes at HEDs (HR = 0.42 [CI = 0.31 to 0.58]). Among visits with sepsis, FREDs had longer times to lactate collection (HR = 0.41 [CI = 0.30 to 0.56]), blood culture collection (HR = 0.24 [CI = 0.11 to 0.51]), and antibiotic administration (HR = 0.61 [CI = 0.26 to 1.42]). Beta agonists were administered for visits with asthma exacerbations in 24 minutes at FREDs and 44 minutes at HEDs (HR = 2.50 [CI = 2.34 to 2.68]), with similar times for anticholinergic and corticosteroid administration.

Conclusions

Freestanding EDs provided more timely care than HEDs for visits with asthma exacerbation and less timely care for acute chest pain, stroke, and sepsis, although absolute differences were small. Even though STEMI patients at FREDs required transfer for catheterization, they tended to receive care in line with national guidelines.
Safety and pharmacokinetic profiles of MGS0274 besylate (TS‐134), a novel metabotropic glutamate 2/3 receptor agonist prodrug, in healthy subjects
Authors: Watanabe Mai , Marcy Brian , Kinoshita Kohnosuke , Fukasawa Misako , Hikichi Hirohiko , Chaki Shigeyuki , Okuyama Shigeru , Gevorkyan Hakop , Yoshida Shigeru
Published: April 2020

Aims

The safety and pharmacokinetics of single and multiple doses of a novel mGlu2/3 receptor agonist prodrug, MGS0274 besylate (TS‐134), were investigated in healthy subjects.

Methods

Phase 1 single‐ascending dose (5–20 mg) and multiple‐ascending dose titration (5–80 mg) studies were conducted in healthy male and female subjects. Both studies were randomized, double‐blinded and placebo‐controlled. In one cohort of single‐ascending dose study (10 mg), concentrations of MGS0008, the active compound, in the cerebrospinal fluid (CSF) were measured for up to 24 hours postdose.

Results

Following single and multiple oral administrations, MGS0274 was rapidly absorbed and extensively converted into MGS0008, which reached a maximum concentration (Cmax) in plasma within 4 hours postdose and declined with a terminal half‐life (t1/2) of around 10 hours. Plasma exposure to MGS0274 was minimal, accounting for approximately 3% of the area under the concentration–time curve (AUC) of MGS0008. Plasma Cmax and AUC of MGS0008 at steady state increased dose proportionally (5–80 mg). MGS0008 penetrated into CSF, with a CSF‐to‐plasma Cmax ratio of 3.66%, and was eliminated with a t1/2 of approximately 16 hours. The most frequent treatment‐emergent adverse events observed following single and multiple oral administration included headache, nausea, somnolence, dizziness and vomiting.

Conclusion

TS‐134 is orally bioavailable in humans and converts rapidly and extensively to MGS0008, which exhibits good CSF penetration. Orally administered TS‐134 was safe and generally well‐tolerated; hence, TS‐134 is a promising candidate for further clinical development for the treatment of disorders in which glutamatergic abnormalities are involved, such as schizophrenia.
Semi‐mechanistic modelling platform to assess cardiac contractility and haemodynamics in preclinical cardiovascular safety profiling of new molecular entities
Authors: Venkatasubramanian Raja , Collins Teresa A. , Lesko Lawrence J. , Mettetal Jerome T. , Trame Mirjam N.
Published: April 2020

Background and Purpose

Cardiovascular safety is one of the most frequent causes of safety‐related attrition both preclinically and clinically. Preclinical cardiovascular safety is routinely assessed using dog telemetry monitoring key cardiovascular functions. The present research was to develop a semi‐mechanistic modelling platform to simultaneously assess changes in contractility (dPdtmax), heart rate (HR) and mean arterial pressure (MAP) in preclinical studies.

Experimental Approach

Data from dPdtmax, HR, preload (left ventricular end‐diastolic pressure [LVEDP]) and MAP were available from dog telemetry studies after dosing with atenolol (n = 27), salbutamol (n = 5), L–NG–nitroarginine methyl ester (L–NAME; n = 4), milrinone (n = 4), verapamil (n = 12), dofetilide (n = 8), flecainide (n = 4) and AZ001 (n = 14). Literature model for rat CV function was used for the structural population pharmacodynamic model development. LVEDP was evaluated as covariate to account for the effect of preload on dPdtmax.

Key Results

The model was able to describe drug‐induced changes in dPdtmax, HR and MAP for all drugs included in the developed framework adequately, by incorporating appropriate drug effects on dPdtmax, HR and/or total peripheral resistance. Consistent with the Starling's law, incorporation of LVEDP as a covariate on dPdtmax to correct for the preload effect was found to be statistically significant.

Conclusions and Implications

The contractility and haemodynamics semi‐mechanistic modelling platform accounts for diurnal variation, drug‐induced changes and inter‐animal variation. It can be used to hypothesize and evaluate pharmacological effects and provide a holistic cardiovascular safety profile for new drugs.
Along‐strike structural linkage and interaction in an active thrust fault system: A case study from the western Sichuan foreland basin, China
Authors: Song Gonghua , Wang Maomao , Jiang Danqi , Chen Zhuxin , Yan Bing , Feng Wang
Published: April 2020

Along‐strike structural linkage and interaction between faults is common in various compressional settings worldwide. Understanding the kinematic history of fault interaction processes can provide important constraints on the geometry and evolution of the lateral growth of segmented faults in the fold‐and‐thrust belts, which are important to seismic hazard assessment and hydrocarbon trap development. In this study, we study lateral structural geometry (fault displacement and horizon shortening) of thrust fault linkages and interactions along the Qiongxi anticline in the western Sichuan foreland basin, China, using a high‐resolution 3D seismic reflection dataset. Seismic interpretation suggests that the Qiongxi anticline can be related to three west‐dipping, hard‐linked thrust fault segments that sole onto a regional shallow detachment. Results reveal that the lateral linkage of fault segments limited their development, affecting the along‐strike fault displacement distributions. A deficit between shortening and displacement is observed to increase in linkage zones where complex structural processes occur, such as fault surface bifurcation and secondary faulting, demonstrating the effect of fault linkage process on structural deformation within a thrust array. The distribution of the geometrical characteristics shows that thrust fault development in the area can be described by both the isolated fault model and the coherent fault model. Our measurements show that new fault surfaces bifurcate from the main thrust ramp, which influences both strain distribution in the relay zone and along‐strike fault slip distribution. This work fully describes the geometric and kinematic characteristics of lateral thrust fault linkage, and may provide insights into seismic interpretation strategies in other complex fault transfer zones.
Mdm2: Open questions
Authors: Dobbelstein Matthias , Levine Arnold J.
Published: April 2020

The Mdm2 oncoprotein and its association with p53 were discovered 30 years ago, and a cornucopia of activities and regulatory pathways have been associated with it. In this review, we will raise questions about Mdm2 and its cousin Mdm4 that we consider worth pursuing in future research, reaching from molecular structures and intracellular activities all the way to development, evolution, and cancer therapy. We anticipate that such research will not only close a few gaps in our knowledge but could add new dimensions to our current view. This compilation of questions contributes to the preparation for the 10th Mdm2 Workshop in Tokyo.
Raising Children With High Self‐Esteem (But Not Narcissism)
Authors: Brummelman Eddie , Sedikides Constantine
Published: April 2020

With the rise of individualism since the 1960s, Western parents have become increasingly concerned with raising their children’s self‐esteem. This is understandable, given the benefits of self‐esteem for children’s psychological health. However, parents’ well‐intentioned attempts to raise self‐esteem, such as through inflated praise, may inadvertently breed narcissism. How can parents raise self‐esteem without breeding narcissism? In this article, we propose a tripartite model of self‐regard, which holds that the development of self‐esteem without narcissism can be cultivated through realistic feedback (rather than inflated praise), a focus on growth (rather than on outperforming others), and unconditional regard (rather than regard that is conditional). We review evidence in support of these practices and outline promising directions for research. Our model integrates existing research, stimulates the development of theory, and identifies leverage points for intervention to raise self‐esteem and curtail narcissism from a young age.
Oral health literacy, self‐rated oral health, and oral health‐related quality of life in Brazilian adults
Authors: Bado Fernanda Maria Rovai , De Checchi Maria Helena Ribeiro , Cortellazzi Karine Laura , Ju Xiangqun , Jamieson Lisa , Mialhe Fábio Luiz
Published: April 2020

The aim of this study was to investigate associations between oral health literacy (OHL), self‐rated oral health (SROH), and oral health‐related quality of life (OHRQoL) in Brazilian adults. A sample of 523 Brazilian adults completed the short‐form Health Literacy in Dentistry (HeLD‐14) and the Oral Health Impact Profile‐14 (OHIP‐14) instruments that measure OHL and OHRQoL, respectively. The prevalence ratios (PRs) for outcome variables and their 95% CIs were quantified. Multivariable log‐binomial regression models were applied, as the statistical models, to estimate bivariate and multivariable relationships of oral health outcomes with OHL, after adjusting for covariates. No significant association was found between poor SROH (as measured by single items) and OHL (PR = 1.28; 95% CI: 0.87–1.88); by contrast, significant associations were found between poor SROH and income (PR = 1.52; 95% CI: 1.04–2.21), toothbrushing frequency (PR = 1.69; 95% CI: 1.11–2.58), reason for dental visiting (PR = 1.48; 95% CI: 1.03–2.13), and self‐rated general health (PR = 3.44; 95% CI: 2.38–4.97). The OHL level (PR = 1.76; 95% CI: 1.21–2.56), educational level (PR = 0.62; 95% CI: 0.41–0.93), reason for dental visiting (PR = 1.84; 95% CI: 1.30–2.61), and self‐rated general health (PR = 1.51; 95% CI: 1.03–2.23) were associated with poor OHRQoL.
Structural analysis of the reducing‐end xylose‐releasing exo‐oligoxylanase Rex8A from Paenibacillus barcinonensis BP‐23 deciphers its molecular specificity
Authors: Jiménez‐Ortega Elena , Valenzuela Susana , Ramírez‐Escudero Mercedes , Pastor Francisco Javier , Sanz‐Aparicio Julia
Published: April 2020

Reducing‐end xylose‐releasing exo‐oligoxylanases (Rex) are GH8 enzymes that depolymerize xylooligosaccharides complementing xylan degradation by endoxylanases in an exo manner. We have studied Paenibacillus barcinonensis Rex8A and showed the release of xylose from xylooligomers decorated with methylglucuronic acid (UXOS) or with arabinose (AXOS). This gives the enzyme a distinctive trait among known Rex, which show activity only on linear xylooligosaccharides. The structure of the enzyme has been solved by X‐ray crystallography showing a (α/α)6 folding common to GH8 enzymes. Analysis of inactived Rex8A‐E70A complexed with xylotetraose revealed the existence of at least four binding subsites in Rex8A, with the oligosaccharide occupying subsites −3 to +1. The enzyme shows an extended Leu320‐His321‐Pro322 loop, common to other Rex, which blocks the binding of longer substrates to positive subsites further than +1 and seems responsible for the lack or diminished activity of Rex enzymes on xylan. Mutants with smaller residues in this loop failed to increase Rex8A activity on the polymer. Analysis of the complexes with AXOS showed the accommodation of arabinose at subsite −2, which cannot be allocated at subsite −1. Arabinose substitutions at the xylose O2 or O3 are accommodated by hydrophobic interaction and seem tolerated rather than recognized by Rex8A. A strained binding of the branch is facilitated by the lack of direct polar interactions of the xylose occupying this subsite, its water‐mediated links allowing some conformational flexibility of the sugar. The plasticity of Rex8A is a notable property of the enzyme for its application in xylan deconstruction and upgrading.

Database

Structural data are available in PDB database under the accession numbers 6SRD (native form), 6TPP (E70A mutant in complex with EDO), 6TOW (E70A in complex with Xyl4), 6SUD (L320A mutant in complex with xylose), 6SHY (L320A/H321S double mutant in complex with EDO), 6TO0 (E70A in complex with AX3), and 6TRH (E70A in complex with AX4).
Microbial colonization of metal sulfide minerals at a diffuse‐flow deep‐sea hydrothermal vent at 9°50′N on the East Pacific Rise
Authors: Wang Chloe H. , Gulmann Lara K. , Zhang Tong , Farfan Gabriela A. , Hansel Colleen M. , Sievert Stefan M.
Published: April 2020

Metal sulfide minerals, including mercury sulfides (HgS), are widespread in hydrothermal vent systems where sulfur‐oxidizing microbes are prevalent. Questions remain as to the impact of mineral composition and structure on sulfur‐oxidizing microbial populations at deep‐sea hydrothermal vents, including the possible role of microbial activity in remobilizing elemental Hg from HgS. In the present study, metal sulfides varying in metal composition, structure, and surface area were incubated for 13 days on and near a diffuse‐flow hydrothermal vent at 9°50′N on the East Pacific Rise. Upon retrieval, incubated minerals were examined by scanning electron microscopy with energy‐dispersive X‐ray spectroscopy (SEM‐EDS), X‐ray diffraction (XRD), and epifluorescence microscopy (EFM). DNA was extracted from mineral samples, and the 16S ribosomal RNA gene sequenced to characterize colonizing microbes. Sulfur‐oxidizing genera common to newly exposed surfaces (Sulfurimonas, Sulfurovum, and Arcobacter) were present on all samples. Differences in their relative abundance between and within incubation sites point to constraining effects of the immediate environment and the minerals themselves. Greater variability in colonizing community composition on off‐vent samples suggests that the bioavailability of mineral‐derived sulfide (as influenced by surface area, crystal structure, and reactivity) exerted greater control on microbial colonization in the ambient environment than in the vent environment, where dissolved sulfide is more abundant. The availability of mineral‐derived sulfide as an electron donor may thus be a key control on the activity and proliferation of deep‐sea chemosynthetic communities, and this interpretation supports the potential for microbial dissolution of HgS at hydrothermal vents.
Students’ perceptions, academic departments’ image, and major‐choice in business administration studies—The example of Hamburg Business School
Authors: Korfmann Frauke , Müller Sven , Ehlert Sebastian , Haase Knut
Published: April 2020

In Germany enrolment in majors is of considerable interest to academic departments, because their budget depends on the number of enrolled students. Besides observed factors, we presume that unobserved latent variables influence the major‐choice decision of students. Using stated preferences data from a discrete choice experiment among students pursuing a bachelor’s degree in business administration at Hamburg Business School (HBS), we employ an integrated choice and latent variable model (ICLV). Thereby, we model the influence of a major‐specific latent variable, labeled image, on the major‐choice decision of the students. To identify the latent variables, we utilise ordered categorical indicators that we obtained from the assessment of major‐specific psychometric factors among students. Our findings reveal a significant impact of the latent variable image on the major‐choice decision. We further show the advantageous characteristic of an ICLV model by illustrating the cause‐and‐effect relationship compared to classic multinomial logit models. Based on our results, we examine practice‐oriented, requirements, research, and supervision to be the most relevant psychometric factors that lead to the identification of the latent variables and provide insights on how academic departments at HBS can raise their major’s attractiveness from the student’s perspective.

Abstrakt

In Deutschland ist die Immatrikulation in den Studiengängen für die Fachbereiche von großem Interesse, da ihr Budget von der Anzahl der eingeschriebenen Studierenden abhängt. Neben den beobachteten Faktoren nehmen wir an, dass nicht beobachtete latente Variablen die Schwerpunktwahl der Studierenden beeinflussen. Auf der Grundlage von Präferenzdaten aus einem diskreten Auswahlexperiment unter den Studierenden des Bachelor‐Studiengangs der Betriebswirtschaftslehre an der Hamburg Business School (HBS) verwenden wir ein integriertes Wahl‐ und latente Variablenmodell (ICLV). Dabei modellieren wir den Einfluss einer Schwerpunkt‐spezifischen latenten Variable, die als Image bezeichnet wird, auf die Schwerpunktwahl der Studierenden. Um die latente Variable zu identifizieren, verwenden wir geordnete kategorische Indikatoren, die wir aus der Bewertung der Schwerpunkt‐spezifischen psychometrischen Faktoren erhalten haben. Unsere Ergebnisse zeigen einen signifikanten Einfluss der latenten Variable Image auf die Schwerpunktwahl. Wir zeigen ferner die vorteilhafte Eigenschaft eines ICLV‐Modells, indem wir die Ursache‐Wirkungs‐Beziehung im Vergleich zu klassischen multinomialen Logit‐Modellen veranschaulichen. Basierend auf unseren Ergebnissen untersuchen wir Praxisorientierung, Anforderung, Forschung und Betreuung als die relevantesten psychometrischen Faktoren, die zur Identifizierung der latenten Variable führen und Einblicke geben, wie die Schwerpunkte der HBS die Attraktivität ihres Studienfachs aus der Perspektive der Studierenden erhöhen können.
Reproducing crystal glass from three 18th‐20th centuries Portuguese glass arcana
Authors: Santos Catarina Reis , Vilarigues Márcia , Dabas Prashant , Coutinho Inês , Palomar Teresa
Published: April 2020

The present work aims to study the glasses commonly named crystal glass produced in Portuguese factories from the 18th to the 20th centuries through their arcana or batch books. Recipes for colorless crystal glasses were selected, analyzed, and reproduced in the laboratory. Five recipes were chosen from the Marinha Grande arcanum, five recipes from the Gaivotas’ Factory arcanum, and three recipes from the Castro and Oliveira Guerra arcanum. To characterize the composition and thermal‐physical properties of reproduced glasses, different analytical techniques were used such as micro‐energy dispersive X‐ray fluorescence, µ‐ Raman spectroscopy, differential scanning calorimetry, dilatometry, Vickers hardness, optical microscopy, and UV‐Vis absorbance spectroscopy. The selected recipes were proven viable for reproduction and the obtained glasses presented good thermal properties that allow the workability and creation of objects. It was also proven that there is a similarity in terms of chemical composition to some of the historical glasses attributed to Portuguese production in Portuguese museums.
An oral brush of cilia in the feeding larvae of Micronephtys cornuta (Annelida, Nephtyidae)
Authors: Pernet Bruno
Published: April 2020

Larvae of many phyllodocidan annelids are planktotrophic, but the feeding mechanisms of larvae in this diverse clade are poorly known. Many larvae belonging to one large clade of phyllodocidans, Aphroditiformia, bear a bundle of long cilia attached to the left side of the prototroch, the oral brush, which they use in feeding. In 1936, D.P. Wilson observed that trochophore larvae of Nephtys hombergi, a member of the phyllodocidan family Nephtyidae, bore a strikingly similar bundle of long cilia on the left side of the body. Since Wilson's observation, numerous descriptions of nephtyid larvae have been published, but none remark on the presence of an oral brush. Here I show that metatrochophore I and II larvae of Micronephtys cornuta bear an oral brush, but that it is lost in the transition to the nectochaete stage, during which the larval mouth and foregut are also being remodeled to function in benthic feeding by juveniles. That an oral brush is clearly present in at least some larval stages of two genera suggests that oral brushes may be widespread in the feeding larvae of nephtyids, but have simply been overlooked for more than 80 years. Additional work is needed to make inferences on the evolutionary history of the oral brush in phyllodocidan annelids, and to distinguish among several hypotheses on the function of this peculiar group of cilia in larval feeding.
A method for deriving the genetic matrix needed for selection across combinations of breeds
Authors: Barwick Stephen A. , Johnston David J. , Walmsley Bradley J. , Jeyaruban M. Gilbert , Boerner Vincent
Published: April 2020

A method is described for deriving the genetic matrix G needed for breeders to select across breeds for any breeding objective. The matrix comprises partitions among selection criteria (G11), between selection criteria and the breeding objective traits (G12), and among the breeding objective traits (G22). A weighting procedure is used to combine the G matrix of individual breeds with known breed differences. Between‐breed variances are added to the diagonals of the matrix. Selection across many breeds can be quite different from that across a subset of the breeds. The particular breeds, and the numbers of each breed, that the breeder is prepared to consider in selection changes the genetic matrix and the selection index that should be used.
Smad2/3‐pathway ligand trap luspatercept enhances erythroid differentiation in murine β‐thalassaemia by increasing GATA‐1 availability
Authors: Martinez Pedro A. , Li Robert , Ramanathan Harish N. , Bhasin Manoj , Pearsall R. Scott , Kumar Ravindra , Suragani Rajasekhar N. V. S.
Published: April 2020

In β‐thalassaemia, anaemia results from ineffective erythropoiesis characterized by inhibition of late‐stage erythroid differentiation. We earlier used luspatercept and RAP‐536 protein traps for certain Smad2/3‐pathway ligands to implicate Smad2/3‐pathway overactivation in dysregulated erythroid differentiation associated with murine β‐thalassaemia and myelodysplasia. Importantly, luspatercept alleviates anaemia and has been shown to reduce transfusion burden in patients with β‐thalassaemia or myelodysplasia. Here, we investigated the molecular mechanisms underlying luspatercept action and pSmad2/3‐mediated inhibition of erythroid differentiation. In murine erythroleukemic (MEL) cells in vitro, ligand‐mediated overactivation of the Smad2/3 pathway reduced nuclear levels of GATA‐1 (GATA‐binding factor‐1) and its transcriptional activator TIF1γ (transcription intermediary factor 1γ), increased levels of reactive oxygen species, reduced cell viability and haemoglobin levels, and inhibited erythroid differentiation. Co‐treatment with luspatercept in MEL cells partially or completely restored each of these. In β‐thalassaemic mice, RAP‐536 up‐regulated Gata1 and its target gene signature in erythroid precursors determined by transcriptional profiling and gene set enrichment analysis, restored nuclear levels of GATA‐1 in erythroid precursors, and nuclear distribution of TIF1γ in erythroblasts. Bone marrow cells from β‐thalassaemic mice treated with luspatercept also exhibited restored nuclear availability of GATA‐1 ex vivo. Our results implicate GATA‐1, and likely TIF1γ, as key mediators of luspatercept/RAP‐536 action in alleviating ineffective erythropoiesis.
Diabetes aggravates myocardial ischaemia reperfusion injury via activating Nox2‐related programmed cell death in an AMPK‐dependent manner
Authors: Wang Chunyan , Zhu Lijie , Yuan Wenlin , Sun Lingbin , Xia Zhengyuan , Zhang Zhongjun , Yao Weifeng
Published: April 2020

Cardiovascular diseases such as myocardial ischaemia have a high fatality rate in patients with diabetes. This study was designed to expose the crosstalk between oxidative stress and AMPK, a vital molecule that controls biological energy metabolism, in myocardial ischaemia reperfusion injury (I/RI) in diabetic rats. Diabetes was stimulated in rats using streptozotocin injection. Rats were separated on random into control, control + I/R, Diabetes, Diabetes + I/R, Diabetes + I/R + N‐acetylcysteine and Diabetes + I/R + Vas2870 groups. Myocardial infarct size was determined, and the predominant Nox family isoforms were analysed. In vitro, the H9C2 cells were administered excess glucose and exposed to hypoxia/reoxygenation to mimic diabetes and I/R. The AMPK siRNA or AICAR was used to inhibit or activate AMPK expression in H9C2 cells, respectively. Then, myocardial oxidative stress and programmed cell death were measured. Diabetes or high glucose levels were found to aggravate myocardial I/RI or hypoxia/reoxygenation in H9C2 cells, as demonstrated by an increase in myocardial infarct size or lactate dehydrogenase levels, oxidative stress generation and induction of programmed cell death. In diabetic rat hearts, cardiac Nox1, Nox2 and Nox4 were all heightened. The suppression of Nox2 expression using Vas2870 or Nox2‐siRNA treatment in vivo or in vitro, respectively, protected diabetic rats from myocardial I/RI. AMPK gene knockout increased Nox2 protein expression while AMPK agonist decreased Nox2 expression. Therefore, diabetes aggravates myocardial I/RI by generating of Nox2‐associated oxidative stress in an AMPK‐dependent manner, which led to the induction of programmed cell death such as apoptosis, pyroptosis and ferroptosis.
Medication errors in outpatient pharmacies: comparison of an electronic and a paper-based prescription system
Authors: Ababneh Mera A , Al-Azzam Sayer I , Alzoubi Karem H , Rababa'h Abeer M
Published: April 2020

Objectives

Medication errors are among the most common medical errors. They can result in mortality, morbidity and additional healthcare costs. Surveillance of medication errors is encouraged to identify gaps in the healthcare system and work on them. This study aimed to compare medication errors in outpatient prescriptions in two hospitals in Jordan: one with a paper-based and one with an electronic prescription system.

Methods

This was a cross-sectional observational study in two large hospitals in Jordan over a three-month period. Prescribing and dispensing of medicines were screened for medication errors in both centres: 2500 prescriptions were screened in each hospital.

Key findings

In the hospital with electronic prescriptions, of the 2500 prescriptions screened, 631 medication errors were detected: 231 (36.6%) prescription errors and 400 (63.4%) dispensing errors. In the hospital with paper-based prescriptions, 3714 medication errors were found: 288 (7.8%) prescription errors and 3426 (92.2%) dispensing errors. The most common prescription and dispensing errors in electronic prescriptions were, respectively, prescription of drugs that could have a drug–drug interaction, and omitting to dispense a drug on the prescription. In the paper prescriptions, the most common prescription and dispensing errors were, respectively, inappropriate dose/quantity/frequency or route of administration, and inappropriate and/or inadequate labelling of medication when dispensed, of which there were a large number (2496 (67.2%)).

Conclusion

This study highlights the effect of the prescription system used by hospitals. Fewer medication errors were found in the electronic system. Healthcare policymakers, professionals and administrators are encouraged to invest in electronic systems to minimize medication errors.
Outcome of SUB placement for the treatment of benign ureteral obstruction in dogs: nine dogs and 12 renal units (2013 to 2017)
Authors: Milligan M. L. , Berent A. C. , Weisse C. W. , Lamb K. , Toizer E.
Published: April 2020

Objectives

To describe a group of dogs with benign ureteral obstruction(s) treated by subcutaneous ureteral bypass and report the intra‐operative, peri‐operative, short‐ and long‐term outcomes.

Materials and Methods

Review of medical records of dogs that underwent subcutaneous ureteral bypass.

Results

Nine dogs (12 renal units) were included. Causes of obstruction included: ureterolithiasis (n=9) extraluminal compression (n=2), and stricture (n=1). Eleven of 12 ureters had a previously placed stent and required subcutaneous ureteral bypass for: recurrent stricture (n=4), diffuse ureteritis (n=4) or stent migration (n=3). Placement was successful in all renal units and there were no peri‐operative or procedure‐related deaths. Median hospitalisation time was 3 days. The median creatinine values pre‐operatively and 3 month post‐operatively were 186 and 106 μmol/L, respectively. No dog had worsening azotaemia in the short‐term. The most common long‐term complication was mineralisation of six devices, of which four required exchange. All dogs that were infected post‐operatively (n=5) had a history of at least one urinary tract infection pre‐operatively. One of the nine dogs had a chronic post‐operative urinary tract infection and had been chronically infected before placing the bypass. The median survival time was >774 days, with five of nine dogs alive at the time of publication.

Clinical Significance

Placement of a subcutaneous ureteral bypass was an effective short‐term treatment option for benign ureteral obstructions in dogs but there was a high rate of device mineralisation.
The Implications of Firm‐Specific Policy Risk, Policy Uncertainty, and Industry Factors for Inventory: A Resource Dependence Perspective
Authors: Darby Jessica L. , Ketchen David J. , Williams Brent D. , Tokar Travis
Published: April 2020

The risk created by government policymaking can be daunting, but little is known about the extent to which this risk is disruptive to business in general and to supply chain operations in particular. Because government is a powerful and omnipresent entity, scholars and executives alike could benefit from greater understanding of how firms react to risk emanating from the policymaking process. To help address this gap, we use resource dependence theory to develop hypotheses concerning the accumulation of inventory by firms to buffer against their exposure to potential policy changes and how such a link might be moderated by macro‐level and industry‐level factors. Data from 19,634 firm‐year observations reveal that firms accumulate more inventory as a buffer against policy risk under conditions of high policy uncertainty and high industry dynamism. Overall, our findings support the predictions of resource dependence theory and refine understanding of supply chain responses to macro‐level uncertainty by demonstrating the contingent influence of government policy. In doing so, our study provides a foundation for future research to explore the intersections between government actions and supply chain activities and offers insights for managers and policymakers about how to factor government into their decision calculi.
Maternal nutritional status mediates the association between maternal age and birth outcomes
Authors: Workicho Abdulhalik , Belachew Tefera , Argaw Alemayehu , Roba Alemzewed , Ghosh Shibani , Kershaw Meghan , Lachat Carl , Kolsteren Patrick
Published: April 2020

Young maternal age during pregnancy is linked with adverse birth outcomes. This study examined the role of maternal nutritional status in the association between maternal age and small for gestational age (SGA) delivery and birth length. We used data from a birth cohort study in Ethiopia, involving women who were 15–24 years of age and their newborns. A mediation analysis was fitted in a sample of 1,422 mother infant dyads for whom data on birth length were available, and 777 dyads for whom gestational age and birth weight was measured. We used commands, medeff for the mediation analysis and medsens for sensitivity analysis in STATA 14. Maternal nutritional status, measured by mid‐upper arm circumference, mediated 21% of the association between maternal age and birth length and 14% of the association with SGA delivery. The average direct effect (ADE) of maternal age on birth length was (β = 0.45, 95% CI [0.17, 0.99]) and the average causal mediated effect (ACME) was (β = 0.12, 95% CI [0.02, 0.15]). We also found an ADE (β = 0.31, 95% CI [0.09, 0.47]) and an ACME of (β = 0.05, 95% CI [0.003, 0.205]) of maternal age on SGA delivery. The sensitivity analysis suggests an unmeasured confounder with a positive correlation of 0.15 and 0.20 between the mediator and the outcome could explain the observed ACME for birth length and SGA, respectively. We cannot make strong causal assertions as the findings suggest the mediator partly explained the total effect of maternal age on both outcomes.
After Study Abroad: The Maintenance of Multilingual Identity Among Anglophone Languages Graduates
Authors: MITCHELL ROSAMOND , TRACY–VENTURA NICOLE , HUENSCH AMANDA
Published: April 2020

For L2 learners from English‐dominant societies, study abroad (SA) is an especially significant opportunity for linguistic, sociocultural, and personal development. Less is known about the durability of these SA‐related developments, once Anglophone language specialists complete their home studies and then progress to graduate careers. This article reports a study of 33 specialist languages graduates from a UK university, 3 years postgraduation, who had previously participated in a longitudinal study tracking their linguistic, social, and personal development through a 2‐semester stay abroad. The follow‐up study gathered further data on maintenance, development, or attrition of their principal SA‐related second language (L2); on social and professional uses of L2 and other languages; and on attitudes and beliefs relating to language identity. Personal biographies and career pathways were documented through questionnaires and interviews. This article provides insights into the career entry and related ongoing development of linguistic identity among Anglophone languages graduates, including the ongoing impact of SA‐related influences. Implications are briefly drawn for management of the SA experience and post‐SA education, so as to support participants’ ambitions for interculturality and a full multilingual identity.
Tomato T2 ribonuclease LE is involved in the response to pathogens
Authors: Singh Naveen Kumar , Paz Einat , Kutsher Yaarit , Reuveni Moshe , Lers Amnon
Published: April 2020

T2 ribonucleases (RNases) are RNA‐degrading enzymes that function in various cellular processes, mostly via RNA metabolism. T2 RNase‐encoding genes have been identified in various organisms, from bacteria to mammals, and are most diverse in plants. The existence of T2 RNase genes in almost every organism suggests an important biological function that has been conserved through evolution. In plants, T2 RNases are suggested to be involved in phosphate scavenging and recycling, and are implicated in defence responses to pathogens. We investigated the function of the tomato T2 RNase LE, known to be induced by phosphate deficiency and wounding. The possible involvement of LE in pathogen responses was examined. Expression analysis showed LE induction during fungal infection and by stimuli known to be associated with pathogen inoculation, including oxalic acid and hydrogen peroxide. Analysis of LE‐suppressed transgenic tomato lines revealed higher susceptibility to oxalic acid, a cell death‐inducing factor, compared to the wild type. This elevated sensitivity of LE‐suppressed lines was evidenced by visual signs of necrosis, and increased ion leakage and reactive oxygen species levels, indicating acceleration of cell death. Challenge of the LE‐suppressed lines with the necrotrophic pathogen Botrytis cinerea resulted in accelerated development of disease symptoms compared to the wild type, associated with suppressed expression of pathogenesis‐related marker genes. The results suggest a role for plant endogenous T2 RNases in antifungal activity.
Mouth breathing impairs the development of temporomandibular joint at a very early stage
Authors: Hu Zhekai , Sun Huijun , Wu Yanqi , Wu Xingwen , Mei Peng , Wang Bing , Zhu Min
Published: April 2020

Objectives

The study aimed to explore the effects of mouth breathing and hypoxia on the condyle of temporomandibular joint (TMJ) via two animal models.

Methods

24 four‐week‐old rats were randomly separated into three groups, consisting of eight control rats, eight intermittent hypoxia (IH) rats, and eight intermittent nasal obstruction (INO) rats. We use the IH model and the INO model to simulate children suffering from hypoxia and mouth breathing. After 16 days, the condyle of TMJ and surrounding white adipose tissue (WAT) and skeletal muscle tissue were obtained for further staining and qRT‐PCR. Finally, RNA‐seq was used to verify the results.

Results

The intermittent hypoxia cannot significantly change the overall structure in the cause of short‐term hypoxia stimulation, but the intermittent nasal obstruction can alter the condyle, WAT, and muscle, while also introducing noticeable structural changes in tissue hypoxia and macrophage infiltration. Sequencing data verified these findings and also suggested that this process might involve the Hif‐1α/Vegf axis.

Conclusions

Our findings reveal the very early structural impact of mouth breathing on condyle reconstruction in rat models, and hypoxia does not induce evident alteration on condyle. However, since these results are mainly focused on rats, further studies are needed to understand its effects on humans.
De novo perihilar cholangiocarcinoma arising in the allograft liver 15 years post‐transplantation for biliary atresia
Authors: Zen Yoh , Srinivasan Parthi , Kitagawa Misa , Suzuki Koichi , Heneghan Michael , Prachalias Andreas
Published: April 2020

Most primary liver cancers diagnosed in allograft livers are recurrent tumors of the native liver origin, while donor‐derived primary liver cancers are markedly less common. A 21‐year‐old woman who had liver transplantation for post‐Kasai biliary atresia was recently referred for post‐transplant biliary stricture. Her transplantation was performed at the age of 6 years using the whole liver graft from a 10‐year‐old donor and choledocho‐jejunostomy. The post‐transplant course was uneventful in the first 15 years until she presented with obstructive jaundice. The stricture was located at the level of the hepaticojejunostomy, and required percutaneous transhepatic drainage and bile duct dilatation. She underwent an exploratory laparotomy, which suggested a neoplastic process widely involving the extrahepatic and intrahepatic large bile ducts. The histological examination of the resected extrahepatic bile duct confirmed infiltrating moderately differentiated adenocarcinoma. Molecular tests of multiple short tandem repeat loci confirmed the donor origin of the tumor. After four cycles of chemotherapy with gemicitabine and cisplatin, she is currently on radiotherapy in view of potential re‐transplantation. De novo, post‐transplant cholangiocarcinoma of graft origin is extremely uncommon with only three other cases reported. Two were associated with recurrent primary sclerosing cholangitis, and all had choledocho‐jejunostomy at the time of transplantation.
Heavy metal pollution improves allelopathic effects of Canada goldenrod on lettuce germination
Authors: Wei M. , Wang S. , Wu B. , Cheng H. , Wang C.
Published: April 2020

Large amounts of heavy metals have been released into the environment. Thus, the allelopathic effects of invasive alien species on the germination performance of co-occurring indigenous species may be altered or even heightened with the rapid growth in heavy metal pollution.

This study evaluated the impacts of Canada goldenrod (Solidago canadensis L.) leaf extracts at concentrations of 0, 10 or 20 gl 1 on the germination of lettuce under different forms of heavy metal pollution (Cu2+, Pb2+ or a combination of Cu2+ and Pb2+; 35 mgl 1) during incubation in Petri dishes for 10 days.

Goldenrod leaf extracts (high concentration) reduced growth of aboveground and belowground parts of lettuce as well as competition for light and soil nutrients. However, low concentrations of goldenrod leaf extracts dramatically improved growth of lettuce roots, competition for light, soil nutrient availability, leaf photosynthetic area and growth competitiveness. The combination of goldenrod leaf extracts and heavy metal pollution was synergistic on most lettuce germination parameters, probably because high concentrations of goldenrod leaf extracts together with heavy metal pollution had a synergistic negative impact on lettuce germination.

Consequently, increased levels of heavy metal pollution may favour invasion of invasive alien species while largely suppressing germination of indigenous species.
The complex Hamiltonian systems and quasi‐periodic solutions in the derivative nonlinear Schrödinger equations
Authors: Chen Jinbing , Zhang Runsu
Published: April 2020

The complex Hamiltonian systems with real‐valued Hamiltonians are generalized to deduce quasi‐periodic solutions for a hierarchy of derivative nonlinear Schrödinger (DNLS) equations. The DNLS hierarchy is decomposed into a family of complex finite‐dimensional Hamiltonian systems by separating the temporal and spatial variables, and the complex Hamiltonian systems are then proved to be integrable in the Liouville sense. Due to the commutability of complex Hamiltonian flows, the relationship between the DNLS equations and the complex Hamiltonian systems is specified via the Bargmann map. The Abel‐Jacobi variable is elaborated to straighten out the DNLS flows as linear superpositions on the Jacobi variety of an invariant Riemann surface. Finally, by using the technique of Riemann‐Jacobi inversion, some quasi‐periodic solutions are obtained for the DNLS equations in view of the Riemann theorem and the trace formulas.