bluuebunny/crossref_metadata_2025 huggingface dataset:
Losing your footing, losing your morality
Authors: Li Heng , Cao Yu
Published: January 2020

What influences how people render their moral judgment? Focusing specifically on the conceptual metaphors “moral is upright” and “immoral is tilted”, we sought to investigate whether physical slant can influence people’s harsh moral judgment. Experiment 1 induced physical slant by having participants complete the questionnaire at a tilt table. We observed a significant effect with participants who experienced physical slant rendering a less severe moral judgment than did those who wrote their responses at a level table. Using a new manipulation of physical slant and a larger, more diverse sample, Experiment 2 asked participants to complete the questionnaires with rotated text or normal text. We observed a difference between the two groups: compared to participants who read the normal text, those with a visual experience of slant lessened the severity of their moral judgments. Taken together, the results showed that the consequence of tilted experience exerts downstream effects on moral reasoning, which suggests that incidental bodily experience affects how people render their decisions.
Mechanical and tribological behaviours of aluminium hybrid composites reinforced by CDA-B4C
Authors: Manikandan R , Arjunan T V
Published: January 2020

This study focuses on fabricating aluminium hybrid metal matrix composites reinforced with eco-friendly agro waste, cow dung ash and boron carbide by two stage stir casting. Weight percentage of cow dung ash and boron carbide were added in ratios of 2.5:7.5, 5:5, and 7.5:2.5. The effects on mechanical properties like hardness, tensile strength, impact strength, flexural strength and wear behaviour were studied. SEM and EDX analysis were employed to study the fracture mechanism for tensile, impact and wear specimens. Optical microstructure images reveal uniform distribution of particles and XRD analysis confirms the presence of reinforcements. Increasing CDA particles has reduced the density of the hybrid composite up to 8%. A maximum increase in hardness, tensile strength and wear resistance was up to 30%, 56% and 56% respectively, and then a slight decrease in impact was found in increasing the CDA particles. Dimples, transgranular cleavage facets, cracks and micro ploughing, micro cuttings are revealed from the fractured specimens of tensile, impact and wear respectively.
Enhancement the rhodamine 6G adsorption property on Fe3O4-composited biochar derived from rice husk
Authors: Suwunwong Thitipone , Patho Pimchanok , Choto Patcharanan , Phoungthong Khamphe
Published: January 2020

Magnetic biochars were prepared using Fe3O4 nanoparticle composites onto the surface of biochar derived from rice husk. The characteristics of magnetic biochar were characterized by scanning electron microscope, x-ray powder diffraction and Fourier-transform infrared techniques. The removal of rhodamine 6G dye by magnetic biochar, compared to pristine biochar was studied. The effects of pyrolysis temperature on rhodamine 6G adsorption was evaluated. Kinetic, isotherms and thermodynamic studies were carried out to investigate the adsorption mechanism of rhodamine 6G dye on magnetic biochar surface. The rhodamine 6G removal efficiency of Fe3O4-composited biochar (pyrolyzed at 500 °C) is higher than that of pristine biochar with maximum efficiency of 94% removal. The adsorption isotherm and kinetic studies indicated that the langmuir model, pseudo-first order and pseudo-second order models described well the rhodamine adsorption onto magnetic Fe3O4-biochar.
BMDx: a graphical Shiny application to perform Benchmark Dose analysis for transcriptomics data
Authors: Serra Angela , Saarimäki Laura Aliisa , Fratello Michele , Marwah Veer Singh , Greco Dario
Published: January 2020

Motivation

The analysis of dose-dependent effects on the gene expression is gaining attention in the field of toxicogenomics. Currently available computational methods are usually limited to specific omics platforms or biological annotations and are able to analyse only one experiment at a time.

Results

We developed the software BMDx with a graphical user interface for the Benchmark Dose (BMD) analysis of transcriptomics data. We implemented an approach based on the fitting of multiple models and the selection of the optimal model based on the Akaike Information Criterion. The BMDx tool takes as an input a gene expression matrix and a phenotype table, computes the BMD, its related values, and IC50/EC50 estimations. It reports interactive tables and plots that the user can investigate for further details of the fitting, dose effects and functional enrichment. BMDx allows a fast and convenient comparison of the BMD values of a transcriptomics experiment at different time points and an effortless way to interpret the results. Furthermore, BMDx allows to analyse and to compare multiple experiments at once.

Availability and implementation

BMDx is implemented as an R/Shiny software and is available at https://github.com/Greco-Lab/BMDx/.

Supplementary information

Supplementary data are available at Bioinformatics online.
RxnBLAST: molecular scaffold and reactive chemical environment feature extractor for biochemical reactions
Authors: Cheng Xingxiang , Sun Dandan , Zhang Dachuan , Tian Yu , Ding Shaozhen , Cai Pengli , Hu Qian-Nan
Published: January 2020

Motivation

Molecular scaffolds are useful in medicinal chemistry to describe, discuss and visualize series of chemical compounds, biochemical transformations and associated biological properties.

Results

Here, we present RxnBLAST as a web-based tool for analyzing scaffold transformations and reactive chemical environment features in bioreactions. RxnBLAST extracts chemical features from bioreactions including atom–atom mapping, reaction centers, rules and functional groups to help understand chemical compositions and reaction patterns. Core-to-Core is proposed, which can be utilized in scaffold networks and for constructing a reaction space, as well as providing guidance for subsequent biosynthesis efforts.

Availability and implementation

RxnBLAST is available at: http://design.rxnfinder.org/rxnblast/.
Plasma neutrophil gelatinase-associated lipocalin at intensive care unit admission as a predictor of acute kidney injury progression
Authors: Koeze Jacqueline , van der Horst Iwan C C , Keus Frederik , Wiersema Renske , Dieperink Wim , Kootstra-Ros Jenny E , Zijlstra Jan G , van Meurs Matijs
Published: January 2020

Background

Acute kidney injury (AKI) is a common complication in patients during intensive care unit (ICU) admission. AKI is defined as an increase in serum creatinine (SCr) and/or a reduction in urine output. SCr is a marker of renal function with several limitations, which led to the search for biomarkers for earlier AKI detection. Our aim was to study the predictive value of plasma neutrophil gelatinase-associated lipocalin (NGAL) at admission as a biomarker for AKI progression during the first 48 h of ICU admission in an unselected, heterogeneous ICU patient population.

Methods

We conducted a prospective observational study in an academic tertiary referral ICU population. We recorded AKI progression in all ICU patients during the first 48 h of ICU admission in a 6-week period. Plasma NGAL was measured at admission but levels were not reported to the attending clinicians. As possible predictors of AKI progression, pre-existing AKI risk factors were recorded. We examined the association of clinical parameters and plasma NGAL levels at ICU admission with the incidence and progression of AKI within the first 48 h of the ICU stay.

Results

A total of 361 patients were included. Patients without AKI progression during the first 48 h of ICU admission had median NGAL levels at admission of 115 ng/mL [interquartile range (IQR) 81–201]. Patients with AKI progression during the first 48 h of ICU admission had median NGAL levels at admission of 156 ng/mL (IQR 97–267). To predict AKI progression, a multivariant model with age, sex, diabetes mellitus, body mass index, admission type, Acute Physiology and Chronic Health Evaluation score and SCr at admission had an area under the receiver operating characteristics (ROC) curve of 0.765. Adding NGAL to this model showed a small increase in the area under the ROC curve to 0.783 (95% confidence interval 0.714–0.853).

Conclusions

NGAL levels at admission were higher in patients with progression of AKI during the first 48 h of ICU admission, but adding NGAL levels at admission to a model predicting this AKI progression showed no significant additive value.
Spectral analysis for gene communities in cancer cells
Authors: Kikkawa Ayumi
Published: January 2020

We investigate gene interaction networks in various cancer cells by spectral analysis of the adjacency matrices. We observe the localization of the networks on hub genes, which have an extraordinary number of links. The eigenvector centralities take finite values only on special nodes when the hub degree exceeds the critical value $d_c \simeq 40$. The degree correlation function shows the disassortative behaviour in the large degrees, and the nodes whose degrees are $d \gtrsim 40$ have a tendency to link to small degree nodes. The communities of the gene networks centred at the hub genes are extracted based on the amount of node degree discrepancies between linked nodes. We verify the Wigner–Dyson distribution of the nearest neighbour eigenvalues spacing distribution $P(s)$ in the small degree discrepancy communities (the assortative communities), and the Poisson $P(s)$ in the communities of large degree discrepancies (the disassortative communities) including the hubs.
Antibiotic resistance patterns of Pseudomonas spp. isolated from faecal wastes in the environment and contaminated surface water
Authors: Camiade Mathilde , Bodilis Josselin , Chaftar Naouel , Riah-Anglet Wassila , Gardères Johan , Buquet Sylvaine , Ribeiro Angela Flores , Pawlak Barbara
Published: January 2020

The Pseudomonas genus, which includes environmental and pathogenic species, is known to present antibiotic resistances, and can receive resistance genes from multi-resistant enteric bacteria released into the environment via faecal rejects. This study was aimed to investigate the resistome of Pseudomonas populations that have been in contact with these faecal bacteria. Thus, faecal discharges originating from human or cattle were sampled (from 12 points and two sampling campaigns) and 41 Pseudomonas species identified (316 isolates studied). The resistance phenotype to 25 antibiotics was determined in all isolates, and we propose a specific antibiotic resistance pattern for 14 species (from 2 to 9 resistances). None showed resistance to aminoglycosides, tetracycline, or polymyxins. Four species carried a very low number of resistances, with none to β-lactams. Interestingly, we observed the absence of the transcriptional activator soxR gene in these four species. No plasmid transfer was highlighted by conjugation assays, and a few class 1 but no class 2 integrons were detected in strains that may have received resistance genes from Enterobacteria. These results imply that the contribution of the Pseudomonas genus to the resistome of an ecosystem first depends on the structure of the Pseudomonas populations, as they may have very different resistance profiles.
Prevalence of gastroesophageal reflux disease: a population-based cross-sectional study in southern Chile
Authors: Manterola Carlos , Grande Luis , Bustos Luis , Otzen Tamara
Published: January 2020

Background

This study assessed the prevalence of gastroesophageal reflux disease (GERD) in a general adult population from Temuco in southern Chile. The association of GERD with demographic variables was also examined.

Methods

A cross-sectional study among the general population of Temuco in southern Chile was conducted in 2017, using a validated and reliable questionnaire for detecting GERD. The urban area of Temuco, with a population of 245,317 inhabitants (2002 census), was divided into four zones, which were representative of the socioeconomic sectors of the city. The sample size was estimated assuming a prevalence of 52.8%, an accuracy of 3.0%, a confidence level of 95.0%, and a design effect of 1.15. Area sampling was used to build clusters. The prevalence of GERD was determined and associated factors were studied by means of bivariate and multivariate analyses.

Results

A total of 1,069 subjects (47.9% women, median age 40 years) from the selected subareas were interviewed. The prevalence of GERD was 44.8%. The most frequently reported symptom was regurgitation (54.8%). One-third of subjects took medication to control symptoms and was considered ‘sick’ by the instrument, although >68% of them had never sought medical consultation. There was a significant association between GERD and age (P < 0.001) and female gender (P = 0.001).

Conclusions

In this population-based study, the prevalence of GERD was high (44.8%). GERD was associated with age and female gender.
Mechanisms of Racial Disparities in Cognitive Aging: An Examination of Material and Psychosocial Well-Being
Authors: Peterson Rachel L , Butler Emily A , Ehiri John E , Fain Mindy J , Carvajal Scott C
Published: January 2020

Objectives

We tested the hypothesis that education’s effect on cognitive aging operates in part through measures of material and psychosocial well-being.

Method

Our sample was of non-Latino black and white participants of the National Social Life Health and Aging Project who had valid cognitive assessments in Waves 2 and 3 (n = 2,951; age range: 48–95). We used structural equation modeling to test for mediation and moderated mediation by income, assets, perceived stress, social status, and allostatic load on the relationships between race, education, and cognition at two time points.

Results

Education consistently mediated the race–cognition relationship, explaining about 20% of the relationship between race and cognition in all models. Income and assets were moderated by race; these factors were associated with cognition for whites but not blacks. Social status mediated the association between race and cognition, and social status and perceived stress mediated the education–cognition pathway. Allostatic load was not a mediator of any relationship.

Discussion

Education remains the best explanatory factor for cognitive aging disparities, though material well-being and subjective social status help to explain a portion of the racial disparity in cognitive aging.
Internet Use and Loneliness of Older Adults Over Time: The Mediating Effect of Social Contact
Authors: Yu Kexin , Wu Shinyi , Chi Iris
Published: January 2020

Objectives

The internet is increasingly commonly used by older adults. However, it remains controversial in the literature on whether older people are more or less lonely with internet adoption. The current paper aims to test the longitudinal association of internet use and loneliness and to theorize the relationship by examining the mediating effect of social contact.

Method

This study employed data from 2006, 2010, and 2014 waves of the Health and Retirement Study. Loneliness was measured with the three-item UCLA loneliness scale, social contact was operationalized as contact frequency with family and friends, and internet use was measured using a self-assessed dichotomous item. Longitudinal associations and mediation effects were tested using hierarchical linear modeling.

Results

Internet use was associated with decreased loneliness over an 8-year period (b = −0.049, p < .001) and more social contact (b = 0.285, p < .001), which was related to lower perceived loneliness (b = −0.088, p < .001). On a scale ranges from 0 to 2 (0 = never lonely, 2 = often lonely), the total effect of internet use on loneliness was −0.060, and the mediated effect was −0.025.

Discussion

These findings imply that internet use may be an effective tool for reducing loneliness in older people by maintaining social contact.
Repairing Symbolic Reparations: Assessing the Effectiveness of Memorialization in the Inter-American System of Human Rights
Authors: Greeley Robin Adèle , Orwicz Michael R , Falconi José Luis , Reyes Ana María , Rosenberg Fernando J , Laplante Lisa J
Published: January 2020

ABSTRACT∞

The power of memorialization is widely recognized as a form of symbolic reparation aimed at overcoming deep social divisions in the aftermath of mass violence. Yet memorialization as a juridical tool of repair lacks systematic conceptual elaboration, and its potential remains underutilized. This often results in ineffective, even detrimental monuments, and in programmatic failures to integrate memorial practices into multilayered strategies for justice and social reconciliation. This article explores three case studies from the Inter-American Human Rights System in order to examine the strengths and shortcomings of existing approaches to memorialization. We then offer recommendations for expanding the reparative and transformative capacities of symbolic reparations. We conclude by summarizing our observations on how the fundamentally expressive nature of symbolic reparations provides a potentially powerful tool of repair and transformation.
Risk of Burn Injury in Patients With Narcolepsy: A Nationwide Population-Based Cohort Study
Authors: Chang En-Ting , Lin Cheng-Li , Chen Shih-Fen , Shen Yu-Chih
Published: January 2020

Narcolepsy is a rare brain disorder characterized by excessive daytime sleepiness (EDS), cataplexy, hypnagogic hallucinations, and sleep paralysis. Stimulants have been used to relieve the symptoms of EDS. Narcolepsy symptoms may pose a risk to burn injury. The study aimed to investigate the risk of burn injury in narcolepsy patients and to examine the relationship between the use of stimulants and the risk of burn injury. In all, 507 narcolepsy patients and 504 controls matched by gender, age, index year, and Charlson Comorbidity Index (CCI) score were enrolled between 1998 and 2012, then followed until the end of 2013 using Taiwan’s National Health Insurance Research Database. During the follow-up period, participants who developed burn injury were identified. Cox regression analysis was used to calculate the hazard ratio (HR) with 95% confidence interval (CI) of the burn incidence rate between narcolepsy patients and unaffected controls. Narcolepsy patients had a significantly increased risk of burn injury compared to unaffected controls (5.37 versus 2.69 per 1,000 person-years, HR: 2.04, 95% CI: 1.13–3.67) after adjusting for gender, age, CCI score, urbanization degree, and duration of stimulants use. Also, the use of stimulants in narcolepsy patients was associated with a lower incidence rate of developing burn injury, but the risk estimate was not statistically significant after adjusting for the above-mentioned variables. This study shows narcolepsy patients have an increased risk of burn injury and the use of stimulants may reduce the burn incidence rate, providing a reference for developing prevention interventions.
Cimex lectularius Linnaeus, 1758 (Hemiptera: Cimicidae) in Costa Rica: First Case Report Confirmed by Molecular Methods in Central America
Authors: Cambronero-Heinrichs Juan Carlos , Sánchez-Portilla Laura Sofía , Calderón-Arguedas Ólger , Troyo Adriana
Published: January 2020

Cimex lectularius and Cimex hemipterus are the most common species of bedbugs that infest homes. Although case reports decreased substantially by the end of the 20th century, bed bugs, and especially C. lectularius, are currently suffering a resurgence mostly attributed to insecticide resistance, inadequate pest control, and increased travel. Here, we report, to the best of our knowledge, the first molecular confirmation of C. lectularius in Central America. Specimens were obtained from an apartment located in Heredia, Costa Rica. These specimens were identified morphologically as C. lectularius. The species identification was confirmed by amplifying and sequencing fragments of the cytochrome oxidase subunit I (COI) and the 16S rRNA (16S) genes. The phylogenetic analysis showed that the sequences obtained were more closely related to a C. lectularius mitochondrial complete genome sequence from China, with similarities of 98.84% (686/694) for COI and 98.97% (387/391) for 16S. The finding of C. lectularius in Costa Rica will require further investigation in order to determine the extent of current infestations and the susceptibility to insecticides, especially due to the impact that this species can have in human health, as well as the tourism industry in the region.
Oil and Security: The Necessity of Political Economy
Authors: Colgan Jeff D
Published: January 2020

Many international conflicts are in some way related to energy, ever since oil became the world's preeminent strategic commodity in the early 20th century. I argue that the most important energy-related variable for international conflict is a state's net oil import position. Oil politics tends to appear in one of three ways in security studies. Some have emphasized resource wars; others have focused on the needs of oil importers; and still others on the pathologies of oil exporters. These disparate approaches, largely isolated from each other, can better be understood as relating to a single explanatory variable. Lots of other variables matter but none are as central as net oil imports. This means that to understand energy and security, a political economy framework is a necessity. For oil exporters, external petro-aggression and internal pathologies of the resource curse are the key mechanisms. For oil importers, energy consumption needs generate a plethora of mechanisms that complicate conflict dynamics. A sophisticated understanding of these mechanisms can improve our understanding of both national and global security.
Coinfection With Human Herpesvirus (HHV)-6B in Immunocompetent, Healthy Individuals With Chromosomally Integrated HHV-6A
Authors: Miura Hiroki , Ohye Tamae , Kozawa Kei , Hattori Fumihiko , Kawamura Yoshiki , Ihira Masaru , Kurahashi Hiroki , Yoshikawa Tetsushi
Published: January 2020

Immunocompetent sisters with chromosomally integrated human herpesvirus 6A (HHV-6A) transiently excreted HHV-6B genome in their saliva. They did not have past histories of exanthema subitum but had antibodies against HHV-6A and HHV-6B. This suggests that endogenous HHV-6A may modify the clinical features of HHV-6B coinfection.
A New Interpretation of Leviticus 18:22 (Par. 20:13) and its Ethical Implications*
Authors: Joosten Jan
Published: January 2020

The laws in Lev. 18:22 and 20:13 are general considered to prohibit homosexual intercourse between men. A renewed investigation of the vocabulary used in the prohibition, taking an important cue from Gen. 49:4, points the way to a different understanding. As Reuben lay on his father’s bed, having intercourse with his father’s concubine, so the man addressed in Lev. 18:22 and par. is prohibited to lie on the bed of a woman, having sex with her man. The laws prohibit homosexual intercourse involving a married man.
Three previously characterized resistances to yellow rust are encoded by a single locus Wtk1
Authors: Klymiuk Valentyna , Fatiukha Andrii , Raats Dina , Bocharova Valeria , Huang Lin , Feng Lihua , Jaiwar Samidha , Pozniak Curtis , Coaker Gitta , Dubcovsky Jorge , Fahima Tzion
Published: January 2020

The wild emmer wheat (Triticum turgidum ssp. dicoccoides; WEW) yellow (stripe) rust resistance genes Yr15, YrG303, and YrH52 were discovered in natural populations from different geographic locations. They all localize to chromosome 1B but were thought to be non-allelic based on differences in resistance response. We recently cloned Yr15 as a Wheat Tandem Kinase 1 (WTK1) and show here that these three resistance loci co-segregate in fine-mapping populations and share an identical full-length genomic sequence of functional Wtk1. Independent ethyl methanesulfonate (EMS)-mutagenized susceptible yrG303 and yrH52 lines carried single nucleotide mutations in Wtk1 that disrupted function. A comparison of the mutations for yr15, yrG303, and yrH52 mutants showed that while key conserved residues were intact, other conserved regions in critical kinase subdomains were frequently affected. Thus, we concluded that Yr15-, YrG303-, and YrH52-mediated resistances to yellow rust are encoded by a single locus, Wtk1. Introgression of Wtk1 into multiple genetic backgrounds resulted in variable phenotypic responses, confirming that Wtk1-mediated resistance is part of a complex immune response network. WEW natural populations subjected to natural selection and adaptation have potential to serve as a good source for evolutionary studies of different traits and multifaceted gene networks.
The Crisis of Enlightenment: Jewish Discourses on German Cultural Traditions in National Socialist Germany
Authors: Schoor Kerstin
Published: January 2020

This article explores the self-conceptions of German Jews in National Socialist Germany in the context of a critical rereading of 1930s receptions of the German and European Enlightenment. The transformation of the Jewish community and Jewish culture into a part of bourgeois society had taken place in the course of the German and European Enlightenment, from its beginnings to the foundation of the German Empire in 1871. The efforts of the Jewish minority to ‘emancipate’ itself from any form of heteronomy from around 1820—to become self-reliant and responsible citizens in thought and deed—had become a kind of symbol for the progressive reasoning of the Enlightenment. Consequently, given the aggressive antisemitic policies of the National Socialist state, the German-Jewish relationship to the Enlightenment in internal and public debates after 1933 must be viewed as key when exploring the externally damaged self-conceptions of large parts of the German-Jewish minority. For the writers and artists of Jewish descent examined in this article, the relationship to the Enlightenment—and to German and Jewish culture—was once more open to debate.
Decision-theoretic and risk-based approaches to naked statistical evidence: some consequences and challenges
Authors: Urbaniak Rafal , Kowalewska Alicja , Janda Pavel , Dziurosz-Serafinowicz Patryk
Published: January 2020

In the debate about the legal value of naked statistical evidence, Di Bello argues that (1) the likelihood ratio of such evidence is unknown, (2) the decision-theoretic considerations indicate that a conviction based on such evidence is unacceptable when expected utility maximization is combined with fairness constraints, and (3) the risk of mistaken conviction based on such evidence cannot be evaluated and is potentially too high. We argue that Di Bello’s argument for (1) works in a rather narrow context, and that (1) is not exactly in line with the way expert witnesses are required to formulate their opinions. Consequently, Di Bello’s argument for (2), which assumes (1), does not apply uniformly to all convictions based on naked evidence. Moreover, if Di Bello’s analysis is correct, it applies also to eyewitness testimony, given empirical results about its quality, and so the distinctions drawn by DiBello cut across the distinction between naked statistical evidence and other types of evidence. Finally, if we weaken the rather strong requirement of precise measurability of the risk of mistaken conviction, to the availability of reasonable but imprecise and fallible estimates, many field and empirical studies show that often the risk of mistaken conviction based on naked statistical evidence can be estimated to a similar extent as the risk of mistaken conviction based on any other sort of evidence.
Plasma and cerebrospinal fluid pharmacokinetics of the DNA methyltransferase inhibitor, 5-azacytidine, alone and with inulin, in nonhuman primate models
Authors: Lester McCully Cynthia , Rodgers Louis T , Cruz Rafael , Thomas Marvin L , Peer Cody J , Figg William D , Warren Katherine E
Published: January 2020

Background

Epigenetic modifiers are being investigated for a number of CNS malignancies as tumor-associated mutations such as isocitrate dehydrogenase mutations (IDH1/IDH2) and H3K27M mutations, which result in aberrant signaling, are identified. We evaluated the CNS exposure of the DNA methyltransferase inhibitor, 5-azacytidine (5-AZA), in preclinical nonhuman primate (NHP) models to inform its clinical development for CNS tumors.

Methods

5-AZA and 5-AZA+Inulin pharmacokinetics (PK) were evaluated in NHPs (n = 10) following systemic (intravenous [IV]) and intrathecal (intraventricular [IT-V], intralumbar [IT-L], and cisternal [IT-C]) administration. Plasma, cerebrospinal fluid (CSF), cortical extracellular fluid (ECF), and tissues were collected. 5-AZA levels were quantified via ultra-high-performance liquid chromatography with tandem mass spectrometric detection assay and inulin via ELISA. PK parameters were calculated using noncompartmental methods.

Results

After IV administration, minimal plasma exposure (area under the curve [AUC] range: 2.4–3.2 h*µM) and negligible CSF exposure were noted. CSF exposure was notably higher after IT-V administration (AUCINF 1234.6–5368.4 h*µM) compared to IT-L administration (AUCINF 7.5–19.3 h*µM). CSF clearance after IT administration exceeded the mean inulin CSF flow rate of 0.018 ± 0.003 ml/min as determined by inulin IT-V administration. 5-AZA IT-V administration with inulin increased the 5-AZA CSF duration of exposure by 2.2-fold. IT-C administration yielded no quantifiable 5-AZA ECF concentrations but resulted in quantifiable tissue levels.

Conclusions

IT administration of 5-AZA is necessary to achieve adequate CNS exposure. IT administration results in pronounced and prolonged 5-AZA CSF exposure above the reported IC50 range for IDH-mutated glioma cell lines. Inulin administered with 5-AZA increased the duration of exposure for 5-AZA.
Vaccination practices and influenza in professional football players in Greece
Authors: Papagiannis D , Rachiotis G , Xanthopoulos A , Simou A , Zilidis C , Triposkiadis F
Published: January 2020

Background

There is limited data on vaccination practices for professional footballers globally.

Aims

To record vaccination practices employed by medical staff of individual football teams of the Super League Greece, and absenteeism of footballers related to influenza illness.

Methods

A brief questionnaire was distributed to chief medical officers (CMOs) of the sixteen teams of the Super League Greece. Participants were asked to report vaccines they recommended for footballers. In addition, the questionnaire included questions on new cases of influenza and absenteeism due to influenza. Descriptive statistics (absolute and relative frequencies) were used for the presentation of the results.

Results

Overall, 87% of the CMOs recommended seasonal influenza vaccine, 62% hepatitis B vaccine and 50% pneumococcal vaccine. Fourteen CMOs (87%) reported that the occurrence of seasonal influenza in the 2016–17 northern hemisphere season ranged from one to five cases, while two medical officers (12%) reported zero workdays lost due to influenza.

Conclusions

Our survey shows considerable variation in vaccination practices of CMOs of the Super League Greece. The results of this survey should stimulate further evaluation of vaccination policy and influenza-related absenteeism in footballers.
Epidemiological and Microbiome Associations Between Klebsiella pneumoniae and Vancomycin-Resistant Enterococcus Colonization in Intensive Care Unit Patients
Authors: Collingwood Abigail , Blostein Freida , Seekatz Anna M , Wobus Christiane E , Woods Robert J , Foxman Betsy , Bachman Michael A
Published: January 2020

Background

Prior colonization by Klebsiella pneumoniae and vancomycin-resistant Enterococci (VRE) is associated with subsequent infection, particularly in intensive care unit (ICU) populations. Screening for VRE colonization, but not K. pneumoniae, is routinely performed in some health care systems. Identification of patient factors associated with K. pneumoniae colonization could enable infection prevention.

Methods

ICU patients were screened for VRE and K. pneumoniae by rectal swab culture over 2 time periods: July–October 2014 (n = 1209) and January–May 2016 (n = 1243). Patient demographics, baseline laboratory data, comorbidities, and outcomes were analyzed. 16S rRNA gene-based analysis was performed on a subset of patients (n = 248) to identify microbiota characteristics associated with VRE and K. pneumoniae colonization.

Results

K. pneumoniae colonization (17.3% of patients in the 2014 cohort, 7.3% in 2016) was significantly associated with VRE colonization in multivariable analysis (P = .03 in 2016; P = .08 in 2014). VRE colonization was associated with poor underlying health, whereas K. pneumoniae colonization was associated with advanced age. The most prevalent operational taxonomic units were Escherichia coli/Shigella spp., Klebsiella, and Enterococcus, consistent with high rates of detectable K. pneumoniae and VRE by culture. Microbial community structure in noncolonized patients was significantly different from those with VRE, K. pneumoniae, or both, attributable to differences in the relative abundance of Klebsiella and Enterococcus.

Conclusions

K. pneumoniae co-colonizes with VRE and is a predominant taxon in ICU patients, but colonization was not associated with significant comorbidities. Screening for K. pneumoniae and VRE simultaneously could be an efficient approach for novel infection prevention strategies.
Clinical and Safety Evaluation of Continuously Infused Ceftolozane/Tazobactam in the Outpatient Setting
Authors: Jones Bruce M , Huelfer Kathryn , Bland Christopher M
Published: January 2020

Background

Ceftolozane/tazobactam (C/T) is a novel cephalosporin/β-lactamase inhibitor currently dosed by 8-hour intervals to treat complicated and multidrug-resistant Pseudomonas aeruginosa infections in inpatients. This dosing strategy limits the ability to transition patients to outpatient antimicrobial therapy. There are limited data in the literature to support continuous infusion (CI) dosing.

Methods

This study is a retrospective chart review of patients who received CI C/T at an infusion center part of a community health system. Patients were evaluated from August 2016 through January 2018. Patients were included in the study if they were ≥18 years old and received their entire course of C/T as a CI in the outpatient setting. Patients were excluded if they received any part of their therapy as an inpatient.

Results

The primary outcome evaluated was symptom resolution. Secondary outcomes evaluated were microbiologic resolution as well as patient satisfaction. Seven patients received either 4.5 or 9 grams of continuous infusion C/T every 24 hours in the outpatient setting over the study period. For the primary outcome, 6 of 7 patients had symptom resolution. For the secondary outcomes, 3 of 3 patients had microbiologic resolution, and patient satisfaction scores were overall positive among respondents.

Conclusions

Ceftolozane/tazobactam delivered as a continuous infusion may be a safe, effective, and convenient way to treat infections caused by P aeruginosa. This novel treatment regimen can be an option for patients to avoid hospital admission or discharge to complete therapy as an outpatient.
Burden of Active Tuberculosis in an Integrated Health Care System, 1997–2016: Incidence, Mortality, and Excess Health Care Utilization
Authors: Wada Paul Y , Lee-Rodriguez Christian , Hung Yun-Yi , Skarbinski Jacek
Published: January 2020

Active tuberculosis (TB) is preventable. To quantify the potential value of prevention, we assessed active TB burden in a large health system from 1997 to 2016. Compared with a matched non-TB cohort, patients with active TB had higher mortality (8.4% vs 1.3%), mean number of hospitalizations (0.55 vs 0.10), emergency department visits (0.78 vs 0.28), and outpatient visits (14.6 vs 5.9) in the first year. TB-associated hospital use (mean number of hospitalizations and total length of stay) increased from 1997–2000 compared with 2013–2016 despite decreasing active TB incidence. Active TB is associated with high mortality and health care utilization and has remained stable or increased over time.
Repeated Syphilis Episodes in HIV-Infected Men Who Have Sex With Men: A Multicenter Prospective Cohort Study on Risk Factors and the Potential Role of Syphilis Immunity
Authors: Roth Jan A , Franzeck Fabian C , Balakrishna Suraj , Lautenschlager Stephan , Thurnheer Maria Christine , Trellu Laurence Toutous , Cavassini Matthias , Vernazza Pietro , Bernasconi Enos , Braun Dominique , Kouyos Roger D , Battegay Manuel ,   the Swiss HIV Cohort Study (SHCS), Anagnostopoulos A , Battegay M , Bernasconi E , Böni J , Braun D L , Bucher H C , Calmy A , Cavassini M , Ciuffi A , Dollenmaier G , Egger M , Elzi L , Fehr J , Fellay J , Furrer H , Fux C A , Günthard H F , Haerry D , Hasse B , Hirsch H H , Hoffmann M , Hösli I , Huber M , Kahlert C R , Kaiser L , Keiser O , Klimkait T , Kouyos R D , Kovari H , Ledergerber B , Martinetti G , Martinez de Tejada B , Marzolini C , Metzner K J , Müller N , Nicca D , Paioni P , Pantaleo G , Perreau M , Rauch A , Rudin C , Scherrer A U , Schmid P , Speck R , Stöckle M , Tarr P , Trkola A , Vernazza P , Wandeler G , Weber R , Yerly S
Published: January 2020

Background

Syphilis is re-emerging globally in general and HIV-infected populations, and repeated syphilis episodes may play a central role in syphilis transmission among core groups. Besides sexual behavioral factors, little is known about determinants of repeated syphilis episodes in HIV-infected individuals—including the potential impact of preceding syphilis episodes on subsequent syphilis risk.

Methods

In the prospective Swiss HIV cohort study, with routine syphilis testing since 2004, we analyzed HIV-infected men who have sex with men (MSM). Our primary outcome was first and repeated syphilis episodes. We used univariable and multivariable Andersen-Gill models to evaluate risk factors for first and repeated incident syphilis episodes.

Results

Within the 14-year observation period, we included 2513 HIV-infected MSM with an initially negative syphilis test. In the univariable and multivariable analysis, the number of prior syphilis episodes (adjusted hazard ratio [aHR] per 1-episode increase, 1.15; 95% confidence interval [CI], 1.01–1.31), having occasional sexual partners with or without condomless anal sex (aHR, 4.99; 95% CI, 4.08–6.11; and aHR, 2.54; 95% CI, 2.10–3.07), and being currently on antiretroviral therapy (aHR, 1.62; 95% CI, 1.21–2.16) were associated with incident syphilis.

Conclusions

In HIV-infected MSM, we observed no indication of decreased syphilis risk with repeated syphilis episodes. The extent of sexual risk behavior over time was the strongest risk factor for repeated syphilis episodes. The observed association of antiretroviral therapy with repeated syphilis episodes warrants further immunological and epidemiological investigation.
Secondary electron emission measurement from Cr and Cu bombarded by an Ne10+ beam at 6 MeV/n
Authors: Higashi A , Hashimoto Y , Ohsawa D , Shirai T , Noda K
Published: January 2020

Backward secondary-electron-emission yield ($\delta$) from plates of 0.1 mm-thick Cu and 1 mm Cr and Al have been measured by irradiation of a fully stripped Ne$^{10+}$ beam at 6 MeV/$n$ stopped within each plate. A difference between $\delta$s from Cr and Cu larger than the ambiguity of this measurement ($\pm$3%) has been observed, with the discrepancy of the predicted small difference by kinetic emission based on stopping power and work function of each metal. The measured $\delta$ from Cr is larger than that from Cu, and also than previous measurements of other transition metals of the 3$d$ series, not only for the process of potential emission but also for kinetic. The conduction-electron density of states around the Fermi level calculated for the metals shows that the number of electrons just below the Fermi level and excited over it to an empty level by many kinds of reaction with the beam irradiation has to be considered. The number involved in this emission from Cr thus seems to be much larger than from Cu, which explains the relation of magnitudes for $\delta$. The measured $\delta$ from Al is larger than previous results, but is still consistent due to the existence of Al$_2$O$_3$ on the Al.
Clinically significant substance use and residential stability among homeless or vulnerably housed persons in Canada: a longitudinal cohort study
Authors: Nasmith Trudy E , Gadermann Anne , Jaworsky Denise , Norena Monica , To Matthew J , Hwang Stephen W , Palepu Anita
Published: January 2020

Background

We examined clinically significant substance use among homeless or vulnerably housed persons in three Canadian cities and its association with residential stability over time using data from the Health and Housing in Transition study.

Methods

In 2009, 1190 homeless or vulnerably housed individuals were recruited in three Canadian cities and followed for 4 years. We collected information on housing and incarceration history, drug and alcohol use, having a primary care provider at baseline and annually for 4 years. Participants who screened positive for substance use at baseline were included in the analyses. We used a generalized logistic mixed effect regression model to examine the association between clinically significant substance use and residential stability, adjusting for confounders.

Results

Initially, 437 participants met the criteria for clinically significant substance use. The proportion of clinically significant substance use declined, while the proportion of participants who achieved residential stability increased over time. Clinically significant substance use was negatively associated with achieving residential stability over the 4-year period (AOR 0.7; 95% CI 0.57, 0.86).

Conclusions

In this cohort of homeless or vulnerably housed individuals, clinically significant substance use was negatively associated with achieving residential stability over time, highlighting the need to better address substance use in this population.
The effect of cognitive and behavioral therapy for insomnia on week-to-week changes in sleepiness and sleep parameters in patients with comorbid insomnia and sleep apnea: a randomized controlled trial
Authors: Sweetman Alexander , McEvoy R Doug , Smith Simon , Catcheside Peter G , Antic Nick A , Chai-Coetzer Ching Li , Douglas James , O’Grady Amanda , Dunn Nicola , Robinson Jan , Paul Denzil , Williamson Paul , Lack Leon
Published: January 2020

Study Objectives

While cognitive and behavioral therapy for insomnia (CBTi) is an effective treatment in patients with comorbid moderate and severe obstructive sleep apnea (OSA), there is concern that the bedtime restriction component of CBTi might dangerously exacerbate daytime sleepiness in such patients. We examined randomized controlled trial data to investigate the effect of OSA severity, and pretreatment daytime sleepiness on week-to-week changes in daytime sleepiness and sleep parameters during CBTi and no-treatment control.

Methods

One hundred and forty-five patients with untreated physician-diagnosed OSA (apnea–hypopnea index ≥15) and psychologist-diagnosed insomnia (ICSD-3) were randomized to a 4-week CBTi program (n = 72) or no-treatment control (n = 73). The Epworth sleepiness scale (ESS) and sleep diaries were completed during pretreatment, weekly CBTi sessions, and posttreatment. Effects of OSA severity, pretreatment daytime sleepiness, and intervention group on weekly changes in daytime sleepiness and sleep parameters were investigated.

Results

The CBTi group reported a 15% increase in ESS scores following the first week of bedtime restriction (M change = 1.3 points, 95% CI = 0.1–2.5, p = 0.031, Cohen’s d = 0.27) which immediately returned to pretreatment levels for all subsequent weeks, while sleep parameters gradually improved throughout CBTi. There were no differences in changes in daytime sleepiness during treatment between CBTi and control groups or OSA-severity groups. Higher pretreatment ESS scores were associated with a greater ESS reduction during CBTi.

Conclusions

CBTi appears to be a safe and effective treatment in the presence of comorbid moderate and severe OSA. Nevertheless, patients living with comorbid insomnia and sleep apnea and treated with CBTi should be monitored closely for increased daytime sleepiness during the initial weeks of bedtime restriction therapy.

Clinical Trial Registration

Treating comorbid insomnia with obstructive sleep apnoea (COMISA) study: A new treatment strategy for patients with combined insomnia and sleep apnoea, https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id = 365184 Australian New Zealand Clinical Trials Registry: ACTRN12613001178730. Universal Trial Number: U1111-1149-4230.
Insights into paradoxical (REM) sleep homeostatic regulation in mice using an innovative automated sleep deprivation method
Authors: Arthaud Sébastien , Libourel Paul-Antoine , Luppi Pierre-Hervé , Peyron Christelle
Published: January 2020

Identifying the precise neuronal networks activated during paradoxical sleep (PS, also called REM sleep) has been a challenge since its discovery. Similarly, our understanding of the homeostatic mechanisms regulating PS, whether through external modulation by circadian and ultradian drives or via intrinsic homeostatic regulation, is still limited, largely due to interfering factors rendering the investigation difficult. Indeed, none of the studies published so far were able to manipulate PS without significantly altering slow-wave sleep and/or stress level, thus introducing a potential bias in the analyses. With the aim of achieving a better understanding of PS homeostasis, we developed a new method based on automated scoring of vigilance states—using electroencephalogram and electromyogram features—and which involves closed-loop PS deprivation through the induction of cage floor movements when PS is detected. Vigilance states were analyzed during 6 and 48 h of PS deprivation as well as their following recovery periods. Using this new automated methodology, we were able to deprive mice of PS with high efficiency and specificity, for short or longer periods of time, observing no sign of stress (as evaluated by plasma corticosterone level and sleep latency) and requiring no human intervention or environmental changes. We show here that PS can be homeostatically modulated and regulated while no significant changes are induced on slow-wave sleep and wakefulness, with a PS rebound duration depending on the amount of prior PS deficit. We also show that PS interval duration is not correlated with prior PS episode duration in the context of recovery from PS deprivation.
Japan taxation of trusts
Authors: Shikuma Michael H
Published: January 2020

Although trusts are not widely used for estate planning purposes in Japan, the taxation of trusts is becoming an important issue as the scope of Japan’s gift and inheritance taxes have expanded to include settlors or beneficiaries residing in Japan, and Japanese and non-Japanese national settlors or beneficiaries residing abroad. Despite the 2007 revision of the Japan trust and trust taxation rules, the taxation of foreign trusts is often unclear, in part because of the differences in Japan and foreign trust structures. This article is designed to provide a general overview of the Japan taxation of trusts.