bluuebunny/crossref_metadata_2025_split huggingface dataset:
In vivo and in vitro assessment of mirtazapine pharmacokinetics in cats with liver disease
Authors: Fitzpatrick Rikki L. , Quimby Jessica M. , Benson Kellyi K. , Ramirez Dominique , Sieberg Liberty G. , Wittenburg Luke A. , Gustafson Daniel L. 
Published: October 2018

BackgroundLiver disease (LD) prolongs mirtazapine half‐life in humans, but it is unknown if this occurs in cats with LD and healthy cats.Hypothesis/ObjectivesTo determine pharmacokinetics of administered orally mirtazapine in vivo and in vitro (liver microsomes) in cats with LD and healthy cats.AnimalsEleven LD and 11 age‐matched control cats.MethodsCase‐control study. Serum was obtained 1 and 4 hours (22 cats) and 24 hours (14 cats) after oral administration of 1.88 mg mirtazapine. Mirtazapine concentrations were measured by liquid chromatography with tandem mass spectrometry. Drug exposure and half‐life were predicted using limited sampling modeling and estimated using noncompartmental methods. in vitro mirtazapine pharmacokinetics were assessed using liver microsomes from 3 LD cats and 4 cats without LD.ResultsThere was a significant difference in time to maximum serum concentration between LD cats and control cats (median [range]: 4 [1‐4] hours versus 1 [1‐4] hours; P = .03). The calculated half‐life of LD cats was significantly prolonged compared to controls (median [range]: 13.8 [7.9‐61.4] hours versus 7.4 [6.7‐9.1] hours; P < .002). Mirtazapine half‐life was correlated with ALT (P = .002; r = .76), ALP (P < .0001; r = .89), and total bilirubin (P = .0008; r = .81). The rate of loss of mirtazapine was significantly different between microsomes of LD cats (–0.0022 min−1, CI: −0.0050 to 0.00054 min−1) and cats without LD (0.01849 min−1, CI: −0.025 to −0.012 min−1; P = .002).Conclusions and Clinical ImportanceCats with LD might require less frequent administration of mirtazapine than normal cats.
Value‐at‐Risk bounds with two‐sided dependence information
Authors: Lux Thibaut , Rüschendorf Ludger 
Published: October 2018

AbstractValue‐at‐Risk (VaR) bounds for aggregated risks have been derived in the literature in settings where, besides the marginal distributions of the individual risk factors, one‐sided bounds for the joint distribution or the copula of the risks are available. In applications, it turns out that these improved standard bounds on VaR tend to be too wide to be relevant for practical applications, especially when the number of risk factors is large or when the dependence restriction is not strong enough. In this paper, we develop a method to compute VaR bounds when besides the marginal distributions of the risk factors, two‐sided dependence information in form of an upper and a lower bound on the copula of the risk factors is available. The method is based on a relaxation of the exact dual bounds that we derive by means of the Monge–Kantorovich transportation duality. In several applications, we illustrate that two‐sided dependence information typically leads to strongly improved bounds on the VaR of aggregations.
Terrestrial species adapted to sea dispersal: Differences in propagule dispersal of two Caribbean mangroves
Authors: Hodel Richard G. J. , Knowles L. Lacey , McDaniel Stuart F. , Payton Adam C. , Dunaway Jordan F. , Soltis Pamela S. , Soltis Douglas E. 
Published: October 2018

AbstractA central goal of comparative phylogeography is to understand how species‐specific traits interact with geomorphological history to govern the geographic distribution of genetic variation within species. One key biotic trait with an immense impact on the spatial patterns of intraspecific genetic differentiation is dispersal. Here, we quantify how species‐specific traits directly related to dispersal affect genetic variation in terrestrial organisms with adaptations for dispersal by sea, not land—the mangroves of the Caribbean. We investigate the phylogeography of white mangroves (Laguncularia racemosa, Combretaceae) and red mangroves (Rhizophora mangle, Rhizophoraceae) using chloroplast genomes and nuclear markers (thousands of RAD‐Seq loci) from individuals throughout the Caribbean. Both coastal tree species have viviparous propagules that can float in salt water for months, meaning they are capable of dispersing long distances. Spatially explicit tests of the role of ocean currents on patterning genetic diversity revealed that ocean currents act as a mechanism for facilitating dispersal, but other means of moving genetic material are also important. We measured pollen‐ vs. propagule‐mediated gene flow and discovered that in white mangroves, seeds were more important for promoting genetic connectivity between populations, but in red mangroves, the opposite was true: pollen contributed more. This result challenges our concept of the importance of both proximity to ocean currents for moving mangrove seeds and the extent of long‐distance pollen dispersal. This study also highlights the importance of spatially explicit quantification of both abiotic (ocean currents) and biotic (dispersal) factors contributing to gene flow to understand fully the phylogeographic histories of species.
Biodiversity–function relationships in methanogenic communities
Authors: Sierocinski Pawel , Bayer Florian , Yvon‐Durocher Gabriel , Burdon Melia , Großkopf Tobias , Alston Mark , Swarbreck David , Hobbs Phil J. , Soyer Orkun S. , Buckling Angus 
Published: October 2018

AbstractMethanogenic communities play a crucial role in carbon cycling and biotechnology (anaerobic digestion), but our understanding of how their diversity, or composition in general, determines the rate of methane production is very limited. Studies to date have been correlational because of the difficulty in cultivating their constituent species in pure culture. Here, we investigate the causal link between methanogenesis and diversity in laboratory anaerobic digesters by experimentally manipulating the diversity of cultures by dilution and subsequent equilibration of biomass. This process necessarily leads to the loss of the rarer species from communities. We find a positive relationship between methane production and the number of taxa, with little evidence of functional saturation, suggesting that rare species play an important role in methane‐producing communities. No correlations were found between the initial composition and methane production across natural communities, but a positive relationship between species richness and methane production emerged following ecological selection imposed by the laboratory conditions. Our data suggest methanogenic communities show little functional redundancy, and hence, any loss of diversity—both natural and resulting from changes in propagation conditions during anaerobic digestion—is likely to reduce methane production.
Klage der Natur
Authors: Prade‐Weiss Juliane 
Published: October 2018

AbstractDie Studie analysiert die Rolle der Sprache des Klagens in Herders sowie Benjamins Überlegungen zum Sprachursprung, die der für das systematische Verständnis der Sprache ebenso grundlegenden wie vernachlässigten Frage nachgehen, wie wechselseitiger Austausch in der Struktur der Sprache verankert ist. Herder und Benjamin greifen das alte Motiv der Klage der Natur auf, das in der Dichtung seit der Antike eine phonetisch‐affektive Kontaktzone zwischen natürlichen Tönen sowie Äußerungen von Lebewesen einerseits und andererseits der artikulierten Wortsprache darstellt. HerdersAbhandlung über den Ursprung der Sprache(1772) und BenjaminsÜber Sprache überhaupt und über die Sprache des Menschen(1916) erschließen die phonetische Materialität und affektive Motivation der menschlichen Sprache in der Lektüre von SophoklesʾPhiloktetund der Genesis. In der Adaption von Szenen dieser Texte übernehmen sie auch die Maßgabe der Betrachtung aus der Distanz, die neben szenischen auch theoretischen Texten eingeschrieben ist. HerdersAbhandlungschildert die geniun menschliche Sprache just dadurch als Abstraktionsvermögen, dass sie Abstand nimmt von dem Affektausdruck, der durch Akzentuierung der wahrnehmbaren Materialität der Sprache Gehör und Erwiderung erheischt. Benjamins Diskurs stellt die apodiktische Gewaltsamkeit des theoretischen Vorgehens aus, den spezifisch menschlichen Zugang der Welt vermittels der Sprache zu begründen durch Absehen von der Natur.
Propofol pharmacokinetic and pharmacodynamic profile and its electroencephalographic interaction with remifentanil in children
Authors: Fuentes Ricardo , Cortínez Luis Ignacio , Contreras Víctor , Ibacache Mauricio , Anderson Brian J. 
Published: October 2018

SummaryBackgroundPropofol and remifentanil are commonly combined during total intravenous anesthesia. The impact of remifentanil in this relationship is poorly quantified in children. Derivation of an integrated pharmacokinetic and pharmacodynamic propofol model, containing remifentanil pharmacodynamic interaction information, enables propofol effect‐site target‐controlled infusion in children with a better prediction of its hypnotic effect when both drugs are combined.AimsWe designed this study to derive an integrated propofol pharmacokinetic‐pharmacodynamic model in children and to describe the pharmacodynamic interaction between propofol and remifentanil on the electroencephalographic bispectral index effect.MethodsThirty children (mean age: 5.45 years, range 1.3‐11.9; mean weight: 23.5 kg, range 8.5‐61) scheduled for elective surgery with general anesthesia were studied. After sevoflurane induction, maintenance of anesthesia was based on propofol and remifentanil. Blood samples to measure propofol concentration were collected during anesthesia maintenance and up to 6 hours in the postoperative period. Bispectral index data were continuously recorded throughout the study. A pharmacokinetic‐pharmacodynamic model was developed using population modeling. The Greco model was used to examine the pharmacokinetic‐pharmacodynamic interaction between propofol and remifentanil for BIS responseResultsPropofol pharmacokinetic data from a previous study in 53 children were pooled with current data and simultaneously analyzed. Propofol pharmacokinetics were adequately described by a three‐compartment distribution model with first‐order elimination. Theory‐based allometric relationships based on TBW improved the model fit. The Greco model supported an additive interaction between propofol and remifentanil. Remifentanil showed only a minor effect in BIS response.ConclusionWe have developed an integrated propofol pharmacokinetic‐pharmacodynamic model that can describe the pharmacodynamic interaction between propofol and remifentanil for BIS response. An additive interaction was supported by our modeling analysis.
A novel glycerophosphodiester phosphodiesterase improves phosphate deficiency tolerance in rice
Authors: Mehra Poonam , Pandey Bipin K. , Verma Lokesh , Giri Jitender 
Published: October 2018

AbstractSoil phosphate (Pi) deficiency is major constraint for rice cultivation worldwide. Cellular membranes account for one third of cellular organic phosphorus (P) in the form of phospholipids. Therefore, remobilization of Pi from membrane phospholipids under Pi deficiency can be an important strategy to improve phosphorus use efficiency. Glycerophosphodiester phosphodiesterases (GDPDs) hydrolyse intermediate product of phospholipid catabolism, glycerophosphodiesters to glycerol‐3‐phosphate, a precursor for P and non P‐lipid biosynthesis. Here, we show that OsGDPD2 is a Pi deficiency responsive gene, which is transcriptionally regulated by OsPHR2. In silico analysis of active site residues and enzymatic assays confirmed phosphodiesterase activity of OsGDPD2. All overexpression lines showed higher GDPD activity, Pi content, root growth, and biomass accumulation as compared with wild type. Conversely, silencing of OsGDPD2 led to decreased GDPD activity and Pi content. Notably, most of the P‐containing metabolites and fatty acids were elevated in transgenic lines. Further, quantitative analysis of polar lipids revealed higher accumulation of several classes of phospholipids and galactolipids in overexpression lines indicating a potential role of OsGDPD2 in de novo glycerolipid biosynthesis. Thus, present study provides insights into novel physiological roles of OsGDPD2 in low Pi acclimation in rice.
Modifiable life style factors and risk for incident endometriosis
Authors: Hemmert Rachael , Schliep Karen C. , Willis Sydney , Peterson Charles Matthew , Louis Germaine Buck , Allen‐Brady Kristina , Simonsen Sara E. , Stanford Joseph B. , Byun Jiyoung , Smith Ken R. 
Published: October 2018

AbstractBackgroundCaffeine, alcohol, smoking and physical activity are known to alter sex steroid synthesis, which may affect hormone‐dependent gynaecologic disease risk, such as endometriosis; however, few studies have assessed life style factors prior to endometriosis diagnosis.MethodsFour hundred and seventy three women, ages 18‐44 years, underwent laparoscopy or laparotomy, regardless of clinical indication, at 14 clinic sites, 2007‐2009. Women with prior surgically confirmed endometriosis were excluded. Life style factors were assessed prior to surgery. Adjusted risk ratios (RR) of endometriosis by caffeine, alcohol, smoking (serum cotinine), and physical activity were estimated, adjusting for age, marital status, education, race/ethnicity, age at menarche, gravidity, BMI, study site, and other life style factors.ResultsThere were no associations between women with endometriosis and alcohol consumption (RR 0.9, 95% CI 0.7, 1.3), caffeine consumption (RR 1.1, 95% CI 0.8, 1.5), or smoking (serum cotinine <10 vs ≥10 ng/mL; RR 1.0, 95% CI 0.7, 1.6). Similar null findings were found between endometriosis and weekly occurrences of physical activity and total walking, moderate, and vigorous activity; a modest trend was found between total daily sitting time and increased endometriosis risk.ConclusionsThis study, which is unique in its capture of life style exposures prior to incident endometriosis diagnosis, largely found no association between alcohol, caffeine, smoking, and physical activity and risk of endometriosis.
Serum cytokine measurements and biological therapy of psoriasis – Prospects for personalized treatment?
Authors: Solberg Silje M. , Sandvik Lene F. , Eidsheim Marianne , Jonsson Roland , Bryceson Yenan T. , Appel Silke 
Published: October 2018

AbstractPsoriasis is an immune‐mediated disease where the IL‐23/Th17 axis as well as TNF comprise main targets of biological therapy. Immune profiling has so far not been embraced as a clinical tool. We aimed to investigate relationships between individual serum cytokine levels in 40 psoriasis patients before and after receiving biological therapy and Psoriasis Area and Severity Index (PASI) and Dermatological Life Quality Index (DLQI). Serum concentration of 25 cytokines was determined by Luminex technology. Mean PASI and DLQI decreased by 71% and 65%, respectively. Increase of IL‐2 positively correlated with improvement of PASI and DLQI. Moreover, increase of IL‐5, IL‐10, IL‐12, IL‐22 and GM‐CSF correlated with treatment effect. Notably, logistic regression revealed four times higher risk of having severe psoriasis when IL‐17A increased by 1 pg/mL (OR: 4.06, P < 0.05). Selected serum cytokines might constitute useful biomarkers for monitoring disease activity and optimizing therapeutic strategies in psoriasis patients.
Impulsivity, Painful and Provocative Events, and Suicide Intent: Testing the Interpersonal Theory of Suicide
Authors: Jordan Joshua T. , Samuelson Kristin W. , Tiet Quyen Q. 
Published: October 2018

ObjectiveThe Interpersonal Theory of Suicide (IPTS; Joiner, 2005.Why People Die by Suicide. Cambridge, MA: Harvard University Press) hypothesizes that repeated exposure to painful and provocative events (PPE) increases capability for suicide (CS), therefore facilitating the development of suicidal intent, and that impulsive individuals are more likely to experience these painful and provocative events, creating an indirect relationship between impulsivity andCS. Research to date largely supports this hypothesis but has not translated this theory to actual suicidal intent.MethodThe present study used data from the MacArthur Violence Risk Assessment Study to examine the relationship betweenPPEand intent, and the indirect relationship between impulsivity and intent among a sample of 245 recent suicide attempters, using the clinician‐rated Suicide Intent Scale as an objective measure of intent.ResultsResults supported the hypothesized direct relationship betweenPPEand intent, and the indirect relationship between impulsivity and intent throughPPE. There was no direct relationship between impulsivity and intent, suggesting that the relationship between impulsivity and intent occurs entirely through exposure toPPE.ConclusionsThese findings suggest that assessing exposure to painful and provocative events is critical in evaluating risk of suicide, and that impulsivity itself does not confer an increased risk of lethal or nearly lethal attempts.
Children’s reasoning about unequal gender‐based distributions
Authors: Conry‐Murray Clare 
Published: October 2018

AbstractChildren ages 7 (N = 56, Mage = 7.24, SD = 0.83), 9 (N = 55, Mage = 9.25, SD = 0.52), and 11 (N = 52, Mage = 11.60, SD = 0.79), and emerging adults (N = 50, Mage = 20.76, SD = 0.87) judged distributions of different items to boys and girls, when the items distributed varied by gender valence (related or unrelated to gender norms) and equivalency (equivalent or unequal). Distributions were judged to be acceptable most when the items were consistent with gender norms, especially for participants at ages 7 and 9, indicating that in middle childhood, children judge unequal treatment as fair when it is related to gender norms. Items were judged to be more likable when they were gendered, and likability judgments predicted more positive evaluations of the distributions, even when controlling for age.
Spatio‐temporal distribution of vertically transmitted dengue viruses by Aedes aegypti (Diptera: Culicidae) from Arroyo Naranjo, Havana, Cuba
Authors: Gutiérrez‐Bugallo Gladys , Rodríguez‐Roche Rosmari , Díaz Gisell , Pérez Magaly , Mendizábal María Elena , Peraza Iris , Vázquez Antonio A. , Alvarez Mayling , Rodríguez Magdalena , Bisset Juan A. , Guzmán María G. 
Published: October 2018

AbstractObjectiveTo study the distribution of vertical transmission of dengue viruses in field‐collected Aedes aegypti larvae in the municipality of Arroyo Naranjo in Havana, Cuba.MethodsAedes aegypti larvae and pupae were collected monthly between September 2013 and July 2014 in the seven Municipal Health Areas of Arroyo Naranjo. Pools formed of 30–55 larvae were examined through PCR and sequencing to detect the presence of each serotype.ResultsWe analysed 111 pools of larvae and pupae (4102 individuals) of which 37 tested positive for at least one DENV. More than one DENV type was observed in 10 of the 37 positive pools. Infected pools were detected every month, except in January, suggesting a sustained circulation of DENV in the vector populations. DENV‐1 and DENV‐3 were the most frequent and dispersed, though all four DENV types were detected. Nucleotide sequencing from positive pools confirmed RT‐PCR results for DENV‐1 (genotype V), DENV‐3 (genotype III) and DENV‐4 (genotype II). DENV‐2 was detected by RT‐PCR but could not be confirmed by nucleotide sequencing.ConclusionOur study of the distribution of natural vertical transmission of dengue virus types highlights extrinsic virus activity patterns in the area and could be used as a new surveillance tool.
Environmental temperature and case fatality of patients with Ebola virus disease in Sierra Leone and Liberia, 2014–2015: a retrospective cohort study
Authors: Peters Jillian L. , Cho Daniel K. , Aluisio Adam R. , Kennedy Stephen B. , Massaquoi Moses B. F. , Sahr Foday , Perera Shiromi M. , Levine Adam C. 
Published: October 2018

AbstractObjectiveFluid loss during Ebola virus disease (EVD) infections from gastrointestinal dysfunction leads to volume depletion. It is possible that high environmental temperatures may exacerbate volume depletion or interfere with the provision of medical care by providers in full personal protective equipment. We investigated the effect of environmental temperature on case fatality.MethodsThe International Medical Corps (IMC) operated five Ebola Treatment Units (ETUs) in Liberia and Sierra Leone during the 2014–2016 epidemic. Demographic and outcomes variables for 465 patients with EVD were sourced from a de‐identified, quality‐checked clinical database collected by IMC. Daily environmental temperature data for Liberia and Sierra Leone were collected from a publicly available database (Weather Underground). Mean daily environmental temperatures were averaged across each patient's ETU stay and environmental temperature thresholds were determined. Multiple logistic regression was utilised, with forward variable selection and threshold for entry of P < 0.1. Statistical significance was defined as P < 0.05. The following variables were analysed as potential confounders: age, sex, ETU, length of ETU operation and date of treatment.ResultsCase fatality was 57.6% among patients diagnosed with EVD. Analysis of case fatality across environmental temperature quintiles indicated a threshold effect; the optimal threshold for average environmental temperature during a patient's ETU stay was determined empirically to be 27.4 °C (81.3 °F). Case fatality was significantly greater for patients with average environmental temperatures above the threshold (70.4%) vs. below (52.0%) (P < 0.001). In multiple regression, patients with average environmental temperature above the threshold during their ETU stay were significantly more likely to die than patients below the threshold (aOR = 2.5, 95% CI 1.6–3.8, P < 0.001). This trend was observed only among patients treated in white tent ETUs, and not in ETUs with aluminium roofs.DiscussionThese findings suggest that an average environmental temperature above 27.4 °C (81.3 °F) during patients’ ETU stay is associated with greater risk of death among patients with EVD. Further studies should investigate this effect. These results have potential implications for reducing case fatality through improved ETU construction or other temperature control methods within ETUs during future outbreaks.