bluuebunny/crossref_metadata_2025 huggingface dataset:
Pyrimethamine toxicosis in horses given a compounded medication
Authors: MacKay R. , McLellan J. , Mallicote M.
Published: September 2017

Eight Thoroughbred horses in race training began convulsing within 24 h of dosing with a compounded medication containing toltrazuril and pyrimethamine (PYR); seizures were generalised and multiple in six of the horses. One horse died within 2 h of onset and another persistently recumbent horse was subjected to euthanasia 3 days later. Neurological signs resolved within 4 days of dosing in the remaining six horses but hyperthermia, neutropenia, oral mucositis and alopecia developed in four horses beginning on Day 6. After treatment with folinic acid and folic acid for presumptivePYR‐induced folate deficiency these signs resolved within 3 weeks. One horse developed laminitis and was ultimately subjected to euthanasia >2 months after dosing. The remaining five horses recovered and were discharged. Laboratory analysis of the suspect medication revealed that the concentrations of the two ingredients had accidentally been switched during formulation by the compounding pharmacy so that thePYRconcentration was 405 g/L rather than the intended 17 g/L. This incident highlights the need for caution when using compounded preparations of potentially toxic drugs.
Epigenetics at the crossroads between genes, environment and resilience in anxiety disorders
Authors: Schiele M. A. , Domschke K.
Published: September 2017

The pathogenesis of anxiety disorders is multifactorial, involving complex interactions between biological factors, environmental influences and psychological mechanisms. Recent advances have highlighted the role of epigenetics in bridging the gap between multiple contributing risk factors toward an increased understanding of the pathomechanisms underlying anxiety. In this review, we present an overview of the current state of knowledge regarding putative risk mechanisms in the pathogenesis of anxiety disorders, placing a particular focus on the role of protective factors serving to buffer a risk factor constellation and the role of epigenetic processes functioning as a potent turnstile changing passage direction toward disorder risk or resilience. We discuss promising future directions in epigenetic research regarding the prediction, prevention and personalized treatment of anxiety disorders.
Detection of climate change‐driven trends in phytoplankton phenology
Authors: Henson Stephanie A. , Cole Harriet S. , Hopkins Jason , Martin Adrian P. , Yool Andrew
Published: September 2017

The timing of the annual phytoplankton spring bloom is likely to be altered in response to climate change. Quantifying that response has, however, been limited by the typically coarse temporal resolution (monthly) of global climate models. Here, we use higher resolution model output (maximum 5 days) to investigate how phytoplankton bloom timing changes in response to projected 21st century climate change, and how the temporal resolution of data influences the detection of long‐term trends. We find that bloom timing generally shifts later at mid‐latitudes and earlier at high and low latitudes by ~5 days per decade to 2100. The spatial patterns of bloom timing are similar in both low (monthly) and high (5 day) resolution data, although initiation dates are later at low resolution. The magnitude of the trends in bloom timing from 2006 to 2100 is very similar at high and low resolution, with the result that the number of years of data needed to detect a trend in phytoplankton phenology is relatively insensitive to data temporal resolution. We also investigate the influence of spatial scales on bloom timing and find that trends are generally more rapidly detectable after spatial averaging of data. Our results suggest that, if pinpointing the start date of the spring bloom is the priority, the highest possible temporal resolution data should be used. However, if the priority is detecting long‐term trends in bloom timing, data at a temporal resolution of 20 days are likely to be sufficient. Furthermore, our results suggest that data sources which allow for spatial averaging will promote more rapid trend detection.
The origin of soil organic matter controls its composition and bioreactivity across a mesic boreal forest latitudinal gradient
Authors: Kohl Lukas , Philben Michael , Edwards Kate A. , Podrebarac Frances A. , Warren Jamie , Ziegler Susan E.
Published: September 2017

Warmer climates have been associated with reduced bioreactivity of soil organic matter (SOM) typically attributed to increased diagenesis; the combined biological and physiochemical transformation of SOM. In addition, cross‐site studies have indicated that ecosystem regime shifts, associated with long‐term climate warming, can affect SOM properties through changes in vegetation and plant litter production thereby altering the composition of soil inputs. The relative importance of these two controls, diagenesis and inputs, on SOM properties as ecosystems experience climate warming, however, remains poorly understood. To address this issue we characterized the elemental, chemical (nuclear magnetic resonance spectroscopy and total hydrolysable amino acids analysis), and isotopic composition of plant litter and SOM across a well‐constrained mesic boreal forest latitudinal transect in Atlantic Canada. Results across forest sites within each of three climate regions indicated that (1) climate history and diagenesis affect distinct parameters of SOM chemistry, (2) increases in SOM bioreactivity with latitude were associated with elevated proportions of carbohydrates relative to plant waxes and lignin, and (3) despite the common forest type across regions, differences in SOM chemistry by climate region were associated with chemically distinct litter inputs and not different degrees of diagenesis. The observed climate effects on vascular plant litter chemistry, however, explained only part of the regional differences in SOM chemistry, most notably the higher protein content of SOM from warmer regions. Greater proportions of lignin and aliphatic compounds and smaller proportions of carbohydrates in warmer sites' soils were explained by the higher proportion of vascular plant relative to moss litter in the warmer relative to cooler forests. These results indicate that climate change induced decreases in the proportion of moss inputs not only impacts SOM chemistry but also increases the resistance of SOM to decomposition, thus significantly altering SOM cycling in these boreal forest soils.
New directions in researching regional economic resilience and adaptation
Authors: Evenhuis Emil
Published: September 2017

The paper has two objectives. Firstly, to disentangle several debates with regard to regional economic resilience: What is it exactly? Which types can we distinguish? How can we operationalise it? And how can we conceptualise how it works? The second objective is to outline new directions for researching regional economic resilience. Thus far, research on regional economic resilience has been dominated by quantitative studies looking at how regional economies resisted and recovered from macro‐economic downturns (especially the most recent one). I will argue that fruitful new directions are to be found in further developing evolutionary conceptions of regional economic resilience, especially in relation to structural changes in the wider economy. Such evolutionary conceptions do away with notions of equilibrium altogether and can thus encompass the complete transformation of regional economies. In terms of research focus, this entails homing in on the possible mechanisms through which the processes of reorganisation and reorientation take place within regional economies that undergo adaptation. And in terms of research methodology, this will require more research based on a comparative case study design, using a mix of quantitative and qualitative methods.
Monitoring joint health in haemophilia: Factors associated with deterioration
Authors: Kuijlaars I. A. R. , Timmer M. A. , de Kleijn P. , Pisters M. F. , Fischer K.
Published: September 2017

Introduction

Joint bleeds in patients with haemophilia may result in haemophilic arthropathy. Monitoring joint health is essential for identifying early signs of deterioration and allows timely adjustment of treatment.

Aim

The aim was to describe changes in joint health over 5‐10 years follow‐up and identify factors associated with joint health deterioration in patients with haemophilia.

Methods

A post hoc analysis was performed from previous cohort studies in patients with moderate/severe haemophilia, ≥16 years. Joint health of ankles, knees and elbows was measured with the Haemophilia Joint Health Score (HJHS) from 2006‐2008 (T0) to 2011‐2016 (T1). Analyses were performed on patient level (ΔHJHS‐total) and joint level (ΔHJHS‐joint). Deterioration was defined as ΔHJHS‐total ≥4 and ΔHJHS‐joint ≥2.

Results

Sixty‐two patients (median age 25, 73% severe haemophilia, median [interquartile range] 0.0 [0.0;2.0] joint bleeds between T0 to T1) were included. After median 8 years, HJHS‐total deteriorated in 37% and HJHS‐joint in 17%. Ankle joints (31%) showed deterioration more often than elbows (19%) and knees (3%). Deterioration of HJHS‐total was only associated with severe haemophilia. Deterioration of HJHS‐joint was weakly associated with a lower HJHS at baseline and more self‐reported limitations in activities, and strongly with more joint bleeds between T0 and T1 and presence of synovitis.

Conclusion

In 37% of patients with moderate/severe haemophilia and low joint bleeding rates, joint health deteriorated over 5‐10 years. Ankle and elbow joints showed deterioration most frequently. Factors found in this study help to identify which joints need frequent monitoring in patients with haemophilia with access to early prophylaxis.
Differences in bleeding phenotype and provider interventions in postmenarchal adolescents when compared to adult women with bleeding disorders and heavy menstrual bleeding
Authors: Srivaths L. V. , Zhang Q. C. , Byams V. R. , Dietrich J. E. , James A. H. , Kouides P. A. , Kulkarni R. ,   the Hemophilia Treatment Centers Network Investigators
Published: September 2017

Introduction

Due to lack of patient/health care provider awareness causing delayed diagnosis, the bleeding phenotype and provider interventions in adolescents with heavy menstrual bleeding (HMB) and bleeding disorders (BD) may be different when compared to adults.

Aim

The aim of this study was to compare/characterize bleeding phenotype and provider interventions in postmenarchal adolescents < 18 years and premenopausal adults ≥ 18 years with HMB and BD.

Methods

Patient demographics, BD, and provider interventions/therapy details for HMB were compared between both age groups enrolled in the Centers for Disease Control and Prevention (CDC) Female Universal Data Collection (UDC) surveillance project in United States hemophilia treatment centres. Cross‐sectional descriptive analyses including frequency distributions, summary statistics, bivariate and logistic regression analyses were performed.

Results

Of 269 females (79 adolescents; median age 16 years, interquartile range (IQR) = 2; 190 adults; median age 27 years, IQR = 13) evaluated, BD distribution was similar in both groups. Compared to adolescents, adults more often had family history of bleeding (Adjusted odds ratios [AOR] = 2.6, 1.3‐5.6), delay in diagnosis (AOR = 2.5, 1.2‐4.9), bleeding with dental procedures (AOR = 2.0, 1.0‐4.0), gastrointestinal bleeding (AOR = 4.6, 1.0‐21.9), anaemia (AOR = 2.7, 1.4‐5.2), utilized desmopressin less often (AOR = 0.4, 0.2‐0.8) and underwent gynaecologic procedure/surgery more frequently (AOR = 5.9, 1.3‐27.3).

Conclusion

Bleeding phenotypes of adolescents and adults with HMB and BD were different with more frequent bleeding complications, anaemia, gynaecologic procedures/surgeries, less desmopressin use and more delay in diagnosing BD in adults. Longitudinal studies are needed to determine whether improved patient/provider awareness and education will translate to early diagnosis and timely management of BD/HMB in adolescents that may prevent/reduce future haematologic/gynaecologic complications.
1. CARL SCHMITT BETWEEN HISTORY AND MYTH
Authors: FINCHELSTEIN FEDERICO
Published: September 2017

Carl Schmitt's work defines the history and theory of political myth. But analyzing it represents a challenge to historians and theorists alike. For many historians, Schmitt should be analyzed in his own context, whereas theorists study his writings without enough consideration of the specific context in which he conceived his texts. In this essay, I argue that Schmitt not only contributed to the fascist glorification of the mythical and its novel enactment as the driving force of fascism, but he also represents one of the most intriguing and influential interpreters of the political theory of myth, challenging in turn theories of democracy and the role of reason and secularism in historiography.
THE UNRESOLVED PROBLEMS OF LATE CRITICAL THEORY
Authors: Bernstein Richard J.
Published: September 2017

Martin Jay's sweeping account of reason in Western philosophy provides the context for understanding the crisis that the Frankfurt School thinkers faced when they spoke of the “eclipse of reason.” In the background of the thinking of the first generation of Frankfurt thinkers such as Max Horkheimer, Theodor Adorno, and Herbert Marcuse is a hankering for a more substantive conception of reason that bears affinities with what Hegel called Vernunft (reason), which he contrasted with Verstand (understanding). According to Jay, the first generation of Frankfurt thinkers never quite succeeded in elaborating this substantive concept of reason and grew increasingly pessimistic in the face of the self‐destruction of reason. Habermas sought to elaborate a communicative theory of rationality that did not fall into the misleading promises of Hegelian Vernunft but could nevertheless provide a normative basis for the critique of instrumental, strategic, and systems rationality—a normative basis for critical theory. Jay presents an extremely lucid account of Jürgen Habermas's theory of communicative rationality. He concludes by reviewing some of the outstanding problems and questions that have been raised about the adequacy and success of Habermas's project. I seek to do justice to the strengths and weaknesses of Jay's narrative, and I focus on a number of deep, unresolved issues that confront the future of critical theory in its attempt to develop an adequate conception of rationality. I also raise concerns about what precisely is distinctive about critical theory today.
“UNABLE TO RESIST”: ON THE “POSSIBILITY” OF “IMPOSSIBILITY” AND CHRISTOPHE BOUTON'S TIME AND FREEDOM
Authors: Wilkerson Dale A.
Published: September 2017

This essay reflects critically on Martin Heidegger's remarks about authenticity and death with the aid of Christophe Bouton's Temps et liberté (2002), translated by Christopher Macann as Time and Freedom (2014). It first raises general questions concerning the possible thematic relationship between human endeavoring (action) and the experiences of finitude and freedom. Heidegger's Being and Time is particularly useful for exploring this relationship, but certain problems emerge when using this text for accessing the essay's themes. To wit: there are good reasons for mistrusting readings of Being and Time as a “practical” guide for grounding action. Against the practical reading, the essay wishes to reclaim the ontological‐existential significance of Heidegger's text. Although Bouton's treatment of Being and Time excludes its ontological dimensions and is entirely practical, even to the point of disregarding certain theoretical risks inherent in this approach, Bouton's study is indispensable for situating Being and Time in a historical‐intellectual context, whereby the experiences of freedom and time are understood within certain metaphysical presuppositions rendering them difficult to establish together on reliable grounds. Following Bouton's lead, the essay shows that the hermeneutic differences between practical and ontological readings of Being and Time can be explored through reflections on what Heidegger might have meant by the term “Möglichkeit” (“possibility”), from which Bouton infers “freedom.” It is alleged that Bouton does not fully consider all of Heidegger's assertions regarding Möglichkeit, most problematically the claim that the human being's most essential “possibility” is its “impossibility,” that is to say, its death.
Variation in melanin pigmentation of a sexually selected plumage trait and its adaptive value in the Common SnipeGallinago gallinago
Authors: Minias Piotr , Surmacki Adrian , Kudelska Karolina , Podlaszczuk Patrycja , Kamiński Maciej , Kaczmarek Krzysztof , Włodarczyk Radosław , Janiszewski Tomasz
Published: September 2017

There is increasing evidence that melanin‐based plumage coloration correlates with different components of fitness and that it may act as a social or sexual signal of individual quality. We analysed variation in melanin pigmentation in the outermost tail feathers of the Common SnipeGallinago gallinago. During courtship flights, male Snipe use their outermost tail feathers to generate a drumming sound, which plays a role in territory establishment and mate choice. As the outermost tail feathers are displayed to females during these flights, we predicted that conspicuous variation in their rusty‐brown (pheomelanin‐based) coloration may act as an honest signal of individual quality. To test this prediction, we spectrophotometrically measured brightness (an indicator of total melanin content) and red chroma (an indicator of pheomelanin content) of the outermost tail feathers in 180 juvenile and adult Common Snipe. An age‐related decline in feather brightness was found exclusively in females, suggesting that melanization could have evolved by natural selection to camouflage incubating birds. In both sexes, brightness of the tail feathers was inversely correlated with their structural quality (as measured with mass–length residuals), suggesting that melanization could increase mechanical properties of feathers and, in males, enhance the quality of courtship sonation. Red chroma positively correlated with total plasma protein concentration, supporting our prediction that pheomelanin pigmentation of tail feathers may act as an honest signal of condition. Our study indicated that variation in the melanin‐based coloration of the outermost tail feathers in the Common Snipe could have evolved as a result of several different selection pressures and it emphasizes the complexity of the processes that underlie the evolution of melanin‐based plumage coloration in birds.
Under‐representation of avian studies in landscape genetics
Authors: Kozakiewicz Christopher P. , Carver Scott , Burridge Christopher P.
Published: September 2017

Landscape genetics is a rapidly growing discipline that examines how heterogeneous landscapes and other environmental factors influence population genetic variation. We conducted a systematic review of the landscape genetic literature which demonstrates that birds are severely under‐represented relative to their species diversity and general publication prevalence. Most avian studies were on species that have relatively low dispersal ability, and we suggest that this reflects an assumed high vagility of birds that precludes spatial genetic variation relatable to landscape heterogeneity. However, spatial genetic variation exists in several bird species with very high dispersal ability, but this has not been considered in the context of landscape features. Genetic patterns may also relate to landscape due to breeding habitat selection and territorial behaviour, despite the fact that species may be able to move throughout different landscape elements with minimal movement costs. Habitat loss and fragmentation are continuing globally and are strongly related to declines in bird populations. Landscape genetic studies provide a means to understand, predict and mitigate the effects of anthropogenic landscape change on birds. This review promotes the need for landscape genetic studies of birds, such that a greater understanding of the drivers of their genetic structuring can be developed and generalizations can be made from landscape genetic studies that apply more broadly across taxa.
Robust multi‐response surface optimization: a posterior preference approach
Authors: Bashiri Mahdi , Moslemi Amir , Akhavan Niaki Seyed Taghi
Published: September 2017

This paper discusses the use of multi‐response surface optimization (MRSO) to select the preferred solutions from among various non‐dominated solutions (NDS). Since MSRO often involves conflicting responses, the decision‐maker's (DM) preference information should be included in the model in order to choose the preferred solutions. In some approaches this information is added to the model after the problem is solved. In contrast, this paper proposes a three‐stage method for solving the problem. In the first stage, a robust approach is used to construct a regression model. In the second phase, non‐dominated solutions are generated by the ε‐constraint approach. The robust solutions obtained in the third phase are NDS that are more likely to be Pareto solutions during consecutive iterations. A simulation study is then presented to show the effective performance of the proposed approach. Finally, a numerical example from the literature is brought in to demonstrate the efficiency and applicability of the proposed methodology.
Controllable τf value of barium silicate microwave dielectric ceramics with different Ba/Si ratios
Authors: Lei Wen , Zou Zheng‐Yu , Chen Ze‐Hao , Ullah Burhan , Zeb Aurang , Lan Xue‐Kai , Lu Wen‐Zhong , Fan Gui‐Fen , Wang Xiao‐Hong , Wang Xiao‐Chuan
Published: September 2017

Ba1+1/M[Si2O5+1/M] low‐permittivity microwave dielectric ceramics are prepared using the conventional solid‐state method. Pure phases are obtained in barium silicates with M = 1, 3, 4, 5, and ∞, except for M = 7, in which two phases, Ba5Si8O21 and BaSi2O5, are observed. As the complexity of the crystal structure described by the Shannon information per reduced unit cell increases, the τf value tends to change from a negative to a positive value, except for M = 5, which has the highest complexity. A single Ba5Si8O21 phase with εr anomaly peak at −180°C exhibits a rare positive τf value (+25 ppm/°C), which is a novel temperature compensator.
Phase transformations in the relaxor Na1/2Bi1/2TiO3 studied by means of density functional theory calculations
Authors: Meyer Kai‐Christian , Koch Leonie , Albe Karsten
Published: September 2017

The relaxor material Na1/2Bi1/2TiO3 (NBT) is an important basis for the development of lead‐free piezoceramics, but still many features of this material are not well understood. Here, we study the kinetics of phase transformations by octahedral tilts and A‐cation displacements in NBT by means of density functional theory calculations, employing ab initio molecular dynamics and nudged elastic band calculations. Our results show that the energetic differences between the low temperature rhombohedral, intermediate orthorhombic and other metastable phases are close to the room temperature thermal energy. Therefore, it is likely that above room temperature, several octahedral tilt patterns are present simultaneously on the local scale, just because of thermal vibration of the oxygen ions. Octahedral tilt transformations and A‐cation displacements show similarly high energy barriers, however, since the vibrational frequency of oxygen is higher, tilt transformations occur more frequently. Further, tilt transformations in which the oxygen octahedra get deformed the least are more probable to occur. We also find that the chemical A‐cation order affects energy barriers, influences the coupling between rotational and displacive modes and determines the stability of certain octahedral tilt orders. We conclude that the so‐called polar nanoregions in this material result from local octahedral tilt transformations and subsequent A‐cation displacements, which are driven by thermal vibration and are mediated by the underlying chemical order.
Experimental phase equilibria studies of the PbO–SiO2 system
Authors: Shevchenko Maxim , Jak Evgueni
Published: September 2017

Phase equilibria of the PbO–SiO2 system have been established for a wide range of compositions: (i) liquid in equilibrium with silica polymorphs (quartz, tridymite, and cristobalite) between 740°C and 1580°C, at 60‐90 mol% SiO2; (ii) with lead silicates (PbSiO3, Pb2SiO4, and Pb11Si3O17) and lead oxide (PbO) between 700°C and 810°C. A high‐temperature equilibration/quenching/electron probe X‐ray microanalysis (EPMA) technique has been used to accurately determine the compositions of the phases in equilibrium in the system. Significantly, no liquid immiscibility has been found in the high‐silica range, and the liquidus in this high‐silica region has been accurately measured. The phase equilibria information in the PbO–SiO2 system is of practical importance for the improvement of the existing thermodynamic database of lead‐containing slag systems (Pb–Zn–Fe–Cu–Si–Ca–Al–Mg–O).
New calcium‐free Na2O–Al2O3–P2O5 bioactive glasses with potential applications in bone tissue engineering
Authors: Jeznach Oliwia , Gajc Marcin , Korzeb Karolina , Kłos Andrzej , Orliński Krzysztof , Stępień Ryszard , Krok‐Borkowicz Małgorzata , Rumian Łucja , Pietryga Krzysztof , Reczyńska Katarzyna , Pamuła Elżbieta , Pawlak Dorota A.
Published: September 2017

Sodium aluminophosphate glasses were evaluated for their bone repair ability. The glasses belonging to the system 45Na2O–xAl2O3‐(55‐x)P2O5, with x = (3, 5, 7, 10 mol%) were prepared by a melt‐quenching method. We assessed the effect of Al2O3 content on the properties of Na2O–Al2O3–P2O5 (NAP) glasses, which were characterized by density measurements, DSC analyses, solubility, bioactivity in simulated body fluid and cytocompatibility with MG‐63 cells. To the best of our knowledge, this is the first investigation of calcium‐free Na2O–Al2O3–P2O5 system glasses as bioactive materials for bone tissue engineering.
A Multivariate Time‐Series Examination of Motor Carrier Safety Behaviors
Authors: Miller Jason W.
Published: September 2017

Motor carriers’ operational safety affects multiple stakeholders including truck drivers, motor carriers, insurance companies, shippers, and the general public. In this article, I devise and test theory regarding motor carriers’ longitudinal performance for three classes of safety behaviors linked to carriers’ accident rates—Unsafe Driving, Hours‐of‐Service Compliance, and Vehicle Maintenance—tracked by the Federal Motor Carrier Safety Administration as part of the Compliance, Safety, and Accountability (CSA) program. Specifically, I draw on core concepts from sociological agency theory and resource dependency theory to devise middle‐range theory that generates never‐before‐tested hypotheses regarding carriers’ longitudinal safety performance for these classes of safety behaviors after the start of the CSA program. The hypothesized predictions are tested by fitting a series of multivariate latent curve models to four years of panel data for a random sample of 484 large, for‐hire motor carriers operating in the United States. The empirical findings corroborate the theoretical predictions and remain after robustness testing. These findings have important implications for scholars, motor carrier managers, procurers of motor carrier transportation services, and public policy makers.
Attention to the model's face when learning from video modeling examples in adolescents with and without autism spectrum disorder
Authors: van Wermeskerken Margot , Grimmius Bianca , van Gog Tamara
Published: September 2017

We investigated the effects of seeing the instructor's (i.e., the model's) face in video modeling examples on students' attention and their learning outcomes. Research with university students suggested that the model's face attracts students' attention away from what the model is doing, but this did not hamper learning. We aimed to investigate whether we would replicate this finding in adolescents (prevocational education) and to establish how adolescents with autism spectrum disorder, who have been found to look less at faces generally, would process video examples in which the model's face is visible. Results showed that typically developing adolescents who did see the model's face paid significantly less attention to the task area than typically developing adolescents who did not see the model's face. Adolescents with autism spectrum disorder paid less attention to the model's face and more to the task demonstration area than typically developing adolescents who saw the model's face. These differences in viewing behavior, however, did not affect learning outcomes. This study provides further evidence that seeing the model's face in video examples affects students' attention but not their learning outcomes.
Introduction of a prediction model to assigning periodontal prognosis based on survival time
Authors: Martinez‐Canut Pedro , Alcaraz Jaime , Alcaraz Jaime , Alvarez‐Novoa Pablo , Alvarez‐Novoa Carmen , Marcos Ana , Noguerol Blas , Noguerol Fernando , Zabalegui Ion
Published: September 2017

Aims

To develop a prediction model for tooth loss due to periodontal disease (TLPD) in patients following periodontal maintenance (PM), and assess its performance using a multicentre approach.

Material and methods

A multilevel analysis of eleven predictors of TLPD in 500 patients following PM was carried out to calculate the probability of TLPD. This algorithm was applied to three different TLPD samples (369 teeth) gathered retrospectively by nine periodontist, associating several intervals of probability with the corresponding survival time, based on significant differences in the mean survival time. The reproducibility of these associations was assessed in each sample (One‐way ANOVA and pairwise comparison with Bonferroni corrections).

Results

The model presented high specificity and moderate sensitivity, with optimal calibration and discrimination measurements. Seven intervals of probability were associated with seven survival time and these associations contained close to 80% of the cases: the probability predicted the survival time at this percentage. The model performed well in the three samples, as the mean survival time of each association were significantly different within each sample, while no significant differences between the samples were found in pairwise comparisons of means.

Conclusions

This model might be useful for predicting survival time in different TLPD samples.
Do different probing depths exhibit striking differences in microbial profiles?
Authors: Pérez‐Chaparro Paula Juliana , McCulloch John Anthony , Mamizuka Elsa Masae , Moraes Aline da Costa Lima , Faveri Marcelo , Figueiredo Luciene Cristina , Duarte Poliana Mendes , Feres Magda
Published: September 2017

Aim

To perform a thorough characterization of the subgingival microbiota of shallow, moderate and deep sites in subjects with chronic periodontitis (ChP).

Material and methods

Subgingival samples were collected from subjects with ChP (n = 3/category of probing depth: ≤3, 4–6 and ≥7 mm) and periodontal health (PH). Individual samples were submitted to 16S rDNA high‐ throughput sequencing and the analysis was made using mothur and R packages.

Results

Nine subjects with ChP and seven with PH were included and 101 samples were evaluated. Thirteen phyla, 118 genera and 211 OTUs were detected. Taxa from Chloroflexi and Spirochaetes phyla were associated with initial stages of disease. Fretibacterium, Eubacterium[XI][G‐6], Desulfobulbus, Peptostreptococcaceae[XI][G‐1] and [G‐3], Bacteroidetes[G‐3], Bacteroidaceae[G‐1] genera and Filifactor alocis, Fretibacterium fastidiosum, Johnsonella spHOT166, Peptostreptococcaceae[XIII][G‐1]HOT113, Porphyromonas endodontalis and Treponema sp. HOT258, which are not conventionally associated with disease, increased with the deepening of the pockets and/or were elevated in ChP; while Streptococcus, Corynebacterium and Bergeyella genera were associated with PH (p < .05).

Conclusion

Striking differences were observed between the microbiota of shallow and moderate/deep sites, but not between moderate and deep sites in ChP subjects. Differences between shallow sites in PH and ChP were also observed. The characterized microbiota included known oral microorganisms and newly identified periodontal taxa, some of them not‐yet‐cultured.
Language and reading comprehension in middle childhood predicts emotional and behaviour difficulties in adolescence for those with permanent childhood hearing loss
Authors: Stevenson Jim , Pimperton Hannah , Kreppner Jana , Worsfold Sarah , Terlektsi Emmanouela , Mahon Merle , Kennedy Colin
Published: September 2017

Background

Permanent childhood hearing loss (PCHL) is associated with an elevated level of emotional and behaviour difficulties (EBD). In children and adolescents with PCHL, EBD has been found to be linked to language ability in children with PCHL. The present study was designed to test whether childhood language and/or reading comprehension abilities of children with PCHL predict subsequent EBD in adolescence.

Methods

Language comprehension (LC) and reading comprehension (RC) were measured at ages 6–10 years (Time 1) and 13–20 years (Time 2) in participants with PCHL who preferred to communicate using spoken language (n = 57) and a hearing comparison group (n = 38). EBD was measured at both time points by parent and by teacher ratings on the Strengths and Difficulties Questionnaire.

Results

Within the PCHL group there were negative correlations between EBD scores and concurrent LC and RC scores at Time 1 and at Time 2. Cross‐lagged latent variable models fitted to the longitudinal data indicated that the associations between LC, RC and teacher‐rated EBD were more likely to arise from the impact of LC and RC on behaviour rather than the other way around.

Conclusions

In those with PCHL, poor language and reading comprehension in middle childhood increased the risk of emotional and behaviour difficulties at school in the teenage years. The results suggest that effective language and literacy interventions for children with hearing loss may also bring benefits to their mental health.
Patterns and Predictors of Frailty Transitions in Older Men: The Osteoporotic Fractures in Men Study
Authors: Pollack Lauren R. , Litwack‐Harrison Stephanie , Cawthon Peggy M. , Ensrud Kristine , Lane Nancy E. , Barrett‐Connor Elizabeth , Dam Thuy‐Tien
Published: September 2017

Objectives

To describe the natural history of frailty transitions in a large cohort of community‐dwelling older men and identify predictors associated with progression to or improvement from states of greater frailty.

Design

Prospective cohort study.

Setting

Six U.S. sites.

Participants

Community‐dwelling men aged 65 and older (N = 5,086).

Measurements

Frailty was measured at baseline and an average of 4.6 years later. Frailty was defined as having three or more of the following components (low lean mass, weakness, self‐reported exhaustion, low activity level, and slow walking speed); prefrailty was defined as having one or two components. Separate multivariable logistic regression models were analyzed for progression and improvement in frailty status.

Results

Of the 5,086 men, 8% were frail, 46% were prefrail, and 46% were robust at baseline. Between baseline and follow‐up, 35% progressed in frailty status or died, 56% had no change in frailty status, and 15% of prefrail or frail participants improved, although only 0.5% improved across two levels, from frail to robust. In multivariable models, factors associated with improvement in frailty status included greater leg power, being married, and good or excellent self‐reported health, whereas presence of any instrumental activity of daily living (IADL) limitations, low albumin levels, high interleukin‐6 levels, and presence of chronic obstructive pulmonary disease or diabetes mellitus were associated with lower likelihood of improvement in frailty status.

Conclusion

Improvement in frailty status was possible in this cohort of community‐dwelling older men, but improvement from frail to robust was rare. Several predictors were identified as possible targets for intervention, including prevention and management of comorbid medical conditions, prevention of IADL disability, physical exercise, and nutritional and social support.
Regulation of hypothalamic corticotropin‐releasing hormone neurone excitability by oxytocin
Authors: Jamieson B. B. , Nair B. B. , Iremonger K. J.
Published: September 2017

Oxytocin (OT) is a neuropeptide that exerts multiple actions throughout the brain and periphery. Within the brain, OT regulates diverse neural populations, including neural networks controlling responses to stress. Local release of OT within the paraventricular nucleus (PVN) of the hypothalamus has been suggested to regulate stress responses by modulating the excitability of neighbouring corticotropin‐releasing hormone (CRH) neurones. However, the mechanisms by which OT regulates CRH neurone excitability are unclear. In the present study, we investigated the morphological relationship between OT and CRH neurones and determined the effects of OT on CRH neurone excitability. Morphological analysis revealed that the processes of OT and CRH neurones were highly intermingled within the PVN, possibly allowing for local cell‐to‐cell cross‐talk. Whole‐cell patch‐clamp recordings from CRH neurones were used to study the impact of OT on postsynaptic excitability and synaptic innervation. Bath‐applied OT did not alter CRH neurone holding current, spiking output or any action potential parameters. Recordings of evoked excitatory and inhibitory postsynaptic currents (EPSCs/IPSCs) revealed no net effect of OT on current amplitude; however, subgroups of CRH neurones appeared to respond differentially to OT. Analysis of spontaneous EPSC events uncovered a significant reduction in spontaneous EPSC frequency but no change in spontaneous EPSC amplitude in response to OT. Together, these data demonstrate that OT exerts a subtle modulation of synaptic transmission onto CRH neurones providing one potential mechanism by which OT could suppress CRH neurone excitability and stress axis activity.
Development of a direct contact astrocyte-human cerebral microvessel endothelial cells blood–brain barrier coculture model
Authors: Kulczar Chris , Lubin Kelsey E , Lefebvre Sylvia , Miller Donald W , Knipp Gregory T
Published: September 2017

Objectives

In conventional in-vitro blood–brain barrier (BBB) models, primary and immortalized brain microvessel endothelial cell (BMEC) lines are often cultured in a monolayer or indirect coculture or triculture configurations with astrocytes or pericytes, for screening permeation of therapeutic or potentially neurotoxic compounds. In each of these cases, the physiological relevancy associated with the direct contact between the BMECs, pericytes and astrocytes that form the BBB and resulting synergistic interactions are lost. We look to overcome this limitation with a direct contact coculture model.

Methods

We established and optimized a direct interaction coculture system where primary human astrocytes are cultured on the apical surface of a Transwell® filter support and then human cerebral microvessel endothelial cells (hCMEC/D3) seeded directly on the astrocyte lawn.

Key findings

The studies suggest the direct coculture model may provide a more restrictive and physiologically relevant model through a significant reduction in paracellular transport of model compounds in comparison with monoculture and indirect coculture. In comparison with existing methods, the indirect coculture and monoculture models utilized may limit cell–cell signaling between human astrocytes and BMECs that are possible with direct configurations.

Conclusions

Paracellular permeability reductions with the direct coculture system may enhance therapeutic agent and potential neurotoxicant screening for BBB permeability better than the currently available monoculture and indirect coculture in-vitro models.
Characterization and pharmacokinetic study of itraconazole solid dispersions prepared by solvent-controlled precipitation and spray-dry methods
Authors: Sim Taehoon , Lim Chaemin , Lee Jun Won , Kim Dong Wuk , Kim Youngsam , Kim Minsoo , Choi Seungmok , Choi Han-Gon , Lee Eun Seong , Kim Kil-Soo , Kang Wonku , Oh Kyung Taek
Published: September 2017

Objectives

Solid dispersion formulations have attracted attention to improve solubility and bioavailability of water-insoluble drugs. In this study, the variation of solubility and bioavailability by different preparation methods were studied using itraconazole (ITZ) solid dispersions.

Methods

Itraconazole solid dispersions were prepared by a solvent-controlled precipitation method (SCPM) using HPMCAS-LF, HCl antisolvent or a spray-drying method (SDM) for comparison. Dissolution tests by pH transition and pharmacokinetic study using male Sprague Dawley rats were conducted.

Key findings

Itraconazole solid dispersion dissolution tests by pH transition exhibited better dissolution compared to naive ITZ, limited dissolution in acidic conditions and a burst release at neutral pH. The ITZ solid dispersions by SCPM indicated a smaller-sized particle dispersion, limited dissolution at acidic pH and a higher release at neutral pH compared to those by SDM, suggesting that the increased protonation of anionic polymers and HPMCAS-LF by acidic antisolvent could form a tighter hydrophobic aggregation with ITZ in solid dispersions. ITZ solid dispersion prepared by SCPM also showed improved ITZ absorption in male Sprague Dawley rats compared to SDM and naïve ITZ.

Conclusions

This study suggests that the SCPM method can be widely used for solid dispersion preparations due to improved dissolution and PK profile.
Liposomal α-galactosylceramide is taken up by gut-associated lymphoid tissue and stimulates local and systemic immune responses
Authors: Kaneko Kan , McDowell Arlene , Ishii Yasuyuki , Hook Sarah
Published: September 2017

Objectives

α-Galactosylceramide (α-GalCer), a synthetic glycosphingolipid that exhibits potent immunostimulatory effects through activation of natural killer T (NKT) cells, can be used to treat conditions such as atopy, cancer, infection and autoimmunity. Administration of therapeutics through the oral route has advantages such as patient convenience, safety and reduced cost; however, there has been little research to investigate whether oral delivery of α-GalCer is possible. The aim of this study was therefore to determine whether α-GalCer formulated in either DMSO/Tween 80 or in liposomes, could access lymphoid tissue and stimulate immune activation following oral administration.

Methods

Fluorescently labelled cationic liposomes incorporating α-GalCer were prepared, characterized and administered by oral gavage to fasted mice.

Key findings

Liposomes were detected inside the Peyer's patches (PPs), in the subepithelial dome just under the follicle-associated epithelium. CD11b+ cells and CD11c+ were shown to have taken up the formulation in a higher proportion compared to the total cell proportion in the PPs, suggesting that cells with these markers may be the prominent antigen-presenting cells involved in selective uptake. Finally, the liposomal formulation demonstrated a higher degree of immune stimulation compared to the DMSO/Tween 80 solubilized α-GalCer in the PPs, mesenteric lymph nodes and spleen as shown by the increased expression of IL-4 mRNA expression and increased proportion of NKT cells at 6 h and 3 days after administration.

Conclusions

These results show that oral delivery of a liposomal α-GalCer can stimulate local and systemic immune responses to a different degree compared to the non-liposomal form.
Does the adjunctive use of statins provide additional benefits to nonsurgical periodontal treatment? A systematic review and meta‐analysis
Authors: Ambrósio L. M. B. , Rovai E. S. , Sendyk D. I. , Holzhausen M. , Pannuti C. M.
Published: September 2017

Adjunctive therapeutic agents may be used to improve the response to nonsurgical periodontal therapy. Local delivery of statins (simvastatin, artovastatin and rosuvastatin) is a promising adjunct to scaling and root planing (SRP). Thus, the aim of this review is to evaluate if adjunctive local delivery of statins is more effective thanSRPalone. Randomized clinical trials that presented a test group evaluating local delivery of statins as adjuncts in healthy, diabetic and smoking patients were included. Medline and the Cochrane library database were searched up to November 2016. Random effects meta‐analyses were conducted for pocket depth change and clinical attachment gain. One hundred and twenty‐five studies potentially related to the aim of this review were screened, but only 10 were included. The majority of the trials reported additional clinical benefits in the groups that were treated with adjunctive local delivery of statins. Pooled calculations showed that local delivery of statins resulted in additional reduction of pocket depth and clinical attachment gain in healthy people, smokers and diabetic patients. Local statins may offer additional clinical benefits toSRP, even in smokers and diabetics.
Modeling the Proactive Driving Behavior of Connected Vehicles: A Cell‐Based Simulation Approach
Authors: Zhu Feng , Ukkusuri Satish V.
Published: September 2017

Connected vehicles are able to proactively change speed to adapt to the prevailing traffic condition. Even in the mixed traffic environment, connected vehicles may function as leading vehicles, hence influencing the driving pattern of following nonconnected vehicles. This article proposes a cell‐based simulation approach to model the proactive driving behavior of connected vehicles. First, a state variable of connected vehicles is introduced to track the trajectory of connected vehicles. Then the exit flow of cells containing connected vehicles is adjusted to simulate the proactive driving behavior, such that the traffic light is green when the connected vehicle arrives at the signalized intersection. The second part of the article conducts numerical tests to examine the effect of the proactive driving behavior of connected vehicles. Extensive test results consistently show that the presence of connected vehicles contributes significantly to the smoothing of traffic flow and vehicular emission reductions in the network.