bluuebunny/crossref_metadata_2025 huggingface dataset:
Nondestructive Corrosion Evaluation of Reinforced Concrete Bridge Decks with Overlays: An Experimental Study
Authors: Meng Dewei , Lin Shibin , Azari Hoda
Published: March 2019

Concrete corrosion induced by deicing agents can decrease the durability of concrete bridge decks by causing cross-sectional loss of reinforcement, concrete delamination, and spalling owing to the expansion of corroded reinforcement. The installation of overlays can extend the service life of the deteriorated decks. However, overlays present challenges in the evaluation of the corrosion condition of the underlying decks. This laboratory study employed three nondestructive testing (NDT) methods to assess the effects of seven types of overlays on corrosion evaluation for concrete bridge decks. The NDT methods were electrical resistivity (ER), ground-penetrating radar (GPR), and half-cell potential (HCP). The ER method could not evaluate the corrosive environment in the concrete decks through the overlays. The GPR method could detect the corrosive environment through four of the seven overlays. The HCP method could detect the decrease of electrical potential over the actively corroded reinforcement for all seven specimens; however, only two of the seven specimens could be identified as having active corrosion per ASTM C876-15, Standard Test Method for Corrosion Potentials of Uncoated Reinforcing Steel in Concrete. Overlay debonding did not affect GPR and HCP testing results in this study.
Brain Region-Specific Gene Signatures Revealed by Distinct Astrocyte Subpopulations Unveil Links to Glioma and Neurodegenerative Diseases
Authors: Cuevas-Diaz Duran Raquel , Wang Chih-Yen , Zheng Hui , Deneen Benjamin , Wu Jia Qian
Published: March 2019

Currently, there are no effective treatments for glioma or for neurodegenerative diseases because of, in part, our limited understanding of the pathophysiology and cellular heterogeneity of these diseases. Mounting evidence suggests that astrocytes play an active role in the pathogenesis of these diseases by contributing to a diverse range of pathophysiological states. In a previous study, five molecularly distinct astrocyte subpopulations from three different brain regions were identified. To further delineate the underlying diversity of these populations, we obtained mouse brain region-specific gene signatures for both protein-coding and long non-coding RNA and found that these astrocyte subpopulations are endowed with unique molecular signatures across diverse brain regions. Additional gene set and single-sample enrichment analyses revealed that gene signatures of different subpopulations are differentially correlated with glioma tumors that harbor distinct genomic alterations. To the best of our knowledge, this is the first study that links transcriptional profiles of astrocyte subpopulations with glioma genomic mutations. Furthermore, our results demonstrated that subpopulations of astrocytes in select brain regions are associated with specific neurodegenerative diseases. Overall, the present study provides a new perspective for understanding the pathophysiology of glioma and neurodegenerative diseases and highlights the potential contributions of diverse astrocyte populations to normal, malignant, and degenerative brain functions.
Development of Local Circuit Connections to Hilar Mossy Cells in the Mouse Dentate Gyrus
Authors: Shi Yulin , Grieco Steven F. , Holmes Todd C. , Xu Xiangmin
Published: March 2019

Hilar mossy cells in the dentate gyrus (DG) shape the firing and function of the hippocampal circuit. However, the neural circuitry providing afferent input to mossy cells is incompletely understood, and little is known about the development of these inputs. Thus, we used whole-cell recording and laser scanning photostimulation (LSPS) to characterize the developmental trajectory of local excitatory and inhibitory synaptic inputs to mossy cells in the mouse hippocampus. Hilar mossy cells were targeted by visualizing non-red fluorescent cells in the dentate hilus of GAD2-Cre; Ai9 mice that expressed tdTomato in GAD+ neurons, and were confirmed by post hoc morphological characterization. Our results show that at postnatal day (P)6–P7, mossy cells received more excitatory input from neurons in the proximal CA3 versus those in the DG. In contrast, at P13–P14 and P21–P28, the largest source of excitatory input originated in DG cells, while the strength of CA3 and hilar inputs declined. A developmental trend was also evident for inhibitory inputs. Overall inhibitory input at P6–P7 was weak, while inhibitory inputs from the DG cell layer and the hilus predominated at P13–P14 and P21–P28. The strength of local DG excitation and inhibition to mossy cells peaked at P13–P14 and decreased slightly in older P21–P28 mice. Together, these data provide new detailed information on the development of local synaptic connectivity of mossy cells, and suggests mechanisms through which developmental changes in local circuit inputs to hilar mossy cells shape their physiology and vulnerability to injury during postnatal periods.
Phase Coherent Currents Underlying Neocortical Seizure-Like State Transitions
Authors: Breton Vanessa , Bardakjian Berj , Carlen Peter
Published: March 2019

In the epileptic brain, phase amplitude cross-frequency coupling (CFC) features have been used to objectively classify seizure-related states, and the inter-seizure state has been demonstrated as being random, in contrast to the seizure state being predictable; however, the excitatory and inhibitory networks underlying their dynamics remain unclear. Therefore, the objectives of this study are to classify the dynamics of seizure sub-states labeling seizure-like event (SLE) onset and termination intervals using CFC features and to obtain their underlying excitatory/inhibitory cellular correlates. SLEs were induced in mouse neocortical brain slices using a low-magnesium perfusate, and were recorded in Layer II/III using simultaneous local field potential (LFP) and whole-cell voltage clamp electrodes. Classification of onset and termination of SLE transitions was investigated using CFC features in conjunction with an unsupervised two-state hidden Markov model (HMM). γ-Distributions of their durations indicated that both are predictable. Furthermore, omitting 4 Hz from the HMM classifier switched both SLE sub-states from statistically deterministic to random without changing the dynamics of the SLE state. These results were generalized to 4-aminopyridine (4-AP)-induced SLEs and human seizure traces. Only during these sub-states, both excitatory and inhibitory currents coupled with the field. Where excitatory currents phase locked to a broad range of frequencies between 1 and 12 Hz, inhibitory currents dominantly phase locked at 4 Hz. We conclude that inhibition underlies the predictability of neocortical CFC-defined SLE transition sub-states.
Unraveling the connection between GABA and kisspeptin in the control of reproduction
Authors: Di Giorgio Noelia P , Bizzozzero-Hiriart Marianne , Libertun Carlos , Lux-Lantos Victoria
Published: March 2019

Neuroendocrine control of reproduction involves the interplay of various factors that become active at some point along development. GnRH is the main neurohormone controlling reproduction and among the most important inputs modulating GnRH synthesis/secretion are GABA and kisspeptins. These interactions of GABA and kisspeptin in the control of GnRH secretion can take place by the presence of the receptors of both factors on the GnRH neuron or alternatively by the actions of GABA on kisspeptin neurons and/or the actions of kisspeptin on GABA neurons. Kisspeptin acts on the Kiss1R, a seven transmembrane domain, Gαq/11-coupled receptor that activates phospholipase C, although some Gαq/11-independent pathways in mediating part of the effects of Kiss1R activation have also been proposed. GABA acts through two kinds of receptors, ionotropic GABAA/C receptors involving a chloride channel and associated with fast inhibitory/stimulatory conductance and metabotropic GABAB receptors (GABABR) that are Gi/0protein linked inducing late slow hyperpolarization. In this review, we aim to summarize the different ways in which these two actors, kisspeptin and GABA, interact to modulate GnRH secretion across the reproductive lifespan.
Cristología integral y cruz de Jesús: aportes a la teología de la cruz desde Karl Rahner y su “Curso fundamental sobre la fe”
Authors: Quevedo Rodríguez Andrés Mauricio
Published: March 2019

Karl Rahner es uno de los teólogos más importantes del siglo pasado. De hecho, su trabajo acerca de la antropología trascendental ha permitido revisar los lugares comunes de la teología, con el fin de darles nuevos significados. Consecuentemente, a partir de la cristología integral propuesta en el libro Curso fundamental sobre la fe: introducción al concepto de cristiano, este artículo muestra cómo es posible pensar la pasión de Jesús desde una perspectiva que incluya no solo el momento de la muerte, sino el conjunto de su vida. Para lograrlo, el texto hace un acercamiento biográfico al autor, explica el fundamento de la cristología trascendental y relee la cruz desde esta opción teológica.
Redundant and Cryptic Enhancer Activities of theDrosophila yellowGene
Authors: Kalay Gizem , Lachowiec Jennifer , Rosas Ulises , Dome Mackenzie R , Wittkopp Patricia
Published: March 2019

Evolutionary changes in enhancers, which control gene expression, often contribute to phenotypic evolution. Here, Kalay et al. examine how enhancer activities are encoded within non-coding sequences surrounding the pigmentation gene yellow from three Drosophila species...

Cis-regulatory sequences known as enhancers play a key role in regulating gene expression. Evolutionary changes in these DNA sequences contribute to phenotypic evolution. The Drosophila  yellow gene, which is required for pigmentation, has emerged as a model system for understanding how cis-regulatory sequences evolve, providing some of the most detailed insights available into how activities of orthologous enhancers have diverged between species. Here, we examine the evolution of yellow cis-regulatory sequences on a broader scale, by comparing the distribution and function of yellow enhancer activities throughout the 5′ intergenic and intronic sequences of Drosophila melanogaster, D. pseudoobscura, and D. willistoni. We find that cis-regulatory sequences driving expression in a particular tissue are not as modular as previously described, but rather have many redundant and cryptic enhancer activities distributed throughout the regions surveyed. Interestingly, cryptic enhancer activities of sequences from one species often drove patterns of expression observed in other species, suggesting that the frequent evolutionary changes in yellow expression observed among Drosophila species may be facilitated by gaining and losing repression of preexisting cis-regulatory sequences.
Exercise-Induced Purpura in Children
Authors: Paul Sarah S. , Scalzi Lisabeth V.
Published: March 2019

Exercise-induced purpura, which has also been called “golfer’s purpura,” is a phenomenon that has been rarely reported in the pediatric literature. This is the first case series in which this benign vasculopathy, which is most often associated with warm weather and high-impact activity, is described. In this series, we describe 5 patients, most of whom had an erythematous purpuric rash above the sock line that extended to the knees and was associated with warm weather and prolonged activity. Exercise-induced purpura may be mistaken for Henoch-Schönlein purpura or as a manifestation of a possible systemic vasculitis. Recognition of this benign condition is vital to avoid an unnecessary workup and a costly evaluation with accompanying anxiety.
Enhancing the Quality of Left Ventricular Ejection Fraction Assessment by Echocardiography
Authors: Johri Amer M , Crerar Matthew I , Sanfilippo Anthony J
Published: March 2019

The assessment of left ventricular ejection fraction is a key clinical investigation guiding the diagnosis, management and prognosis of cardiology patients. Echocardiography is an inexpensive, safe, and portable method commonly used to provide this information. Improvement in the quality of assessment provided by echocardiography continues to be the subject of current clinical programs and investigations. Contrast-enhanced echocardiography is an established method to reduce both inter- and intra-observer variability in the echocardiography lab. The implementation of teaching interventions has also been shown to reduce variability in the qualitative and quantitative assessment of ejection fraction. Newer investigative methods, such as 3D imaging and speckle tracking, show promise as tools to further enhance the quality of left ventricular ejection fraction assessment in the echocardiography lab.
High-sensitivity Troponins—Difficult Friends in Acute Coronary Syndromes
Authors: Klingenberg Roland , Matter Christian M , Wyss Christophe , Hof Danielle , von Eckardstein Arnold , Lüscher Thomas F
Published: March 2019

The introduction of novel high-sensitivity cardiac troponin (hs-cTn) assays has made it possible to measure cardiac troponin levels that are up to 10-fold lower than those detectable by conventional cardiac troponin (cTn) assays. With such novel assays, an elevated risk of major adverse cardiovascular events was noted across the continuum of cTn levels, with an incremental risk of increasing levels even in healthy individuals, but also in patients with stable coronary artery disease, congestive heart failure or acute coronary syndrome (ACS). The rapid triage of patients presenting to the accident and emergency department with chest pain is critical to ensure optimal management, and the novel hs-cTn assays provide a valuable tool for a more rapid exclusion of acute myocardial infarction (AMI), with a higher sensitivity, negative predictive value and diagnostic accuracy compared with conventional cTn assays. The associated decrease in specificity and positive predictive value for the diagnosis of AMI can be overcome by serial measurements to assess the absolute and relative increases in cTn levels. This article provides a contemporary overview of the role of hs-cTn in the detection of individuals with subclinical disease, diagnosis of ACS, risk stratification and clinical management. Furthermore, aspects of uncertainty, such as cut-offs, and the role of hs-cTn for clinical decision-making are addressed.
Percutaneous Coronary Intervention in Patients with Diabetes and Multivessel or Left Main Disease—A Review
Authors: Cutlip Donald E
Published: March 2019

Coronary artery disease in patients with diabetes is frequently a diffuse process with multivessel involvement and is associated with increased risk for myocardial infarction and death. The role of percutaneous coronary intervention (PCI) versus coronary artery bypass grafting (CABG) in patients with diabetes and multivessel disease who require revascularization has been debated and remains uncertain. The debate has been continued mainly because of the question to what degree an increased risk for in-stent restenosis among patients with diabetes contributes to other late adverse outcomes. This article reviews outcomes from early trials of balloon angioplasty versus CABG through later trials of bare-metal stents versus CABG and more recent data with drug-eluting stents as the comparator. although not all studies have been powered to show statistical significance, the results have been generally consistent with a mortality benefit for caBG versus PCI, despite differential risks for restenosis with the various PCI approaches. The review also considers the impact of mammary artery grafting of the left anterior descending artery and individual case selection on these results, and proposes an algorithm for selection of patients in whom PCI remains a reasonable strategy.
Ecological features of enzyme activity distribution in edaphotops of technogenic landscapes
Authors: Chorna V. I. , Wagner I. V. , Katsevych V. V.
Published: March 2019

Specific features of distribution total, available phosphorus concentrations and levels of phosphatase enzymatic activity at the layers of artificial soil, sod-lithogenic soils onto gray-green and red-brown clays and on loess-like loams in the Nikopol manganese ore basin are established. It is presented general assessment of technosoil status by evaluation of phosphatase enzyme activity; this enzyme enriches the soil with mineral phosphorus and thereby improves its availability for living organisms. Among current bioindication methodology, soil enzymatic method is the most reliable and promising because enzymatic activity serves a stable indicator of soil biogenicity in comparison with other indicators. Soil enzymatic activity determines both intensity and targeting of biogeochemical processes. High correlation between concentrations of soluble phosphorus and phosphatase activity values by layers of artificial soil (r = 0.87), sod-lithogenic soils onto gray-green (r = 0.77), red-brown clays (r = 0.62) and onto loess-like loam (r = 0.95) was determined. Tendency of decreasing hydrolytic enzyme activity, phosphatase, with depth in all types of artificial soil studied was established. High efficiency of the enzymatic activity study in diagnostics of soil fertility dynamics under impact of various anthropogenic and natural ecosystems was determined. Advantages of using this method are capability to determine rapidly the changes occurring in ecosystems in the early stages of degradation processes and prediction of their targeting and, accordingly, their intensity. It has been found that levels of phosphatase activity and values of mobile phosphorus compounds in complex biogeocoenotic systems are sensitive quantitative indicators of changes in environmental conditions in man-made environment, and they generate good data about processes occurred within the soil column. The use of phosphatase activity level can be a reliable and promising method on biomonitoring of technogenic edaphotops.
Una clasificación del discurso didascálico desde una perspectiva polifónica de la enunciación
Authors: Zucchi Mariano Nicolás
Published: March 2019

En términos generales, los estudios teatrales tradicionales parecen pasar por alto el hecho de que las didascalias no constituyen un conjunto homogéneo de enunciados, sino que, por el contrario, existen una serie de diferencias formales que permiten identificar distintos subtipos, cada uno de ellos con una función específica en la construcción de sentido. Por consiguiente, en este trabajo buscamos proponer una clasificación del discurso didascálico que atienda a sus características lingüísticas específicas. Al respecto, sugerimos distinguir entre las “didascalias paratextuales” (aquellas que son externas a la narración), las “didascalias generales” (enunciados que cumplen la función de construir una representación de la situación dramática) y las “didascalias particulares” (expresiones que acompañan cada una de las réplicas de los personajes y se especializan en definir su “escenografía” (véase MAINGUENEAU, 2002)). Para probar nuestra hipótesis, nos enmarcaremos en el Enfoque dialógico de la argumentación y la polifonía enunciativa (véase GARCÍA NEGRONI, 2009, 2016a, 2016b, 2017), teoría no referencial del significado lingüístico y no unicista del sujeto. Finalmente, respecto al corpus de trabajo, haremos uso de la pieza Misterio del ramo de rosas (2009), del escritor argentino Manuel Puig, para ejemplificar los distintos subtipos que proponemos en nuestra categorización del discurso didascálico. *** Uma classificação do discurso didascálico desde uma perspectiva polifônica da enunciação ***De um modo geral, os estudos de teatro tradicionais parecem ignorar o fato de que as direções de palco não são um conjunto homogêneo de declarações, mas por outro lado, há uma série de diferenças formais que identificam diferentes subtipos, cada um com uma função específica na construção do significado. Portanto, neste artigo, procuramos propor uma classificação do discurso didascálico que aborde suas características linguísticas específicas. Neste sentido, sugerimos distinguir entre “didascalias paratextuales” (aquelas que são externas à narrativa), as “didascalias generales” (declarações que funcionam para construir uma representação da situação dramática) e as “didascalias particulares” (expressões que acompanham cada uma das réplicas dos personagens e se especializam na definição de sua “cenografia” (ver MAINGUENEAU, 2002)). Para testar a nossa hipótese, vamos enquadrar no Enfoque dialógico de la argumentación y la polifonía enunciativa (ver GARCÍA NEGRONI, 2009, 2016a, 2016b, 2017), a teoria não-referencial do significado linguístico e não unicista do assunto. Finalmente, quanto ao corpus do trabalho, vamos usar o Misterio del ramo de rosas (2009), do escritor argentino Manuel Puig, para exemplificar os diferentes subtipos que propomos na nossa categorização de expressão didascálica.Palavras-chave: Argumentação; Didascália; Polifonia; Réplica; Texto dramático.
Factores que afectan la producción en primera lactancia de vacas lecheras de Costa Rica
Authors: Castillo-Badilla Gloriana , Vargas-Leitón Bernardo , Hueckmann-Voss Frank , Romero-Zúñiga Juan José
Published: March 2019

Introducción. El método de crianza que se brinda a una ternera, determina la vaca productora del futuro. Por lo tanto, las técnicas de salud, nutrición y alimentación pueden afectar el inicio y rendimiento de la vida productiva de una hembra bovina. Objetivo. El objetivo de este trabajo fue determinar el efecto de los factores del animal y del ambiente, modificables y no modificables, sobre la producción de la primera lactancia (PPL) en hatos lecheros especializados de Costa Rica. Materiales y métodos. Se realizó un estudio de cohorte retrospectivo. Se incluyeron 2747 vacas de razas Jersey y Holstein, con primer parto entre los años 2013 y 2015, de veintidós hatos lecheros especializados de diferentes zonas ecológicas de Costa Rica, con datos en el programa VAMPP Bovino. Se analizaron los datos mediante estadística descriptiva y un modelo lineal generalizado. Resultados. La PPL promedio a 305 días fue de 5485,8 kg (± 1547,8). Las variables no modificables del individuo, como la raza, presentaron efectos significativos sobre la PPL, con valores de 5360,1 kg (IC95%: 5158,2-5562,1) y 4694,1 kg (IC95%: 4578,5-4809,7) en la raza Holstein y Jersey, respectivamente. Se observó una tendencia a incrementar los niveles de producción conforme se aumentó la edad al primer parto hasta los veintiséis meses (P<0,001), después de lo cual se mantuvo estable. Se determinó un efecto significativo de la variable modificable de manejo (P<0,0001); fincas con protocolos de alta calidad de crianza de terneras produjeron 213,9 kg (PPL: 5809,0; IC95%: 5570,6-6047,4) más de leche en su primera lactancia, que las novillas con una crianza media, y 1133,7 kg más que las de sistemas de baja calidad de manejo (PPL: 4676,3; IC95%: 4158,3-5194,3). Conclusión. Estos resultados evidencian la influencia que tienen los métodos de crianza de terneras sobre el rendimiento productivo posterior del animal en sistemas tropicales. Las condiciones del medio ambiente tropical, incluyendo temperatura, humedad y precipitación, afectan de manera considerable el comportamiento productivo de las vacas lecheras.
The Effectiveness of Anatomy Laboratory Videos on Osteopathic Medical Students’ Performance
Authors: Sakthi Velavan Sumathilatha , Castellanos Bedia
Published: March 2019

This article was migrated. The article was not marked as recommended. Introduction: The usage of audio-visual aids in medical education has always been rewarding. This study aimed at evaluating the efficacy of supplementing traditional dissection based laboratories with the video demonstration of specimens. Methods: The study was conducted among first-year osteopathic medical students of two consecutive years. The laboratory demonstration videos were recorded and provided to the experimental group and the previous class served as the historical controls. Two Likert scale based questionnaires were completed by the experimental group before and after their final examination. The students' performance in the Anatomy practical examinations were compared between the two groups. Results: The students' response showed that the videos added value to their knowledge. The videos helped them in understanding the structures in the dissection lab with ease they felt more confident about the examinations. The experimental group scored significantly higher grades in the practical examinations than the control group. The results confirm that the video demonstration has a positive impact on the traditional dissection method. Conclusion: The effect on the student's perception is impressive and the positive outcome in the examination grades adds on to the significance of this teaching methodology. Integration of multimedia with dissection is suggested as a helpful model to improve Anatomy learning process.
Pilot simulation-based research for evaluation, training and assessment of holistic nursing at four intensive care unit sites
Authors: Shiao Tsu-Hui , Wu Chen-Yi , Yang Ying-Ying , Chang Shi-Chuan , Shulruf Boaz , Yang Ling-Yu , Chen Chen-Huan , Lee Fa-Yauh
Published: March 2019

This article was migrated. The article was marked as recommended. Background: Holistic nursing of intensive care unit (ICU) patients encompasses diverse challenges requiring regular in situ evaluation, training and assessment. Simulation has been adopted as a research and training tool in medicine; however, evidence for its use in enhancing holistic care at multi-sites is limited. Objective: This study aims to conduct a simulation-based research (SBR) at four ICU for standardized training of holistic nursing. Methods: There are stages of evaluating, training+in-training assessment and post-course assessment in this SBR. Specifically, the curriculum-mapped scenarios were developed according to the deficiency of each site after evaluating stage. At the training stage, the first simulation by team was defined as preparation step and the in-training assessment was undertaken at the second simulation. Results: From January 2017 to October 2018, sixty-four ICU nurses (16 teams, 4 teams in each site) at RCU, PICU, NICU and GYN ICU, attend 8 similar courses (2 courses at each site) over 20 months. In comparison with baseline performance, in-training assessments revealed the significant improvement of attendee's skills of holistic nursing. Attendees commented that simulation was a valuable training modality to enhance skills of holistic care including history taking, physical examination, communication and teamwork that are rarely taught among ICU nurses. Post-course workplace assessment by senior nurses revealed the high frequency of clinical application of holistic nursing by attendees. Additionally, post-course self assessment revealed a high attendee's confidence of holistic approaching in ICU. Conclusion: This pilot SBR demonstrated the feasibility of a standardized holistic care simulation program across four ICUs. In situ simulation and post-course workplace assessment affords situational learning without compromising patient safety and is an exciting and novel training of holistic nursing for ICU that could be integrated into regular intervention.
From Diagnostic-Therapeutic Pathways to Real-World Data: A Multicenter Prospective Study on Upfront Treatment for EGFR-Positive Non-Small Cell Lung Cancer (MOST Study)
Authors: Pasello Giulia , Vicario Giovanni , Zustovich Fable , Oniga Francesco , Gori Stefania , Rosetti Francesco , Bonetti Andrea , Favaretto Adolfo , Toso Silvia , Redelotti Roberta , Santo Antonio , Bernardi Daniele , Giovanis Petros , Oliani Cristina , Calvetti Lorenzo , Gatti Carlo , Palazzolo Giovanni , Baretta Zora , Bortolami Alberto , Bonanno Laura , Basso Marco , Menis Jessica , Corte Donatella Da , Frega Stefano , Guarneri Valentina , Conte PierFranco ,   on behalf of Veneto Oncology Network
Published: March 2019

Introduction

Gefitinib, erlotinib, and afatinib represent the approved first-line options for epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC). Because pivotal trials frequently lack external validity, real-world data may help to depict the diagnostic-therapeutic pathway and treatment outcome in clinical practice.

Methods

MOST is a multicenter observational study promoted by the Veneto Oncology Network, aiming at monitoring the diagnostic-therapeutic pathway of patients with nonsquamous EGFR-mutant NSCLC. We reported treatment outcome in terms of median time to treatment failure (mTTF) and assessed the impact of each agent on the expense of the regional health system, comparing it with a prediction based on the pivotal trials.

Results

An EGFR mutation test was performed in 447 enrolled patients, of whom 124 had EGFR mutation and who received gefitinib (n = 69, 55%), erlotinib (n = 33, 27%), or afatinib (n = 22, 18%) as first-line treatment. Because erlotinib was administered within a clinical trial to 15 patients, final analysis was limited to 109 patients. mTTF was 15.3 months, regardless of the type of tyrosine kinase inhibitor (TKI) used. In the MOST study, the budget impact analysis showed a total expense of €3,238,602.17, whereas the cost estimation according to median progression-free survival from pivotal phase III trials was €1,813,557.88.

Conclusion

Good regional adherence and compliance to the diagnostic-therapeutic pathway defined for patients with nonsquamous NSCLC was shown. mTTF did not significantly differ among the three targeted TKIs. Our budget impact analysis suggests the potential application of real-world data in the process of drug price negotiation.
Experimental and numerical studies of a strip footing on geosynthetic-reinforced sand
Authors: Xu Youwei , Yan Guanxi , Williams David J. , Serati Mehdi , Scheuermann Alexander , Vangsness Timothy
Published: March 2019

The behaviour of footings on geosynthetic-reinforced soils has been investigated by many researchers through experimental and numerical modelling under stress-controlled or strain-controlled conditions. A new experimental set-up was designed under a stress-controlled condition, with the application of the particle image velocimetry (PIV) technique. A series of model footing tests was carried out using this equipment to investigate the behaviour of the geosynthetic-reinforced soil below a strip footing. The deformation inside the soil mass below the strip footing was determined using the PIV technique. The reinforcing performances of single-layer and multi-layer geotextile and single-layer geogrid embedded at different depths were compared and discussed by analysing the load–settlement curves. It is found that there is a stepwise increase phenomenon in settlement under the stress-controlled condition. The ultimate bearing capacities were determined from the obtained stepwise load–settlement curves using three approaches: the tangent intersection method, the tail linear method and the allowable settlement method. The three approaches were coded in a Python program in order easily to determine and compare the results. In addition, the experimental model footing tests were simulated using the finite-element method under the same stress condition with good agreement for a settlement range within 0·1B.
Gendered politics in rural roads: gender mainstreaming in Tanzania's transport sector
Authors: Mulongo Godfrey , Porter Gina , Tewodros Amleset
Published: March 2019

This paper explores the impacts of gender mainstreaming initiatives in Tanzania's transport sector on the everyday reality of rural women's lives, including those facing multiple forms of discrimination. Using qualitative methods, including co-investigation with community members, data were triangulated from diverse sources: vulnerable women and other residents in two Tanzanian districts, road contractors, professionals engaged in supporting the country's transport programmes and staff in donor agencies. The results indicate that progress in mainstreaming has been slow. Despite government directives, few women have benefitted from employment in road construction except through two national programmes: the Village Travel and Transport Programme and the Tanzania Social Action Fund. However, most women, particularly those disadvantaged, derive benefit from road improvement, even if only as pedestrians or wheelchair users taking advantage of a smoother surface, or better travel security when vegetation is cut back. For women with the funds and independence to access the expanded transport services that tend to follow road improvements, there can be significant benefits – faster travel, improved access to farms and markets and sometimes lower transport costs. Nevertheless, women's constrained resources and prevailing cultural mores continue to militate against them directly operating transport, whether for personal or business use.
Single-Cell RNA Profiling of Glomerular Cells Shows Dynamic Changes in Experimental Diabetic Kidney Disease
Authors: Fu Jia , Akat Kemal M. , Sun Zeguo , Zhang Weijia , Schlondorff Detlef , Liu Zhihong , Tuschl Thomas , Lee Kyung , He John Cijiang
Published: March 2019

Significance Statement

Although transcriptomic profiling of kidney tissues or isolated glomeruli has provided insights into broad changes in the pathogenesis of diabetic kidney disease, the presence of multiple cell types in kidney samples limits what can be discerned about changes in specific types of cells. To better elucidate the mechanisms of early diabetic kidney injury, the authors used single-cell RNA sequencing technology to perform a gene expression analysis of individual kidney glomerular cells of a diabetic mouse model. A comparison of gene expression in normal versus diabetic mouse kidney cells at a single-cell level showed dynamic changes in the pattern of expressed genes. This approach may help identify important factors underlying the pathophysiology of diabetic kidney disease progression and point to potential new therapeutic approaches.

Background

Recent single-cell RNA sequencing (scRNA-seq) analyses have offered much insight into cell-specific gene expression profiles in normal kidneys. However, in diseased kidneys, understanding of changes in specific cells, particularly glomerular cells, remains limited.

Methods

To elucidate the glomerular cell–specific gene expression changes in diabetic kidney disease, we performed scRNA-seq analysis of isolated glomerular cells from streptozotocin-induced diabetic endothelial nitric oxide synthase (eNOS)–deficient (eNOS−/−) mice and control eNOS−/− mice.

Results

We identified five distinct cell populations, including glomerular endothelial cells, mesangial cells, podocytes, immune cells, and tubular cells. Using scRNA-seq analysis, we confirmed the expression of glomerular cell–specific markers and also identified several new potential markers of glomerular cells. The number of immune cells was significantly higher in diabetic glomeruli compared with control glomeruli, and further cluster analysis showed that these immune cells were predominantly macrophages. Analysis of differential gene expression in endothelial and mesangial cells of diabetic and control mice showed dynamic changes in the pattern of expressed genes, many of which are known to be involved in diabetic kidney disease. Moreover, gene expression analysis showed variable responses of individual cells to diabetic injury.

Conclusions

Our findings demonstrate the ability of scRNA-seq analysis in isolated glomerular cells from diabetic and control mice to reveal dynamic changes in gene expression in diabetic kidneys, with variable responses of individual cells. Such changes, which might not be apparent in bulk transcriptomic analysis of glomerular cells, may help identify important pathophysiologic factors contributing to the progression of diabetic kidney disease.
Comparação da Fidelidade da Cor de Cerâmicas quando comparadas com as suas respectivas Escalas
Authors: Goyatá Frederico dos Reis , Moreno Amália , De Aguiar Amanda Nascimento , Barreiros Ivan Doche , Moreira lanza Célia Regina , Talma Elissa , Cortes Segura Maria Esperanza , Novaes Júnior João Batista
Published: March 2019

Introdução: As cerâmicas dentárias são consideradas os materiais de escolha para a confecção de facetas e coroas protéticas em dentes anteriores e posteriores e apresentam características estéticas e biomecânicas semelhantes aos tecidos dentais além de reproduzir com maior fidelidade a cor dos dentes. A etapa clínica da seleção de cor dos dentes do paciente, para posterior confecção da prótese pelo TPD, determina o resultado estético das coroas protéticas em cerâmica.Objetivo: Este trabalho teve como objetivo avaliar a fidelidade da cor de diferentes cerâmicas feldspáticas: Porcelain EX-3 (Noritake, Japão), StarLight (Dentsply, Brasil) e HeramCeram (Heraeus, Alemanha) com as respectivas escalas de cor: Shade Guide (Noritake, Japão), Vita Clássica (Vita, Alemanha) e Pala (Heraeus, Alemanha).Metodologia: Foram confeccionadas facetas cerâmicas  reproduzindo os aspectos estéticos (forma, matiz, croma e valor) padronizadas no momento da estratificação e aplicação laboratorial da cerâmica.Resultados: As facetas confeccionadas após a determinação da cor foram comparadas à escala original do fabricante de cada cerâmica e apresentaram grandes diferenças nos aspectos estéticos avaliados, ratificando a importância do conhecimento das cerâmicas e tipo de escala utilizada.Conclusão: A falta do conhecimento no momento da seleção da cor influencia no registro e mapeamento da cor dos dentes que serão reabilitados pelo cirurgião dentista, podendo levar a insucessos na transmissão de informação com o laboratório de Prótese.
Cooling of the heated circular porous disc with a circular jet
Authors: GÜRTÜRK Mert , OZTOP Hakan F.
Published: March 2019

In this
study, an experimental analysis has been performed on jet impingement onto close-cell
porous material which is the shape of a circular porous disc which is aluminum foam. This porous material was located on the circular heater and temperature distribution,
local and average Nusselt number were observed at the different situations.
Experiments were carried out by considering different parameters which are Reynolds
number (1048, 2620, 4192), the thickness
of porous disc (6, 8, 10 mm) and heater power (3.6, 6.8, 10.5 W). The results
show that the maximum average Nu number value is calculated as 464.06 at Re =
4192, P = 10.5 W. It is observed that for the lowest average Nu number value is
obtained at P = 3.6 W and Re = 1048 for without porous material. The lowest
average Nu number value is calculated as 94.201. It is found that the porous
materials can be used to control heat transfer.
The Near-Term Forward Yield Spread as a Leading Indicator: A Less Distorted Mirror
Authors: Engstrom Eric C. , Sharpe Steven A.
Published: March 2019

The spread between the yield on a 10-year Treasury note and the yield on a shorter maturity security, such as a 2-year Treasury note, is commonly used as an indicator for predicting U.S. recessions. We show that such "long-term spreads" are statistically dominated in models that predict recessions or GDP growth by an economically more intuitive alternative, a "near-term forward spread." The latter can be interpreted as a measure of the market's expectations for the near-term trajectory of conventional monetary policy rates. Its predictive power suggests that, when market participants expected—and priced in—a monetary policy easing over the subsequent year and a half, a recession was quite likely in the offing. We also find that the near-term spread predicts four-quarter GDP growth with greater accuracy than survey consensus forecasts and that it has substantial predictive power for stock returns. Yields on bonds maturing beyond 6-8 quarters are shown to have no added value for forecasting either recessions, GDP growth, or stock returns.
A influência da empatia como competência socioafetiva na atuação de tutores a distância
Authors: Tenório André , Araújo Costa Maria de Fátima , Tenório Thaís
Published: March 2019

A contribuição da empatia para a atuação de tutores a distância em ambientes virtuais de aprendizagem foi investigada. Foram consideradas as percepções de doze tutores de cursos de graduação de uma universidade privada no estado do Rio de Janeiro. Metade dos pesquisados foi capaz de identificar o significado de empatia, apesar de pouco a utilizarem em sua prática. Para dez dos tutores, ter personalidade extrovertida seria imprescindível para cativar a empatia dos alunos. Entretanto, fatores como ser nativo digital ou ter o hábito de participar de redes sociais virtuais seriam irrelevantes para que os tutores conquistassem a empatia dos estudantes. De maneira geral, os tutores classificaram a empatia como a competência socioafetiva menos importante para a atuação a distância, estando atrás de cordialidade, honradez e aceita- ção. Não obstante, admitiram seu potencial de promover a cumplicidade e a confiança na relação tutor-aluno, aspectos tão necessários nessa modalidade educacional.
Fluência tecnológica na visão dos tutores e seus desafios
Authors: Freitas dos Santos Maria das Graças , Pirola Santos Mantilla Samira
Published: March 2019

Este trabalho apresenta uma proposta de estudo sobre a competência tecnológica dos tutores a distância, também denominada de fluência tecnológica, fundamentada em estudiosos da Educação a Distância no contexto atual. Visa identificar, analisar e compreender as competências essenciais dos tutores a distância, com foco na fluência tecnológica que engloba as fluências técnica, prática e emancipatória. Para isso, foi realizado um estudo de caso em uma instituição de ensino particular, onde foi aplicado um questionário on-line para 24 tutores de um curso de graduação a distância. De acordo com os resultados, os tutores respondentes possuem domínio tecnológico (fluência técnica, prática e emancipatória), entretanto, no que tange à fluência emancipatória, observou-se que eles não possuem autonomia na tomada de decisões e não mantêm outros meios de comunicação com os estudantes, além da plataforma e do e-mail. Em relação às sugestões e críticas, verificou-se que os tutores estão preocupados com a difusão do conhecimento sobre as novidades tecnológicas, na medida em que as tecnologias estão em constante transformação. Assim, faz-se necessária uma capacitação constante dos tutores on-line para que eles possam utilizar com autoridade essas novas tecnologias na prática da tutoria a distância.
Bench top CUT&Tag v1
Authors: S Kaya-Okur Hatice , Henikoff Steven
Published: March 2019

Here we describe a single-tube bench top protocol for Cleavage Under Targets and Tagmentation (CUT&Tag), an enzyme-tethering strategy that provides efficient high-resolution sequencing libraries for profiling diverse chromatin components. In CUT&Tag, a chromatin protein is bound in situ by a specific antibody, which then tethers a proteinA-Tn5 transposase fusion protein. Activation of the transposase efficiently generates fragment libraries with high resolution and exceptionally low background. All steps from live cells to sequencing-ready libraries can be performed in a single tube on the benchtop or a microwell in a high-throughput pipeline (see the Kaya-Okur high-throughput protocol), and the entire procedure can be performed in one day. We have demonstrated the utility of CUT&Tag by profiling histone modifications, RNA Polymerase II and transcription factors on low cell numbers and single cells.
Binary synthetic template oligonucleotide positive control for in-house diagnostic real-time RT-PCR v2
Authors: M Mackay Ian , A Northill Judy
Published: March 2019

This protocol details how to make and use a pair of synthetic template oligonucleotides (STOs) for use as real-time reverse transcription polymerase chain reaction (RT-rPCR) controls. The method can also be used for PCR controls. This binary positive control approach is easy to replicate once mastered, quick to produce, results in enough RNA stock for years of PCR runs, and provides several benefits over the use of a wild-type positive control such as the nucleic acids extracted from virus culture or from a known previously-positive clinical specimen. The method is an adaptation of a previsouly published approach [Ref 1] and has recently been described in some publications.[Ref 2] Our approach to a positive control requires that each PCR run includes two additional reactions. one controls for primer function (PRIMER control). This STO includes hybridisation sites for the specific target assay's primers bouding a generic probe hybridisation target site one controls for probe function (PROBE control). This STO includes a hybridisation site for the specific target assay's probe(s), bounded by a pair of generic primer hybridisation target sites REFERENCES. Smith G, Smith I, Harrower B, Warrilow D, Bletchly C. A simple method for preparing synthetic controls for conventional and real-time PCR for the identification of endemic and exotic disease agents. J Virol Methods. 2006 Aug;135(2):229-34. https://www.ncbi.nlm.nih.gov/pubmed/16677717 Hall-Mendelin S, Pyke AT, Moore PR, Mackay IM, McMahon JL, Ritchie SA, Taylor CT, Moore FA, van den Hurk AF. Assessment of Local Mosquito Species Incriminates Aedes aegypti as the Potential Vector of Zika Virus in Australia. PLoS Negl Trop Dis. 2016 Sep 19;10(9):e0004959. https://www.ncbi.nlm.nih.gov/pubmed/27643685 Transcription of RNA templates by T7 RNA polymerase. Nucl. Acids Res. (1998) 26 (15): 3550-3554. Arnaud-Barbe et al.
Loop and uLoop assembly v4
Authors: Pollak Bernardo
Published: March 2019

This protocol is used for performing Type IIS assembly by either BsaI or SapI-mediated restriction/ligation using Loop assembly with either Loop or uLoop plasmids. Loop assembly comprises8receiver plasmids in odd and even levels (4 per level), which containdirectional overhangs for higher level assembly. Odd and even level receiver plasmids are used in a recursive schemafor assembly initerative 'loops'. Any assembly (except for L0 part composition into a L1 transcriptional unit) requires the usage of 4 donorplasmids (each ina specific position) and one receiver plasmid. BsaI is used for assembly into odd levels using kanamycin selection, and SapI is used in even levels using spectynomycin selection.Loop odd receivers use theCommon Syntax standard for L0 part assembly into TUs (Patron,et al.2015 [10.1111/nph.13532]). Then, 4 L1 plasmids (positions 1-4) are assembled into aneven receiver plasmid to provide a L2 assembly (4 TUs). For higher level assemblies the same assembly structure is followed, 4 L2 plasmids (positions 1-4)with anodd receiver to yield a L3 assembly (16 TUs). TheLoop type IIS assembly protocol is based on: “Patron, NJ (2016) DNA Assembly for Plant Biology. Current Protocols in Plant Biology 1:1-13 [doi: 10.1002/cppb.20038]”, but with slight modifications for DNA concentrations: Thisprotocol uses a target amount of each donor DNA of 15 fmol and 7.5 fmol forreceiver plasmid DNA in a 10 µL reaction. In order to performaccurate dispensing, the plasmid DNA is diluted to their correspondingconcentration of 15 fmol/µL for donor parts and of 7.5 fmol/µL for the receiver plasmid, and then 1 µL of each plasmid is added to the DNA mix.Theplasmid part target concentration(in ng/uL) equals to eachdonor plasmid length / 100, and of the receiver plasmid length / 200. Volumes CAN be reduced by half, but expect more variability from aliquoting.