bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of feeding rice whole crop silage on growth rate, levels of vitamin A, β‐carotene, vitamin E and IGF‐1 in plasma and skeletal muscle protein degradation in Japanese black calves
Authors: Tsuruoka Katsuhiko , Kurahara Takami , Kanamaru Hidenobu , Takahashi Hideyuki , Gotoh Takafumi
Published: April 2019

This study evaluated the effects of rice whole crop silage (RWCS) on growth, plasma levels of vitamin A, β‐carotene, vitamin E and IGF‐1, and expression of genes involved in muscle protein degradation and synthesis in Japanese Black calves. Eleven calves were divided into RWCS (fed RWCS ad libitum and concentrate, n = 5) and control groups (fed hay ad libitum and concentrate, n = 6). Final body weight and dairy gain were significantly larger in the RWCS group compared with the control group. Plasma β‐carotene and vitamin E concentrations were significantly higher in the RWCS group compared with control group. Although plasma vitamin E concentration in the RWCS group significantly increased from 4 to 9 months of age, it did not increase in the control group. At 6 months of age in the RWCS group, ubiquitin B (p < 0.05) and calpain 1 (p = 0.097) mRNA expression were lower than control group, but they were not different between groups at 9 months of age. These results indicate that RWCS increases plasma β‐carotene level and promotes muscle growth because of a decrease in the rate of protein degradation, but the effect is lost with the increase in plasma vitamin E level.
Fast Bayesian Inference in Large Gaussian Graphical Models
Authors: Leday Gwenaël G. R. , Richardson Sylvia
Published: April 2019

Despite major methodological developments, Bayesian inference in Gaussian graphical models remains challenging in high dimension due to the tremendous size of the model space. This article proposes a method to infer the marginal and conditional independence structures between variables by multiple testing, which bypasses the exploration of the model space. Specifically, we introduce closed-form Bayes factors under the Gaussian conjugate model to evaluate the null hypotheses of marginal and conditional independence between variables. Their computation for all pairs of variables is shown to be extremely efficient, thereby allowing us to address large problems with thousands of nodes as required by modern applications. Moreover, we derive exact tail probabilities from the null distributions of the Bayes factors. These allow the use of any multiplicity correction procedure to control error rates for incorrect edge inclusion. We demonstrate the proposed approach on various simulated examples as well as on a large gene expression data set from The Cancer Genome Atlas.
Copula-Based Semiparametric Models for Spatiotemporal Data
Authors: Tang Yanlin , Wang Huixia J. , Sun Ying , Hering Amanda S.
Published: April 2019

The joint analysis of spatial and temporal processes poses computational challenges due to the data's high dimensionality. Furthermore, such data are commonly non-Gaussian. In this paper, we introduce a copula-based spatiotemporal model for analyzing spatiotemporal data and propose a semiparametric estimator. The proposed algorithm is computationally simple, since it models the marginal distribution and the spatiotemporal dependence separately. Instead of assuming a parametric distribution, the proposed method models the marginal distributions nonparametrically and thus offers more flexibility. The method also provides a convenient way to construct both point and interval predictions at new times and locations, based on the estimated conditional quantiles. Through a simulation study and an analysis of wind speeds observed along the border between Oregon and Washington, we show that our method produces more accurate point and interval predictions for skewed data than those based on normality assumptions.
Using a Surrogate Marker for Early Testing of a Treatment Effect
Authors: Parast Layla , Cai Tianxi , Tian Lu
Published: April 2019

The development of methods to identify, validate, and use surrogate markers to test for a treatment effect has been an area of intense research interest given the potential for valid surrogate markers to reduce the required costs and follow-up times of future studies. Several quantities and procedures have been proposed to assess the utility of a surrogate marker. However, few methods have been proposed to address how one might use the surrogate marker information to test for a treatment effect at an earlier time point, especially in settings where the primary outcome and the surrogate marker are subject to censoring. In this paper, we propose a novel test statistic to test for a treatment effect using surrogate marker information measured prior to the end of the study in a time-to-event outcome setting. We propose a robust nonparametric estimation procedure and propose inference procedures. In addition, we evaluate the power for the design of a future study based on surrogate marker information. We illustrate the proposed procedure and relative power of the proposed test compared to a test performed at the end of the study using simulation studies and an application to data from the Diabetes Prevention Program.
Integrative Analysis of Genetical Genomics Data Incorporating Network Structures
Authors: Gao Bin , Liu Xu , Li Hongzhe , Cui Yuehua
Published: April 2019

In a living organism, tens of thousands of genes are expressed and interact with each other to achieve necessary cellular functions. Gene regulatory networks contain information on regulatory mechanisms and the functions of gene expressions. Thus, incorporating network structures, discerned either through biological experiments or statistical estimations, could potentially increase the selection and estimation accuracy of genes associated with a phenotype of interest. Here, we considered a gene selection problem using gene expression data and the graphical structures found in gene networks. Because gene expression measurements are intermediate phenotypes between a trait and its associated genes, we adopted an instrumental variable regression approach. We treated genetic variants as instrumental variables to address the endogeneity issue. We proposed a two-step estimation procedure. In the first step, we applied the LASSO algorithm to estimate the effects of genetic variants on gene expression measurements. In the second step, the projected expression measurements obtained from the first step were treated as input variables. A graph-constrained regularization method was adopted to improve the efficiency of gene selection and estimation. We theoretically showed the selection consistency of the estimation method and derived the bound of the estimates. Simulation and real data analyses were conducted to demonstrate the effectiveness of our method and to compare it with its counterparts.
Detection of Differentially Expressed Genes in Discrete Single-Cell RNA Sequencing Data Using a Hurdle Model With Correlated Random Effects
Authors: Sekula Michael , Gaskins Jeremy , Datta Susmita
Published: April 2019

Single-cell RNA sequencing (scRNA-seq) technologies are revolutionary tools allowing researchers to examine gene expression at the level of a single cell. Traditionally, transcriptomic data have been analyzed from bulk samples, masking the heterogeneity now seen across individual cells. Even within the same cellular population, genes can be highly expressed in some cells but not expressed (or lowly expressed) in others. Therefore, the computational approaches used to analyze bulk RNA sequencing data are not appropriate for the analysis of scRNA-seq data. Here, we present a novel statistical model for high dimensional and zero-inflated scRNA-seq count data to identify differentially expressed (DE) genes across cell types. Correlated random effects are employed based on an initial clustering of cells to capture the cell-to-cell variability within treatment groups. Moreover, this model is flexible and can be easily adapted to an independent random effect structure if needed. We apply our proposed methodology to both simulated and real data and compare results to other popular methods designed for detecting DE genes. Due to the hurdle model's ability to detect differences in the proportion of cells expressed and the average expression level (among the expressed cells), our methods naturally identify some genes as DE that other methods do not, and we demonstrate with real data that these uniquely detected genes are associated with similar biological processes and functions.
Experience, represent, apply (ERA): A heuristic for digital engagement in the early years
Authors: Lowrie Tom , Larkin Kevin
Published: April 2019

This paper presents an heuristic that underpinned the development of a range of early years applications (apps) as part of the Early Learning Science, Technology, Engineering and Mathematics (STEM) Australia (ELSA) project (2016–19). The heuristic was developed to address a range of challenges that accompany the use of digital technologies in the year before formal schooling. These include the role of digital technologies in play‐based learning environments, screen time and the importance of agency when young children are using digital technologies. In an increasingly digital world, the issue of screen time looms large as a particularly contested aspect of technology use by young children. The ELSA project responded to this challenge by developing a pedagogical framework that embedded digital technologies into context‐rich, play‐based STEM learning. The Experience, Represent, Apply (ERA) heuristic discussed in this paper is a component of the project's overall pedagogical framework and provides early years educators with the opportunity, and the know‐how, to integrate digital technologies into STEM activities through intentional teaching and play‐based engagement. It was evident from educator feedback at the four days of workshops we delivered, and in other comments throughout the year long trial, that the educators were able to embrace the cyclic nature of the ERA heuristic and ensure that the time spent on the tablet (Represent) was connected to contextualised learning opportunities (Experience and Apply). Importantly, the tablets provided affordances for the children to utilise User Generated Content (UGC) to support active engagement when using the tablets.
Biological responses of human bone mesenchymal stem cells to Ti and TiZr implant materials
Authors: Yin Lihua , Chang Yaoren , You Yuanhe , Liu Chun , Li Jie , Lai Hong‐Chang
Published: April 2019

Background

Titanium‐zirconium alloy (TiZr1317) is a new material used for biological implants. There are several studies on the effects of TiZr implants on the biological characteristics of human bone mesenchymal stem cells (hBMSCs).

Purpose

The purpose of this study was to investigate the biological responses of hBMSCs to implant holes affected by the physicochemical properties of oral implants (TiSLA, TiSLActive, TiZrSLA, and TiZrSLActive).

Materials and Methods

Grade 4 Ti and TiZr (13‐17% Zr) substrates were modified by sand‐blasted large‐grit acid‐etched (SLA) or hydrophilic sand‐blasted large‐grit acid‐etched (SLActive), resulting in four types of surface with complex microstructures corresponding to the commercially‐available implants SLA, RoxolidSLA, SLActive, and RoxolidSLActive (Institute Straumann AG, Basel, Switzerland). Physicochemical properties were detected and the biological responses of hBMSCs were observed.

Results

Surface morphology characterization by scanning electron microscopy and atomic force microscopy revealed differences between the four groups. SLActive had higher surface energy/wettability than SLA, indicating that increased surface energy/wettability can promote the absorption of osteogenic proteins and enhance osseointegration. hBMSCs seeded on SLActive substrates exhibited better performance in terms of cell attachment, proliferation and osteoblastic differentiation than cells seeded on SLA.

Conclusion

Because of their more suitable physicochemical properties, TiSLActive and TiZrSLActive materials demonstrated more pronounced effects on the biological responses of hBMSCs compared with TiSLA and TiZrSLA.
Phase transformation and fracture load of stock and CAD/CAM‐customized zirconia abutments after 1 year of clinical function
Authors: Schepke Ulf , Gresnigt Marco M. M. , Browne Wesley R. , Abdolahzadeh Shaghayegh , Nijkamp Joey , Cune Marco S.
Published: April 2019

Objectives

Functional loading and low‐temperature degradation may give rise to impaired clinical long‐term service of zirconia implant abutments. The aim of this study was to compare the fracture strength (primary outcome measure) and the volume percentage of monoclinic surface zirconia (m‐ZrO2) of stock and CAD/CAM‐customized zirconia implant abutments that functioned clinically for 1 year with geometrically identical pristine controls in an ex vivo experiment.

Material and methods

Twenty‐three stock (ZirDesign™) and 23 CAD/CAM‐customized (Atlantis™) zirconia implant abutments were retrieved after 1 year of clinical service. They were compared with pristine copies with respect to the volume fraction of the monoclinic phase using Raman spectroscopy and their fracture load by means of a single load‐to‐fracture test. Failure analysis was performed using optical and SEM microscopy. After verification of normal distribution, paired t tests were used for comparison of fracture loads between pristine and clinically aged specimen. All statistical tests employed a level of significance of α = 0.05.

Results

The fracture loads of the stock zirconia abutments were significantly (p < 0.05) reduced to 78.8% (SD 29.5%) after one year of clinical function. For the CAD/CAM abutments, no reduction in fracture load was found. No m‐ZrO2 volume percentages beyond the detection threshold of 5% were observed in any of the samples.

Conclusions

After 1 year of clinical service, no difference in fracture strength of the CAD/CAM‐customized zirconia implant abutments could be demonstrated, whereas the stock zirconia abutments decreased considerably in fracture strength. No substantial tetragonal‐to‐monoclinic transformation was observed.
Voluntary, permanent land protection reduces forest loss and development in a rural‐urban landscape
Authors: Nolte Christoph , Meyer Spencer R. , Sims Katharine R. E. , Thompson Jonathan R.
Published: April 2019

Voluntary, permanent land protection is a key conservation process in many countries. Concerns with the effectiveness of such decentralized processes exist due to the potential for (1) selection bias, that is, the protection of parcels whose land cover would have been conserved in the absence of protection, and (2) local spillover effects, that is, protection increasing the likelihood that adjacent parcels lose land cover due to additional conversion. We examine the validity of both concerns using a quasi‐experimental approach and a dataset of 220,187 parcels and 26 years of protection and land‐cover change in Massachusetts. We find that land acquisitions and conservation restrictions implemented by state, local, and nongovernmental actors reduced forest loss and conversion to developed uses without increasing either type of land‐cover change on adjacent parcels. Our results suggest that voluntary, permanent land protection can make significant contributions in protecting land cover in landscapes dominated by private ownership.
Oral intramuscular hemangioma: Report of three cases
Authors: Lescura Carlos M. , de Andrade Bruno A. B. , Bezerra Kelly T. , Agostini Michelle , Ankha Milagros V. A. , de Castro Felix , Carvalho Yasmin R. , Romañach Mário J. , Anbinder Ana Lia
Published: April 2019

Intramuscular hemangioma (IMH) represents less than 1% of all hemangiomas. In the head and neck region, it occurs mostly in the masseter, temporalis and sternocleidomastoid muscles. Despite its infiltrative growth pattern and several worrisome histological features, such as increased mitotic activity, plumpness of the nuclei, intraluminal papillary projections or perineural infiltration, the lesion is benign, and complete surgical excision is the preferred treatment for such oral lesions. Herein, we report three rare cases of IMH in the tongue and lip, discuss the clinical and histological aspects, and review the literature regarding this lesion.
Langerhans cell histiocytosis and multiple reticulohistiocytomas in a patient with TAR syndrome: An association not previously described
Authors: Hipólito Lucía N. , Mendoza‐Cembranos María D. , Villaescusa María T. , Jo‐Velasco Margarita , Requena Luis , Alegría‐Landa Victoria
Published: April 2019

We describe a patient with thrombocytopenia‐absent radius (TAR) syndrome, multisystemic Langerhans cell histiocytosis and multiple reticulohistiocytomas. A mutational study by massive sequencing identified the Val600Glu (V600E) BRAF mutation in the Langerhans cell histiocytosis lesions, but no molecular alterations were found in the reticulohistiocytoma lesions. The concomitant presence in the same patient of more than one type of histiocytosis from two different groups recognized in the most recent Histiocyte Society classification is an extremely rare event. Our case is the first reported case of multisystemic Langerhans cell histiocytosis and multiple reticulohistiocytomas in a patient with TAR syndrome.
Water contaminant levels interact with parenting environment to predict development of depressive symptoms in adolescents
Authors: Manczak Erika M. , Miller Jonas G. , Gotlib Ian H.
Published: April 2019

Contaminants in drinking water, such as lead, nitrate, and arsenic, have been linked to negative physical health outcomes. We know less, however, about whether such pollutants also predict mental health problems and, if so, the conditions under which such effects are strongest. In this longitudinal study, we examined whether drinking water contaminants interact with negative family environments (parental psychological control) to predict changes in depressive symptoms in 110 adolescents—a developmental period when symptoms often first emerge. We found that for adolescents in psychologically controlling families, levels of drinking water contaminants prospectively predicted depressive symptoms 2 years later; this effect was not present in adolescents in non‐controlling families. Importantly, these associations were not accounted for by family‐ or community‐level socioeconomic resources, demographic features, or by the adolescents’ stress exposure. These findings highlight the interplay of physical and psychological environments in influencing depressive symptoms in adolescents. A video abstract of this article can be viewed at https://youtu.be/thBV-DwnGcY
DFID governance programming in Nigeria: What difference has thinking and working politically made in practice?
Authors: Williams Gareth , Owen Olly , Duncan Alex , Kingsmill William , Paterson Anna
Published: April 2019

The UK Department for International Development's country office in Nigeria (DFID Nigeria) has gradually adopted a thinking and working politically (TWP) approach in its governance programming. The initial focus on strengthening analysis has progressively been linked to discussion about the country and programme strategy, as well as programme‐management practices. Important lessons can be learned from this experience on how the TWP approach can be applied in practice. The article addresses three research questions: (1) To what extent have DFID Nigeria and its governance programmes adopted a TWP approach? (2) How has the TWP approach influenced the design and delivery of programming? (3) Has the application of the TWP approach enhanced the results of the DFID governance programming?

Using project documentation and wider theoretical literature, but mainly relying on extensive participant observation within DFID Nigeria programmes, the article uses a historical perspective to outline how the TWP approach has been applied in Nigeria over 15 years of programme design, delivery, lesson‐learning and refinement. Published evaluation reports are used to provide evidence of programme results. DFID Nigeria and its programmes have progressively adopted TWP principles. This has led to clear changes in country strategy and programme design, as well as programme‐management practices. There is some evidence that the adoption of these principles has enhanced the results of DFID Nigeria programmes. By focusing on experimentation and “small bets,” TWP has proven relatively successful in generating and supporting ‘islands of effectiveness,’ but has had more limited impact in terms of generating more systemic, transformational change. The results obtained in Nigeria using the TWP approach have depended not only on Nigeria's political economy but also on the political economy of the development agency and donor country. DFID Nigeria's ability to engage in critical self‐reflection and to create an authorizing environment for risk‐taking have been vital to create enabling conditions for the TWP approach. However, other aspects of DFID and the UK's political economy are creating constraints that limit the prospects to go further and to go deeper in adopting the principles of TWP.
A comparative analysis of the safety profile of direct oral anticoagulants using the FDA adverse event reporting system
Authors: DeLoughery Emma P. , Shatzel Joseph J.
Published: April 2019

Introduction

Direct oral anticoagulants (DOACs) are being increasingly used. However, unlike warfarin, less is known regarding their long‐term side effects. To better evaluate the rates of DOAC‐related adverse events (AEs) on a population level, we examined AEs reported to the FDA for three commonly used DOACs and warfarin.

Methods

We evaluated the FDA Adverse Event Reporting System (FAERS) database, which compiles reported drug‐related AEs from 1969 onwards. The safety profiles of the included drugs were assessed by comparing AEs per outpatient prescription and with proportional reporting ratios (PRR).

Results

Rivaroxaban had the highest proportion of reported AEs. Most notably the rate for breakthrough venous thromboembolism (VTE) was higher than other DOACs. Dabigatran had the highest reported rates of ischemic stroke. When the DOAC data were analyzed using PRR, reported rates of VTE were again higher with rivaroxaban while dabigatran again showed slightly higher than expected rates of ischemic stroke. Apixaban did not show higher than expected rates in any category.

Conclusion

Our analysis found rates of reported breakthrough VTE were significantly higher with rivaroxaban, while apixaban had no higher than expected rates of any studied AEs.
N‐Methyl‐d‐aspartate receptor open‐channel blockers memantine and magnesium modulate nociceptive trigeminovascular neurotransmission in rats
Authors: Hoffmann Jan , Storer Robin James , Park Jeong‐Wook , Goadsby Peter J.
Published: April 2019

Experimental and clinical studies suggest that the low‐affinity N‐methyl‐d‐aspartate (NMDA) receptor open‐channel blockers Mg2+ and memantine are effective in reducing trigeminal nociceptive activation. The aim of this study was to investigate the apparent effectiveness of these channel blockers using a model of trigeminal activation in vivo. Rats were anaesthetized before electrically stimulating the dura mater adjacent the middle meningeal artery. Neurons responding to stimulation were recorded extracellularly using electrophysiological methods. l‐Glutamate or NMDA, and Mg2+, memantine, or sodium controls were applied locally using microiontophoresis. Microiontophoretic application of Mg2+ or memantine into the trigeminocervical complex inhibited mechanically and electrically stimulated craniovascular afferents,  and l‐glutamate or NMDA‐evoked neuronal activity at the second‐order trigeminal synapse of craniovascular afferents. By contrast, intravenous administration of MgSO4 (100 mg/kg) or memantine (10 mg/kg) did not significantly affect electrically stimulated afferent‐evoked activity within the trigeminocervical complex. The Mg2+ and memantine concentrations achieved after systemic administration may not effectively inhibit activation of the trigeminocervical complex, perhaps providing an explanation for the relatively poor efficacy of these NMDA receptor open‐channel blockers for headache treatment in clinical studies. Nevertheless, the present results suggest blocking of NMDA‐receptor open channels inhibits nociceptive activation of the trigeminocervical complex. Further exploration of such channel blockers as a therapeutic strategy for primary head pain is warranted.
Reproducibility of interictal spike propagation in children with refractory epilepsy
Authors: Tomlinson Samuel B. , Wong Jeremy N. , Conrad Erin C. , Kennedy Benjamin C. , Marsh Eric D.
Published: April 2019

Objective

Interictal spikes are a characteristic feature of invasive electroencephalography (EEG) recordings in children with refractory epilepsy. Spikes frequently co‐occur across multiple brain regions with discernable latencies, suggesting that spikes can propagate through distributed neural networks. The purpose of this study was to examine the long‐term reproducibility of spike propagation patterns over hours to days of interictal recording.

Methods

Twelve children (mean age 13.1 years) were retrospectively studied. A mean ± standard deviation (SD) of 47.2 ± 40.1 hours of interictal EEG recordings were examined per patient (range 17.5‐166.5 hours). Interictal recordings were divided into 30‐minute segments. Networks were extracted based on the frequency of spike coactivation between pairs of electrodes. For each 30‐minute segment, electrodes were assigned a “Degree Preference (DP)” based on the tendency to appear upstream or downstream within propagation sequences. The consistency of DPs across segments (“DP‐Stability”) was quantified using the Spearman rank correlation.

Results

Regions exhibited highly stable preferences to appear upstream, intermediate, or downstream in spike propagation sequences. Across networks, the mean ± SD DP‐Stability was 0.88 ± 0.07, indicating that propagation patterns observed in 30‐minute segments were representative of the patterns observed in the full interictal window. At the group level, regions involved in seizure generation appeared more upstream in spike propagation sequences.

Significance

Interictal spike propagation is a highly reproducible output of epileptic networks. These findings shed new light on the spatiotemporal dynamics that may constrain the network mechanisms of refractory epilepsy.
Sudden change in long‐term ocean climate fluctuations corresponds with ecosystem alterations and reduced recruitment in Norwegian spring‐spawning herring (Clupea harengus, Clupeidae)
Authors: Toresen Reidar , Skjoldal Hein Rune , Vikebø Frode , Martinussen Monica Bente
Published: April 2019

Fish stocks vary in abundance. The causes behind the fluctuations may be difficult to determine, especially ones caused by natural fluctuations, but long‐term data series may provide indications of the mechanisms. Assessments show that the recruitment to the Norwegian spring‐spawning herring (Clupea harengus, Clupeidae) has remained low since 2004, a year which produced the last really rich year‐class. Long time‐series of estimated recruitment and mean winter temperature in the ocean showed a significant positive correlation for the period 1921–2004. Here, we show that this positive correlation did not continue from 2005 onwards as the winter temperature increased to high levels while herring recruitment decreased and has remained low. The density of zooplankton in the drift route of the herring larvae dropped significantly after 2004, and their centre of gravity shifted northwards. There may currently be heavy predation on the larvae by Atlanic mackerel (Scomber scombrus, Scombridae), and top‐down regulation is suggested to hamper successful recruitment. Our analysis indicates that the presence of food and overlap with high food concentrations are likely important regulators of survival in herring larvae. The findings may be important for future management and planning of fisheries of this stock because recruitment failure may continue if temperature remains high and food abundance remains low.
Asymmetric news responses of high‐frequency and non‐high‐frequency traders
Authors: Zhang S. Sarah
Published: April 2019

Using NASDAQ trade and Reuters news data, I show that the response of aggressive non‐high‐frequency traders (nHFTs) to news is stronger than that of aggressive high‐frequency traders (HFTs). Classifying news into quantitative (“hard”) and less quantitative (“softer”) news, the trading response of aggressive nHFTs to softer news exceeds HFTs’ response. Positive news elicits greater return and nHFT responses than negative news during the 2008 financial crisis period. As this phenomenon persists even after excluding the 2008 short‐sale ban, the results support the hypothesis of nHFTs exhibiting stronger asymmetric responses during crisis periods.
The molecular biogeography of the Indo‐Pacific: Testing hypotheses with multispecies genetic patterns
Authors: Crandall Eric D. , Riginos Cynthia , Bird Chris E. , Liggins Libby , Treml Eric , Beger Maria , Barber Paul H. , Connolly Sean R. , Cowman Peter F. , DiBattista Joseph D. , Eble Jeff A. , Magnuson Sharon F. , Horne John B. , Kochzius Marc , Lessios Harilaos A. , Liu Shang Yin Vanson , Ludt William B. , Madduppa Hawis , Pandolfi John M. , Toonen Robert J. ,   Contributing Members of the Diversity of the Indo‐Pacific Network, Gaither Michelle R.
Published: April 2019

Aim

To test hypothesized biogeographic partitions of the tropical Indo‐Pacific Ocean with phylogeographic data from 56 taxa, and to evaluate the strength and nature of barriers emerging from this test.

Location

The Indo‐Pacific Ocean.

Time period

Pliocene through the Holocene.

Major taxa studied

Fifty‐six marine species.

Methods

We tested eight biogeographic hypotheses for partitioning of the Indo‐Pacific using a novel modification to analysis of molecular variance. Putative barriers to gene flow emerging from this analysis were evaluated for pairwise ΦST, and these ΦST distributions were compared to distributions from randomized datasets and simple coalescent simulations of vicariance arising from the Last Glacial Maximum. We then weighed the relative contribution of distance versus environmental or geographic barriers to pairwise ΦST with a distance‐based redundancy analysis (dbRDA).

Results

We observed a diversity of outcomes, although the majority of species fit a few broad biogeographic regions. Repeated coalescent simulation of a simple vicariance model yielded a wide distribution of pairwise ΦST that was very similar to empirical distributions observed across five putative barriers to gene flow. Three of these barriers had median ΦST that were significantly larger than random expectation. Only 21 of 52 species analysed with dbRDA rejected the null model. Among these, 15 had overwater distance as a significant predictor of pairwise ΦST, while 11 were significant for geographic or environmental barriers other than distance.

Main conclusions

Although there is support for three previously described barriers, phylogeographic discordance in the Indo‐Pacific Ocean indicates incongruity between processes shaping the distributions of diversity at the species and population levels. Among the many possible causes of this incongruity, genetic drift provides the most compelling explanation: given massive effective population sizes of Indo‐Pacific species, even hard vicariance for tens of thousands of years can yield ΦST values that range from 0 to nearly 0.5.
PGT: Visualizing temporal and spatial biogeographic patterns
Authors: Xia Xuhua
Published: April 2019

Aim

A geophylogeny, generated by mapping a phylogeny onto geographic regions, graphically summarizes large‐scale genetic variation over space and time, and is consequently crucial for conceptual understanding and visualization of global biogeographic patterns. The rapidly expanding DNA barcoding data with geographic coordinates associated with each specimen have dramatically increased the number of global phylogeographic studies that would benefit from software generating geophylogenies. A number of software programs have been developed, some with advanced features, but they either require additional software or are lacking in quality, especially in geographic resolution.

Innovation

PGT (Phylogeographic Tree), freely available at http://dambe.bio.uottawa.ca/PGT/PGT.aspx, combines the highest map quality and user‐friendliness. It accesses Microsoft Bing Maps and Google Maps seamlessly and generates geophylogenies on high‐resolution regular or terrain maps. Only a few mouse clicks are needed from PGT installation to the generation of high‐resolution geophylogenies, making PGT perfect for both teaching and research in global ecology and biogeography. The input tree can be in NEXUS or Newick format, and the geographic data with latitude and longitude values can be in tab‐delimited or comma‐delimited format such as those exported from spreadsheet programs. A Quick‐Start guide is included in the built‐in help system.

Main conclusions

PGT is simpler, more elegant, and of much higher quality than alternatives for plotting phylogenetic trees over geographic regions for visualizing distribution of biodiversity over space and time.
Retirement migration and transnational grandparental support: a Spanish case study
Authors: REPETTI MARION , CALASANTI TONI
Published: April 2019

People who migrate in retirement often do so to join younger generations who have already migrated, and to help with grandchildren. But what about those retirees who migrate away from their families? Do they still provide grandparental support? To address this question, we examine retirement migrants who reside permanently in their new country, Spain. We find that they are aware of grandparental support expectations, and that their migration decision sometimes creates conflict with their offspring. At the same time, these retirement migrants reshape the meaning of grandparental support. Care considerations influence their destination and housing choices, and they continue to provide care. They feel that their familial relationships are now of a higher quality, despite the distance. At the same time, gender still emerges as a key dimension of grandparental support. The grandparenting of these retirement migrants challenges facile depictions of their motivations and of the equation of quantity and quality of contacts.
Role of cyclin‐dependent kinases (CDKs) in hepatocellular carcinoma: Therapeutic potential of targeting the CDK signaling pathway
Authors: Shen Shen , Dean Dylan C. , Yu Zujiang , Duan Zhenfeng
Published: April 2019

Liver cancer is the fourth leading cause of cancer related mortality in the world, with hepatocellular carcinoma (HCC) representing the most common primary subtype. Two‐thirds of HCC patients have advanced disease when diagnosed, and for these patients, treatment strategies remain limited. In addition, there is a high incidence of tumor recurrence after surgical resection with the current treatment regimens. The development of novel and more effective agents is required. Cyclin‐dependent kinases (CDKs) constitute a family of 21 different protein kinases involved in regulating cell proliferation, apoptosis, and drug resistance, and are evaluated in preclinical and clinical trials as chemotherapeutics. To summarize and discuss the therapeutic potential of targeting CDKs in HCC, recent published articles identified from PubMed were comprehensively reviewed. The key words included hepatocellular carcinoma, cyclin‐dependent kinases, and CDK inhibitors. This review focuses on the emerging evidence from studies describing the genetic and functional aspects of CDKs in HCC. We also present an overview of CDK inhibitors that have shown efficacy in laboratory studies of HCC. Although many of the studies assessing CDK‐targeting therapies in HCC are at the preclinical stage, there is significant evidence that CDK inhibitors used alone or in combination with established chemotherapy drugs could have significant applications in HCC.
Parenteral drug use as the main barrier to hepatitis C treatment uptake in HIV‐infected patients
Authors: Rivero‐Juarez A , Tellez F , Castaño‐Carracedo M , Merino D , Espinosa N , Santos J , Macias J , Paniagua‐García M , Zapata‐Lopez A , Collado A , Gómez‐Vidal MA , Perez‐Stachowski J , Muñoz‐Medina L , Fernandez‐Fuertes E , Rivero A ,   the Grupo de estudio de Hepatitis virales (HEPAVIR) of the Sociedad Andaluza de Enfermedades Infecciosas (SAEI)
Published: April 2019

Objectives

Our objective was to identify patient factors associated with being untreated for hepatitis C virus (HCV) infection in HIV‐coinfected patients.

Methods

A prospective longitudinal study was carried out. HIV‐infected patients with active chronic HCV infection included in the HERACLES cohort (NCT02511496) constituted the study population. The main study outcome was receipt of HCV direct‐acting antiviral (DAA) treatment from 1 May 2015 to 1 May 2017. The population was divided into patients who were receiving HCV treatment during follow‐up and those who were not.

Results

Of the 15 556 HIV‐infected patients in care, 3075 (19.7%) presented with chronic HCV infection and constituted the study population. At the end of the follow‐up, 1957 patients initiated HCV therapy (63.6%). Age < 50 years, absence of or minimal liver fibrosis, being treatment‐naïve, HCV genotype 3 infection, being in the category of people who inject drugs using opioid substitutive therapy (OST‐PWID), and being in the category of recent PWID were identified as significant independent risk factors associated with low odds of DAA implementation. When a multivariate analysis was performed including only the PWID population, both OST‐PWID [odds ratio (OR) 0.552; 95% confidence interval (CI) 0.409–0.746) and recent PWID (OR 0.019; 95% CI 0.004–0.087) were identified as independent factors associated with low odds of treatment implementation.

Conclusions

We identified factors, which did not include prioritization of a DAA uptake strategy, that limited access to HCV therapy. The low treatment uptake in several populations seriously jeopardizes the elimination of HCV infection in the coming years.
A bibliometric study of the top 100 most‐cited randomized controlled trials, systematic reviews and meta‐analyses published in endodontic journals
Authors: Ahmad P. , Dummer P. M. H. , Chaudhry A. , Rashid U. , Saif S. , Asif J. A.
Published: April 2019

Aim

To identify and analyse the main features of the top 100 most‐cited randomized controlled trials, systematic reviews and meta‐analyses published in endodontic journals from 1961 to 2018.

Methodology

The Clarivate Analytics’ Web of Science ‘All Databases’ was used to search and analyse the 100 most frequently cited randomized controlled trials, systematic reviews and meta‐analyses having ‘randomized’, ‘randomised’, ‘randomized controlled’, ‘randomised controlled’, ‘randomized controlled trial’, ‘randomized controlled trials’, ‘clinical trial’, ‘systematic’, ‘systematic review’, ‘meta‐analysis’, and ‘meta‐analyses’ in the title section. The ‘International Endodontic Journal’, ‘Journal of Endodontics’, ‘Oral Surgery Oral Medicine Oral Pathology Oral Radiology and Endodontology’, ‘Australian Endodontic Journal’, ‘Endodontics & Dental Traumatology’, ‘Endo‐Endodontic Practice Today’ and ‘European Endodontic Journal’ were included in the publication name section. After ranking the articles in a descending order based on their citation counts, each article was cross‐matched with the citation counts in Elsevier's Scopus and Google Scholar. The articles were analysed, and information on citation counts, citation density, year of publication, contributing authors, institutions and countries, journal of publication, study design, topic of the article and keywords was extracted.

Results

The citation counts of the 100 most‐cited articles varied from 235 to 20 (Web of Science), 276 to 17 (Scopus) and 696 to 1 (Google Scholar). The year in which the top 100 articles were published was 2010 (n = 13). Among 373 authors, the greatest number of articles was associated with three individuals namely Reader A (n = 5), Beck M (n = 5) and Kvist T (n = 5). Most of the articles originated from the United States (n = 24) with the greatest contribution from Ohio State University (USA) (n = 5). Randomized controlled trials were the most frequent study design (n = 45) followed by systematic reviews (n = 30) with outcome studies of root canal treatment being the major topic (n = 35). The Journal of Endodontics published the largest number of included articles (n = 70) followed by the International Endodontic Journal (n = 27). Among 259 unique keywords, meta‐analysis (n = 23) and systematic review (n = 23) were the most frequently used.

Conclusion

This study has revealed that year of publication had no obvious impact on citation count. The bibliometric analysis highlighted the quantity and quality of research, and the evolution of scientific advancements made in the field of Endodontology over time. Articles before 1996, that is prior to the CONSORT statement that encouraged authors to include specific terms in the title and keywords, may not have been included in this electronic search.
Office‐based dermatologic diagnostic procedure utilization in the United States Medicare population from 2000‐2016
Authors: Guzman Anthony K. , Kaffenberger Benjamin H.
Published: April 2019

Background

Potassium hydroxide preparations (KOH) and tissue examinations for ova and parasites (O&P) are cost‐effective office‐based tests. No studies have quantified their utilization and economic impact.

Methods

The objective is to determine the billing patterns and costs of office‐based diagnostic procedures in the Medicare population. We conducted a cross sectional study using the Part B National Summary Data File (2000–2016) and the Physician and Other Supplier Public Use File (2012–2015) released by the Centers for Medicare & Medicaid Services.

Results

In 2016, the total number of claims among all providers was 28,432 (KOH) and 52,182 (O&P), representing a decrease since 2000 (KOH, −41.8%; O&P, −43.4%). The total claims for in‐office procedures by dermatologists per 10,000 beneficiaries decreased between 2012 and 2015 (KOH, −18.8%; O&P, −26.6%). Fewer dermatologists submitted claims for the tests (KOH, −11.3%; O&P, −16.6%). The total single (SB) and multiple (MB) biopsy claims by dermatologists per 10,000 beneficiaries decreased between 2012 and 2015 (SB, −1.8%; MB, −2.7%). The 2016 aggregate payments (% change since 2000) for KOH and O&P were $163,127.75 (−60.4%) and $299,074.18 (−61.6%), respectively; for SB and MB, they were $240,047,487.98 (+142.3%) and $38,214,117.22 (+79.2%), respectively.

Conclusion

Fewer dermatologists submit claims for KOH and O&P each year. Future studies should evaluate whether this is due to a loss of cost‐efficacy, and secondly, if it is related to decreased reimbursement, burdensome in‐office laboratory regulations, or changing provider preferences.
Melanonychia striata: clarifying behind the Black Curtain. A review on clinical evaluation and management of the 21st century
Authors: Leung Alexander K. C. , Lam Joseph M. , Leong Kin Fon , Sergi Consolato M.
Published: April 2019

Melanonychia striata is characterized by a tan, brown, or black longitudinal streak within the nail plate that runs from the proximal nail fold to the distal part of the nail plate. Melanonychia striata is due to increased activity of melanocytes or melanocytic hyperplasia in the nail matrix with subsequently increased melanin deposition in the nail plate. The most common cause of melanonychia striata associated with melanocytic activation is ethnic melanonychia which occurs in dark‐skinned individuals. Other causes of melanonychia striata related to melanocytic activation include pregnancy, chronic local trauma, infections, medications, dermatological disorders, endocrine disorders, alkaptonuria, hemochromatosis, porphyria, graft‐vs‐host disease, Peutz‐Jeghers syndrome, and Laugier‐Hunziker syndrome. Causes of melanonychia striata associated with melanocytic hyperplasia include nail matrix melanocytic nevus, nail lentigo, and nail apparatus/subungual in situ and invasive melanoma. In most cases, melanonychia striata is a benign condition, especially in children. Consequently, most investigators advocate a wait‐and‐see approach. Nail apparatus/subungual melanoma should be suspected if there is an abrupt onset after middle age, personal or family history of melanoma, rapid growth, darkening of a melanonychia band, pigment variegation, blurry lateral borders, irregular elevation of the surface, a bandwidth >3 mm, proximal widening, associated nail plate dystrophy, single rather than multiple digit involvement, and periungual spread of pigmentation onto the adjacent cuticle and/or proximal and/or lateral nail folds (Hutchinson sign). Prolonged follow‐up is mandatory for early detection of possible malignant changes.
Supplemental home care and topping‐up: A shift from service universalism towards a new and privatised public service model?
Authors: Hjelmar Ulf , Rostgaard Tine
Published: April 2019

How does a public service model based on service universalism react to the introduction of market principles of topping up? In a recent so‐called Free Municipality Scheme (an experimental scheme that allowed for greater operational autonomy locally in an effort to reduce state bureaucracy), a number of Danish municipalities were for the first time ever allowed to compete with for‐profit providers of home care in selling supplemental home care services paid entirely by the user. The take‐home message from this experience is that the introduction of supplemental home care entails challenges and eventually wider implications for the public service model, on an economic, organisational and cultural level. Supplemental services represent a new and potentially powerful combination of market and state logics that eventually redirects away from the universalist welfare state and towards a new and increasingly privatised public service model – a model where the service level is determined by the user's capacity to purchase and pay for services. The introduction of such services therefore implies a change of the potential of the Nordic welfare state to ensure equal access regardless of class and income.
Chimeric antigen receptor T cell persistence and memory cell formation
Authors: McLellan Alexander D , Ali Hosseini Rad Seyed M
Published: April 2019

It is now becoming clear that less differentiated naive and memory T cells are superior to effector T cells in the transfer of immunity for adoptive cell therapy. This review will outline the challenges faced by chimeric antigen receptor (CAR) T cell therapy in the generation of persistence and memory for CAR T cells, and summarize recent strategies to improve CAR T cell persistence, with a focus on memory cell formation. The relevance of enhancing persistence in more differentiated effector T cells is also covered, because genetic and pharmacological interventions may prolong effector T cell activity and lifespan, thereby improving anti‐cancer activity. In particular, it may be possible to enforce epigenetic changes in differentiated T cells to enhance memory CAR T cell formation. Optimizing the generation of self‐renewing T cell populations (e.g. memory cells), while maintaining differentiated effector T cells through epigenome modification, will help overcome barriers to T cell expansion and survival, thereby improving clinical outcomes in CAR T cell therapy.