bluuebunny/crossref_metadata_2025 huggingface dataset:
Desert grassland responses to climate and soil moisture suggest divergent vulnerabilities across the southwestern United States
Authors: Gremer Jennifer R. , Bradford John B. , Munson Seth M. , Duniway Michael C.
Published: July 2015

Climate change predictions include warming and drying trends, which are expected to be particularly pronounced in the southwestern United States. In this region, grassland dynamics are tightly linked to available moisture, yet it has proven difficult to resolve what aspects of climate drive vegetation change. In part, this is because it is unclear how heterogeneity in soils affects plant responses to climate. Here, we combine climate and soil properties with a mechanistic soil water model to explain temporal fluctuations in perennial grass cover, quantify where and the degree to which incorporating soil water dynamics enhances our ability to understand temporal patterns, and explore the potential consequences of climate change by assessing future trajectories of important climate and soil water variables. Our analyses focused on long‐term (20–56 years) perennial grass dynamics across the Colorado Plateau, Sonoran, and Chihuahuan Desert regions. Our results suggest that climate variability has negative effects on grass cover, and that precipitation subsidies that extend growing seasons are beneficial. Soil water metrics, including the number of dry days and availability of water from deeper (>30 cm) soil layers, explained additional grass cover variability. While individual climate variables were ranked as more important in explaining grass cover, collectively soil water accounted for 40–60% of the total explained variance. Soil water conditions were more useful for understanding the responses of C3 than C4 grass species. Projections of water balance variables under climate change indicate that conditions that currently support perennial grasses will be less common in the future, and these altered conditions will be more pronounced in the Chihuahuan Desert and Colorado Plateau. We conclude that incorporating multiple aspects of climate and accounting for soil variability can improve our ability to understand patterns, identify areas of vulnerability, and predict the future of desert grasslands.
Long‐term impacts of manure amendments on carbon and greenhouse gas dynamics of rangelands
Authors: Owen Justine J. , Parton William J. , Silver Whendee L.
Published: July 2015

Livestock manure is applied to rangelands as an organic fertilizer to stimulate forage production, but the long‐term impacts of this practice on soil carbon (C) and greenhouse gas (GHG) dynamics are poorly known. We collected soil samples from manured and nonmanured fields on commercial dairies and found that manure amendments increased soil C stocks by 19.0 ± 7.3 Mg C ha−1 and N stocks by 1.94 ± 0.63 Mg N ha−1 compared to nonmanured fields (0–20 cm depth). Long‐term historical (1700–present) and future (present–2100) impacts of management on soil C and N dynamics, net primary productivity (NPP), and GHG emissions were modeled with DayCent. Modeled total soil C and N stocks increased with the onset of dairying. Nitrous oxide (N2O) emissions also increased by ~2 kg N2O‐N ha−1 yr−1. These emissions were proportional to total N additions and offset 75–100% of soil C sequestration. All fields were small net methane (CH4) sinks, averaging −4.7 ± 1.2 kg CH4‐C ha−1 yr−1. Overall, manured fields were net GHG sinks between 1954 and 2011 (−0.74 ± 0.73 Mg CO2 e ha−1 yr−1, CO2e are carbon dioxide equivalents), whereas nonmanured fields varied around zero. Future soil C pools stabilized 40–60 years faster in manured fields than nonmanured fields, at which point manured fields were significantly larger sources than nonmanured fields (1.45 ± 0.52 Mg CO2e ha−1 yr−1 and 0.51 ± 0.60 Mg CO2e ha−1 yr−1, respectively). Modeling also revealed a large background loss of soil C from the passive soil pool associated with the shift from perennial to annual grasses, equivalent to 29.4 ± 1.47 Tg CO2e in California between 1820 and 2011. Manure applications increased NPP and soil C storage, but plant community changes and GHG emissions decreased, and eventually eliminated, the net climate benefit of this practice.
Resource partitioning based on body size contributes to the species diversity of wood‐boring beetles and arboreal nesting ants
Authors: Satoh Toshiyuki , Yoshida Tomohiro , Koyama Satoshi , Yamagami Akira , Takata Mamoru , Doi Hayato , Kurachi Takuma , Hayashi Shinya , Hirobe Takuya , Hata Yasuo
Published: July 2015

The need to understand the mechanisms enhancing species coexistence and diversity is one of the central issues of community ecology. Theoretical work suggests that resource partitioning based on body size contributes to the coexistence of competing species, resulting in increased species diversity. Nevertheless, few empirical studies have investigated this. The species composition of wood‐dwelling arthropods was surveyed to examine resource partitioning based on body size in the dead wood of the ubame oak (Quercus phillyraeoides A. Grey) trees.

Greater resource sizes (larger dead wood diameter) retained a lower overall density of wood‐dwelling beetles per resource volume, greater total beetle biomass per resource volume and larger bodied individuals of the dominant species (Cerambycidae; Anaglyptus nipponensis Bates). A gradient in the species composition of arboreal ant assemblages along resource size and a positive correlation between resource size and ant body size was observed. These results suggest that the incidence of wood‐boring beetles was limited by the size of the available resource, resulting in resource partitioning by the ants according to the sizes of galleries made by the beetles.

Our findings indicate that resource size leads both directly and indirectly to body size‐dependent resource partitioning in beetle and ant assemblages, and contributes to the maintenance of species coexistence in the assemblages present in dead wood.
Changing face of care for patients with moderate to severe inflammatory bowel disease: the role of specialist nurses in the governance of anti‐TNF prescribing
Authors: Connell W. R. , Samyue T. , Gibson P. R. , Lachal S. , Moore G. T. , Macrae F. A. , Van Langenberg D. R.
Published: July 2015

Background

Anti‐tumour necrosis factor (TNF) therapy is highly effective for inflammatory bowel disease (IBD), but expensive and potentially toxic. Meticulous supervision prior to and during anti‐TNF treatment is required to screen and monitor patients for adverse clinical events. In addition, a systematic administrative process is necessary to comply with Australian Medicare requirements and ensure ongoing therapy is uninterrupted. IBD nurses are essential components of multidisciplinary IBD services, but their role in facilitating the safe and timely delivery of anti‐TNF drugs is unacknowledged.

Aim

The aim of the study was to calculate time spent by IBD nurses on anti‐TNF drug governance and its indirect cost.

Methods

Time spent on activities related to anti‐TNF governance was retrospectively assessed by questionnaire among IBD nurses employed at Melbourne hospitals. The capacity of IBD clinics at these hospitals was separately evaluated by surveying medical heads of clinics.

Results

On average, each Melbourne IBD service handled 150 existing and 40 new anti‐TNF referrals in 2013. The average annual time spent by nurses supervising an existing and newly referred anti‐TNF patient was 3.5 and 5.25 h respectively, or a minimum of two full working days per week. If clinicians undertook this activity during normal clinic time, the organisational opportunity cost was at least 58%.

Conclusions

Anti‐TNF therapy governance is an essential quality component of IBD care that is associated with a definite, indirect cost for every patient treated. IBD nurses are best positioned to undertake this role, but an activity‐based funding model is urgently required to resource this element of their work.
How to Succeed in a Transnational Labor Market: Job Search and Wages among Hungarian, Slovak, and Czech Commuters in Austria
Authors: Verwiebe Roland , Reinprecht Christoph , Haindorfer Raimund , Wiesboeck Laura
Published: July 2015

This paper deals with job search strategies and wages among cross-border commuters residing in the Central European Region (CENTROPE). Our main aim is to investigate the role of social networks as constitutive for job searching and for successful labor market integration. We build upon a theoretical framework developed by Aguilera and Massey, reflecting on the nexus of social networks, job search methods, and related labor market outcomes. Methodologically, we use a new quantitative survey on the employment careers of cross-border commuters residing in the regions of the Czech Republic, Slovakia, and Hungary bordering on Austria, conducted in the winter/spring of 2012/2013 (N = 2,573). Our results corroborate the hypothesis that human and social capital resources as well as labor market characteristics serve as key factors for job search and labor market integration among cross-border commuters in the CENTROPE transnational labor market.
Clinical Significance of Epsilon Waves in Arrhythmogenic Cardiomyopathy
Authors: PROTONOTARIOS ALEXANDROS , ANASTASAKIS ARIS , TSATSOPOULOU ADALENA , ANTONIADES LOIZOS , PRAPPA EFSTATHIA , SYRRIS PETROS , TOUSOULIS DIMITRIOS , McKENNA WILLIAM J. , PROTONOTARIOS NIKOS
Published: July 2015

Epsilon Waves in ACM

Introduction

Epsilon waves are hallmark features of arrhythmogenic cardiomyopathy (ACM) but information about their clinical significance is variable. We evaluated epsilon wave prevalence, characteristics, and their clinical significance in an ACM population.

Methods and Results

Eighty‐six unselected patients fulfilling the 2010 Task Force criteria were enrolled. Seventy‐six of them were carriers of desmosomal mutations. All subjects were serially evaluated with standard 12‐lead ECG and 2‐dimensional echocardiography. Epsilon waves were evaluated in all precordial and inferior leads. Novel parameters assessed included their duration and precordial/inferior lead extension. Twenty‐five subjects (29%) had epsilon waves that were present in lead V3 and beyond in 9, and in the inferior leads in 7. Epsilon waves were associated with right ventricular outflow tract (RVOT) (P = 0.001) but not RV posterior wall (P = 0.21), RV apex (P = 0.30), or left ventricular (P = 0.94) wall motion abnormalities. Patients with epsilon waves had increased RVOT diameter (P < 0.0001). Extension of epsilon waves in lead V3 and beyond was associated with increased epsilon wave duration (P = 0.002) and RVOT diameter (P = 0.04). The duration of epsilon waves was positively correlated with RVOT diameter (r = 0.70, P = 0.0001). Epsilon waves were also associated with episodes of sustained ventricular tachycardia (P = 0.004) but not with heart failure (P = 0.41) or sudden cardiac death (P = 0.31).

Conclusion

Detection of epsilon waves on 12‐lead ECG reflects significant RVOT involvement, which was associated with episodes of sustained ventricular tachycardia but not sudden cardiac death.
European Monetary Integration and the Incompatibility of National Varieties of Capitalism
Authors: Johnston Alison , Regan Aidan
Published: July 2015

The Varieties of Capitalism literature offers two competing hypotheses on institutional resilience. One argues that globalization promotes convergence towards a neo‐liberal system. Another stipulates that diverse capitalist regimes promote different comparative advantages, enabling diverse political economies to co‐exist. In this article, we argue that the compatibility of diverse models of capitalism is contingent upon monetary regime. We examine how different currency regimes influence the mutual co‐existence of export‐led growth models (euro core) and domestic demand‐led growth models (euro periphery). Under EMU, we find that these two models have become increasing incompatible, as unsustainable divergences in external balances have emerged between them. We hypothesize that external imbalances between these two growth regimes did not emerge prior to EMU because of the presence of two inflation adjustment mechanisms in the real exchange rate; the nominal exchange rate (in soft currency regimes) and national central banks’ promotion of inflation convergence (in hard currency regimes).
Analysis of genetic diversity and population structure of peanut cultivars and breeding lines from China, India and the US using simple sequence repeat markers
Authors: Wang Hui , Khera Pawan , Huang Bingyan , Yuan Mei , Katam Ramesh , Zhuang Weijian , Harris‐Shultz Karen , Moore Kim M. , Culbreath Albert K. , Zhang Xinyou , Varshney Rajeev K. , Xie Lianhui , Guo Baozhu
Published: July 2015

Cultivated peanut is grown worldwide as rich‐source of oil and protein. A broad genetic base is needed for cultivar improvement. The objectives of this study were to develop highly informative simple sequence repeat (SSR) markers and to assess the genetic diversity and population structure of peanut cultivars and breeding lines from different breeding programs in China, India and the US. A total of 111 SSR markers were selected for this study, resulting in a total of 472 alleles. The mean values of gene diversity and polymorphic information content (PIC) were 0.480 and 0.429, respectively. Country‐wise analysis revealed that alleles per locus in three countries were similar. The mean gene diversity in the US, China and India was 0.363, 0.489 and 0.47 with an average PIC of 0.323, 0.43 and 0.412, respectively. Genetic analysis using the STRUCTURE divided these peanut lines into two populations (P1, P2), which was consistent with the dendrogram based on genetic distance (G1, G2) and the clustering of principal component analysis. The groupings were related to peanut market types and the geographic origin with a few admixtures. The results could be used by breeding programs to assess the genetic diversity of breeding materials to broaden the genetic base and for molecular genetics studies.
The “Difficult Game” of Selling Brazilian Ethanol: Untangling Science–Business Relationships in the Global Biofuel Policy Nexus
Authors: Newberry Derek
Published: July 2015

O etanol brasileiro tem sido criticado por seus potenciais contribuições à mudança climática, criando uma controvérsia científica com grandes implicações econômicas, sendo que o resultado vai afeitar políticas globais que regulam exportações dessa energia. Os cientistas brasileiros envolvidos neste conflito político são vistos como motivados por interesses econômicos e nacionais, devido à sua colaboração com representantes da indústria de cana de açúcar em influenciar a política internacional de biocombustíveis. Proponho que esse alinhamento é um fenômeno emergente que é formado pelo envolvimento desses cientistas num processo político que é percebido como dominado pelas preocupações e normas dos participantes americanos e europeios. Definindo redes de políticas internacionais assim, como ambientes institucionais que influenciam e restringem ativamente os interesses dos atores envolvidos, teremos uma análise mais útil de como "interesses brasileiros" em relação a questões como a produção de energia e mudança climática são formados e traduzidos em políticas públicas.
Fibroblast growth factor 2 mRNA expression evoked by amitriptyline involves extracellular signal‐regulated kinase‐dependent early growth response 1 production in rat primary cultured astrocytes
Authors: Kajitani Naoto , Hisaoka‐Nakashima Kazue , Okada‐Tsuchioka Mami , Hosoi Mayu , Yokoe Toshiki , Morioka Norimitsu , Nakata Yoshihiro , Takebayashi Minoru
Published: July 2015

Recently, we demonstrated that several antidepressants including amitriptyline increased fibroblast growth factor 2 (FGF2) mRNA expression slowly over 24 h through de novo protein synthesis in rat primary cultured astrocytes. This study defined the signaling cascade that mediates amitriptyline‐induced FGF2 production in rat primary cultured astrocytes. Amitriptyline treatment significantly increased early growth response 1 (EGR1), a transcription factor known to regulate FGF2 expression. Knockdown of EGR1 using siRNA blocked amitriptyline‐evoked FGF2 mRNA expression. Treatment with several different classes of antidepressants leads to expression of EGR1 mRNA as well as FGF2 mRNA. These results confirm that EGR1 production is likely to be indispensable for the amitriptyline‐evoked FGF2 mRNA expression. Signal transduction inhibitors were used to elaborate the cellular signaling cascade that leads to EGR1‐mediated FGF2 expression following amitriptyline treatment. Amitriptyline‐evoked EGR1‐mediated FGF2 mRNA expression was blocked by mitogen‐activated protein kinase/extracellular signal‐regulated kinase kinase (MEK)1/2 inhibitor. Furthermore, extracellular signal‐regulated kinase/EGR1‐mediated FGF2 mRNA expression evoked by amitriptyline was blocked by inhibitors of the FGF receptor, epidermal growth factor receptor (EGFR), and matrix metalloproteinase. Taken together, these results demonstrate that amitriptyline increases FGF2 mRNA expression through a matrix metalloproteinase/receptor tyrosine kinases (RTK) (FGF receptor and EGFR)/extracellular signal‐regulated kinase/EGR1 signaling pathway in rat primary cultured astrocytes.

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Recent studies suggest that fibroblast growth factor 2 (FGF2) is involved in the antidepressant effect in the model of depression. The production of ERK‐dependent early growth response 1 (EGR1) is a crucial part of the amitriptyline‐induced FGF2 expression signaling cascade in rat primary cultured astrocytes. The findings elaborate an astrocytic mechanism that could be used to develop antidepressants.
Early intervention with glucagon‐like peptide 1 analog liraglutide prevents tau hyperphosphorylation in diabetic db/db mice
Authors: Ma De‐Lin , Chen Fu‐Qiong , Xu Wei‐Jie , Yue Wen‐Zhu , Yuan Gang , Yang Yan
Published: July 2015

Increasing evidence has shown that type 2 diabetes (T2D) is a risk factor for Alzheimer's disease. Neurofibrillary tangles, which consist of hyperphosphorylated tau and misfolded microtubules, is one of the neuropathological hallmarks of Alzheimer's disease. Db/db mice, a rodent model of T2D, also exhibited age‐dependent tau hyperphosphorylation. Glucagon‐like peptide‐1 (GLP‐1) mimetics, a type of drug used in T2D, has been found to have neuroprotective effects. The aim of this study was to explore the potential effects of liraglutide (a GLP‐1 analog), or insulin, on tau phosphorylation in T2D animals. Male db/db mice (3–3.5 weeks) were daily injected subcutaneously with liraglutide (n = 27), insulin (n = 27), or saline (n = 26), and five to seven mice were killed every 2 weeks for analysis of plasma and cerebrospinal (CSF) insulin levels by ELISA, and protein levels in the hippocampal formation by western blot. We found that db/db mice treated with saline exhibited an age‐dependent decrease in CSF insulin and an increase in hippocampal tau phosphorylation. Liraglutide injection reversed the CSF insulin to ~1 mIU/L by the end of 8 weeks treatment, and prevented the hyperphosphorylation of tau protein in the hippocampal formation. By contrast, insulin injection had no effects on CSF insulin or phosphorylation of tau protein. In summary, this study indicates that early GLP‐1 analog intervention prevented the age‐dependent tau hyperphosphorylation in T2D mice brain, probably by facilitating sequential activation in an insulin signaling pathway reflected in increased basal activation of Akt and basal suppression of glycogen synthase kinase‐3 beta.

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We found that liraglutide, a GLP‐1 (glucagon‐like peptide‐1) analog, prevented the age‐dependent Alzheimer‐like tau hyperphosphorylation in diabetic db/db mice. We proposed that liraglutide crosses the blood–brain barrier, and binds GLP‐1 receptors from which G beta gamma dissociates intracellularly to activate PI3K, resulting in activation of Akt, which suppress GSK‐3β (glycogen synthase kinase‐3β), and thereby prevents it from phosphorylating tau. IRS‐1: insulin receptor substrate 1; IRS‐2: insulin receptor substrate 2; PI3K: phosphatidylinositol 3‐kinase.
Experience of self‐management of medications among older people with multimorbidity
Authors: Summer Meranius Martina , Engstrom Gabriella
Published: July 2015

Aims and objectives

To explore the experience of self‐managing medication among older people with multimorbidity.

Background

Older people with multimorbidity are now more likely to live at home and to self‐medicate. Reduced assistance from professional caregivers is associated with medical errors.

Design

Face‐to‐face interviews were conducted with older people with multimorbidity.

Methods

Participants aged ≥75 years with ≥2 medical diagnoses and living at home or in special accommodation were interviewed. Twenty‐eight men and women (mean age 84 years) participated. Interviews lasted from 45 minutes–2 hours and were transcribed verbatim. A lifeworld‐based phenomenological method was used for analysis.

Results

Uncertainty among the participants increased with their experience of side effects and concern that the medication might be harmful. These uncertainties were reinforced by a fear of malpractice when several physicians were involved. This meant living with ambivalence when taking the medication, which required a trade‐off between symptom relief and reducing side effects. A lack of continuity with physicians and nurses led to uncertainty in maintaining an overview of the medications. By contrast, when the relationships were supportive and caring, the uncertainties diminished. Four concepts were used to describe the various meanings of this experience: adapting to a new lifestyle; ambivalence towards medicine; experience of side effects and concerns about medical errors; and relationships as sources of feeling secure.

Conclusions

Medications can cause side effects, and unclear benefits increase the uncertainty for older people with multimorbidity. Health care professionals need to develop an understanding of each patient's experience of such uncertainty.

Relevance to clinical practice

Health care professionals can give support and show understanding for older people's existential uncertainty by creating good relationships and continuity in care, and offering appropriate information. Regular visits should be scheduled to manage any problems patients might have when self‐medicating.
Nursing staffs' emotional well‐being and caring behaviours
Authors: Chana Navtej , Kennedy Paul , Chessell Zoë J
Published: July 2015

Aims and objectives

To examine the relationships between structural factors (work stressors), individual factors (demographics and the personal resources of resilience and social support) and transactional factors (appraisals and coping), and nursing staffs' levels of burnout, psychological distress and caring behaviours. A further aim was to examine the relationships between nursing staffs' levels of burnout and psychological distress and their caring behaviours.

Background

Burnout and psychological distress levels have been found to be high in National Health Service nursing staff and furthermore this emotional distress has been found to affect patient care. In a National Health Service striving to provide high‐quality patient‐centred care, it is essential that factors affecting nursing staffs' well‐being and their caring behaviours are examined.

Design

A cross‐sectional correlation‐based survey design.

Methods

A sample of 102 nursing staff from an Acute National Health Service Trust were recruited in 2010. Participants completed the questionnaires: Nursing Stress Scale, Social Support Questionnaire‐Short Form, Connor and Davidson Resilience Scale‐2, Occupational Coping Self‐Efficacy Scale for Nurses, PsychNurse Scale, Maslach Burnout Inventory, The Hospital Anxiety and Depression Scale and Caring Behaviours Inventory‐revised. Due to the nonparametric nature of part of the data, Spearman's Rho correlations were used for analysis.

Results

Demographics were not found to be regularly correlated with nursing staffs' burnout, psychological distress or caring behaviours. Work stressors, coping strategies and self‐efficacy were found to be significantly correlated with nursing staffs' burnout and psychological distress. Caring behaviours were also correlated with coping strategies and self‐efficacy. Importantly, correlations were found between caring behaviours and nursing staffs' burnout and psychological distress.

Conclusion

It is extremely important that the emotional well‐being of nursing staff is supported, both for them, and for the effect this has on patient care. Action points are suggested for National Health Service employers to enable this to happen.

Relevance to clinical practice

To address the poor emotional well‐being found, it is suggested that changes are needed within current clinical practice, for example through provision of enhanced training, use of model‐based clinical supervision and reviews conducted on staffing levels and workload issues.
A phase 1, randomized, dose‐ranging study of GS‐5816, a once‐daily NS5A inhibitor, in patients with genotype 1–4 hepatitis C virus
Authors: Lawitz E. , Freilich B. , Link J. , German P. , Mo H. , Han L. , Brainard D. M. , McNally J. , Marbury T. , Rodriguez‐Torres M.
Published: July 2015

GS‐5816 is an inhibitor of the hepatitis C virus (HCV) NS5A protein that has demonstrated pan‐genotypic activity and a high barrier to resistance in HCV replicon assays. The aim of this study was to evaluate the safety, antiviral activity and pharmacokinetics of once‐daily doses of GS‐5816 in patients with genotype 1–4 HCV infection. Patients with genotype 1–4 HCV infection were randomized to 3 days of GS‐5816 at doses ranging from 5 to 150 mg or placebo. Adverse events were recorded, and plasma samples obtained for analysis of pharmacokinetics, HCV RNA and NS5A sequencing studies. GS‐5816 5–150 mg for 3 days was well tolerated and resulted in rapid declines in HCV RNA that were sustained over the dosing period. In patients treated with the 150 mg dose of GS‐5816, the mean maximal HCV RNA declines were 4.0, 4.0, 4.4, 3.3 and 3.5 log10 IU/mL in patients with genotype 1a, 1b, 2, 3 and 4 HCV infection, respectively. Pretreatment NS5A resistance‐associated polymorphisms were detected in 31% (22/70) of patients. Genotype 1 and 3 HCV‐infected patients without pretreatment NS5A resistance‐associated polymorphisms had greater declines in HCV RNA than patients with resistance‐associated polymorphisms. Plasma pharmacokinetics were supportive of once‐daily dosing. GS‐5816 demonstrated pangenotypic antiviral activity in patients with genotype 1‐4 HCV infection. It will be further evaluated in combination with other pangenotypic direct‐acting antivirals to achieve the goal of developing a well‐tolerated, highly effective treatment for all HCV genotypes.
A Review of Paclitaxel and Novel Formulations Including Those Suitable for Use in Dogs
Authors: Khanna C. , Rosenberg M. , Vail D. M.
Published: July 2015

Paclitaxel is a commonly used chemotherapeutic agent with a broad spectrum of activity against cancers in humans. In 1992, paclitaxel was approved by the U.S. Food and Drug Administration (FDA) as Taxol® for use in advanced ovarian cancer. Two years later, it was approved for the treatment of metastatic breast cancer. Paclitaxel was originally isolated from the bark of the Pacific yew tree, Taxus brevifolia in 1971. Taxanes are a family of microtubule inhibitors. As a member of this family, paclitaxel suppresses spindle microtubule dynamics. This activity results in the blockage of the metaphase‐anaphase transitions, and ultimately in the inhibition of mitosis, and induction of apoptosis in a wide spectrum of cancer cells. Additional anticancer activities of paclitaxel have been defined that are independent of these effects on the microtubules and may include the suppression of cell proliferation as well as antiangiogenic effects. Based on its targeting of a fundamental feature of the cancer phenotype, the mitotic complex, it is not surprising that paclitaxel has been found to be active in a wide variety of cancers in humans. This review summarizes the evidence in support of paclitaxel's broad anticancer activity and introduces the rationale for, and the progress in development of novel formulations of paclitaxel that may preferentially target cancers and that are not associated with the risks for hypersensitivity in dogs. Of note, a novel nanoparticle formulation of paclitaxel that substantially limits hypersensitivity was recently given conditional approval by the FDA Center for Veterinary Medicine for use in dogs with resectable and nonresectable squamous cell carcinoma and nonresectable stage III, IV and V mammary carcinoma.
Thromboelastographic Evaluation of Dogs with Acute Liver Disease
Authors: Kelley D. , Lester C. , Shaw S. , de Laforcade A. , Webster C.R.L.
Published: July 2015

Background

Given the liver's pivotal role in hemostasis and fibrinolysis, the coagulopathy accompanying hepatic disease is complex.

Hypothesis/Objectives

To prospectively evaluate kaolin‐activated thromboelastography (TEG) in dogs with acute liver disease (ALD) and compare with plasma‐based coagulation tests.

Animals

Twenty‐one dogs with a diagnosis of ALD based on recent onset of clinical signs accompanied by increases in serum bilirubin concentration and alanine aminotransferase activity.

Methods

Clinical presentation, CBC, serum biochemistry, platelet count, prothrombin time (PT), activated partial thromboplastin time (aPTT), and TEG analysis were evaluated in 21 dogs with a subset also having fibrinogen, antithrombin (AT) activity, protein C (PC) activity, d‐dimers, and von Willebrand's factor (vWF) activity analyzed. A PT >1.5 times the upper limit of normal defined acute liver failure (ALF).

Results

Dogs with ALD had mean increases in R, K, LY30, PT, aPTT, and vWF activity, and decreases in angle, maximal amplitude (MA), G, AT activity, and PC activity. The TEG results defined dogs as hypocoagulable (11/21), normocoagulable (8/21), or hypercoagulable (2/21). Increases in LY30 defined 8/21 dogs as hyperfibrinolytic. Hypocoagulable and hyperfibrinolytic dogs had lower fibrinogen and PC activity than dogs without these abnormalities. Overall, ALF dogs had greater increases in K and LY30, and decreases in MA, G, and PC activity than dogs with less severe hepatic impairment. Results for MA and LY30 were positively correlated with serum bilirubin concentration and white blood cell count, and negatively correlated with serum cholesterol concentration.

Conclusions and Clinical Importance

ALD dogs have a range of coagulation abnormalities that trend toward hypocoagulability and hyperfibrinolysis as functional impairment occurs.
Supermarket Speak: Increasing Talk Among Low‐Socioeconomic Status Families
Authors: Ridge Katherine E. , Weisberg Deena Skolnick , Ilgaz Hande , Hirsh‐Pasek Kathryn A. , Golinkoff Roberta Michnick
Published: July 2015

Children from low‐socioeconomic status (SES) families often fall behind their middle‐class peers in early language development. But interventions designed to support their language skills are often costly and labor‐intensive. This study implements an inexpensive and subtle language intervention aimed at sparking parent–child interaction in a place that families naturally visit: the supermarket. We placed signs encouraging adult–child dialogue in supermarkets serving low‐ and mid‐SES neighborhoods. Using an unobtrusive observational methodology, we tested how these signs affected adult–child interactions. When signs were present in supermarkets serving low‐SES neighborhoods, both the amount and the quality of talk between adults and children increased significantly, compared to when the signs were not present; signs had little effect in middle‐SES supermarkets. This study demonstrates that implementing simple, cost‐effective interventions in everyday environments may bolster children's language development and school readiness skills.
Diurnal and nocturnal transcriptomic variation in the Caribbean staghorn coral, Acropora cervicornis
Authors: Hemond Elizabeth M. , Vollmer Steven V.
Published: July 2015

Reef‐building corals experience large diel shifts in their environment, both externally due to changes in light intensity, predator activity and prey availability, and internally as a result of diel fluctuations in photosynthesis by their endosymbiotic algae, Symbiodinium. Diel patterns of tentacle behaviour, skeletal growth and gene expression indicate reactions of the coral animal in response to light and through circadian regulation. Some corals, such as the Caribbean Acroporas, have strong within‐colony division of labour, including specialized fast‐growing apical polyps, accompanied by large gene expression differences. Here we use RNA‐seq to evaluate how diel changes in gene expression vary within the branching Caribbean staghorn coral, Acropora cervicornis, between branch tips and branch bases. Multifactor generalized linear model analysis indicated that 6% (3005) of transcripts were differentially expressed between branch tips and bases, while 1% (441) of transcripts were differentially expressed between day and night. The gene expression patterns of 220 transcripts were affected by both time of day and location within the colony. In particular, photoreceptors, putative circadian genes, stress response genes and metabolic genes were differentially expressed between day and night, and some of these, including Amcry1, tef and hebp2, exhibited location‐specific regulation within the coral colony as well. These findings indicate that the genetic response of the coral to day and night conditions varies within the colony. Both time of day and location within the colony are factors that should be considered in future coral gene expression experiments.
A practical guide to environmental association analysis in landscape genomics
Authors: Rellstab Christian , Gugerli Felix , Eckert Andrew J. , Hancock Angela M. , Holderegger Rolf
Published: July 2015

Landscape genomics is an emerging research field that aims to identify the environmental factors that shape adaptive genetic variation and the gene variants that drive local adaptation. Its development has been facilitated by next‐generation sequencing, which allows for screening thousands to millions of single nucleotide polymorphisms in many individuals and populations at reasonable costs. In parallel, data sets describing environmental factors have greatly improved and increasingly become publicly accessible. Accordingly, numerous analytical methods for environmental association studies have been developed. Environmental association analysis identifies genetic variants associated with particular environmental factors and has the potential to uncover adaptive patterns that are not discovered by traditional tests for the detection of outlier loci based on population genetic differentiation. We review methods for conducting environmental association analysis including categorical tests, logistic regressions, matrix correlations, general linear models and mixed effects models. We discuss the advantages and disadvantages of different approaches, provide a list of dedicated software packages and their specific properties, and stress the importance of incorporating neutral genetic structure in the analysis. We also touch on additional important aspects such as sampling design, environmental data preparation, pooled and reduced‐representation sequencing, candidate‐gene approaches, linearity of allele–environment associations and the combination of environmental association analyses with traditional outlier detection tests. We conclude by summarizing expected future directions in the field, such as the extension of statistical approaches, environmental association analysis for ecological gene annotation, and the need for replication and post hoc validation studies.
Bayesian inference of selection in a heterogeneous environment from genetic time‐series data
Authors: Gompert Zachariah
Published: July 2015

Evolutionary geneticists have sought to characterize the causes and molecular targets of selection in natural populations for many years. Although this research programme has been somewhat successful, most statistical methods employed were designed to detect consistent, weak to moderate selection. In contrast, phenotypic studies in nature show that selection varies in time and that individual bouts of selection can be strong. Measurements of the genomic consequences of such fluctuating selection could help test and refine hypotheses concerning the causes of ecological specialization and the maintenance of genetic variation in populations. Herein, I proposed a Bayesian nonhomogeneous hidden Markov model to estimate effective population sizes and quantify variable selection in heterogeneous environments from genetic time‐series data. The model is described and then evaluated using a series of simulated data, including cases where selection occurs on a trait with a simple or polygenic molecular basis. The proposed method accurately distinguished neutral loci from non‐neutral loci under strong selection, but not from those under weak selection. Selection coefficients were accurately estimated when selection was constant or when the fitness values of genotypes varied linearly with the environment, but these estimates were less accurate when fitness was polygenic or the relationship between the environment and the fitness of genotypes was nonlinear. Past studies of temporal evolutionary dynamics in laboratory populations have been remarkably successful. The proposed method makes similar analyses of genetic time‐series data from natural populations more feasible and thereby could help answer fundamental questions about the causes and consequences of evolution in the wild.
Comparative integrated molecular analysis of intraocular medulloepitheliomas and central nervous system embryonal tumors with multilayered rosettes confirms that they are distinct nosologic entities
Authors: Korshunov Andrey , Jakobiec Frederick A. , Eberhart Charles G. , Hovestadt Volker , Capper David , Jones David T.W. , Sturm Dominik , Stagner Anna M. , Edward Deepak P. , Eagle Ralph C. , Proia Alan D. , Koch Arend , Ryzhova Marina , Ektova Anastasia , Schüller Ulrich , Zheludkova Olga , Lichter Peter , von Deimling Andreas , Pfister Stefan M. , Kool Marcel
Published: July 2015

Intraocular medulloepithelioma (IO MEPL) is an uncommon embryonal neuroepithelial neoplasm of the eye. These ocular neoplasms have been compared with intracranial medulloepitheliomas or other histologic variants of CNS embryonal tumor with multilayered rosettes (CNS ETMR) due to their morphological mimicry. We performed comprehensive molecular analysis to explore the histogenetic and biologic relationships between 22 IO MEPL and 68 CNS ETMR. Routinely prepared paraffin‐embedded samples were assessed for genome‐wide methylation profiles using the Illumina Methylation 450k BeadChip array. We identified strong cytogenetic and epigenetic differences between ocular neoplasms and CNS ETMR. None of the IO MEPL cases displayed the ETMR‐specific amplification of the C19MC locus. Instead, cytogenetic analysis of the IO MEPL showed numerous copy number aberrations which involved either whole chromosomes or chromosomal arms; recurrent aberrations in these tumors affected chromosomes 1p, 4, 8 and 16p. DNA methylation patterns were also strikingly different between these two tumor entities, suggesting that they do not share common origins and biological behaviors. Comparative cluster analysis of 198 pediatric CNS tumors and 22 IO MEPL revealed a clear demarcation of the CNS ETMR and IO MEPL profiles from other CNS entities. In conclusion, although IO MEPL shares some histopathological features with CNS ETMR, they manifest striking molecular diversity at the cytogenetic and epigenetic levels. Consequently they deserve a separate nosologic designation in future tumor classifications, where CNS MEPL could be designated as a histological variant of CNS ETMR.
Targeting fatty acid metabolism to improve glucose metabolism
Authors: Stinkens R. , Goossens G. H. , Jocken J. W. E. , Blaak E. E.
Published: July 2015

Disturbances in fatty acid metabolism in adipose tissue, liver, skeletal muscle, gut and pancreas play an important role in the development of insulin resistance, impaired glucose metabolism and type 2 diabetes mellitus. Alterations in diet composition may contribute to prevent and/or reverse these disturbances through modulation of fatty acid metabolism.

Besides an increased fat mass, adipose tissue dysfunction, characterized by an altered capacity to store lipids and an altered secretion of adipokines, may result in lipid overflow, systemic inflammation and excessive lipid accumulation in non‐adipose tissues like liver, skeletal muscle and the pancreas. These impairments together promote the development of impaired glucose metabolism, insulin resistance and type 2 diabetes mellitus. Furthermore, intrinsic functional impairments in either of these organs may contribute to lipotoxicity and insulin resistance. The present review provides an overview of fatty acid metabolism‐related pathways in adipose tissue, liver, skeletal muscle, pancreas and gut, which can be targeted by diet or food components, thereby improving glucose metabolism.
Effects of Different Anesthetics on Pain Processing in an Experimental Human Pain Model
Authors: Nickel Florian T. , Ott Stephan , Möhringer Susanne , Münster Tino , Rieß Simon , Filitz Jörg , Koppert Wolfgang , Maihöfner Christian
Published: July 2015

Objective

After surgical procedures, anesthesia itself may affect pain perception. Particularly, there is increasing evidence that opioids not only have analgesic effects but also provoke pronociceptive changes, that is, opioid‐induced hyperalgesia. We investigated the effect of different anesthetic regimens on pain processing in volunteers using a transdermal electrical pain model. In this model, stimulation of epidermal nerve fibers representing mainly peptidergic C‐nociceptors leads to secondary hyperalgesia and habituation to the stimulus.

Methods

Forty‐eight healthy volunteers underwent conditioning noxious stimulation (CS) over 5 days. On day 2, the volunteers were randomized into 4 groups: control group (no anesthesia) and 3 groups receiving anesthesia before CS in anesthetic doses: propofol (P), propofol/remifentanil (PR), and propofol/remifentanil/S‐ketamine (PRK). Quantitative sensory testing was performed on days 1 through 5 and on day 22.

Results

In every group, CS was associated with short‐ and long‐term habituation to the electrical stimulus. Repetitive CS resulted in unmodified short‐term sensitization with stable areas of hyperalgesia. Although the PR group showed a trend toward increased areas of hyperalgesia on day 2, no significant differences were detectable between the groups. In contrast, anesthesia resulted in decreased intensity of the electrically evoked pain on day 2. Finally, the mechanical pain threshold before CS on day 5 was increased in all groups and remained elevated 3 weeks after the first CS, consistent with a long‐term antinociceptive effect after CS.

Conclusions

The results suggest a short‐term analgesic effect of general anesthesia. Furthermore, the conditioning stimulation over several days induced differential modulation of pro‐ and antinociceptive systems.
Experiences of continued presence: On the practical consequences of ‘hallucinations’ in bereavement
Authors: Hayes Jacqueline , Leudar Ivan
Published: July 2015

Objectives

We document the properties of experiences of continued presence (ECPs) helping to resolve controversies about their significance.

Method

We used qualitative methods in data collection and analysis. This enabled us to document the properties of ECPs. Narrative biographic interviews were carried out with 17 bereaved informants, and conversation analysis was used to identify the sources of meaning and functions of these experiences.

Results

Our informants heard voices of the deceased, saw their images, felt their touch, and sometimes felt their presence unspecified in any of the senses. Analysis revealed that ECPs were meaningfully connected to the immediate environments in which they happened but also to the personal histories of the bereaved. The narratives reveal helpful and destructive potentials of these experiences. In all cases, the functions relied on the relationship with the deceased.

Conclusions

The authors warn against oversimplification of ECPs, as significantly contrasting practical consequences commonly occurred within as well as between cases. The findings support the use of talking therapies based on personal meanings to help those disturbed by their experiences of presence.

Practitioner points

Practitioners should not assume that ECPs are signs of pathology – often they have healing consequences.

Where ECPs cause distress, the problem is likely to concern relationship difficulties with the deceased.

Therapists can help clients with distressing ECPs by working on the relationship with the deceased.
Variation in fluxes estimated from nitrogen isotope discrimination corresponds with independent measures of nitrogen flux in Populus balsamifera L.
Authors: Kalcsits Lee A. , Guy Robert D.
Published: July 2015

Acquisition of mineral nitrogen by roots from the surrounding environment is often not completely efficient, in which a variable amount of leakage (efflux) relative to gross uptake (influx) occurs. The efflux/influx ratio (E/I) is, therefore, inversely related to the efficiency of nutrient uptake at the root level. Time‐integrated estimates of E/I and other nitrogen‐use traits may be obtainable from variation in stable isotope ratios or through compartmental analysis of tracer efflux (CATE) using radioactive or stable isotopes. To compare these two methods, Populus balsamifera L. genotypes were selected, a priori, for high or low nitrogen isotope discrimination. Vegetative cuttings were grown hydroponically, and E/I was calculated using an isotope mass balance model (IMB) and compared to E/I calculated using 15N CATE. Both methods indicated that plants grown with ammonium had greater E/I than nitrate‐grown plants. Genotypes with high or low E/I using CATE also had similarly high or low estimates of E/I using IMB, respectively. Genotype‐specific means were linearly correlated (r = 0.77; P = 0.0065). Discrepancies in E/I between methods may reflect uncertainties in discrimination factors for the assimilatory enzymes, or temporal differences in uptake patterns. By utilizing genotypes with known variation in nitrogen isotope discrimination, a relationship between nitrogen isotope discrimination and bidirectional nitrogen fluxes at the root level was observed.
A Partial Defense of Permissivism
Authors: Sharadin Nathaniel
Published: July 2015

Permissivism is the view that sometimes an agent's total evidential state entails both that she is epistemically permitted to believe that P and that she is epistemically permitted to believe that Q, where P and Q are contradictories. Uniqueness is the denial of Permissivism. Permissivism has recently come under attack on several fronts. If these attacks are successful, then we may be forced to accept an unwelcome asymmetry between epistemic and practical rationality. In this essay I clarify the debate by distinguishing two versions (each) of Permissiveness and Uniqueness. I then respond to several recent challenges to Permissivism in an attempt to even the score between Permissivism and Uniqueness. I will also respond to a worry – arising out of my discussion – that a defense of Permissivism itself introduces an unwelcome asymmetry between epistemic and practical rationality.