bluuebunny/crossref_metadata_2025_split huggingface dataset:
The accuracy of Fastloc‐GPS locations and implications for animal tracking
Authors: Dujon Antoine M. , Lindstrom R. Todd , Hays Graeme C. 
Published: October 2014

Summary

Over recent years, a major breakthrough in marine animal tracking has occurred with the advent of Fastloc‐GPS that provides highly accurate location data even for animals that only surface briefly such as sea turtles, marine mammals and penguins.

We assessed the accuracy of Fastloc‐GPS locations using fixed trials of tags in which >45 000 locations were obtained. Procedures for determining the speed of travel and heading were developed by simulating tracks and then adding Fastloc‐GPS location errors. The levels of detail achievable for speed and heading estimates were illustrated by using empirical Fastloc‐GPS data for a green turtle (Chelonia mydas, Linnaeus, 1758) travelling over 3000 km across the Indian Ocean.

The accuracy of Fastloc‐GPS locations varied as a function of the number of GPS satellites used in the location calculation. For example, when Fastloc‐GPS locations were calculated using 4 GPS satellites, 50% of locations were within 36 m and 95% within 724 m of the true position. These values improved to 18 and 70 m, respectively, when 6 satellites were used. Simulations indicated that for animals travelling around 2·5 km h−1 (e.g. turtles, penguins and seals) and depending on the number of satellites used in the location calculation, robust speed and heading estimates would usually be obtained for locations only 1–6 h apart.

Fastloc‐GPS accuracy is several orders of magnitude better that conventional Argos tracking or light‐based geolocation and consequently will allow new insights into small‐scale movement patterns of marine animals.
A pharmacokinetic and pharmacodynamic comparison of a novel pegylated recombinant consensus interferon‐α variant with peginterferon‐α‐2a in healthy subjects
Authors: Zheng Li , Li Mao Ping , Gou Zhong Ping , Wang Ying , Xu Nan , Cai Yong Ming , Luo Hua 
Published: October 2014

AimsThe aims of the study were to assess the pharmacokinetics, pharmacodynamics, safety and tolerability of a novel, pegylated recombinant human consensus interferon‐α variant (PEG‐IFN‐SA) in healthy volunteers. A pharmacokinetic and pharmacodynamic comparison of PEG‐IFN‐SA and peginterferon‐α‐2a in healthy subjects was evaluated.MethodsA randomized, dose‐escalating, single administration dose phase I clinical study was conducted. Thirty healthy subjects received PEG‐IFN‐SA as a single dose of 0.5–2.0 μg kg−1 by subcutaneous (s.c.) injection in four parallel groups. Eight subjects received peginterferon‐α‐2a as a single dose of 180 μg s.c.ResultsThe incidence rates of adverse events for PEG‐IFN‐SA and peginterferon‐α‐2a were 29 of 30 and 7 of 8, respectively. The adverse events for PEG‐IFN‐SA were mild to moderate and similar to those of peginterferon‐α‐2a. Within 168 h after injection, the mean values of maximal concentration and area under the plasma concentration–time curve from time of dosing to 168 h [AUC(0–168h)] for 2′,5′‐oligoadenylate, neopterin and β2‐microglobulin for PEG‐IFN‐SA at 1.5 μg kg−1 s.c. were similar to or higher than those for peginterferon‐α‐2a at a dose of 180 μg s.c. After s.c. injection of PEG‐IFN‐SA at 1.5 μg kg−1, the mean geometric mean values of plasma half‐life, time to maximal concentration, maximal concentration and AUC(0–168h) were 55.3 h, 26.9 h, 0.53 μg l−1 and 44.0 μg l−1 h, respectively.ConclusionsThe tolerance, pharmacokinetic and pharmacodynamic characteristics of PEG‐IFN‐SA support its administration by s.c. injection as a single dose of 1.5 μg kg−1 or at 2.0 μg kg−1 per week.
Model Choice Problems Using Approximate Bayesian Computation with Applications to Pathogen Transmission Data Sets
Authors: Lee Xing Ju , Drovandi Christopher C. , Pettitt Anthony N. 
Published: October 2014

Summary
Analytically or computationally intractable likelihood functions can arise in complex statistical inferential problems making them inaccessible to standard Bayesian inferential methods. Approximate Bayesian computation (ABC) methods address such inferential problems by replacing direct likelihood evaluations with repeated sampling from the model. ABC methods have been predominantly applied to parameter estimation problems and less to model choice problems due to the added difficulty of handling multiple model spaces. The ABC algorithm proposed here addresses model choice problems by extending Fearnhead and Prangle (2012, Journal of the Royal Statistical Society, Series B 74, 1–28) where the posterior mean of the model parameters estimated through regression formed the summary statistics used in the discrepancy measure. An additional stepwise multinomial logistic regression is performed on the model indicator variable in the regression step and the estimated model probabilities are incorporated into the set of summary statistics for model choice purposes. A reversible jump Markov chain Monte Carlo step is also included in the algorithm to increase model diversity for thorough exploration of the model space. This algorithm was applied to a validating example to demonstrate the robustness of the algorithm across a wide range of true model probabilities. Its subsequent use in three pathogen transmission examples of varying complexity illustrates the utility of the algorithm in inferring preference of particular transmission models for the pathogens.
Estimation of Treatment Effects in All-Comers Randomized Clinical Trials with a Predictive Marker
Authors: Choai Yuki , Matsui Shigeyuki 
Published: October 2014

Summary
Recent advances in genomics and biotechnologies have accelerated the development of molecularly targeted treatments and accompanying markers to predict treatment responsiveness. However, it is common at the initiation of a definitive phase III clinical trial that there is no compelling biological basis or early trial data for a candidate marker regarding its capability in predicting treatment effects. In this case, it is reasonable to include all patients as eligible for randomization, but to plan for prospective subgroup analysis based on the marker. One analysis plan in such all-comers designs is the so-called fallback approach that first tests for overall treatment efficacy and then proceeds to testing in a biomarker-positive subgroup if the first test is not significant. In this approach, owing to the adaptive nature of the analysis and a correlation between the two tests, a bias will arise in estimating the treatment effect in the biomarker-positive subgroup after a non-significant first overall test. In this article, we formulate the bias function and show a difficulty in obtaining unbiased estimators for a whole range of an associated parameter. To address this issue, we propose bias-corrected estimation methods, including those based on an approximation of the bias function under a bounded range of the parameter using polynomials. We also provide an interval estimation method based on a bivariate doubly truncated normal distribution. Simulation experiments demonstrated a success in bias reduction. Application to a phase III trial for lung cancer is provided.
Spatial Variable Selection Methods for Investigating Acute Health Effects of Fine Particulate Matter Components
Authors: Boehm Vock Laura F. , Reich Brian J. , Fuentes Montserrat , Dominici Francesca 
Published: October 2014

Summary
Multi-site time series studies have reported evidence of an association between short term exposure to particulate matter (PM) and adverse health effects, but the effect size varies across the United States. Variability in the effect may partially be due to differing community level exposure and health characteristics, but also due to the chemical composition of PM which is known to vary greatly by location and time. The objective of this article is to identify particularly harmful components of this chemical mixture. Because of the large number of highly-correlated components, we must incorporate some regularization into a statistical model. We assume that, at each spatial location, the regression coefficients come from a mixture model with the flavor of stochastic search variable selection, but utilize a copula to share information about variable inclusion and effect magnitude across locations. The model differs from current spatial variable selection techniques by accommodating both local and global variable selection. The model is used to study the association between fine PM (PM 2.5m) components, measured at 115 counties nationally over the period 2000–2008, and cardiovascular emergency room admissions among Medicare patients.
Protective effects of n‐6 fatty acids‐enriched diet on intestinal ischaemia/reperfusion injury involve lipoxin A4 and its receptor
Authors: Gobbetti T , Ducheix S , le Faouder P , Perez T , Riols F , Boue J , Bertrand‐Michel J , Dubourdeau M , Guillou H , Perretti M , Vergnolle N , Cenac N 
Published: October 2014

Background and PurposeLong‐term intake of dietary fatty acids is known to predispose to chronic inflammation, but their effects on acute intestinal ischaemia/reperfusion (I/R) injury is unknown. The aim of this study was to determine the consequences of a diet rich in n‐3 or n‐6 polyunsaturated fatty acids (PUFA) on intestinal I/R‐induced damage.Experimental ApproachMice were fed three different isocaloric diets: a balanced diet used as a control and two different PUFA‐enriched diets, providing either high levels of n‐3 or of n‐6 PUFA. Intestinal injury was evaluated after intestinal I/R. PUFA metabolites were quantitated in intestinal tissues by LC‐MS/MS.Key ResultsIn control diet‐fed mice, intestinal I/R caused inflammation and increased COX and lipoxygenase‐derived metabolites compared with sham‐operated animals. Lipoxin A4 (LxA4) was significantly and selectively increased after ischaemia. Animals fed a high n‐3 diet did not display a different inflammatory profile following intestinal I/R compared with control diet‐fed animals. In contrast, intestinal inflammation was decreased in the I/R group fed with high n‐6 diet and level of LxA4 was increased post‐ischaemia compared with control diet‐fed mice. Blockade of the LxA4 receptor (Fpr2), prevented the anti‐inflammatory effects associated with the n‐6 rich diet.Conclusions and ImplicationsThis study indicates that high levels of dietary n‐6, but not n‐3, PUFAs provides significant protection against intestinal I/R‐induced damage and demonstrates that the endogenous production of LxA4 can be influenced by diet.
Serelaxin‐mediated signal transduction in human vascular cells: bell‐shaped concentration–response curves reflect differential coupling to G proteins
Authors: Sarwar M , Samuel C S , Bathgate R A , Stewart D R , Summers R J 
Published: October 2014

Background and PurposeIn a recently conducted phase III clinical trial, RELAX‐AHF, serelaxin infusion over 48 h improved short‐ and long‐term clinical outcomes in patients with acute heart failure. In this study we used human primary cells from the umbilical vasculature to better understand the signalling mechanisms activated by serelaxin.Experimental ApproachWe examined the acute effects of serelaxin on signal transduction mechanisms in primary human umbilical vascular cells and its chronic actions on markers of cardiovascular function and disease.Key ResultsThe RXFP1 receptor, the cognate serelaxin receptor, was expressed at the cell surface in HUVECs and human umbilical vein smooth muscle cells (HUVSMCs), human umbilical artery smooth muscle cells (HUASMCs) and human cardiac fibroblasts (HCFs), but not human umbilical artery endothelial cells. In HUVECs and HUVSMCs, serelaxin increased cAMP, cGMP accumulation and pERK1/2, and the concentration–response curves (CRCs) were bell‐shaped. Similar bell‐shaped CRCs for cGMP and pERK1/2 were observed in HCFs, whereas in HUASMCs, serelaxin increased cAMP, cGMP and pERK1/2 with sigmoidal CRCs. Gαi/o and lipid raft disruption, but not Gαs inhibition, altered the serelaxin CRC for cAMP and cGMP accumulation in HUVSMC but not HUASMC. Longer term serelaxin exposure increased the expression of neuronal NOS, VEGF, ETβ receptors and MMPs (gelatinases) in RXFP1 receptor‐expressing cells.Conclusions and ImplicationsSerelaxin caused acute and chronic changes in human umbilical vascular cells that were cell background dependent. Bell‐shaped CRCs that were observed only in venous cells and fibroblasts involved Gαi/o located within membrane lipid rafts.
Biased β2‐adrenoceptor signalling in heart failure: pathophysiology and drug discovery
Authors: Woo Anthony Yiu‐Ho , Song Ying , Xiao Rui‐Ping , Zhu Weizhong 
Published: October 2014

The body is constantly faced with a dynamic requirement for blood flow. The heart is able to respond to these changing needs by adjusting cardiac output based on cues emitted by circulating catecholamine levels. Cardiac β‐adrenoceptors transduce the signal produced by catecholamine stimulation via Gs proteins to their downstream effectors to increase heart contractility. During heart failure, cardiac output is insufficient to meet the needs of the body; catecholamine levels are high and β‐adrenoceptors become hyperstimulated. The hyperstimulated β1‐adrenoceptors induce a cardiotoxic effect, which could be counteracted by the cardioprotective effect of β2‐adrenoceptor‐mediated Gi signalling. However, β2‐adrenoceptor‐Gi signalling negates the stimulatory effect of the Gs signalling on cardiomyocyte contraction and further exacerbates cardiodepression. Here, further to the localization of β1‐ and β2‐adrenoceptors and β2‐adrenoceptor‐mediated β‐arrestin signalling in cardiomyocytes, we discuss features of the dysregulation of β‐adrenoceptor subtype signalling in the failing heart, and conclude that Gi‐biased β2‐adrenoceptor signalling is a pathogenic pathway in heart failure that plays a crucial role in cardiac remodelling. In contrast, β2‐adrenoceptor‐Gs signalling increases cardiomyocyte contractility without causing cardiotoxicity. Finally, we discuss a novel therapeutic approach for heart failure using a Gs‐biased β2‐adrenoceptor agonist and a β1‐adrenoceptor antagonist in combination. This combination treatment normalizes the β‐adrenoceptor subtype signalling in the failing heart and produces therapeutic effects that outperform traditional heart failure therapies in animal models. The present review illustrates how the concept of biased signalling can be applied to increase our understanding of the pathophysiology of diseases and in the development of novel therapies.Linked ArticlesThis article is part of a themed section on Chinese Innovation in Cardiovascular Drug Discovery. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2015.172.issue-23
Diadenosine tetraphosphate induces tight junction disassembly thus increasing corneal epithelial permeability
Authors: Loma P , Guzman‐Aranguez A , Pérez de Lara M J , Pintor J 
Published: October 2014

Background and PurposeHere, we have studied the effects of the dinucleotide P1, P4‐Di (adenosine‐5′) tetraphosphate (Ap4A) on corneal barrier function conferred by the tight junction (TJ) proteins and its possible involvement in ocular drug delivery and therapeutic efficiency.Experimental ApproachExperiments in vitro were performed using human corneal epithelial cells (HCLEs) treated with Ap4A (100 μM) for 5 min. Western blot analysis and transepithelial electrical resistance (TEER) were performed to study the TJ protein levels and barrier function respectively. Intracellular pathways involved were determined using an ERK inhibitor and P2Y2 receptor siRNAs. In in vivo assays with New Zealand rabbits, TJ integrity was examined by zonula occludens‐1 (ZO‐1) staining. The hypotensive compound 5‐methoxycarbonylamino‐N‐acetyltryptamine (5‐MCA‐NAT) was used to assess improved delivery, measuring its levels by HPLC and measuring intraocular pressure using 5‐MCA‐NAT, P2Y receptor antagonists and P2Y2 siRNAs.Key ResultsTwo hours after Ap4A pretreatment, TJ protein levels in HCLE cells were reduced around 40% compared with control. TEER values were significantly reduced at 2 and 4 h (68 and 52% respectively). TJ reduction and ERK activation were blocked by the ERK inhibitor U012 and P2Y2 siRNAs. In vivo, topical application of Ap4A disrupted ZO‐1 membrane distribution. 5‐MCA‐NAT levels in the aqueous humour were higher when Ap4A was previously instilled and its hypotensive effect was also increased. This action was reversed by P2Y receptor antagonists and P2Y2 siRNA.Conclusions and ImplicationsAp4A increased corneal epithelial barrier permeability. Its application could improve ocular drug delivery and consequently therapeutic efficiency.
The relationship between parental fatigue, parenting self‐efficacy and behaviour: implications for supporting parents in the early parenting period
Authors: Chau V. , Giallo R. 
Published: October 2014

AbstractBackgroundEmerging evidence indicates that parental fatigue is associated with low warmth and increased hostility in parent–child interactions. One possible pathway by which fatigue may impact on parenting behaviour is via parental self‐efficacy (PSE), whereby high fatigue may undermine PSE, which is often associated with suboptimal parenting behaviour. The current study sought to explore a model of the relationships between parental fatigue, parenting warmth and hostility, where PSE mediates these relationships and whether the nature of these relationships differ by social or family context.MethodsThe current sample was drawn from a larger Australian community sample survey on parent well‐being and parenting. It consisted of 1143 parents (mothers, n = 1003; fathers, n = 140) of children aged 0–4 years.ResultsPath analysis revealed that the relationship between fatigue and parenting warmth and hostility was fully mediated by PSE.ConclusionsThese results indicate that fatigue has the potential to negatively influence parenting behaviours that are important for their children's well‐being and development, and that fatigue plays a mediating role in this relationship. Implications of the study for psycho‐education and interventions targeting the management of parental fatigue are discussed.
The well‐being of children of parents with a mental illness: the responsiveness of crisis mental health services in Wellington, New Zealand
Authors: Pfeiffenberger Ari S. , D'Souza Amanda J. , Huthwaite Mark A. , Romans Sarah E. 
Published: October 2014

AbstractLittle is known about how mental health services consider the parenting role and the well‐being of children when assessing parents with acute mental illness. This paper investigated how crisis mental health services addressed child well‐being in the Wellington region, New Zealand. This mixed‐method case study included: (i) an audit of the electronic clinical records of all adults presenting to the crisis assessment team; (ii) interviews with 22 key informants; and (iii) a documentary review. We found that data about children were not systematically collected. Less than half of (49 of the 104) the records of patients who were parents included information on their child's well‐being; only six (6%) contained a specified plan for action. The focus for services was the adult patient. Key informants were unclear about their role. They identified inadequate training and institutional support, inflexible funding models and limited availability or inappropriateness of referral services as problems. They saw a need for children to become more visible, for collaborative working to improve the use of existing services and for new funding models, resources and roles. Existing national policy documents contained little guidance and no practice guidelines were in use. These were lost opportunities to improve support for the parenting role and promote child well‐being.
A single‐center experience with 200 dual kidney transplantations
Authors: Rigotti Paolo , Capovilla Giovanni , Di Bella Caterina , Silvestre Cristina , Donato Paola , Baldan Nicola , Furian Lucrezia 
Published: October 2014

AbstractThis study reports on a large series of 200 dual kidney transplantations (DKTs) from expanded criteria donors (ECDs) and proposes specific ways to optimize outcomes. Data concerning 200 DKTs performed in the last 14 yr were retrospectively analyzed. Kidneys from high‐risk ECD were allocated for use in DKTs on an old‐for‐old basis after histological assessment. Different surgical techniques and immunosuppressant regimens were used over time, and the outcomes are discussed. Donors and recipients were a median 73 (70–77) and a 62 (58–67) yr old, respectively. Delayed graft function occurred in 31.5% of cases, and acute rejection in 13.5%. Patient and graft survival at five yr were 90.4% and 85.8%, respectively. Unilateral kidney placement was preferred for 75% of patients, and was associated with a low rate of surgical complications. Our current standard therapy comprising low‐dose calcineurin inhibitors (CNIs) associated with mammalian target of rapamycin inhibitors (mTOR) and steroids appears to offer the best risk/benefit profile for elderly patients undergoing DKT. In our experience, outcomes after DKT can be improved by: (i) kidney clinical–histological assessment; (ii) unilateral kidney placement; (iii) minimal use of CNI associated with mTOR.
Underwater evaluation of habitat partitioning in a European river between a non‐native invader, the racer goby and a threatened native fish, the European bullhead
Authors: Kakareko Tomasz , Kobak Jarosław , Poznańska Małgorzata , Jermacz Łukasz , Copp Gordon H. 
Published: October 2014

AbstractWe conducted underwater surveys using SCUBA gear to examine habitat and microhabitat competition between the Ponto‐Caspian racer goby Babka gymnotrachelus and native European bullhead Cottus gobio to assess the potential for competitive displacement of the native species by the invading species. In summer, 88 surveys were made in a tributary of the River Vistula within defined benthic areas across the entire width of the river bed. The occurrence of fish by total length class (small: <6 cm; large: >6 cm) and environmental conditions (depth, water velocity, substratum type, plant cover, shelter type) was recorded. We found a substantial separation between the species and size classes in relation to substratum, shelter type and water velocity. European bullheads were limited to lotic areas with stony bottoms, whereas racer gobies also occupied lentic areas over sand or mud. European bullheads usually took refuge under stones in contrast to a wider range of shelters used by racer goby, including tree roots and rubbish. In general, the breadth of habitat used by the racer goby was wider than that of the European bullhead, although habitat overlap between the species was not statistically significant except for the type of shelter occupied by small fish, selecting smaller stones. An inverse relationship was observed between small European bullheads and all racer gobies in areas where they co‐occurred, suggesting that invader may be having an adverse effect on the distribution and habitat use of small native bullheads, particularly in areas of moderate water velocities over small stones and gravel.