bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mild external heating and reduction in spontaneous contractions of the bladder
Authors: Kitney Darryl G. , Jabr Rita I. , Vahabi Bahareh , Fry Christopher H. 
Published: June 2017

ObjectivesTo measure the effect of external heating on bladder wall contractile function, histological structure and expression of proteins related to tissue protection and apoptosis.Material and MethodsIn vitro preparations of bladder wall and ex vivo perfused pig bladders were heated from 37 to 42°C, 46 and 50°C for 15 min. Isolated preparations were heated by radiant energy and perfused bladders were heated by altering perfusate temperature. Spontaneous contractions or pressure variations were recorded, as well as responses to the muscarinic agonist carbachol or motor nerve excitation in vitro during heating. Tissue histology in control and after heating was analysed using haematoxylin and eosin staining and 4′‐6‐diamidino‐2‐phenylindole (DAPI) nuclear labelling. The effects of heating on protein expression levels of (i) heat shock proteins HSP27‐pSer82 and inducible‐HSP70 and (ii) caspase‐3 and its downstream DNA‐repair substrate poly‐[ADP‐ribose] polymerase (PARP) were measured.ResultsHeating to 42°C reduced spontaneous contractions or pressure variations by ~70%; effects were fully reversible. There were no effects on carbachol or nerve‐mediated responses. Tissue histology was unaffected by heating, and expression of heat shock proteins as well as caspase‐3 and PARP were also unaltered. A TRPV1 antagonist had no effect on the reduction of spontaneous activity. Heating to 46°C had a similar effect on spontaneous activity and also reduced the carbachol contracture. Urothelial structure was damaged, caspase‐3 levels were increased and inducible‐HSP70 levels declined. At 50°C evoked contractions were abolished, the urothelium was absent and heat shock proteins and PARP expression was reduced with raised caspase‐3 expression.ConclusionsHeating to 42°C caused a profound, reversible and reproducible attenuation of spontaneous activity, with no tissue damage and no initiation of apoptosis pathways. Higher temperatures caused tissue damage and activation of apoptotic mechanisms. Mild heating offers a novel approach to reducing bladder spontaneous activity.
Recent advances in the development of T‐type calcium channel blockers for pain intervention
Authors: Snutch Terrance P , Zamponi Gerald W 
Published: June 2017

Cav3.2 T‐type calcium channels are important regulators of pain signals in the afferent pain pathway, and their activities are dysregulated during various chronic pain states. Therefore, it is reasonable to predict that inhibiting T‐type calcium channels in dorsal root ganglion neurons and in the spinal dorsal horn can be targeted for pain relief. This is supported by early pharmacological studies with T‐type channel blockers, such as ethosuximide, and by analgesic effects of siRNA depletion of Cav3.2 channels. In the past 5 years, considerable effort has been applied towards identifying novel classes of T‐type calcium channel blockers. Here, we review recent developments in the discovery of novel classes of T‐type calcium channel blockers, and their analgesic effects in animal models of pain and in clinical trials.Linked ArticlesThis article is part of a themed section on Recent Advances in Targeting Ion Channels to Treat Chronic Pain. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.12/issuetoc
A novel individual‐cell‐based mathematical model based on multicellular tumour spheroids for evaluating doxorubicin‐related delivery in avascular regions
Authors: Liu Jiali , Yan Fangrong , Chen Hongzhu , Wang Wenjie , Liu Wenyue , Hao Kun , Wang Guangji , Zhou Fang , Zhang Jingwei 
Published: June 2017

Background and PurposeEffective drug delivery in the avascular regions of tumours, which is crucial for the promising antitumour activity of doxorubicin‐related therapy, is governed by two inseparable processes: intercellular diffusion and intracellular retention. To accurately evaluate doxorubicin‐related delivery in the avascular regions, these two processes should be assessed together. Here we describe a new approach to such an assessment.Experimental ApproachAn individual‐cell‐based mathematical model based on multicellular tumour spheroids was developed that describes the different intercellular diffusion and intracellular retention kinetics of doxorubicin in each cell layer. The different effects of a P‐glycoprotein inhibitor (LY335979) and a hypoxia inhibitor (YC‐1) were quantitatively evaluated and compared, in vitro (tumour spheroids) and in vivo (HepG2 tumours in mice). This approach was further tested by evaluating in these models, an experimental doxorubicin derivative, INNO 206, which is in Phase II clinical trials.Key ResultsInhomogeneous, hypoxia‐induced, P‐glycoprotein expression compromised active transport of doxorubicin in the central area, that is, far from the vasculature. LY335979 inhibited efflux due to P‐glycoprotein but limited levels of doxorubicin outside the inner cells, whereas YC‐1 co‐administration specifically increased doxorubicin accumulation in the inner cells without affecting the extracellular levels. INNO 206 exhibited a more effective distribution profile than doxorubicin.Conclusions and ImplicationsThe individual‐cell‐based mathematical model accurately evaluated and predicted doxorubicin‐related delivery and regulation in the avascular regions of tumours. The described framework provides a mechanistic basis for the proper development of doxorubicin‐related drug co‐administration profiles and nanoparticle development and could avoid unnecessary clinical trials.
Sensitivity to Shared Information in Social Learning
Authors: Whalen Andrew , Griffiths Thomas L. , Buchsbaum Daphna 
Published: June 2017

AbstractSocial learning has been shown to be an evolutionarily adaptive strategy, but it can be implemented via many different cognitive mechanisms. The adaptive advantage of social learning depends crucially on the ability of each learner to obtain relevant and accurate information from informants. The source of informants’ knowledge is a particularly important cue for evaluating advice from multiple informants; if the informants share the source of their information or have obtained their information from each other, then their testimony is statistically dependent and may be less reliable than testimony from informants who do not share information. In this study, we use a Bayesian model to determine how rational learners should incorporate the effects of shared information when learning from other people, conducting three experiments that examine whether human learners behave similarly. We find that people are sensitive to a number of different patterns of dependency, supporting the use of a sophisticated strategy for social learning that goes beyond copying the majority, and broadening the situations in which social learning is likely to be an adaptive strategy.
Long‐term safety and efficacy of canagliflozin as add‐on therapy to teneligliptin in Japanese patients with type 2 diabetes
Authors: Kadowaki Takashi , Inagaki Nobuya , Kondo Kazuoki , Nishimura Kenichi , Kaneko Genki , Maruyama Nobuko , Nakanishi Nobuhiro , Watanabe Yumi , Gouda Maki , Iijima Hiroaki 
Published: June 2017

AimTo evaluate the long‐term safety and efficacy of canagliflozin as add‐on therapy in patients with type 2 diabetes mellitus (T2DM) who had inadequate glycaemic control with teneligliptin monotherapy.MethodsThis open‐label 52‐week study was conducted in Japan. Patients received canagliflozin 100 mg added to teneligliptin 20 mg orally once daily for 52 weeks. The safety endpoint was the incidence of adverse events (AEs). The efficacy endpoints included changes in glycated haemoglobin (HbA1c), fasting plasma glucose (FPG) and body weight from baseline to week 52 (with last observation carried forward).ResultsOverall, 153 patients entered the treatment period and 142 completed the study. The overall incidence rates of AEs and drug‐related AEs were 69.9% and 22.9%, respectively. Most AEs and drug‐related AEs were mild or moderate in severity. There were no previously undescribed safety signals. The mean changes in HbA1c, FPG and body weight were −0.99% (95% confidence interval [CI] −1.12 to −0.85), −38.6 mg/dL (95% CI −43.4 to −33.9) and −3.92% (95% CI −4.53 to −3.31), respectively. These effects were maintained for 52 weeks without attenuation. HbA1c and body weight were both decreased in 82.24% of patients at the end of the treatment period. Reductions in postprandial glucose were observed at weeks 24 and 52.ConclusionsNo new safety risks with this combination were identified, and sustained improvements in HbA1c, FPG and body weight were observed. The findings suggest that long‐term co‐administration of canagliflozin with teneligliptin is well tolerated and effective in Japanese patients with T2DM who have inadequate glycaemic control on teneligliptin alone.
Cascading effects of herbivore protective symbionts on hyperparasitoids
Authors: MCLEAN AILSA H. C. , HRČEK JAN , PARKER BENJAMIN J. , GODFRAY H. CHARLES J. 
Published: June 2017

1. Microbial symbionts can play an important role in defending their insect hosts against natural enemies. However, researchers have little idea how the presence of such protective symbionts impacts food web interactions and species diversity.2. This study investigated the effects of a protective symbiont (Hamiltonella defensa) in pea aphids (Acyrthosiphon pisum) on hyperparasitoids, which are a trophic level above the natural enemy target of the symbiont (primary parasitoids).3. Pea aphids, with and without their natural infections of H. defensa, were exposed first to a primary parasitoid against which the symbiont provides partial protection (either Aphidius ervi or Aphelinus abdominalis), and second to a hyperparasitoid known to attack the primary parasitoid species.4. It was found that hyperparasitoid hatch rate was substantially affected by the presence of the symbiont. This effect appears to be entirely due to the removal of potential hosts by the action of the symbiont: there was no additional benefit or cost experienced by the hyperparasitoids in response to symbiont presence. The results were similar across the two different aphid–parasitoid–hyperparasitoid interactions we studied.5. It is concluded that protective symbionts can have an important cascading effect on multiple trophic levels by altering the success of natural enemies, but that there is no evidence for more complex interactions. These findings demonstrate that the potential influence of protective symbionts on the wider community should be considered in future food web studies.
Pupal colour dimorphism in a desert swallowtail (Lepidoptera: Papilionidae) is driven by changes in food availability, not photoperiod
Authors: PIÑONES‐TAPIA DANIEL , RIOS RODRIGO S. , GIANOLI ERNESTO 
Published: June 2017

1. The swallowtail butterfly Battus polydamas archidamas Boisduval, 1936, exhibits polyphenism for pupal coloration (green and brown). It is distributed across arid regions with winter rains and is monophagous on Aristolochia plants, which emerge after the winter rains and dry out the during summer. Thus, day length does not covary positively with host plant productivity. It was hypothesised that pupal colour was driven by food availability, not photoperiod. The benefits of pupal coloration matching the colour of pupation sites in terms of field survival were also investigated to evaluate the adaptive value of pupa colour.2. Larvae were reared under a factorial array of two photoperiods (LD 10:14 h and LD 14:10 h) and two food availability regimes (leaves ad libitum and available every other day) to assess the frequency of green and brown pupae. Field survival of green and brown pupae was quantified in three commonly used habitats that differ in background coloration (cacti, rocks and shrubs).3. Food availability determined pupal colour. Larvae in the ad libitum regime resulted mostly in green pupae, while those with restricted food were mostly brown. In contrast, photoperiod did not influence pupal colour. Survival probability of pupae placed on cacti was higher than those placed on rocks and shrubs, and the lowest predation risk across habitats was for green pupae on cacti.4. Food availability plays a major role in the seasonal polyphenism for pupal colour of specialist butterflies inhabiting arid environments with winter rains.
Less favourable climates constrain demographic strategies in plants
Authors: Csergő Anna M. , Salguero‐Gómez Roberto , Broennimann Olivier , Coutts Shaun R. , Guisan Antoine , Angert Amy L. , Welk Erik , Stott Iain , Enquist Brian J. , McGill Brian , Svenning Jens‐Christian , Violle Cyrille , Buckley Yvonne M. 
Published: June 2017

AbstractCorrelative species distribution models are based on the observed relationship between species’ occurrence and macroclimate or other environmental variables. In climates predicted less favourable populations are expected to decline, and in favourable climates they are expected to persist. However, little comparative empirical support exists for a relationship between predicted climate suitability and population performance. We found that the performance of 93 populations of 34 plant species worldwide – as measured by in situ population growth rate, its temporal variation and extinction risk – was not correlated with climate suitability. However, correlations of demographic processes underpinning population performance with climate suitability indicated both resistance and vulnerability pathways of population responses to climate: in less suitable climates, plants experienced greater retrogression (resistance pathway) and greater variability in some demographic rates (vulnerability pathway). While a range of demographic strategies occur within species’ climatic niches, demographic strategies are more constrained in climates predicted to be less suitable.
Prevalence of headshaking within the equine population in the UK
Authors: Ross S. E. , Murray J. K. , Roberts V. L. H. 
Published: June 2017

SummaryReason for performing studyHeadshaking in horses has been reported to be most commonly due to idiopathic neuropathic facial pain (trigeminal‐mediated headshaking). The prevalence of headshaking in horses in the UK is unknown.ObjectivesTo estimate owner‐reported prevalence of headshaking in horses in the UK and to report their case background and disease characteristics, as reported by owners.Study designCross‐sectional web based owner questionnaire.MethodsThe questionnaire was advertised online via social media, horse forums, veterinary websites and equestrian magazines from 17th June 2016, until >1000 responses had been obtained. All UK horse owners were eligible to complete the questionnaire, however only one questionnaire could be completed per owner.ResultsThe estimated prevalence of owner‐reported headshaking in the sample population of horses (n = 1014), within the last year, was 4.6% (95% confidence interval 3.5–6.1), whereas 6.2% (95% confidence interval 4.9–7.9) of horses were reported by their owners to have shown signs of headshaking at any time‐point since ownership. There was no association of sex or breed. Nineteen percent of headshaking horses were reported to show headshaking at rest. Fewer than one‐third (30.2%, n = 19) of headshaking horses had been examined by a veterinarian for headshaking. Of horses seen by a veterinarian, the cause for headshaking remained unknown in the majority of cases (57.9% responses) and trigeminal‐mediated headshaking was reported as a diagnosis in just one case.Main limitationsThe accuracy in data reporting by horse owners was not verified in this study. There may be a potential for bias towards over‐reporting due to the nature of survey participation.ConclusionsWithin this sample, owner‐reported prevalence of signs of headshaking within the last year, in horses in the UK was 4.6%. Over two‐thirds of owners of headshaking horses did not seek veterinary intervention for headshaking. Trigeminal‐mediated headshaking was rarely reported by owners as a diagnosis.
Investigation of bird strike events on composite wing panels
Authors: Diamantakos I. , Fotopoulos K. , Jamin M. , Eberhardt A. , Lampeas G. 
Published: June 2017

AbstractOne of the most important events during an aircraft's service life is the impact of a bird (ie, bird strike), which could possibly lead to catastrophic failure. According to airworthiness authorities, compliance of an aircraft structure to bird‐strike certification specifications can potentially be proved by simulation. In the present work, combined experimental and numerical investigations are performed, aiming to provide a validated numerical simulation tool for the certification of a composite leading edge structure. To increase the numerical simulation efficiency, the stacked shell approach in the frame of the finite element method is adopted. Comparison of numerical and experimental results shows that the proposed methodology is very promising for the simulation of impact events on complex composite structures. The proposed methodology has been applied for the development of a numerical tool for the simulation of bird strike on a composite leading edge structure.
Quantification of different effects occurring during fatigue tests on bituminous mixtures
Authors: Phan Cong Viet , Di Benedetto Hervé , Sauzéat Cédric , Dayde Josselin , Pouget Simon 
Published: June 2017

AbstractQuantification of different effects (nonlinearity, heating, thixotropy, and fatigue) occurring during fatigue tests on bituminous mixtures is presented in this paper. A focus is given on the nonlinearity phenomenon.Continuous fatigue tests and a test with specific protocol (called fatigue tests to estimate biasing effects) were performed in tension/compression mode on cylindrical samples of the same material. The analysis of results reveals that reversible effects (nonlinearity, heating, and thixotropy) are important (more than 90% decrease at 100,000 cycles for a strain amplitude of 100 μm/m at 10 Hz) and cannot be ignored when interpreting classical fatigue tests. The nonlinearity effects respect the time‐temperature superposition principle, and they are more pronounced at “high” temperature (at the same frequency). Direction of nonlinearity curve in the Cole‐Cole axes is shown to be independent of temperature and frequency for the considered range.
Influence of strain range on fatigue life reduction of stainless steel in PWR primary water
Authors: Kamaya Masayuki 
Published: June 2017

AbstractThe environmental effect in the pressurized water reactor (PWR) water was investigated for various applied strain range using a type 316 stainless steel. The tests were conducted using cylindrical hollow specimens at 325°C. It was shown that the ratio of the fatigue life in the PWR water environment to that in air was about 0.3 to 0.4 regardless of the strain range when the applied strain ranges were 0.8% or more. Crack growth rates identified from spacing of striations observed on fractured surfaces were used to demonstrate that the fatigue life reduction in the PWR water environment could be attributed to the crack growth acceleration. The fractured surface observations revealed that crack initiation was enhanced by the PWR water environment. On the other hand, the reduction in the fatigue life was not significant when the strain ranges were 0.5% and 0.44%, and the specimens did not fail when the strain ranges were 0.38% or less. It was deduced that the crack initiation was not enhanced for the relatively small strain range, and the crack growth was not accelerated. Since the fatigue limit of the test material was 0.4% in the strain range in air, it was concluded that the fatigue limit was not reduced in the PWR water environment.
Developing Potentiometric Surfaces and Flow Fields with a Head‐Specified MODFLOW Model
Authors: Abrams Daniel B. , Roadcap George S. , Mannix Devin 
Published: June 2017

AbstractInvestigating changes in an aquifer system often involves comparison of observed heads from different synoptic measurements, generally with potentiometric surfaces developed by hand or a statistical approach. Alternatively, head‐specified MODFLOW models, in which constant head cells simulate observed heads, generate gridded potentiometric surfaces that explicitly account for Darcy's Law and mass balance. We developed a transient head‐specified MODFLOW model for the stratified Cambrian‐Ordovician sandstone aquifer system of northeastern Illinois to analyze flow within its 275 m deep cone of depression. Potentiometric surfaces were developed using static heads from production wells regardless of open interval; hence assuming no vertical head difference. This assumption was tested against steady‐state, head‐specified models of each sandstone strata for 1980 and 2014. The results indicate that the original conceptual model was appropriate in 1980 but not 2014, where a vertical head difference had developed at the center of the cone of depression. For earlier years, when the head difference was minimal, the transient head‐specified model compared well with a traditional, flow‐specified model. In later years, the transient head‐specified model overestimated removal of water from storage. MODFLOW facilitates the development of a time‐series of potentiometric surfaces and can easily be modified to test the impacts of different conceptual models, such as assumptions on vertical head differences. For this study of a deep confined aquifer, MODFLOW also offers advantages in generating potentiometric surfaces and flow fields over statistical interpolation techniques, although future research is needed to assess its performance in other settings.
Commencement of cardioselective beta‐blockers during hospitalisation for acute exacerbations of chronic obstructive pulmonary disease
Authors: Neef Pieter A. , Burrell Louise M. , McDonald Christine F. , Irving Louis B. , Johnson Douglas F. , Steinfort Daniel P. 
Published: June 2017

AbstractBackgroundIn patients with chronic obstructive pulmonary disease (COPD) and co‐morbid cardiovascular disease, emerging evidence suggests a benefit in commencing cardioselective beta‐blockers.AimOur objective was to determine the safety of beta‐blocker commencement during hospitalisation for acute exacerbation ofCOPD.MethodsA retrospective cohort study of 1071 patients hospitalised for acute exacerbation ofCOPDwas conducted across two tertiary hospitals over a 12‐month period. We identified 36 patients in whom beta‐blocker therapy was commenced during admission. The primary outcome of the study was to assess cardiovascular and respiratory adverse events related to the commencement of beta‐blocker therapy.ResultsThe most common indications for beta‐blockers were atrial fibrillation (53%) and acute coronary syndrome (36%). Metoprolol was the most commonly prescribed beta‐blocker (75%). No patients suffered clinically significant declines of respiratory function following the commencement of a beta‐blocker, including worsening respiratory symptoms, oxygen, bronchodilator or ventilation requirements. These results were demonstrable in patients with reversible airways disease and advancedCOPD. Only one patient (2.8%) experienced symptomatic hypotension after 48 h of therapy.ConclusionThe commencement of cardioselective beta‐blockers during acute exacerbations ofCOPDappears to be well‐tolerated.