bluuebunny/crossref_metadata_2025_split huggingface dataset:
Low free drug concentration prevents inhibition of F508del CFTR functional expression by the potentiator VX‐770 (ivacaftor)
Authors: Matthes Elizabeth , Goepp Julie , Carlile Graeme W , Luo Yishan , Dejgaard Kurt , Billet Arnaud , Robert Renaud , Thomas David Y , Hanrahan John W 
Published: October 2015

Background and PurposeThe most common cystic fibrosis (CF) mutation F508del inhibits the gating and surface expression of CFTR, a plasma membrane anion channel. Optimal pharmacotherapies will probably require both a ‘potentiator’ to increase channel open probability and a ‘corrector’ that improves folding and trafficking of the mutant protein and its stability at the cell surface. Interaction between CF drugs has been reported but remains poorly understood.Experimental ApproachCF bronchial epithelial cells were exposed to the corrector VX‐809 (lumacaftor) and potentiator VX‐770 (ivacaftor) individually or in combination. Functional expression of CFTR was assayed as the forskolin‐stimulated short‐circuit current (Isc) across airway epithelial monolayers expressing F508del CFTR.Key ResultsThe potentiated Isc response during forskolin stimulation was increased sixfold after pretreatment with VX‐809 alone and reached ~11% that measured across non‐CF monolayers. VX‐770 (100 nM) and genistein (50 μM) caused similar levels of potentiation, which were not additive and were abolished by the CFTR inhibitor CFTRinh‐172. The unbound fraction of VX‐770 in plasma was 0.13 ± 0.04%, which together with previous measurements in patients given 250 mg p.o. twice daily, suggests a peak free plasma concentration of 1.5–8.5 nM. Chronic exposure to high VX‐770 concentrations (>1 μM) inhibited functional correction by VX‐809 but not in the presence of physiological protein levels (20–40 mg·mL−1). Chronic exposure to a low concentration of VX‐770 (100 nM) together with VX‐809 (1 μM) also did not reduce the forskolin‐stimulated Isc, relative to cells chronically exposed to VX‐809 alone, provided it was assayed acutely using the same, clinically relevant concentration of potentiator.Conclusions and ImplicationsChronic exposure to clinically relevant concentrations of VX‐770 did not reduce F508del CFTR function. Therapeutic benefit of VX‐770 + VX‐809 (Orkambi) is probably limited by the efficacy of VX‐809 rather than by inhibition by VX‐770.
The production of unequal vulnerability to flood hazards: A conceptual framework for hazards research in Canada's cities
Authors: Oulahen Greg 
Published: October 2015

Key Messages

Flood risk is a growing concern in Canada's cities but residents have differential risk.
Factors related to societal structural forces, human agency, and place interact to produce unequal vulnerability to hazards.
This review essay provides a conceptual framework for looking across scales and across actors to identify and situate the factors that influence vulnerability to flood hazards in Canada's cities.
The prevalence of developmental delay among children aged 3–60 months in Izmir, Turkey
Authors: Demirci A. , Kartal M. 
Published: October 2015

AbstractBackgroundsDevelopmental delay is defined as delays in speech and language development, motor development, social‐emotional development and cognitive development. On a global scale, the prevalence estimations in paediatric population range between 5% and 15%. However, no prevalence studies on developmental delay have been conducted in primary care in Turkey. The aim of this study was to determine the prevalence of developmental delay among children aged 3–60 months in Izmir.MethodsThis cross‐sectional, descriptive study involved 1514 children aged 3–60 months, who were at 12 primary health centres for various reasons in Izmir between 1 November 2013 and 31 January 2014. The questionnaire and age‐specific Turkish version of the Ages and Stages Questionnaires were applied to mothers via face‐to‐face interview.ResultsThe prevalence of developmental delay was 6.4% (95% confidence interval 5.2–7.7). The prevalence for age groups varied between 3.3% and 12.1%. Significant associations were found between developmental delay and maternal age, maternal/paternal education, socio‐economic level of the family and the presence of consanguineous marriage.ConclusionsIdentifying developmental delay in children earlier by a validated, reliable, parent‐completed questionnaire like Ages and Stages Questionnaires and detecting risk factors for delay are crucial for primary care where their growth and development are monitored. Identifying developmental delay and early referral to rehabilitation services may help improve children's quality of life.
The nature of peer‐directed behaviours in children with profound intellectual and multiple disabilities and its relationship with social scaffolding behaviours of the direct support worker
Authors: Nijs S. , Vlaskamp C. , Maes B. 
Published: October 2015

AbstractBackgroundThe multiple and complex disabilities of persons with profound intellectual and multiple disabilities (PIMD) form a barrier for peer interactions and peer‐directed behaviours. In this study, we further explore the nature of peer‐directed behaviours in persons with PIMD and its relationship with social scaffolding behaviour of direct support workers (DSWs).MethodsFourteen dyads of children with PIMD, who knew each other for at least 12 months, participated. They were sitting in close proximity while they were filmed with and without the presence of the DSW. Video recordings were coded continuously making use of observation schemes for the peer‐directed behaviours of the children and the peer interaction influencing behaviours of the DSW.ResultsSignificantly more singular peer‐directed behaviour (without DSW: 18.00%; with DSW: 3.81%) was observed than multiple peer‐directed behaviour (without DSW: 4.01%; with DSW: 0.52%). The amount of time the singular and multiple peer‐directed behaviours were observed was significantly lower in the presence of a DSW. When the DSW shows peer interaction influencing behaviour, it was mostly social scaffolding behaviour (2.17%). The conditional probability of observing social scaffolding behaviour in the 10 s following on singular peer‐directed behaviour was 0.02 with a Yule's Q of 0.04 and following on multiple peer‐directed behaviour 0.04 with a Yule's Q of 0.33.ConclusionThe way in which peer interactions in children with PIMD are defined could have an impact on the amount of observed peer‐directed behaviours and on the effect of the social scaffolding behaviours presented by DSW.
Factors that influence outcomes in cochlear implantation in adults, based on patient‐related characteristics – a retrospective study
Authors: Kraaijenga V.J.C. , Smit A.L. , Stegeman I. , Smilde J.J.M. , van Zanten G.A. , Grolman W. 
Published: October 2015

ObjectiveOutcomes in speech perception following cochlear implantation in adults vary widely. Many studies have been carried out to identify and quantify factors that influence outcomes. This study adds a new dimension to pre‐existing literature.DesignSingle‐centre retrospective cohort study.SettingUniversity Medical Center Utrecht, the Netherlands.ParticipantsA total of 428 adults with bilateral severe‐to‐profound sensorineural hearing loss, unilaterally implanted between February 1988 and March 2014.Main outcome measuresUnivariable and multivariable linear regression analyses were carried out to identify factors that may influence outcome after cochlear implantation. Consonant‐vowel‐consonant word scores were recorded pre‐ and post‐implant and were used as outcome measure in two groups of patients (prelingually and postlingually deafened adults). As an added dimension, multiple imputation was implemented and evaluated to tackle 4% (17/407) missing data.ResultsFor postlinguals, pre‐implant speech perception score and age at onset of deafness are positive predictors and meningitis and otosclerosis as cause of deafness are negative predictors of post‐implant speech perception. This model accounted for 26% of variance. For prelinguals, pre‐implant speech perception score is the only strong positive predictor (β 0.524; P < 0.001). This model accounted for 31% of variance. Age at implantation was not a significant predictor in either group.ConclusionsSpeech perception is predicted by pre‐implant speech perception, age at onset of deafness and aetiology (meningitis and otosclerosis) for postlinguals and solely pre‐implant speech perception for prelinguals. Age at implantation is of lesser importance in predicting speech perception outcome post‐implant. Multiple imputation is a useful statistical technique when analysing incomplete data sets.
A SPoARC in the Dark: Spatialization in Verbal Immediate Memory
Authors: Guida Alessandro , Leroux Aurélie , Lavielle‐Guida Magali , Noël Yvonnick 
Published: October 2015

AbstractIn 2011, van Dijck and Fias described a positional SNARC (Spatial‐Numerical Association of Response Codes) effect: the SPoARC (Spatial‐Positional Association of Response Codes). To‐be‐remembered items (e.g., numbers, words) presented centrally on a screen seemed to acquire a left‐to‐right spatial dimension. If confirmed, this spatialization could be crucial for immediate memory theories. However, given the intricate links between visual and spatial dimensions, this effect could be due to the visual presentation (on a computer screen), which could have probed the left‐to‐right direction of reading/writing. To allow a generalization of this effect, we adapted van Dijck and Fias's (2011) task using an auditory version of Sternberg's paradigm. Lists of five consonants were auditorily presented at a rate of 3 s/item. A SPoARC effect was observed. The consequences are discussed first from an immediate memory perspective, putting forward the view that order could be coded through spatialization, and then in terms of similarities between SPoARC and SNARC.
Past landscape explains forest periphery‐to‐core gradient of understorey plant communities in a reforestation context
Authors: Bergès Laurent , Avon Catherine , Arnaudet Lucie , Archaux Frédéric , Chauchard Sandrine , Dupouey Jean‐Luc 
Published: October 2015

AbstractAimTo disentangle whether long‐range periphery‐to‐core gradient of forest understorey plants could be attributed to past forest landscape and/or to current environmental filtering processes. We investigated (1) whether species response to past land use (ancientversusrecent forest) was consistent with species response to distance to present forest edge (coreversusperiphery) (2) what life‐history traits explained plant response to distance to present edge and past land use (3) whether distance to past forest edge explained current species distribution better than distance to present forest edge.LocationTemperate forests in the northern half of France (80,000 km²).MethodsLocal climate, soil and stand characteristics, past land use, and present and past landscape metrics were collected on 11,936 plots using National Forest Inventory data and historical maps from 1831. Logistic regressions were applied to determine the response patterns of 181 species to present and past landscape, while controlling for local habitat quality (soil, climate and stand).ResultsSpecies response to distance to present edge very well matched response to past land use. Plant traits related to colonization capacity explained species response to present edge and past land use. The spatial distribution of 42 species was better explained by distance to forest edge in 1831, 37 species were better explained by distance to present edge and 24 species were better explained by distance to present edge and past land use.Main conclusionsTwo mechanisms were responsible for the long‐range periphery‐to‐core gradient: (1) past landscape and colonization processes and (2) present edge‐related mechanisms. This suggests that plant community differences between periphery and core zones are thus related to dispersal limitation and not only to environmental filters. Our results underline the need to combine landscape ecology and history and have important implications for forest plant dynamics and conservation in the context of climate change.
Effect of socioeconomic status (SES) disparity on neural development in female African‐American infants at age 1 month
Authors: Betancourt Laura M. , Avants Brian , Farah Martha J. , Brodsky Nancy L. , Wu Jue , Ashtari Manzar , Hurt Hallam 
Published: October 2015

AbstractThere is increasing interest in both the cumulative and long‐term impact of early life adversity on brain structure and function, especially as the brain is both highly vulnerable and highly adaptive during childhood. Relationships between SES and neural development have been shown in children older than age 2 years. Less is known regarding the impact of SES on neural development in children before age 2. This paper examines the effect of SES, indexed by income‐to‐needs (ITN) and maternal education, on cortical gray, deep gray, and white matter volumes in term, healthy, appropriate for gestational age, African‐American, female infants. At 5 weeks postnatal age, unsedated infants underwent MRI (3.0T Siemens Verio scanner, 32‐channel head coil). Images were segmented based on a locally constructed template. Utilizing hierarchical linear regression, SES effects on MRI volumes were examined. In this cohort of healthy African‐American female infants of varying SES, lower SES was associated with smaller cortical gray and deep gray matter volumes. These SES effects on neural outcome at such a young age build on similar studies of older children, suggesting that the biological embedding of adversity may occur very early in development.
A multi‐center, multinational age‐ and gender‐adjusted normative dataset for immunofluorescent intraepidermal nerve fiber density at the distal leg
Authors: Provitera V. , Gibbons C. H. , Wendelschafer‐Crabb G. , Donadio V. , Vitale D. F. , Stancanelli A. , Caporaso G. , Liguori R. , Wang N. , Santoro L. , Kennedy W. R. , Nolano M. 
Published: October 2015

Background and purposeQuantification of intraepidermal nerve fibers (IENFs) in skin biopsies is now the tool of choice to diagnose small fiber neuropathies. An adequate normative dataset, necessary to assess normality cutoffs, is available for brightfield microscopy but not for immunofluorescence.MethodsIntraepidermal nerve fiber density data in distal leg skin samples processed with immunofluorescence were collected from 528 healthy individuals from four experienced laboratories worldwide. In all laboratories skin samples were collected, processed and analyzed according to standard procedures. Quantile regression analysis was employed to tailor the fit of the 5° percentile as the normal cutoff value and to test and measure the effect of age, gender, body mass index, race, biopsy site (lateral distal lower leg or medial posterior mid‐calf) and participating laboratory as possible influential variables.ResultsAge, gender and biopsy site showed an independent linear correlation with IENF density. For each decade the 5° quantile IENF cutoff showed a 0.54 fibers/mm decrease, whilst females exhibited a 1.0 fiber/mm cutoff greater than males. Compared to the lateral distal lower leg, biopsies from the calf showed a 3.4 fibers/mm lower 5° percentile cutoff, documenting a variation linked by site.ConclusionsAn age‐ and gender‐adjusted normative dataset for IENF density at the lateral distal lower leg obtained with indirect immunofluorescence is presented for the first time by sharing data from four experienced laboratories worldwide. This dataset can be used as reference for laboratories processing skin biopsies with this technique.
Facial varicosity affecting the lower eyelid of a horse
Authors: Reardon R. J. M. , Dixon P. M. , Kane‐Smyth J. 
Published: October 2015

SummaryA 12‐year‐old Clydesdale cross mare was referred for investigation of right periocular vascular distension. Physical examination and ultrasonography confirmed the presence of a varicosity of the veins of the lower eyelid and transverse facial vein. The size of the varicose vein led to concerns about the potential progression in size of the lower eyelid to obstruct vision. Percutaneous encircling sutures were ineffective at occluding the vessel and surgical excision of the abnormal vein was performed. This treatment approach proved effective and 7 months post operatively the swelling has not recurred. This case demonstrates that varicosities can be successfully surgically resected in horses if there is a clinical indication.
Are strong fire–vegetation feedbacks needed to explain the spatial distribution of tropical tree cover?
Authors: Good Peter , Harper Anna , Meesters Antoon , Robertson Eddy , Betts Richard 
Published: October 2015

AbstractAimThe spatial pattern of tropical fire‐induced tree mortality is partly determined by climate, but feedbacks of tree cover on fire are also important. We re‐examine some recent observations proposed as evidence for very strong tree‐cover feedbacks on fire, sufficient to allow savanna and forest to be alternative stable states over large areas of the tropics. Two pieces of previously reported observational evidence are examined: (1) the trimodal statistical distribution of tropical tree fraction, and (2) the fact that different tree fractional cover is found at different locations in the tropics with similar rainfall.LocationGlobal tropics.MethodsFor point (1) above we analyse the statistical distribution of tree fraction predicted by the logistic equation of tree growth and self‐competition, with spatially varying mortality rates. For (2), the relationship between mean annual rainfall and mean net primary productivity (NPP) in a climate model is examined.Results(1) A trimodal distribution of tree cover does not necessarily require tree‐cover feedback on fire. It can arise from a combination of two factors: nonlinearities in vegetation dynamics and climate‐driven spatial variation in mortality (the intermediate fire–productivity hypothesis). (2) Different locations in the tropics can have identical rainfall but significantly different NPP, even with no feedback of tree cover on fire.Main conclusionsOur results show that strong tree‐cover feedback on fire is not necessary to explain observations (1) and (2). However, it is still possible that strong fire–vegetation feedback is the primary explanation – our results do not rule this out. We simply demonstrate the possibility of an alternative hypothesis (of strong climate control). In reality, it is likely that both tree‐cover feedback and climate contribute. It is challenging to separate these two effects cleanly. More work is needed to quantify their separate effects. We show that plots of mortality versus productivity are useful tools for understanding spatial variations in tree cover.
An application of Kleene's fixed point theorem to dynamic programming
Authors: Kamihigashi Takashi , Reffett Kevin , Yao Masayuki 
Published: October 2015

AbstractWe show that the least fixed point of the Bellman operator in a certain set can be computed by value iteration whether or not the fixed point is the value function. As an application, we give a simpler proof of one of Kamihigashi's main results.
Population‐dependent acclimatization capacity of thermal tolerance in larvae of the rocky‐shore barnaclePollicipes elegans
Authors: Crickenberger Sam , Walther Kathleen , Marchant Sergio , Marko Peter B. , Moran Amy L. 
Published: October 2015

AbstractAs environmental temperatures increase and become more seasonally variable, the ability of individuals to plastically alter their physiological responses to temperature (=acclimatize) may affect the potential for species persistence. Among marine organisms, the larval stage is often the most physiologically sensitive; larvae are also often the main dispersal stage in the life history. However, studies that address the acclimatization of marine larvae are rare. We investigated whether larvae of the gooseneck barnaclePollicipes elegansfrom two temperate populations, one from the Northern Hemisphere (Mexico) and one from the Southern Hemisphere (Peru), show patterns of seasonal acclimatization to temperature. We compared the effects of temperature on swimming activity, oxygen consumption, and mortality of larvae from the two populations in both warm and cold seasons. Larvae from Mexico had higher thermal tolerances when collected in the boreal summer compared to the boreal winter, while no similar indication of seasonal acclimatization was seen in larvae from Peru. The lack of acclimatization in larvae ofP. elegansfrom Peru may be related to recent thermal history, low selection for acclimatization due to irregular patterns of seasonal temperature change duringENSOevents, or to different phylogeographic histories of Northern‐ and Southern‐hemisphere populations.
Chasing the Mirage: a grounded theory of the clinical reasoning processes that Registered Nurses use to recognize delirium
Authors: El Hussein Mohamed , Hirst Sandra 
Published: October 2015

AbstractAimThe aim of this study was to construct a grounded theory that explains the clinical reasoning processes that registered nurses use to recognize delirium in older adults in acute care hospitals.BackgroundDelirium is under‐recognized in acute hospital settings, this may stem from underdeveloped clinical reasoning processes. Little is known about registered nurses’ (RNs) clinical reasoning processes in complex situations such as delirium recognition.DesignA grounded theory approach was used to analyse interview data about the clinical reasoning processes of RNs in acute hospital settings.MethodSeventeen RNs were recruited. Concurrent data collection and comparative analysis and theoretical sampling were conducted in 2013–2014.FindingsThe core category to emerge from the data was ‘chasing the mirage’, which describes RNs’ clinical reasoning processes to recognize delirium during their interaction with older adults.ConclusionUnderstanding the reasoning that contributes to delirium under‐recognition provides a strategy by which, this problem can be brought to the forefront of RNs’ awareness and intervention. Delirium recognition will contribute to quality care for older adults.
Fostering critical thinking and reflection through blog‐mediated peer feedback
Authors: Novakovich J. 
Published: October 2015

AbstractThe introduction of digital literacy practices has created a tension in academia, with many academics challenging the view that critical thinking can be fostered on social networks. A quasi‐experimental study was conducted on two sections of university‐level writing classrooms to determine if there were meaningful differences in the quality of writing and peer feedback generated through in‐class draft workshops using traditional methods as compared to draft workshops using a blogging platform. The results indicated that blogs produced a higher quality of writing as measured by grades, f(42) = 11.512, p < .002 and acceptance scores, f(42) = 8.364, p < .006. Furthermore, blog‐mediated peer workshops produced a statistically significantly higher number of critical comments, f(42) = 120.438, p < .000; and directive comments, f(42) = 33.861, p < .000. There were no statistically significant differences in the number of editing comments, f(42) = .001, p < .974, and traditional draft workshops produced a statistically significant higher number of naïve comments, f(42) = 14.119, p < .001. Within the study, critical comments were found to correlate positively with learning outcomes, b = 1.115, t(41) = 2.716, p < .01. The findings suggest that blogging software improved learner performance and fostered complex literacy skills.