bluuebunny/crossref_metadata_2025_split huggingface dataset:
Opinions and potential solutions regarding dissemination bias from funding agencies of biomedical research in Europe
Authors: Pardo‐Hernandez Hector , Urrútia Gerard , Meerpohl Joerg J. , Marušić Ana , Wager Elizabeth , Bonfill Xavier ,   on behalf of the OPEN Project Consortium
Published: January 2017

AbstractRationale, aims, and objectivesSeveral studies have found that about half of research results from clinical trials are never published. Until now, there has been little information on the views that funding agencies of biomedical research in Europe have regarding this issue and its possible solutions.MethodsAn electronic survey was conducted among funding agencies from 34 European countries. Participants were asked about their opinions, policies, and potential solutions regarding dissemination bias. On the basis of the results of this survey and the input of the OPEN Consortium and of representatives of stakeholder groups in the knowledge generation process, we formulated recommendations for funding agencies to reduce dissemination bias.ResultsWe received responses from 64 funding agencies of biomedical medicine from most European countries, out of 245 that were contacted (26%). Of these, 56 funded research at the national and/or international level and were therefore eligible to participate. Policies encouraging publication increased over time: 33 (58.9%) of agencies enforced them in 2005 compared to 38 (67.6%) in 2012. However, only 13 (23.2%) had knowledge of the publications related to research funded in 2005, 23 (41.1%) were able to provide only an estimate, and 20 (35.7%) did not know at all. Regarding recommendations to control dissemination bias, we propose that funding agencies request the dissemination of research results irrespective of the direction of findings. We also call for measures that allow evaluating funded projects past the contractual period and until dissemination of results. Funding agencies should create publicly accessible databases with information on funded projects and dissemination efforts.ConclusionDespite having policies to encourage publication of results, most funding agencies fail to implement such measures or to ensure compliance. We propose recommendations that could be incorporated in the blueprint of calls for proposals and contracts agreed upon by funding agencies and grant recipients.
Notes on the use of randomised controlled trials to evaluate complex interventions: Community treatment orders as an illustrative case
Authors: Mustafa Feras Ali 
Published: January 2017

AbstractOver the past seven decades, randomised controlled trials (RCTs) have revolutionised clinical research and achieved a gold standard status. However, extending their use to evaluate complex interventions is problematic. In this paper we will demonstrate that complex intervention RCTs violate the necessary premises that govern the RCTs logic and underpin their rigour. The lack of blinding, heterogeneity of participants, as well as poor treatment standardisation and difficulty of controlling for confounders, which characterise complex intervention RCTs, can potentially be profoundly detrimental to their integrity. Proponents of this approach argue that matching “real world” circumstances, while maintaining the randomised design, enhances external validity. We counter this argument by pointing out that an inverted U relation exists between internal and external validity, and thus relaxing the experimental conditions beyond a certain threshold can potentially paradoxically render the RCT externally invalid, i.e. its results cannot be used anywhere. We shall illustrate the inappropriate use of RCTs to evaluate community treatment orders and propose an alternative epistemic model that is based on mechanistic reasoning and Cartwright's capacity concept.
Effect of prucalopride on intestinal gas tolerance in patients with functional bowel disorders and constipation
Authors: Malagelada Carolina , Nieto Adoración , Mendez Sara , Accarino Anna , Santos Javier , Malagelada Juan‐R , Azpiroz Fernando 
Published: January 2017

AbstractBackground and AimPatients with functional bowel disorders develop gas retention and symptoms in response to intestinal gas loads that are well tolerated by healthy subjects. Stimulation of 5HT‐4 receptors in the gut has both prokinetic and antinociceptive effects. The aim of this study is to determine the effect of prucalopride, a highly selective 5HT‐4 agonist, on gas transit and tolerance in women with functional bowel disorders complaining of constipation.MethodsTwenty‐four women with functional bowel disorders complaining of constipation were included in the study. Patients were studied twice on separate days in a cross‐over design. On each study day, an intestinal gas challenge test was performed. During the five previous days, prucalopride (2 mg/day) or placebo was administered. Abdominal symptoms, stool frequency, and stool consistency were recorded during the treatment period on daily questionnaires.ResultsDuring the gas challenge test, prucalopride did not decrease the volume of gas retained in the subset of patients who had significant gas retention (≥ 200 mL) while on placebo. However, in those patients who had increased symptoms during the gas test (≥ 3 on a 0 to 6 scale) when on placebo, prucalopride did significantly reduce the perception of symptoms (2.3 ± 0.5 mean score vs 3.5 ± 0.3 on placebo; P = 0.045).During the treatment period with prucalopride, patients exhibited an increase in the total number of bowel movements and decreased stool consistency compared with placebo.ConclusionPrucalopride reduces abdominal symptoms without modifying gas retention when patients with functional bowel disorders are challenged with the gas transit and tolerance test. European Clinical Trials Database (EudraCT2011‐006354‐86).
Changes in objectively measured physical activity in adolescents with Down syndrome: the UP&DOWN longitudinal study
Authors: Izquierdo‐Gomez R. , Martinez‐Gómez D. , Esteban‐Cornejo I. , Hallal P. C. , García‐Cervantes L. , Villagra A. , Veiga O. L. ,   on behalf of the UP&DOWN study group
Published: January 2017

AbstractBackgroundIt is a priority to understand that physical activity behaviour over time is a priority in Down syndrome population in order to design and promote succesfull interventions to maintain or increase levels of physical activity. We aimed to study 1 and 2‐year changes in objectively measured physical activity among a relatively large sample of adolescents with Down syndrome.MethodsThis study comprised a total of 99 adolescents with Down syndrome (38 girls) aged from 11 to 20 years old at baseline. Participants with valid accelerometer data at baseline and at least one of the follow‐up visits were included in the analysis.ResultsOverall, levels of physical activity observed in adolescents with Down syndrome declined from baseline to follow‐ups, but these changes were not significant (all P > 0.05). Moderate‐to‐moderately high tracking of physical activity was observed in adolescents with Down syndrome (all P < 0.001). Youths who met physical activity guidelines at baseline demonstrated a greater decline in physical activity in 1 and 2‐year changes (P < 0.05), although they were also more likely to meet physical activity guidelines at 1 and 2‐year follow‐ups (P < 0.05).ConclusionsAdolescents with Down syndrome do not change their levels of physical activity at 2‐year follow‐ups, but those who met physical activity guidelines presented stronger declines in physical activity over time.
The Mandarin Chinese version of the Beach Centre Family Quality of Life Scale: development and psychometric properties in Taiwanese families of children with developmental delay
Authors: Chiu S. ‐J. , Chen P. ‐T. , Chou Y. ‐T. , Chien L. ‐Y. 
Published: January 2017

AbstractBackgroundEarly intervention (EI) practitioners provide individualised family‐centred services to enhance the quality of life (QOL) of families of children with developmental delay (DD). Family QOL (FQOL) could be an important outcome indictor for EI, but there is no measurement tool for FQOL in Mandarin Chinese. The purpose of this study was to translate the Beach Centre FQOL Scale (BCFQOL) into Mandarin Chinese and to examine the psychometric properties of the scale in families of children with DD.MethodsTwo independent translations were performed by two bilingual professors whose mother tongue was Mandarin, and two back‐translations were performed by two bilingual professionals whose mother tongue was English. The translated and back‐translated questionnaires were reviewed to revise the questionnaire. Five experts assessed the accuracy, equivalence and cultural appropriateness of the scale, and 10 parents of children with DD were interviewed to examine its readability, clarity and cultural appropriateness. From July to November 2014, we recruited 360 primary caregivers of children with DD who were receiving EI in northern Taiwan to validate the scale. The participants completed the BCFQOL as well as a one item overall ratings of their FQOL.ResultsItem analysis was performed to assess each item. Confirmatory factor analysis supported the following five‐factor structure as in the original scale: family interaction, parenting, emotional well‐being, physical/material well‐being and disability‐related support. The scale exhibited excellent internal consistency reliability (Cronbach's alpha = 0.96) and test–retest reliability at a 2‐week interval (intra‐class correlation coefficient = 0.92). Contrasted group validity was supported by significantly higher BCFQOL scores in the top quartile of the overall FQOL rating than the lowest quartile. The convergent validity was supported by the significant correlation between the FQOL item and the BCFQOL (r = 0.608, p < 0.01).ConclusionsThis study showed that the Mandarin Chinese version of the BCFQOL is reliable and valid for Taiwanese families of children with DD. The instrument could be applied to assess FQOL in families of children with DD who are receiving EI in order to evaluate family services and supports.
Immune modulation by the hepatitis C virus core protein
Authors: Fernández‐Ponce C. , Dominguez‐Villar M. , Muñoz‐Miranda J. P. , Arbulo‐Echevarria M. M. , Litrán R. , Aguado E. , García‐Cozar F. 
Published: January 2017

SummaryHepatitis C virus (HCV) infection is currently the most important cause of chronic viral hepatitis in the world and one of the most frequent indications for liver transplantation. HCV uses different strategies to evade the innate and adaptive immune response, and this evasion plays a key role in determining viral persistence. Several HCV viral proteins have been described as immune modulators. In this review, we will focus on the effect of HCV nucleocapsid core protein in the function of immune cells and its correlation with the findings observed in HCV chronically infected patients. Effects on immune cell function related to both extracellular and intracellular HCV core localization will be considered. This review provides an updated perspective on the mechanisms involved in HCV evasion related to one single HCV protein, which could become a key tool in the development of new antiviral strategies able to control and/or eradicate HCV infection.
Species differences in hepatic biotransformation of the anthelmintic drug flubendazole
Authors: Maté M. L. , Geary T. , Mackenzie C. , Lanusse C. , Virkel G. 
Published: January 2017

Flubendazole (FLBZ) is a broad‐spectrum benzimidazole anthelmintic used in pigs, poultry, and humans. It has been proposed as a candidate for development for use in elimination programmes for lymphatic filariasis and onchocerciasis in humans. Moreover, FLBZ has shown promise in cancer chemotherapy, particularly for neuroblastoma. This work investigated the hepatic carbonyl‐reducing pathway of FLBZ in different species, including humans. Microsomal and cytosolic fractions were obtained from sheep, cattle, pig, hen, rat, and human liver. Both subcellular fractions of each species converted FLBZ into a reduced metabolite (red‐FLBZ). The rate of microsomal red‐FLBZ production was highest in sheep (1.92 ± 0.13 nmol/min.mg) and lowest in pigs (0.04 ± 0.02 nmol/min.mg); cytosolic red‐FLBZ production ranged from 0.02 ± 0.01 (pig) to 1.86 ± 0.61 nmol/min.mg (sheep). Only subcellular fractions from sheep liver oxidized red‐FLBZ to FLBZ in a NADP+‐dependent oxidative reaction. Liver microsomes from both pigs and humans transformed FLBZ to red‐FLBZ and a hydrolyzed metabolite. Very significant differences in the pattern of FLBZ metabolism were observed among the tested species and humans. These results reinforce the need for caution in extrapolating data on metabolism, efficacy, and safety of drugs derived from studies performed in different species.
Autumn and winter feeding ecology of waterfowl at the Ouse Washes, England
Authors: Thomas G. J. 
Published: January 2017

The potential foods available to waterfowl at the Ouse Washes in autumn and winter are described. All were commonly found in the river, pool, marsh and flooded grassland habitats of the washes and in the surrounding arable fields. Gadwall Anas strepera, Wigeon A. penelope, Moorhen Gallinula chloropusand Coot Fulica atramainly consumed vegetative foods, especially the leaves of grasses and in the case of the first named, water plants. Mallard A. platyrhynchos, Pintail A. acuta, Teal A. crecca, Pochard Aythya ferinaand Moorhen fed extensively on fruits and seeds with the first three species supplementing their diets with cereal grains from stubbles. Shoveler A. clypeata, Tufted duck Aythya fuligula, Pochard and Moorhen consumed the largest amounts of invertebrates. Within these three groupings there were further interspecific differences in diet. With most species diets also differed under low and high floods, being most similar under the latter. Amongst the dabbling ducks Anasspp. there were differences, probably minor, in foods taken attributable to differences in the bill lamellae on the outer margins of the upper jaw.The feeding methods used under low and high floods are described and some differences may further serve to ecologically separate the waterfowl. There was a high degree of adaptability, especially amongst the dabbling ducks, with some species changing the feeding postures completely under high floods. All species fed diurnally. Wigeon, Gadwall, Coot and Moorhen all fed for at least 90% of the daylight hours. Shoveler, Teal, Mallard and Pintail were most active in the mornings and afternoons. A partially objective analysis of ecological niches shows that all but two species pairs were clearly separated by either habitat or food factors. There is some overlap between Pochard and Tufted duck and greater overlap between Mallard and Pintail. This may be because they are utilizing the temporarily abundant foods present at this site.
The breeding biology of magpies Pica pica in an urban environment
Authors: Tatner Paul 
Published: January 2017

The colonisation of British cities by magpies is a recent phenomenon. This work presents an analysis of magpie breeding biology in the urban environment of south Manchester; laying date, nesting success, clutch size, incubation period, hatching success and nestling success have been investigated and where possible, are contrasted with the situation in rural areas.A proportion of magpies in Manchester renovate an old nest for the breeding attempt, a habit which is uncommon in rural populations. As a result of this, the average laying date for urban magpies is advanced relative to that of the surrounding rural areas. Another aspect of the urban breeding ecology which differed from that of rural magpies was the high frequency and success rate of repeat breeding attempts following an initial failure. These increased fledgling productivity by 25%, so that the average annual breeding sucess in the Manchester urban environment was 1·55 young per pair, which is one of the highest recorded for the magpie.
Network structure and local adaptation in co‐evolving bacteria–phage interactions
Authors: Gurney James , Aldakak Lafi , Betts Alex , Gougat‐Barbera Claire , Poisot Timothée , Kaltz Oliver , Hochberg Michael E. 
Published: January 2017

AbstractNumerous theoretical and experimental studies have investigated antagonistic co‐evolution between parasites and their hosts. Although experimental tests of theory from a range of biological systems are largely concordant regarding the influence of several driving processes, we know little as to how mechanisms acting at the smallest scales (individual molecular and phenotypic changes) may result in the emergence of structures at larger scales, such as co‐evolutionary dynamics and local adaptation. We capitalized on methods commonly employed in community ecology to quantify how the structure of community interaction matrices, so‐called bipartite networks, reflected observed co‐evolutionary dynamics, and how phages from these communities may or may not have adapted locally to their bacterial hosts. We found a consistent nested network structure for two phage types, one previously demonstrated to exhibit arms race co‐evolutionary dynamics and the other fluctuating co‐evolutionary dynamics. Both phages increased their host ranges through evolutionary time, but we found no evidence for a trade‐off with impact on bacteria. Finally, only bacteria from the arms race phage showed local adaptation, and we provide preliminary evidence that these bacteria underwent (sometimes different) molecular changes in the wzy gene associated with the LPS receptor, while bacteria co‐evolving with the fluctuating selection phage did not show local adaptation and had partial deletions of the pilF gene associated with type IV pili. We conclude that the structure of phage–bacteria interaction networks is not necessarily specific to co‐evolutionary dynamics, and discuss hypotheses for why only one of the two phages was, nevertheless, locally adapted.
Thinking About a Word—Love, for Example
Authors: Forsberg Niklas 
Published: January 2017

AbstractWhat is it we do when we philosophize about a word? How are we to act as we ask the philosophical question par excellence, “What is … ?” These questions are addressed here with particular focus on Troy Jollimore's Love's Vision and contemporary theories of love. Jollimore's rationalist account of love, based on a specific understanding of “reasons for love,” illustrates a particular philosophical mistake: When we think about a word, we are prone to believe that even though “the sense of the word” that we investigate may be up for grabs, the other words we use when we do these investigations are not. Jollimore's exploration of love is guided by specific conceptions of “reasons” and “rationality” that remain unquestioned. The article argues that we may have to rethink a great number of words as we embark on the task of uncovering the sense of one word.
Extensive Philosophical Agreement and Progress
Authors: Frances Bryan 
Published: January 2017

AbstractThis article argues, first, that there is plenty of agreement among philosophers on philosophically substantive claims, which fall into three categories: reasons for or against certain views, elementary truths regarding fundamental notions, and highly conditionalized claims. This agreement suggests that there is important philosophical progress. It then argues that although it's easy to list several potential kinds of philosophical progress, it is much harder to determine whether the potential is actual. Then the article attempts to articulate the truth that the deniers of philosophical progress are latching on to. Finally, it comments on the significance of the agreement and (potential) progress.
On the Domain of Metaphilosophy
Authors: Plant Bob 
Published: January 2017

AbstractThis article argues for four interrelated claims: (i) Metaphilosophy is not one sub‐discipline of philosophy, nor is it restricted to questions of methodology. Rather, metaphilosophical inquiry encompasses the general background conditions of philosophical practice. (ii) These background conditions are of various sorts, not only those routinely considered “philosophical” but also those considered biographical, historical, and sociological. Accordingly, we should be wary of the customary distinction between what is proper (internal) and merely contingent (external) to philosophy. (iii) “What is philosophy?” is best understood as a practical question concerning how members of different philosophical sub‐communities identify what is pertinent to their respective activities and self‐conceptions. (iv) Given (i)–(iii), understanding what philosophy is requires us to take more seriously the social‐institutional dimension of contemporary philosophical practice.
Disagreements Over Analogies
Authors: Laas Oliver 
Published: January 2017

AbstractThis essay presents a dialogical framework for treating philosophical disagreements as persuasion dialogues with analogical argumentation, with the aim of recasting philosophical disputes as disagreements over analogies. This has two benefits: (1) it allows us to temporarily bypass conflicting metaphysical intuitions by focusing on paradigmatic examples, (dis)similarities, and the plausibility of conclusions for or against a given point of view; and (2) it can reveal new avenues of argumentation regarding a given issue. This approach to philosophical disagreements is illustrated by studying the role of argumentation by analogy in disputes over Lockean justifications of intellectual property rights, and disagreements over whether artificial agents should be treated as moral agents. Finally, a nonexhaustive list of possible global and local points of contention over analogical arguments is identified in order to highlight potential avenues of argumentation in disagreements over analogies.
LlFH1‐mediated interaction between actin fringe and exocytic vesicles is involved in pollen tube tip growth
Authors: Li Shanwei , Dong Huaijian , Pei Weike , Liu Chaonan , Zhang Sha , Sun Tiantian , Xue Xiuhua , Ren Haiyun 
Published: January 2017

Summary

Pollen tube tip growth is an extreme form of polarized cell growth, which requires polarized exocytosis based on a dynamic actin cytoskeleton. However, the molecular basis for the connection between actin filaments and exocytic vesicles is unclear.

Here, we identified a Lilium longiflorum pollen‐specific formin (LlFH1) and found that it localized at the apical vesicles and plasma membrane (PM). Overexpression of LlFH1 induced excessive actin cables in the tube tip region, and downregulation of LlFH1 eliminated the actin fringe. Fluorescence recovery after photobleaching (FRAP) analysis revealed that LlFH1‐labeled exocytic vesicles exhibited an initial accumulation at the shoulder of the apex and coincided with the leading edge of the actin fringe. Time‐lapse analysis suggested that nascent actin filaments followed the emergence of the apical vesicles, implying that LlFH1 at apical vesicles could initiate actin polymerization.

Biochemical assays showed that LlFH1 FH1FH2 could nucleate actin polymerization, but then capped the actin filament at the barbed end and inhibited its elongation. However, in the presence of lily profilins, LlFH1 FH1FH2 could accelerate barbed‐end actin elongation. In addition, LlFH1 FH1FH2 was able to bundle actin filaments.

Thus, we propose that LlFH1 and profilin coordinate the interaction between the actin fringe and exocytic vesicle trafficking during pollen tube growth of lily.