bluuebunny/crossref_metadata_2025_split huggingface dataset:
Analysis of the level of general clinical skills of physician assistant students using an objective structured clinical examination
Authors: van Vught Anneke J. A. H. , Hettinga Agatha M. , Denessen Eddie J. P. G. , Gerhardus Martin J. T. , Bouwmans Geert A. M. , van den Brink Geert T. W. J. , Postma Cornelis T. 
Published: September 2015

AbstractRationale, aims and objectivesThe physician assistant (PA) is trained to perform clinical tasks traditionally performed by medical doctors (MDs). Previous research showed no difference in the level of clinical skills of PAs compared with MDs in a specific niche, that is the specialty in which they are employed. However, MDs as well as PAs working within a specialty have to be able to recognize medical problems in the full scope of medicine. The objective is to examine PA students' level of general clinical skills across the breadth of clinical cases.MethodA cross‐sectional study was conducted. PA students and recently graduated MDs in the Netherlands were observed on their clinical skills by means of an objective structured clinical examination comprising five stations with common medical cases. The level of mastering history taking, physical examination, communication and clinical reasoning of PA students and MDs were described in means and standard deviation. Cohen's d was used to present effect sizes.ResultsPA students and MDs score about equal on history taking (PA 5.8 ± 0.8 vs. MD 5.7 ± 0.7), physical examination (PA 4.8 ± 1.3 vs. MD 5.4 ± 0.8) and communication (PA: 8.2 ± 0.8 vs. MD: 8.6 ± 0.5) in the full scope of medicine. In the quality of the report, including the patient management plan, PA students scored a mean of 6.0 ± 0.6 and MDs 6.8 ± 0.6.ConclusionsIn this setting in the Netherlands, PA students and MDs score about equal in the appraisal of common cases in medical practice. The slightly lower scores of PA students' clinical reasoning in the full scope of clinical care may have raise attention to medical teams working with PAs and PA training programmes.
New insights on molecular regulation of biofilm formation in plant‐associated bacteria
Authors: Castiblanco Luisa F. , Sundin George W. 
Published: September 2015

AbstractBiofilms are complex bacterial assemblages with a defined three‐dimensional architecture, attached to solid surfaces, and surrounded by a self‐produced matrix generally composed of exopolysaccharides, proteins, lipids and extracellular DNA. Biofilm formation has evolved as an adaptive strategy of bacteria to cope with harsh environmental conditions as well as to establish antagonistic or beneficial interactions with their host. Plant‐associated bacteria attach and form biofilms on different tissues including leaves, stems, vasculature, seeds and roots. In this review, we examine the formation of biofilms from the plant‐associated bacterial perspective and detail the recently‐described mechanisms of genetic regulation used by these organisms to orchestrate biofilm formation on plant surfaces. In addition, we describe plant host signals that bacterial pathogens recognize to activate the transition from a planktonic lifestyle to multicellular behavior.
Visual Assessment of Brain Perfusion MRI Scans in Dementia: A Pilot Study
Authors: Fällmar David , Lilja Johan , Velickaite Vilma , Danfors Torsten , Lubberink Mark , Ahlgren André , van Osch Matthias J.P. , Kilander Lena , Larsson Elna‐Marie 
Published: September 2015

ABSTRACTPURPOSEFunctional imaging is becoming increasingly important for the detection of neurodegenerative disorders. Perfusion MRI with arterial spin labeling (ASL) has been reported to provide promising diagnostic possibilities but is not yet widely used in routine clinical work. The aim of this study was to compare, in a clinical setting, the visual assessment of subtracted ASL CBF maps with and without additional smoothing, to FDG‐PET data.METHODSTen patients with a clinical diagnosis of dementia and 11 age‐matched cognitively healthy controls were examined with pseudo‐continuous ASL (pCASL) and 18F‐Fluorodeoxyglucose positron emission tomography (FDG‐PET). Three diagnostic physicians visually assessed the pCASL maps after subtraction only, and after postprocessing using Gaussian smoothing and GLM‐based beta estimate functions. The assessment scores were compared to FDG PET values. Furthermore, the ability to discriminate patients from healthy elderly controls was assessed.RESULTSSmoothing improved the correlation between visually assessed regional ASL perfusion scores and the FDG PET SUV‐r values from the corresponding regions. However, subtracted pCASL maps discriminated patients from healthy controls better than smoothed maps. Smoothing increased the number of false‐positive patient identifications. Application of beta estimate functions had only a marginal effect.CONCLUSIONSpatial smoothing of ASL images increased false positive results in the discrimination of hypoperfusion conditions from healthy elderly. It also decreased interreader agreement. However, regional characterization and subjective perception of image quality was improved.
Neamine and 2-deoxystreptamine neomycin derivatives exhibit antinociceptive activity in rat models of phasic, incision and neuropathic pain
Authors: Prado Wiliam A. , Rossaneis Ana C. , Carvalho Ivone , Zamoner Luis Otávio B. , Corrado Alexandre P. 
Published: September 2015

Abstract

Objectives
To assess the antinociceptive activity of the neomycin derivatives neamine and 2-deoxystreptamine following intraspinal administration in rats.

Methods
We used the tail-flick test and measured the threshold to mechanical stimulation in models of incisional and neuropathic pain.

Key findings
The derivatives produced antinociception in the tail-flick test and reduced mechanical allodynia in models of incisional and neuropathic pain. The approximate ED50 in milligrams (confidence limits in parenthesis) in these tests were 1.35 mg (0.61; 2.95), 0.20 mg (0.14; 0.27) and 0.28 mg (0.12; 0.63) for neamine, and 1.05 mg (0.68; 1.60), 0.78 mg (0.776; 0.783) and 0.79 mg (0.46; 1.34) for 2-deoxystreptamine, respectively. Neamine was more potent than 2-deoxystreptamine in the incisional and neuropathic pain models, but they had similar potency in the tail-flick test. Tetra-azidoneamine, a neamine derivative in which free amino groups are replaced with azido groups, did not change the incisional mechanical allodynia. The reduction of incisional allodynia by neamine and 2-deoxystreptamine was transitorily antagonized by intrathecal administration of calcium chloride.

Conclusions
The intraspinal administration of neamine and 2-deoxystreptamine is antinociceptive in rats. The presence of amino groups in the structure of these derivatives is fundamental to their antinociceptive effect, which may be due to a calcium antagonist activity.
Phylogenetic tree of vascular plants reveals the origins of aquatic angiosperms
Authors: Du Zhi‐Yuan , Wang Qing‐Feng ,   China Phylogeny Consortium
Published: September 2015

AbstractAlthough aquatic plants are discussed as a unified biological group, they are phylogenetically well dispersed across the angiosperms. In this study, we annotated the aquatic taxa on the tree of vascular plants, and extracted the topology of these aquatic lineages to construct the tree of aquatic angiosperms. We also reconstructed the ancestral areas of aquatic families. We found that aquatic angiosperms could be divided into two different categories: the four aquatic orders and the aquatic taxa in terrestrial orders. Aquatic lineages evolved early in the radiation of angiosperms, both in the orders Nymphaeales and Ceratophyllales and among basal monocots (Acorales and Alismatales). These aquatic orders do not have any extant terrestrial relatives. They originated from aquatic habitats during the Early Cretaceous. Asia would have been one of the centers for early diversification of aquatic angiosperms. The aquatic families within terrestrial orders may originate from other areas besides Asia, such as America or Australia. The lineages leading to extant angiosperms diversified early in underexploited freshwater habitats. The four extant aquatic orders were relicts of an early radiation of angiosperm in aquatic environments. Their extinct ancestors might be aquatic early angiosperms.
Association of incident restless legs syndrome with outcomes in a large cohort of US veterans
Authors: Molnar Miklos Z. , Lu Jun L. , Kalantar‐Zadeh Kamyar , Kovesdy Csaba P. 
Published: September 2015

SummaryRestless legs syndrome is a common sleep disorder, but there is a paucity of large cohort studies examining the association of restless legs syndrome with clinical outcomes, including all‐cause mortality, incident coronary heart disease, stroke and chronic kidney disease. From a nationally representative prospective cohort of over 3 million US veterans [93% male, median follow‐up time of 8.1 years (interquartile range: 7.0–8.5 years)] with baseline estimated glomerular filtration rate ≥60 mL min−1 1.73 m−2, a propensity‐matched cohort of 7392 patients was created, and the association between incident restless legs syndrome and the following was examined: (1) all‐cause mortality; (2) incident coronary heart disease; (3) incident strokes; and (4) incident chronic kidney disease defined as estimated glomerular filtration rate <60 mL min−1 1.73 m−2. Associations were examined using Cox models. The mean ± SD age of the propensity‐matched cohort at baseline was 59 ± 12 years; 89 and 8% of patients were white and black, respectively; 31% of the patients were diabetic; and the mean baseline estimated glomerular filtration rate was 83.9 ± 15.1 mL min−1 1.73 m−2. Propensity matching resulted in a balanced cohort, with the disappearance in baseline differences in comorbidities. Compared with restless legs syndrome‐negative patients, incident restless legs syndrome was associated with 88% higher mortality risk [hazard ratio and 95% confidence interval: 1.88 (1.70–2.08)], and almost four times higher risk of coronary heart disease and stroke [hazard ratio: 3.97 (3.26–4.84) and 3.89 (3.07–4.94), respectively]. The risk of incident chronic kidney disease was also significantly higher in incident restless legs syndrome patients [hazard ratio: 3.17 (2.74–3.66)] compared with restless legs syndrome‐negative counterparts. In this large and contemporary cohort of US veterans, incident restless legs syndrome was associated with higher risk of mortality, incident coronary heart disease, stroke and chronic kidney disease.
Is it possible to be a phenomenological Thomist? An investigation of the notions of esse and esse commune
Authors: Brook Angus 
Published: September 2015

AbstractThis article tests whether it is possible to be a ‘phenomenological-Thomist’ through the provision of the first stages of a loosely speaking Heideggerian phenomenological interpretation of the meaning of being an entity as it is disclosed in experience. In the process, the article will unpack and reinterpret the concepts of esse and esse commune in the thought of Thomas Aquinas.
Knock‐down of transcript abundance of a family ofKunitz proteinase inhibitorgenes in white clover (Trifolium repens) reveals a redundancy and diversity of gene function
Authors: Islam Afsana , Leung Susanna , Burgess Elisabeth P. J. , Laing William A. , Richardson Kim A. , Hofmann Rainer W. , Dijkwel Paul P. , McManus Michael T. 
Published: September 2015

SummaryThe transcriptional regulation of four phylogenetically distinct members of a family ofKunitz proteinase inhibitor(KPI) genes isolated from white clover (Trifolium repens; designatedTr‐KPI1,Tr‐KPI2,Tr‐KPI4andTr‐KPI5) has been investigated to determine their wider functional role.The four genes displayed differential transcription during seed germination, and in different tissues of the mature plant, and transcription was also ontogenetically regulated. Heterologous over‐expression ofTr‐KPI1,Tr‐KPI2,Tr‐KPI4andTr‐KPI5inNicotiana tabacumretarded larval growth of the herbivoreSpodoptera litura, and an increase in the transcription of the pathogenesis‐related genesPR1andPR4was observed in theTr‐KPI1andTr‐KPI4over‐expressing lines.RNA interference (RNAi) knock‐down lines in white clover displayed significantly altered vegetative growth phenotypes with inhibition of shoot growth and a stimulation of root growth, while knock‐down ofTr‐KPI1,Tr‐KPI2andTr‐KPI5transcript abundance also retarded larval growth ofS. litura. Examination of theseRNAi lines revealed constitutive stress‐associated phenotypes as well as altered transcription of cellular signalling genes.These results reveal a functional redundancy across members of theKPIgene family. Further, the regulation of transcription of at least one member of the family,Tr‐KPI2, may occupy a central role in the maintenance of a cellular homeostasis.
Perceptions of Public and Private Performance: Evidence from a Survey Experiment
Authors: Hvidman Ulrik , Andersen Simon Calmar 
Published: September 2015

AbstractMedia, politicians, and reform proponents frequently assert that public sector organizations are inefficient and burdened by administrative procedures. But are negative stereotypes of the public sector reflected in people's perceptions of public service provision? Given the methodological challenges of isolating the perception of publicness from other factors related to public organizations, little is known about whether public organizations have a negative image. The authors use a survey experimental design to isolate the effect of publicness on perceptions of the performance of hospitals. The results suggest that public sector organizations have a negative image on productivity‐related aspects of performance but not on normative aspects of performance. As this article is a randomized experiment, it provides strong evidence regarding the causal nature of the relationship between publicness and perceptions of performance. Implications for researchers aiming to understand these mechanisms and for public managers concerned about the image of their organization are discussed.
Second‐order Accurate Confidence Regions Based on Members of the Generalized Power Divergence Family
Authors: Lunardon Nicola , Adimari Gianfranco 
Published: September 2015

AbstractRecently, a technique based on pseudo‐observations has been proposed to tackle the so‐called convex hull problem for the empirical likelihood statistic. The resulting adjusted empirical likelihood also achieves the high‐order precision of the Bartlett correction. Nevertheless, the technique induces an upper bound on the resulting statistic that may lead, in certain circumstances, to worthless confidence regions equal to the whole parameter space. In this paper, we show that suitable pseudo‐observations can be deployed to make each element of the generalized power divergence family Bartlett‐correctable and released from the convex hull problem. Our approach is conceived to achieve this goal by means of two distinct sets of pseudo‐observations with different tasks. An important effect of our formulation is to provide a solution that permits to overcome the problem of the upper bound. The proposal, which effectiveness is confirmed by simulation results, gives back attractiveness to a broad class of statistics that potentially contains good alternatives to the empirical likelihood.
Selection Strategy for Covariance Structure of Random Effects in Linear Mixed‐effects Models
Authors: Zhang Xinyu , Liang Hua , Liu Anna , Ruppert David , Zou Guohua 
Published: September 2015

AbstractLinear mixed‐effects models are a powerful tool for modelling longitudinal data and are widely used in practice. For a given set of covariates in a linear mixed‐effects model, selecting the covariance structure of random effects is an important problem. In this paper, we develop a joint likelihood‐based selection criterion. Our criterion is the approximately unbiased estimator of the expected Kullback–Leibler information. This criterion is also asymptotically optimal in the sense that for large samples, estimates based on the covariance matrix selected by the criterion minimize the approximate Kullback–Leibler information. Finite sample performance of the proposed method is assessed by simulation experiments. As an illustration, the criterion is applied to a data set from an AIDS clinical trial.
Contrasting actions of a convulsant barbiturate and its anticonvulsant enantiomer on the α1β3γ2L GABAA receptor account for their in vivo effects
Authors: Desai Rooma , Savechenkov Pavel Y. , Zolkowska Dorota , Ge Ri Le , Rogawski Michael A. , Bruzik Karol S. , Forman Stuart A. , Raines Douglas E. , Miller Keith W. 
Published: September 2015

Key Points
Most barbiturates are anaesthetics but unexpectedly a few are convulsants whose mechanism of action is poorly understood.
We synthesized and characterized a novel pair of chiral barbiturates that are capable of photolabelling their binding sites on GABAA receptors. In mice the S‐enantiomer is a convulsant, but the R‐enantiomer is an anticonvulsant.
The convulsant S‐enantiomer binds solely at an inhibitory site. It is both an open state inhibitor and a resting state inhibitor. Its action is pH independent, suggesting the pyrimidine ring plays little part in binding. The inhibitory site is not enantioselective because the R‐enantiomer inhibits with equal affinity.
In contrast, only the anticonvulsant R‐enantiomer binds to the enhancing site on open channels, causing them to stay open longer. The enhancing site is enantioselective.
The in vivo actions of the convulsant S‐enantiomer are accounted for by its interactions with GABAA receptors.
AbstractMost barbiturates are anaesthetics but a few unexpectedly are convulsants. We recently located the anaesthetic sites on GABAA receptors (GABAARs) by photolabelling with an anaesthetic barbiturate. To apply the same strategy to locate the convulsant sites requires the creation and mechanistic characterization of a suitable agent. We synthesized enantiomers of a novel, photoactivable barbiturate, 1‐methyl‐5‐propyly‐5‐(m‐trifluoromethyldiazirinyl) phenyl barbituric acid (mTFD‐MPPB). In mice, S‐mTFD‐MPPB acted as a convulsant, whereas R‐mTFD‐MPPB acted as an anticonvulsant. Using patch clamp electrophysiology and fast solution exchange on recombinant human α1β3γ2L GABAARs expressed in HEK cells, we found that S‐mTFD‐MPPB inhibited GABA‐induced currents, whereas R‐mTFD‐MPPB enhanced them. S‐mTFD‐MPPB caused inhibition by binding to either of two inhibitory sites on open channels with bimolecular kinetics. It also inhibited closed, resting state receptors at similar concentrations, decreasing the channel opening rate and shifting the GABA concentration–response curve to the right. R‐mTFD‐MPPB, like most anaesthetics, enhanced receptor gating by rapidly binding to allosteric sites on open channels, initiating a rate‐limiting conformation change to stabilized open channel states. These states had slower closing rates, thus shifting the GABA concentration–response curve to the left. Under conditions when most GABAARs were open, an inhibitory action of R‐mTFD‐MPPB was revealed that had a similar IC50 to that of S‐mTFD‐MPPB. Thus, the inhibitory sites are not enantioselective, and the convulsant action of S‐mTFD‐MPPB results from its negligible affinity for the enhancing, anaesthetic sites. Interactions with these two classes of barbiturate binding sites on GABAARs underlie the enantiomers’ different pharmacological activities in mice.
Placental phenotype and resource allocation to fetal growth are modified by the timing and degree of hypoxia during mouse pregnancy
Authors: Higgins J. S. , Vaughan O. R. , Fernandez de Liger E. , Fowden A. L. , Sferruzzi‐Perri A. N. 
Published: September 2015

Key points
Hypoxia is a major cause of fetal growth restriction, particularly at high altitude, although little is known about its effects on placental phenotype and resource allocation to fetal growth.
In the present study, maternal hypoxia induced morphological and functional changes in the mouse placenta, which depended on the timing and severity of hypoxia, as well as the degree of maternal hypophagia.
Hypoxia at 13% inspired oxygen induced beneficial changes in placental morphology, nutrient transport and metabolic signalling pathways associated with little or no change in fetal growth, irrespective of gestational age.
Hypoxia at 10% inspired oxygen adversely affected placental phenotype and resulted in severe fetal growth restriction, which was due partly to maternal hypophagia.
There is a threshold between 13% and 10% inspired oxygen, corresponding to altitudes of ∼3700 m and 5800 m, respectively, at which the mouse placenta no longer adapts to support fetal resource allocation. This has implications for high altitude human pregnancies.
AbstractThe placenta adapts its transport capacity to nutritional cues developmentally, although relatively little is known about placental transport phenotype in response to hypoxia, a major cause of fetal growth restriction. The present study determined the effects of both moderate hypoxia (13% inspired O2) between days (D)11 and D16 or D14 and D19 of pregnancy and severe hypoxia (10% inspired O2) from D14 to D19 on placental morphology, transport capacity and fetal growth on D16 and D19 (term∼D20.5), relative to normoxic mice in 21% O2. Placental morphology adapted beneficially to 13% O2; fetal capillary volume increased at both ages, exchange area increased at D16 and exchange barrier thickness reduced at D19. Exposure to 13% O2 had no effect on placental nutrient transport on D16 but increased placental uptake and clearance of 3H‐methyl‐d‐glucose at D19. By contrast, 10% O2 impaired fetal vascularity, increased barrier thickness and reduced placental 14C‐methylaminoisobutyric acid clearance at D19. Consequently, fetal growth was only marginally affected in 13% O2 (unchanged at D16 and −5% at D19) but was severely restricted in 10% O2 (−21% at D19). The hypoxia‐induced changes in placental phenotype were accompanied by altered placental insulin‐like growth factor (IGF)‐2 expression and insulin/IGF signalling, as well as by maternal hypophagia depending on the timing and severity of the hypoxia. Overall, the present study shows that the mouse placenta can integrate signals of oxygen and nutrient availability, possibly through the insulin‐IGF pathway, to adapt its phenotype and optimize maternal resource allocation to fetal growth during late pregnancy. It also suggests that there is a threshold between 13% and 10% inspired O2 at which these adaptations no longer occur.