bluuebunny/crossref_metadata_2025 huggingface dataset:
Biogenic amine content in Chilean Gauda cheese: physico‐chemical and microbiological factors that may influence this content
Authors: Brito Carmen , Cid Natalia , Muñoz Ociel , Báez Andrea , Horzella Mariela
Published: July 2014

The presence of four biogenic amines in Chilean Gauda cheese was studied, and the effect of certain factors may influence the production of those amines. Histamine, tyramine, putrescine and cadaverine were quantified with high‐performance liquid chromatography (HPLC), in cheeses from the three major Chilean cheese manufacturers. Multiple regression analysis revealed that water activity, free amino acid content and the Enterobacteriaceae count all favoured production of biogenic amines. The total amount of biogenic amines in the samples studied was between 47.9 and 150.5 mg/kg of cheese, much lower than that associated with a possible consumer health risk (1000 mg/kg).
‘Where Lies this Power Divine?’: The Representation of Kingship in Aphra Behn's Early Tragicomedies
Authors: Pacheco Anita
Published: July 2014

This article argues that Behn's two early tragicomedies The Young King (probably written in the 1660s but not staged until 1679) and The Forc'd Marriage (1670) provide critiques of divine right kingship as astute and incisive as that found in their immediate successor, The Amorous Prince (1671). It demonstrates that these plays reveal Behn's serious reservations about royalist political theory in the first decade after the Restoration and also, perhaps, given The Young King's belated first performance in 1679, during the early stages of the Exclusion Crisis.
mTORC2‐SGK‐1 acts in two environmentally responsive pathways with opposing effects on longevity
Authors: Mizunuma Masaki , Neumann‐Haefelin Elke , Moroz Natalie , Li Yujie , Blackwell T. Keith
Published: July 2014

The nematode worm Caenorhabditis elegans provides a powerful system for elucidating how genetic, metabolic, nutritional, and environmental factors influence aging. The mechanistic target of rapamycin (mTOR) kinase is important in growth, disease, and aging and is present in the mTORC1 and mTORC2 complexes. In diverse eukaryotes, lifespan can be increased by inhibition of mTORC1, which transduces anabolic signals to stimulate protein synthesis and inhibit autophagy. Less is understood about mTORC2, which affects C. elegans lifespan in a complex manner that is influenced by the bacterial food source. mTORC2 regulates C. elegans growth, reproduction, and lipid metabolism by activating the SGK‐1 kinase, but current data on SGK‐1 and lifespan seem to be conflicting. Here, by analyzing the mTORC2 component Rictor (RICT‐1), we show that mTORC2 modulates longevity by activating SGK‐1 in two pathways that affect lifespan oppositely. RICT‐1/mTORC2 limits longevity by directing SGK‐1 to inhibit the stress‐response transcription factor SKN‐1/Nrf in the intestine. Signals produced by the bacterial food source determine how this pathway affects SKN‐1 and lifespan. In addition, RICT‐1/mTORC2 functions in neurons in an SGK‐1‐mediated pathway that increases lifespan at lower temperatures. RICT‐1/mTORC2 and SGK‐1 therefore oppose or accelerate aging depending upon the context in which they are active. Our findings reconcile data on SGK‐1 and aging, show that the bacterial microenvironment influences SKN‐1/Nrf, mTORC2 functions, and aging, and identify two longevity‐related mTORC2 functions that involve SGK‐regulated responses to environmental cues.
Tolerance to egg proteins in egg‐sensitized infants without previous consumption
Authors: Álvaro M. , García‐Paba Mª. B. , Giner Mª. T. , Piquer M. , Domínguez O. , Lozano J. , Jiménez R. , Machinena A. , Martín‐Mateos M. A. , Plaza A. Mª.
Published: July 2014

Background

Egg‐sensitized infants who have never eaten egg may react at first ingestion. We sought to determine the association between skin prick test (SPT) and specific IgE (sIgE) to egg proteins (EP) and oral food challenge (OFC) outcomes to find cut‐off points which can diagnose egg allergy.

Methods

One hundred and fifty‐four infants up to 18 months, with cow's milk allergy (CMA) and/or atopic dermatitis (AD) without previous egg consumption, were recruited. SPT to EP were performed. If it was positive, sIgE was performed. If positive SPT and/or sIgE (n = 94), OFC was performed between 12 and 18 months. Receiver operating characteristic (ROC) curves were plotted, and the outcome of the OFC was related to SPT and sIgE. The cut‐off points with the best diagnostic accuracy were found.

Results

Ninety‐four patients were sensitized to egg (69%) and 60 nonsensitized (31%). Of the sensitized, 27 tolerated cooked (CE) and raw egg (RE) (28.7%). Sixty‐seven were allergic (71.3%): 29 reacted to CE, seven to egg yolk (EY) and 22 to egg white (EW) and 38 reacted to RE. 69.2% tolerated CE. EW SPT and ovalbumin (OVA) sIgE have the best area under the curve (AUC). The higher positive predictive values (PPV) were obtained for EW SPT and EW sIgE.

Conclusions

In egg‐sensitized infants with EW SPT ≥8 mm and/or EW sIgE ≥8.36 KU/l, egg diagnostic OFC can be avoided as there is 94% probability of becoming positive. In the other patients, OFC should be performed safely and early to avoid unnecessary diets.
Gaviscon Double Action Liquid (antacid & alginate) is more effective than antacid in controlling post‐prandial oesophageal acid exposure in GERD patients: a double‐blind crossover study
Authors: De Ruigh A. , Roman S. , Chen J. , Pandolfino J. E. , Kahrilas P. J.
Published: July 2014

Background

Recent studies have shown that Gaviscon Double Action Liquid (a combination alginate‐antacid) administered post‐prandially co‐localises with the acid pocket, the ‘reservoir’ for post‐prandial acid reflux.

Aim

To compare the effectiveness of Gaviscon Double Action Liquid to an equivalent strength antacid without alginate in controlling post‐prandial acid reflux in GERD patients.

Methods

Fourteen GERD patients undertook two 3.5‐h high‐resolution manometry/pH‐impedance studies during which they ate a standardised meal. In a double‐blinded randomised crossover design they then took Gaviscon or CVS brand antacid, each with ~18 mmol/L acid neutralising capacity. The primary outcome was distal oesophageal acid exposure; secondary outcomes were number of reflux events, proximal extent of reflux, nadir pH of the refluxate, mechanism of reflux and reflux symptoms scored with a validated instrument.

Results

Ten patients completed the study. Gaviscon studies had significantly less distal oesophageal acid exposure and greater nadir refluxate pH in the 30–150 min post‐prandial period than antacid studies. There were no differences in the number of reflux events (acid or weakly acidic) or the number of proximal reflux events (15–17 cm above the LES) with either study medication.

Conclusions

Gaviscon Double Action Liquid is more effective than an antacid without alginate in controlling post‐prandial oesophageal acid exposure. However, the number and spatial distribution of reflux events within the oesophagus are similar. This suggests that Gaviscon main effectiveness relates to its co‐localisation with and displacement/neutralisation of the post‐prandial acid pocket, rather than preventing reflux.
A randomized phase 1 pharmacokinetic trial comparing the potential biosimilarPF‐05280014 with trastuzumab in healthy volunteers (REFLECTIONS B327‐01)
Authors: Yin Donghua , Barker Kerry B. , Li Ruifeng , Meng Xu , Reich Steven D. , Ricart Alejandro D. , Rudin Dan , Taylor Carrie T. , Zacharchuk Charles M. , Hansson Arne G.
Published: July 2014

Aims

The pharmacokinetic (PK) similarity betweenPF‐05280014, a proposed trastuzumab biosimilar, trastuzumab sourced fromEuropeanUnion (trastuzumab‐EU) or fromUnitedStates (trastuzumab‐US) was evaluated. Safety and immunogenicity were also assessed.

Methods

In this phase 1, double‐blind trial (NCT01603264), 105 healthy male volunteers were randomized 1:1:1 to receive a single 6 mg kg−1intravenous dose ofPF‐05280014, trastuzumab‐EU, or trastuzumab‐US, and evaluated for 70 days. Drug concentration–time data were analyzed by non‐compartmental methods.PKsimilarity for the comparisons ofPF‐05280014 to each of trastuzumab‐EUand trastuzumab‐US, and trastuzumab‐EUto trastuzumab‐USwere determined using the standard 80.00% to 125.00% bioequivalence criteria.

Results

Baseline demographics for the 101 subjects evaluable forPKwere similar across all arms. The three products exhibited similarPKprofiles with target‐mediated disposition. The 90%CIsfor the ratios ofCmax,andAUC(0,∞)were within 80.00% to 125.00% for all three pairwise comparisons. Adverse events (AEs) were similar across all arms with treatment‐relatedAEsreported by 71.4%, 68.6% and 65.7% subjects in thePF‐05280014, trastuzumab‐EU, and trastuzumab‐USarms, respectively. The most commonAEswere infusion‐related reactions, headache, chills, pyrexia and nausea. TheAEterm ‘pyrexia’ was numerically greater in thePF‐05280014 arm. All post‐dose samples, except 1, tested negative for anti‐drug antibodies (ADA).

Conclusions

This study demonstratesPKsimilarity amongPF‐05280014, trastuzumab‐EUand trastuzumab‐US. The safety and immunogenicity profiles observed for the three products in this study are consistent with previous reports for trastuzumab.
Clinical features of narcolepsy in children vaccinated with AS03 adjuvanted pandemic A/H1N1 2009 influenza vaccine in England
Authors: Winstone Anne Marie , Stellitano Lesley , Verity Christopher , Andrews Nick , Miller Elizabeth , Stowe Julia , Shneerson John
Published: July 2014

Aim

The aim of this study was to investigate whether children in England with narcolepsy who received the ASO3 adjuvanted pandemic A/H1N1 2009 influenza vaccine (Pandemrix) differed clinically from unvaccinated patients.

Method

A retrospective review was conducted in children with narcolepsy diagnosed by sleep centres and paediatric neurologists in 16 English hospitals. The inclusion criteria were patient age 4 to 18 years, onset of narcolepsy after January 2008, and diagnosis by the time of the key data‐gathering visit in 2011. Clinical data came from hospital notes and general practitioner questionnaires. An expert panel validated the diagnoses.

Results

Seventy‐five patients with narcolepsy were identified (43 males, 32 females; mean age at onset 10y 4mo, range 3–18y). Of these patients, 11 received the Pandemrix vaccine before narcolepsy onset. On first presentation, there were more frequent reports of cataplexy, among other features, in vaccinated than in unvaccinated patients (82% vs 55%), but only excessive weight gain (55% vs 20%) was significantly more frequent (p=0.03). Facial hypotonia (p=0.03) and tongue protrusion (p=0.01) were eventually seen more frequently in vaccinated children. When considering patients diagnosed within a year of onset, vaccinated children were not diagnosed more rapidly than unvaccinated children.

Interpretation

Some symptoms and signs of narcolepsy were more frequently reported in Pandemrix–vaccinated patients. There was no evidence of the more rapid diagnosis in vaccinated patients that has been reported in Finland and Sweden.
Risperidone for non‐psychotic disorders in paediatric patients: which child is to benefit?
Authors: Hoekstra Pieter J
Published: July 2014

This commentary is on the original article by Youngster et al. on pages 990–994 of this issue.
Common pathways of intracranial calcification and the role of the pericyte: insights from neuropathology
Authors: Livingston John
Published: July 2014

This commentary is on the original article by McCartney and Squier on pages 1009–1015 of this issue.
Dysmorphic features and developmental outcome of 2‐year‐old children
Authors: Seggers Jorien , Haadsma Maaike L , Bos Arend F , Heineman Maas Jan , Middelburg Karin J , van den Heuvel Edwin R , Hadders‐Algra Mijna
Published: July 2014

Aim

The aim of this study was to assess the associations between dysmorphic features and neurological, mental, psychomotor, and behavioural development in order to improve our understanding of aetiological pathways leading to minor developmental problems.

Method

In our cross‐sectional study, 272 generally healthy 2‐year‐olds (143 males, 129 females; median gestational age 39 weeks, [range 30–43wks]), born after a parental history of subfertility either with or without fertility treatment, were examined. Dysmorphic features were classified as abnormalities (clinically relevant or not), minor anomalies, or common variants according to Merks' classification system. Hempel's neurological assessment resulted in a neurological optimality score (NOS) and fluency score. Mental and psychomotor development were assessed with the Dutch version of the Bayley Scales of Infant Development and behavioural development with the Achenbach Child Behaviour Checklist.

Results

Of the different types of dysmorphic feature, clinically relevant abnormalities were most strongly associated with a lower NOS (difference −2.53, 95% confidence interval [CI] −4.23 to −0.83) and fluency score (difference −0.62, 95% CI −1.1 to −0.15). The presence of one or more abnormalities (clinically relevant or not) or one or more common variants was significantly associated with a lower NOS, and the presence of three or more minor anomalies was associated with lower fluency scores. Dysmorphic features were not associated with mental, psychomotor, or behavioural development.

Interpretation

As dysmorphic features originate during the first trimester of pregnancy, the association between dysmorphic features and minor alterations in neurodevelopment may suggest an early ontogenetic origin of subtle neurological deviations.
Longitudinal trajectories of behavior problems and social competence in children with new onset epilepsy
Authors: Zhao Qianqian , Rathouz Paul J , Jones Jana E , Jackson Daren C , Hsu David A , Stafstrom Carl E , Seidenberg Michael , Hermann Bruce P
Published: July 2014

Aim

To characterize the prospective trajectory of parent‐reported behavior and social competence problems in children with new or recent onset epilepsy from diagnosis to 5 to 6 years after diagnosis compared to healthy control participants.

Method

Thirty‐five children (21 males, 14 females; mean age 14y 1mo [SD 3y 4mo] range 8–18y) with new/recent onset idiopathic generalized (IGE) and 34 children with localization‐related epilepsies (LRE; 19 males, 15 females; mean age 10y 8mo [SD 2y 2mo] range 8–18y) underwent behavioral assessment (Child Behavior Checklist) at baseline, 2 years, and 5 to 6 years after diagnosis. The assessment comprised the summary scales Total Behavior Problems Internalizing Problems, Externalizing Problems, and Total Competence. Sixty‐two children with normal development served as comparison participants. Analyses were based on random effects regression modeling comparing trajectories with respect to time since epilepsy diagnosis among groups.

Results

Differences in parent‐reported behavioral problems between LRE and IGE syndrome groups and healthy comparison participants were detectable at or near the time of diagnosis and remained either stable (competence) or tended to abate (behavior problems) over the ensuing 5 to 6 years without evidence of progressive worsening. These trends were evident for both LRE and IGE groups, with no differences between them.

Interpretation

Behavior and competence problems in children with LRE and IGE are not characterized by progressive worsening over a 5‐ to 6‐year period. Behavioral problems are present near the time of diagnosis and tend to abate over time, with competence problems being more persistent across serial assessments, and present in both LRE and IGE groups.
Asymmetrical cortical vessel sign on susceptibility‐weighted imaging: a novel imaging marker for early neurological deterioration and unfavorable prognosis
Authors: Sun W. , Liu W. , Zhang Z. , Xiao L. , Duan Z. , Liu D. , Xiong Y. , Zhu W. , Lu G. , Liu X.
Published: July 2014

Background and purpose

Susceptibility‐weighted imaging (SWI) is a high spatial resolution technique that can indirectly demonstrate increased cerebral oxygen extraction. Our aim was to assess whether asymmetric cortical vessel sign (ACVS) on SWI could be associated with early neurological deterioration (END) as well as 90‐day unfavorable outcome in patients with acute ischaemic stroke.

Materials and methods

Consecutive patients with acute middle cerebral artery (MCA) territory infarction were prospectively enrolled. ACVS was defined as more and/or larger vessels with greater signal loss than those in the opposite hemisphere on minimum intensity projection of SWI. The neurofunctional fluctuation during acute phase as well as 90‐day outcomes were assessed. A National Institutes of Health Stroke Scale increment ≥2 points and ≥4 points despite standard treatment in the first 72 h after admission was defined as END2 and END4, respectively.

Results

In all, 572 patients were finally enrolled. ACVS on SWI was present in 39 (6.8%) subjects. Multivariate analysis indicated that ACVS is an independent predictor for END2 [odds ratio (OR) 4.47, 95% confidence interval (CI) 1.99–10.05) and END4 (OR 4.24, 95% CI 1.94–9.23). Furthermore, ACVS also correlates with 90‐day unfavorable outcome defined as a modified Rankin Scale score >1 point (OR 2.93, 95% CI 1.15–7.48). Both positive and negative predictive values of ACVS for END2, END4 and 90‐day prognosis were reasonable and both could be slightly enhanced as long as patients with contralateral artery stenosis or occlusion were excluded.

Conclusion

In patients with MCA territory acute ischaemic stroke, especially in those without contralateral internal carotid artery/MCA stenosis or occlusion, ACVS might be considered as a neuroimaging predictor for END and unfavorable prognosis.
Vitamin D and white matter abnormalities in older adults: a cross‐sectional neuroimaging study
Authors: Annweiler C. , Annweiler T. , Bartha R. , Herrmann F. R. , Camicioli R. , Beauchet O.
Published: July 2014

Background and purpose

Morphological brain changes related to hypovitaminosis D have been poorly studied. In particular, the age‐related decrease in vitamin D concentrations may explain the onset of white matter abnormalities (WMA) in older adults. Our objectives were (i) to investigate whether there was an association between serum 25‐hydroxyvitamin D (25OHD) concentration and the grade of WMA in older adults and (ii) to determine whether the location of WMA was associated with 25OHD concentration.

Methods

One hundred and thirty‐three Caucasian older community‐dwellers with no clinical hydrocephalus (mean 71.6 ± 5.6 years; 43.6% female) received a blood test and a magnetic resonance imaging scan of the brain. The grades of total, periventricular and deep WMA were scored using semiquantitative visual rating scales from T2‐weighted fluid‐attenuated inversion recovery images. The association of WMA with as‐measured and deseasonalized 25OHD concentrations was evaluated with the following covariates: age, gender, body mass index, use of anti‐vascular drugs, number of comorbidities, impaired mobility, education level, Mini‐Mental State Examination score, medial temporal lobe atrophy, serum concentrations of calcium, thyroid‐stimulating hormone and vitamin B12, and estimated glomerular filtration rate.

Results

Both as‐measured and deseasonalized serum 25OHD concentrations were found to be inversely associated with the grade of total WMA (adjusted β = −0.32, P = 0.027), specifically with periventricular WMA (adjusted β = −0.15, P = 0.009) but not with deep WMA (adjusted β = −0.12, P = 0.090). Similarly, participants with 25OHD concentration <75 nM had on average a 33% higher grade of periventricular WMA than those with 25OHD ≥75 nM (P = 0.024). No difference in average grade was found for deep WMA (P = 0.949).

Conclusions

Lower serum 25OHD concentration was associated with higher grade of WMA, particularly periventricular WMA. These findings provide a scientific basis for vitamin D replacement trials.
Fuzzy Boundaries: Hybridizing Location‐based Services, Volunteered Geographic Information and Geovisualization Literature
Authors: Ricker Britta , Daniel Sylvie , Hedley Nick
Published: July 2014

Mobile applications are particularly exciting to geographers due to their ability to collect swathes of spatial data from citizens, to present information relevant to a user's current location, and to present data via interactive visualizations. While these functions are presented together within a single mobile location‐based application (LBApps), the academic literatures pertaining to each of these three functions are highly fragmented. Thus, we ask: what is the relationship between the three major components of LBApps: location‐based services (LBS), volunteered geographic information (VGI), and geovisualization? Additionally, what are some of the possible resulting implications for users' spatial understandings after interaction with these three components? Here, we present literature from VGI, LBS, and geovisualization that is relevant to mobile applications. We seek to reveal the synergistic relationship between these mechanisms in addition to the existing overlaps and gaps in the literature. We hope that this is a starting point for geographers interested in researching mobile applications to further enhance the collection, distribution, and visualization of spatial data. Like traditional cartography, it is imperative to keep the intended audience in mind during each step of the LBApp design and research process.
Geography and the Anthropocene II: Current Contributions
Authors: Castree Noel
Published: July 2014

This and two companion papers (The Anthropocene and Geography I: The back story and The Anthropocene and Geography III: Future Directions) consider the relevance of ‘the Anthropocene’ to present and future research in Geography. Along with the concept of ‘planetary boundaries’, the idea that humanity has entered a new geological epoch of its own making is currently attracting considerable attention – both within and beyond the world of Earth surface science from whence both notions originate. This paper's predecessor detailed the invention and evolution of the two scientific neologisms, ending with a general discussion of their potential relevance to Geography. The present essay examines how that relevance is being actualised in practice. Though the Anthropocene and planetary boundaries concepts are the progeny of certain biophysical scientists, some human geographers are already going beyond the science to explore their socio‐ecological implications. Accordingly, the paper describes how various physical, environmental and human geographers have thus far examined the (supposed) end of the Holocene. By detailing the full range of geographers' discussions of the two ideas, it comprehensively maps intellectual territory that a (so‐far select) group of geographers have been exploring independently of each other, albeit layered on previous research into global environmental change. Its successor (The Anthropocene and geography III: Future directions) speculates about the future directions geographers' discussions of the Anthropocene and planetary boundaries might take.
Exploration of the relationship between parent/guardian sociodemographics, intention, and knowledge and the oral health status of their children/wards enrolled in a Central Florida Head Start Program
Authors: Weatherwax JA , Bray KK , Williams KB , Gadbury‐Amyot CC
Published: July 2014

Objective

The purpose of this study was to identify possible relationships between parent/guardian sociodemographics, intention, knowledge, and the oral health status of their child/ward. Intention includes three factors as defined in the Theory of Planned Behavior: attitudes, subjective norms and perceived control, and oral health status was measured by decayed, missing and filled teeth (dmft) scores.

Methods

A convenience sample of parent/guardian with child/ward with age of three to five (n = 181 dyads) enrolled in a Head Start program in the state of Florida participated. A cross‐sectional observational study comprised of two components, parent/guardian questionnaire and an oral health status form for recording dmft scores of participating child/ward was employed.

Results

Parent/guardian race/ethnicity and years of education were significantly related to dmft of child/ward. The highest rates of severe early childhood caries (ECC) were found in child/ward whose parent/guardian is Hispanic and parent/guardian with less than a high school education. Multivariate regression analysis found that increased education level of parent/guardian was significantly associated with lower dmft in this population. No significant relationship was found between parent/guardian self‐reported intention (attitudes, subjective norms and perceived control), knowledge and dmft scores of the child/ward.

Conclusion

Researchers have called for greater attention to the impact of parental influences in the aetiology of ECC. Results from this study were consistent with current studies where parent/guardian race/ethnicity and educational level served as predictors of oral health status of children. In this study population, parent/guardian intention and knowledge were not shown to significantly impact the oral health status of their child/ward.
Platform Pricing Structure and Moral Hazard
Authors: Roger Guillaume , Vasconcelos Luís
Published: July 2014

We study pricing by a two‐sided platform when it faces moral hazard on the sellers' side. In doing so, we introduce an equilibrium notion of platform reputation in an infinite horizon model. We find that with transaction fees only, the platform cannot eliminate the loss of reputation induced by moral hazard. If registration fees can be levied, moral hazard can be overcome. The registration fee determines the participation threshold of sellers and extracts them, whereas (lower) transaction fees provide incentives for good behavior. This provides a motivation for platforms to use registration fees in addition to transaction fees.
Exit Deterrence
Authors: Byford Martin C. , Gans Joshua S.
Published: July 2014

This paper is the first to provide a general context whereby potential entry can lead incumbent firms to permanently reduce the intensity of competition in a market. All previous results found that potential entry would lead to lower prices and greater competition. Examining markets where entry occurs by the acquisition of access rights from an existing incumbent, we demonstrate that, where competitive choices are strategic complements, a more efficient entrant may be unable to acquire those rights from a less efficient incumbent due to the unilateral accommodating behavior of the efficient incumbent. Similarly, such accommodating behavior may deter efficient investment by an incumbent. These results have implications as to how economists view potential entry and its benefits.
Switching to Green: The Timing of Socially Responsible Innovation
Authors: Galasso Alberto , Tombak Mihkel
Published: July 2014

We develop a timing game for adopting a product technology that features a public good. We investigate the effects of the degree of product market competition, product differentiation, the private benefits from contributing to the public good, and firm asymmetries on the timing of adoption. We then examine the effects of consumer subsidies on equilibrium timings and the proliferation of the public good.
Spatial Price Discrimination in the Spokes Model
Authors: Reggiani Carlo
Published: July 2014

The spokes model allows to address nonlocalized spatial competition between firms. In a spatial context, firms can price discriminate using location‐contingent pricing. Nonlocalized competition implies that neighboring effects are not relevant to firms. This paper analyzes spatial price discrimination and location choices in the spokes model. Highly asymmetric location patterns are one outcome if the number of firms is sufficiently high: in that case, one firm supplies a generally appealing product whereas others focus on a specific niche. Moreover, multiple equilibria arise for intermediate values of the number of firms. In this case, the location patterns do not always globally minimize the sum of transport costs: asymmetric configurations distribute more efficiently the cost between firms.
Conventions or foundations? A response to Miles Little's ex nihilo nihil fit? Medicine rests on solid foundations
Authors: Upshur Ross E. G.
Published: July 2014

In this essay, I respond to the critique of my work by Professor Miles Little.
Morphology and Phylogeny of Thelohanellus marginatus n. sp. (Myxozoa: Myxosporea), a Parasite Infecting the Gills of the Fish Hypophthalmus marginatus (Teleostei: Pimelodidae) in the Amazon River
Authors: Rocha Sónia , Casal Graça , Velasco Michele , Alves Ângela , Matos Edilson , Al‐Quraishy Saleh , Azevedo Carlos
Published: July 2014

Thelohanellus marginatus n. sp., a new myxosporean parasite infecting the primary gill filaments of the teleost fish Hypophthalmus marginatus (Pimelodidae) in the Amazon River, is described on the basis of microscopic and molecular procedures. The parasite forms whitish and ellipsoidal cysts up to 250 μm in diam. Myxospores ellipsoidal with a slightly more pointed anterior end, measuring 17.1 ± 0.6 μm in length, 6.9 ± 0.4 μm in width, and 5.1 ± 0.5 μm in thickness. A single pyriform polar capsule, 9.0 ± 0.3 μm long and 6.1 ± 0.4 μm wide, positioned slightly right to the medial plane in valvular view, contains a polar filament arranged in 4–5 coils. Molecular analysis of the SSU rRNA gene by Maximum Parsimony, Neighbor‐Joining, and Maximum Likelihood revealed the parasite clustering among other myxobolids, namely Henneguya and Myxobolus. Host affinity is supported as an important evolutionary signal for the phylogeny of myxobolids. The parasite here described represents the first record of the genus Thelohanellus Kudo, 1933 from the South American fauna.
Morphology, Ontogeny, and Phylogeny of Two Brackish Urostylid Ciliates (Protist, Ciliophora, Hypotricha)
Authors: Chen Xumiao , Miao Miao , Ma Honggang , Al‐Rasheid Khaled A. S. , Xu Kuidong , Lin Xiaofeng
Published: July 2014

The diversity of hypotrichous ciliates has encouraged numerous researchers to use a combination of morphological, morphogenetic, and phylogenetic data to provide a better understanding of the evolutionary relationships within this complex group. In this study, we investigate the morphology and morphogenesis of Pseudourostyla subtropica sp. nov., isolated from mangrove wetland. The new species can be distinguished from its congeners by the huge body size, many more adoral membranelles and marginal cirral rows, and numerous macronuclear nodules. In addition, we provide a morphological characterization of a population of Pseudourostyla nova Wiackowski 1988 from an estuarine habitat. The main events during binary fission of P. subtropica sp. nov. and the Chinese population of P. nova are also revealed to be conservative. The morphological, ontogenetic, and phylogenetic analyses based on the SSU rDNA sequences corroborate the monophyly of Pseudourostyla Borror, 1972, which corresponds well with previous research. The phylogenetic analyses also show that Pseudourostyla and Hemicycliostyla Stokes, 1886, both of which are assigned to the family Pseudourostylidae based on morphological and morphogenetic data, in fact fall into separated clades. The approximately unbiased tests, however, do not reject the possibility that the family Pseudourostylidae is a monophyletic lineage.
Ephrin‐A3 reverse signaling regulates hippocampal neuronal damage and astrocytic glutamate transport after transient global ischemia
Authors: Yang Jinshan , Luo Xiang , Huang Xiaojiang , Ning Qin , Xie Minjie , Wang Wei
Published: July 2014

Increasing evidence indicates that the Eph receptors and their ephrin ligands are involved in the regulation of interactions between neurons and astrocytes. Moreover, astrocytic ephrin‐A3 reverse signaling mediated by EphA4 receptors is necessary for controlling the abundance of glial glutamate transporters. However, the role of ephrin‐A3 reverse signaling in astrocytic function and neuronal death under ischemic conditions remains unclear. In the present study, we found that the EphA4 receptor and its ephrin‐A3 ligand, which were distributed in neurons and astrocytes, respectively, in the hippocampus showed a coincident up‐regulation of protein expression in the early stage of ischemia. Application of clustered EphA4 decreased the expressions of astrocytic glutamate transporters together with astrocytic glutamate uptake capacity through activating ephrin‐A3 reverse signaling. In consequence, neuronal loss was aggravated in the CA1 region of the hippocampus accompanied by impaired hippocampus‐dependent spatial memory when clustered EphA4 treatment was administered prior to transient global ischemia. These findings indicate that EphA4‐mediated ephrin‐A3 reverse signaling is a crucial mechanism for astrocytes to control glial glutamate transporters and prevent glutamate excitotoxicity under pathological conditions.

image

Astrocytic ephrin‐A3 reverse signaling mediated by EphA4 receptor is necessary for controlling the abundance of glial glutamate transporters under physiological conditions. However, the role of ephrin‐A3 reverse signaling in astrocytic function and neuronal death under ischemic conditions remains unclear. We found EphA4‐mediated ephrin‐A3 reverse signaling to be a crucial mechanism for astrocytes to control glial glutamate transporters and protect hippocampal neurons from glutamate excitotoxicity under ischemic conditions, this cascade representing a potential therapeutic target for stroke.
High flow nasal cannula for continuous positive airway pressure weaning in preterm neonates: A single‐centre experience
Authors: Sasi Arun , Malhotra Atul
Published: July 2014

Aim

High flow nasal cannula therapy (HFNC) is an emerging method of non‐invasive respiratory support therapy for premature infants. Recent evidence around its safety and efficacy for post‐extubation respiratory support is encouraging. However, its effect on long‐term respiratory outcomes is not known. The aim of this study is to determine the effect of HFNC on respiratory outcomes (chronic lung disease (CLD), need for home oxygen) when used to wean babies from continuous positive airway pressure (CPAP).

Methods

This retrospective study compared respiratory outcomes in infants born <32 weeks gestation needing any respiratory support at birth in two epochs – epoch I (2004–2007) verus epoch II (2008–2011). HFNC was available to be used as a CPAP weaning modality in epoch II.

Results

A total of 1286 infants (epoch I: 597 vs. epoch II: 689), mean (standard deviation) gestation, 28.1 (2.2) versus 28.5 (2.3) weeks were enrolled, with 222 (32%) receiving HFNC in epoch II. Overall median duration of respiratory support increased by 150 h in epoch II (P = 0.03), primarily as HFNC hours. A reduction in duration of invasive ventilation and CPAP along with 6% (P = 0.01) reduction in CLD rates was observed in epoch II. No change in home oxygen therapy rates was noted. In logistic regression, HFNC had no significant effect on rates of CLD or home oxygen.

Conclusions

Introduction of HFNC for weaning nasal CPAP seems to have a minimal effect on CLD rates. The effect of HFNC on long‐term outcomes needs to be further evaluated.
Management of treatment‐naïve chronic hepatitisCgenotype 1 patients: a cost‐effectiveness analysis of treatment options
Authors: Cortesi P. A. , Ciaccio A. , Rota M. , Lim J. K. , De Salvia S. , Okolicsanyi S. , Vinci M. , Belli L. S. , Mantovani L. G. , Strazzabosco M.
Published: July 2014

New and more promising therapies for chronic hepatitis C (CHC) genotype 1 (G1) naive patients have recently been approved in the United States and Europe, and several more regimens are expected to become available within the next several years. While this scenario unfolds, it is necessary to develop a rational method to allocate current treatment inCHCG1 patients. We performed a cost‐effectiveness analysis of boceprevir (BOC)‐ and telaprevir (TVR)‐based triple therapy according to different patients’ selection strategies. A semi‐Markov model ofCHCnatural history and progression towards end‐stage liver disease was built. We considered 3 selection strategies based onMETAVIRfibrosis stage: (i) treat all patients with F1–F4 fibrosis, (ii) only F2–F4 and (iii) only F3–F4. For each strategy,TVRinterleukin‐28B‐guided (IL28B‐guided) andBOCrapid virologic response‐guided (RVR‐guided) therapies were applied. The model assessed the costs and outcomes, using a lifetime and 5‐year time horizon, and adopting the Italian National Health System perspective. The incremental cost‐effectiveness ratio (ICER) for F1–F4 strategy relative to F3–F4 was €5132 per quality‐adjusted life years gained, acrossTVR IL‐28B‐guided therapy, and €7042 in theBOC RVR‐guided therapy. Conversely, in the 5‐year scenario, theICERfor F1–F4 strategy relative to F3–F4 was €1 818 679 (TVR IL28B‐guided) and €1 866 437 (BOC RVR‐guided) per end‐stage liver disease or death (ESLD‐D) avoided. In view of anticipated improvement in the efficacy of future regimens, selective treatment of only patients with advanced fibrosis and cirrhosis withTVRorBOCcould represent the most cost‐effective strategy to optimize resource utilization.
microRNA‐122 regulates hypoxia‐inducible factor‐1 and vimentin in hepatocytes and correlates with fibrosis in diet‐induced steatohepatitis
Authors: Csak Timea , Bala Shashi , Lippai Dora , Satishchandran Abishek , Catalano Donna , Kodys Karen , Szabo Gyongyi
Published: July 2014

Background & Aims

miR‐122 is the most abundant miRNA in the liver particularly in hepatocytes where it targets cholesterol metabolism. Steatosis, a key component of non‐alcoholic fatty liver disease, is regulated by hypoxia‐inducible factor‐1α (HIF‐1α). Here, we hypothesized that reduced miR‐122 has a pathogenic role in steatohepatitis.

Methods

miR‐122 and its target genes were evaluated in mouse livers and/or isolated hepatocytes after methionine–choline‐deficient (MCD) or methionine–choline‐supplemented (MCS) diet.

Results

Liver and hepatocyte miR‐122 expression was significantly decreased in steatohepatitis. A maximum reduction in miR‐122 occurred at the fibrosis stage (8 weeks of MCD diet). MAP3K3, a miR‐122 target gene, was induced at all stages of non‐alcoholic steatohepatitis (NASH; 3–8 weeks) only at the mRNA level. Increased NF‐κB activation was found in MCD diet‐fed mice and MAP3K3 regulated the NF‐κB DNA binding in naive hepatocytes. HIF‐1α mRNA and DNA binding and expression of the HIF‐1α target gene, profibrotic lysyl oxidase, was increased in advanced steatohepatitis (8 weeks). In addition, increase in vimentin and Sirius red staining (liver fibrosis) was found at 8 weeks of MCD diet. Using miR‐122 overexpression and inhibition approaches, we confirmed that HIF‐1α, vimentin and MAP3K3 are novel miR‐122 targets in hepatocytes. We report transcriptional repression of miR‐122 in NASH. Decreased liver miR‐122 was associated with elevated circulating miR‐122 in both exosome‐rich and protein‐rich serum fractions.

Conclusions

Our novel data suggest that decreased liver miR‐122 contributes to upregulation of modulators of tissue remodelling (HIF‐1α, vimentin and MAP3K3) and might play a role in NASH‐induced liver fibrosis.
MicroRNA‐425‐3p predicts response to sorafenib therapy in patients with hepatocellular carcinoma
Authors: Vaira Valentina , Roncalli Massimo , Carnaghi Carlo , Faversani Alice , Maggioni Marco , Augello Claudia , Rimassa Lorenza , Pressiani Tiziana , Spagnuolo Gaia , Di Tommaso Luca , Fagiuoli Stefano , Rota Caremoli Elena , Barberis Massimo , Labianca Roberto , Santoro Armando , Bosari Silvano
Published: July 2014

Background & Aims

Sorafenib is the standard of care in advanced hepatocellular carcinoma (HCC), however no criteria have been established to select patients likely to benefit from this therapy. In this study, we evaluated the predictive role of microRNAs (miRNAs) in this setting of patients.

Methods

We profiled 522 miRNA in a series of 26 HCC patients treated with sorafenib (training set) and validated the results in an independent series of 58 patients (validation set). Formalin‐fixed paraffin‐embedded tumour and cirrhotic liver biopsies were used for RNA extraction and miRNAs profiling with TaqMan Arrays technology. Statistical analyses were used to correlate miRNA levels with clinical outcome, including time to progression (TTP), progression free (PFS), and overall survival. Cell viability and cell motility of HuH‐7 or HepG2 HCC cells were tested in vitro after transfection with specific miRNA precursor, inhibitor or controls and sorafenib treatment.

Results

Six miRNAs were significantly associated with clinical variables in the training set and only miR‐425‐3p could be further validated. Higher levels of miR‐425‐3p were associated with longer TTP and PFS (P = 0.0008; HR = 0.4; 95% CI = 0.2–0.7 and P = 0.007; HR = 0.5; 95% CI = 0.3–0.9 respectively). Multivariate analysis confirmed the predictive significance of miR‐425‐3p. Furthermore, an association between increased miR‐425‐3p, cell death and reduced cell motility was defined in vitro in HCC cell lines treated with sorafenib.

Conclusions

Assessment of miR‐425‐3p levels in liver biopsies could help in stratifying patients with advanced HCC for sorafenib treatment. These promising results need to be confirmed in a large prospective study.
Burden of HIV and hepatitis C co‐infection: the changing epidemiology of hepatitis C in HIV‐infected patients in France
Authors: Cacoub Patrice , Dabis François , Costagliola Dominique , Almeida Kayigan , Lert France , Piroth Lionel , Semaille Caroline
Published: July 2014

Background & Aims

To better evaluate the HIV–HCV co‐infection burden in the context of new effective HCV treatment.

Methods

We reviewed all the epidemiological data available on HCV‐related disease in HIV‐infected patients in France. Sources of data have been selected using the following criteria: (i) prospective cohorts or cross‐sectional surveys; (ii) conducted at a national level; (iii) in the HIV‐infected population; (iv) able to identify HCV co‐infection and chronic active hepatitis C (HCV RNA positive); and (v) conducted during the period 2003–2012.

Results

The overall prevalence of HIV–HCV co‐infection has decreased from 22–24% to 16–18%. This prevalence decreased from 93% to 87% among injecting drug users while it increased from 4% to 6% among men who have sex with men. The characteristics of patients have changed: decrease in the proportion of patients with chronic active hepatitis C (HCV RNA positive) from 77% to 63% and in the genotypes 2 and 3 HCV infection; increase in the proportion of HCV genotype 1 (from 45–50% to 58%) and genotype 4 (from 15% to 22%). The proportion of patients treated with highly active antiretroviral therapy increased from 76% to 95%, with higher rates of undetectable HIV viral load (47% in 2004 vs. 85% in 2012).

Conclusion

The decreasing prevalence and the change in patients profile in HIV–HCV co‐infection underline the importance of continuing efforts to educate physicians and patients. This should increase the benefit of viral risk reduction policies and increase the access of co‐infected patients to HCV treatment.
Temporary Protection, Enduring Contradiction: The Contested and Contradictory Meanings of Temporary Immigration Status
Authors: Hallett Miranda Cady
Published: July 2014

In the construction of immigration status categories in law and social practice, the power of the nation‐state to define migrants’ status is pervasive but far from absolute. In this article, I examine the conditioned legality known as Temporary Protected Status (TPS) in US immigration law through a discussion of legal structures, historical frames, local discourses, and Salvadoran migrants’ lived experiences with liminal legality in rural Arkansas in the first decade of the twenty‐first century. I argue that migration policy, though fraught with ambiguity and contradiction (see Coutin 2007; Coutin and Yngvesson 2008), functions both to reproduce and to mask the benefits to the nation‐state from the ambiguous inclusion and simultaneous exclusion of migrant workers. In spite of the efficacious ways immigration policies discipline and constrain, within these limits migrants, legal practitioners, and others respond as critical agents to the policy structures shaping their lives.
Flexing Work Boundaries: The Spillover and Crossover of Workplace Support
Authors: Ferguson Merideth , Carlson Dawn , Kacmar K. Michele
Published: July 2014

Using boundary theory and conservation of resources theory, we examined how job incumbents’ perceptions of supervisor instrumental support and organizational segmentation support influence outcomes for both the incumbent and the spouse. First, we examined how supervisor instrumental support and organizational segmentation support shape incumbents’ perceived ability to flex work boundaries and thus affect their experience of family functioning and their organizational commitment. Second, we examine the effects of supervisor instrumental support and organizational segmentation support on spousal martial satisfaction and the spouse's commitment to the incumbent's employing organization as mediated through boundary flexibility and the spouse's perception of successful boundary management by the incumbent. Using a matched set of 503 subordinates and their spouses, this study found that both supervisor instrumental support and organizational segmentation support contribute to work boundary flexibility. Further, for the incumbent, family functioning and organizational commitment were enhanced through work boundary flexibility, whereas for the spouse, marital satisfaction and commitment to the incumbent's organization were enhanced through both incumbent work boundary flexibility and the spouse's perception of successful boundary management by the incumbent. We discuss the study's implications for theory, research, and practice while suggesting new research directions.
Studying the dynamics of autonomic activity during emotional experience
Authors: Golland Yulia , Keissar Kobi , Levit‐Binnun Nava
Published: July 2014

Recent theories emphasize the dynamic aspects of emotions. However, the physiological measures and the methodological approaches that can capture the dynamics of emotions are underdeveloped. In the current study, we investigated whether moment‐to‐moment changes in autonomic nervous system (ANS) activity are reliably associated with the unfolding of emotional experience. We obtained cardiovascular and electrodermal signals from participants while they viewed emotional movies. We found that theANSsignals were temporally aligned across individuals, indicating a reliable stimulus‐driven response. The degree of response reliability was associated with the emotional time line of the movie. Finally, individual differences inANSresponse reliability were strongly correlated with the subjective emotional responses. The current research offers a methodological approach for studying physiological responses during dynamic emotional situations.
Giovanna d'Austria and the art of appearances: textiles and dress at the Florentine court
Authors: Bercusson Sarah
Published: July 2014

This article examines the potential value of textiles and clothing as a means for a female consort, whose position was dependent on a variety of mutable factors and who frequently lacked access to independent institutional authority, to exert influence, gain loyalty, assert status and express ambiguity and even conflict. Taking the underexplored subject of Giovanna d'Austria, wife of Francesco de' Medici and the first Grand Duchess of Florence, as a case study, I examine her use of material culture in the context of her increasingly precarious position at the Florentine court. Drawing on a wide range of sources, from account books and receipts to ambassadors' reports and private correspondence, Giovanna's activities are contextualized through comparison with her predecessor, Eleonora di Toledo; her husband Francesco's mistress, Bianca Cappello and her sisters, Barbara, Duchess of Ferrara, and Eleonora of Austria, Duchess of Mantua.