bluuebunny/crossref_metadata_2025 huggingface dataset:
RISK‐MINIMIZATION FOR LIFE INSURANCE LIABILITIES WITH DEPENDENT MORTALITY RISK
Authors: Biagini Francesca , Botero Camila , Schreiber Irene
Published: June 2015

In this paper, we study the pricing and hedging of typical life insurance liabilities for an insurance portfolio with dependent mortality risk by means of the well‐known risk‐minimization approach. As the insurance portfolio consists of individuals of different age cohorts in order to capture the cross‐generational dependency structure of the portfolio, we introduce affine models for the mortality intensities based on Gaussian random fields that deliver analytically tractable results. We also provide specific examples consistent with historical mortality data and correlation structures. Main novelties of this work are the explicit computations of risk‐minimizing strategies for life insurance liabilities written on an insurance portfolio composed of primary financial assets (a risky asset and a money market account) and a family of longevity bonds, and the simultaneous consideration of different age cohorts.
MODEL UNCERTAINTY AND SCENARIO AGGREGATION
Authors: Cambou Mathieu , Filipović Damir
Published: June 2015

This paper provides a coherent method for scenario aggregation addressing model uncertainty. It is based on divergence minimization from a reference probability measure subject to scenario constraints. An example from regulatory practice motivates the definition of five fundamental criteria that serve as a basis for our method. Standard risk measures, such as value‐at‐risk and expected shortfall, are shown to be robust with respect to minimum divergence scenario aggregation. Various examples illustrate the tractability of our method.
DYNAMIC TRADING VOLUME
Authors: Guasoni Paolo , Weber Marko
Published: June 2015

We derive the process followed by trading volume, in a market with finite depth and constant investment opportunities, where a large investor, with a long horizon and constant relative risk aversion, trades a safe and a risky asset. Trading volume approximately follows a Gaussian, mean‐reverting diffusion, and increases with depth, volatility, and risk aversion. Unlike the frictionless theory, finite depth excludes leverage and short sales because such positions may not be solvent even with continuous trading.
Phenotypic plasticity and divergence in gene expression
Authors: Healy Timothy M. , Schulte Patricia M.
Published: June 2015

The extent to which phenotypic plasticity, or the ability of a single genotype to produce different phenotypes in different environments, impedes or promotes genetic divergence has been a matter of debate within evolutionary biology for many decades (see, for example, Ghalambor et al. ; Pfennig et al. ). Similarly, the role of evolution in shaping phenotypic plasticity remains poorly understood (Pigliucci ). In this issue of Molecular Ecology, Dayan et al. () provide empirical data relevant to these questions by assessing the extent of plasticity and divergence in the expression levels of 2272 genes in muscle tissue from killifish (genus Fundulus) exposed to different temperatures. F. heteroclitus (Fig. A) and F. grandis are minnows that inhabit estuarine marshes (Fig. B) along the coasts of the Atlantic Ocean and Gulf of Mexico in North America. These habitats undergo large variations in temperature both daily and seasonally, and these fish are known to demonstrate substantial phenotypic plasticity in response to temperature change (e.g. Fangue et al. ). Furthermore, the range of F. heteroclitus spans a large latitudinal gradient of temperatures, such that northern populations experience temperatures that are on average ~10°C colder than do southern populations (Schulte ). By comparing gene expression patterns between populations of these fish from different thermal habitats held in the laboratory at three different temperatures, Dayan et al. () address two important questions regarding the interacting effects of plasticity and evolution: (i) How does phenotypic plasticity affect adaptive divergence? and (ii) How does adaptive divergence affect plasticity?
DiagnosticSNPs reveal widespread introgressive hybridization between introduced bighead and silver carp in theMississippiRiverBasin
Authors: Lamer James T. , Ruebush Blake C. , Arbieva Zarema H. , McClelland Michael A. , Epifanio John M. , Sass Greg G.
Published: June 2015

Hybridization among conspecifics in native and introduced habitats has important implications for biological invasions in new ecosystems. Bighead (Hypophthalmichthys nobilis) and silver carp (H. molitrix) are genetically isolated and occur in sympatry within their native range. Following their introduction to North America, however, introgressant hybrids have been reported throughout their expanded range within the Mississippi River Basin (MRB). The extent of introgression, both spatially and generationally, is largely unknown. Therefore, we examined mixed‐species populations from across theMRBto characterize the extent of interspecific gene flow. We assayed 2798 individuals from nine locations with a suite of species‐diagnosticSNPs (57 nuclear and one mitochondrial). Forty‐four per cent (n = 1244) of individuals displayed hybrid genotypes. Moreover, the composition of hybrid genotypes varied among locations and represented complex hybrid swarms with multiple generations of gene flow. Introgressive hybrids were identified from all locations, were bidirectional and followed a bimodal distribution consisting primarily of parental or parental‐like genotypes and phenotypes. All described hybrid categories were present among individuals from 1999 to 2008, with parents and later‐generation backcrosses representing the largest proportion of individuals among years. Our mitochondrialSNP(COII), tested on a subset of 730 individuals, revealed a silver carp maternal bias in 13 of 21 (62%) F1hybrids, in all silver carp backcrosses, and maintained throughout many of the bighead carp backcrosses. The application of this suite of diagnostic markers and the spatial coverage permits a deeper examination of the complexity in hybrid swarms between two invasive, introduced species.
The southwestern Carpathians as an ancient centre of diversity of freshwater gammarid amphipods: insights from the Gammarus fossarum species complex
Authors: Copilaş‐Ciocianu Denis , Petrusek Adam
Published: June 2015

Gammarus fossarum is a diverse species complex of epigean freshwater amphipods throughout Europe. Due to their poor dispersal capabilities and ubiquity, these crustaceans may serve as a model for investigating the influence of historical factors on the contemporary distribution and diversity patterns of freshwater macrozoobenthos. Here, we investigate the fine‐scale phylogeographic structure of this complex across its range in the southwestern Carpathian Mountains, which comprises two areas that are geographically isolated from its main European distribution area as well as from each other. Given the Tertiary age of many freshwater Gammarus species, we hypothesize that the southwestern Carpathian populations reflect a relict distribution pattern. We used two mitochondrial and three nuclear markers from 32 localities to reconstruct phylogenetic relationships and estimate the timings of divergence among southwestern Carpathian and non‐Carpathian lineages. Cryptic diversity was evaluated from mitochondrial markers by employing phylogenetic and distance‐based methods. We distinguished at least 16 cryptic microendemic taxa, some of them coexisting, distributed in the southwestern Carpathians in a mosaic‐like pattern. These lineages form a monophyletic group together with several lineages from southeastern Europe. Estimated divergence times indicate a Middle Miocene origin of this clade, with many deep splits dating back to more than 10 Ma. This time frame corresponds with a period of intense geological subsidence in the region that gave birth to the Pannonian Basin. We conclude that subsidence could have been an important driver of diversification in freshwater Gammarus and that the southwestern Carpathians represent an ancient centre of diversity for these crustaceans.
Association of UBP1 to ribonucleoprotein complexes is regulated by interaction with the trypanosome ortholog of the human multifunctional P32 protein
Authors: Cassola Alejandro , Romaniuk María Albertina , Primrose Debora , Cervini Gabriela , D'Orso Iván , Frasch Alberto Carlos
Published: June 2015

Regulation of gene expression in trypanosomatid parasitic protozoa is mainly achieved posttranscriptionally. RNA‐binding proteins (RBPs) associate to 3′ untranslated regions in mRNAs through dedicated domains such as the RNA recognition motif (RRM). Trypanosoma cruzi UBP1 (TcUBP1) is an RRM‐type RBP involved in stabilization/degradation of mRNAs. TcUBP1 uses its RRM to associate with cytoplasmic mRNA and to mRNA granules under starvation stress. Here, we show that under starvation stress, TcUBP1 is tightly associated with condensed cytoplasmic mRNA granules. Conversely, under high nutrient/low density‐growing conditions, TcUBP1 ribonucleoprotein (RNP) complexes are lax and permeable to mRNA degradation and disassembly. After dissociating from mRNA, TcUBP1 can be phosphorylated only in unstressed parasites. We have identified TcP22, the ortholog of mammalian P32/C1QBP, as an interactor of TcUBP1 RRM. Overexpression of TcP22 decreased the number of TcUBP1 granules in starved parasites in vivo. Endogenous TcUBP1 RNP complexes could be dissociated in vitro by addition of recombinant TcP22, a condition stimulating TcUBP1 phosphorylation. Biochemical and in silico analysis revealed that TcP22 interacts with the RNA‐binding surface of TcUBP1 RRM. We propose a model for the decondensation of TcUBP1 RNP complexes in T. cruzi through direct interaction with TcP22 and phosphorylation.
Emmonsiellopsis, a new genus related to the thermally dimorphic fungi of the family Ajellomycetaceae
Authors: Marin‐Felix Y. , Stchigel A. M. , Cano‐Lira J. F. , Sanchis M. , Mayayo E. , Guarro J.
Published: June 2015

Two interesting fungi were isolated from fluvial sediments collected in the North of Spain. They were morphologically related to the thermally dimorphic fungi of the family Ajellomycetaceae, but the analysis of the internal transcribed spacer region of the rDNA, and the domains D1 and D2 of the 28S rRNA gene sequences confirmed that they were different from all the species described in that family. They were accommodated in the new genus Emmonsiellopsis as E. coralliformis sp. nov. and E. terrestris sp. nov. The two species are distinguished mainly by the maximum temper‐ature of growth (up to 33 °C for E. coralliformis and to 42 °C for E. terrestris), the dendritic mycelium of E. coralliformis and the conidial ornamentation (verrucose in E. coralliformis and spinulose in E. terrestris). In addition, the phylogenetic data demonstrated that Ajellomyces griseus also represents a new genus within the Ajellomycetaceae, namely Helicocarpus. This new genus is easily distinguished by the lack of asexual morph, the production of brownish gymnothecial ascomata and oblate to lenticular, sparingly pitted ascospores. The proposal of both new genera was confirmed by the analysis of actin gene sequences.
FatalFusarium solanispecies complex infections in elasmobranchs: the first case report for black spotted stingray (Taeniura melanopsila) and a literature review
Authors: Fernando Nimal , Hui Suk‐Wai , Tsang Chi‐Ching , Leung Shui‐Yee , Ngan Antonio H. Y. , Leung Raymond W. W. , Groff Joseph M. , Lau Susanna K. P. , Woo Patrick C. Y.
Published: June 2015

Fusariumspecies are environmental saprophytic fungi. Among the manyFusariumspecies, members of theFusarium solanispecies complex (FSSC) are the most prevalent and virulent in causing human and animal infections. In this study, we describe the first case of fatalFSSCinfection in a black spotted stingray and three concomitant infections in scalloped hammerhead sharks. In the stingray, cutaneous lesions were characterised by ulcers and haemorrhage of the ventral pectoral fin, or ‘ray’, especially around the head; while cutaneous lesions in the sharks were characterised by ulcers, haemorrhage, as well as white and purulent exudates at the cephalic canals of the cephalofoil and lateral line. Histological sections of the cutaneous lesions revealed slender (1–4 μm in diameter), branching, septate fungal hyphae. Internal transcribed spacer region and 28S nrDNAsequencing of the fungal isolates from the fish showed two isolates wereF. keratoplasticum(FSSC2) and the other two wereFSSC12. Environmental investigation revealed theFSSCstrains isolated from water and biofilms in tanks that housed the elasmobranchs were alsoF. keratoplasticumandFSSC12.Fusariumis associated with major infections in elasmobranchs andFSSC12 is an emerging cause of infections in marine animals.DNAsequencing is so far the most reliable method for accurate identification ofFusariumspecies.
Decisions and Higher‐Order Knowledge
Authors: Schulz Moritz
Published: June 2015

A knowledge‐based decision theory faces what has been called the prodigality problem (Greco, 2013): given that many propositions are assigned probability 1, agents will be inclined to risk everything when betting on propositions which are known. In order to undo probability 1 assignments in high risk situations, the paper develops a theory which systematically connects higher level goods with higher‐order knowledge.
Endurantism vs. Perdurantism?: A Debate Reconsidered
Authors: Magidor Ofra
Published: June 2015

One of the central debates in contemporary metaphysics has been the debate between endurantism and perdurantism about persistence. In this paper I argue that much of this debate has been misconstrued: most (if not all) of the arguments in the debate crucially rely on theses which are strictly orthogonal to the endurantism/perdurantism debate.

To show this, I note that the arguments in the endurantism/perdurantism debate typically take the following form: one presents a challenge that endurantists (/perdurantists) allegedly have some trouble addressing, and to which perdurantism (/endurantism) apparently has a straightforward response. I argue, however, that in each case, there are versions of endurantism (/perdurantism) that can offer precisely the same (or at least a highly analogous) response to the challenge, and thus the ability to provide this particular solution does not directly tell in favour of one the two views.

In §1, I elaborate two views which will be particularly prominent in the discussion: liberal endurantism and restrictive perdurantism. In §2–6 I discuss in turn the central pro‐perdurantism arguments: the argument from anthropocentricism, the argument from vagueness, the argument from recombination, the argument from temporary intrinsics, and the argument from coincidence. In §7–8, I discuss the main pro‐endurantism arguments: the arguments from motion, and the argument from permanent coincidence. Finally, in §9, I discuss what conclusion can be drawn from this discussion.
Perception of photoperiod in individual buds of mature trees regulates leaf‐out
Authors: Zohner Constantin M. , Renner Susanne S.
Published: June 2015

Experimental data on the perception of day length and temperature in dormant temperate zone trees are surprisingly scarce.

In order to investigate when and where these environmental signals are perceived, we carried out bagging experiments in which buds on branches of Fagus sylvatica, Aesculus hippocastanum and Picea abies trees were exposed to natural light increase or kept at constant 8‐h days from December until June. Parallel experiments used twigs cut from the same trees, harvesting treated and control twigs seven times and then exposing them to 8‐ or 16‐h days in a glasshouse.

Under 8‐h days, budburst in Fagus outdoors was delayed by 41 d and in Aesculus by 4 d; in Picea, day length had no effect. Buds on nearby branches reacted autonomously, and leaf primordia only reacted to light cues in late dormancy after accumulating warm days. Experiments applying different wavelength spectra and high‐resolution spectrometry to buds indicate a phytochrome‐mediated photoperiod control.

By demonstrating local photoperiodic control of buds, revealing the time when these signals are perceived, and showing the interplay between photoperiod and chilling, this study contributes to improved modelling of the impact of climate warming on photosensitive species.
Cholinergic anti‐inflammatory pathway in the non‐obese diabetic mouse model
Authors: Koopman FA , Vosters JL , Roescher N , Broekstra N , Tak PP , Vervoordeldonk MJ
Published: June 2015

Objective

Activation of the cholinergic anti‐inflammatory pathway (CAP) has been shown to reduce inflammation in animal models, while abrogation of the pathway increases inflammation. We investigated whether modulation of CAP influences inflammation in the non‐obese diabetic (NOD) mouse model for Sjögren's syndrome and type 1 diabetes.

Methods

The alpha‐7 nicotinic acetylcholine receptor (α7nAChR) was stimulated with AR‐R17779 or nicotine in NOD mice. In a second study, unilateral cervical vagotomy was performed. α7nAChR expression, focus scores, and salivary flow were evaluated in salivary glands (SG) and insulitis score in the pancreas. Cytokines were measured in serum and SG.

Results

α7nAChR was expressed on myoepithelial cells in SG. Monocyte chemotactic protein‐1 levels were reduced in SG after AR‐R17779 treatment and tumor necrosis factor production was increased in the SG of the vagotomy group compared to controls. Focus score and salivary flow were unaffected. NOD mice developed diabetes more rapidly after vagotomy, but at completion of the study there were no statistically significant differences in number of mice that developed diabetes or in insulitis scores.

Conclusion

Intervention of the CAP in NOD mice leads to minimal changes in inflammatory cytokines, but did not affect overall inflammation and function of SG or development of diabetes.
The effect of infraorbital nerve block on emergence agitation in children undergoing cleft lip surgery under general anesthesia with sevoflurane
Authors: Wang Hong , Liu Gang , Fu Wei , Li Shi‐tong
Published: June 2015

Background

Sevoflurane is widely used in pediatric anesthesia. However, a high incidence of emergence agitation (EA) after general anesthesia with sevoflurane has been reported and pain has been regarded as a significant contributing factor. The objective of this prospective randomized, placebo‐controlled trial was to determine whether infraorbital nerve block reduces EA in children undergoing repair of cleft lip after sevoflurane.

Methods

In this randomized, placebo‐controlled trial, we enrolled 110 children (5 months to 6 years of age), who were scheduled for cleft lip surgery, and randomized them to the following two groups: Group S and Group B, where 1.5 ml saline (Group S) or 1.5 ml 0.25% bupivacaine (Group B) were administered in the infraorbital foramen. Emergence behavior was assessed in the postanesthesia care unit using the Pediatric Anesthesia Emergence Delirium (PAED) scale and a 5‐point scale described by Cole. Pain was evaluated using the Children and Infants Postoperative Pain Scale (CHIPPS).

Results

One‐hundred children (n = 50 per group) completed the study. The endtidal concentration of sevoflurane in Group B was lower than that in Group S. The incidence of EA was 16% in Group B and 42% in Group S (P = 0.008). The PAED scale score in Group B (mean [95% CI] 9 [8–12]) was lower than that in Group S (11.5 [9.8–15]). The duration of EA in Group B was shorter than that in Group S. CHIPPS score in postanesthetic care unit were lower in Group B (mean [95% CI] 3 [2–3.3]) compared with that in Group S (5 [4–6]).

Conclusion

In children undergoing cleft lip repair surgery, infraorbital nerve block at the beginning of surgery significantly decreased the incidence of EA and the duration of EA, and provided satisfactory postoperative analgesia without delaying the time to extubation with sevoflurane anesthesia.
Fast‐track recovery after day case surgery
Authors: Rhondali Ossam , Villeneuve Edith , Queyrel Géraldine , Delorme Mijanou , Vischoff Daniel , Saindon Sophie , Girard Marie‐Andrée , Charest Jean , Mathews Sylvain
Published: June 2015

Background

Fast‐track recovery processes are implemented for pediatric day case surgery. We conducted a prospective study to evaluate postoperative comfort and parental satisfaction of children included in this process to improve quality of care.

Methods

We included all children scheduled for superficial procedures or dental treatment outside the operating room. A questionnaire was explained to parents before hospital discharge to evaluate the first night at home. Postoperative comfort evaluation included postoperative pain score (FLACC scale), incidence of postoperative nausea and vomiting, and postoperative behavior disorders. Incidence of posthospital behavior disturbance was evaluated measuring postoperative agitation at home, and disinterest with toys and games. Parental satisfaction was evaluated with a four‐point Likert scale (1 = not satisfied at all, 2 = not satisfied, 3 = satisfied, 4 = very satisfied).

Results

One hundred and forty‐three questionnaires were returned to hospital. Despite reduced length of stay in short‐stay unit after anesthesia (28 ± 34 min), we did not report serious complications, and global parental satisfaction was good about the care process. Pain scores (FLACC >3) were higher in the group scheduled for dental procedures, but were very low for the other superficial surgery. With an odd ratio of 5.8 (95% confidence interval 2–17; P = 0.001), postoperative behavior modification (agitation or disinterest with toys or games) was the strongest variable that can predict parental dissatisfaction.

Conclusion

Optimal pain management, better parental information about risks of postoperative behavior disturbances, and program integrating parent and child preparation should improve quality of care and global satisfaction in the fast‐track recovery process.
Preoperative preparation workshop reduces postoperative maladaptive behavior in children
Authors: Hilly Julie , Hörlin Anne‐Laure , Kinderf Joelle , Ghez Cecile , Menrath Sabrina , Delivet Honorine , Brasher Christopher , Nivoche Yves , Dahmani Souhayl
Published: June 2015

Introduction

Postoperative maladaptive behaviors (POMBs) are common following pediatric anesthesia, and preoperative anxiety is associated with POMBs. A family‐centered preoperative preparation workshop was instituted with the aim of reducing the incidence of POMB and preoperative anxiety, and the study was constructed to evaluate its effectiveness.

Material and methods

A prospective cohort study was constructed, comparing patients who attended the workshop (workshop group) with patients who did not attend and who were matched for age and type of surgery (comparison group). Preoperative anxiety was measured using the mYPAS score, postoperative emergence agitation (EA) was measured using the PAED score, POMBs were assessed with the Post‐Hospital Behavior Questionnaire (PHBQ) on postoperative day 7, and PACU morphine consumption and PACU length of stay were recorded. Statistical analysis was performed employing the X² test, the Fisher's exact test, and the Mann–Whitney test as appropriate. Data were expressed as median [minimum, maximum].

Results

Fifty‐six patients from 3 to 18 years of age were recruited. Twenty‐seven patients in the workshop group were compared to 26 in the comparison group, after exclusions for missing data. Significant differences were demonstrated between groups for POMBs intensity (PHBQ score 2 [0; 9] vs 5 [0; 10], P = 0.008) and incidence (PHBQ score >6: 3.6% vs 35.7%, P = 0.003), and for mYPAS score (28 [23; 87] vs 37 [23;100], P = 0.015). No difference was found for EA, PACU morphine consumption, or PACU length of stay.

Conclusion

The workshop appears to result in reduced preoperative anxiety and POMBs.
Dexmedetomidine as adjunct to ilioinguinal/iliohypogastric nerve blocks for pediatric inguinal hernia repair: an exploratory randomized controlled trial
Authors: Lundblad Märit , Marhofer Daniela , Eksborg Staffan , Lönnqvist Per‐Arne
Published: June 2015

Background

Adult meta‐analysis has identified dexmedetomidine as a potentially useful adjunct to prolong the duration of peripheral nerve blocks. However, no data exist regarding the adjuvant use of dexmedetomidine in the setting of pediatric peripheral nerve blocks.

Methods

Using a prospective, randomized, double‐blind design, children (1½–8 years, ASA 1–2) scheduled for outpatient inguinal hernia repair were randomized to receive either an ultrasound‐guided ilioinguinal/iliohypogastric nerve block (IINB) with plain ropivacaine 0.197% (Group LA; n = 21) or ropivacaine 0.197% with adjunct dexmedetomidine 0.3 μg·kg−1 (Group LAD; n = 22). The primary endpoint of the study was time to first postoperative administration of supplemental analgesia (FPASA) triggered by a pain score ≥4 (CHIPPS or NRS scale). Intention‐to‐treat (ITT) analysis was decided as the primary statistical analysis of the data.

Results

The median time to FPASA was prolonged by 88% following the use of adjunct dexmedetomidine (4.0 and 7.6 h in group LA and LAD, respectively) (P = 0.0717). Patients in Group LA displayed a significantly higher number of patients with a CHIPPS score ≥4 in the PACU (7 vs 0; P = 0.0029) as well as a higher incidence of PAED (4 vs 0; P = 0.0485) when compared to patients in Group LAD. No adverse events were recorded in any of the study groups.

Conclusions

The use of dexmedetomidine as an adjunct to an IINB resulted in reduced incidences of CHIPPS pain scores ≥4 and PAED scores of ≥11 during early recovery following pediatric inguinal hernia repair. In addition, the use of adjunct dexmedetomidine was associated with a prolongation of the period to first supplemental analgesia demand. The results of the present exploratory study must be viewed as preliminary and need further validation by future larger sized studies and/or meta‐analysis.
Effectiveness of Tapentadol Prolonged Release (PR) Compared with Oxycodone/Naloxone PR for the Management of Severe Chronic Low Back Pain with a Neuropathic Component: A Randomized, Controlled, Open‐Label, Phase 3b/4 Study
Authors: Baron Ralf , Likar Rudolf , Martin‐Mola Emilio , Blanco Francisco J. , Kennes Lieven , Müller Matthias , Falke Dietmar , Steigerwald Ilona
Published: June 2015

Objective

To evaluate the effectiveness of tapentadol prolonged release (PR) vs. oxycodone/naloxone PR in non–opioid‐pretreated patients with severe chronic low back pain with a neuropathic pain component.

Methods

Eligible patients (average pain intensity [numerical rating scale‐3 (NRS‐3)] ≥6; painDETECT positive/unclear) were randomized to twice‐daily tapentadol PR 50 mg or oxycodone/naloxone PR 10 mg/5 mg. After a 21‐day titration (maximum twice‐daily doses: tapentadol PR 250 mg, or oxycodone/naloxone PR 40 mg/20 mg plus oxycodone PR 10 mg), target doses were continued for 9 weeks. The primary effectiveness endpoint was the change in NRS‐3 from baseline to final evaluation; the exact repeated confidence interval (RCI) for tapentadol PR minus oxycodone/naloxone PR was used to establish noninferiority (upper limit <1.3) and superiority (confirmatory analyses).

Results

For the primary effectiveness endpoint, tapentadol PR was noninferior to oxycodone/naloxone PR (97.5% RCI: [−1.820, −0.184]; P < 0.001). This exact RCI also yielded evidence of superiority for tapentadol PR vs. oxycodone/naloxone PR (significantly greater reduction in pain intensity; P = 0.003). Improvements (baseline to final evaluation) in painDETECT and Neuropathic Pain Symptom Inventory scores were significantly greater with tapentadol PR vs. oxycodone/naloxone PR (all P ≤ 0.005).

Conclusions

The study was formally shown to be positive and demonstrated, in the primary effectiveness endpoint, the noninferiority for tapentadol PR vs. oxycodone/naloxone PR. The effectiveness of tapentadol PR was superior to that of oxycodone/naloxone PR by means of clinical relevance and statistical significance (confirmatory evidence of superiority). Tapentadol PR was associated with significantly greater improvements in neuropathic pain‐related symptoms and global health status than oxycodone/naloxone PR and with a significantly better gastrointestinal tolerability profile. Tapentadol PR may be considered a first‐line option for managing severe chronic low back pain with a neuropathic pain component.
ZmABA2, an interacting protein of ZmMPK5, is involved in abscisic acid biosynthesis and functions
Authors: Ma Fangfang , Ni Lan , Liu Libo , Li Xi , Zhang Huan , Zhang Aying , Tan Mingpu , Jiang Mingyi
Published: June 2015

In maize (Zea mays), the mitogen‐activated protein kinase ZmMPK5 has been shown to be involved in abscisic acid (ABA)‐induced antioxidant defence and to enhance the tolerance of plants to drought, salt stress and oxidative stress. However, the underlying molecular mechanisms are poorly understood. Here, using ZmMPK5 as bait in yeast two‐hybrid screening, a protein interacting with ZmMPK5 named ZmABA2, which belongs to a member of the short‐chain dehydrogenase/reductase family, was identified. Pull‐down assay and bimolecular fluorescence complementation analysis and co‐immunoprecipitation test confirmed that ZmMPK5 interacts with ZmABA2 in vitro and in vivo. Phosphorylation of Ser173 in ZmABA2 by ZmMPK5 was shown to increase the activity of ZmABA2 and the protein stability. Various abiotic stimuli induced the expression of ZmABA2 in leaves of maize plants. Pharmacological, biochemical and molecular biology and genetic analyses showed that both ZmMPK5 and ZmABA2 coordinately regulate the content of ABA. Overexpression of ZmABA2 in tobacco plants was found to elevate the content of ABA, regulate seed germination and root growth under drought and salt stress and enhance the tolerance of tobacco plants to drought and salt stress. These results suggest that ZmABA2 is a direct target of ZmMPK5 and is involved in ABA biosynthesis and functions.
Effectiveness of the Photoactive Dye Methylene Blue versus Caspofungin on the Candida parapsilosis Biofilm in vitro and ex vivo
Authors: Černáková Lucia , Chupáčová Jaroslava , Židlíková Katarína , Bujdáková Helena
Published: June 2015

This research studied the effectiveness of the photoactive compound methylene blue (MB) activated with red LED light (576–672 nm) compared to that of caspofungin (CAS) on 1 Candida albicans and 3 Candida parapsilosis strains. Results were evaluated in terms of SMIC50 for CAS or in PDI (photodynamic inactivation)‐SMIC50 for MB (minimal inhibitory concentration inhibiting sessile biofilm to 50% in comparison to the control without CAS or after irradiation in comparison to the control without MB). While all strains were susceptible to CAS in planktonic form, the SMIC50 was determined to be >16 μg mL−1 when CAS was added to a 24 h biofilm. However, PDI‐MIC50s (1.67 mW cm−2, fluence 15 J cm−2) were 0.0075–0.03 mmol L−1. For biofilm, PDI‐SMIC50s were in the range from 0.7 to 1.35 mmol L−1. MB concentration of 1 mmol L−1 prevented a biofilm being formed ex vivo on mouse tongues after irradiation regardless of the application time, in contrast to CAS, which was only effective at a concentration of 16 μg mL−1 when it was added at the beginning of biofilm formation. PDI seems to be a promising method for the prevention of microbial biofilms that do not respond significantly to conventional drugs.
Moral Worth and Moral Knowledge
Authors: Sliwa Paulina
Published: June 2015

To have moral worth an action not only needs to conform to the correct normative theory (whatever it is); it also needs to be motivated in the right way. I argue that morally worthy actions are motivated by the rightness of the action; they are motivated by an agent's concern for doing what's right and her knowledge that her action is morally right. Call this the Rightness Condition. On the Rightness Condition moral motivation involves both a conative and a cognitive element—in particular, it involves moral knowledge. I argue that the Rightness Condition is both necessary and sufficient for moral worth. I also argue that the Rightness Condition gives us an attractive account of actions performed under imperfect epistemic circumstances: by agents who rely on moral testimony or by those who, like Huckleberry Finn, have false moral convictions.
Relative expression analysis of IL‐5 and IL‐6 genes in tropical sheep breed Pelibuey infected with Haemonchus contortus
Authors: Estrada‐Reyes Z. M. , López‐Reyes A. G. , Lagunas‐Martínez A. , Ramírez‐ Vargas G. , Olazarán‐Jenkins S. , Hernández‐Romano J. , Mendoza‐de‐Gives P. , López‐Arellano M. E.
Published: June 2015

Haemonchus contortus is a parasitic nematode of Pelibuey sheep, a meat breed used in tropical regions. Due to anthelmintic problems, the identification of hosts resistant to H. contortus is another option of control. The aim of this study was to analyse the relative expression of IL‐5 and IL‐6 genes in Pelibuey sheep after H. contortus infection. Nineteen lambs infected with H. contortus and three more lambs without infection were studied. The haemonchosis was determined by the number of eggs per gram of faeces (epg) and by the estimation of the percentage of the packed cell volume (%pcv). Peripheral blood mononuclear cells (PBMCs) were obtained to extract RNA at 0, 1, 2, 7, 14, 21 and 28 days after infection to quantify the relative expression of IL‐5, IL‐6 and GAPDH by real‐time PCR. Five lambs were classified as low responders (lr) to haemonchosis with averages of 1519 ± 315·3 epg and 31·49 ± 5·13%pcv, and 14 lambs were identified as high responders (hr) with averages of 530 ± 132 epg and 34·88 ± 3·75%pcv. The expression ratio of IL‐5 was significantly different compared with control lambs at 2, 7 and 14 days post‐infection (PI), and IL‐6 was significantly different after 14 days. The highest level of relative expression for IL‐5 and IL‐6 genes was 9·9‐fold and 12‐fold after 2 and 14 days for hr hosts (P < 0·05) compared with control group, respectively. In conclusion, the Pelibuey breed in grazing areas exhibited different expression of IL‐5 and IL‐6 obtained from PBMCs against H. contortus, suggesting the importance of these cytokines in regulating the nematode infection.
Competition and The Operational Performance of Hospitals: The Role of Hospital Objectives
Authors: Andritsos Dimitrios A. , Aflaki Sam
Published: June 2015

We examine the effect of a hospital's objective (i.e., non‐profit vs. for‐profit) in hospital markets for elective care. Using game‐theoretic analysis and queueing models to capture the operational performance of hospitals, we compare the equilibrium behavior of three market settings in terms of such criteria as waiting times and patient costs from waiting and hospital payments. In the first setting, a monopoly, patients are served exclusively by a single non‐profit hospital; in the second, a homogeneous duopoly, patients are served by two competing non‐profit hospitals. In our third setting, a heterogeneous duopoly, the market is served by one non‐profit hospital and one for‐profit hospital. A non‐profit hospital provides free care to patients, although they may have to wait; for‐profit hospitals charge a fee to provide care with minimal waiting. A comparison between the monopolistic and each of the duopolistic settings reveals that the introduction of competition can hamper a hospital's ability to attain economies of scale and can also increase waiting times. Moreover, the presence of a for‐profit sector may be desirable only when the hospital market is sufficiently competitive. A comparison across the duopolistic settings indicates that the choice between homogeneous and heterogeneous competition depends on the patients' willingness to wait before receiving care and the reimbursement level of the non‐profit sector. When the public funder is not financially constrained, the presence of a for‐profit sector may allow the funder to lower both the financial costs of providing coverage and the total costs to patients. Finally, our analysis suggests that the public funder should exercise caution when using policy tools that support the for‐profit sector—for example, patient subsidies—because such tools may increase patient costs in the long run; it might be preferable to raise the non‐profit sector's level of reimbursement.
Testing and modelling the potential of three diploid plants in Poaceae as a new pathosystem to investigate the interactions between cereal hosts and cereal cyst nematode (Heterodera avenae)
Authors: Kong L. A. , Wu D. Q. , Cui J. K. , Huang W. K. , Peng H. , Peng D. L.
Published: June 2015

Cereal cyst nematode (CCN), Heterodera avenae, is one of the most important pathogens of wheat worldwide, and causes significant yield losses. Research on CCN–wheat interactions is hampered by the lack of an effective model pathosystem. This study investigated the potential of the model cereal Brachypodium distachyon (Bd21‐3) and diploid wheat 2A (G1812) and 2D (AL8/78) as model hosts for CCN. Nematode infection analysis showed that although some CCN penetrated Bd21‐3 roots, these nematodes failed to develop to the later developmental stages or form cysts, indicating B. distachyon is not a host for CCN. A strong burst of reactive oxygen species (ROS) within Bd21‐3 roots infected with CCN was induced 3 days after infection and the expression of seven ROS‐producing genes was significantly increased. In contrast, CCN completed its life cycle in both diploid wheat 2A and 2D, and formed normal syncytia in these hosts. Although CCN developmental processes within both diploid wheat 2A and 2D were very similar to those in the susceptible control, the number of cysts formed on diploid wheat 2D was less than those formed on diploid wheat 2A and the susceptible control, indicating that diploid wheat 2A was a more suitable host for CCN than 2D. This is the first report of a potential new pathosystem for CCN–host interactions using diploid wheat.
Frequency of occurrence and genetic variability of Grapevine fanleaf virus satellite RNA
Authors: Čepin U. , Gutiérrez‐Aguirre I. , Ravnikar M. , Pompe‐Novak M.
Published: June 2015

Little is known about the natural occurrence and genetic variability of nepovirus large satellite RNA (satRNA). This study screened 71 Grapevine fanleaf virus (GFLV) isolates mainly from Slovenia, but also from other countries in Europe and the USA, for the presence of satRNA, using a newly developed RT‐PCR assay. GFLV satRNA (satGFLV) was detected in 72% of naturally GFLV‐infected grapevines analysed, which is the highest frequency of occurrence of satGFLV reported to date. From 39 naturally GFLV‐infected grapevines, 122 satGFLV clones were sequenced and compared to publicly available sequences of satGFLVs and the closely related satRNAs from Arabis mosaic virus (satArMVs). Phylogenetic analyses of these satRNAs revealed that their evolution was driven by substitutions, insertions, deletions, recombinations and reassortments between closely related helper viruses. Phylogenetic relationships of the satGFLVs and satArMVs show their separate and subsequent common evolution. Furthermore, the satGFLVs varied in size and showed higher variability at the amino acid level than at the nucleotide level, just as the 2AHP gene of their helper virus. This study shows that satGFLVs are also similar to their helper virus with respect to their quasispecies nature and their transmission route through anthropogenic exchange of propagation material.
Transcriptional programs regulated by both LEAFY and APETALA1 at the time of flower formation
Authors: Winter Cara M. , Yamaguchi Nobutoshi , Wu Miin‐Feng , Wagner Doris
Published: June 2015

Two key regulators of the switch to flower formation and of flower patterning in Arabidopsis are the plant‐specific helix‐turn‐helix transcription factor LEAFY (LFY) and the MADS box transcription factor APETALA1 (AP1). The interactions between these two transcriptional regulators are complex. AP1 is both a direct target of LFY and can act in parallel with LFY. Available genetic and molecular evidence suggests that LFY and AP1 together orchestrate the switch to flower formation and early events during flower morphogenesis by altering transcriptional programs. However, very little is known about target genes regulated by both transcription factors. Here, we performed a meta‐analysis of public datasets to identify genes that are likely to be regulated by both LFY and AP1. Our analyses uncovered known and novel direct LFY and AP1 targets with a role in the control of onset of flower formation. It also identified additional families of proteins and regulatory pathways that may be under transcriptional control by both transcription factors. In particular, several of these genes are linked to response to hormones, to transport and to development. Finally, we show that the gibberellin catabolism enzyme ELA1, which was recently shown to be important for the timing of the switch to flower formation, is positively feedback‐regulated by AP1. Our study contributes to the elucidation of the regulatory network that leads to formation of a vital plant organ system, the flower.
CLE peptide signaling in plants – the power of moving around
Authors: Kucukoglu Melis , Nilsson Ove
Published: June 2015

The CLAVATA3 (CLV3)/EMBRYO SURROUNDING REGION (ESR)‐RELATED (CLE) gene family encodes small secreted peptide ligands in plants. These peptides function non‐cell autonomously through interactions with plasma membrane‐associated LEUCINE‐RICH REPEAT RECEPTOR‐LIKE KINASEs (LRR‐RLKs). These interactions are critical for cell‐to‐cell communications and control a variety of developmental and physiological processes in plants, such as regulation of stem cell proliferation and differentiation in the meristems, embryo and endosperm development, vascular development and autoregulation of nodulation. Here, we review the current knowledge in the field of CLE polypeptide signaling.
A systematic review of the mismatch negativity as an index for auditory sensory memory: From basic research to clinical and developmental perspectives
Authors: Bartha‐Doering Lisa , Deuster Dirk , Giordano Vito , am Zehnhoff‐Dinnesen Antoinette , Dobel Christian
Published: June 2015

Auditory sensory memory is an important ability for successful language acquisition and processing. The mismatch negativity (MMN) in response to auditory stimuli has been proposed as an objective tool to measure the existence of auditory sensory memory traces. By increasing interstimulus intervals, attenuation of MMN peak amplitude and increased MMN peak latency have been suggested to reflect duration and decay of sensory memory traces. The aim of the present study is to conduct a systematic review of studies investigating sensory memory duration with MMN. Searches of electronic databases yielded 743 articles. Of these, 37 studies met final eligibility criteria. Results point to maturational changes in the time span of auditory sensory memory from birth on with a peak in young adulthood, as well as to a decrease of sensory memory duration in healthy aging. Furthermore, this review suggests that sensory memory decline is related to diverse neurological, psychiatric, and pediatric diseases, including Alzheimer's disease, alcohol abuse, schizophrenia, and language disorders. This review underlines that the MMN provides a unique window to the cognitive processes of auditory sensory memory. However, further studies combining electrophysiological and behavioral data, and further studies in clinical populations are needed, also on individual levels, to validate the MMN as a clinical tool for the assessment of sensory memory duration.
A Dilemma for the Doomsday Argument
Authors: Northcott Robert
Published: June 2015

I present a new case in which the Doomsday Argument (‘DA’) runs afoul of epistemic intuition much more strongly than before. This leads to a dilemma: in the new case either DA is committed to unacceptable counterintuitiveness and belief in miracles, or else it is irrelevant. I then explore under what conditions DA can escape this dilemma. The discussion turns on several issues that have not been much emphasised in previous work on DA: a concern that I label trumping; the degree of uncertainty about relevant probability estimates; and the exact sequence in which we integrate DA and empirical concerns. I conclude that only given a particular configuration of these factors might DA still be of interest.
Evidence of Spontaneous Recovery of Granulosa‐Theca Cell Tumour in a Heifer: A Retrospective Report
Authors: El‐Sheikh Ali H , Kitahara G , Torisu S , Nibe K , Kaneko Y , Hidaka Y , Osawa T
Published: June 2015

Contents

A 14‐month‐old Japanese Black heifer was evaluated on Day 0 (D 0) for enlargement of the right ovary (RO). Transrectal ultrasonography (TRUS) revealed that theROwas markedly enlarged and multicystic, while the left ovary (LO) was small and inactive. The presumptive diagnosis was granulosa‐theca cell tumour (GTCT), which was confirmed by markedly elevated plasma anti‐Müllerian hormone (AMH) of 4.42 ng/ml. Therefore, ovariectomy of theROwas the treatment of choice. The heifer was checked byTRUSand blood sampling on D 42, D 63 and immediately before ovariectomy on D 85. On D 42,TRUSdid not show marked changes in either ovary in comparison with D 0. However, on D 63, theROhad transformed into a single cyst, and on D 85, theLOhad resumed cyclic activity. TheROwas extracted on D 85 by hand‐assisted laparoscopic ovariectomy to allow better control. Unexpectedly, histopathology revealed the lesion to be a fluid‐filled cystic structure, with no neoplastic proliferation of follicular epithelium that would indicateGTCT. The wall of the cystic structure consisted of collagen fibres and a few degenerated granulosa cells. The retrospective hormonal analysis revealed that theAMHconcentrations had markedly dropped on D 63 and 85, which coincided with resumption of cyclicity in theLO. These findings suggest that theGTCThad self‐cured and transformed into a cyst‐like structure. The heifer then received an oestrous synchronization regime on D 105, was artificially inseminated on D 115 and became pregnant.
Doppler and Contrast‐Enhanced Ultrasonography of Testicles in Adult Domestic Felines
Authors: de Brito MBS , Feliciano MAR , Coutinho LN , Uscategui RR , Simões APR , Maronezi MC , de Almeida VT , Crivelaro RM , Gasser B , Pavan L , Russiano WR
Published: June 2015

Contents

The objective was to characterize the vascular patterns of testicular blood flow of adult cats, measuring the systolic velocity (SV), diastolic velocity (DV), resistance index (RI), gate time (wash‐in) peak enhancement and output time (wash‐out) of the contrast and addition of tissue fill characteristics. Forty‐five adult cats were selected, and the echotexture, echogenicity, size, contours and margins of testicles were assessed via ultrasound. By Doppler were evaluated the blood flow and determined of vascular index in testicular artery (SV, DV and RI) and via contrast‐enhanced ultrasonography determine the time for phases: wash‐in, wash‐out and peak enhancement. Sonographic findings presented normal. Testicular artery was observed in the spermatic cord with tortuous patter and showed monophasic‐patterned waves and low vascular resistance and with systolic peak evident. Values of indices vascular were as follows: SV = 6.73 cm/s, DV = 2.8 cm/s and RI = 0.54 for left testicles; and SV = 6.23 cm/s, DV = 2.77 cm/s and RI = 0.53 for right testicles. Contrast filled the subcapsular vascular structures and after a few seconds, a homogeneous moderate enhancement of the parenchyma, with parenchymal vessels still distinguishable and after the peak phase, a rapid homogeneous decrease in echogenicity. Values of time for contrast‐enhanced ultrasonography were as follows: wash‐in = 8.78 s, peak enhancement = 21.62 s and wash‐out = 75.36 for left testicles; and wash‐in = 10.76 s, peak enhancement = 21.50 s and wash‐out = 81.81 for right testicles. Doppler and contrast‐enhanced ultrasonography of the testicles in healthy adult cats was easily implemented and may provide baseline data for this organ to allow the use of these techniques as a diagnostic tool for evaluating testicular abnormalities in sick cats.