bluuebunny/crossref_metadata_2025 huggingface dataset:
A rapid assessment of a poorly known insect group
Authors: Hardwick Bess , Kaartinen Riikka , Koponen Martti , Roslin Tomas
Published: September 2015

'Conservation planning and ecological analyses require large‐scale data on species’ abundance and distribution. We describe a national effort to quickly establish the distributions of taxa with hard‐to‐identify adults but easily identifiable larval stages: cynipid gall wasps (Hymenoptera: Cynipidae, Cynipini) on oak (Quercus robur).

The survey was implemented by volunteers across 239 sites over 687 km of latitude. It yielded 10 523 galls, which were identified by specialists. The material revealed two species new to Finland and the national distributions and local abundances of 16 species.

The likelihood of finding a given species was significantly affected by the visual apparency of its galls. This suggests that some cryptic generations may have been missed in the sampling.

At the national level, our study exposed systematic changes in the species richness of insect taxa associated with a patchily distributed host plant towards its range margin. Species’ incidences decline as host trees grow increasingly scattered within the landscape.

From a conservation perspective, the data increased eight‐fold the known records of gall wasps from Finland, and informed the first assessment of national threat status of these taxa.

Our study reveals how the efforts of the public may be efficiently harnessed for revealing the current status of poorly known taxa. In addition to delivering a first survey of the target taxa, and of factors affecting their distribution, such ‘citizen science’ may generate a permanent base of enthusiasts for the future monitoring of changes and trends.
Singing Delays the Onset of Infant Distress
Authors: Corbeil Mariève , Trehub Sandra E. , Peretz Isabelle
Published: September 2015

Much is known about the efficacy of infant‐directed (ID) speech and singing for capturing attention, but little is known about their role in regulating affect. In Experiment 1, infants 7–10 months of age listened to scripted recordings of ID speech, adult‐directed speech, or singing in an unfamiliar language (Turkish) until they met a criterion of distress based on negative facial expression. They listened to singing for roughly twice as long as speech before meeting the distress criterion. In Experiment 2, they were exposed to natural recordings of ID speech or singing in a familiar language. As in Experiment 1, ID singing was considerably more effective than speech for delaying the onset of distress. We suggest that the temporal patterning of ID singing, with its regular beat, metrical organization, and tempo, plays an important role in inhibiting distress, perhaps by promoting entrainment and predictive listening.
Oxide Electrolytes for Lithium Batteries
Authors: Ren Yaoyu , Chen Kai , Chen Rujun , Liu Ting , Zhang Yibo , Nan Ce‐Wen
Published: September 2015

As the most promising candidate of the solid electrolyte materials for future lithium batteries, oxide electrolytes with high–lithium‐ion conductivity have experienced a rapid development in the past few decades. Existing oxide electrolytes are divided into two groups, i.e., crystalline group including NASICON, perovskite, garnet, and some newly developing structures, and amorphous/glass group including Li2O–MOx (M = Si, B, P, etc.) and LiPON‐related materials. After a historical perspective on the general development of oxide electrolytes, we try to give a comprehensive review on the oxide electrolytes with high–lithium‐ion conductivity, with special emphasis on the aspect of materials selection and design for applications as solid electrolytes in lithium batteries. Some successful examples and meaningful attempts on the incorporation of oxide electrolytes in lithium batteries are also presented. In the conclusion part, an outlook for the future direction of oxide electrolytes development is given.
PULSE‐SMART: Pulse‐Based Arrhythmia Discrimination Using a Novel Smartphone Application
Authors: McMANUS DAVID D. , CHONG JO WOON , SONI APURV , SACZYNSKI JANE S. , ESA NADA , NAPOLITANO CRAIG , DARLING CHAD E. , BOYER EDWARD , ROSEN ROCHELLE K. , FLOYD KEVIN C. , CHON KI H.
Published: September 2015

Automated Arrhythmia Discrimination Using a Smartphone

Background

Atrial fibrillation (AF) is a common and dangerous rhythm abnormality. Smartphones are increasingly used for mobile health applications by older patients at risk for AF and may be useful for AF screening.

Objectives

To test whether an enhanced smartphone app for AF detection can discriminate between sinus rhythm (SR), AF, premature atrial contractions (PACs), and premature ventricular contractions (PVCs).

Methods

We analyzed two hundred and nineteen 2‐minute pulse recordings from 121 participants with AF (n = 98), PACs (n = 15), or PVCs (n = 15) using an iPhone 4S. We obtained pulsatile time series recordings in 91 participants after successful cardioversion to sinus rhythm from preexisting AF. The PULSE‐SMART app conducted pulse analysis using 3 methods (Root Mean Square of Successive RR Differences; Shannon Entropy; Poincare plot). We examined the sensitivity, specificity, and predictive accuracy of the app for AF, PAC, and PVC discrimination from sinus rhythm using the 12‐lead EKG or 3‐lead telemetry as the gold standard. We also administered a brief usability questionnaire to a subgroup (n = 65) of app users.

Results

The smartphone‐based app demonstrated excellent sensitivity (0.970), specificity (0.935), and accuracy (0.951) for real‐time identification of an irregular pulse during AF. The app also showed good accuracy for PAC (0.955) and PVC discrimination (0.960). The vast majority of surveyed app users (83%) reported that it was “useful” and “not complex” to use.

Conclusion

A smartphone app can accurately discriminate pulse recordings during AF from sinus rhythm, PACs, and PVCs.
Periodontal clinical and microbiological characteristics in healthy versus generalized aggressive periodontitis families
Authors: Monteiro Mabelle de F. , Casati Marcio Z. , Taiete Tiago , do Vale Hugo F. , Nociti Francisco Humberto , Sallum Enilson Antônio , Silvério Karina G. , Casarin Renato C. V.
Published: September 2015

Aim

Generalized aggressive periodontitis (GAP) is a severe and multifactorial disease in which a familial aggregation and a specific microbiological profile have been suggested. Thus, this case–control study evaluated the clinical and subgingival microbial profile of GAP subjects and their families compared to healthy families.

Methods

Fifteen families with parents presenting periodontal health and 15 with parents with a history of GAP were selected. Each family should have at least one child between 6 and 12 years old. Plaque index (PI), gingival index (GI), and periodontal probing depth (PPD), as well as Porphyromonas gingivalis, Tannerella forsythia, and Aggregatibacter actinomycetemcomitans (Aa) amounts (by qPCR), were assessed from all subjects.

Results

Children of GAP families showed a higher PI, GI, and PPD when compared to children of healthy families (p ≤ 0.05). A higher frequency of detection and amounts of Aa was observed in GAP children compared to children of healthy families (p ≤ 0.05). Moreover, a significant association between Aa amounts and gingival bleeding was observed in children (p ≤ 0.05, r = 0.37).

Conclusion

Children from GAP families have worst clinical conditions, i.e. higher levels of PI, GI, and PPD, a more pathogenic microbiological profile, and the amount of Aa are associated with a higher marginal inflammation.
Children with autism spectrum disorder and social skills groups at school: a randomized trial comparing intervention approach and peer composition
Authors: Kasari Connie , Dean Michelle , Kretzmann Mark , Shih Wendy , Orlich Felice , Whitney Rondalyn , Landa Rebecca , Lord Catherine , King Bryan
Published: September 2015

Background

Peer relationships improve for children with autism spectrum disorder (ASD) in clinic‐based social skills groups but rarely generalize to real world contexts. This study compares child outcomes of two social skills interventions conducted in schools with children in Kindergarten through fifth grade.

Method

Children with ASD were randomized to one of two interventions that varied on group composition (mixed typical and ASD vs. all ASD or social difficulties) and intervention approach (didactic SKILLS based vs. activity‐based ENGAGE groups). Interventions were implemented at school for 8 weeks (16 sessions) with an 8‐week follow‐up. Innovative measures of peer nomination and playground peer engagement, as well as teacher reports of child behavior problems and teacher–child relationship were analyzed for 137 children with ASD across four sites.

Results

On the primary outcome of social network connections from the peer nomination measure, there was no main effect of treatment, but there were moderator effects. Children with low teacher–child closeness or high conflict improved more in their social connections if they received the SKILLS intervention, whereas children with higher teacher–child closeness improved more if they received the ENGAGE intervention. Only two secondary outcome measures yielded significant effects of treatment. Children in the SKILLS groups increased peer engagement and decreased isolation during recess. Child behavior problems and teacher–child closeness moderated peer engagement such that children with higher behavior problems and lower closeness benefitted more from SKILLS groups.

Conclusions

These findings suggest that social skills groups conducted at school can affect both peer engagement during recess as well as peer acceptability. Child characteristics and teacher–child relationship prior to intervention yield important information on who might benefit from a specific social skills intervention.
THE GOVERNANCE OF FINANCIAL SUPERVISION: RECENT DEVELOPMENTS
Authors: Masciandaro Donato , Quintyn Marc
Published: September 2015

This paper examines the evolution of financial supervision as a policy tool over the last three decades, with a focus on the issues raised by the Global Crisis. It considers a sample of advanced and emerging economies to discuss the four main questions debated in the literature, and addressed in the economic policy arena: the architecture of supervision, the role of the central bank as supervisor, the governance of supervision, and financial supervision vs. the internationalization of finance. Our survey finds that, on each of these issues, theory and practice do not offer clear‐cut answers and unambiguous optimal solutions. At the same time, the most promising approach is to tackle financial supervision as a principal‐agent problem, where economics and political economy approaches must be used in combination to improve both positive and normative analyses of supervisory governance.
Development issues regarding Bunot Lake: the Lesser Lake among the seven lakes of San Pablo City, Philippines
Authors: Brillo Bing Baltazar C.
Published: September 2015

Bunot Lake exhibits the worst conditions among the seven crater lakes of San Pablo City in the Philippines. It is the most polluted lake, being oversaturated with fish pens/cages. It also hosts the largest concentration of illegal settlements. These attributes strongly suggest that Bunot Lake merits much greater attention in the agenda of its two administrative agencies, the Laguna Lake Development Authority (LLDA) and the City Government. The reality, however, is that Bunot Lake is lacking key development initiatives and programmes and seems to occupy a low priority to the LLDA and the City Government. This reality is particularly perplexing as the lake is located very near the urban centre, is closest to the premier lake (Sampaloc Lake), and is the site of the first commercial production of tilapia in floating cages in the city. Against this background, the present study identifies and analyses the immediate development issues for Bunot Lake. It contends that Bunot Lake should be given preference by the LLDA and the City Government, specifically by: (i) modifying their model‐template approach; and (ii) taking steps to tackle a basic need of Bunot Lake, namely the formulation of a zoning‐development plan. The present study also was designed to directly address the lacuna in Philippine lake studies, namely the paucity of research under the social science perspective (which is currently dominated by the natural science perspective) and on small lakes (which is currently concentrated on the largest lakes in the country).
Environmental control of the dominant phytoplankton in Aras Reservoir (Iran): A multivariate approach
Authors: Mohebbi Fereidun , Riahi Hossein , Sheidaei Masoud , Shariatmadari Zeinab , Manaffar Ramin
Published: September 2015

This study was undertaken to determine the phytoplankton structure and the environmental variables comprising the driving factors leading to cyanobacterial blooms in Aras Reservoir. Sampling was carried out seasonally at five sampling sites along the main body of the reservoir. Samples were collected for phytoplankton identification and enumeration, chemical analyses and chlorophyll‐a (Chl‐a) concentrations at each sampling site. Principal component analysis (PCA) and two‐way unweighted pair group method with arithmetic mean (UPGMA) were performed to determine the environmental variables affecting phytoplankton community dynamics. Seventy‐two species belonging to five divisions were determined during this study. Cyanobacteria contained the highest density (74%) during the study period, with Pseudanabaena limnetica being the most abundant species. The Shannon diversity index was low (0.44–1.87), indicating a high level of cyanobacteria dominance and eutrophic water status. Principal component analysis indicated that total phosphorus and temperature were significantly associated with cyanobacteria growth. Two‐way clustering by UPGMA indicated a close relationship among sampling sites during the same season from the perspective of the phytoplankton density. The findings of this study suggested Aras Reservoir could be highly affected by agricultural runoff and untreated sewage loadings. Thus, the proper use of fertilizers and sewage treatment should be taken into account in considering effective conservation and management plans.
Tonle Sap Lake, Cambodia: A perspective on its transborder hydrological and resources governance
Authors: Sithirith Mak
Published: September 2015

Tonle Sap Lake is the largest freshwater lake in South East Asia, being situated at the heart of the Mekong River Basin. Governance of the lake over the recent past has been weak and overly complex, and the basin governance structure has changed over time in terms of its fisheries management framework. The governance framework initially focused on the commercial exploitation of fish resources, but has more recently switched to a community‐based fisheries management, biodiversity conservation and open access model. This study discusses how the water flows occurring between the Mekong River and Tonle Sap Lake complicate the governance of the lake, and particularly its fisheries, biodiversity, land and water management activities. The establishment of the Tonle Sap Authority (TSA) in 2007 sought to address the governance challenges facing the lake. The current study concludes, however, that the TSA alone is not sufficient and that global, regional and national stakeholders must make an effort to ensure the water flows between the lake and the Mekong River are themselves considered a core governance issue for the Tonle Sap.
Trait‐based partner selection drives mycorrhizal network assembly
Authors: Chagnon Pierre‐Luc , Bradley Robert L. , Klironomos John N.
Published: September 2015

Plants and their microbial symbionts are often found to interact non‐randomly in nature, but we have yet to understand the mechanisms responsible for such preferential species associations. Theory predicts that host plants should select symbiotic partners bearing traits complementary to their own, as this should favor cooperation and evolutionary stability of mutualisms. Here, we present the first field‐based empirical test for this hypothesis using arbuscular mycorrhizas (AM), the oldest and most widespread plant symbiosis. Preferential associations occurring within a local plant–AM fungal community could not be predicted by the spatial distributions of interacting partners, nor by gradients in soil properties. Rather, plants with similar traits preferentially hosted similar AM fungi and, likewise, phylogenetically related AM fungi (assumed to have similar functional traits) interacted with similar plants. Our results suggest that trait‐based partner selection may have been a strong force in maintaining plant–AM fungal symbioses since the evolution of land plants.
A systematic review and meta‐analysis of acute severe complications of pediatric anesthesia
Authors: Mir ghassemi Asadollah , Neira Victor , Ufholz Lee‐Anne , Barrowman Nick , Mulla Jamila , Bradbury Carol L. , Bould Matthew Dylan
Published: September 2015

Background

Quantification of acute severe complications of pediatric anesthesia is essential to plan clinical guidelines and educational curricula.

Aim

Our aim was to identify complications in terms of frequency and outcomes.

Methods

We defined acute severe complications as an unexpected perioperative event, which without intervention by the anesthesiologist within 30 min may lead to disability or death. A systematic search was performed using MEDLINE, EMBASE, and CINAHL. Screening and data extraction were performed independently. Assessment of bias was conducted using GRADE guidelines.

Results

Of 3002 abstracts, 25 met all inclusion criteria. The most common acute severe complications in pediatric anesthesia are related to airway management and respiratory system, followed by cardiovascular events. There was a great variation in reporting the methods, particularly poor definitions of diagnostic criteria for complications. Data were heterogeneous and pooled estimates may not be generalizable. Some studies failed to define potential source of bias, explain how missing data were addressed, describe acute severe complications, and had incomplete postoperative follow‐up.

Conclusion

The data on pediatric anesthesia acute severe complications are poorly defined with large variation in the specificity of diagnostic reporting even within studies. We suggest that it is vital for future studies in this area to be based on a standardized system of diagnostic reporting (possibly with a hierarchical system of coding) with adequate description of population details to describe heterogeneity of data.
Mobility in China
Authors: Chen Yi , Cowell Frank A.
Published: September 2015

The evidence on rank and income mobility in China reveals an important change around the year 2000. Using panel data from the China Health and Nutrition Survey we show that rank mobility fell markedly from the decade immediately preceding the millennium to the decade immediately following: in this respect China is becoming noticeably more rigid. By contrast income mobility has carried on increasing; so has income inequality. The simultaneous increase in rigidity and inequality presents China with a challenging policy problem.
Bayesian Spatial Modelling for High Dimensional Seismic Inverse Problems
Authors: Zhang Ran , Czado Claudia , Sigloch Karin
Published: September 2015

We study the application of Bayesian spatial modelling to seismic tomography, a geophysical, high dimensional, linearized inverse problem that infers the three-dimensional structure of the Earth’s interior. We develop a spatial dependence model of seismic wave velocity variations in the Earth’s mantle based on a Gaussian Matérn field approximation. Using the theory of stochastic partial differential equations, this model quantifies the uncertainties in the parameter space by means of the integrated nested Laplace approximation. In resolution tests using simulated data and in inversions using real data, our model matches the performance of conventional deterministic optimization approaches in retrieving three-dimensional structure of the Earth’s mantle. In addition it delivers estimates of the full parameter covariance matrix. Our model substantially improves on previous work relying on Markov chain Monte Carlo methods in terms of statistical misfits and computing time.
Forward Guidance and the Predictability of Monetary Policy: A Wavelet-Based Jump Detection Approach
Authors: Winkelmann Lars
Published: September 2015

The publication of a projected path of future policy decisions by central banks is a controversially debated method to improve monetary policy guidance. The paper proposes a new approach to evaluate the effect of the guidance strategy on the predictability of monetary policy. The empirical investigation is based on jump probabilities of Norwegian interest rates on announcement days of the Norges Bank before and after the introduction of quantitative guidance. Within the standard semimartingale framework, we propose a new methodology to detect jumps. We derive a representation of the quadratic variation in terms of a wavelet spectrum. An adaptive threshold procedure on wavelet spectrum estimates aims at localizing jumps. Our main empirical result indicates that quantitative guidance significantly improves the predictability of monetary policy.
Mixed Effects Historical Varying-Coefficient Model for Evaluating Dose–Response in Flexible Dose Trials
Authors: Misumi Toshihiro , Konishi Sadanori
Published: September 2015

Varying-coefficient models provide a useful tool to explore the dynamic pattern in various fields of science, such as epidemiology, medical research and ecology. Crucial issues arise in assessing the dose–response relationship from flexible dose clinical trial data: the current response is affected by not only the current dose level but also past dose levels, i.e. there is a time lag in the effectiveness of treatment and, also, there is considerable variability between subjects. To address these issues, we propose a novel non-linear varying-coefficient model, called a mixed effects historical varying-coefficient model (MEHVCM), for estimating dose–response curves in longitudinal flexible dose trials. This model enables us to describe historical effectiveness curves and subject-specific curves. Unknown parameters included in the MEHVCM are estimated by the maximum penalized likelihood method along with the EM algorithm. Monte Carlo experiments are conducted to investigate the performance of the MEHVCM for evaluating dose–response relationships in flexible dose trials. We apply the proposed model to the analysis of data from a multiple-sclerosis clinical trial.
SOCS3 in retinal neurons and glial cells suppresses VEGF signaling to prevent pathological neovascular growth
Authors: Sun Ye , Ju Meihua , Lin Zhiqiang , Fredrick Thomas W. , Evans Lucy P. , Tian Katherine T. , Saba Nicholas J. , Morss Peyton C. , Pu William T. , Chen Jing , Stahl Andreas , Joyal Jean-Sébastien , Smith Lois E. H.
Published: September 2015

Enhancing SOCS3 activity in neurons and glial cells in the retina may prevent abnormal blood vessel formation in proliferative retinopathies.
Conjugated Linoleic Acid Reduces Cholera Toxin Production
In Vitro
and
In Vivo
by Inhibiting Vibrio cholerae ToxT Activity
Authors: Withey Jeffrey H. , Nag Dhrubajyoti , Plecha Sarah C. , Sinha Ritam , Koley Hemanta
Published: September 2015

The severe diarrheal disease cholera is endemic in over 50 countries. Current therapies for cholera patients involve oral and/or intravenous rehydration, often combined with the use of antibiotics to shorten the duration and intensity of the disease. However, as antibiotic resistance increases, treatment options will become limited. Linoleic acid has been shown to be a potent negative effector of
V. cholerae
virulence that acts on the major virulence transcription regulator protein, ToxT, to inhibit virulence gene expression. ToxT activates transcription of the two major virulence factors required for disease, cholera toxin (CT) and toxin-coregulated pilus (TCP). A conjugated form of linoleic acid (CLA) is currently sold over the counter as a dietary supplement and is generally recognized as safe by the U.S. Food and Drug Administration. This study examined whether CLA could be used as a new therapy to reduce CT production, which, in turn, would decrease disease duration and intensity in cholera patients. CLA could be used in place of traditional antibiotics and would be very unlikely to generate resistance, as it affects only virulence factor production and not bacterial growth or survival.
High-Throughput Intracellular Antimicrobial Susceptibility Testing of Legionella pneumophila
Authors: Chiaraviglio Lucius , Kirby James E.
Published: September 2015

Legionella pneumophila
is a Gram-negative opportunistic human pathogen that causes a severe pneumonia known as Legionnaires' disease. Notably, in the human host, the organism is believed to replicate solely within an intracellular compartment, predominantly within pulmonary macrophages. Consequently, successful therapy is predicated on antimicrobials penetrating into this intracellular growth niche. However, standard antimicrobial susceptibility testing methods test solely for extracellular growth inhibition. Here, we make use of a high-throughput assay to characterize intracellular growth inhibition activity of known antimicrobials. For select antimicrobials, high-resolution dose-response analysis was then performed to characterize and compare activity levels in both macrophage infection and axenic growth assays. Results support the superiority of several classes of nonpolar antimicrobials in abrogating intracellular growth. Importantly, our assay results show excellent correlations with prior clinical observations of antimicrobial efficacy. Furthermore, we also show the applicability of high-throughput automation to two- and three-dimensional synergy testing. High-resolution isocontour isobolograms provide
in vitro
support for specific combination antimicrobial therapy. Taken together, findings suggest that high-throughput screening technology may be successfully applied to identify and characterize antimicrobials that target bacterial pathogens that make use of an intracellular growth niche.
Old Drugs To Treat Resistant Bugs: Methicillin-Resistant Staphylococcus aureus Isolates with
mecC
Are Susceptible to a Combination of Penicillin and Clavulanic Acid
Authors: Ba Xiaoliang , Harrison Ewan M. , Lovering Andrew L. , Gleadall Nicholas , Zadoks Ruth , Parkhill Julian , Peacock Sharon J. , Holden Matthew T. G. , Paterson Gavin K. , Holmes Mark A.
Published: September 2015

β-Lactam resistance in methicillin-resistant
Staphylococcus aureus
(MRSA) is mediated by the expression of an alternative penicillin-binding protein 2a (PBP2a) (encoded by
mecA
) with a low affinity for β-lactam antibiotics. Recently, a novel variant of
mecA
, known as
mecC
, was identified in MRSA isolates from both humans and animals. In this study, we demonstrate that
mecC
-encoded PBP2c does not mediate resistance to penicillin. Rather, broad-spectrum β-lactam resistance in MRSA strains carrying
mecC
(
mecC
-MRSA strains) is mediated by a combination of both PBP2c and the distinct β-lactamase encoded by the
blaZ
gene of strain LGA251 (
blaZ
LGA251
), which is part of
mecC
-encoding staphylococcal cassette chromosome
mec
(SCC
mec
) type XI. We further demonstrate that
mecC
-MRSA strains are susceptible to the combination of penicillin and the β-lactam inhibitor clavulanic acid
in vitro
and that the same combination is effective
in vivo
for the treatment of experimental
mecC
-MRSA infection in wax moth larvae. Thus, we demonstrate how the distinct biological differences between
mecA
- and
mecC
-encoded PBP2a and PBP2c have the potential to be exploited as a novel approach for the treatment of
mecC
-MRSA infections.
Chronic Invasive Aspergillus Sinusitis and Otitis with Meningeal Extension Successfully Treated with Voriconazole
Authors: Morgand Marjolaine , Rammaert Blandine , Poirée Sylvain , Bougnoux Marie-Elisabeth , Tran Hugo , Kania Romain , Chrétien Fabrice , Jouvion Gregory , Lortholary Olivier
Published: September 2015

Invasive aspergillosis (IA) is a severe disseminated fungal disease that occurs mostly in immunocompromised patients. However, central nervous system IA, combining meningitis and skull base involvement, does not occur only in groups with classic risk factors for IA; patients with chronic renal failure and diabetes mellitus are also at risk for more chronic forms. In both of our proven IA cases, voriconazole monotherapy was effective without surgery, and cerebrospinal fluid and serum 1,3-β-
d
-glucan test results were initially positive, in contrast to galactomannan antigen results.
Substitutions at NS3 Residue 155, 156, or 168 of Hepatitis C Virus Genotypes 2 to 6 Induce Complex Patterns of Protease Inhibitor Resistance
Authors: Jensen Sanne B. , Serre Stéphanie B. N. , Humes Daryl G. , Ramirez Santseharay , Li Yi-Ping , Bukh Jens , Gottwein Judith M.
Published: September 2015

Various protease inhibitors (PIs) currently are becoming available for treatment of hepatitis C virus (HCV). For genotype 1, substitutions at NS3 protease positions 155, 156, and 168 are the main determinants of PI resistance. For other genotypes, similar substitutions were selected during PI treatment but were not characterized systematically. To elucidate the impact of key PI resistance substitutions on genotypes 2 to 6, we engineered the substitutions R155A/E/G/H/K/Q/T, A156G/S/T/V, and D/Q168A/E/G/H/N/V into HCV recombinants expressing genotype 2 to 6 proteases. We evaluated viral fitness and sensitivity to nine PIs (telaprevir, boceprevir, simeprevir, asunaprevir, vaniprevir, faldaprevir, paritaprevir, deldeprevir, and grazoprevir) in Huh7.5 cells. We found that most variants showed decreased fitness compared to that of the original viruses. Overall, R155K, A156G/S, and D/Q168A/E/H/N/V variants showed the highest fitness; however, genotype 4 position 168 variants showed strong fitness impairment. Most variants tested were resistant to several PIs. Resistance levels varied significantly depending on the specific substitution, genotype, and PI. For telaprevir and boceprevir, specific 155 and 156, but not 168, variants proved resistant. For the remaining PIs, most genotype 2, 4, 5, and 6, but not genotype 3, variants showed various resistance levels. Overall, grazoprevir (MK-5172) had the highest efficacy against original viruses and variants. This is the first comprehensive study revealing the impact of described key PI resistance substitutions on fitness and PI resistance of HCV genotypes 2 to 6. In conclusion, the studied substitutions induced resistance to a panel of clinically relevant PIs, including the newer PIs paritaprevir, deldeprevir, and grazoprevir. We discovered complex patterns of resistance, with the impact of substitutions varying from increased sensitivity to high resistance.
Escherichia coli Free Radical-Based Killing Mechanism Driven by a Unique Combination of Iron Restriction and Certain Antibiotics
Authors: Ma Li , Gao Yongjun , Maresso Anthony W.
Published: September 2015

Bacterial resistance to antibiotics is precipitating a medical crisis, and new antibacterial strategies are being sought. Hypothesizing that a growth-restricting strategy could be used to enhance the efficacy of antibiotics, we determined the effect of FDA-approved iron chelators and various antibiotic combinations on invasive and multidrug-resistant extraintestinal pathogenic
Escherichia coli
(ExPEC), the Gram-negative bacterium most frequently isolated from the bloodstreams of hospitalized patients. We report that certain antibiotics used at sublethal concentrations display enhanced growth inhibition and/or killing when combined with the iron chelator deferiprone (DFP). Inductively coupled plasma optical emission spectrometry reveals abnormally high levels of cell-associated iron under these conditions, a response that correlates with an iron starvation response and supraphysiologic levels of reactive oxygen species (ROS). The high ROS level is reversed upon the addition of antioxidants, which restores bacterial growth, suggesting that the cells are inhibited or killed by excessive free radicals. A model is proposed in which peptidoglycan-targeting antibiotics facilitate the entry of lethal levels of iron-complexed DFP into the bacterial cytoplasm, a process that drives the generation of ROS. This new finding suggests that, in addition to restriction of access to iron as a general growth-restricting strategy, targeting of cellular pathways or networks that selectively disrupt normal iron homeostasis can have potent bactericidal outcomes.

IMPORTANCE
The prospect that common bacteria will become resistant to all antibiotics is challenging the medical community. In addition to the development of next-generation antibiotics, new bacterial targets that display cytotoxic properties when altered need to be identified. Data presented here demonstrate that combining subinhibitory levels of both iron chelators and certain antibiotics kills pathogenic
Escherichia coli
. The mechanism of this effect is the production of supraphysiologic levels of reactive oxygen species, likely powered by the excessive import of iron. These findings were consistent for both clinically relevant and no longer clinically used antibiotics and may extend to
Staphylococcus aureus
as well.
Cervical deciduosis imitating dysplasia
Authors: van Diepen Diederik Anthony , Hellebrekers Bart , Haaften Anne-Marie van , Natté Remco
Published: September 2015

Ectopic cervical deciduosis is generally an accidental finding during pregnancy, and usually presents without any symptoms or need for therapeutic intervention. However, it can sometimes imitate dysplasia or carcinoma. We report a case of a 34-year-old G2P0, with a history of cervical dysplasia, presenting at 11 weeks of gestation, with vaginal blood loss. During examination, lesions mimicking dysplasia were found on the cervix. Histological examination reported cervical deciduosis. Deciduosis is a benign change during pregnancy and will resolve spontaneously. With the increasing use of cytology and colposcopy, the reported incidence is growing. When it is hard to differentiate between dysplasia and deciduosis, histological confirmation should be considered.
Adolescent-onset Krabbe disease with an initial diagnosis of multiple sclerosis and a novel mutation
Authors: Tomás José , Durães João , Lacerda Lúcia , Macário Maria Carmo
Published: September 2015

Krabbe disease is a rare autosomal recessive leucodystrophy, with <5% of the cases having an adolescent-onset form. A 30-year-old woman with a history of a subacute episode of gait impairment at 14 years of age, and mild spastic paraparesis since then, was followed with an initial diagnosis of multiple sclerosis. After 10 years of slow disease progression without response to treatment, the initial diagnosis was reviewed, and an extensive metabolic work up revealed decreased activity of galactocerebrosidase. Genetic testing of the GALC gene proved the diagnosis of Krabbe disease and found a novel mutation. This case highlights the value of a critical eye in the initial differential diagnosis, mainly in the presence of atypical findings.
Unintentional baclofen intoxication in the management of alcohol use disorder
Authors: Reichmuth Philipp , Blanc Anne-Laure , Tagan Damien
Published: September 2015

In recent years, there has been a growing interest in using baclofen for the management of alcohol use disorder. Thisoff-labelindication usually involves high doses of the medication. We report a case of severe baclofen overdose in a 66-year-old man. The patient was found severely agitated, and he presented with delirium and auditory hallucinations. At hospital admission, his daily dose was 180 mg baclofen. He was admitted to the intensive care unit for sedation and supportive care. When sedation was withdrawn, the patient presented with a normal neurological status. In this clinical context, baclofen intoxication was suspected. This was confirmed by measuring blood baclofen levels. This intoxication was probably mediated by a combination of risk factors including a high daily dose of baclofen and acute renal failure, conducive to drug accumulation.
A novel non-invasive index using AFP and APTT is associated with liver fibrosis in patients with chronic hepatitis B infection: a retrospective cohort study
Authors: Feng Limin , Sun Ke , Zhang Jie , Feng Guofang , Zhao Ying
Published: September 2015

Objective

A liver biopsy is the ‘reference standard’ for diagnosing and staging liver fibrosis but with many disadvantages. Therefore, developing a non-invasive index for predicting fibrosis is very valuable. We developed and validated a novel non-invasive index for predicting significant fibrosis in patients with chronic hepatitis B infection.

Design

A retrospective cohort study.

Setting

Chronic hepatitis B virus-infected patients were recruited in the Department of Infectious Disease in the First Affiliated Hospital of Zhejiang University.

Participants

A total of 506 patients were enrolled, and patients were randomly divided into estimation (n=253) and validation (n=253) cohorts.

Primary and secondary outcome measures

Chronic hepatitis B virus-infected patients were studied retrospectively using routine parameters. A novel index was developed from an estimation cohort and validated in another cohort. Liver histology was assessed for fibrosis according to the Xi'an Meeting Scoring System. The novel index using α-fetal protein (AFP) and activated partial thromboplastin time (APTT; denoted AA index) was compared with 10 other indices using receiving operating characteristics curves. Multivariate forward stepwise regression analysis revealed that AFP and APTT were significantly associated with the Xi'an Meeting Scoring System, and were used to calculate the AA index (log index=−9.164+0.114×AFP+0.236×APTT).

Results

The AA index predicted significant fibrosis with an area under the curve of 0.822, exhibited a significantly higher area compared with the other 10 indices in the estimation cohort, and was validated in the validation cohort.

Conclusions

The AA index can be used to predict significant fibrosis, and may decrease the need for liver biopsy in patients with chronic hepatitis B infection.
The vulnerability of Arctic shelf sediments to climate change
Authors: Macdonald Robie W. , Kuzyk Zou Zou A. , Johannessen Sophia C.
Published: September 2015

The sediments of the pan-Arctic shelves contribute an important component to the Arctic Ocean ecosystem by providing a habitat for biota (benthos), a repository for organic and inorganic non-conservative substances entering or produced within the ocean, a reactor and source of transformed substances back to the water column, and a mechanism of burial. Sediments interact with ice, ocean, and the surrounding land over a wide range of space and time scales. We discuss the vulnerability of shelf sediment to changes in (i) organic carbon sources, (ii) pathways of sediment and organic carbon supply, and (iii) physical and biogeochemical alteration (diagenesis). Sedimentary environments of the shelves and basins are likely to exhibit a wide variance in their response to global change because of their wide variation in sediment sources, processes, and metabolic conditions. In particular, the Chukchi and Barents shelves are dominated by inflowing waters from oceans to the south, whereas the interior shelves are more closely tied to terrigenous sources due to river inflow and coastal erosion.
Controlling crystallization process and thermal stability of a binary Cu–Zr bulk metallic glass via minor element addition
Authors: Zhang S. T. , Wang Q. , Liu T. T. , Liu J. J.
Published: September 2015

In this paper, the effect of minor element addition on the initial structural evolution during crystallization in a simple binary Cu–Zr bulk metallic glass (BMG) forming liquid has been investigated by using differential scanning calorimetry (DSC) and X-ray diffraction (XRD). Despite no changes in the completely crystallized products, the remarkable opposite impacts on the supercooled liquid region (SLR) and crystallization reaction rate constant [Formula: see text] are observed as a result of minor selective additions of an affine element, i.e., Sn and an immiscible element, i.e., Nb into the Cu–Zr BMG alloy, respectively. Furthermore, it is demonstrated that the primary devitrification pathway and crystalline phases are simultaneously modified, which leads to significant changes in kinetics of atomic rearrangement and thus thermal stability of this material. Such a finding offers a promising way to control the type of primary crystalline phases of BMG-forming metallic supercooled liquids to synthesize novel BMGs or BMG matrix composites for structural or functional applications.
The stability of a connection on Hermitian vector bundles over a Riemannian manifold
Authors: Bakhshandeh-Chamazkoti Rohollah , Nadjafikhah Mehdi
Published: September 2015

In this attempt, the stability of a connection on Hermitian vector bundles over a Riemannian manifold for the generalized Jensen-type functional equation [Formula: see text] is discussed. In fact, the main purpose of this paper is to prove the generalized Hyers–Ulam–Rassias stability of connection on between Hermitian [Formula: see text] and [Formula: see text]. Also we will use the fixed point method to prove the stability of this connection for the above generalized Jensen-type functional equation.
Global existence and boundedness of classical solutions to the Owen–Sherratt model
Authors: Baghaei Khadijeh , Hesaaraki Mahmoud
Published: September 2015

In this paper, we study the mathematical model proposed by Owen and Sherratt in 1997. We prove that the classical solutions to this model are uniformly-in-time bounded.
On some interesting properties for a new subclass of multivalent functions
Authors: Ahmad M. Z. , Ibrahim Rabha W. , Al-Janaby Hiba F.
Published: September 2015

In this paper, we establish a new subfamily [Formula: see text] of multivalent functions with negative coefficients that involve certain linear operator. We first investigate sharp results concerning coefficients, then obtain the distortion theorem, radius of convexity and close-to-convexity, closure theorem, neighborhood property, partial sums and integral representation.
Quantitative seismic interpretation using inverse rock physics modelling
Authors: Bredesen Kenneth , Jensen Erling Hugo , Johansen Tor Arne , Avseth Per
Published: September 2015

Extracting information about reservoir quality from seismic data is a key challenge in exploration, appraisal and production of hydrocarbons. We demonstrate how to perform quantitative reservoir characterization by using inverse rock physics modelling on seismic inversion data. This allows us to evaluate the non-uniqueness of our predictions. We demonstrate our methodology on a gas–condensate Norwegian Sea field under appraisal and production, and perform reservoir quality predictions along a selected seismic cross-section where we have well control. Even though such a seismic dataset is more uncertain than well log data, which have been used previously in similar analysis, we still achieve reasonable and consistent predictions of reservoir quality.
An MINLP Model for Scheduling and Placement of Quantum Circuits with a Heuristic Solution Approach
Authors: Bahreini Tayebeh , Mohammadzadeh Naser
Published: September 2015

Recent works on quantum physical design have pushed the scheduling and placement of quantum circuit into their prominent positions. In this article, a mixed integer nonlinear programming model is proposed for the placement and scheduling of quantum circuits in such a way that latency is minimized. The proposed model determines locations of gates and the sequence of operations. The proposed model is proved reducible to a quadratic assignment problem which is a well-known NP-complete combinatorial optimization problem. Since it is impossible to find the optimal solution of this NP-complete problem for large quantum circuits within a reasonable amount of time, a metaheuristic solution method is developed for the proposed model. Some experiments are conducted to evaluate the performance of the developed solution approach. Experimental results show that the proposed approach improves average latency by about 24.09% for the attempted benchmarks.
Performance of Faulty Loss Systems with Persistent Connections
Authors: Patch Brendan , Taimre Thomas , Nazarathy Yoni
Published: September 2015

We consider a finite capacity Erlang loss system that alternates between active and inactive states according to a two state modulating Markov process. Work arrives to the system as a Poisson process but is blocked from entry when the system is at capacity or inactive. Blocked jobs cost the owner a fixed amount that depends on whether blockage was due to the system being at capacity or due to the system being inactive. Jobs which are present in the system when it becomes inactive pause processing until the system becomes active again.

A Laplace transform expression for the expected undiscounted revenue lost in [0, t] due to blocking is found. Further, an expression for the total time discounted expected lost revenue in [0,?) is provided. We also derive a second order approximation to the former that can be used when the computing power to invert the Laplace transform is not available. These expressions can be used to ascribe a value to four alternatives for improving system performance: (i) increasing capacity, (ii) increasing the service rate, (iii) increasing the repair rate, or (iv) decreasing the failure rate.
Network calculus for parallel processing
Authors: Kesidis G. , Shan Y. , Urgaonkar B. , Liebeherr J.
Published: September 2015

In this paper, we present preliminary results on the use of "network calculus" for parallel processing (fork join) systems,
e.g.
, MapReduce. We derive a probabilistic bound that the delay through a single parallel processing stage exceeds a threshold.
Maximizing Cache Hit Ratios by Variance Reduction
Authors: Berger Daniel S. , Henningsen Sebastian , Ciucu Florin , Schmitt Jens B.
Published: September 2015

TTL cache models provide an attractive unified approximation framework for caching policies like LRU and FIFO, whose exact analysis is notoriously hard. In this paper, we advance the understanding of TTL models by explicitly considering stochastic capacity constraints. We find in particular that reducing the variance of the cache occupancy is instrumental to optimize the cache hit ratio in an online setting. To enforce such a desired low variance, we propose a novel extension of the TTL model by rewarding popular objects with longer TTLs. An attractive feature of the proposed model is that it remains closed under an exact network analysis.