bluuebunny/crossref_metadata_2025 huggingface dataset:
Amazon River water in the northeastern Caribbean Sea and its effect on larval reef fish assemblages during April 2009
Authors: Johns E. M. , Muhling B. A. , Perez R. C. , Müller‐Karger F. E. , Melo N. , Smith R. H. , Lamkin J. T. , Gerard T. L. , Malca E.
Published: November 2014

During April to June 2009, a large bolus of Amazon River water impacted the northeastern Caribbean Sea. Shipboard observations collected near Saba Bank, the U.S. and British Virgin Islands, and the Anegada Passage showed low surface salinity (35.76 ± 0.05 Practical Salinity Unit (PSU)), elevated surface temperature (26.77 ± 0.14°C), high chlorophyll‐a (1.26 ± 0.21 mg m−3) and high dissolved oxygen (4.90 ± 0.06 mL L−1) in a 20‐ to 30‐m thick surface layer in the riverine plume. The water was ~1°C warmer, 1 PSU fresher, 0.3 mL L−1 higher in oxygen and 1.2 mg m−3 higher in chlorophyll‐a than Atlantic Ocean waters to the north, with Caribbean surface waters showing intermediate values. Plankton net tows obtained in the upper 100 m of the water column revealed larval fish assemblages within the plume that were significantly different from those of the surrounding waters and from those encountered in the area in previous years. The plume waters contained higher concentrations of mesopelagic fish larvae from the families Myctophidae and Nomeidae, which as adults typically inhabit offshore, deep water habitats. Concentrations of larvae from inshore and reef‐associated families such as Scaridae, Serranidae, Labridae and Clupeidae were lower than those found outside the plume in similar shallow areas, particularly in near‐surface waters. An event like the one observed in 2009 had not been documented in at least the past 30 yr, and yet it was followed by another similarly extreme event in 2010. The ecological implications, including any long‐term consequences of such recent extreme events, are important and merit further study.
Trajectories of English Acquisition among Foreign-born Spanish-Language Children in the United States
Authors: Stevens Gillian
Published: November 2014

The rapidity with which immigrant children learn the dominant language of their country of residence has important short-term and long-term consequences for their educational achievements and for their future. In this paper I use US Census data to model trajectories of English acquisition among foreign-born children living in Spanish-language households. The results show, as expected, that children's English proficiency increases with length of residence in the United States. However, the results also show a clear trend by age at arrival. The older children are when they arrive in the United States, the less rapid their progress in acquiring proficiency in English.
Gender Differences in the Role of Migrant Networks: Comparing Congolese and Senegalese Migration Flows
Authors: Toma Sorana , Vause Sophie
Published: November 2014

This paper uses recent longitudinal data collected within the Migration between Africa and Europe (MAFE) project to investigate gender differences in the role of migrant networks in international mobility. Furthermore, we compare Congolese and Senegalese migration streams to examine how the interplay between gender and networks varies across contexts of origin. We go beyond previous studies by considering the case of spousal reunification alongside other forms of migration: we separate the role of the migrant spouse from other network ties, as failing to do so overestimates the role of migrant networks in female mobility. We further find that Senegalese women are more likely than men to rely on geographically concentrated networks, composed of close kin and established abroad for a long time. Gender differences are much less pronounced in the Congolese case, which we relate to the more rigid patriarchal norms in Senegal, restricting female autonomy both in terms of mobility and economic activity.
Two‐echelon manufacturer–retailer supply chain strategies with price, quality, and promotional effort sensitive demand
Authors: Pal Brojeswar , Sana Shib Sankar , Chaudhuri Kripasindhu
Published: November 2014

This study deals with the two‐layer supply chain model of one manufacturer and one retailer for a single commodity where market demand is assumed to be dependent on selling price, quality of the products, and promotional effort of the retailer. We investigate the behavior of the supply chain under centralized, manufacturer Stackelberg, conditional manufacturer Stackelberg, retailer Stackelberg, conditional retailer Stackelberg, and vertical Nash model structure. The nature of the above models provides great insights to a firm's manager for achieving optimal strategy in a competitive marketing system. Quite often, not all items produced in a firm are of perfect quality; some are perfect (conforming) quality and others are imperfect (nonconforming) quality. The nonconforming products are sold in a secondary shop or by other retailers. The procurement cost of finished products depends on the quality of the products due to more investment in advanced technology, better raw materials, and skilled labor, etc. The warranty policy for the products is also imposed to attract the customers to buy more. Here, both members (manufacturer and retailer) jointly share the cost of the warranty policy. The objective of this paper is to determine the optimal selling price and promotional effort of the retailer, while the optimal wholesale price and quality of the products are determined by the manufacturer so that the above strategies are maximized. Finally, numerical examples with sensitivity analysis of the key parameters are illustrated to investigate the proposed model.
Association between sugar‐sweetened beverages and type 2 diabetes: A meta‐analysis
Authors: Wang Meng , Yu Min , Fang Le , Hu Ru‐Ying
Published: November 2014

Aims/Introduction

Many studies have been carried out to examine the association between sugar‐sweetened beverages and the incident of type 2 diabetes, but results are mixed. The aim of the present study was to estimate the association between sugar‐sweetened beverage intake and the risk of type 2 diabetes.

Materials and Methods

PubMed, Springer Link and Elsevier databases were searched up to July 2014. Prospective studies published on the association between sugar‐sweetened beverage intake and the risk of type 2 diabetes were included. The pooled relative risks (RRs) and 95% confidence intervals (CIs) for highest versus lowest category of sugar‐sweetened beverages were estimated using a random‐effects model.

Results

The pooled effect estimate of sugar‐sweetened beverage intake was 1.30 (95% confidence interval [CI] 1.21–1.39) for type 2 diabetes; stratified by geographic region of the studies, the pooled effect estimates were 1.34 (95% CI 0.74–2.43), 1.30 (95% CI 1.20–1.40), 1.29 (95% CI 1.09–1.53) in Asia, the USA and Europe,respectively; the pooled effect estimates were 1.26 (95% CI 1.16–1.36) with adjusting body mass index and 1.38 (95% CI 1.23–1.56) without adjusting body mass index.

Conclusions

Our findings suggested that sugar‐sweetened beverage intake was associated with an increased risk of type 2 diabetes, and the association was attenuated by adjustment for body mass index. Specifically, the associations were also found to be significantly positive in the USA and Europe.
Psoriasis in the elderly: epidemiological and clinical aspects, and evaluation of patients with very late onset psoriasis
Authors: Phan C. , Sigal M.‐L. , Estève E. , Reguiai Z. , Barthélémy H. , Beneton N. , Maccari F. , Lahfa M. , Thomas‐Beaulieu D. , Le Guyadec T. , Vermersch‐Langlin A. , Mery‐Bossard L. , Pallure V. , Kemula M. , Labeille B. , Beauchet A. , Mahé E. ,   GEM RESOPSO
Published: November 2014

Background

Age of the patients and age of onset of psoriasis may have an impact on the disease. There is little information about psoriasis in elderly patients.

Objective

We evaluated epidemiological, clinical aspects, comorbidities and treatments of psoriasis in the elderly (>70 years) patients, and in patients with very late onset psoriasis (onset ≥ 70 years).

Methods

This observational multicentre non‐interventional study of adults with psoriasis was conducted in 29 departments of dermatology in France. A total of 2210 adults with psoriasis were included.

Results

A total of 212 (9.5%) patients were elderly. This group had a higher frequency of females (P = 0.005), a later onset of the disease (P < 0.0001), a lower frequency of familial (P < 0.0001) and plaque psoriasis (P < 0.0001), but higher frequency of guttate and inverse psoriasis (P ≤ 0.005). Hypertension, diabetes, dyslipidaemia, and major cardiovascular events (MACE) were more frequent in this group (P < 0.0001), but not tobacco (P < 0.0001). Systemic and biological therapies were used less frequently in the elderly group (P < 0.0001).

Fifty‐eight (2.7%) patients had late onset psoriasis. Patients with very late onset psoriasis were more frequently women (P = 0.02) and older (P < 0.0001), among elderly group. They had significantly less frequently familial (P < 0.0001) and plaque psoriasis (P < 0.0001), and were less often on systemic treatment including biological. Frequencies of comorbidities were not statically different but patients with ‘early’ onset psoriasis have a tendency (P < 0.5) to have higher frequencies of obesity, diabetes, dyslipidaemia, hypertension and MACE.

Conclusion

This study highlights phenotypic features of psoriasis in elderly and in very late onset psoriasis. The management of these fragile patients remains poorly codified and needs further investigation.
Melatonin blunts the mitochondrial/NLRP3 connection and protects against radiation‐induced oral mucositis
Authors: Ortiz Francisco , Acuña‐Castroviejo Darío , Doerrier Carolina , Dayoub José C. , López Luis C. , Venegas Carmen , García José A. , López Ana , Volt Huayqui , Luna‐Sánchez Marta , Escames Germaine
Published: November 2014

Mucositis is a common and distressing side effect of chemotherapy or radiotherapy that has potentially severe consequences, and no treatment is available. The purpose of this study was to analyze the molecular pathways involved in the development of oral mucositis and to evaluate whether melatonin can prevent this pathology. The tongue of male Wistar rats was subjected to irradiation (X‐ray YXLON Y.Tu 320‐D03 irradiator; the animals received a dose of 7.5 Gy/day for 5 days). Rats were treated with 45 mg/day melatonin or vehicle for 21 days postirradiation, either by local application into their mouths (melatonin gel) or by subcutaneous injection. A connection between reactive oxygen species, generating mitochondria and the NLRP3 (NLR‐related protein 3 nucleotide‐binding domain leucine‐rich repeat containing receptor‐related protein 3) inflammasome, has been reported in mucositis. Here, we show that mitochondrial oxidative stress, bioenergetic impairment and subsequent NLRP3 inflammasome activation are involved in the development of oral mucositis after irradiation and that melatonin synthesized in the rat tongue is depleted after irradiation. The application of melatonin gel restores physiological melatonin levels in the tongue and prevents mucosal disruption and ulcer formation. Melatonin gel protects the mitochondria from radiation damage and blunts the NF‐κB/NLRP3 inflammasome signaling activation in the tongue. Our results suggest new molecular pathways involved in radiotherapy‐induced mucositis that are inhibited by topical melatonin application, suggesting a potential preventive therapy for mucositis in patients with cancer.
A Study of Possible Associations Between Single Nucleotide Polymorphisms in the Estrogen Receptor 2 Gene and Female Sexual Desire
Authors: Gunst Annika , Jern Patrick , Westberg Lars , Johansson Ada , Salo Benny , Burri Andrea , Spector Tim , Eriksson Elias , Sandnabba N. Kenneth , Santtila Pekka
Published: November 2014

Introduction

Female sexual desire and arousal problems have been shown to have a heritable component of moderate size. Previous molecular genetic studies on sexual desire have mainly focused on genes associated with neurotransmitters such as dopamine and serotonin. Nevertheless, there is reason to believe that hormones with more specific functions concerning sexuality could have an impact on sexual desire and arousal.

Aim

The aim of the present study was to investigate the possible effects of 17 single nucleotide polymorphisms (SNPs) located in estrogen receptor genes on female sexual desire and subjective and genital arousal (lubrication). Based on previous research, we hypothesized that ESR1 and ESR2 are relevant genes that contribute to female sexual desire and arousal.

Main Outcome Measures

The desire, arousal, and lubrication subdomains of the Female Sexual Function Index self-report questionnaire were used.

Methods

The present study involved 2,448 female twins and their sisters aged 18–49 who had submitted saliva samples for genotyping. The participants were a subset from a large-scale, population-based sample.

Results

We found nominally significant main effects on sexual desire for three ESR2-linked SNPs when controlled for anxiety, suggesting that individuals homozygous for the G allele of the rs1271572 SNP, and the A allele of the rs4986938 and rs928554 SNPs had lower levels of sexual desire. The rs4986938 SNP also had a nominally significant effect on lubrication. No effects for any of the SNPs on subjective arousal could be detected.

Conclusions

The number of nominally significant results for SNPs in the ESR2 gene before correcting for multiple testing suggests that further studies on the possible influence of this gene on interindividual variation in female sexual functioning are warranted. In contrast, no support for an involvement of ESR1 was obtained. Our results should be interpreted with caution until replicated in independent, large samples.
High dermatophyte contamination levels in hairdressing salons of a West African suburban community
Authors: Coulibaly O. , Thera M. A. , Piarroux R. , Doumbo O. K. , Ranque S.
Published: November 2014

Tinea capitis is a dermatophyte infection of scalp is commonly spread by currently infected patients, asymptomatic carriers or by fomites, such as hairdressing tools. However, studies on the risk factors of Tinea capitis remain scarce. The aim of this study was to evaluate the dermatophytes contamination level of the hairdressing tools to which hairdressing salon customers are exposed in Sirakoro‐Méguétana, a suburb of Bamako, the capital city of Mali. A total of 41 hairdressing tools were sampled in five hairdressing salons. Two anthropophilic dermatophytes species, Microsporum audouinii (53.3%) and Trichophyton soudanense (46.7%), were cultured from 30 (73.2%) samples. This first study, addressing hairdressing salons dermatophyte contamination, revealed a strikingly high contamination of hairdressing tools with dermatophyte propagules, which exposes hairdressing salons customers to an important dermatophytosis risk. The sterilisation of hairdressing tools is central to preventing dermatophytoses spreading. Appropriate community information and hairdressers training should be implemented in this view.
Plasticity to simulated shade is associated with altitude in structured populations of Arabidopsis thaliana
Authors: BOTTO JAVIER F.
Published: November 2014

Plants compete for photosynthesis light and induce a shade avoidance syndrome (SAS) that confers an important advantage in asymmetric competition for light at high canopy densities. Shade plasticity was studied in a greenhouse experiment cultivating Arabidopsis thaliana plants from 15 populations spread across an altitudinal gradient in the northeast area of Spain that contain a high genetic variation into a reduced geographical range. Plants were exposed to sunlight or simulated shade to identify the range of shade plasticity. Fourteen vegetative, flowering and reproductive traits were measured throughout the life cycle. Shade plasticity in flowering time and dry mass was significantly associated with the altitude of population origin. Plants from coastal populations showed higher shade plasticity indexes than those from mountains. The altitudinal variation in flowering leaf plasticity adjusted negatively with average and minimum temperatures, whereas dry mass plasticity was better explained by negative regressions with the average, maximum and minimum temperatures, and by a positive regression with average precipitation of the population origin. The lack of an altitudinal gradient for the widest number of traits suggests that shade light could be a driver explaining the distribution pattern of individuals in smaller geographical scales than those explored here.
Identification of soluble and membrane antigenic markers of acquired toxoplasmosis by immunoblot
Authors: Khammari I. , Saghrouni F. , Lakhal S. , Bougmiza I. , Bouratbine A. , Ben Said M. , Boukadida J.
Published: November 2014

The overall performance of quantitative assays in the detection of anti‐Toxoplasma IgG is satisfactory, but discrepancies between assays are not uncommon especially when IgG concentrations are close to the limit of detection of the tests. The purpose of our study was to identify soluble and membrane antigens extracted from Toxoplasma gondii tachyzoites by immunoblot to select the most relevant antigenic bands to be used for qualitative serodiagnosis of acquired toxoplasmosis. We selected five relevant bands (98, 36, 33, 32 and 21 kDa) with soluble antigens and four relevant bands (42, 35, 32 and 30 kDa) with membrane antigens which gave high sensitivity and/or specificity in immunodiagnosis. The association on the same blot of at least three of the five relevant bands in the soluble antigen immunoblot showed the highest sensitivity/specificity (97·4%/99·0%, respectively). Our results indicate that immunoblot using soluble tachyzoite extract with simultaneous detection of at least three of the five bands (98, 36, 33, 32 and 21 kDa) represents a valuable test for serodiagnosis of acquired toxoplasmosis and should be further evaluated as a confirmatory test for sera which give discrepant results in quantitative assays.
Phenotypic and Genotypic Characterization of Salmonella enterica in Captive Wildlife and Exotic Animal Species in Ohio, USA
Authors: Farias L. F. P. , Oliveira C. J. B. , Medardus J. J. , Molla B. Z. , Wolfe B. A. , Gebreyes W. A.
Published: November 2014

The purpose of this study was to investigate the occurrence, antimicrobial resistance patterns, phenotypic and genotypic relatedness of Salmonella enterica recovered from captive wildlife host species and in the environment in Ohio, USA. A total of 319 samples including faecal (n = 225), feed (n = 38) and environmental (n = 56) were collected from 32 different wild and exotic animal species in captivity and their environment in Ohio. Salmonellae were isolated using conventional culture methods and tested for antimicrobial susceptibility with the Kirby–Bauer disc diffusion method. Salmonella isolates were serotyped, and genotyping was performed using the pulsed‐field gel electrophoresis (PFGE). Salmonella was detected in 56 of 225 (24.9%) faecal samples; six of 56 (10.7%) environmental samples and six of 38 (15.8%) feed samples. Salmonella was more commonly isolated in faecal samples from giraffes (78.2%; 36/46), cranes (75%; 3/4) and raccoons (75%; 3/4). Salmonella enterica serotypes of known public health significance including S. Typhimurium (64.3%), S. Newport (32.1%) and S. Heidelberg (5.3%) were identified. While the majority of the Salmonella isolates were pan‐susceptible (88.2%; 60 of 68), multidrug‐resistant strains including penta‐resistant type, AmStTeKmGm (8.8%; six of 68) were detected. Genotypic diversity was found among S. Typhimurium isolates. The identification of clonally related Salmonella isolates from environment and faeces suggests that indirect transmission of Salmonella among hosts via environmental contamination is an important concern to workers, visitors and other wildlife. Results of this study show the diversity of Salmonella serovars and public health implications of human exposure from wildlife reservoirs.
Adiponectin fine‐tuning of liver regeneration dynamics revealed through cellular network modelling
Authors: Correnti Jason M. , Cook Daniel , Aksamitiene Edita , Swarup Aditi , Ogunnaike Babatunde , Vadigepalli Rajanikanth , Hoek Jan B.
Published: November 2014

Key points

Loss of adiponectin delays the initiation of liver regeneration after partial hepatectomy, but later accelerates regeneration.

Loss of adiponectin modulates these regeneration kinetics through decreased hepatocyte response to inflammation and increased growth factor bioavailability.

Increased adiponectin suppresses liver regeneration through decreased growth factor bioavailability.

Our predictive computational model was able to connect these molecular regulatory events to tissue physiology.

Following partial hepatectomy, the liver initiates a regenerative programme involving hepatocyte priming and replication driven by the coordinated actions of cytokine and growth factors. We investigated the mechanisms underlying adiponectin's (Adn) regulation of liver regeneration through modulation of these mediators. Adn–/– mice showed delayed onset of hepatocyte replication, but accelerated cell cycle progression relative to wild‐type mice, suggesting Adn has multiple effects fine‐tuning the kinetics of liver regeneration. We developed a computational model describing the molecular and physiological kinetics of liver regeneration in Adn–/– mice. We employed this computational model to evaluate the underlying regulatory mechanisms. Our analysis predicted that Adn is required for an efficient early cytokine response to partial hepatectomy, but is inhibitory to later growth factor actions. Consistent with this prediction, Adn knockout reduced hepatocyte responses to interleukin‐6 during the priming phase, but enhanced growth factor levels through peak hepatocyte replication. By contrast, supraphysiological concentrations of Adn resulting from rosiglitazone treatment suppressed regeneration by reducing growth factor levels during S phase, consistent with computational predictions. Together, these results revealed that Adn fine‐tunes the progression of liver regeneration through dynamically modulating molecular mediator networks and cellular interactions within the liver.
Population Pharmacokinetics of Gentamicin and Dosing Optimization for Infants
Authors: Medellín-Garibay Susanna E. , Rueda-Naharro Aída , Peña-Cabia Silvia , García Benito , Romano-Moreno Silvia , Barcia Emilia
Published: November 2014

The aim of this study was to characterize and validate the population pharmacokinetics of gentamicin in infants and to determine the influences of clinically relevant covariates to explain the inter- and intraindividual variabilities associated with this drug. Infants receiving intravenous gentamicin and with routine therapeutic drug monitoring were consecutively enrolled in the study. Plasma concentration and time data were retrospectively collected from 208 infants (1 to 24 months old) of the Hospital Universitario Severo Ochoa (Spain), of whom 44% were males (mean age [± standard deviation], 5.8 ± 4.8 months; mean body weight, 6.4 ± 2.2 kg). Data analysis was performed with NONMEM 7.2. One- and two-compartment open models were analyzed to estimate the gentamicin population parameters and the influences of several covariates. External validation was carried out in another population of 55 infants. The behavior of gentamicin in infants exhibits two-compartment pharmacokinetics, with total body weight being the covariate that mainly influences central volume (
V
c
) and clearance (CL); this parameter was also related to creatinine clearance. Both parameters are age related and different from those reported for neonatal populations. On the basis of clinical presentation and diagnosis, a once-daily dosage regimen of 7 mg/kg of body weight every 24 h is proposed for intravenous gentamicin, followed by therapeutic drug monitoring in order to avoid toxicity and ensure efficacy with minimal blood sampling. Gentamicin pharmacokinetics and disposition were accurately characterized in this pediatric population (infants), with the parameters obtained being different from those reported for neonates and children. These differences should be considered in the dosing and therapeutic monitoring of this antibiotic.
Pharmacodynamic Evaluation of the Activities of Six Parenteral Vancomycin Products Available in the United States
Authors: Louie Arnold , Boyne Michael T. , Patel Vikram , Huntley Clayton , Liu Weiguo , Fikes Steven , Kurhanewicz Stephanie , Rodriquez Jaime , Robbins Nichole , Brown David , Baluya Dodge , Drusano G. L.
Published: November 2014

A recent report found that generic parenteral vancomycin products may not have
in vivo
efficacies equivalent to those of the innovator in a neutropenic murine thigh infection model despite having similar
in vitro
microbiological activities and murine serum pharmacokinetics. We compared the
in vitro
and
in vivo
activities of six of the parenteral vancomycin products available in the United States. The
in vitro
assessments for the potencies of the vancomycin products included MIC/minimal bactericidal concentration (MBC) determinations, quantifying the impact of human and murine serum on the MIC values, and time-kill studies. Also, the potencies of the vancomycin products were quantified with a biological assay, and the human and mouse serum protein binding rates for the vancomycin products were measured. The
in vivo
studies included dose-ranging experiments with the 6 vancomycin products for three isolates of
Staphylococcus aureus
in a neutropenic mouse thigh infection model. The pharmacokinetics of the vancomycin products were assessed in infected mice by population pharmacokinetic modeling. No differences were seen across the vancomycin products with regard to any
in vitro
evaluation. Inhibitory sigmoid maximal bacterial kill (
E
max
) modeling of the relationship between vancomycin dosage and the killing of the bacteria in mice
in vivo
yielded similar
E
max
and EC
50
(drug exposure driving one-half
E
max
) values for bacterial killing. Further, there were no differences in the pharmacokinetic clearances of the 6 vancomycin products from infected mice. There were no important pharmacodynamic differences in the
in vitro
or
in vivo
activities among the six vancomycin products evaluated.
Antiviral Activity of a Single-Domain Antibody Immunotoxin Binding to Glycoprotein D of Herpes Simplex Virus 2
Authors: Geoghegan Eileen M. , Zhang Hong , Desai Prashant J. , Biragyn Arya , Markham Richard B.
Published: November 2014

Despite years of research dedicated to preventing the sexual transmission of herpes simplex virus 2 (HSV-2), there is still no protective vaccine or microbicide against one of the most common sexually transmitted infections in the world. Using a phage display library constructed from a llama immunized with recombinant HSV-2 glycoprotein D, we identified a single-domain antibody VHH, R33, which binds to the viral surface glycoprotein D. Although R33 does not demonstrate any HSV-2 neutralization activity
in vitro
, when expressed with the cytotoxic domain of exotoxin A, the resulting immunotoxin (R33ExoA) specifically and potently kills HSV-2-infected cells, with a 50% neutralizing dilution (IC
50
) of 6.7 nM. We propose that R33ExoA could be used clinically to prevent transmission of HSV-2 through killing of virus-producing epithelial cells during virus reactivation. R33 could also potentially be used to deliver other cytotoxic effectors to HSV-2-infected cells.
Reduced Polymorphism in the Kelch Propeller Domain in Plasmodium vivax Isolates from Cambodia
Authors: Popovici Jean , Kao Sokheng , Eal Leanghor , Bin Sophalai , Kim Saorin , Ménard Didier
Published: November 2014

Polymorphism in the ortholog gene of the
Plasmodium falciparum
K13 gene was investigated in
Plasmodium vivax
isolates collected in Cambodia. All of them were Sal-1 wild-type alleles except two (2/284, 0.7%), and
P. vivax
K12 polymorphism was reduced compared to that of the
P. falciparum
K13 gene. Both mutant allele isolates had the same nonsynonymous mutation at codon 552 (V552I) and were from Ratanak Kiri province. These preliminary data should encourage additional studies for associating artemisinin or chloroquine resistance and K12 polymorphism.
Effect of Steady-State Faldaprevir on the Pharmacokinetics of Steady-State Methadone and Buprenorphine-Naloxone in Subjects Receiving Stable Addiction Management Therapy
Authors: Joseph David , Schobelock Michael J. , Riesenberg Robert R. , Vince Bradley D. , Webster Lynn R. , Adeniji Abidemi , Elgadi Mabrouk , Huang Fenglei
Published: November 2014

The effects of steady-state faldaprevir on the safety, pharmacokinetics, and pharmacodynamics of steady-state methadone and buprenorphine-naloxone were assessed in 34 healthy male and female subjects receiving stable addiction management therapy. Subjects continued receiving a stable oral dose of either methadone (up to a maximum dose of 180 mg per day) or buprenorphine-naloxone (up to a maximum dose of 24 mg-6 mg per day) and also received oral faldaprevir (240 mg) once daily (QD) for 8 days following a 480-mg loading dose. Serial blood samples were taken for pharmacokinetic analysis. The pharmacodynamics of the opioid maintenance regimens were evaluated by the objective and subjective opioid withdrawal scales. Coadministration of faldaprevir with methadone or buprenorphine-naloxone resulted in geometric mean ratios for the steady-state area under the concentration-time curve from 0 to 24 h (AUC
0–24,ss
), the steady-state maximum concentration of the drug in plasma (
C
max,ss
), and the steady-state concentration of the drug in plasma at 24 h (
C
24,ss
) of 0.92 to 1.18 for (
R
)-methadone, (
S
)-methadone, buprenorphine, norbuprenorphine, and naloxone, with 90% confidence intervals including, or very close to including, 1.00 (no effect), suggesting a limited overall effect of faldaprevir. Although individual data showed moderate variability in the exposures between subjects and treatments, there was no evidence of symptoms of opiate overdose or withdrawal either during the coadministration of faldaprevir with methadone or buprenorphine-naloxone or after faldaprevir dosing was stopped. Similar faldaprevir exposures were observed in the methadone- and buprenorphine-naloxone-treated subjects. In conclusion, faldaprevir at 240 mg QD can be coadministered with methadone or buprenorphine-naloxone without dose adjustment, although given the relatively narrow therapeutic windows of these agents, monitoring for opiate overdose and withdrawal may still be appropriate. (This study has been registered at
ClinicalTrials.gov
under registration no. NCT01637922.)
Gastrointestinal Dissemination and Transmission of Staphylococcus aureus following Bacteremia
Authors: Kernbauer Elisabeth , Maurer Katie , Torres Victor J. , Shopsin Bo , Cadwell Ken
Published: November 2014

Mutations that alter virulence and antibiotic susceptibility arise and persist during
Staphylococcus aureus
bacteremia. However, an experimental system demonstrating transmission following bacteremia has been lacking, and thus implications of within-host adaptation for between-host transmission are unknown. We report that
S. aureus
disseminates to the gastrointestinal tract of mice following intravenous injection and readily transmits to cohoused naive mice. Both intestinal dissemination and transmission were linked to the production of virulence factors based on gene deletion studies of the
sae
and
agr
two-component systems. Furthermore, antimicrobial selection for antibiotic-resistant
S. aureus
displaced susceptible
S. aureus
from the intestine of infected hosts, which led to the preferential transmission and dominance of antibiotic-resistant bacteria among cohoused untreated mice. These findings establish an animal model to investigate gastrointestinal dissemination and transmission of
S. aureus
and suggest that adaptation during the course of systemic infection has implications beyond the level of a single host.
Toxin-Mediated Paracellular Transport of Antitoxin Antibodies Facilitates Protection against Clostridium difficile Infection
Authors: Zhang Z. , Chen X. , Hernandez L. D. , Lipari P. , Flattery A. , Chen S.-C. , Kramer S. , Polishook J. D. , Racine F. , Cape H. , Kelly C. P. , Therien A. G.
Published: November 2014

The exotoxins TcdA and TcdB are the major virulence factors of
Clostridium difficile
. Circulating neutralizing antitoxin antibodies are protective in
C. difficile
infection (CDI), as demonstrated, in part, by the protective effects of actoxumab and bezlotoxumab, which bind to and neutralize TcdA and TcdB, respectively. The question of how systemic IgG antibodies neutralize toxins in the gut lumen remains unresolved, although it has been suggested that the Fc receptor FcRn may be involved in active antibody transport across the gut epithelium. In this study, we demonstrated that genetic ablation of FcRn and excess irrelevant human IgG have no impact on actoxumab-bezlotoxumab-mediated protection in murine and hamster models of CDI, suggesting that Fc-dependent transport of antibodies across the gut wall is not required for efficacy. Tissue distribution studies in hamsters suggest, rather, that the transport of antibodies depends on toxin-induced damage to the gut lining. In an
in vitro
two-dimensional culture system that mimics the architecture of the intestinal mucosal epithelium, toxins on the apical side of epithelial cell monolayers are neutralized by basolateral antibodies, and antibody transport across the cell layer is dramatically increased upon addition of toxin to the apical side. Similar data were obtained with F(ab′)
2
fragments, which lack an Fc domain, consistent with FcRn-independent paracellular, rather than transcellular, transport of antibodies. Kinetic studies show that initial damage caused by apical toxin is required for efficient neutralization by basolateral antibodies. These data may represent a general mechanism of humoral response-mediated protection against enteric pathogens.
Late Establishment of the Attaching and Effacing Lesion Caused by Atypical Enteropathogenic Escherichia coli Depends on Protein Expression Regulated by Per
Authors: Bueris Vanessa , Huerta-Cantillo Jazmín , Navarro-Garcia Fernando , Ruiz Renato M. , Cianciarullo Aurora M. , Elias Waldir P.
Published: November 2014

Enteropathogenic
Escherichia coli
(EPEC) is classified as typical (tEPEC) or atypical (aEPEC) based on the presence or absence of the
E. coli
adherence factor plasmid (pEAF), respectively. The hallmark of EPEC infection is the formation of the attaching and effacing (A/E) lesions on the gut mucosa. We compared the kinetics of A/E lesion formation induced by aEPEC and tEPEC. The examination of infected HEp-2 cells clearly demonstrated delayed A/E lesion formation by aEPEC in comparison to tEPEC. This delay was associated with the expression of locus of enterocyte effacement (LEE)-encoded virulence factors (i.e., intimin and EspD). Indeed, the insertion of a plasmid containing
perABC
, a transcriptional regulator of virulence factors involved in A/E formation, into aEPEC strains increased and accelerated the formation of A/E lesions. Interestingly, the enhanced expression and translocation of LEE-encoded proteins, such as those expressed in LEE5 (intimin) and LEE4 (EspD), in aEPEC (
perABC
) was independent of bacterial adhesion. The secretion kinetics of these two proteins representing LEE5 and LEE4 expression correlated with A/E lesion formation. We conclude that the lack of Per in the regulation network of virulence genes is one of the main factors that delay the establishment of A/E lesions induced by aEPEC strains.
Incidence, mechanism and risk factors for injury in youth rock climbers
Authors: Woollings Kaikanani Y , McKay Carly D , Kang Jian , Meeuwisse Willem H , Emery Carolyn A
Published: November 2014

Background

Rock-climbing participation has grown globally in recent years, and the sport was officially recognised by the International Olympic Committee in 2010. The epidemiology of climbing injuries in adults has been examined, but few studies have investigated injury in youth climbers.

Objective

To examine the incidence, mechanisms and risk factors for injury in recreational and elite sport climbers and boulderers aged 11–19 years.

Study design

Cross-sectional.

Methods

Youth (n=116) were recruited from climbing facilities across Alberta, Canada. Participants completed an anonymous questionnaire from October 2012 to March 2013. Climbing injury incidence proportions and incidence rates (IR) were calculated. ORs with corresponding 95% CIs were estimated for possible risk factors.

Results

The injury IR was 4.44 injuries/1000 climbing hours (95% CI 3.74 to 5.23). Sprains (27%) and strains (26%) were the predominant injury types, and repetitive overuse was the primary mechanism of injury (42%). Hands and fingers were the most commonly injured locations (21%). Exploratory analyses showed three risk factors for injury: older age (15–19 vs 11–14 years; OR=11.30, 95% CI 2.33 to 54.85), injury in a sport other than climbing (OR=6.46, 95% CI 1.62 to 25.68) and preventive taping (OR=5.09, 95% CI 1.44 to 18.02).

Conclusions

Injury risk is high in youth climbers. Findings are consistent with the reported rates, types and mechanisms in adults. Modifiable risk factors warrant further investigation to inform the development of injury prevention strategies, targeting high-risk climbers including adolescents and those with previous injury.
Biogeochemical tags in fish: predicting spatial variations in strontium and manganese in Salmo trutta scales using stream water geochemistry
Authors: Ramsay Alice L. , Hughes Roger N. , Chenery Simon R. , McCarthy Ian D.
Published: November 2014

Fish scales of Salmo trutta exhibited regional patterning in Sr and Mn concentrations in major third-order tributaries in a small upland catchment (the Dee catchment in Wales, United Kingdom; drainage area ∼1800 km2) that appeared to reflect regional variability in catchment geology and stream water chemistry. When baseline signatures in scale element concentrations were established at a number of sites (n = 12) among the upper, middle, and lower regions of the Dee catchment, 73% of fish were classified to their region of capture based on Sr and Mn in scales. However, the regional patterning in scale chemistry was degraded when high-resolution catchment-wide variability in scale element concentrations was predicted using element concentrations in stream water as a proxy for Sr and Mn in scales at 792 sites in first-, second-, and third-order tributaries in the catchment (mean distance between neighbouring sites = 738 m, range = 41–3634 m). This analysis indicated that many locations throughout the catchment could be potential source locations and demonstrates that the initial classification accuracy was artificially inflated. We have illustrated limitations of the site-based study design commonly employed in biogeochemical tagging studies. Future studies should take account of potential variation in baseline signatures at fine geographical scales when determining the accuracy of stock discrimination using biogeochemical tags.
Central exclusive dijet production at the Tevatron
Authors: Goulianos Konstantin
Published: November 2014

We present a review of central exclusive dijet production in [Formula: see text] collisions, where the proton and antiproton emerge intact, and only two jets of transverse energy above a certain threshold are present in the final state. The results are published in two papers by the Collider Detector at Fermilab (CDF) Collaboration, a PRL (2000) and a PRD (2008), based on data collected at [Formula: see text] and 1.96 TeV, respectively, and a D0 Collaboration paper from studies at 1.96 TeV. In all three cases predictions for the cross-section of Higgs boson production are discussed, a process that proceeds via a similar mechanism as dijet production. Roman Pot Spectrometers equipped with tracking detectors are used to measure the outgoing antiproton (CDF and D0) and proton (D0), and special forward detectors are employed to help reduce backgrounds and enrich the data in diffractive and exclusive dijet events.
The AFP and CT-PPS projects
Authors: Royon Christophe , Cartiglia Nicolo
Published: November 2014

We present the project to install new forward proton detectors in the CMS and ATLAS experiments called CT-PPS and AFP respectively.
Forward shower counters for diffractive physics at the LHC
Authors: Albrow Michael , Collins Paula , Penzo Aldo
Published: November 2014

The LHC detectors have incomplete angular coverage in the forward direction, for example in the region 6 ≲ |η| ≲ 8, which can be improved with the addition of simple scintillation counters around the beam pipes about 50 m to 120 m from the intersection point. These counters detect showers created by particles hitting the beam pipes and nearby material. The absence of signals in these counters in low pileup conditions is an indication of a forward rapidity gap as a signature of diffraction. In addition, they can be used to detect hadrons from low mass diffractive excitations of the proton, not accompanied by a leading proton but adjacent to a rapidity gap over (e.g.) 3 ≲ |η| ≲ 6. Such a set of forward shower counters, originally used at CDF, was used in CMS (FSC) for high-β* running with TOTEM during LHC Run-1. During LS1 the CMS FSC system is being upgraded for future low pileup runs. A similar system, called HERSCHEL is being installed in LHCb. ALICE is implementing scintillation counters, ADA and ADC, with 4.5 ≲ |η| ≲ 6.4.
On relativistic entanglement and localization of particles and on their comparison with the nonrelativistic theory
Authors: Crater Horace W. , Lusanna Luca
Published: November 2014

We make a critical comparison of relativistic and nonrelativistic classical and quantum mechanics of particles in inertial frames as well of the open problems in particle localization at both levels. The solution of the problems of the relativistic center-of-mass, of the clock synchronization convention needed to define relativistic 3-spaces and of the elimination of the relative times in the relativistic bound states leads to a description with a decoupled nonlocal (nonmeasurable) relativistic center-of-mass and with only relative variables for the particles (single particle subsystems do not exist). We analyze the implications for entanglement of this relativistic spatial nonseparability not existing in nonrelativistic entanglement. Then, we try to reconcile the two visions showing that also at the nonrelativistic level in real experiments only relative variables are measured with their directions determined by the effective mean classical trajectories of particle beams present in the experiment. The existing results about the nonrelativistic and relativistic localization of particles and atoms support the view that detectors only identify effective particles following this type of trajectories: these objects are the phenomenological emergent aspect of the notion of particle defined by means of the Fock spaces of quantum field theory.
Comment on "Eliminating the major tornado threat in Tornado Alley"
Authors: Dahl Johannes M. L. , Markowski Paul M.
Published: November 2014

The authors draw from half a century of meteorological research to expose flaws in a recent proposal to build 300-m-tall tornado-prevention walls across the U.S. Great Plains. The idea behind the walls is that they would prevent cold and warm air masses from clashing and would therefore suppress tornadoes. The problem with this proposal, however, is that atmospheric fronts ("airmass clashes") are neither a necessary nor a sufficient condition for tornadoes and that the proposed walls would not prevent the formation of fronts in the first place. Additional misconceptions about supercells thunderstorms and tornado formation also are identified.
Efficient RNS Converter via Two-Part RNS
Authors: TaghipourEivazi Shiva , Hosseinzadeh Mehdi , HabibizadNovin Ahmad
Published: November 2014

In this paper, a high speed residue to binary converter for three moduli set {2n - 1, 2n + 1, 2n} is presented in this paper, which uses two-part RNS and is based on mixed radix conversion (MRC). By using two-part RNS, the number of modulus in each part decreases; therefore the complexity of reverse converter is reduced. Also, the architecture of the proposed converter is based on subtractors and Multiplexers which are suitable for VLSI implementation. Reducing the number of modulus and simplifying the structure of the proposed converter lead to improvement of the latest presented converter in terms of area and delay. In order to obtain an accurate comparison, the proposed converter and the fastest designs were implemented on Xilinx 12.1 FPGA simulator, area and delay of each converter was measured for various word widths up to 64-bit. As the results indicated the novel proposed method has better Area and conversion time comparing to the previous designs.
Towards a Test Definition Language for Integrated Circuits
Authors: Alshayeb Mohammad , Elrabaa Muhammad E. S. , Hroub Ayman , Al-Aghbari Amran , El-Maleh Aiman H. , Bouhraoua Abdelhafid
Published: November 2014

The Standard Test Interface Language (STIL) is the de-facto standard for transferring test data between the test generation environment and the test equipment. STIL's flexibility and extensibility facilitates its use as the sole input language for automatic test-pattern generation (ATPG). However, STIL format is complex and does not provide support for algorithmic interactive testing which necessitate the use of additional programming languages to do that. In this paper, we propose a new Test Definition Language for Integrated Circuits (TDLIC) based on the Extensible Markup Language (XML). TDLIC is a description language for defining tests of digital ICs in a precise and reusable form. The proposed TDLIC provides a common platform for specifying test data as well as complex test procedures. A case study that includes a validation platform is used to show the full capabilities of TDLIC. The validation platform is an FPGA-based system that emulates the automatic test equipment and a prototype IC with four circuits to be tested.
Constraint on inflation model from BICEP2 and WMAP 9-year data
Authors: Cheng Cheng , Huang Qing-Guo
Published: November 2014

Even though Planck data released in 2013 (P13) is not compatible with Background Imaging of Cosmic Extragalactic Polarization (B2) and some local cosmological observations, including Supernova Legacy Survey (SNLS) samples and H0 prior from Hubble Space Telescope (HST) etc. Wilkinson Microwave Anisotropy Probe 9-year data (W9) is consistent with all of them in the base six-parameter ΛCDM + tensor cosmology quite well. In this paper, we adopt the combinations of B2+W9 and B2+W9+SNLS+BAO+HST to constrain the cosmological parameters in the base six-parameter ΛCDM + tensor model with nt = -r/8, where r and nt are the tensor-to-scalar ratio and the tilt of relic gravitational wave spectrum, and BAO denotes Baryon Acoustic Oscillation (BAO). We find that the Harrison–Zel'dovich (HZ) scale invariant scalar power spectrum is consistent with both data combinations, chaotic inflation is marginally disfavored by the data at around 2σ level, but the power-law inflation model and the inflation model with inverse power-law potential can fit the data nicely.