bluuebunny/crossref_metadata_2025 huggingface dataset:
Determination and validation of volume to be instilled for standardized intra‐abdominal pressure measurement in dogs
Authors: Way Leilani Ireland , Monnet Eric
Published: July 2014

Objectives

The objectives of this study were to determine (1) most appropriate volume of saline to be infused into the bladder prior to intra‐abdominal pressure (IAP) measurement, (2) to determine if a difference exists between IAP measurements before and after abdominal surgery, and (3) to assess the variability in IAP measurements associated with different saline volumes.

Design

Prospective study.

Setting

University teaching hospital.

Animals

Fifteen female research dogs, 7 undergoing ovariohysterectomy (OHE), and 8 undergoing laparoscopy.

Interventions

All dogs had urinary catheters placed and 4 consecutive IAP measurements measured using a different volume of instilled saline (0.25, 0.5, 1, and 2 mL/kg) at baseline. Measurements were repeated intraoperatively in laparoscopy dogs and postoperatively in OHE dogs.

Measurements and main results

For both groups of dogs, the volume infused into the bladder significantly affected IAP measurement. An instilled volume of 1 mL/kg of saline produced the best correlation (R2 = 0.44, P = 0.04) between IAP measurement and laparoscopic insufflator pressure. The mean (±SD) preoperative IAP (cmH2O) using 1 mL/kg instilled saline was 7.9 ± 1.4 and 9.6 ±1.9 for laparoscopy and OHE dogs, respectively. There was no difference in IAP before and after surgery in the dogs undergoing an OHE (P = 0.58). The volume of saline instilled into the bladder significantly affected the IAP (P = 0.0028).

Conclusions

One milliliter per kilogram instilled saline is recommended for standardized IAP pressure measurement in dogs. IAP in clinically normal dogs was not affected by abdominal surgery.
Assessment of a portable prothrombin time analyzer (CoaguChek‐XS) in dogs
Authors: Kelmer Efrat , Segev Gilad , Codner Carolina , Bruchim Yaron , Klainbart Sigal , Aroch Itamar
Published: July 2014

Objectives

To assess the performance of a portable prothrombin time (PT) analyzer (CoaguChek‐XS) in dogs.

Animals

Ninety‐seven dogs composed of 20 healthy dogs, 45 ill dogs, and 32 ill dogs with altered coagulation.

Procedures

Samples were concurrently obtained and PT was measured using the CoaguChek‐XS and an automated coagulation analyzer. Agreement between methods was assessed using Spearman's correlation and Bland–Altman analysis.

Results

The reference interval for PT using the CoaguChek‐XS was 9.6–11.5 s. The CoaguChek‐XS was easy to use, required a small volume of whole blood, and gave results within 1 min. The mean difference in PT between the 2 methods was 2.58 s (SD 3.10), and 94% of the samples fell within limits of agreement. The correlation was moderate, but significant (r = 0.35, P < 0.001). Sensitivity and specificity of the CoaguCheck‐XS PT compared to analyzer PT were 92% and 56%, respectively, and increased to 95% and 77% on intent to treat basis. The coefficient of variance was 0.72%.

The CoaguChek‐XS identified all 8 dogs with anticoagulant rodenticide intoxication, although a discrepancy was noted from the analyzer results. In anemic dogs (PCV≤25%), the CoaguChek‐XS did not display accurate results.

Conclusions

The CoaguChek‐XS is a simple, user‐friendly, highly precise PT analyzer. Results had moderate correlation and good agreement with a standard method. It can be used reliably for screening dogs when the PT is normal. However, when the CoaguChek‐XS PT is prolonged or when the PCV is ≤25%, results should be confirmed using a standard method.
The effect of hetastarch 670/0.75 administered in vivo as a constant rate infusion on platelet closure time in the dog
Authors: Helmbold Kim A. , Mellema Matthew S. , Hopper Kate , Epstein Steven E.
Published: July 2014

Objective

To evaluate the effects of hetastarch 670/0.75 on canine platelet function and clinical bleeding following its administration as a constant rate infusion (CRI) at 1 mL/kg/h and 2 mL/kg/h for 24 hours.

Design

In vivo, prospective, open‐label, crossover study.

Setting

Research laboratory at a university veterinary facility.

Animals

Eight healthy, adult male research dogs.

Interventions

Each dog received 1 mL/kg/h hetastarch for 24 hours then 2 mL/kg/h with a washout period of 10 weeks between each experiment. Platelet closure time (CT) was measured using a platelet function analyzer with collagen adenosine diphosphate (ADP) cartridges. CT measurements were performed at baseline and 6, 12, and 24 hours following initiation of hetastarch infusion.

Measurements and Main Results

At 1 mL/kg/h, mean CT was significantly increased at the 12‐ and 24‐hour time point relative to the baseline value, although mean CT never rose to a value above the reference interval during the 24‐hour infusion. At 2 mL/kg/h, median CT was also significantly increased at the 12‐ and 24‐hour time point relative to the baseline value. Administration of 2 mL/kg/h did progressively prolong the median CT value though only exceeded the reference interval at the 24‐hour time point. Despite the prolongation of median CT, there was no clinical evidence of spontaneous bleeding in any dog during the 24‐hour infusion at either CRI rate.

Conclusions

Hetastarch 670/0.75 when used as a 24‐hour CRI at 1 and 2 mL/kg/h prolongs CT in healthy dogs at 6, 12, and 24 hours. Median CT only exceeded the reference interval at 24 hours at 2 mL/kg/h.
Numerical Analysis of Transient Wave Propagation in Nonlinear One-Dimensional Waveguides by Using the Spectral Finite Element Method
Authors: Liu Yu , Dick Andrew J.
Published: July 2014

In this paper, transient wave propagation in nonlinear one-dimensional (1D) waveguides is studied. A complete nonlinear (CN) 1D model accounting for both axial and transverse displacements is developed and geometric and material nonlinearities are separately modeled. The alternating frequency-time finite element method (AFT-FEM) is implemented for this complete 1D model. Numerical simulations are conducted and the response behaviors for axial and transverse motions are analyzed. Comparison of the responses for the geometrically nonlinear (GN) model with a corresponding linear model supports predictions made from the previous analytical studies that the geometric nonlinearity has limited influence on the response of transient transverse waves in the intermediate strain regime. On the contrary, strong nonlinear behavior appears in the response for the materially nonlinear (MN) models. Depending on the local nonlinear property of the material in the intermediate strain regime, the amplitude of the response can be significantly influenced and additional dispersion can be introduced into the response. An exploration of the interaction between the geometric nonlinearity and the material nonlinearity for a rod model in a large strain regime is also conducted and the responses are analyzed by using time-frequency analysis. The competing effect of the geometric nonlinearity and the material nonlinearity can result in a pseudolinear response in a strong nonlinear system for a given range of impact loading.
Robust Design for Multivariate Quality Characteristics Using Extreme Value Distribution
Authors: Yang Changming , Du Xiaoping
Published: July 2014

Quality characteristics (QCs) are important product performance variables that determine customer satisfaction. Their expected values are optimized and their standard deviations are minimized during robust design (RD). Most of RD methodologies consider only a single QC, but a product is often judged by multiple QCs. It is a challenging task to handle dependent and oftentimes conflicting QCs. This work proposes a new robustness modeling measure that uses the maximum quality loss among multiple QCs for problems where the quality loss is the same no matter which QCs or how many QCs are defective. This treatment makes it easy to model RD with multivariate QCs as a single objective optimization problem and also account for the dependence between QCs. The new method is then applied to problems where bivariate QCs are involved. A numerical method for RD with bivariate QCs is developed based on the first order second moment (FOSM) method. The method is applied to the mechanism synthesis of a four-bar linkage and a piston engine design problem.
Experimental and Numerical Investigation of Turbulent Natural Convection Flow in a Vertical Channel With a Heated Obstacle
Authors: Harnane Yamina , Saury Didier , Bessaïh Rachid , Lemonnier Denis , Bougriou Chérif
Published: July 2014

In the present study, experiments were carried out for natural turbulent convection induced by a heated square bar in a two-dimensional (2D) open vertical channel for different Rayleigh numbers and bar positions. For this purpose, particle image velocimetry (PIV) system has been employed to investigate the velocity field in the vertical center channel plane. The present work is also concerned with computational fluid dynamics (CFD) simulation by employing large Eddy simulation (LES) turbulence model, used in fire dynamic simulation (FDS) code. Calculations were performed for different chimney aspect ratios A* (height Lb over width d) and modified Rayleigh numbers ranging between 4 × 107 and 108. Experimental and numerical results included mean velocity profiles; flow structure and Nusselt number were presented and discussed. To validate CFD code, velocity profiles along channel elevation were compared with our experimental measurements, and a good agreement was observed. Therefore, FDS code is a useful tool to simulate natural turbulent convection dynamic field, and consequently the thermal field in such situation. CFD code has been used to study the best heated bar location (corresponding to the best cooling effect) in the channel as well as the best airflow rate. This best location and its explanation are discussed in this paper.
Effects of an Acute Bout of Exercise on Memory in 6th Grade Children
Authors: Etnier Jennifer , Labban Jeffrey D. , Piepmeier Aaron , Davis Matthew E. , Henning David A.
Published: July 2014

Research supports the positive effects of exercise on cognitive performance by children. However, a limited number of studies have explored the effects specifically on memory. The purpose of this study was to compare the effects of an acute bout of exercise on learning, short-term memory, and long-term memory in a sample of children. Children were randomly assigned to an exercise condition or to a no-treatment control condition and then performed repeated trials on an auditory verbal learning task. In the exercise condition, participants performed the PACER task, an aerobic fitness assessment, in their physical education class before performing the memory task. In the control condition, participants performed the memory task at the beginning of their physical education class. Results showed that participants in the exercise condition demonstrated significantly better learning of the word lists and significantly better recall of the words after a brief delay. There were not significant differences in recognition of the words after an approximately 24-hr delay. These results provide evidence in a school setting that an acute bout of exercise provides benefits for verbal learning and long-term memory. Future research should be designed to identify the extent to which these findings translate to academic measures.
Hormonal, Metabolic, and Cardiorespiratory Responses of Young and Adult Athletes to a Single Session of High-Intensity Cycle Exercise
Authors: Engel Florian , Härtel Sascha , Strahler Jana , Wagner Matthias Oliver , Bös Klaus , Sperlich Billy
Published: July 2014

This study aimed to determine the effects of a single high-intensity interval training (HIIT) session on salivary cortisol (SC) levels, physiological responses, and performance in trained boys and men. Twenty-three boys (11.5 ± 0.8 years) and 25 men (29.7 ± 4.6 years) performed HIIT (4 consecutive Wingate Anaerobic Tests). SC in boys and men increased after HIIT from 5.55 ± 3.3 nmol/l to 15.13 ± 9.7 nmol/l (+173%) and from 7.07 ± 4.7 nmol/l to 19.19 ± 12.7 nmol/l (+171%), respectively (p < .01). Pretest SC as well as posttest changes were comparable in both groups (both p < .01). Peak blood lactate concentration was significantly lower in boys (12.6 ± 3.5 mmol/l) than in men (16.3 ± 3.1 mmol/l; p < .01). Throughout the HIIT, mean heart rates in boys were higher (p < .001) but relative peak oxygen uptake (ml·min−1·kg−1; p < .05) and performance were lower (p < .001) in boys than in men. HIIT in young athletes is associated with a higher activation of the hormonal stress axis than other types of exercise regimes as described in the literature. This study is the first to show a pronounced SC increase to HIIT in trained boys accompanied by elevated levels of blood lactate concentrations and heart rate suggesting a high cardio-respiratory, metabolic, and hormonal response to HIIT in 11-year-old boys.
Comparison Between Lactate Minimum and Critical Speed Throughout Childhood and Adolescence in Swimmers
Authors: Mezzaroba Paulo V. , Papoti Marcelo , Machado Fabiana A.
Published: July 2014

This study aimed to examine the influence of age and degree of maturity on the comparison and relationship between lactate minimum intensity (LM) and critical speed (CS) throughout childhood and adolescence in swimmers. Forty-six male swimmers aged between 10 and 18 years were divided into three age groups according to pubertal stages and training status. Maximal efforts of 100 and 400 m and the LM protocol with 200 m performances were executed. CS was determined with a 3-distances combination (100, 200, and 400 m). One-way and mixed analysis of variance for repeated measures, Bland-Altman, Pearson correlation, percentage difference, and effect size were used to compare and examine the relationship between variables in each age group. The results revealed that LM and CS had differences in comparison with one another throughout childhood and adolescence in swimmers, because CS clearly underestimated LM in the 10 to 12.6-year age group, while overestimating it in the 15.4 to 18-year age group of swimmers. Thus, coaches and swimmers must be aware of the age-dependency of CS for indices of aerobic endurance measurements in the initial ages of systematized swimming training.
Running Activity Profile of Adolescent Tennis Players During Match Play
Authors: Hoppe Matthias W. , Baumgart Christian , Bornefeld Jutta , Sperlich Billy , Freiwald Jürgen , Holmberg Hans-Christer
Published: July 2014

The aims of this study were (1) to assess the running activities of adolescent tennis players during match play with respect to velocity, acceleration, and deceleration; (2) to characterize changes in these activities during the course of a match; and (3) to identify potential differences between winners and losers. Twenty well-trained adolescent male athletes (13 ± 1 y) played one simulated match each (giving a total of 10 matches), during which distances covered at different velocity categories (0 to < 1, 1 to < 2, 2 to < 3, 3 to < 4, and ≥ 4 m·s−1) and number of running activities involving high velocity (≥ 3 m·s−1), acceleration (≥ 2 m·s−2), and deceleration (≤ −2 m·s−2) were monitored using a global positioning system (10 Hz). Heart rate was also assessed. The total match time, total distance covered, peak velocity, and mean heart rate were 81.2 ± 14.6 min, 3362 ± 869 m, 4.4 ± 0.8 ms−1, and 159 ± 12 beats min−1, respectively. Running activities involving high acceleration (0.6 ± 0.2 n·min−1) or deceleration (0.6 ± 0.2 n·min−1) were three times as frequent as those involving high velocity (0.2 ± 0.1 n·min−1). No change in the pattern of running activities (P ≥ .13, d ≤ 0.39) and no differences between winners and losers (P ≥ .22, d ≤ 0.53) were evident during match play. We conclude that training of well-trained adolescent male tennis players need not focus on further development of their running abilities, since this physical component of multifactorial tennis performance does not change during the course of a match and does not differ between the winners and losers.
Physical Activity, Screen Time, and Sitting Among U.S. Adolescents
Authors: Carson Valerie , Staiano Amanda E. , Katzmarzyk Peter T.
Published: July 2014

The purpose of this study was to describe self-reported levels of sitting, moderate- to vigorous-intensity physical activity (MVPA), television viewing, and computer use in a representative sample of US adolescents and to make comparisons between sex, race/ethnicity, weight status, and age groups. Results are based on 3556 adolescents aged 12-19 years from the 2007-2012 National Health and Nutrition Examination Survey. Participants self-reported demographic, sitting, MVPA, television viewing (2011-2012 only) and computer use (2011-2012 only) variables. Height and weight were measured to calculate body mass index. On average, 7.5 hr/day were spent sitting and 34 median min/day were spent participating in MVPA, with females sitting more and participating in less MVPA than males across most demographic groups. Furthermore, obese males sat more and participated in less MVPA than nonoverweight males. Non-Hispanic white females participated in more MVPA than females in all other race/ethnicity groups. For television and computer, 38% and 22% of the sample engaged in >2 hr/day, respectively, and several race/ethnicity differences were observed. This study provides the first U.S. adolescent population estimates on self-reported sitting and updates population estimates on self-reported MVPA, television viewing and computer use. Continued efforts are needed to promote healthy active lifestyles in American adolescents.
Vitamin D Supplementation and Upper Respiratory Tract Infections in Adolescent Swimmers: A Randomized Controlled Trial
Authors: Dubnov-Raz Gal , Hemilä Harri , Cohen Avner H. , Rinat Barak , Choleva Lauryn , Constantini Naama W.
Published: July 2014

Observational studies identified associations between vitamin D insufficiency (serum 25(OH)D > 30ng·ml−1) and risk of upper respiratory infection (URI). Swimmers are highly prone to URIs, which might hinder their performance. The aim of this study was to examine if vitamin D3 supplementation reduces URI burden in vitamin D-insufficient swimmers. Fifty-five competitive adolescent swimmers with vitamin D insufficiency were randomized to receive vitamin D3 (2,000IU·d4) or placebo for 12 winter weeks. A URI symptom questionnaire was completed weekly. Serum 25(OH)D concentrations were measured by radio-immunoassay before and after supplementation. We used linear regression to examine the relation between the change in 25(OH)D concentrations during the trial, and the duration and severity of URIs. There were no between-group differences in the frequency, severity, or duration of URIs. Exploratory analyses revealed that in the placebo group only, the change in 25(OH)D concentrations during the trial was highly associated with the duration of URIs (r = −0.90,p > .001), and moderately associated with the severity of URIs (r = −0.65,p = .043). The between-group differences for duration were highly significant. Vitamin D3 supplementation in adolescent swimmers with vitamin D insufficiency did not reduce URI burden. However, larger decreases in serum 25(OH)D concentrations were associated with significantly longer and more severe URI episodes.
Physical-Capacity-Related Genetic Polymorphisms in Children with Cystic Fibrosis
Authors: Yvert Thomas , Santiago Catalina , Santana-Sosa Elena , Verde Zoraida , Gómez-Gallego Felix , Lopez-Mojares Luis , Pérez Margarita , Garatachea Nuria , Lucia Alejandro
Published: July 2014

In patients with cystic fibrosis (CF), physical capacity (PC) has been correlated with mortality risk. In turn, PC is dependent on genetic factors. This study examines several polymorphisms associated with PC and healthrelated phenotype traits (VO2peak, FEV1, FVC, PImax and muscular strength) in a group of children with CF (n = 66, primary purpose). The same analyses were also performed in a control group of healthy children (n = 113, secondary purpose). The polymorphisms determined were classified as muscle function polymorphisms (ACE rs1799752; AGT rs699; ACTN3 rs1815739; PTK2 rs7843014 and rs7460; MSTN rs1805086; TRHR rs7832552; NOS3 rs2070744) or energy metabolism polymorphisms (PPARGC1A rs8192678; NRF1 rs6949152; NRF2 rs12594956; TFAM rs1937; PPARD rs2267668; ACSL1 rs6552828). No significant polymorphism/phenotype correlations were detected in children with CF, with marginal associations being observed between NOS3 rs2070744 and VO2peak and FEV1, as well as between PPARGC1A rs8192678 and FEV1. Overall, similar findings were observed in the control group, i.e., no major associations. The PC-related polymorphisms examined seem to have no effects on the PC or health of children with CF.
The E3 ligase PARC mediates the degradation of cytosolic cytochrome c to promote survival in neurons and cancer cells
Authors: Gama Vivian , Swahari Vijay , Schafer Johanna , Kole Adam J. , Evans Allyson , Huang Yolanda , Cliffe Anna , Golitz Brian , Sciaky Noah , Pei Xin-Hai , Xiong Yue , Deshmukh Mohanish
Published: July 2014

Neurons and cancer cells rely on the protein PARC to survive mitochondrial stress.
Ceftaroline Is Active against Heteroresistant Methicillin-Resistant Staphylococcus aureus Clinical Strains despite Associated Mutational Mechanisms and Intermediate Levels of Resistance
Authors: Fernandez Regina , Paz Liliana I. , Rosato Roberto R. , Rosato Adriana E.
Published: July 2014

Methicillin-resistantStaphylococcus aureus(MRSA) is an important infectious human pathogen responsible for diseases ranging from skin and soft tissue infections to life-threatening endocarditis. β-Lactam resistance in MRSA involves acquisition of penicillin-binding protein 2a (PBP2a), a protein with low affinity for β-lactams that mediates cell wall assembly when the normal staphylococcal PBPs (PBP1 to -4) are blocked by these agents. Many MRSA strains display heterogeneous expression of resistance (HeR) against β-lactam antibiotics. The β-lactam-mediated homoresistant (HoR) phenotype is associated with both expression of themecAgene and activation of the LexA-RecA-mediated SOS response, a regulatory network induced in response to DNA damage. Ceftaroline (CPT) is the only FDA-approved cephalosporin targeting PBP2a. We investigated the mechanistic basis of CPT activity against HeR-MRSA strains, including a set of strains displaying an intermediate level of resistance to CPT. Mechanistically, we found that 1 exposure of HeR-MRSA to subinhibitory concentrations of CPT selected for the HoR derivative activated the SOS response and increased mutagenesis. Importantly, CPT-selected HoR cells remained susceptible to CPT while still being resistant to most β-lactams, and 2-CPT activity in HeR-MRSA resided in an attenuated induction ofmecAexpression in comparison to other β-lactams. In addition, 3-CPT intermediate-resistant strains displayed a significant increase in CPT-inducedmecAexpression accompanied by mutations in PBP2, which together may interfere with the complete repression by CPT of both PBP2a and PBP2a-PBP2 interactions and thus be a determining factor in the low level of CPT resistance in the absence ofmecAgene mutations. The present study provides mechanistic evidence that CPT represents an alternative therapeutic option for the treatment of heteroresistant MRSA strains.
Avibactam and Class C β-Lactamases: Mechanism of Inhibition, Conservation of the Binding Pocket, and Implications for Resistance
Authors: Lahiri S. D. , Johnstone M. R. , Ross P. L. , McLaughlin R. E. , Olivier N. B. , Alm R. A.
Published: July 2014

Avibactam is a novel non-β-lactam β-lactamase inhibitor that inhibits a wide range of β-lactamases. These include class A, class C, and some class D enzymes, which erode the activity of β-lactam drugs in multidrug-resistant pathogens like
Pseudomonas aeruginosa
and
Enterobacteriaceae
spp. Avibactam is currently in clinical development in combination with the β-lactam antibiotics ceftazidime, ceftaroline fosamil, and aztreonam. Avibactam has the potential to be the first β-lactamase inhibitor that might provide activity against class C-mediated resistance, which represents a growing concern in both hospital- and community-acquired infections. Avibactam has an unusual mechanism of action: it is a covalent inhibitor that acts via ring opening, but in contrast to other currently used β-lactamase inhibitors, this reaction is reversible. Here, we present a high-resolution structure of avibactam bound to a class C β-lactamase, AmpC, from
P. aeruginosa
that provided insight into the mechanism of both acylation and recyclization in this enzyme class and highlighted the differences observed between class A and class C inhibition. Furthermore, variants resistant to avibactam that identified the residues important for inhibition were isolated. Finally, the structural information was used to predict effective inhibition by sequence analysis and functional studies of class C β-lactamases from a large and diverse set of contemporary clinical isolates (
P. aeruginosa
and several
Enterobacteriaceae
spp.) obtained from recent infections to understand any preexisting variability in the binding pocket that might affect inhibition by avibactam.
Revised Reference Broth Microdilution Method for Testing Telavancin: Effect on MIC Results and Correlation with Other Testing Methodologies
Authors: Farrell David J. , Mendes Rodrigo E. , Rhomberg Paul R. , Jones Ronald N.
Published: July 2014

The reference broth microdilution (BMD) antimicrobial susceptibility testing method for telavancin was revised to include dimethyl sulfoxide (DMSO) as a solvent and diluent for frozen-form panel preparation, following the CLSI recommendations for water-insoluble agents. Polysorbate 80 (P-80) was also added to the test medium to minimize proven drug losses associated with binding to plastic surfaces. Four hundred sixty-two Gram-positive isolates, including a challenge set of organisms with reduced susceptibilities to comparator agents, were selected and tested using the revised method for telavancin, and the MIC results were compared with those tested by the previously established method and several Sensititre dry-form BMD panel formulations. The revised method provided MIC results 2- to 8-fold lower than the previous method when tested against staphylococci and enterococci, resulting in MIC
50
values of 0.03 to 0.06 μg/ml for staphylococci and 0.03 and 0.12 μg/ml for
Enterococcus faecium
and
Enterococcus faecalis
, respectively. Less-significant MIC decreases (1 to 2 log
2
dilution steps) were observed when testing streptococci in broth supplemented with blood, which showed similar MIC
50
values for both methods. However,
Streptococcus pneumoniae
had MIC
50
results of 0.008 and 0.03 μg/ml when tested by the revised and previous methods, respectively. Highest essential agreement rates (≥94.0%) were noted for one candidate dry-form panel formulation compared to the revised test. The revised BMD method provides lower MIC results for telavancin, especially when tested against staphylococci and enterococci. This is secondary to the use of DMSO for panel production and the presence of P-80, which ensure the proper telavancin testing concentration and result in a more accurate MIC determination. Moreover, earlier studies where the previous method was applied underestimated the
in vitro
drug potency.
Role for Streptococcal Collagen-Like Protein 1 in M1T1 Group A Streptococcus Resistance to Neutrophil Extracellular Traps
Authors: Döhrmann Simon , Anik Sabina , Olson Joshua , Anderson Ericka L. , Etesami Neelou , No Hyewon , Snipper Joshua , Nizet Victor , Okumura Cheryl Y. M.
Published: July 2014

Streptococcal collagen-like protein 1 (Scl-1) is one of the most highly expressed proteins in the invasive M1T1 serotype group A
Streptococcus
(GAS), a globally disseminated clone associated with higher risk of severe invasive infections. Previous studies using recombinant Scl-1 protein suggested a role in cell attachment and binding and inhibition of serum proteins. Here, we studied the contribution of Scl-1 to the virulence of the M1T1 clone in the physiological context of the live bacterium by generating an isogenic strain lacking the
scl-1
gene. Upon subcutaneous infection in mice, wild-type bacteria induced larger lesions than the Δ
scl
mutant. However, loss of Scl-1 did not alter bacterial adherence to or invasion of skin keratinocytes. We found instead that Scl-1 plays a critical role in GAS resistance to human and murine phagocytic cells, allowing the bacteria to persist at the site of infection. Phenotypic analyses demonstrated that Scl-1 mediates bacterial survival in neutrophil extracellular traps (NETs) and protects GAS from antimicrobial peptides found within the NETs. Additionally, Scl-1 interferes with myeloperoxidase (MPO) release, a prerequisite for NET production, thereby suppressing NET formation. We conclude that Scl-1 is a virulence determinant in the M1T1 GAS clone, allowing GAS to subvert innate immune functions that are critical in clearing bacterial infections.
An Optimized, Synthetic DNA Vaccine Encoding the Toxin A and Toxin B Receptor Binding Domains of Clostridium difficile Induces Protective Antibody ResponsesIn Vivo
Authors: Baliban Scott M. , Michael Amanda , Shammassian Berje , Mudakha Shikata , Khan Amir S. , Cocklin Simon , Zentner Isaac , Latimer Brian P. , Bouillaut Laurent , Hunter Meredith , Marx Preston , Sardesai Niranjan Y. , Welles Seth L. , Jacobson Jeffrey M. , Weiner David B. , Kutzler Michele A.
Published: July 2014

Clostridium difficile-associated disease (CDAD) constitutes a large majority of nosocomial diarrhea cases in industrialized nations and is mediated by the effects of two secreted toxins, toxin A (TcdA) and toxin B (TcdB). Patients who develop strong antitoxin antibody responses can clearC. difficileinfection and remain disease free. Key toxin-neutralizing epitopes have been found within the carboxy-terminal receptor binding domains (RBDs) of TcdA and TcdB, which has generated interest in developing the RBD as a viable vaccine target. While numerous platforms have been studied, very little data describes the potential of DNA vaccination against CDAD. Therefore, we created highly optimized plasmids encoding the RBDs from TcdA and TcdB in which any putativeN-linked glycosylation sites were altered. Mice and nonhuman primates were immunized intramuscularly, followed byin vivoelectroporation, and in these animal models, vaccination induced significant levels of both anti-RBD antibodies (blood and stool) and RBD-specific antibody-secreting cells. Further characterization revealed that sera from immunized mice and nonhuman primates could detect RBD protein from transfected cells, as well as neutralize purified toxins in anin vitrocytotoxicity assay. Mice that were immunized with plasmids or given nonhuman-primate sera were protected from a lethal challenge with purified TcdA and/or TcdB. Moreover, immunized mice were significantly protected when challenged withC. difficilespores from homologous (VPI 10463) and heterologous, epidemic (UK1) strains. These data demonstrate the robust immunogenicity and efficacy of a TcdA/B RBD-based DNA vaccine in preclinical models of acute toxin-associated and intragastric, spore-induced colonic disease.
Role of YpeB in Cortex Hydrolysis during Germination of Bacillus anthracis Spores
Authors: Bernhards Casey B. , Popham David L.
Published: July 2014

The infectious agent of the disease anthrax is the spore of
Bacillus anthracis
. Bacterial spores are extremely resistant to environmental stresses, which greatly hinders spore decontamination efforts. The spore cortex, a thick layer of modified peptidoglycan, contributes to spore dormancy and resistance by maintaining the low water content of the spore core. The cortex is degraded by germination-specific lytic enzymes (GSLEs) during spore germination, rendering the cells vulnerable to common disinfection techniques. This study investigates the relationship between SleB, a GSLE in
B. anthracis
, and YpeB, a protein necessary for SleB stability and function. The results indicate that Δ
sleB
and Δ
ypeB
spores exhibit similar germination phenotypes and that the two proteins have a strict codependency for their incorporation into the dormant spore. In the absence of its partner protein, SleB or YpeB is proteolytically degraded soon after expression during sporulation, rather than escaping the developing spore. The three PepSY domains of YpeB were examined for their roles in the interaction with SleB. YpeB truncation mutants illustrate the necessity of a region beyond the first PepSY domain for SleB stability. Furthermore, site-directed mutagenesis of highly conserved residues within the PepSY domains resulted in germination defects corresponding to reduced levels of both SleB and YpeB in the mutant spores. These results identify residues involved in the stability of both proteins and reiterate their codependent relationship. It is hoped that the study of GSLEs and interacting proteins will lead to the use of GSLEs as targets for efficient activation of spore germination and facilitation of spore cleanup.
An atypical presentation of an extremely late stent thrombosis after more than 7 years (2634 days) of DES implantation in a patient without obvious risk factors on regular dual antiplatelet therapy
Authors: Parekh Pritesh , Agrawal Navin , Vasavada Apurva , Vinchurkar Mahesh
Published: July 2014

Very late stent thrombosis is a rare complication of percutaneous coronary intervention in the era of dual antiplatelet therapy. The risk factors for stent thrombosis are drug default, age, diabetes, renal dysfunction, left ventricular dysfunction, smoking or procedure-related factors and complications. We are describing the case of a 55-year-old non-smoker patient without the conventional risk factors for stent thrombosis maintaining good compliance with dual antiplatelet (aspirin and clopidogrel) drugs in standard doses. The patient had a history of having received a Cypher stent more than 7 years (2634 days) ago in the left circumflex artery for the management of in-stent restenosis of a bare metal stent implanted previously. He was referred with acute stent thrombosis with an atypical presentation of non-ST elevation myocardial infarction having unexplainable spontaneous resolution of electrocardiographic changes. The patient was successfully managed with newer generation drug-eluting stents reimplantation. The presence of acute onset of symptoms and thrombus containing soft lesion as documented during intervention supported the diagnosis of acute stent thrombosis. To the best of our knowledge this case is one of the longest duration of presentation with acute stent thrombosis after stent implantation ever reported in literature and is also unique in its unusual mode of presentation.
Systematic review on the primary and secondary reporting of the prevalence of ghostwriting in the medical literature
Authors: Stretton Serina
Published: July 2014

Background

Ghostwriting of industry-sponsored articles is unethical and is perceived to be common practice.

Objective

To systematically review how evidence for the prevalence of ghostwriting is reported in the medical literature.

Data sources

MEDLINE via PubMed 1966+, EMBASE 1966+, The Cochrane Library 1988+, Medical Writing 1998+, The American Medical Writers Association (AMWA) Journal 1986+, Council of Science Editors Annual Meetings 2007+, and the Peer Review Congress 1994+ were searched electronically (23 May 2013) using the search terms ghostwrit*, ghostauthor*, ghost AND writ*, ghost AND author*.

Eligibility criteria

All publication types were considered; only publications reporting a numerical estimate of possible ghostwriting prevalence were included.

Data extraction

Two independent reviewers screened the publications; discrepancies were resolved by consensus. Data to be collected included a numerical estimate of the prevalence of possible ghostwriting (primary outcome measure), definitions of ghostwriting reported, source of the reported prevalence, publication type and year, study design and sample population.

Results

Of the 848 publications retrieved and screened for eligibility, 48 reported numerical estimates for the prevalence of possible ghostwriting. Sixteen primary publications reported findings from cross-sectional surveys or descriptive analyses of published articles; 32 secondary publications cited published or unpublished evidence. Estimates on the prevalence of possible ghostwriting in primary and secondary publications varied markedly. Primary estimates were not suitable for meta-analysis because of the various definitions of ghostwriting used, study designs and types of populations or samples. Secondary estimates were not always reported or cited correctly or appropriately.

Conclusions

Evidence for the prevalence of ghostwriting in the medical literature is limited and can be outdated, misleading or mistaken. Researchers should not inflate estimates using non-standard definitions of ghostwriting nor conflate ghostwriting with other unethical authorship practices. Editors and peer reviewers should not accept articles that incorrectly cite or interpret primary publications that report the prevalence of ghostwriting.
Work outcomes of sickness absence related to mental disorders: a systematic literature review
Authors: Dewa Carolyn S , Loong Desmond , Bonato Sarah
Published: July 2014

Objectives

The purpose of this systematic literature review is to examine the current state of knowledge regarding the return-to-work outcomes of sickness absences related to mental disorders that increase costs borne by employers. We address two questions: (1) Based on the existing literature, from the employer's perspective, what are the relevant economic return-to-work outcomes for sickness absences related to mental disorders? and (2) From the employer's economic perspective, are there gaps in knowledge about the relevant return-to-work outcomes for sickness absences related to mental disorders?

Setting

The included studies used administrative data from either an employer, insurer or occupational healthcare provider.

Participants

Studies included working adults between 18 and 65 years old who had a sickness absence related to a mental disorder.

Primary and secondary outcome measures

The studies considered two general return-to-work outcome categories: (1) outcomes focusing on return-to-work and (2) outcomes focusing on sickness absence recurrence.

Results

A total of 3820 unique citations were identified. Of these, 10 studies were identified whose quality ranged from good to excellent. Half of the identified studies came from one country. The studies considered two characteristics of sickness absence: (1) whether and how long it took for a worker to return-to-work and (2) sickness absence recurrence. None of the studies examined return-to-work outcomes related to work reintegration.

Conclusions

The existing literature suggests that along with the incidence of sickness absence related to mental disorders, the length of sickness absence episodes and sickness absence recurrence (ie, number and time between) should be areas of concern. However, there also seems to be gaps in the literature regarding the work reintegration process and its associated costs.
MOND as the basis for an extended theory of gravity
Authors: Mendoza S.
Published: July 2014

This review describes why the geometric nature of space–time, the Einstein equivalence principle, and the geodesic motion of particles show the possibility of building an extended relativistic theory of gravity on regions where the Tully–Fisher law is valid. It is also shown how a metric construction of gravity can have a modified Newtonian dynamics behaviour compatible with the Tully–Fisher law and the bending of light observed in individual, groups, and clusters of galaxies. It is also reviewed how this metric theory of gravity fits reasonably well on cosmological scales explaining the current acceleration of the universe.
Analysis of the 40K contamination in NaI(Tl) crystals from different providers in the frame of the ANAIS project
Authors: Cuesta C. , Amaré J. , Cebrián S. , García E. , Ginestra C. , Martínez M. , Oliván M. A. , Ortigoza Y. , Ortiz De Solórzano A. , Pobes C. , Puimedón J. , Sarsa M. L. , Villar J. A. , Villar P.
Published: July 2014

NaI(Tl) large crystals are applied in the search for galactic dark matter particles through their elastic scattering off the target nuclei in the detector by measuring the scintillation signal produced. However, energies deposited in the form of nuclear recoils are small, which added to the low efficiency to convert that energy into scintillation, makes that events at or very near the energy threshold, attributed either to radioactive backgrounds or to spurious noise (nonbulk NaI(Tl) scintillation events), can compromise the sensitivity goals of such an experiment. DAMA/LIBRA experiment, using 250 kg NaI(Tl) target, reported first evidence of the presence of an annual modulation in the detection rate compatible with that expected for a dark matter signal just in the region below 6 keVee (electron equivalent energy). In the frame of the ANAIS (Annual modulation with NaI Scintillators) dark matter search project a large and long effort has been carried out in order to understand the origin of events at very low energy in large sodium iodide detectors and develop convenient filters to reject those nonattributable to scintillation in the bulk NaI(Tl) crystal. 40K is probably the most relevant radioactive contaminant in the bulk for NaI(Tl) detectors because of its important contribution to the background at very low energy. ANAIS goal is to achieve levels at or below 20 ppb natural potassium. In this paper we will report on our effort to determine the 40K contamination in several NaI(Tl) crystals, by measuring in coincidence between two (or more) of them. Results obtained for the 40K content of crystals from different providers will be compared and prospects of the ANAIS dark matter search experiment will be briefly reviewed.
Influence of magnetic field and Rashba spin–orbit coupling on strong-coupling magnetopolarons in quantum disks
Authors: Xin Wei , Han Chao , Eerdunchaolu
Published: July 2014

On the basis of Lee–Low–Pines (LLP) unitary transformation, the influence of external magnetic field, Rashba spin–orbit coupling and quantum size effect on the ground-state interaction energy of strong-coupling magnetopolarons in quantum disks (QDs) is studied by using the Tokuda improved linear combine operator method. The results show that the ground-state interaction energy of magnetopolarons consists of four parts: the energy caused by the confinement potential of QDs, interaction energy between the electron and external magnetic field, electron and longitudinal-optical (LO) phonon interaction energy and additional term of Rashba effect originating from phonons. The electron–LO phonon interaction energy Ee- ph and additional term of Rashba effect are always negative; the absolute value |Ee- ph | increases with increasing transverse confinement strength ω0, cyclotron frequency of external magnetic field ωc and electron–LO phonon coupling strength α, but decreases with increasing the thickness of QDs L; the state properties of magnetopolarons are closely linked with the sign of the ground-state interaction energy of magnetopolarons E int and change of E int with ωc, ω0, α and L. In addition, the vibration frequency of magnetopolarons λ increases with increasing ωc, ω0 and α, but decreases with increasing L. For the ground state of magnetopolarons in QDs, the electron–LO phonon interaction plays a significant role, meanwhile, the influence of Rashba spin–orbit coupling effect cannot be ignored.
ROBUST NONPARAMETRIC SIMPLIFICATION OF POLYGONAL CHAINS
Authors: DUROCHER STEPHANE , LEBLANC ALEXANDRE , MORRISON JASON , SKALA MATTHEW
Published: July 2014

In this paper we present a novel nonparametric method for simplifying piecewise linear curves and we apply this method as a statistical approximation of structure within sequential data in the plane. Specifically, given a sequence P of n points in the plane that determine a simple polygonal chain consisting of n−1 segments, we describe algorithms for selecting a subsequence Q ⊂ P (including the first and last points of P) that determines a second polygonal chain to approximate P, such that the number of crossings between the two polygonal chains is maximized, and the cardinality of Q is minimized among all such maximizing subsets of P. Our algorithms have respective running times O(n2 log n) (respectively, [Formula: see text]) when P is monotonic and O(n2 log2 n) (respectively, [Formula: see text]) when P is any simple polygonal chain in the Real RAM model (respectively, in the Word RAM model).
On moments of the multiplicity events of slow target fragments in relativistic Sulfur-ion collisions
Authors: Abdelsalam A. , Kamel S. , Rashed N. , Sabry N.
Published: July 2014

A detailed study on the multiplicity characteristics of the slow target fragments emitted in relativistic heavy-ion collisions has been carried out at E Lab = 3.7 A and 200A GeV using 32 S projectile. The beam energy dependence of the black particles produced in the full phase space of 32 S -emulsion (32 S -Em) interactions on the target size in terms of their moments (mean, variance, skewness and kurtosis) is investigated. The various order moments of target fragments emitted in the interactions of 32 S beams with the heavy ( AgBr ) target nuclei are estimated in the forward (FHS) and backward (BHS) hemispheres. The investigated values of ratio of variance to mean at both energies show that the multiplicity distributions (MDs) are not Poissonian and the strongly correlated emission of target fragments are in the forward directions. The degree of anisotropic fragment emission and nature of correlation among the emitted fragments are investigated. The energy dependence of entropy is examined in both hemispheres. The entropy values normalized to average multiplicity are found to be energy independent. Scaling of MD of black particles produced in these interactions has been studied to verify the validity of scaling hypothesis via two scaling (Koba–Nielsen–Olesen (KNO)-scaling and Hegyi-scaling) functions. A simplified universal function has been used in each scaling to display the experimental data.
Zeros of pseudo-ultraspherical polynomials
Authors: Driver Kathy , Muldoon Martin E.
Published: July 2014

The pseudo-ultraspherical polynomial of degree n can be defined by [Formula: see text] where [Formula: see text] is the ultraspherical polynomial. It is known that when λ < -n, the finite set [Formula: see text] is orthogonal on (-∞, ∞) with respect to the weight function (1 + x2)λ-½ and when λ < 1 - n, the polynomial [Formula: see text] has exclusively real and simple zeros. Here, we undertake a deeper study of the zeros of these polynomials including bounds, numbers of real zeros, monotonicity and interlacing properties. Our methods include the Sturm comparison theorem, recurrence relations, and the explicit expression for the polynomials.
Fifth-Order Mapped Semi-Lagrangian Weighted Essentially Nonoscillatory Methods Near Certain Smooth Extrema
Authors: Wu Lang , Zhang Dazhi , Wu Boying , Meng Xiong
Published: July 2014

Fifth-order mapped semi-Lagrangian weighted essentially nonoscillatory (WENO) methods at certain smooth extrema are developed in this study. The schemes contain the mapped semi-Lagrangian finite volume (M-SL-FV) WENO 5 method and the mapped compact semi-Lagrangian finite difference (M-C-SL-FD) WENO 5 method. The weights in the more common scheme lose accuracy at certain smooth extrema. We introduce mapped weighting to handle the problem. In general, a cell average is applied to construct the M-SL-FV WENO 5 reconstruction, and the M-C-SL-FD WENO 5 interpolation scheme is proposed based on an interpolation approach. An accuracy test and numerical examples are used to demonstrate that the two schemes reduce the loss of accuracy and improve the ability to capture discontinuities.