bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of Feeding Dry Glycerol to Primiparous Holstein Dairy Cows on Follicular Development, Reproductive Performance and Metabolic Parameters Related to Fertility during the Early Post‐partum Period
Authors: Karami‐Shabankareh H , Kafilzadeh F , Piri V , Mohammadi H
Published: June 2013

Contents

This study examined the effects of dry glycerol supplementation on follicular growth, post‐partum interval to first ovulation, concentration of serum metabolites and hormones related to fertility, body condition score (BCS) and body weight (BW) in primiparous Holstein dairy cows. Sixty primiparous Holstein dairy cows were randomly assigned to two groups (control: n = 30 and glycerol supplemented: n = 30). Dry glycerol (250 g/day/cow) was fed as a top dressing to the common lactating total mixed ration (TMR) from parturition to 21 days post‐partum. Ovaries were examined four times using ultrasonography on days 13, 19, 25 and 36 post‐partum to determine ovarian follicular growth. Concentration of serum metabolites and hormones was determined weekly. Body condition score was evaluated weekly from weeks 1 to 5 after parturition, and BWs were recorded three times on days 1, 11 and 21 during the experimental period. The cows fed dry glycerol had more large follicles (p < 0.0001) and corpora lutea (CL) (p = 0.02) compared with the control cows. Days to the first ovulation (p = 0.06), days to first oestrus (p = 0.05), services per conception (p = 0.06) and days open (p = 0.004) were positively affected by dry glycerol supplementation. Serum concentration of glucose and insulin was higher in dry glycerol‐supplemented cows (p = 0.1; p = 0.06, respectively). Feeding glycerol had no effect on mean serum concentrations of β‐hydroxybutyrate, non‐esterified fatty acids and IGF‐1 during the experimental period. However, significant differences were observed at concentration of BHBA and IGF‐1 (p = 0.02 and p = 0.04, respectively) between two groups on day 21 after calving. The cows in the glycerol‐fed group had higher serum progesterone concentrations on days 33 (p = 0.007) and 36 (p = 0.004) after calving. Supplemented cows had lower body condition loss during weeks 1–5 after calving compared with the control cows (0.34 vs 0.41 BCS). In week 13 post‐partum, the proportion of cycling cows was 83.3 and 69.9% for those which received supplemented or non‐supplemented diet, respectively. These results demonstrated that feeding dry glycerol as a glucogenic supply may be useful to improve negative energy balance and reproductive efficiency in young cows which calve with high requirement of energy.
Governmentality in Service Provision for Migrated Women in Spain
Authors: Montenegro Karla , Montenegro Marisela
Published: June 2013

A gender perspective has been incorporated in transnational migration studies over the last two decades in Spain. According to feminist inquiry, research has focused mainly on four areas: transnational maternities, transformation in global care regimes, multiple discrimination experiences and change in gender relations by means of migration. In this paper, we suggest that there is a fifth area that has been neglected: one that studies the ways in which governmentality practices, performed within service provision aimed at migrant populations, are enacted in host societies. We argue that mechanisms of categorisation developed in service provision in Spain contribute to the construction of the category of “Third World Women”. A set of discourses and practices that are based on gender and cultural assignation related with stereotyped understandings of migrated women in host societies, situating them as suitable workers for current care regimes within these societies. These mechanisms have an important impact on life situations experienced by many migrated women as they are integrated into a low waged and undervalued work market. Further developments must be made in this last area of inquiry from a critical standpoint, in order to avoid the reproduction of discriminatory practices within institutional intervention settings.
Ten years in the United Nations: Where does Switzerland stand?
Authors: Hug Simon , Wegmann Simone
Published: June 2013

Prior to its full membership in the United Nations, Switzerland was an active observer and even an active member of many specialized UN agencies. However, ten years ago, Swiss voters finally approved full UN membership and in 2002, behavioral data started to become available on Switzerland's involvement in the major UN assemblies. Switzerland was admitted to the UN General Assembly (UNGA) as a full member on September 10th, 2002 and was elected to the newly created UN Human Rights Council (UNHRC) in 2006. Switzerland wished to be an active partner in both of these assemblies. In this research note we describe, based on novel data collected on the UNGA and the UNHRC, how Switzerland positions itself in the “orchestra of nations.”
Virtual Secondary Path Algorithm for Multichannel Active Control of Vehicle Powertrain Noise
Authors: Duan Jie , Li Mingfeng , Lim Teik C. , Lee Ming-Ran , Cheng Ming-Te , Vanhaaften Wayne , Abe Takeshi
Published: June 2013

An enhanced multiple-input multiple-output (MIMO) filtered-x least mean square (FXLMS) algorithm using improved virtual secondary path is proposed as the basis for an active noise control (ANC) system for treating vehicle powertrain noise. This new algorithm is developed to overcome the limitation caused by the frequency-dependent property of the standard FXLMS algorithm and to reduce the variation of convergence speed inherent in multiple-channel cases, in order to improve the overall performance of the control system. In this study, the convergence property of the proposed algorithm is analyzed in the frequency domain in order to yield a better understanding of the physical meaning of the virtual secondary path. In practice, because of the arrangement and sensitivities of the actuators (speakers), transducers (microphones), and physical environment, the magnitude response of the main secondary paths can be very different from each other. This difference will cause difficulty in the overall convergence of the algorithm, which will result in minimal attenuation at some of the channels. The proposed channel equalized (CE) virtual secondary path algorithm is designed to tackle this difficulty by equalizing the mean magnitude level of the main secondary paths and by adjusting other secondary paths correspondingly to keep the coupling effects among the control channels unchanged. The performance of the proposed algorithm is validated by analyzing a two-input two-output active powertrain noise control system.
Wave Vibration Control of L-Shaped and Portal Planar Frames
Authors: Mei C.
Published: June 2013

This paper discusses the control of coupled bending and axial vibrations in L-shaped and portal planar frame structures. The controller is designed based on a wave standpoint, in which vibrations are described as waves traveling along uniform structural waveguides, and being reflected and transmitted at structural discontinuities. Active discontinuities are created using active control forces/moments both along structural elements and at structural joints to control vibration waves. The classical Euler–Bernoulli as well as the advanced Timoshenko bending theories are applied in modeling and controlling the flexural vibrations in planar frames. The axial vibrations are modeled using the elementary theory as it is typically valid for frequencies up to twice the cutoff frequency of Timoshenko bending waves. Results are compared between the two bending vibration theories. It is concluded that for relatively higher frequencies, typically when the transverse dimensions are not negligible with respect to the wavelength, the effects of rotary inertia and shear distortion must be taken into account for both vibration analysis and control design.
Dual-Functional Energy-Harvesting and Vibration Control: Electromagnetic Resonant Shunt Series Tuned Mass Dampers
Authors: Zuo Lei , Cui Wen
Published: June 2013

This paper proposes a novel retrofittable approach for dual-functional energy-harvesting and robust vibration control by integrating the tuned mass damper (TMD) and electromagnetic shunted resonant damping. The viscous dissipative element between the TMD and primary system is replaced by an electromagnetic transducer shunted with a resonant RLC circuit. An efficient gradient based numeric method is presented for the parameter optimization in the control framework for vibration suppression and energy harvesting. A case study is performed based on the Taipei 101 TMD. It is found that by tuning the TMD resonance and circuit resonance close to that of the primary structure, the electromagnetic resonant-shunt TMD achieves the enhanced effectiveness and robustness of double-mass series TMDs, without suffering from the significantly amplified motion stroke. It is also observed that the parameters and performances optimized for vibration suppression are close to those optimized for energy harvesting, and the performance is not sensitive to the resistance of the charging circuit or electrical load.
Surface Modification of Polyimide Thin Films for Peripheral Invasive Neural Interfaces
Authors: Righi M. , Bossi S. , Puleo GL. , Giudetti G. , Wieringa P. , Cutrone A. , Micera S.
Published: June 2013

Despite recognized as one key component for establishing a functional electrical connection with nerves, neural invasive peripheral interfaces are still not optimal for long-term applications in humans. An improvement in the field of biocompatible and non-toxic materials is necessary to overcome the issues of interface/tissue mismatch and physiological reactions. The present work aimed to study, implement and characterize a novel approach to modify the surface of neural mi-crolectrodes basedon polyimide thin films. The purpose was to improve biocompatibility and to promote neuronal migration, growth and differentiation by increasing the surface roughness and endowing the surface with structure-reactivity for thiol-containing amino acids or peptides. L-Cysteine-Rhodamine B, used as a model biomolecule, was successfully grafted on samples surface via the introduction of cross-linkable vinyl groups on polyimide foils. Preliminary in vitro biological analysis allowed to evaluate the tendency of PC12 cells to adhere and to proliferate.
A Joint Kurtosis-Based Adaptive Bandstop Filtering and Iterative Autocorrelation Approach to Bearing Fault Detection
Authors: Zhang Yi , Liang Ming , Li Chuan , Hou Shumin
Published: June 2013

This paper reports a bearing fault detection method based on kurtosis-based adaptive bandstop filtering (KABS) and iterative autocorrelation (IAC). The interferences in the bearing signal can be removed by KABS filtering, whereas IAC is employed for noise reduction and signal enhancement. In the KABS method, two window-merging schemes are proposed to identify the frequency bands potentially containing interferences and to preserve those covering fault frequencies. Issues related to the selection of the number of autocorrection iterations are also discussed. The proposed method can be used for bearing fault detection in a low signal-to-noise ratio (SNR) and low signal-to-interference ratio (SIR) environment. The implementation of the proposed method does not require prior knowledge of the fault-excited resonant frequency. The performance of the proposed method has been examined by simulation analysis, with favorable comparisons to the Hilbert enveloping, energy operator, and spectrum kurtosis methods. Its effectiveness in bearing fault detection has also been demonstrated using experimental data.
Improving IMRT delivery efficiency with reweighted L1‐minimization for inverse planning
Authors: Kim Hojin , Becker Stephen , Lee Rena , Lee Soonhyouk , Shin Sukyoung , Candès Emmanuel , Xing Lei , Li Ruijiang
Published: June 2013

Purpose:

This study presents an improved technique to further simplify the fluence‐map in intensity modulated radiation therapy (IMRT) inverse planning, thereby reducing plan complexity and improving delivery efficiency, while maintaining the plan quality.

Methods:

First‐order total‐variation (TV) minimization (min.) based on L1‐norm has been proposed to reduce the complexity of fluence‐map in IMRT by generating sparse fluence‐map variations. However, with stronger dose sparing to the critical structures, the inevitable increase in the fluence‐map complexity can lead to inefficient dose delivery. Theoretically, L0‐min. is the ideal solution for the sparse signal recovery problem, yet practically intractable due to its nonconvexity of the objective function. As an alternative, the authors use the iteratively reweighted L1‐min. technique to incorporate the benefits of the L0‐norm into the tractability of L1‐min. The weight multiplied to each element is inversely related to the magnitude of the corresponding element, which is iteratively updated by the reweighting process. The proposed penalizing process combined with TV min. further improves sparsity in the fluence‐map variations, hence ultimately enhancing the delivery efficiency. To validate the proposed method, this work compares three treatment plans obtained from quadratic min. (generally used in clinic IMRT), conventional TV min., and our proposed reweighted TV min. techniques, implemented by a large‐scale L1‐solver (template for first‐order conic solver), for five patient clinical data. Criteria such as conformation number (CN), modulation index (MI), and estimated treatment time are employed to assess the relationship between the plan quality and delivery efficiency.

Results:

The proposed method yields simpler fluence‐maps than the quadratic and conventional TV based techniques. To attain a given CN and dose sparing to the critical organs for 5 clinical cases, the proposed method reduces the number of segments by 10–15 and 30–35, relative to TV min. and quadratic min. based plans, while MIs decreases by about 20%–30% and 40%–60% over the plans by two existing techniques, respectively. With such conditions, the total treatment time of the plans obtained from our proposed method can be reduced by 12–30 s and 30–80 s mainly due to greatly shorter multileaf collimator (MLC) traveling time in IMRT step‐and‐shoot delivery.

Conclusions:

The reweighted L1‐minimization technique provides a promising solution to simplify the fluence‐map variations in IMRT inverse planning. It improves the delivery efficiency by reducing the entire segments and treatment time, while maintaining the plan quality in terms of target conformity and critical structure sparing.
Deformable mesh registration for the validation of automatic target localization algorithms
Authors: Robertson Scott , Weiss Elisabeth , Hugo Geoffrey D.
Published: June 2013

Purpose:

To evaluate deformable mesh registration (DMR) as a tool for validating automatic target registration algorithms used during image‐guided radiation therapy.

Methods:

DMR was implemented in a hierarchical model, with rigid, affine, and B‐spline transforms optimized in succession to register a pair of surface meshes. The gross tumor volumes (primary tumor and involved lymph nodes) were contoured by a physician on weekly CT scans in a cohort of lung cancer patients and converted to surface meshes. The meshes from weekly CT images were registered to the mesh from the planning CT, and the resulting registered meshes were compared with the delineated surfaces. Known deformations were also applied to the meshes, followed by mesh registration to recover the known deformation. Mesh registration accuracy was assessed at the mesh surface by computing the symmetric surface distance (SSD) between vertices of each registered mesh pair. Mesh registration quality in regions within 5 mm of the mesh surface was evaluated with respect to a high quality deformable image registration.

Results:

For 18 patients presenting with a total of 19 primary lung tumors and 24 lymph node targets, the SSD averaged 1.3 ± 0.5 and 0.8 ± 0.2 mm, respectively. Vertex registration errors (VRE) relative to the applied known deformation were 0.8 ± 0.7 and 0.2 ± 0.3 mm for the primary tumor and lymph nodes, respectively. Inside the mesh surface, corresponding average VRE ranged from 0.6 to 0.9 and 0.2 to 0.9 mm, respectively. Outside the mesh surface, average VRE ranged from 0.7 to 1.8 and 0.2 to 1.4 mm. The magnitude of errors generally increased with increasing distance away from the mesh.

Conclusions:

Provided that delineated surfaces are available, deformable mesh registration is an accurate and reliable method for obtaining a reference registration to validate automatic target registration algorithms for image‐guided radiation therapy, specifically in regions on or near the target surfaces.
Stefan–Boltzmann law for the tungsten filament of a light bulb: Revisiting the experiment
Authors: Carlà Marcello
Published: June 2013

A classical laboratory experiment to verify the Stefan-Boltzmann radiation law with the tungsten filaments of commercial incandescent lamps has been fully revisited, collecting a fairly large amount of data with a computer-controlled four-channel power supply. In many cases, the total power dissipated by the lamp is well described by a sum of two power-law terms, with one exponent very close to 4, as predicted by the radiation law, and the other very close to 1, as for simple heat conduction. This result was true even for filament surfaces with a shiny metallic appearance, whose emissivity should vary with temperature.
Improving the quantification of Brownian motion
Authors: Catipovic Marco A. , Tyler Paul M. , Trapani Josef G. , Carter Ashley R.
Published: June 2013

Brownian motion experiments have become a staple of the undergraduate advanced laboratory, yet quantification of these experiments is difficult, typically producing errors of 10%–15% or more. Here, we discuss the individual sources of error in the experiment: sampling error, uncertainty in the diffusion coefficient, tracking error, vibration, and microscope drift. We model each source of error using theoretical and computational methods and compare the model to our experimental data. Finally, we describe various ways to reduce each source of error to less than 1%, improving the quantification of Brownian motion.
Combining two reform curricula: An example from a course with well-prepared students
Authors: Lindsey Beth A. , Liu Amy Y.
Published: June 2013

Many studies have separately documented the benefits of research-based curricula and pedagogical methods. Here, we report on the effects of adopting a reform curriculum (Matter and Interactions) in conjunction with a pedagogical tool designed and validated in the context of a traditional treatment of mechanics (Tutorials in Introductory Physics). We document the need for targeted interactive engagement materials (such as the tutorials) even in a course with a population of students who are extremely well-prepared in physics. We describe the modifications necessary to successfully incorporate Tutorials in Introductory Physics into a course using Matter and Interactions, and we present data documenting the success of this approach.
Of pendulums, polymers, and robots: Computational mechanics with constraints
Authors: Vesely Franz J.
Published: June 2013

The motion of point masses under the influence of a potential can be computed by simple methods. However, if the trajectories are restricted by mechanical constraints such as strings, rails, crankshafts, and molecular bonds, special numerical techniques must be invoked. The need for efficient computational strategies is particularly pressing for molecular simulations, where large systems of compound molecules are tracked. The best strategy is the use of Cartesian coordinates in combination with constraint forces in the Lagrange formulation. This approach has led to the extremely successful SHAKE and RATTLE algorithms. The same ideas may be profitably applied in very different fields such as robotics, mechanics, and geometry, and the study of chaos in simple systems.
Ubiquitin System: Direct Effects Join the Signaling
Authors: Chernorudskiy Alexander L. , Gainullin Murat R.
Published: June 2013

By sterically altering protein-protein interactions, ubiquitin modification can directly affect protein function.
Methylation and Methuselah?
Authors: Hurtley Stella M.
Published: June 2013

Reduced protein methyltransferase activity improves progeria-like disease phenotypes.
Almost Open
Authors: Gough Nancy R.
Published: June 2013

Crystal structure analysis reveals that βγ subunits twist the GIRK2 K
+
channel into a conformation closer to open.
Evaluation of Initial and Steady-State Gatifloxacin Pharmacokinetics and Dose in Pulmonary Tuberculosis Patients by Using Monte Carlo Simulations
Authors: Smythe Wynand , Merle Corinne S. , Rustomjee Roxana , Gninafon Martin , Lo Mame Bocar , Bah-Sow Oumou , Olliaro Piero L. , Lienhardt Christian , Horton John , Smith Peter , McIlleron Helen , Simonsson Ulrika S. H.
Published: June 2013

A 4-month regimen of gatifloxacin with rifampin, isoniazid, and pyrazinamide is being evaluated for the treatment of tuberculosis in a phase 3 randomized controlled trial (OFLOTUB). A prior single-dose study found that gatifloxacin exposure increased by 14% in the combination. The aims of the study are to evaluate the initial and steady-state pharmacokinetics of gatifloxacin when daily doses are given to patients with newly diagnosed drug-sensitive pulmonary tuberculosis as part of a combination regimen and to evaluate the gatifloxacin dose with respect to the probability of attaining a pharmacokinetic/pharmacodynamic target. We describe the population pharmacokinetics of gatifloxacin from the first dose to a median of 28 days in 169 adults enrolled in the OFLOTUB trial in Benin, Guinea, Senegal, and South Africa. The probability of achieving a ratio of ≥125 for the area under the concentration time curve to infinity (AUC
0–∞
) for the free fraction of gatifloxacin over the MIC (
f
AUC/MIC) was investigated using Monte Carlo simulations. The median AUC
0–∞
of 41.2 μg · h/ml decreased on average by 14.3% (90% confidence interval [CI], −90.5% to +61.5%) following multiple 400-mg daily doses. At steady state, 90% of patients achieved an
f
AUC/MIC of ≥125 only when the MIC was <0.125 μg/ml. We conclude that systemic exposure to gatifloxacin declines with repeated daily 400-mg doses when used together with rifampin, isoniazid, and pyrazinamide, thus compensating for any initial increase in gatifloxacin levels due to a drug interaction. (The OFLOTUB study has been registered at ClinicalTrials.gov under registration no. NCT00216385.)
Noncompetitive Inhibition of Hepatitis B Virus Reverse Transcriptase Protein Priming and DNA Synthesis by the Nucleoside Analog Clevudine
Authors: Jones Scott A. , Murakami Eisuke , Delaney William , Furman Phillip , Hu Jianming
Published: June 2013

All currently approved antiviral drugs for the treatment of chronic hepatitis B virus (HBV) infection are nucleos(t)ide reverse transcriptase inhibitors (NRTI), which inhibit the DNA synthesis activity of the HBV polymerase. The polymerase is a unique reverse transcriptase (RT) that has a novel protein priming activity in which HP initiates viral DNA synthesis using itself as a protein primer. We have determined the ability of NRTI-triphosphates (TP) to inhibit HBV protein priming and their mechanisms of action. While entecavir-TP (a dGTP analog) inhibited protein priming initiated specifically with dGTP, clevudine-TP (a TTP analog) was able to inhibit protein priming independently of the deoxynucleoside triphosphate (dNTP) substrate and without being incorporated into DNA. We next investigated the effect of NRTIs on the second stage of protein priming, wherein two dAMP nucleotides are added to the initial deoxyguanosine nucleotide. The obtained results indicated that clevudine-TP as well as tenofovir DF-DP strongly inhibited the second stage of protein priming. Tenofovir DF-DP was incorporated into the viral DNA primer, whereas clevudine-TP inhibited the second stage of priming without being incorporated. Finally, kinetic analyses using the HBV endogenous polymerase assay revealed that clevudine-TP inhibited DNA chain elongation by HP in a noncompetitive manner. Thus, clevudine-TP appears to have the unique ability to inhibit HBV RT via binding to and distorting the HP active site, sharing properties with both NRTIs and nonnucleoside RT inhibitors.
HIV-Positive Nigerian Adults Harbor Significantly Higher Serum Lumefantrine Levels than HIV-Negative Individuals Seven Days after Treatment for Plasmodium falciparum Infection
Authors: Chijioke-Nwauche Ifeyinwa , van Wyk Albert , Nwauche Chijioke , Beshir Khalid B. , Kaur Harparkash , Sutherland Colin J.
Published: June 2013

Management of coinfection with malaria and HIV is a major challenge to public health in developing countries, and yet potential drug-drug interactions between antimalarial and antiviral regimens have not been adequately investigated in people with both infections. Each of the constituent components of artemether-lumefantrine, the first-line regimen for malaria treatment in Nigeria, and nevirapine, a major component of highly active antiretroviral therapy, are drugs metabolized by the cytochrome P450 3A4 isoenzyme system, which is also known to be induced by nevirapine. We examined potential interactions between lumefantrine and nevirapine in 68 HIV-positive adults, all of whom were diagnosed with asymptomatic
Plasmodium falciparum
infections by microscopy.
Post hoc
PCR analysis confirmed the presence of
P. falciparum
in only a minority of participants. Day 7 capillary blood levels of lumefantrine were significantly higher in HIV-positive participants than in 99 HIV-negative controls (
P
= 0.0011). Associations between day 7 levels of lumefantrine and risk of persistent parasitemia could not be evaluated due to inadequate power. Further investigations of the impact of nevirapine on
in vivo
malaria treatment outcomes in HIV-infected patients are thus needed.
Group B Streptococcus and Streptococcus suis Capsular Polysaccharides Induce Chemokine Production by Dendritic Cells via Toll-Like Receptor 2- and MyD88-Dependent and -Independent Pathways
Authors: Calzas Cynthia , Goyette-Desjardins Guillaume , Lemire Paul , Gagnon Fleur , Lachance Claude , Van Calsteren Marie-Rose , Segura Mariela
Published: June 2013

Streptococcus agalactiae(also known as group BStreptococcus[GBS]) andStreptococcus suisare encapsulated streptococci causing severe septicemia and meningitis. Bacterial capsular polysaccharides (CPSs) are poorly immunogenic, but anti-CPS antibodies are essential to the host defense against encapsulated bacteria. The mechanisms underlying anti-CPS antibody responses are not fully elucidated, but the biochemistry of CPSs, particularly the presence of sialic acid, may have an immunosuppressive effect. We investigated the ability of highly purifiedS. suisand GBS native (sialylated) CPSs to activate dendritic cells (DCs), which are crucial actors in the initiation of humoral immunity. The influence of CPS biochemistry was studied using CPSs extracted from different serotypes within these two streptococcal species, as well as desialylated CPSs. No interleukin-1β (IL-1β), IL-6, IL-12p70, tumor necrosis factor alpha (TNF-α), or IL-10 production was observed inS. suisor GBS CPS-stimulated DCs. Moreover, these CPSs exerted immunosuppressive effects on DC activation, as a diminution of gamma interferon (IFN-γ)-induced B cell-activating factor of the tumor necrosis factor family (BAFF) expression was observed in CPS-pretreated cells. However,S. suisand GBS CPSs induced significant production of CCL3, via partially Toll-like receptor 2 (TLR2)- and myeloid differentiation factor 88 (MyD88)-dependent pathways, and CCL2, via TLR-independent mechanisms. No major influence of CPS biochemistry was observed on the capacity to induce chemokine production by DCs, indicating that DCs respond to these CPSs in a patterned way rather than a structure-dedicated manner.
Interleukin-17 Protects against the Francisella tularensis Live Vaccine Strain but Not against a Virulent F. tularensis Type A Strain
Authors: Skyberg Jerod A. , Rollins MaryClare F. , Samuel Joshua W. , Sutherland Marjorie D. , Belisle John T. , Pascual David W.
Published: June 2013

Francisella tularensis
is a highly infectious intracellular bacterium that causes the zoonotic infection tularemia. While much literature exists on the host response to
F. tularensis
infection, the vast majority of work has been conducted using attenuated strains of
Francisella
that do not cause disease in humans. However, emerging data indicate that the protective immune response against attenuated
F. tularensis
versus
F. tularensis
type A differs. Several groups have recently reported that interleukin-17 (IL-17) confers protection against the live vaccine strain (LVS) of
Francisella
. While we too have found that IL-17Rα
−/−
mice are more susceptible to
F. tularensis
LVS infection, our studies, using a virulent type A strain of
F. tularensis
(SchuS4), indicate that IL-17Rα
−/−
mice display organ burdens and pulmonary gamma interferon (IFN-γ) responses similar to those of wild-type mice following infection. In addition, oral LVS vaccination conferred equivalent protection against pulmonary challenge with SchuS4 in both IL-17Rα
−/−
and wild-type mice. While IFN-γ was found to be critically important for survival in a convalescent model of SchuS4 infection, IL-17 neutralization from either wild-type or IFN-γ
−/−
mice had no effect on morbidity or mortality in this model. IL-17 protein levels were also higher in the lungs of mice infected with the LVS rather than
F. tularensis
type A, while IL-23p19 mRNA expression was found to be caspase-1 dependent in macrophages infected with LVS but not SchuS4. Collectively, these results demonstrate that IL-17 is dispensable for host immunity to type A
F. tularensis
infection, and that induced and protective immunity differs between attenuated and virulent strains of
F. tularensis
.
Characterization of Streptococcal Platelet-Activating Factor Acetylhydrolase Variants That Are Involved in Innate Immune Evasion
Authors: Liu Guanghui , Liu Mengyao , Xie Gang , Lei Benfang
Published: June 2013

Human pathogen group A streptococcus (GAS) has developed mechanisms to subvert innate immunity. We recently reported that the secreted esterase produced by serotype M1 GAS (SsEM1) reduces neutrophil recruitment by targeting platelet-activating factor (PAF). SsEM1and SsE produced by serotype M28 GAS (SsEM28) have a 37% sequence difference. This study aims at determining whether SsEM28is also a PAF acetylhydrolase and participates in innate immune evasion. We also examined whether SsE evolved to target PAF by characterizing the PAF acetylhydrolase (PAF-AH) activity and substrate specificity of SsEM1, SsEM28, SeE, the SsE homologue inStreptococcus equi, and human plasma PAF-AH (hpPAF-AH). PAF incubated with SsEM28or SeE was converted into lyso-PAF. SsEM1and SsEM28hadkcatvalues of 373 s−1and 467 s−1, respectively, that were ≥30-fold greater than that of hpPAF-AH (12 s−1). The comparison of SsEM1, SsEM28, and hpPAF-AH inkcatandKmin hydrolyzing triglycerides, acetyl esters, and PAF indicates that the SsE proteins are more potent hydrolases against PAF and have high affinity for PAF. SsEM28possesses much lower esterase activities against triglycerides and other esters than SsEM1but have similar potency with SsEM1in PAF hydrolysis. Deletion ofsseM28in acovSdeletion mutant of GAS increased neutrophil recruitment and reduced skin infection, whereas intransexpression of SsEM28in GAS reduced neutrophil infiltration and increased skin invasion in subcutaneous infection of mice. These results suggest that the SsE proteins evolved to target PAF for enhancing innate immune evasion and skin invasion.
Stenotrophomonas maltophilia Encodes a Type II Protein Secretion System That Promotes Detrimental Effects on Lung Epithelial Cells
Authors: Karaba Sara M. , White Richard C. , Cianciotto Nicholas P.
Published: June 2013

The Gram-negative bacterium
Stenotrophomonas maltophilia
is increasingly identified as a multidrug-resistant pathogen, being associated with pneumonia, among other infections. Despite this increasing clinical problem, the genetic and molecular basis of
S. maltophilia
virulence is quite minimally defined. We now report that strain K279a, the first clinical isolate of
S. maltophilia
to be sequenced, encodes a functional type II protein secretion (T2S) system. Indeed, mutants of K279a that contain a mutation in the
xps
locus exhibit a loss of at least seven secreted proteins and three proteolytic activities. Unlike culture supernatants from the parental K279a, supernatants from multiple
xps
mutants also failed to induce the rounding, detachment, and death of A549 cells, a human lung epithelial cell line. Supernatants of the
xps
mutants were also unable to trigger a massive rearrangement in the host cell's actin cytoskeleton that was associated with K279a secretion. In all assays, a complemented
xpsF
mutant behaved as the wild type did, demonstrating that Xps T2S is required for optimal protein secretion and the detrimental effects on host cells. The activities that were defined as being Xps dependent in K279a were evident among other respiratory isolates of
S. maltophilia
. Utilizing a similar type of genetic analysis, we found that a second T2S system (Gsp) encoded by the K279a genome is cryptic under all of the conditions tested. Overall, this study represents the first examination of T2S in
S. maltophilia
, and the data obtained indicate that Xps T2S likely plays an important role in
S. maltophilia
pathogenesis.
Can lenalidomide play a role in the management of scleritis?
Authors: Al-Jafar Hassan A , Abul Nadia , Kumar Niranjan , Al-Awadhi Adel
Published: June 2013

Lenalidomide is an immunomodulatory agent that was approved for the treatment of a monoclonal bone marrow disorders, myelodysplastic syndrome del(5q)(MDS del(5q)), in 2005; the drug was subsequently also approved for the treatment of refractory multiple myeloma, a bone marrow malignancy of the B-lymphocyte lineage. The purpose of this study is to report a case of MDS del(5q) in a female patient, which was most likely secondary to the immunosuppressive drugs that the patient was taking for scleritis. After lenalidomide treatment, the patient's haematological symptoms rapidly resolved and she became transfusion independent, with normal haemoglobin levels. This medication also helped control her dependence on high doses of oral prednisolone. The patient continued to receive treatment with low-dose lenalidomide, and her scleritis has been in long-term remission for 3 years. A larger prospective study can further define the role of lenalidomide in the management of scleritis.
Severe unconjugated hyperbilirubinaemia: one and one makes three?
Authors: Naha Kushal , Dasari Sowjanya , Vivek G , Hande Manjunath , Acharya Vasudev
Published: June 2013

A 38-year-old housewife presented with a 3-month history of gradually progressive fatigue and deepening jaundice as well as a history of mild fluctuating jaundice since childhood. General examination revealed an obvious icterus. Systemic examination was normal. Laboratory tests confirmed unconjugated hyperbilirubinaemia. Further evaluation yielded a diagnosis of vitamin B12deficiency on a background of Gilbert's syndrome.
Neck abscess associated with a piriform fossa sinus tract in an adult
Authors: Adamidou Fotini , Anagnostis Panagiotis , Karras Spyridon , Kita Marina
Published: June 2013

Perithyroidal inflammatory masses deriving from developmental remnants of the 3rd and 4th brancial pouches are rare. We report a case of an otherwise healthy 31-year-old man, who presented with fever and swelling of the left side of the neck. Neck ultrasound showed a displaced left thyroid lobe with induration of the strap muscles. Fine-needle aspiration biopsy revealed pus, positive forStaphylococcus aureusspecies. Antibiotic treatment led to rapid clinical improvement and reversal of imaging features, without the need for surgical intervention. This rare clinical entity should be always considered in the differential diagnosis of an inflammatory neck mass.
Diagnostic, therapeutic and economic consequences of a positive urinary antigen test forLegionellaspp. in patients admitted with community-acquired pneumonia: a 7-year retrospective evaluation
Authors: Engel M F , van Manen L , Hoepelman A I M , Thijsen S , Oosterheert J J
Published: June 2013

Aims

A positive urinary antigen test forLegionellaspp. (Legionella urinary antigen test; LUAT) allows an early switch from empiric to targeted treatment (TT) in hospitalised, community-acquired pneumonia (CAP) patients. We aimed to evaluate the diagnostic, therapeutic and economic consequences of this frequently used test 7 years after its implementation.

Methods

We retrospectively evaluated LUATs performed between 2005 and 2011 in two teaching hospitals. All tests performed in hospitalised CAP patients were used in the economic evaluation and positive tests were included in the treatment evaluation. Data on patient characteristics, admission and outcome were retrieved from the patients’ files. The number of days gained by making a rapid aetiological diagnosis, the number of days TT could be provided and their costs were calculated.

Results

Of 4485 LUATs, 2504 (56%) were performed for CAP including 55 (1%) positive tests (€1041/positive test). In 26 (60%) of the 43 included positive tests, LUAT was the only test showingLegionellaspp. Subsequently, earlier TT was possible in the remaining cases during 209 cumulative admission days (€274/TT day). LUAT led to detection ofLegionellaspp. 13 days earlier per case (€203/day) as compared with culture/serology alone.

Conclusions

Timely LUAT use in accordance with current guidelines allows early detection and treatment of CAP caused byLegionellaspp. at considerable expense.
Addition of rituximab to chemotherapy overcomes the negative prognostic impact of cyclin E expression in diffuse large B-cell lymphoma
Authors: Frei E , Visco C , Xu-Monette Z Y , Dirnhofer S , Dybkær K , Orazi A , Bhagat G , Hsi E D , van Krieken J H , Ponzoni M , Go R S , Piris M A , Møller M B , Young K H , Tzankov A
Published: June 2013

Background

High levels of cyclin E (CCNE) are accompanied by shorter survival in cyclophosphamide, hydroxydaunorubicin, oncovin and prednisone (CHOP)-treated diffuse large B-cell lymphomas (DLBCL), independent of the international prognostic index (IPI). Data on the prognostic role of CCNE in the ‘rituximab (R)-era’ are lacking.

Methods

To test reproducibility and applicability of observations from the ‘pre-R era’ to the ‘R era’, we examined the prognostic role of CCNE expression by immunohistochemistry in 1579 DLBCL on tissue microarrays (TMA); 339 patients were treated by CHOP and 635 by R-CHOP.

Results

1209 samples (77%) were evaluable; failures were due to missing TMA punches and fixation artefacts. Mean expression of CCNE was 13% (0–85%); applying a cut-off of >16%, 382 DLBCL (31%) were positive. CCNE did not correlate with any of the known variables (IPI, primary site, cell of origin, proliferation, andBCL2-orC-MYCrearrangements). We were able to reproduce data suggesting an IPI- and response to therapy independent, negative prognostic impact of CCNE in CHOP-treated DLBCL patients: CCNE-positive cases had a median survival of 16 months compared with 57 months in negative ones (p=0.012). In R-CHOP-treated patients the prognostic impact of CCNE was abrogated and only IPI, cell of origin and response to therapy had a prognostic significance.

Conclusions

Addition of R to CHOP overcomes the negative prognostic impact of CCNE in DLBCL. Thus, R not only prolongs survival in DLBCL but also serves a cautionary note that prognostic factors should not be transferred into the ‘R era’ without proper scientific studies.
Improving equity by removing healthcare fees for children in Burkina Faso
Authors: Ridde V , Haddad S , Heinmüller R
Published: June 2013

Background

This study evaluated the effects on healthcare access inequities of an intervention exempting children under 5 years from user fees in Burkina Faso.

Methods

The design consisted of two complementary studies. The first was an interrupted time series (56 months before and 12 months after) study of daily curative consultations according to distance (<5, 5–9 and ≥10 km) in a stratified random sample of 18 health centres: 12 with the intervention and 6 without. The second was a household panel survey (n=1214) assessing the evolution of health-seeking behaviours. Multilevel regression was used throughout.

Results

Attendance doubled under the intervention, after adjusting forCentres de Santé et de Promotion Socialesize, districts, secular trend and seasonal variation. Utilisation increased for all distance ranges and in all of the 12 health centres of the intervention area. The exemption benefited all children (rate ratios (RR)=1.52 (1.23 to 1.88)), whether their health needs were high (RR=1.69 (1.22 to 2.32)) or not (RR=1.46 (1.10 to 1.93)) and whether the children lived near (RR=1.42 (1.09 to 1.85)) or far from a health centre (RR=1.79 (1.31 to 2.43)). The exemption benefited the children of poor families when health need was high and services near (RR=5.23; (1.30 to 20.99)). The amount saved for a child's treatment by the exemption was on average and median 2500 F CFA (≈US$5).

Conclusions

Exempting children under five from user fees is effective and helps reduce inequities of access. It benefits vulnerable populations, although their service utilisation remains constrained by limitations in geographic accessibility of services.
Diagnosis of cystic fibrosis-related glucose abnormalities: Can we shorten the standard oral glucose tolerance test?
Authors: Coriati Adèle , Elisha Belinda , Virassamynaik Sandrine , Phaneuf Maude , Ziai Sophie , Gauthier Marie-Soleil , Rabasa-Lhoret Rémi
Published: June 2013

Adult patients with cystic fibrosis (APCF) are at high risk of developing impaired glucose tolerance (IGT) and CF-related diabetes (CFRD) and thus an annual screening with a 2-h oral glucose tolerance test (OGTT) is recommended. This population would greatly benefit from a simplified and harmless alternative to the standard OGTT. Thus, we aimed to compare the diagnostic values of HbA1c and glycemias at interval time points during the 2-h OGTT for IGT and CFRD detection in APCF. To do so, we conducted a cross-sectional analysis of 194 APCF with normal fasting plasma glucose values (≤7.0 mmol·L−1) who underwent a 2-h OGTT. Receivers operating characteristic area under the curves (ROC-AUC) were analyzed to assess the diagnostic value of HbA1c and intermediate OGTT glycemias using 2-h OGTT glycemia as reference. For both IGT and CFRD diagnoses, ROC-AUC values obtained from glycemia at 90 min were significantly higher than HbA1c and remaining intermediate glycemias (p < 0.001). The best 90-min OGTT cut-off values for these diagnoses were >9.3 mmol·L−1 (IGT) and ≥11.5 mmol·L−1 (CFRD). A 90-min OGTT glycemia might be a simplified alternative to 2-h OGTT glycemia for earlier glucose tolerance abnormalities diagnosis in APCF. This finding should be confirmed in other APCF cohorts and its predictive value should be established prospectively.
Three-dimensional centrifuge modelling of basement excavation effects on an existing tunnel in dry sand
Authors: Ng Charles W.W. , Shi Jiangwei , Hong Yi
Published: June 2013

Basement excavation may induce unsymmetrical and highly skewed loadings and (or) stress changes in an existing tunnel, not only in the transverse, but also in the longitudinal direction of the tunnel. Although basement–tunnel interaction has attracted intense academic interest recently, it is often simply treated as a plane strain problem. In this study, however, based on a dimensional analysis of the governing parameters, two three-dimensional centrifuge tests were designed and carried out in dry sand to investigate the effects of a basement excavation on an existing tunnel located in two horizontal offsets in relation to the basement. In addition, a preliminary three-dimensional numerical analysis was conducted to back-analyse the centrifuge test and to investigate the effects of the tunnel cover-to-diameter and unloading ratios on the existing tunnel. For the specific conditions simulated and soil type tested, a maximum heave of about 0.07% of the final depth of the basement excavation (He) was induced in the tunnel that ran parallel to and beneath the basement. On the contrary, a maximum settlement of 0.014% Hewas induced in the tunnel located at the side of the basement. For the former tunnel, the influence zone by the basement excavation on vertical tunnel displacement along the longitudinal direction was 1.2L (basement length). By inspecting the measured strains in the longitudinal direction of the existing tunnel, it was found that the inflection point, where the shear force is at a maximum, was located at 0.8L away from the basement centre. Due to stress relief from the basement excavation, the tunnel located directly beneath the basement was vertically elongated, but the one that lay at the side of the basement was distorted. A preliminary numerical parametric study found that tunnel heave decreased as the cover-to-diameter ratio increased, but at a reduced rate.
Influence of data quality and quantity from a multiyear tagging program on an integrated fish stock assessment
Authors: Ziegler Philippe Eric
Published: June 2013

Using a modeling framework for toothfish (Dissostichus spp.) population dynamics, fishing, and data collection, this study investigated how the bias and precision of biomass estimates from an integrated tag-based assessment are influenced by various aspects of a multiyear tagging program, particularly the effects of the size of tagged fish compared with the size of fish in the catch (tag size-overlap), numbers of tagged fish, duration of the tagging program, using catch-at-length or catch-at-age data as auxiliary data, and stock depletion levels. Biomass estimates generally improved with more and better-quality tagging data. The results showed that even when tag releases were distributed over a relatively large number of size classes, low recapture numbers collected in short tagging programs with a 100% tag size-overlap were sufficient for robust and unbiased assessments. Particularly in the early stages of the tagging program, a high tag size-overlap was imperative to maximize the likelihood of a robust assessment. Biomass estimates were largely unaffected by the stock depletion level; however, using catch-at-age compared with catch-at-length improved recruitment estimates and resulted in more conservative biomass estimates.
Cell-bound exopolysaccharides of Lactobacillus brevis KB290: protective role and monosaccharide composition
Authors: Suzuki Shigenori , Yakabe Takafumi , Suganuma Hiroyuki , Fukao Masanori , Saito Tadao , Yajima Nobuhiro
Published: June 2013

We examined the survivability of Lactobacillus brevis KB290 and derivative strain KB392 in artificial digestive juices and bile salts. The strains have similar membrane fatty acids but different amounts of cell-bound exopolysaccharides (EPS). In artificial digestive juices, KB290 showed significantly higher survivability than KB392, and homogenization, which reduced the amount of EPS in KB290 but not in KB392, reduced the survivability only of KB290. In bile salts, KB290 showed significantly higher survivability than KB392, and cell-bound EPS extraction with EDTA reduced the survivability of only KB290. Transmission electron microscopy showed there to be a greater concentration of cell-bound EPS in KB290 than in either KB392 or EDTA-treated or homogenized KB290. We conclude that KB290’s cell-bound EPS (which high performance liquid chromatography showed to be made up of glucose and N-acetylglucosamine) played an important role in bile salt tolerance.