bluuebunny/crossref_metadata_2025 huggingface dataset:
Development of Conservative Form of RELAP5 Thermal Hydraulic Equations: Part I — Theory
Authors: Fu Zheng , Aydogan Fatih , Wagner Richard J.
Published: March 2016

The design and analysis of the thermal/hydraulic systems of nuclear power plants necessitates system codes that can be used in the analysis of steady state and transient conditions. RELAP5 is one of the most commonly used system codes in nuclear organizations. RELAP5 is based on a two-fluid, non-equilibrium, non-homogeneous, hydrodynamic model for the transient simulation of the two-phase system behavior. This model includes six governing equations to describe the mass, energy, and momentum of the two fluids. The “non-conservative” numerical approximation form (which is the current form of RELAP5 code versions) is obtained through the manipulation of selected derivative terms in the equations including the linearization of the product terms in the time derivatives of the equations. For non-conservative technique, the truncation errors introduced in the linearization process can produce mass and energy errors for some classes of transients during time advancements, either resulting in (a) automatic reduction of time steps used in the advancement of the equations and increased run times or (b) the growth of unacceptably large errors in the transient results. To eliminate these difficulties, a new, optional numerical approach has been introduced in RELAP/SCDAPSIM/MOD4.0. This new option uses a more consistent set of the “conservative” numerical approximation to solve non-linearized mass and energy governing equations. The RELAP/SCDAPSIM/MOD4.0 code, being developed as part of the international SCDAP (Severe Core Damage Analysis Package) Development and Training Program (SDTP), is the first version of RELAP5 completely rewritten to FORTRAN 90/95/2000 standards. This paper provides an overview of the original RELAP5 numerical approximations and describes the new theoretical approach. Then the second article introduces the solution strategy of conservative approach and presents some examples of transient problems that have been run using this new approach.
Molten Salt Spectroscopy for Quantification of Radiative Absorption in Novel Metal Chloride-Enhanced Thermal Storage Media
Authors: Myers Philip D. , Goswami D. Yogi , Stefanakos Elias
Published: March 2016

This study describes the development and characterization of novel high-temperature thermal storage media, based on inclusion of transition metal chlorides in the potassium-sodium chloride eutectic system, (K-Na)Cl (melting temperature of 657°C, latent heat of 278 J/g). At the melting temperature of (K-Na)Cl, infrared (IR) radiation can play a major role in the overall heat transfer process — 90 percent of spectral blackbody radiation falls in the range of 2 to 13 μm. The authors propose inclusion of small amounts (less than 0.2 wt %) of IR-active transition metal chlorides to increase radiative absorption and thereby enhance heat transfer rates.

A new IR reflectance apparatus was developed to allow for determination of the spectral absorption coefficient of the newly formulated PCMs in the molten state. The apparatus consisted of an alumina crucible coated at the bottom with a reflective (platinum) or absorptive (graphite) surface, a heated ceramic crucible-holder, and a combination of zinc sulfide (ZnS) and zinc selenide (ZnSe) windows for containment of the salt and allowance of inert purge gas flow. Using this apparatus, IR spectra were obtained for various transition metal chloride additives in (K-Na)Cl, and improved infrared activity and radiative transfer properties were quantified. Further, thermophysical properties relevant to thermal energy storage (i.e., melting temperature, latent heat) are measured for the pure and additive-enhanced thermal storage medium.
Modeling Critical Flow Through Steam Generator Tube Cracks
Authors: Oussoren Andrew , Riznic Jovica R. , Revankar Shripad
Published: March 2016

Modeling of leakage rates through geometries representative of steam generator tube cracks is being investigated. These cracks are characterised by very small flow areas and low length to diameter ratios. Two sets of experiments were conducted by researchers at Purdue University measuring flow rates through several slits in 3.175 mm and 1.3 mm thick samples, with L/D ratios as low as 1.2. A pressure differential of 6.8 MPa was applied across the samples with varying degrees of subcooling. Flow rates through these samples were modeled using the thermal-hydraulic system codes RELAP and TRACE, using different nodalization techniques and both the Henry Fauske and Ransom Trapp critical flow models available in RELAP. Model results are compared to experimental values and modeling techniques are discussed. TRACE and RELAP were found to have similar accuracy in predicting flow rate trends, with higher accuracy at larger L/D. In general best results were achieved by modeling the crack as a junction component.
SpoVG Regulates Cell Wall Metabolism and Oxacillin Resistance in Methicillin-Resistant Staphylococcus aureus Strain N315
Authors: Liu Xiaoyu , Zhang Shijie , Sun Baolin
Published: March 2016

Increasing cases of infections caused by methicillin-resistant
Staphylococcus aureus
(MRSA) strains in healthy individuals have raised concerns worldwide. MRSA strains are resistant to almost the entire family of β-lactam antibiotics due to the acquisition of an extra penicillin-binding protein, PBP2a. Studies have shown that
spoVG
is involved in oxacillin resistance, while the regulatory mechanism remains elusive. In this study, we have found that SpoVG plays a positive role in oxacillin resistance through promoting cell wall synthesis and inhibiting cell wall degradation in MRSA strain N315. Deletion of
spoVG
in strain N315 led to a significant decrease in oxacillin resistance and a dramatic increase in Triton X-100-induced autolytic activity simultaneously. Real-time quantitative reverse transcription-PCR revealed that the expression of 8 genes related to cell wall metabolism or oxacillin resistance was altered in the
spoVG
mutant. Electrophoretic mobility shift assay indicated that SpoVG can directly bind to the putative promoter regions of
lytN
(murein hydrolase),
femA
, and
lytSR
(the two-component system). These findings suggest a molecular mechanism in which SpoVG modulates oxacillin resistance by regulating cell wall metabolism in MRSA.
Candida albicans Airway Colonization Facilitates Subsequent Acinetobacter baumannii Pneumonia in a Rat Model
Authors: Tan Xiaojiang , Chen Ruilan , Zhu Song , Wang Huijun , Yan Dongxing , Zhang Xiangdong , Farmakiotis Dimitrios , Mylonakis Eleftherios
Published: March 2016

The objective of the study was to determine the effects of
Candida albicans
respiratory tract colonization on
Acinetobacter baumannii
pneumonia in a rat model. Rats were colonized with
C. albicans
by instillation of 3 × 10
6
CFU into their airways, while sterile saline was instilled in the control group. The colonized rats were further divided into two groups: treated with amphotericin B or not. The rats were subsequently infected with
A. baumannii
(10
8
CFU by tracheobronchial instillation).
A. baumannii
lung CFU counts, cytokine lung levels, and rates of
A. baumannii
pneumonia were compared between groups.
In vitro
expression of
A. baumannii
virulence genes was measured by reverse transcription (RT)-PCR after 24-hour incubation with
C. albicans
or with Mueller-Hinton (MH) broth alone. Rats with
Candida
colonization developed
A. baumannii
pneumonia more frequently and had higher
A. baumannii
CFU burdens and heavier lungs than controls. After
A. baumannii
infection, lung interleukin 17 (IL-17) concentrations were lower and gamma interferon (IFN-γ) concentrations were higher in
Candida
-colonized rats than in controls.
Candida-
colonized rats treated with amphotericin B had a decreased rate of
A. baumannii
pneumonia and lower IFN-γ levels but higher IL-17 levels than untreated rats. Expression of
basC
,
barB
,
bauA
,
ptk
,
plc2
, and
pld2
was induced while expression of
ompA
and
abaI
was suppressed in
A. baumannii
cultured in the presence of
C. albicans
.
C. albicans
colonization facilitated the development of
A. baumannii
pneumonia in a rat model. Among
Candida
-colonized rats, antifungal treatment lowered the incidence of
A. baumannii
pneumonia. These findings could be due to modification of the host immune response and/or expression of
A. baumannii
virulence genes by
Candida
spp.
Displacement of Pathogens by an Engineered Bacterium Is a Multifactorial Process That Depends on Attachment Competition and Interspecific Antagonism
Authors: Al-Saedi Fitua , Stones Daniel Henry , Vaz Diana Pereira , Krachler Anne Marie
Published: March 2016

Pathogen attachment to host cells is a key process during infection, and inhibition of pathogen adhesion is a promising approach to the prevention of infectious disease. We have previously shown that multivalent adhesion molecules (MAMs) are abundant in both pathogenic and commensal bacterial species, mediate early attachment to host cells, and can contribute to virulence. Here, we investigated the efficacy of an engineered bacterium expressing a commensal MAM on its surface in preventing pathogen attachment and pathogen-mediated cytotoxicity in a tissue culture infection model. We were able to dissect the individual contributions of adhesion and interspecific antagonism on the overall outcome of infection for a range of different pathogens by comparison with the results obtained with a fully synthetic adhesion inhibitor. We found that the potential of the engineered bacterium to outcompete the pathogen is not always solely dependent on its ability to hinder host attachment but, depending on the pathogenic species, may also include elements of interspecific antagonism, such as competition for nutrients and its ability to cause a loss of fitness due to production of antimicrobial factors.
The Inhibitory Site of a Diguanylate Cyclase Is a Necessary Element for Interaction and Signaling with an Effector Protein
Authors: Dahlstrom Kurt M. , Giglio Krista M. , Sondermann Holger , O'Toole George A.
Published: March 2016

Many bacteria contain large cyclic diguanylate (c-di-GMP) signaling networks made of diguanylate cyclases (DGCs) and phosphodiesterases that can direct cellular activities sensitive to c-di-GMP levels. While DGCs synthesize c-di-GMP, many DGCs also contain an autoinhibitory site (I-site) that binds c-di-GMP to halt excess production of this small molecule, thus controlling the amount of c-di-GMP available to bind to target proteins in the cell. Many DGCs studied to date have also been found to signal for a specific c-di-GMP-related process, and although recent studies have suggested that physical interaction between DGCs and target proteins may provide this signaling fidelity, the importance of the I-site has not yet been incorporated into this model. Our results from
Pseudomonas fluorescens
indicate that mutation of residues at the I-site of a DGC disrupts the interaction with its target receptor. By creating various substitutions to a DGC's I-site, we show that signaling between a DGC (GcbC) and its target protein (LapD) is a combined function of the I-site-dependent protein-protein interaction and the level of c-di-GMP production. The dual role of the I-site in modulating DGC activity as well as participating in protein-protein interactions suggests caution in interpreting the function of the I-site as only a means to negatively regulate a cyclase. These results implicate the I-site as an important positive and negative regulatory element of DGCs that may contribute to signaling specificity.

IMPORTANCE
Some bacteria contain several dozen diguanylate cyclases (DGCs), nearly all of which signal to specific receptors using the same small molecule, c-di-GMP. Signaling specificity in these networks may be partially driven by physical interactions between DGCs and their receptors, in addition to the autoinhibitory site of DGCs preventing the overproduction of c-di-GMP. In this study, we show that disruption of the autoinhibitory site of a DGC in
Pseudomonas fluorescens
can result in the loss of interactions with its target receptor and reduced biofilm formation, despite increased production of c-di-GMP. Our findings implicate the autoinhibitory site as both an important feature for signaling specificity through the regulation of c-di-GMP production and a necessary element for the physical interaction between a diguanylate cyclase and its receptor.
Allosteric Activation of Escherichia coli Glucosamine-6-Phosphate Deaminase (NagB)
In Vivo
Justified by Intracellular Amino Sugar Metabolite Concentrations
Authors: Álvarez-Añorve Laura I. , Gaugué Isabelle , Link Hannes , Marcos-Viquez Jorge , Díaz-Jiménez Dana M. , Zonszein Sergio , Bustos-Jaimes Ismael , Schmitz-Afonso Isabelle , Calcagno Mario L. , Plumbridge Jacqueline
Published: March 2016

We have investigated the impact of growth on glucosamine (GlcN) and
N
-acetylglucosamine (GlcNAc) on cellular metabolism by quantifying glycolytic metabolites in
Escherichia coli
. Growth on GlcNAc increased intracellular pools of both GlcNAc6P and GlcN6P 10- to 20-fold compared to growth on glucose. Growth on GlcN produced a 100-fold increase in GlcN6P but only a slight increase in GlcNAc6P. Changes to the amounts of downstream glycolytic intermediates were minor compared to growth on glucose. The enzyme glucosamine-6P deaminase (NagB) is required for growth on both GlcN and GlcNAc. It is an allosteric enzyme in
E. coli
, displaying sigmoid kinetics with respect to its substrate, GlcN6P, and is allosterically activated by GlcNAc6P. The high concentration of GlcN6P, accompanied by the small increase in GlcNAc6P, drives
E. coli
NagB (NagB
Ec
) into its high activity state, as observed during growth on GlcN (L. I. Álvarez-Añorve, I. Bustos-Jaimes, M. L. Calcagno, and J. Plumbridge, J Bacteriol 191:6401–6407, 2009,
http://dx.doi.org/10.1128/JB.00633-09
). The slight increase in GlcNAc6P during growth on GlcN is insufficient to displace NagC, the GlcNAc6P-responsive repressor of the
nag
genes, from its binding sites, so there is only a small increase in
nagB
expression. We replaced the gene for the allosteric NagB
Ec
enzyme with that of the nonallosteric,
B. subtilis
homologue, NagB
Bs
. We detected no effects on growth rates or competitive fitness on glucose or the amino sugars, nor did we detect any effect on the concentrations of central metabolites, thus demonstrating the robustness of amino sugar metabolism and leaving open the question of the role of allostery in the regulation of NagB.

IMPORTANCE
Chitin, the polymer of
N
-acetylglucosamine, is an abundant biomaterial, and both glucosamine and
N
-acetylglucosamine are valuable nutrients for bacteria. The amino sugars are components of numerous essential macromolecules, including bacterial peptidoglycan and mammalian glycosaminoglycans. Controlling the biosynthetic and degradative pathways of amino sugar metabolism is important in all organisms to avoid loss of nitrogen and energy via a futile cycle of synthesis and breakdown. The enzyme glucosamine-6P deaminase (NagB) is central to this control, and
N
-acetylglucosamine-6P is the key signaling molecule regulating amino sugar utilization in
Escherichia coli
. Here, we investigate how the metabolic status of the bacteria impacts on the activity of NagB
Ec
and the
N
-acetylglucosamine-6P-sensitive transcriptional repressor, NagC.
Past and projected temporal trends in arthroscopic hip surgery in England between 2002 and 2013
Authors: Palmer A J R , Malak T T , Broomfield J , Holton J , Majkowski L , Thomas G E R , Taylor A , Andrade A J , Collins G , Watson K , Carr A J , Glyn-Jones S
Published: March 2016

Introduction

Hip arthroscopy is increasingly adopted for the treatment of intra-articular and extra-articular pathologies. Studies from USA demonstrate a 365% increase in the number of procedures performed between 2004 and 2009 and 250% increase between 2007 and 2011. There is limited evidence of long-term efficacy for this procedure and hip arthroscopy is not universally funded across England. The aim of this study is to describe temporal trends in the adoption of hip arthroscopy in England between 2002 and 2013 and to forecast trends for the next 10 years.

Methods

A search of the Hospital Episodes Database was performed for all codes describing arthroscopic hip procedures with patient age, sex and area of residence.

Results

11 329 hip arthroscopies were performed in National Health Service hospitals in England between 2002 and 2013. The number of hip arthroscopies performed increased by 727% (p<0.0001) during this period and is forecast to increase by 1388% in 2023. Females represent 60% of all patients undergoing hip arthroscopy (p<0.001). Median age category is 40–44 for females and 35–39 for males and average age decreased during the study period (p<0.0001). There is significant regional variation in procedure incidence. In the final year of this study the highest incidence was in the Southwest (8.63/100 000 population) and lowest in East Midlands (1.29/100 000 population).

Conclusions

The increase in number of hip arthroscopies performed in England reflects trends in USA and continued increases are forecast. Evidence from robust clinical trials is required to justify the increasing number of procedures performed and regional variation suggests potential inequality in the provision of this intervention.
Association of retirement age with mortality: a population-based longitudinal study among older adults in the USA
Authors: Wu Chenkai , Odden Michelle C , Fisher Gwenith G , Stawski Robert S
Published: March 2016

Background

Retirement is an important transitional process in later life. Despite a large body of research examining the impacts of health on retirement, questions still remain regarding the association of retirement age with survival. We aimed to examine the association between retirement age and mortality among healthy and unhealthy retirees and to investigate whether sociodemographic factors modified this association.

Methods

On the basis of the Health and Retirement Study, 2956 participants who were working at baseline (1992) and completely retired during the follow-up period from 1992 to 2010 were included. Healthy retirees (n=1934) were defined as individuals who self-reported health was not an important reason to retire. The association of retirement age with all-cause mortality was analysed using the Cox model. Sociodemographic effect modifiers of the relation were examined.

Results

Over the study period, 234 healthy and 262 unhealthy retirees died. Among healthy retirees, a 1-year older age at retirement was associated with an 11% lower risk of all-cause mortality (95% CI 8% to 15%), independent of a wide range of sociodemographic, lifestyle and health confounders. Similarly, unhealthy retirees (n=1022) had a lower all-cause mortality risk when retiring later (HR 0.91, 95% CI 0.88 to 0.94). None of the sociodemographic factors were found to modify the association of retirement age with all-cause mortality.

Conclusions

Early retirement may be a risk factor for mortality and prolonged working life may provide survival benefits among US adults.
The role of reactive oxygen species and antioxidants during precooling stages of axis cryopreservation in recalcitrantTrichilia dregeana
Authors: Naidoo Cassandra , Berjak Patricia , Pammenter Norman W. , Varghese Boby
Published: March 2016

Cryopreservation is currently the only feasible method for long-term conservation of non-orthodox germplasm. Previous attempts to cryopreserve embryonic axes of Trichilia dregeana Sond. indicated that the inability to produce shoots, suggestedly associated with a wound-induced burst of reactive oxygen species (ROS) accompanied by declining antioxidant potential, consistently accompanied procedures necessary for cryopreservation. This study involved the provision of cathodic protection, both in the aqueous phase (electrolysis of a solution containing dilute electrolytes) and dry state (rapid drying of axes on a grid on which a static field is generated via the cathode of a power-pack) with the addition of other antioxidants, i.e., ascorbic acid and DMSO, to counteract uncontrolled ROS activity. The production of superoxide ([Formula: see text]), hydrogen peroxide (H2O2), and hydroxyl radical ([Formula: see text]) in conjunction with the corresponding total aqueous antioxidant activity and viability was quantitatively assessed after each stage of the cryoprocedure, with or without cathodic protection and (or) antioxidants. No shoot production occurred in the treatments without cathodic protection and (or) antioxidants. In contrast, 80% of axes produced seedlings after excision, 40% after cryoprotection, and 40% after flash (rapid) drying, when the treatments included a form of cathodic protection.
Sprucing up the mixedwoods: growth response of white spruce (Picea glauca) to partial cutting in the eastern Canadian boreal forest
Authors: Smith Jessica , Harvey Brian D. , Koubaa Ahmed , Brais Suzanne , Mazerolle Marc J.
Published: March 2016

Mixed-species stands present a number of opportunities for and challenges to forest managers. Boreal mixedwood stands in eastern Canada are often characterized by a dominant canopy of shade-intolerant aspen (Populus tremuloides Michx.) with more shade-tolerant conifers in the mid- to sub-canopy layers. Because the aspen and conifer components often attain optimal merchantable sizes at different moments in stand development, there is an interest in developing silvicultural practices that allow partial or total removal of aspen and favour accelerated growth of residual conifers. We tested four partial harvesting treatments in mixed aspen – white spruce (Picea glauca (Moench.) Voss) stands in which different proportions of aspen (0%, 50%, 65%, and 100% basal area) were removed. Ten years after treatments, 72 spruce stems representing dominant, co-dominant, and suppressed social classes were destructively sampled for stem analysis. Using linear mixed effect models, we analyzed growth as a function of treatment intensity, time since treatment, social status, pretreatment growth rate, and neighbourhood competition. Relative to control stands, radial and volume growth responses were detected only in the extreme treatment of 100% aspen removal. In relative terms, suppressed trees showed the greatest magnitude of cumulative growth increase. Compared with control trees, average annual radial and volume increments were, respectively, 23.5% and 7.1% higher for dominant trees, 67.7% and 24.1% higher for co-dominant trees, and 115.8% and 65.6% higher for suppressed trees over the 10 years after treatment. Growth response was proportional to pretreatment growth rate, and among neighbouring trees, only coniferous neighbours had a negative effect on white spruce growth. Our results suggest that in similar mixed-stand conditions, relatively heavy removal of overstory aspen accompanied by thinning of crowded conifers would result in greatest growth response of residual spruce stems.
Temporal variation in the prevalence and species richness of Campylobacter spp. in a prairie watershed impacted by urban and agricultural mixed inputs
Authors: Tambalo Dinah D. , Boa Tyler , Aryal Bijaya , Yost Christopher K.
Published: March 2016

Campylobacter spp. are a substantial cause of gastroenteritis worldwide. Human infection can result from ingestion of contaminated food or water from a variety of sources, including the consumption of fresh produce that is contaminated with the pathogen via the use of contaminated irrigation water. Using molecular methods, we investigated the occurrence of Campylobacter in the Qu’Appelle River watershed, an important source of irrigation water for vegetable producers in southern Saskatchewan, Canada. Water samples were collected from 7 sampling sites from April to September 2009 (145 samples), and from 5 sampling sites from May to October 2013 (116 samples). Campylobacter was detected in 57% and 16% of the samples collected in 2009 and 2013, respectively. Campylobacter detection was highest in May and June for both sampling years. In 2009, the predominant species were Campylobacter lari and Campylobacter jejuni, with prevalences of 84% and 41%, respectively. Other Campylobacter spp. were detected less frequently. Only C. lari was detected in 2013. The results in 2009 demonstrate the species richness of Campylobacter in water sources within the watershed. The occurrence of Campylobacter in the study area also underscores the importance of monitoring irrigation water used to irrigate fresh produce from a public health prospective.
Research on a Dynamic Master-Slave Cournot Triopoly Game Model with Bounded Rational Rule and Its Control
Authors: Tu Hongliang , Wang Xinyu
Published: March 2016

The oligopoly market is modelled by a new dynamic master-slave Cournot triopoly game model with bounded rational rule. The local stabile conditions and the stable region are got by the dynamical systems bifurcation theory. The dynamics characteristics of the system with the changes of the adjustment speed parameters are analyzed by means of bifurcation diagram, largest Lyapunov exponents, phase portrait, and sensitive dependence on initial conditions. Furthermore, the parameters adjustment method is used to control the complex dynamical behaviors of the systems. The derived results have some important theoretical and practical meanings for the oligopoly market.
Improved Biocompatibility of Novel Biodegradable Scaffold Composed of Poly-L-lactic Acid and Amorphous Calcium Phosphate Nanoparticles in Porcine Coronary Artery
Authors: Gu Dongsheng , Feng Gaoke , Kang Guanyang , Zheng Xiaoxin , Bi Yuying , Wang Shihang , Fan Jingyao , Xia Jinxi , Wang Zhimin , Huo Zhicheng , Wang Qun , Wu Tim , Jiang Xuejun , Gu Weiwang , Xiao Jianmin
Published: March 2016

Using poly-L-lactic acid for implantable biodegradable scaffold has potential biocompatibility issue due to its acidic degradation byproducts. We have previously reported that the addition of amorphous calcium phosphate improved poly-L-lactic acid coating biocompatibility. In the present study, poly-L-lactic acid and poly-L-lactic acid/amorphous calcium phosphate scaffolds were implanted in pig coronary arteries for 28 days. At the follow-up angiographic evaluation, no case of stent thrombosis was observed, and the arteries that were stented with the copolymer scaffold had significantly less inflammation and nuclear factor-κB expression and a greater degree of reendothelialization. The serum levels of vascular endothelial growth factor and nitric oxide, as well the expression of endothelial nitric oxide synthase and platelet-endothelial cell adhesion molecule-1, were also significantly higher. In conclusion, the addition of amorphous calcium phosphate to biodegradable poly-L-lactic acid scaffold minimizes the inflammatory response, promotes the growth of endothelial cells, and accelerates the reendothelialization of the stented coronary arteries.
Modules for Pipelined Mixed Radix FFT Processors
Authors: Sergiyenko Anatolij , Serhienko Anastasia
Published: March 2016

A set of soft IP cores for the Winogradr-point fast Fourier transform (FFT) is considered. The cores are designed by the method of spatial SDF mapping into the hardware, which provides the minimized hardware volume at the cost of slowdown of the algorithm byrtimes. Their clock frequency is equal to the data sampling frequency. The cores are intended for the high-speed pipelined FFT processors, which are implemented in FPGA.
Nonsuppressible Oral Dexamethasone Suppression Tests but Not Cushing Syndrome
Authors: Nair Abilash , Dhingra Atul , Gopi Anjana , Jyotsna Viveka P.
Published: March 2016

In spite of the presence of definitive diagnostic criteria to diagnose Cushing syndrome diagnosis may become challenging. We report a young female with mild clinical features of Cushing syndrome, who had nonsuppressible oral dexamethasone suppression tests; also she had a suspicious pituitary lesion. She underwent pituitary surgery and a pituitary microadenoma (non-ACTH staining) was removed. Now she had come to us with similar complaints to those before. Again she had nonsuppressible oral dexamethasone suppression tests. As the diurnal variation of serum and salivary cortisol was maintained and urinary free cortisol was normal, further evaluation with IV dexamethasone suppression test was performed which clearly ruled out Cushing syndrome. The patient was not on any medicines known to alter dexamethasone metabolism. Fat malabsorption was also ruled out using appropriate tests. The reason for this discrepancy is thought to be altered (increased) metabolism of dexamethasone in this patient as it is widely variable in the general population.
Effects of Zoledronate on Mortality and Morbidity after Surgical Treatment of Hip Fractures
Authors: Cengiz Ömer , Polat Gökhan , Karademir Gökhan , Tunç Oytun Derya , Erdil Mehmet , Tuncay İbrahim , Şen Cengiz
Published: March 2016

We aimed to evaluate the effects of intertrochanteric femoral fractures on mortality, morbidity, and cost of zoledronate treatment in elderly patients treated by osteosynthesis. Based on Evans classification, 114 patients with unstable intertrochanteric femoral fractures were treated with osteosynthesis. After the surgical treatment of intertrochanteric fractures, the treatment group (M/F, 24/32; mean age, 76.7 ± SD years) received zoledronate infusion, and the control group (M/F, 20/38; mean age, 80.2 ± SD years) received placebo. Postoperative control visits were performed at 6-week, 3-month, 6-month, and 12-month time points. Functional level of patients was evaluated by the modified Harris hip score and Merle d’Aubigné hip score. By 12 months, the mean HHS in treatment and control groups was 81.93 and 72.9, respectively. For time of death of the patients, mortality was found to be 57.1% (16/28) on the first 3 months and 92.9% (26/28) on the first six months. The mortality rate in the treatment and control groups was 14.3% (8/56) and 34.5% (20/58), respectively. The use of zoledronic acid after surgical treatment of intertrochanteric femoral fractures in osteoporotic elderly patients is a safe treatment modality which helps to reduce mortality, improves functional outcomes, and has less side effects with single dose use per year.
MEG Connectivity and Power Detections with Minimum Norm Estimates Require Different Regularization Parameters
Authors: Hincapié Ana-Sofía , Kujala Jan , Mattout Jérémie , Daligault Sebastien , Delpuech Claude , Mery Domingo , Cosmelli Diego , Jerbi Karim
Published: March 2016

Minimum Norm Estimation (MNE) is an inverse solution method widely used to reconstruct the source time series that underlie magnetoencephalography (MEG) data. MNE addresses the ill-posed nature of MEG source estimation through regularization (e.g., Tikhonov regularization). Selecting the best regularization parameter is a critical step. Generally, once set, it is common practice to keep the same coefficient throughout a study. However, it is yet to be known whether the optimal lambda for spectral power analysis of MEG source data coincides with the optimal regularization for source-level oscillatory coupling analysis. We addressed this question via extensive Monte-Carlo simulations of MEG data, where we generated 21,600 configurations of pairs of coupled sources with varying sizes, signal-to-noise ratio (SNR), and coupling strengths. Then, we searched for the Tikhonov regularization coefficients (lambda) that maximize detection performance for (a) power and (b) coherence. For coherence, the optimal lambda was two orders of magnitude smaller than the best lambda for power. Moreover, we found that the spatial extent of the interacting sources and SNR, but not the extent of coupling, were the main parameters affecting the best choice for lambda. Our findings suggest using less regularization when measuring oscillatory coupling compared to power estimation.
Paradoxical Reaction to Alprazolam in an Elderly Woman with a History of Anxiety, Mood Disorders, and Hypothyroidism
Authors: Kirkpatrick Daniel , Smith Tyler , Kerfeld Mitchell , Ramsdell Taylor , Sadiq Hasnain , Sharma Arun
Published: March 2016

With less than 1% of patients who use benzodiazepines being affected, paradoxical responses to benzodiazepines are rare. In this case report, we outline the course of an 80-year-old female who developed a paradoxical response to benzodiazepines. Significant medical and psychiatric history includes anxiety, mood disorder, hypothyroidism, bilateral mastectomy, goiter removal, and triple bypass. The patient presented with mental status changes, anxiety, motor restlessness, and paranoia. Over time, a temporal relationship between the severity of the patient’s motor agitation and intake of alprazolam was observed. As doses of alprazolam were decreased, her motor agitation became less severe. In addition to motor agitation, the patient also demonstrated increased aggressiveness, a subjective feeling of restlessness, and increased talkativeness. As her dose of alprazolam decreased, many of the patient’s symptoms were observed to decrease. This case report also discusses theories regarding the pathophysiology of paradoxical reactions to benzodiazepines, known risk factors, and appropriate treatment.
Influence of Membrane Materials and Operational Modes on the Performance of Ultrafiltration Modules for Drinking Water Treatment
Authors: Fan Gongduan , Su Zhaoyue , Lin Rujing , Lin Xiuyong , Xu Renxin , Chen Wei
Published: March 2016

Polyethersulfone (PES), polyvinylidene fluoride (PVDF), and polyacrylonitrile (PAN) were prepared to purify micropolluted source water via a pilot-plant test. Integrative devices of in-line coagulation/ultrafiltration (UF) were proposed. Then the treatment performance, operation stability, clean methods, and fresh water recovery rate were assessed. The results showed that the membrane materials and operational modes did not result in significant difference of the removal efficiency of turbidity,CODMn, and NH4-N. The uniform distribution porosity, better hydrophilicity, and higher thermal stability of the PES membrane made its specific flux (SF) more than double those of two other membranes; in addition, the transmembrane pressure (TMP) of PES membrane appeared to be the least influenced by temperature change. The hydrophilicity of UF membrane was not a conclusive factor with the critical flux. The inside-out module with higher fouling load presented higher decay rate of SF under fixed flux operation compared with outside-in modules in single filtration duration. The way of gas washing of outside-in modules as a supplement resulted in recovery improvement. The acid-base staggered method of inside-out module to carry out chemical enhanced backwash (CEB) can effectively intensify the effects of backwashing by water.
Amtolmetin: A Reappraisal of NSAID with Gastroprotection
Authors: Garg Amit , Shoeb Ahsan , Moodahadu Latha Subramanya , Sharma Akhilesh , Gandhi Arul , Akku Shyam
Published: March 2016

Aim. To assess the gastrosparing effect of amtolmetin guacyl (AMG) against other nonsteroidal anti-inflammatory drugs (NSAIDs) in patients with osteo-/rheumatoid arthritis. Methods. A literature search was done in the electronic databases (PubMed, Google Scholar, Embase, and Scopus) with key words “amtolmetin guacyl”, “amtolmetin”, and “arthritis”; filters were applied to obtain publications between 01-Jan-1985 and 01-Oct-2015, which were “clinical trials” in osteo-/rheumatoid arthritis patients and in “English language.” Studies were assessed using the Jadad criteria and trials with score ≥ 3 were included in the analysis to compare the safety and efficacy of AMG against other NSAIDs. Results. Search yielded 19 publications of which 3 were included for analysis. Baseline characteristics of patients were comparable between the AMG group and other NSAIDs (diclofenac, celecoxib, and piroxicam) groups in all trials. Efficacy of AMG was similar to the other NSAIDs compared in the trials. The number of adverse events (AEs) reported was similar between both the groups; however, severe AEs reported were significantly lower in the AMG group. Of note was the significant lower number of duodenal ulcers after treatment in the AMG group. Conclusions. AMG has efficacy similar to other NSAIDs and a safer gastrointestinal AE profile when compared to the other NSAIDs.
Incidence of Type 1 Diabetes among Children and Adolescents in Italy between 2009 and 2013: The Role of a Regional Childhood Diabetes Registry
Authors: Fortunato F. , Cappelli M. G. , Vece M. M. , Caputi G. , Delvecchio M. , Prato R. , Martinelli D. , Registry Workgroup Apulian Childhood-Onset Diabetes
Published: March 2016

Background.Surveillance represents a key strategy to control type 1 diabetes mellitus (T1DM). In Italy, national data are missing. This study aimed at evaluating the incidence of T1DM in subjects <18 year olds in Apulia (a large southeastern region, about 4,000,000 inhabitants) and assessing the sensitivity of the regional Registry of Childhood-Onset Diabetes (RCOD) in the 2009–2013 period.Methods.We performed a retrospective study matching records from regional Hospital Discharge Registry (HDR), User Fee Exempt Registry (UFER), and Drugs Prescription Registry (DPR) and calculated T1DM incidence; completeness of each data source was also estimated. In order to assess the RCOD sensitivity we compared cases from the registry to those extracted from HDR-UFER-DPR matching.Results.During 2009–2013, a total of 917 cases (about 184/year) in at least one of the three sources and an annual incidence of 25.2 per 100,000 were recorded, lower in infant, increasing with age and peaked in 5- to 9-year-olds. The completeness of DPR was 78.7%, higher than that of UFER (64.3%) and of HDR (59.6%). The RCOD’s sensitivity was 39.05% (360/922; 95% CI: 34.01%–44.09%).Conclusions.Apulia appeared as a high-incidence region. A full, active involvement of physicians working in paediatric diabetes clinics would be desirable to improve the RCOD performance.
Obesity Related Coronary Microvascular Dysfunction: From Basic to Clinical Practice
Authors: Selthofer-Relatić K. , Bošnjak I. , Kibel A.
Published: March 2016

Obesity related coronary microvascular disease is a medical entity which is not yet fully elucidated. The pathophysiological basis of coronary microcirculatory dysfunction consists of a heterogeneous group of disorders with individual morphologic/functional/clinical presentation and prognosis. Coronary microcirculatory changes include mechanisms connected with vascular dysfunction, as well as extravascular and vasostructural changes in responses to neural, mechanical, and metabolic factors. Cardiometabolic changes that include obesity, dyslipidemia, diabetes mellitus type II, and hypertension are associated with atherosclerosis of epicardial coronary arteries and/or microvascular coronary dysfunction, with incompletely understood underlying mechanisms. In obesity, microvascular disease is mediated via adipokines/cytokines causing chronic, subclinical inflammation with (a) reduced NO-mediated dilatation, (b) changed endothelial- and smooth muscle-dependent vasoregulating mechanisms, (c) altered vasomotor control with increased sympathetic activity, and (d) obesity related hypertension with cardiomyocytes hypertrophy and impaired cardiac vascular adaptation to metabolic needs. From a clinical point of view it can present itself in acute or chronic form with different prognosis, as a practice problem for real-life diagnosis and treatment.
Firm Growth Function and Extended-Gibrat’s Property
Authors: Ishikawa Atushi , Fujimoto Shouji , Mizuno Takayuki , Watanabe Tsutomu
Published: March 2016

We analytically show that the logarithmic average sales of firms first follow power-law growth and subsequently follow exponential growth, if the growth-rate distributions of the sales obey the extended-Gibrat’s property and Gibrat’s law. Here, the extended-Gibrat’s property and Gibrat’s law are statistically observed in short-term data, which denote the dependence of the growth-rate distributions on the initial values. In the derivation, we analytically show that the parameter of the extended-Gibrat’s property is identical to the power-law growth exponent and that it also decides the parameter of the exponential growth. By employing around one million bits of exhaustive sales data of Japanese firms in the ORBIS database, we confirmed our analytic results.
Novel Adaptive Sliding Mode Control with Nonlinear Disturbance Observer for SMT Assembly Machine
Authors: Qian Rongrong , Luo Minzhou , Zhao Yao , Zhao Jianghai
Published: March 2016

This paper presents a novel adaptive sliding mode control based on nonlinear sliding surface with disturbance observer (ANSMC-DOB) for precision trajectory tracking control of a surface mount technology (SMT) assembly machine. A two-degree-of-freedom model with time-varying parameter uncertainties and disturbances is built to describe the first axial mode of the pick-place actuation axis of the machine. According to the principle of variable damping ratio coefficient which makes the system have a nonovershoot transient response and a short settling time in the second-order system, the nonlinear sliding surface is designed for the sliding mode control (SMC). Since the upper bound value of the disturbances is unknown, the adaptive gain estimation is applied to replace the switching gain in the SMC. In order to settle the problem of SMC unrobust to the mismatched parameter uncertainties and disturbances, the nonlinear disturbance observer is introduced to estimate the mismatched disturbances and form the novel controller of ANSMC-DOB. The stability of sliding surfaces and control laws are verified by the Lyapunov functions. The simulation research and comparative experiments are conducted to verify the improvement of positioning accuracy and robustness by the proposed ANSMC-DOB in the SMT assembly machine.
A Denoising Based Autoassociative Model for Robust Sensor Monitoring in Nuclear Power Plants
Authors: Shaheryar Ahmad , Yin Xu-Cheng , Hao Hong-Wei , Ali Hazrat , Iqbal Khalid
Published: March 2016

Sensors health monitoring is essentially important for reliable functioning of safety-critical chemical and nuclear power plants. Autoassociative neural network (AANN) based empirical sensor models have widely been reported for sensor calibration monitoring. However, such ill-posed data driven models may result in poor generalization and robustness. To address above-mentioned issues, several regularization heuristics such as training with jitter, weight decay, and cross-validation are suggested in literature. Apart from these regularization heuristics, traditional error gradient based supervised learning algorithms for multilayered AANN models are highly susceptible of being trapped in local optimum. In order to address poor regularization and robust learning issues, here, we propose a denoised autoassociative sensor model (DAASM) based on deep learning framework. Proposed DAASM model comprises multiple hidden layers which are pretrained greedily in an unsupervised fashion under denoising autoencoder architecture. In order to improve robustness, dropout heuristic and domain specific data corruption processes are exercised during unsupervised pretraining phase. The proposed sensor model is trained and tested on sensor data from a PWR type nuclear power plant. Accuracy, autosensitivity, spillover, and sequential probability ratio test (SPRT) based fault detectability metrics are used for performance assessment and comparison with extensively reported five-layer AANN model by Kramer.
Novel Small-Molecule CX3CR1 Antagonist Impairs Metastatic Seeding and Colonization of Breast Cancer Cells
Authors: Shen Fei , Zhang Yun , Jernigan Danielle L. , Feng Xin , Yan Jie , Garcia Fernando U. , Meucci Olimpia , Salvino Joseph M. , Fatatis Alessandro
Published: March 2016

Recent evidence indicates that cancer cells, even in the absence of a primary tumor, recirculate from established secondary lesions to further seed and colonize skeleton and soft tissues, thus expanding metastatic dissemination and precipitating the clinical progression to terminal disease. Recently, we reported that breast cancer cells utilize the chemokine receptor CX3CR1 to exit the blood circulation and lodge to the skeleton of experimental animals. Now, we show that CX3CR1 is overexpressed in human breast tumors and skeletal metastases. To assess the clinical potential of targeting CX3CR1 in breast cancer, a functional role of CX3CR1 in metastatic seeding and progression was first validated using a neutralizing antibody for this receptor and transcriptional suppression by CRISPR interference (CRISPRi). Successively, we synthesized and characterized JMS-17-2, a potent and selective small-molecule antagonist of CX3CR1, which was used in preclinical animal models of seeding and established metastasis. Importantly, counteracting CX3CR1 activation impairs the lodging of circulating tumor cells to the skeleton and soft-tissue organs and also negatively affects further growth of established metastases. Furthermore, nine genes were identified that were similarly altered by JMS-17-2 and CRISPRi and could sustain CX3CR1 prometastatic activity. In conclusion, these data support the drug development of CX3CR1 antagonists, and promoting their clinical use will provide novel and effective tools to prevent or contain the progression of metastatic disease in breast cancer patients.

Implications: This work conclusively validates the instrumental role of CX3CR1 in the seeding of circulating cancer cells and is expected to pave the way for pairing novel inhibitors of this receptor with current standards of care for the treatment of breast cancer patients. Mol Cancer Res; 14(6); 518–27. ©2016 AACR.
Complementary Medicine for Cancer Patients in General Practice: Qualitative Interviews with German General Practitioners
Authors: Dahlhaus Anne , Siebenhofer Andrea , Guethlin Corina
Published: March 2016

Background: The aim of this study was to investigate how general practitioners react when their cancer patients show interest in complementary medicine, and how their reaction is related to their knowledge in the field. Methods: We conducted semi-structured interviews with 10 German general practitioners. Interviewees came from 5 different federal states and varied in terms of urban/rural setting, single/joint practice, additional certifications, gender and length of professional experience. Interviews were electronically recorded, transcribed and then analysed using qualitative content analysis according to Mayring. Results: General practitioners feel largely responsible for providing information on complementary medicine to their cancer patients. However, uncertainty and a lack of knowledge concerning CAM lead mainly to reactive responses to patients' needs, and the general practitioners base their recommendations on personal experiences and attitudes. They wish to support their cancer patients and thus, in order to keep their patients' hopes up and maintain a trusting relationship, sometimes support complementary medicine, regardless of their own convictions. Conclusion: Although general practitioners see themselves as an important source of information on complementary medicine for their cancer patients, they also speak of their uncertainties and lack of knowledge. General practitioners would profit from training in complementary medicine enabling them to discuss this topic with their cancer patients in a proactive, open and honest manner.
Problematik der Kostenerstattung für Akupunkturbehandlungen auf Kassenschein
Authors: Trinczek Klaus
Published: March 2016

Akupunktur ist in Deutschland seit 2007 eine Leistung der gesetzlichen Krankenversicherung. Allerding ist diese auf 2 Diagnosen eingegrenzt («chronische Schmerzen der Lendenwirbelsäule» und «chronische Schmerzen der Kniegelenke durch Gonarthrose») und mit semistandardisierten Vorgaben zur Durchführung von Akupunkturbehandlungen verbunden, die teilweise nicht den Weiterbildungsinhalten der Akupunkturausbildung entsprechen. Akupunktur wird vor allem in orthopädischen Praxen angewandt. Hohe Anforderungen an die Qualifizierung und Qualitätssicherung sowie die Schwierigkeit, die Behandlungen wirtschaftlich durchführen zu können, schmälern die Attraktivität, Akupunktur in der gesetzlichen Krankenversicherung zu verankern.