bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of drug price reduction and prescribing restrictions on expenditures and utilisation of antihypertensive drugs in Korea
Authors: Yoo Ki-Bong , Lee Sang Gyu , Park Sohee , Kim Tae Hyun , Ahn Jeonghoon , Cho Mee-Hyun , Park Eun-Cheol
Published: July 2015

Objectives

To evaluate the quantitative effects of the drug price reduction on pharmaceutical expenditures and the new guidelines to restrict prescribing on drug utilisation for antihypertensive drugs.

Design

We used an interrupted time series design with the National patient sample data of Health Insurance Review and Assessment Service in South Korea.

Methods

54 295 participants who were with primary hypertension from the National patient sample data of Health Insurance Review and Assessment Service were included. The study period was from March 2011 to December 2013. The dependent variables were antihypertensive drug costs, antihypertensive drug cost per prescribing day, daily drug utilisation, average number of drugs per month, percentage of original drugs per prescription, drug overutilisation and prohibited combinations. Segmented regression analysis was used.

Results

The drug price reduction reduced expenditure (US$−1.51, −10.2%), and the new guidelines reduced expenditures even more (US$−2.13; −16.2%). These policies saved US$4.22 (28%) of antihypertensive drug costs per patient in December 2013 compared to March 2012. Drug price reduction policy was introduced in April 2012. We established the policy effect by comparing it before (March 2012) with after(21 months later-December 2012). The effects of the guidelines decreased expenditures, daily drug utilisation and the average number of drugs per month more than did the drug price reduction.

Conclusions

Both policies saved money. The guidelines were more effective over time and had fewer side effects such as increasing daily drug utilisation and number of drugs than the effects of drug price reduction.
Effectiveness of community-based peer-led diabetes self-management programmes (COMP-DSMP) for improving clinical outcomes and quality of life of adults with diabetes in primary care settings in low and middle-income countries (LMIC): a systematic review and meta-analysis
Authors: Werfalli Mahmoud , Raubenheimer Peter , Engel Mark , Peer Nasheeta , Kalula Sebastiana , Kengne Andre P , Levitt Naomi S
Published: July 2015

Introduction

Globally, an estimated 380 million people live with diabetes today—80% in low-income and middle-income countries. The Middle East, Western Pacific, Sub-Saharan Africa and South-East Asia remain the most affected regions where economic development has transformed lifestyles, people live longer and there is an increase in the adult population. Although peer support has been used in different conditions with varied results, yet there is limited evidence to date supporting its effectiveness, particularly for individuals with diabetes. In this review, we will focus on community-based peer-led diabetes self-management programmes (COMP-DSMP) and examine the implementation strategies and diabetes-related health outcomes associated with them in LMIC primary healthcare settings.

Methods and analysis

In accordance with reporting equity-focused systematic reviews PRISMA-P (preferred reporting items for systematic review and meta-analysis protocols 2015 checklist) guidelines, a systematic review with meta-analysis of randomised controlled trials (RCTs), non-randomised controlled trials, quasi-randomised controlled trials (CCTs) that involve contact with an individual or group of peers (paid or voluntary). Electronic searches will be performed in The Cochrane Library, MEDLINE, PubMed, SCOUPS, CINAHL and PsycINFO Database for the period January up to July 2000 along with manual searches in the reference lists of relevant papers. The analyses will be performed based on baseline data from RCTs, CCTs and preintervention and postintervention means or proportions will be reported for both intervention and control groups, and the absolute change from baseline will be calculated, together with 95% CIs. For dichotomous outcomes, the relative risk of the outcome will be presented compared to the control group. The risk difference will be calculated, which is the absolute difference in the proportions in each treatment group.

Ethics and dissemination

Ethics is not required for this study, given that this is a protocol for a systematic review, which utilises published data. The findings of this study will be widely disseminated through peer-reviewed publications and conference presentations.

Trial registration number

PROSPERO (2014:CRD42014007531).
Development and validation of a screening tool to predict the risk of chronic low back pain in patients presenting with acute low back pain: a study protocol
Authors: Traeger Adrian , Henschke Nicholas , Hübscher Markus , Williams Christopher M , Kamper Steven J , Maher Chris G , Moseley G Lorimer , McAuley James H
Published: July 2015

Introduction

Around 40% of people presenting to primary care with an episode of acute low back pain develop chronic low back pain. In order to reduce the risk of developing chronic low back pain, effective secondary prevention strategies are needed. Early identification of at-risk patients allows clinicians to make informed decisions based on prognostic profile, and researchers to select appropriate participants for secondary prevention trials. The aim of this study is to develop and validate a prognostic screening tool that identifies patients with acute low back pain in primary care who are at risk of developing chronic low back pain. This paper describes the methods and analysis plan for the development and validation of the tool.

Methods/analysis

The prognostic screening tool will be developed using methods recommended by the Prognosis Research Strategy (PROGRESS) Group and reported using the Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis (TRIPOD) statement. In the development stage, we will use data from 1248 patients recruited for a prospective cohort study of acute low back pain in primary care. We will construct 3 logistic regression models to predict chronic low back pain according to 3 definitions: any pain, high pain and disability at 3 months. In the validation stage, we will use data from a separate sample of 1643 patients with acute low back pain to assess the performance of each prognostic model. We will produce validation plots showing Nagelkerke R2and Brier score (overall performance), area under the curve statistic (discrimination) and the calibration slope and intercept (calibration).

Ethics and dissemination

Ethical approval from the University of Sydney Ethics Committee was obtained for both of the original studies that we plan to analyse using the methods outlined in this protocol (Henschkeet al, ref 11-2002/3/3144; Williamset al, ref 11638).
Inspecting pet shops
Authors: Jepson Lance
Published: July 2015

Anyone wishing to sell vertebrate animals as pets in the UK is obliged to apply for a license from their local authority under the Pet Animals Act (PAA) 1951. Drafted as ‘An Act to regulate the sale of pet animals’, this is a relatively small piece of legislation that is over 60 years old and stands out as something of an anomaly against other, more recent legislation. In short, pet shop inspections can suffer from a lack of joined‐up legislation. This article looks at some of the background issues of pet shop licensing and gives practical advice on how to conduct such an inspection.
Educational inequalities in obesity and gross domestic product: evidence from 70 countries
Authors: Kinge Jonas Minet , Strand Bjørn Heine , Vollset Stein Emil , Skirbekk Vegard
Published: July 2015

Background

We test the reversal hypothesis, which suggests that the relationship between obesity and education depends on the economic development in the country; in poor countries, obesity is more prevalent in the higher educated groups, while in rich countries the association is reversed—higher prevalence in the lower educated.

Methods

We assembled a data set on obesity and education including 412 921 individuals from 70 countries in the period 2002–2013. Gross domestic product (GDP) per capita was used as a measure of economic development. We assessed the association between obesity and GDP by education using a two-stage mixed effects model. Country-specific educational inequalities in obesity were investigated using regression-based inequality indices.

Results

The reversal hypothesis was supported by our results in men and women. Obesity was positively associated with country GDP only among individuals with lower levels of education, while this association was absent or reduced in those with higher levels of education. This pattern was more pronounced in women than in men. Furthermore, educational inequalities in obesity were reversed with GDP; in low-income countries, obesity was more prevalent in individuals with higher education, in medium-income and high-income countries, obesity shifts to be more prevalent among those with lower levels of education.

Conclusions

Obesity and economic development were positively associated. Our findings suggest that education might mitigate this effect. Global and national action aimed at the obesity epidemic should take this into account.
Ten‐minute chat
Authors: Saunders Richard
Published: July 2015

Richard Saunders works predominantly with zoo and exotic pet animal species and is based at Bristol Zoological Gardens. He also teaches at the University of Bristol and consults at a local small animal referral centre.
The signature of positive braids is linearly bounded by their first Betti number
Authors: Feller Peter
Published: July 2015

We provide linear lower bounds for the signature of positive braids in terms of the three-genus of their braid closure. This yields linear bounds for the topological slice genus of knots that arise as closures of positive braids.
Quantum transport with long-range steps on Watts–Strogatz networks
Authors: Wang Yan , Xu Xin-Jian
Published: July 2015

We study transport dynamics of quantum systems with long-range steps on the Watts–Strogatz network (WSN) which is generated by rewiring links of the regular ring. First, we probe physical systems modeled by the discrete nonlinear schrödinger (DNLS) equation. Using the localized initial condition, we compute the time-averaged occupation probability of the initial site, which is related to the nonlinearity, the long-range steps and rewiring links. Self-trapping transitions occur at large (small) nonlinear parameters for coupling [Formula: see text] (1), as long-range interactions are intensified. The structure disorder induced by random rewiring, however, has dual effects for [Formula: see text] and inhibits the self-trapping behavior for [Formula: see text]. Second, we investigate continuous-time quantum walks (CTQW) on the regular ring ruled by the discrete linear schrödinger (DLS) equation. It is found that only the presence of the long-range steps does not affect the efficiency of the coherent exciton transport, while only the allowance of random rewiring enhances the partial localization. If both factors are considered simultaneously, localization is greatly strengthened, and the transport becomes worse.
CCP interoperability and system stability
Authors: Feng Xiaobing , Hu Haibo
Published: July 2015

To control counterparty risk, financial regulations such as the Dodd–Frank Act are increasingly requiring standardized derivatives trades to be cleared by central counterparties (CCPs). It is anticipated that in the near term future, CCPs across the world will be linked through interoperability agreements that facilitate risk sharing but also serve as a conduit for transmitting shocks. This paper theoretically studies a networked network with CCPs that are linked through interoperability arrangements. The major finding is that the different configurations of networked network CCPs contribute to the different properties of the cascading failures.
The ellipsoidal nested sampling and the expression of the model uncertainty in measurements
Authors: Gervino Gianpiero , Mana Giovanni , Palmisano Carlo
Published: July 2015

In this paper, we consider the problems of identifying the most appropriate model for a given physical system and of assessing the model contribution to the measurement uncertainty. The above problems are studied in terms of Bayesian model selection and model averaging. As the evaluation of the “evidence” [Formula: see text], i.e., the integral of Likelihood × Prior over the space of the measurand and the parameters, becomes impracticable when this space has [Formula: see text] dimensions, it is necessary to consider an appropriate numerical strategy. Among the many algorithms for calculating [Formula: see text], we have investigated the ellipsoidal nested sampling, which is a technique based on three pillars: The study of the iso-likelihood contour lines of the integrand, a probabilistic estimate of the volume of the parameter space contained within the iso-likelihood contours and the random samplings from hyperellipsoids embedded in the integration variables. This paper lays out the essential ideas of this approach.
First principles investigation of the diffusion of interstitial Cu, Ag and Au in ZnTe
Authors: Chen Li An , Zhu Xing Feng , Chen Ling Fu
Published: July 2015

The diffusion is of great significance in many applications when the impurities are employed to tune the semiconductor's electrical or optical properties. It is necessary to understand how dopant defects diffuse in semiconductors. Using first-principles calculations, we consider interstitial diffusion mechanisms and calculate the migration barrier energies of interstitial Cu, Ag and Au atoms in II–VI compounds ZnTe. We find that the relative size of dopant and bulk atoms is an important factor which affects the diffusion behavior. The high symmetry Tc site, which is tetrahedrally coordinated by four cation atoms, is the global minimum energy location for Ag and Au interstitials. The size of Cu adatom is small, so Cu is more stable when it locates at the Ta site which is tetrahedrally coordinated by four anion atoms. But the global minimum energy location for Cu interstitials is M site which is of smaller space than Ta. Cu adatoms show an asymmetric curve of energy diffusion barrier with two energetically distinct extremum in the pathway. Ag diffuses along nearly straight line paths along [111] or equivalent directions. Diffusion for Cu or Au deviates from the straight line paths along 〈111〉 avoiding high symmetric sites.
Phase noise-induced double coherence resonances in a neuronal model
Authors: Jia Yanbing , Gu Huaguang
Published: July 2015

Phase noise-induced single coherence resonance (CR) has been reported in previous studies. It is reported here that double CRs can be induced in the FitzHugh–Nagumo (FHN) model by phase noise when the oscillation period of phase noise is much larger than the firing period of the FHN model. By analyzing peaks in the power spectrums for the fast voltage variable and the coefficient variations (CVs) of interspike interval (ISI) series, we find that double CRs corresponding to the frequency of phase noise and the firing frequency of the FHN model respectively appear at small and large noise intensities. This implies that there are double chances for the FHN model to take advantage of the benefits of phase noise. Possible causes of the single CR are also discussed.
Strategies to Maximize Burst Lengths in Rhythmic Anti-Phase Activity of Networks with Reciprocal Inhibition
Authors: Bose Amitabha , Rubin Jonathan E.
Published: July 2015

We consider repetitive activity patterns in which a pair of oscillators take turns becoming active, motivated by anti-phase bursting activity in neuronal networks. In our framework, when one unit is active, it inhibits the other, as occurs with inhibitory synaptic coupling of neurons; when the inhibition is strong enough, the inhibited unit is prevented from activating. We assume that the coupling resources available to each oscillator are constrained and allow each unit to select the amount of input that it provides to the other each time that it activates. In this setting, we investigate the strategies that each oscillator should utilize in order to maximize the number of spikes it can fire (or equivalently the amount of time it is active), corresponding to a burst of spikes in a neuron, before the other unit takes over. We derive a one-dimensional map whose fixed points correspond to periodic anti-phase bursting solutions. We introduce a novel numerical method to obtain the graph of this map and we extend the analysis to select solutions that achieve consistency between coupling resource use and recovery. Our analysis shows that corresponding to each fixed point of the map, there is actually an infinite number of related strategies that yield the same number of spikes per burst.
Comparison of Dynamical Behaviors Between Monofunctional and Bifunctional Two-Component Signaling Modules
Authors: Yang Xiyan , Wu Yahao , Yuan Zhanjiang
Published: July 2015

Two-component signaling modules exist extensively in bacteria and microbes. These modules can be, based on their distinct network structures, divided into two types: the monofunctional system (denoted by MFS) where the sensor kinase (SK) modulates only phosphorylation of the response regulator (RR), and the bifunctional system (denoted by BFS) where the SK catalyzes both phosphorylation and dephosphorylation of the RR. Here, we analyze dynamical behaviors of these two systems based on stability theory, focusing on differences between them. The analysis of the deterministic behavior indicates that there is no difference between the two modules, that is, each system has the unique stable steady state. However, there are significant differences in stochastic behavior between them. Specifically, if the mean phosphorylated SK level is kept the same for the two modules, then the variance and the Fano factor for the phosphorylated RR in the BFS are always no less than those in the MFS, indicating that bifunctionality always enhances fluctuations. The correlation between the phosphorylated SK and the phosphorylated RR in the BFS is always positive mainly due to competition between system components, but this correlation in the MFS may be positive, almost zero, or negative, depending on the ratio between two rate constants. Our overall analysis indicates that differences between dynamical behaviors of monofunctional and bifunctional signaling modules are mainly in the stochastic rather than deterministic aspect.
A Computational Method for Robust Bifurcation Analysis and Its Application to Biomolecular Systems
Authors: Inoue Masaki , Ikuta Hikaru , Adachi Shuichi , Imura Jun-Ichi , Aihara Kazuyuki
Published: July 2015

We consider a general uncertain nonlinear dynamical system defined in a certain model set, and reformulate a problem of robustness bifurcation analysis (RBA), which has been originally formulated in our previous work. As such, we develop an efficient computational method for the RBA, which can be used for quantitative evaluation of bifurcation robustness in uncertain dynamical systems. Specifically, we first linearize the uncertain system properly and then apply a feedback transformation technique to reduce the RBA problem to a linear robustness analysis one, which can be solved using μ-analysis, a common analysis technique in robust control theory. Finally, we provide robustness analysis of a gene regulatory network model where oscillatory behavior appears according to Hopf bifurcation. We give quantitative evaluation of the bifurcation robustness using the RBA method proposed here.
Bifurcation and Stability in a Delayed Predator–Prey Model with Mixed Functional Responses
Authors: Yafia R. , Aziz-Alaoui M. A. , Merdan H. , Tewa J. J.
Published: July 2015

The model analyzed in this paper is based on the model set forth by Aziz Alaoui et al. [Aziz Alaoui & Daher Okiye, 2003; Nindjin et al., 2006] with time delay, which describes the competition between the predator and prey. This model incorporates a modified version of the Leslie–Gower functional response as well as that of Beddington–DeAngelis. In this paper, we consider the model with one delay consisting of a unique nontrivial equilibrium E* and three others which are trivial. Their dynamics are studied in terms of local and global stabilities and of the description of Hopf bifurcation at E*. At the third trivial equilibrium, the existence of the Hopf bifurcation is proven as the delay (taken as a parameter of bifurcation) that crosses some critical values.
Broué's isotypy conjecture for the sporadic groups and their covers and automorphism groups
Authors: Sambale Benjamin
Published: July 2015

Let B be a p-block of a finite group G with abelian defect group D such that S ≤ G ≤ Aut (S), S′ = S and S/Z(S) is a sporadic simple group. We show that B is isotypic to its Brauer correspondent in N G(D) in the sense of Broué. This has been done by Rouquier for principal blocks and it remains to deal with the non-principal blocks.
Hadron freeze-out and Unruh radiation
Authors: Castorina Paolo , Iorio Alfredo , Satz Helmut
Published: July 2015

In this paper, we consider hadron production in high energy collisions as an Unruh radiation phenomenon. This mechanism describes the production pattern of newly formed hadrons and is directly applicable at vanishing baryon chemical potential, μ ≃ 0. It had already been found to correctly yield the hadronization temperature, [Formula: see text] in terms of the string tension σ. Here, we show that the Unruh mechanism also predicts hadronic freeze-out conditions, giving [Formula: see text] in terms of the entropy density s and [Formula: see text] for the average energy per hadron. These predictions provide a theoretical basis for previous phenomenological results and are also in accord with recent lattice studies.
Neutron stars and supernova explosions in the framework of Landau's theory
Authors: Zheng Hua , Sahagun Jaime , Bonasera Aldo
Published: July 2015

In this paper, a general formula of the symmetry energy for many-body interaction is proposed and the commonly used two-body interaction symmetry energy is recovered. Within Landau's theory (Lt), we generalize two equations of state (EoS) CCSδ3 and CCSδ5 to asymmetric nuclear matter. We assume that the density and density difference between protons and neutrons divided by their sum are order parameters. We use different EoS to study neutron stars by solving the TOV equations. We demonstrate that different EoS give different mass and radius relation for neutron stars even when they have exactly the same ground state (gs) properties (E/A, ρ0, K, S, L and K sym ). Furthermore, for one EoS we change K sym and fix all the other gs parameters. We find that for some K sym the EoS becomes unstable at high density even for neutron matter. This suggests that a neutron star (NS) can exist below and above the instability region but in different states: a quark gluon plasma (QGP) at high density and baryonic matter at low density. If the star's central density is in the instability region, then we associate these conditions to the occurrence of supernovae (SN).
Analysis of Acoustic-Structure Interaction Using a High-Order Doubly Asymptotic Approximation
Authors: Woo Heekyu , Shin Young S.
Published: July 2015

In this paper, a new third-order approximation model for an acoustic-structure interaction problem is introduced. The new approximation model is designed to be an accurate and a stable model for predicting the response of a submerged structure. The proposed model is obtained by combining two lower order approximation models instead of using an operator matching method. The stability of this model is checked by a modal analysis. Finally, the approximation model is coupled to the spherical shell structure, and its performance is checked by a shock analysis.
An All-Stage Truncated Multiple Change Point Model for Software Reliability Assessment
Authors: Inoue Shinji , Taniguchi Saki , Yamada Shigeru
Published: July 2015

We propose a software reliability growth modeling framework with multiple change point occurrence environment. Especially in our modeling framework, the probability distribution of the initial fault content follows a zero-truncated Poisson distribution. Therefore, our modeling approach in this paper can derive the proper mean time between software failures (MTBF), which is one of the important reliability assessment measures and is not able to derive in the usual nonhomogeneous Poisson process modeling, which is one of the well-known software reliability modeling approach. This paper also show numerical examples of application of our proposed multiple change point model to software reliability assessment by using actual fault counting data.
Public Participation in Environmental Impact Assessments Between Spain and Portugal
Authors: Vicente Fernando , Fidélis Teresa , Méndez Gonzalo
Published: July 2015

Since 2000, the Transboundary Environmental Impact Assessment (TEIA) process in the Iberian context has undergone significant development due to new circumstances that came into play at the bilateral and European levels: (i) the adoption of a collaborative TEIA Protocol between Spain and Portugal in 2008; and (ii) the increasing number of cross-border projects supported by European Union funds. Despite these developments, the impact of this bilateral regulation on public participation, the cornerstone of any Environmental Impact Assessment (EIA), has not yet been fully examined. Drawing from specific literature focusing on the involvement of the public as the basis of effective improvement of the TEIA, this paper critically analyses if the lates transboundary provision has encouraged public participation in this context. Although the analysis of the TEIA enforcement revealed a considerable increase in the number of consultations between the neighbouring states compared to the previous situation, public involvement has not increased. Based on these findings, this paper presents a set of recommendations to more effectively involve the public in transboundary consultations.
Effective kernel FCM: Finding appropriate structure in cancer database
Authors: Kannan S. R. , Devi R. , Ramathilagam S. , Hong T. P. , Ravikumar A.
Published: July 2015

Finding available subclasses in high-dimensional medical databases using clustering techniques is considered as very important one in medical field. Due to similar intensities between the datapoints in high-dimensionality cancer medical database clustering techniques have failed to cluster the available subclasses with less error. Therefore this paper presents suitable fuzzy-based clustering techniques to find available subclasses in high-dimensional prostate and breast cancer databases. In addition this paper presents prototype initialization algorithm to avoid random initialization of initial prototypes. In order to evaluate the performance of proposed clustering techniques experimental study has been performed on benchmark databases. Finally the proposed methods have been successfully implemented to find the subclasses of cancers in prostate and breast cancer databases. The clustering results of proposed methods have been validated by evaluating clustering accuracy.
The Strawberry Bank Lagerstätte reveals insights into Early Jurassic life
Authors: Williams Matt , Benton Michael J. , Ross Andrew
Published: July 2015

The Strawberry Bank Lagerstätte provides a rich insight into Early Jurassic marine vertebrate life, revealing exquisite anatomical detail of marine reptiles and large pachycormid fishes thanks to exceptional preservation, and especially the uncrushed, 3D nature of the fossils. The site documents a fauna of Early Jurassic nektonic marine animals (five species of fishes, one species of marine crocodilian, two species of ichthyosaurs, cephalopods and crustaceans), but also over 20 species of insects. Unlike other fossil sites of similar age, the 3D preservation at Strawberry Bank provides unique evidence on palatal and braincase structures in the fishes and reptiles. The age of the site is important, documenting a marine ecosystem during recovery from the end-Triassic mass extinction, but also exactly coincident with the height of the Toarcian Oceanic Anoxic Event, a further time of turmoil in evolution.
TAK1 is a key modulator of the profibrogenic phenotype of human ileal myofibroblasts in Crohn's disease
Authors: Grillo Alessia Rosaria , Scarpa Melania , D'Incà Renata , Brun Paola , Scarpa Marco , Porzionato Andrea , De Caro Raffaele , Martines Diego , Buda Andrea , Angriman Imerio , Palù Giorgio , Sturniolo Giacomo Carlo , Castagliuolo Ignazio
Published: July 2015

Transforming growth factor (TGF)-β-activated kinase 1 (TAK1) signaling can mediate inflammatory responses as well as tissue remodeling. Intestinal mucosal myofibroblast (IMF) activation drives gut fibrosis in Crohn's disease (CD); however, the molecular pathways involved are largely unknown. Thus we investigated the yet-unknown expression and function of TAK1 in human CD-associated fibrosis. Ileal surgical specimens, ileal biopsies, and IMF isolated from controls and CD patients were analyzed for TAK1 and its active phosphorylated form (pTAK1) by Western blotting, immunohistochemistry, and real-time quantitative PCR. TAK1 pharmacological inhibition and silencing were used to assess its role in collagen and inflammatory cytokine synthesis in IMF. TAK1 and pTAK1 levels increased in ileum specimens from CD patients compared with controls and correlated to tissue fibrosis. Similarly, TAK1 mRNA in ileal biopsies of CD patients correlated with fibrogenic marker expression but not inflammatory cytokines. CD-derived IMF showed higher TAK1 and pTAK1 expression associated with increased collagen1(α)1 mRNA levels compared with control IMF. TGF-β1 promoted pTAK1 nuclear translocation and collagen synthesis. TAK1 inhibition or silencing significantly reduced TGF-β1-stimulated collagen production and normalized the profibrogenic phenotype of CD-derived IMF. Taken together, these data suggest that TAK1 activation and nuclear translocation induce and maintain a fibrogenic phenotype in the IMF. Thus the TAK1 signaling pathway may represent a suitable target to design new, antifibrotic therapies.
Ultrastructural and immunohistochemical localization of plasma membrane Ca2+-ATPase 4 in Ca2+-transporting epithelia
Authors: Alexander R. Todd , Beggs Megan R. , Zamani Reza , Marcussen Niels , Frische Sebastian , Dimke Henrik
Published: July 2015

Plasma membrane Ca2+-ATPases (PMCAs) participate in epithelial Ca2+transport and intracellular Ca2+signaling. The Pmca4 isoform is enriched in distal nephron isolates and decreased in mice lacking the epithelial transient receptor potential vanilloid 5 Ca2+channel. We therefore hypothesized that Pmca4 plays a significant role in transcellular Ca2+flux and investigated the localization and regulation of Pmca4 in Ca2+-transporting epithelia. Using antibodies directed specifically against Pmca4, we found it expressed only in the smooth muscle layer of mouse and human intestines, whereas pan-specific Pmca antibodies detected Pmca1 in lateral membranes of enterocytes. In the kidney, Pmca4 showed broad localization to the distal nephron. In the mouse, expression was most abundant in segments coexpressing the epithelial ransient receptor potential vanilloid 5 Ca2+channel. Significant, albeit lower, expression was also evident in the region encompassing the cortical thick ascending limbs, macula densa, and early distal tubules as well as smooth muscle layers surrounding renal vessels. In the human kidney, a similar pattern of distribution was observed, with the highest PMCA4 expression in Na+-Cl−cotransporter-positive tubules. Electron microscopy demonstrated Pmca4 localization in distal nephron cells at both the basolateral membrane and intracellular perinuclear compartments but not submembranous vesicles, suggesting rapid trafficking to the plasma membrane is unlikely to occur in vivo. Pmca4 expression was not altered by perturbations in Ca2+balance, pointing to a housekeeping function of the pump in Ca2+-transporting epithelia. In conclusion, Pmca4 shows a divergent expression pattern in Ca2+-transporting epithelia, inferring diverse roles for this isoform not limited to transepithelial Ca2+transport.
Common therapeutic mechanisms of pallidal deep brain stimulation for hypo- and hyperkinetic movement disorders
Authors: McCairn Kevin W. , Iriki Atsushi , Isoda Masaki
Published: July 2015

Abnormalities in cortico-basal ganglia (CBG) networks can cause a variety of movement disorders ranging from hypokinetic disorders, such as Parkinson's disease (PD), to hyperkinetic conditions, such as Tourette syndrome (TS). Each condition is characterized by distinct patterns of abnormal neural discharge (dysrhythmia) at both the local single-neuron level and the global network level. Despite divergent etiologies, behavioral phenotypes, and neurophysiological profiles, high-frequency deep brain stimulation (HF-DBS) in the basal ganglia has been shown to be effective for both hypo- and hyperkinetic disorders. The aim of this review is to compare and contrast the electrophysiological hallmarks of PD and TS phenotypes in nonhuman primates and discuss why the same treatment (HF-DBS targeted to the globus pallidus internus, GPi-DBS) is capable of ameliorating both symptom profiles. Recent studies have shown that therapeutic GPi-DBS entrains the spiking of neurons located in the vicinity of the stimulating electrode, resulting in strong stimulus-locked modulations in firing probability with minimal changes in the population-scale firing rate. This stimulus effect normalizes/suppresses the pathological firing patterns and dysrhythmia that underlie specific phenotypes in both the PD and TS models. We propose that the elimination of pathological states via stimulus-driven entrainment and suppression, while maintaining thalamocortical network excitability within a normal physiological range, provides a common therapeutic mechanism through which HF-DBS permits information transfer for purposive motor behavior through the CBG while ameliorating conditions with widely different symptom profiles.
Neurotensin inhibits both dopamine- and GABA-mediated inhibition of ventral tegmental area dopamine neurons
Authors: Stuhrman Katherine , Roseberry Aaron G.
Published: July 2015

Dopamine is an essential neurotransmitter that plays an important role in a number of different physiological processes and disorders. There is substantial evidence that the neuropeptide neurotensin interacts with the mesolimbic dopamine system and can regulate dopamine neuron activity. In these studies we have used whole cell patch-clamp electrophysiology in brain slices from mice to examine how neurotensin regulates dopamine neuron activity by examining the effect of neurotensin on the inhibitory postsynaptic current generated by somatodendritic dopamine release (D2R IPSC) in ventral tegmental area (VTA) dopamine neurons. Neurotensin inhibited the D2R IPSC and activated an inward current in VTA dopamine neurons that appeared to be at least partially mediated by activation of a transient receptor potential C-type channel. Neither the inward current nor the inhibition of the D2R IPSC was affected by blocking PKC or calcium release from intracellular stores, and the inhibition of the D2R IPSC was greater with neurotensin compared with activation of other Gq-coupled receptors. Interestingly, the effects of neurotensin were not specific to D2R signaling as neurotensin also inhibited GABABinhibitory postsynaptic currents in VTA dopamine neurons. Finally, the effects of neurotensin were significantly larger when intracellular Ca2+was strongly buffered, suggesting that reduced intracellular calcium facilitates these effects. Overall these results suggest that neurotensin may inhibit the D2R and GABABIPSCs downstream of receptor activation, potentially through regulation of G protein-coupled inwardly rectifying potassium channels. These studies provide an important advance in our understanding of dopamine neuron activity and how it is controlled by neurotensin.
Neurochemical changes in the pericalcarine cortex in congenital blindness attributable to bilateral anophthalmia
Authors: Coullon Gaelle S. L. , Emir Uzay E. , Fine Ione , Watkins Kate E. , Bridge Holly
Published: July 2015

Congenital blindness leads to large-scale functional and structural reorganization in the occipital cortex, but relatively little is known about the neurochemical changes underlying this cross-modal plasticity. To investigate the effect of complete and early visual deafferentation on the concentration of metabolites in the pericalcarine cortex,1H magnetic resonance spectroscopy was performed in 14 sighted subjects and 5 subjects with bilateral anophthalmia, a condition in which both eyes fail to develop. In the pericalcarine cortex, where primary visual cortex is normally located, the proportion of gray matter was significantly greater, and levels of choline, glutamate, glutamine, myo-inositol, and total creatine were elevated in anophthalmic relative to sighted subjects. Anophthalmia had no effect on the structure or neurochemistry of a sensorimotor cortex control region. More gray matter, combined with high levels of choline and myo-inositol, resembles the profile of the cortex at birth and suggests that the lack of visual input from the eyes might have delayed or arrested the maturation of this cortical region. High levels of choline and glutamate/glutamine are consistent with enhanced excitatory circuits in the anophthalmic occipital cortex, which could reflect a shift toward enhanced plasticity or sensitivity that could in turn mediate or unmask cross-modal responses. Finally, it is possible that the change in function of the occipital cortex results in biochemical profiles that resemble those of auditory, language, or somatosensory cortex.
Approximation Algorithms for Maximum Link Scheduling under SINR-Based Interference Model
Authors: Zhou Zi-Ao , Li Chang-Geng
Published: July 2015

A fundamental problem in wireless networks is the maximum link scheduling (MLS) problem. In this problem, interference is a key issue and past researchers have shown that determining reception using Signal-to-Interference plus Noise Ratio (SINR) is more realistic than graph-based interference models. Unfortunately, the MLS problem has been proven to be NP-hard for SINR interference models. To date, several approximation algorithms have been proposed to solve MLS under the SINR-based interference model. However, most of these works do not have either an approximation bound or a distributed version. To this end, we present a novel scheduling method with a constant approximation ratio which is much simpler and only 1/28 of it in past research. The improvement of constant ϕ also offers a better MLS set. In addition, based on our centralized method, we present a polynomial time, randomized, distributed algorithm, which only requires estimates of the number of links, and maximum and minimum link lengths. We prove its correctness and show that it can compute a MLS with time complexity of [Formula: see text], where n is an estimate of the number of links.
Multivariate Spectral Gradient Algorithm for Nonsmooth Convex Optimization Problems
Authors: Hu Yaping
Published: July 2015

We propose an extended multivariate spectral gradient algorithm to solve the nonsmooth convex optimization problem. First, by using Moreau-Yosida regularization, we convert the original objective function to a continuously differentiable function; then we use approximate function and gradient values of the Moreau-Yosida regularization to substitute the corresponding exact values in the algorithm. The global convergence is proved under suitable assumptions. Numerical experiments are presented to show the effectiveness of this algorithm.
Insulin Resistance of Normal Weight Central Obese Adolescents in Korea Stratified by Waist to Height Ratio: Results from the Korea National Health and Nutrition Examination Surveys 2008–2010
Authors: Cho Won Kyoung , Kim Hyojin , Lee Hyun Young , Han Kyung Do , Jeon Yeon Jin , Jung In Ah , Kim Shin Hee , Cho Kyoung Soon , Park So Hyun , Jung Min Ho , Suh Byung-Kyu
Published: July 2015

Background. To evaluate insulin resistance of normal weight central obese 13–18-year-old male and female adolescents stratified by waist to height ratio (WHR).Methods. Data were obtained from the Korea National Health and Nutrition Examination Survey (K-NHANES) conducted during 2008–2010. Central obesity was defined as that in the upper quartile of age and sex specific WHR. Subjects were classified into no central obesity normal weight (NW), central obesity normal weight (CONW), no central obesity overweight (OW), and central obesity overweight (COOW).Results. The prevalence of CONW was 9.6% (83/832) in female and 7.0% (61/909) in male. CONW showed higher levels of insulin (P<0.006), HOMA-IR (P<0.006), and ALT (P<0.001) than NW in female. CONW had higher levels of insulin (P<0.0001), HOMA-IR (P<0.0001), and WBC count (P<0.021) and lower level of HDL (P<0.0001) than NW in male. WHR and BMI had similar significant correlations with MS components. CONW showed 2.5 times (95% confidence interval, 1.21–5.00) more likelihood to have high insulin resistance than NW in male.Conclusions. Screening for central obesity using WHR in clinical setting is recommended.
Giant Cell Myocarditis: Not Always a Presentation of Cardiogenic Shock
Authors: Tompkins Rose , Cole William J. , Rosenzweig Barry P. , Axel Leon , Bangalore Sripal , Lala Anuradha
Published: July 2015

Giant cell myocarditis is a rare and often fatal disease. The most obvious presentation often described in the literature is one of rapid hemodynamic deterioration due to cardiogenic shock necessitating urgent consideration of mechanical circulatory support and heart transplantation. We present the case of a 60-year-old man whose initial presentation was consistent with myopericarditis but who went on to develop a rapid decline in left ventricular systolic function without overt hemodynamic compromise or dramatic symptomatology. Giant cell myocarditis was confirmed via endomyocardial biopsy. Combined immunosuppression with corticosteroids and calcineurin inhibitor resulted in resolution of symptoms and sustained recovery of left ventricular function one year later. Our case highlights that giant cell myocarditis does not always present with cardiogenic shock and should be considered in the evaluation of new onset cardiomyopathy of uncertain etiology as a timely diagnosis has distinct clinical implications on management and prognosis.
New Interaction Solutions of (3+1)-Dimensional KP and (2+1)-Dimensional Boussinesq Equations
Authors: Ren Bo , Yu Jun , Liu Xi-Zhong
Published: July 2015

The consistent tanh expansion (CTE) method has been succeeded to apply to the nonintegrable (3+1)-dimensional Kadomtsev-Petviashvili (KP) and (2+1)-dimensional Boussinesq equations. The interaction solution between one soliton and one resonant soliton solution for the (3+1)-dimensional KP equation is obtained with CTE method. The interaction solutions among one soliton and cnoidal waves for these two equations are also explicitly given. These interaction solutions are investigated in both analytical and graphical ways. It demonstrates that the interactions between one soliton and cnoidal waves are elastic with phase shifts.
Isolation and Time Lapse Microscopy of Highly Pure Hepatic Stellate Cells
Authors: Bartneck Matthias , Warzecha Klaudia Theresa , Tag Carmen Gabriele , Sauer-Lehnen Sibille , Heymann Felix , Trautwein Christian , Weiskirchen Ralf , Tacke Frank
Published: July 2015

Hepatic stellate cells (HSC) are the main effector cells for liver fibrosis. We aimed at optimizing HSC isolation by an additional step of fluorescence-activated cell sorting (FACS) via a UV laser. HSC were isolated from livers of healthy mice and animals subjected to experimental fibrosis. HSC isolation by iohexol- (Nycodenz) based density centrifugation was compared to a method with subsequent FACS-based sorting. We assessed cellular purity, viability, morphology, and functional properties like proliferation, migration, activation marker, and collagen expression. FACS-augmented isolation resulted in a significantly increased purity of stellate cells (>99%) compared to iohexol-based density centrifugation (60–95%), primarily by excluding doublets of HSC and Kupffer cells (KC). Importantly, this method is also applicable to young animals and mice with liver fibrosis. Viability, migratory properties, and HSC transdifferentiationin vitrowere preserved upon FACS-based isolation, as assessed using time lapse microscopy. During maturation of HSC in culture, we did not observe HSC cell division using time lapse microscopy. Strikingly, FACS-isolated, differentiated HSC showed very limited molecular and functional responses to LPS stimulation. In conclusion, isolating HSC from mouse liver by additional FACS significantly increases cell purity by removing contaminations from other cell populations especially KC, without affecting HSC viability, migration, or differentiation.
A Robust Numerical Procedure for the Thermomechanical Flow Simulation of Friction Stir Welding Process Using an Adaptive Element-Free Galerkin Method
Authors: Wu C. T. , Hu Wei , Wang Hui-Ping , Lu Hongsheng
Published: July 2015

A meshfree modeling technique of material flow in the three-dimensional multiphysics thermomechanical friction stir welding process is presented. In this numerical model, the discretization in space is derived by the Element-Free Galerkin method using a Lagrangian meshfree convex approximation. The discrete thermal and mechanical equations are weakly coupled as the time advances using a forward difference scheme. A mortar contact algorithm is employed to model the stirring effect and heat generation due to frictional contact. Heat conductance between contacting bodies is considered as a function of contact pressure. A two-way adaptive procedure is introduced to the coupled thermomechanical system to surpass potential numerical problems associated with the extensive material deformation and spatial discretization. In each adaptive phase, a consistent projection operation utilizing the first-order meshfree convex approximation is performed to remap the solution variables. Finally, a three-dimensional multiphysics thermomechanical coupled friction stir welding problem is analyzed to demonstrate the effectiveness of the present meshfree numerical procedure.
Traumatic Cervical Spondyloptosis in a Neurologically Stable Patient: A Therapeutic Challenge
Authors: Munakomi Sunil , Bhattarai Binod , Cherian Iype
Published: July 2015

This is a case report of a neurologically intact patient following posttraumatic cervical spondyloptosis. We discuss the disease, management protocol and some surgical nuances to prevent any damage to the cord during different stages of its treatment.