bluuebunny/crossref_metadata_2025 huggingface dataset:
Are hospital services for self-harm getting better? An observational study examining management, service provision and temporal trends in England
Authors: Cooper J , Steeg S , Bennewith O , Lowe M , Gunnell D , House A , Hawton K , Kapur N
Published: November 2013

Objectives

To describe the characteristics and management of individuals attending hospital with self-harm and assess changes in management and service quality since an earlier study in 2001, a period in which national guidance has been available.

Design

Observational study.

Setting

A stratified random sample of 32 hospitals in England, UK.

Participants:

6442 individuals presenting with 7689 episodes of self-harm during a 3-month audit period between 2010 and 2011.

Outcome

Self-harm episodes, key aspects of individual management relating to psychosocial assessment and follow-up, and a 21-item measure of service quality.

Results

Overall, 56% (3583/6442) of individuals were women and 51% (3274/6442) were aged under 35 years. Hospitals varied markedly in their management. The proportion of episodes that received a psychosocial assessment by a mental health professional ranged from 22% to 88% (median 58%, IQR 48–70%); the proportion of episodes resulting in admission to general hospitals varied from 22% to 85% (median 54%, IQR 41–63%); a referral for specialist mental health follow-up was made in 11–64% of episodes (median 28%, IQR 22–38%); a referral to non-statutory services was made in 4–62% of episodes (median 15%, IQR 8–23%); 0–21% of episodes resulted in psychiatric admission (median 7%, QR 4–12%). The specialist assessment rate varied by method of harm; the median rate for self-cutting was 45% (IQR 28–63%) vs 58% (IQR 48–73%) for self-poisoning. Compared with the 2001 study, there was little difference in the proportion of episodes receiving specialist assessment; there was a significant increase in general hospital admission but a decrease in referrals for specialist mental health follow-up. However, scores on the service quality scale had increased from a median of 11.5–14.5 (a 26% increase).

Conclusions

Services for the hospital management of self-harm remain variable despite national guidelines and policy initiatives. We found no evidence for increasing levels of assessment over time but markers of service quality may have improved.

This paper forms part of the study ‘Variations in self-harm service delivery: an observational study examining outcomes and temporal trends’. The National Institute for Health Research Clinical Research Network (NIHR CRN) Portfolio database registration number: HOMASH 2 (7333). The NIHR Coordinated System for gaining NHS Permission (CSP) registration number: 23226.
POSITIVITY VIOLATIONS IN QCD
Authors: CORNWALL JOHN M.
Published: November 2013

Both lattice simulations and theoretical studies show that the spectral function of the gluon propagator of QCD (in various gauges, as well as for the gauge-invariant Pinch Technique, or PT, propagator) is not nonnegative everywhere, although it should be if it has a physical interpretation as in QED. Theory says moreover that the non-positive spectral function of the Landau-gauge or of the PT gluon propagator is further constrained to obey a superconvergence relation (the integral of the spectral function vanishes). We review the theoretical and lattice evidence for violation of positivity as well as various interpretations of this violation, and consider methods for checking superconvergence on the lattice (so far undone). The most common interpretation is that positivity violation implies confinement of gluons, so the gluon propagator does not describe processes with physical gluons. Another more direct and gauge-invariant interpretation arises from the PT: Asymptotic freedom alone demands non-positivity and superconvergence.
RELIABILITY MEASURES OF A COLD STANDBY SYSTEM WITH PREVENTIVE MAINTENANCE AND REPAIR
Authors: MALIK S. C. , BARAK SUDESH K.
Published: November 2013

The purpose of the present study is to determine reliability measures of a two-unit cold standby system with preventive maintenance and repair. The units are identical in nature subject to constant failure from normal mode. Preventive maintenance of the operative unit is carried out after a pre-specific time "t" up to which no failure occurs. However, repair of the unit is done at its failure. The unit works as new after repair and preventive maintenance. The switch devices are perfect. The distributions of failure time and the time by which unit undergoes for preventive maintenance are taken as negative exponential while that of preventive maintenance and repair times are assumed as arbitrary with different probability density functions. The random variables associated with failure, preventive maintenance and repair times are statistically independent. The semi-Markov process and regenerative point technique are adopted to derive the expressions for system performance measures in steady state. The graphical behavior of MTSF, availability and profit function have been observed with respect to preventive maintenance rate for particular values of other parameters and costs.
Far-space neglect in conjunction but not feature search following transcranial magnetic stimulation over right posterior parietal cortex
Authors: Mahayana Indra T. , Liu Chia-Lun , Chang Chi Fu , Hung Daisy L. , Tzeng Ovid J. L. , Juan Chi-Hung , Muggleton Neil G.
Published: November 2013

Near- and far-space coding in the human brain is a dynamic process. Areas in dorsal, as well as ventral visual association cortex, including right posterior parietal cortex (rPPC), right frontal eye field (rFEF), and right ventral occipital cortex (rVO), have been shown to be important in visuospatial processing, but the involvement of these areas when the information is in near or far space remains unclear. There is a need for investigations of these representations to help explain the pathophysiology of hemispatial neglect, and the role of near and far space is crucial to this. We used a conjunction visual search task using an elliptical array to investigate the effects of transcranial magnetic stimulation delivered over rFEF, rPPC, and rVO on the processing of targets in near and far space and at a range of horizontal eccentricities. As in previous studies, we found that rVO was involved in far-space search, and rFEF was involved regardless of the distance to the array. It was found that rPPC was involved in search only in far space, with a neglect-like effect when the target was located in the most eccentric locations. No effects were seen for any site for a feature search task. As the search arrays had higher predictability with respect to target location than is often the case, these data may form a basis for clarifying both the role of PPC in visual search and its contribution to neglect, as well as the importance of near and far space in these.
A novel protocol to investigate motor training-induced plasticity and sensorimotor integration in the cerebellum and motor cortex
Authors: Baarbé Julianne , Yielder Paul , Daligadu Julian , Behbahani Hushyar , Haavik Heidi , Murphy Bernadette
Published: November 2013

Our group set out to develop a sensitive technique, capable of detecting output changes from the posterior fossa following a motor acquisition task. Transcranial magnetic stimulation (TMS) was applied over the right cerebellar cortex 5 ms in advance of test stimuli over the left cerebral motor cortex (M1), suppressing test motor-evoked potentials (MEPs) recorded in a distal hand muscle. Ten participants typed the letters Z, D, F, and P in randomized 8-letter sequences for ∼15 min, and 10 participants took part in the control condition. Cerebellar-M1 recruitment curves were established before and after the motor acquisition task. Cerebellar inhibition at 50% (CBI50) was defined as the intensity of cerebellar-M1 stimulations that produced MEPs that were 50% of the initial test MEP. Collection also occurred at stimulator intensities 5 and 10% above CBI50. A significant interaction effect of group (experimental and control) vs. time (pre- and postintervention) was observed [ F(1,18) = 4.617, P = 0.046]. Post hoc tests showed a significant effect for the learning task in the experimental group [ F(1,9) = 10.28, P = 0.01]. Further analysis showed specific disinhibition at CBI50 ( P = 0.04), CBI50+5% ( P = 0.008), and CBI50+10% ( P = 0.01) for the experimental group only. Reaction time ( P < 0.001) and accuracy ( P = 0.006) improved significantly following practice, implying that disinhibition coincides with motor learning. No changes, however, were seen in the control condition. We conclude that this protocol is a sensitive technique that may be used to study cerebellar disinhibition with motor acquisition in vivo.
Global Dynamics Analysis of Homogeneous New Products Diffusion Model
Authors: Li Shuping , Jin Zhen
Published: November 2013

A mathematical model with stage structures is presented that incorporates the awareness stage and the decision-making stage; individuals exchange product information by two channels: mass media and interpersonal communication. When the persuasive advertisement is neglected in the decision-making stage, we find a threshold value about whether new products diffusion is successful or not. When the persuasive advertisement is considered, there must exist a positive equilibrium under some parameter condition; moreover, it must be globally asymptotically stable as long as it exists. Results show that the persuasive advertisement in the decision-making stage does not influence new products' successful diffusion, but the critical value that new products diffuse successfully decreases when the persuasive advertisement is considered. Some numerical simulations confirm our theoretical analysis and demonstrate the influence of parameters on the system. Corresponding to the analysis results, some diffusion strategies are provided.
An Adaptive Model for Calculating the Correlation Degree of Multiple Adjacent Signalized Intersections
Authors: Wang Linhong , Bie Yiming
Published: November 2013

As an important component of the urban adaptive traffic control system, subarea partition algorithm divides the road network into some small subareas and then determines the optimal signal control mode for each signalized intersection. Correlation model is the core of subarea partition algorithm because it can quantify the correlation degree of adjacent signalized intersections and decides whether these intersections can be grouped into one subarea. In most cases, there are more than two intersections in one subarea. However, current researches only focus on the correlation model for two adjacent intersections. The objective of this study is to develop a model which can calculate the correlation degree of multiple intersections adaptively. The cycle lengths, link lengths, number of intersections, and path flow between upstream and downstream coordinated phases were selected as the contributing factors of the correlation model. Their jointly impacts on the performance of the coordinated control mode relative to the isolated control mode were further studied using numerical experiments. The paper then proposed a correlation index (CI) as an alternative to relative performance. The relationship between CI and the four contributing factors was established in order to predict the correlation, which determined whether adjacent intersections could be partitioned into one subarea. A value of 0 was set as the threshold of CI. If CI was larger than 0, multiple intersections could be partitioned into one subarea; otherwise, they should be separated. Finally, case studies were conducted in a real-life signalized network to evaluate the performance of the model. The results show that the CI simulates the relative performance well and could be a reliable index for subarea partition.
A Case of Placental Mesenchymal Dysplasia
Authors: Taga Shigeki , Haraga Junko , Sawada Mari , Nagai Aya , Yamamoto Dan , Hayase Ryoji
Published: November 2013

Placental mesenchymal dysplasia (PMD) rarely complicates with pregnancy. A 30-year-old woman, gravida 3, para 3, presenting with placentomegaly, was referred to our department at 18 weeks of gestation. An ultrasonography revealed a normal fetus with a large multicystic placenta, measuring 125 × 42 × 80 mm. The border between the lesion and normal region was not clear. Color doppler revealed little blood flow in the lesion. Magnetic resonance imaging revealed normal fetus and a large multicystic placenta. Serum human chorionic gonadotropin level was 20124.97 U/L, which was normal at 20 weeks of gestation. Thus, placental mesenchymal dysplasia rather than hydatidiform mole with coexistent fetus was suspected. Then, routine checkup was continued. Because she had the history of Cesarean section, an elective Cesarean section was performed at 37 weeks of gestation, and 2520 g female infant with apgar score 8/9 was delivered. The baby was normal with no evidence of Beckwith-Wiedemann syndrome. Placenta of 20 × 16 × 2 cm, weighing 720 g, was bulky with grape like vesicles involving whole placenta. Microscopic examination revealed dilated villi and vessels with thick wall which was lacking trophoblast proliferation. Large hydropic stem villi with myxomatous struma and cistern formation were seen. PMD was histopathologically confirmed.
Overdiagnosis of Bipolar Disorder: A Critical Analysis of the Literature
Authors: Ghouse Amna A. , Sanches Marsal , Zunta-Soares Giovana , Swann Alan C. , Soares Jair C.
Published: November 2013

Bipolar disorder (BD) is considered one of the most disabling mental conditions, with high rates of morbidity, disability, and premature death from suicide. Although BD is often misdiagnosed as major depressive disorder, some attention has recently been drawn to the possibility that BD could be overdiagnosed in some settings. The present paper focuses on a critical analysis of the overdiagnosis issue among bipolar patients. It includes a review of the available literature findings, followed by some recommendations aiming at optimizing the diagnosis of BD and increasing its reliability.
TESLA GPUs versus MPI with OpenMP for the Forward Modeling of Gravity and Gravity Gradient of Large Prisms Ensemble
Authors: Couder-Castañeda Carlos , Ortiz-Alemán Carlos , Orozco-del-Castillo Mauricio Gabriel , Nava-Flores Mauricio
Published: November 2013

An implementation with the CUDA technology in a single and in several graphics processing units (GPUs) is presented for the calculation of the forward modeling of gravitational fields from a tridimensional volumetric ensemble composed by unitary prisms of constant density. We compared the performance results obtained with the GPUs against a previous version coded in OpenMP with MPI, and we analyzed the results on both platforms. Today, the use of GPUs represents a breakthrough in parallel computing, which has led to the development of several applications with various applications. Nevertheless, in some applications the decomposition of the tasks is not trivial, as can be appreciated in this paper. Unlike a trivial decomposition of the domain, we proposed to decompose the problem by sets of prisms and use different memory spaces per processing CUDA core, avoiding the performance decay as a result of the constant calls to kernels functions which would be needed in a parallelization by observations points. The design and implementation created are the main contributions of this work, because the parallelization scheme implemented is not trivial. The performance results obtained are comparable to those of a small processing cluster.
Average Consensus Analysis of Distributed Inference with Uncertain Markovian Transition Probability
Authors: Kim Won Il , Xiong Rong , Zhu Qiuguo , Wu Jun
Published: November 2013

The average consensus problem of distributed inference in a wireless sensor network under Markovian communication topology of uncertain transition probability is studied. A sufficient condition for average consensus of linear distributed inference algorithm is presented. Based on linear matrix inequalities and numerical optimization, a design method of fast distributed inference is provided.
A Sphere-Based Calibration Method for Line Structured Light Vision Sensor
Authors: Wei Zhenzhong , Shao Mingwei , Wang Yali , Hu Mengjie
Published: November 2013

A major difficulty in calibrating line structured light vision sensor is how to obtain enough calibration feature points, due to the fact that known world points on the calibration target do not rightly fall onto the light stripe plane. This paper presents a calibration method using a target, consisting of one sphere and a reference board, to obtain feature points on the light stripe, which is the intersection of the structured-light plane and the reference board. By moving the sphere into several positions on the fixed reference board, we can get a plane in parallel with the reference one. From the acquired right-circular cone and known radius of the sphere, the function of the reference board can be deduced. Moving the target randomly into different positions, enough points lying on the structured-light plane can be obtained. Experiment results show that the accuracy of the proposed calibration method can reach 0.102 mm within the view field of 200 mm * 200 mm; meanwhile, robustness and easy operation can be indicated.
The Exit Time and the Dividend Value Function for One-Dimensional Diffusion Processes
Authors: Li Peng , Yin Chuancun , Zhou Ming
Published: November 2013

We investigate the exit times from an interval for a general one-dimensional time-homogeneous diffusion process and their applications to the dividend problem in risk theory. Specifically, we first use Dynkin’s formula to derive the ordinary differential equations satisfied by the Laplace transform of the exit times. Then, as some examples, we solve the closed-form expression of the Laplace transform of the exit times for several popular diffusions, which are commonly used in modelling of finance and insurance market. Most interestingly, as the applications of the exit times, we create the connect between the dividend value function and the Laplace transform of the exit times. Both the barrier and threshold dividend value function are clearly expressed in terms of the Laplace transform of the exit times.
A Static Control Algorithm for Adaptive Beam String Structures Based on Minimal Displacement
Authors: Shen Yanbin , Cheng Huaqiang , Yang Pengcheng , Luo Yaozhi
Published: November 2013

The beam string structure (BSS) is a type of prestressed structure and has been widely used in large span structures nowadays. The adaptive BSS is a typical smart structure that can optimize the working status itself by controlling the length of active struts via certain control device. The control device commonly consists of actuators in all struts and sensors on the beam. The key point of the control process is to determine the length adjustment values of actuators according to the data obtained by preinstalled sensors. In this paper, a static control algorithm for adaptive BSS has been presented for the adjustment solution. To begin with, an optimization model of adaptive BSS with multiple active struts is established, which uses a sensitivity analysis method. Next, a linear displacement control process is presented, and the adjustment values of struts are calculated by a simulated annealing algorithm. A nonlinear iteration procedure is used afterwards to calibrate the results of linear calculation. Finally, an example of adaptive BSS under different external loads is carried out to verify the feasibility and accuracy of the algorithm. And the results also show that the adaptive BSS has much better adaptivity and capability than the noncontrolled BSS.
Spectral-Collocation Methods for Fractional Pantograph Delay-Integrodifferential Equations
Authors: Yang Yin , Huang Yunqing
Published: November 2013

We propose and analyze a spectral Jacobi-collocation approximation for fractional order integrodifferential equations of Volterra type with pantograph delay. The fractional derivative is described in the Caputo sense. We provide a rigorous error analysis for the collocation method, which shows that the error of approximate solution decays exponentially inL∞norm and weightedL2-norm. The numerical examples are given to illustrate the theoretical results.
Nonlinear Modelling, Design, and Test of Steel Blast-Resistant Doors
Authors: Salomoni V. A. , Mazzucco G. , Xotta G. , Fincato R. , Majorana C. E. , Schiavon M.
Published: November 2013

The nonlinear dynamic response for steel blast-resistant doors is here described, referring to an innovative experience at both national and international level requiring an ad hoc design and specific numerical simulations. The elements capability to sustain thermal loads due to fire hazards is additionally accounted for. The study has been conducted to define and characterize the nonlinear behaviour of a large number of doors, with the objective of sustaining dynamic loads from explosive hazards of fixed magnitude, as well as variable design and clearing times. The local overcome of the material strength limit (with correspondent plastic response) and possible formation of plastic hinges has been critically discussed. Numerical models have allowed for refining first design sketches and subsequently understanding the real thermomechanical behaviour for the investigated elements. Some experimental tests have been additionally performed, verifying the correctness of the already available numerical results, validating the adopted procedures, and correspondingly guaranteeing the doors' structural efficiency even under dynamic loads higher than design ones.
Planar Waves of the Buffered Bistable System
Authors: Wang Xiaohuan , Lv Guangying
Published: November 2013

This paper is concerned with the large time behavior of disturbed planar fronts in the buffered bistable system inℝn(n≥2). We first show that the large time behavior of the disturbed fronts can be approximated by that of the mean curvature flow with a drift term for all large time up tot=+∞. And then we prove that the planar front is asymptotically stable inL∞(ℝn)under ergodic perturbations, which include quasiperiodic and almost periodic ones as special cases.
Circulating Insulin-Like Growth Factor-Binding Protein 3 Levels, Independent of Insulin-Like Growth Factor 1, Associate with Truncal Fat and Systolic Blood Pressure in South Asian and White European Preschool Children
Authors: Patel Leena , Whatmore Andrew , Davies Jill , Bansal Narinder , Vyas Avni , Gemmell Isla , Oldroyd John , Cruickshank J. Kennedy , Clayton Peter
Published: November 2013

Aims: To study the effect of the insulin-like growth factor (IGF) system on growth, adiposity and systolic blood pressure (SBP) in early life in British-born South Asian (SA) and White European (WE) children. Methods: The effect of IGF-1 and insulin-like growth factor-binding protein 3 (IGFBP-3) over the first 4 years in 204 healthy SA and WE children was investigated by mixed linear regression modelling. This enabled inclusion of all follow-up observations and adjustment for repeated measures. Results: At birth, SA babies were shorter and lighter than WE babies. Over 4 years, SA ethnicity was associated with lower height, weight and body mass index (BMI) standard deviation score (SDS), higher subscapular/triceps skinfold thickness (Ss/Tr SFT) and lower SBP (all p < 0.01). IGF-1 was associated with greater height (p = 0.03), weight (p < 0.001) and BMI SDS (p < 0.001), and IGFBP-3 with greater weight SDS (p < 0.001), BMI SDS (p = 0.001), Ss/Tr SFT (p = 0.003) and SBP (p = 0.023). Conclusions: Over this first 4-year period of life, SA ethnicity was associated with being shorter, lighter, having more superficial truncal adiposity and lower SBP. IGFBP-3 (and not IGF-1) was independently associated with both superficial truncal adiposity and SBP, suggesting that IGFBP-3 is a potential metabolic and cardiovascular marker in healthy children in the early years of life.
Breast Implant-Associated Anaplastic Large-Cell Lymphoma Can Be a Diagnostic Challenge for Pathologists
Authors: Talagas Matthieu , Uguen Arnaud , Charles-Petillon Françoise , Conan-Charlet Virginie , Marion Véronique , Hu Weigo , Amice Jean , De Braekeleer Marc
Published: November 2013

Background: Primary anaplastic large-cell lymphoma (ALCL) occurring in women with breast implants is very rare. It is usually described as tumor cells infiltrating the periprosthetic capsule. These are most often revealed by a periprosthetic recurrent isolated effusion (seroma cavity), occurring late after implantation of the prosthesis. ALCL is more rarely a tumor or periprosthetic capsular contracture. Case: We report a 66-year-old woman, initially diagnosed by cytological examination of breast effusion, in whom ALCL appeared two and a half months after the removal of a ruptured implant. Repeated biopsies of the periprosthetic capsule performed in parallel showed fibrous tissue, without tumor proliferation. Only meticulous histological examination of the total capsulectomy identified tumor cells as a thin and discontinuous layer along the inner surface of the capsule without capsular invasion. Conclusion: Awareness of the histological pattern of this new clinical entity is important. A total capsulectomy with a good sampling for microscopic examination should be conducted for any suspicion of breast implant-associated ALCL. Cytology-histology correlation is essential.
Outcome Impact of Coronary Revascularization Strategy Reclassification With Fractional Flow Reserve at Time of Diagnostic Angiography
Authors: Van Belle Eric , Rioufol Gilles , Pouillot Christophe , Cuisset Thomas , Bougrini Karim , Teiger Emmanuel , Champagne Stéphane , Belle Loic , Barreau Didier , Hanssen Michel , Besnard Cyril , Dauphin Raphael , Dallongeville Jean , El Hahi Yassine , Sideris Georgios , Bretelle Christophe , Lhoest Nicolas , Barnay Pierre , Leborgne Laurent , Dupouy Patrick
Published: November 2013

Background—

There is no large report of the impact of fractional flow reserve (FFR) on the reclassification of the coronary revascularization strategy on individual patients referred for diagnostic angiography.

Methods and Results—

The Registre Français de la FFR (R3F) investigated 1075 consecutive patients undergoing diagnostic angiography including an FFR investigation at 20 French centers. Investigators were asked to define prospectively their revascularization strategy a priori based on angiography before performing the FFR. The final revascularization strategy, reclassification of the strategy by FFR, and 1-year clinical follow-up were prospectively recorded. The strategy a priori based on angiography was medical therapy in 55% and revascularization in 45% (percutaneous coronary intervention, 38%; coronary artery bypass surgery, 7%). Patients were treated according to FFR in 1028/1075 (95.7%). The applied strategy after FFR was medical therapy in 58% and revascularization in 42% (percutaneous coronary intervention, 32%; coronary artery bypass surgery, 10%). The final strategy applied differed from the strategy a priori in 43% of cases: in 33% of a priori medical patients, in 56% of patients undergoing a priori percutaneous coronary intervention, and in 51% of patients undergoing a priori coronary artery bypass surgery. In reclassified patients treated based on FFR and in disagreement with the angiography-based a priori decision (n=464), the 1-year outcome (major cardiac event, 11.2%) was as good as in patients in whom final applied strategy concurred with the angiography-based a priori decision (n=611; major cardiac event, 11.9%; log-rank,
P
=0.78). At 1 year, >93% patients were asymptomatic without difference between reclassified and nonreclassified patients (Generalized Linear Mixed Model,
P
=0.75). Reclassification safety was preserved in high-risk patients.

Conclusion—

This study shows that performing FFR during diagnostic angiography is associated with reclassification of the revascularization decision in about half of the patients. It further demonstrates that it is safe to pursue a revascularization strategy divergent from that suggested by angiography but guided by FFR.
Design of a noncontact spherical bearing based on near-field acoustic levitation
Authors: Chen Chao , Wang Junshan , Jia Bing , Li Fan
Published: November 2013

Based on near-field acoustic levitation, a noncontact bearing with a spherical rotor was proposed to explore its potential application for novel supporting bearing of suspended gyro. The stator of the noncontact bearing has a hollow bowl-shaped configuration, in order to produce acoustic levitation force for a spherical object. Two orthogonal flexural standing waves were piezoelectrically generated and led to a traveling wave in the stator, and then the induced high-intensity sound in the air gap between the stator and spherical rotor could apply levitation force and even driving force for the spherical rotor. In this article, finite element model of a bowl-shaped piezoelectric stator was built, and the dynamic analysis and parametric optimization for the stator have been conducted. The prototypes were manufactured and vibration parameters of the stators were experimentally obtained. The test system for the noncontact spherical bearing was built, and its levitation and driving characteristics were measured. The spherical rotor successfully achieved levitation and noncontact rotation based on near-field acoustic levitation and the experimental results preliminarily indicate the feasibility of near-field acoustic levitation for suspended gyro.
CD44 targets Wnt/β-catenin pathway to mediate the proliferation of K562 cells
Authors: Chang Guoqiang , Zhang Hongju , Wang Jian , Zhang Yujuan , Xu Hua , Wang Chijuan , Zhang Hairui , Ma Li , Li Qinghua , Pang Tianxiang
Published: November 2013

Background

Chronic myeloid leukemia is a clonal myeloproliferative disorder disease in which BCR/ABL plays an important role as an oncoprotein and molecular target. Despite the success of targeted therapy using tyrosine kinase inhibitors, CML remains largely incurable, most likely due to the treatment resistance after firstly chemical therapy. So know well the unique molecular pathway of CML is very important.

Methods

The expressions of CD44 in different leukemia patients and cell lines were detected by real-time PCR and western blotting. The effects of CD44 on proliferation of K562 cells were determined using the MTT and colony formation assays, and even in a nude mouse transplantation model. Then, the cell cycle changes were detected by flow cytometric analysis and the early apoptosis of cells was detected by the annexin V/propidium iodide double-staining assay. The expressions of the cycles and apoptosis-related proteins p21, Cyclin D1 and Bcl-2 were analyzed by western blot and real-time PCR assay. Finally, the decreased nuclear accumulation of β-catenin was detected by western blotting and immunefluorescence.

Results

Firstly, we showed that CD44 expression was increased in several kinds of leukemia patients and K562 cells. By contrast, the down-regulation of CD44 resulted in decreased proliferation with a G0/G1 arrest of cell cycle in K562 cells according to the MTT assay and the flow cytometric analysis. And no significant induction of both the early and late phases of apoptosis was shown by the annexin V-FITC and PI staining. During this process, p21 and cyclin D1 are the major causes for cell cycle arrest. In addition, we found CD44 down-regulation decreased the expression of β-catenin and increased the expression of phosphorylated β-catenin. The instability of Wnt/β-catenin pathway induced by increased expression of p-β-catenin resulted in a decreased nuclear accumulation in CD44 silenced K562 cells. In the nude mouse transplantation model, we also found the same results.

Conclusions

These results show that K562 cells depend to a greater extent on CD44 for proliferation, and CD44 down-regulation may induce a cell cycle arrest through Wnt/β-catenin pathway. CD44 blockade may be beneficial in therapy of CML.
Differential expression of prolyl hydroxylase 1 in patients with ulcerative colitis versus patients with Crohn’s disease/infectious colitis and healthy controls
Authors: Van Welden Sophie , Laukens Debby , Ferdinande Liesbeth , De Vos Martine , Hindryckx Pieter
Published: November 2013

Background

Inhibition of prolyl hydroxylases (PHDs) leads to the induction of a transcriptional program that, in the gut, promotes intestinal epithelial cell survival. PHD inhibitors have recently been suggested as a promising alternative treatment for inflammatory bowel disease (IBD). In this study, we explored the colonic mucosal expression of the different PHD-isoforms (PHD1, 2 and 3) in order to identify the key isoform(s) involved in the pathogenesis of IBD.

Methods

The mRNA expression of inflammatory cytokines (IL-8 and TNF-α), an apoptosis marker (caspase 3) and PHD1, 2 and 3 was analysed in biopsies of IBD patients (UC and CD), patients with infectious colitis and healthy controls using qRT-PCR. PHD protein levels were evaluated using western blot. Cellular localization of PHD 1, 2 and 3 was determined by immunohistochemistry.

Results

PHD1 was significantly up-regulated in IBD patients, both at the mRNA (UC: p < 0.0001 and CD: p < 0.05) and at the protein level (UC: p < 0.05 and CD: p < 0.05), and showed a very good correlation with the expression of the inflammatory cytokines IL-8 and TNF-α and the apoptosis marker caspase 3. Colonic mucosal PHD2 mRNA and protein expressions were not altered in IBD. PHD3 expression was increased in inflamed biopsies from UC patients (p < 0.0001), but only at the mRNA level. PHD1 and PHD2 expression was found both in the colonic lamina propria and the epithelium while PHD3 was mainly located in the endothelium of blood vessels.

Conclusions

In this exploratory expression analysis, PHD1 comes forward as the primary therapeutic target for UC and, to a lesser extent, for (colonic) CD.
Flow-induced voltage generation over monolayer graphene in the presence of herringbone grooves
Authors: Lee Seung Ho , Kang Young Bok , Jung Wonsuk , Jung Yousung , Kim Soohyun , Noh Hongseok
Published: November 2013

While flow-induced voltage over a graphene layer has been reported, its origin remains unclear. In our previous study, we suggested different mechanisms for different experimental configurations: phonon dragging effect for the parallel alignment and an enhanced out-of-plane phonon mode for the perpendicular alignment (Appl. Phys. Lett. 102:063116, 2011). In order to further examine the origin of flow-induced voltage, we introduced a transverse flow component by integrating staggered herringbone grooves in the microchannel. We found that the flow-induced voltage decreased significantly in the presence of herringbone grooves in both parallel and perpendicular alignments. These results support our previous interpretation.
Fulvestrant up regulates UGT1A4 and MRP s through ERα and c-Myb pathways: a possible primary drug disposition mechanism
Authors: Edavana Vineetha K , Penney Rosalind B , Yao-Borengasser Aiwei , Williams Suzanne , Rogers Lora , Dhakal Ishwori B , Kadlubar Susan
Published: November 2013

Fulvestrant (Faslodex™) is a pure antiestrogen that is effective in treating estrogen receptor-(ER) positive breast cancer tumors that are resistant to selective estrogen receptor modulators such as tamoxifen. Clinical trials investigating the utility of adding fulvestrant to other therapeutics have not been shown to affect cytochrome P450-mediated metabolism. Effects on phase II metabolism and drug resistance have not been explored. This study demonstrates that fulvestrant up regulates the expression of UDP glucuronosyltransferase 1A4 (UGT1A4) >2.5- and >3.5-fold in MCF7 and HepG2 cells, respectively. Up regulation occurred in a time- and concentration-dependent manner, and was inhibited by siRNA silencing of ERα. Fulvestrant also up regulates multidrug resistance-associated proteins (MRPs). There was an up regulation of MRP 2 (1.5- and 3.5-fold), and MRP 3 (5.5- and 4.5-fold) in MCF7 and HepG2 cell lines, respectively, and an up regulation of MRP1 (4-fold) in MCF7 cells. UGT1A4 mRNA up regulation was significantly correlated with UGT1A4 protein expression, anastrozole glucuronidation, ERα mRNA expression and MRP mRNA expression, but not with ERα protein expression. Genetic variants in the UGT1A4 promoter (-163A, -217G and -219T) reduced the basal activity of UGT1A4 by 40-60%. In silico analysis indicated that transcription factor c-Myb binding capacity may be affected by these variations. Luciferase activity assays demonstrate that silencing c-Myb abolished UGT1A4 up regulation by fulvestrant in promoters with the common genotype (-163G, -217 T and -219C) in MCF7 cells. These data indicate that fulvestrant can influence the disposition of other UGT1A4 substrates. These findings suggest a clinically significant role for UGT1A4 and MRP s in drug efficacy.
Individual and combined effects of DNA methylation and copy number alterations on miRNA expression in breast tumors
Authors: Aure Miriam Ragle , Leivonen Suvi-Katri , Fleischer Thomas , Zhu Qian , Overgaard Jens , Alsner Jan , Tramm Trine , Louhimo Riku , Alnæs Grethe I Grenaker , Perälä Merja , Busato Florence , Touleimat Nizar , Tost Jörg , Børresen-Dale Anne-Lise , Hautaniemi Sampsa , Troyanskaya Olga G , Lingjærde Ole Christian , Sahlberg Kristine Kleivi , Kristensen Vessela N
Published: November 2013

Background

The global effect of copy number and epigenetic alterations on miRNA expression in cancer is poorly understood. In the present study, we integrate genome-wide DNA methylation, copy number and miRNA expression and identify genetic mechanisms underlying miRNA dysregulation in breast cancer.

Results

We identify 70 miRNAs whose expression was associated with alterations in copy number or methylation, or both. Among these, five miRNA families are represented. Interestingly, the members of these families are encoded on different chromosomes and are complementarily altered by gain or hypomethylation across the patients. In an independent breast cancer cohort of 123 patients, 41 of the 70 miRNAs were confirmed with respect to aberration pattern and association to expression. In vitro functional experiments were performed in breast cancer cell lines with miRNA mimics to evaluate the phenotype of the replicated miRNAs. let-7e-3p, which in tumors is found associated with hypermethylation, is shown to induce apoptosis and reduce cell viability, and low let-7e-3p expression is associated with poorer prognosis. The overexpression of three other miRNAs associated with copy number gain, miR-21-3p, miR-148b-3p and miR-151a-5p, increases proliferation of breast cancer cell lines. In addition, miR-151a-5p enhances the levels of phosphorylated AKT protein.

Conclusions

Our data provide novel evidence of the mechanisms behind miRNA dysregulation in breast cancer. The study contributes to the understanding of how methylation and copy number alterations influence miRNA expression, emphasizing miRNA functionality through redundant encoding, and suggests novel miRNAs important in breast cancer.
Long-term Prognostic Value for Patients with Chronic Heart Failure of Estimated Glomerular Filtration Rate Calculated with the New CKD-EPI Equations Containing Cystatin C
Authors: Zamora Elisabet , Lupón Josep , de Antonio Marta , Vila Joan , Peñafiel Judith , Galán Amparo , Urrutia Agustín , Domingo Mar , Bayes-Genis Antoni
Published: November 2013

BACKGROUND

Correct estimation of renal function is crucial in assessing prognosis of patients with heart failure (HF). Recently, two new equations have been proposed to calculate estimated glomerular filtration rate (eGFR) with cystatin C alone or both creatinine and cystatin C. We assessed the prognostic value of eGFR estimated by these new equations in outpatients with HF.

METHODS

The study included 879 patients with median age, 70.4 years; main etiology of HF ischemic heart disease, 52.7%; and median LVEF, 34%.

RESULTS

eGFR estimates by the new equations correlated significantly with eGFR estimates from previous equations, with the best correlation observed between the 2 equations containing cystatin C [intraclass correlation coefficient 0.95 (95% confidence interval 0.94–0.95)]. During a median follow-up of 3.94 years, 371 patients died. The Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) equations containing cystatin C were found to be best for predicting death [area under the ROC curve 0.685 for CKD-EPI-cystatin C and 0.672 for CKD-EPI-creatinine-cystatin C vs 0.632 for simplified Modification of Diet in Renal Disease Study traceable to isotope dilution mass spectrometry and 0.643 for CKD-EPI (all P < 0.001)]. The CKD-EPI-cystatin C equations also showed significantly better calibration and reclassification measurements for both integrated discrimination improvement and net reclassification improvement in predicting death (P < 0.001). Reclassification with these new equations was particularly better in the subgroup with intermediate eGFR [45–74 mL · min−1 · (1.73 m2)−1].

CONCLUSIONS

The two new CKD-EPI equations containing cystatin C are useful for HF risk stratification and show better prognostic performance than creatinine-only based eGFR equations, mostly in patients with intermediate eGFR. These equations seem appropriate for assessing prognosis of HF patients with moderate renal insufficiency.
Prognostic Relevance of Viable Circulating Tumor Cells Detected by EPISPOT in Metastatic Breast Cancer Patients
Authors: Ramirez Jean-Marie , Fehm Tanja , Orsini Mattea , Cayrefourcq Laure , Maudelonde Thierry , Pantel Klaus , Alix-Panabières Catherine
Published: November 2013

BACKGROUND

Detection of circulating tumor cells (CTC) in breast cancer patients is currently performed in many clinical trials, using different technologies, in particular the EpCAM-dependent CellSearch® system. The purpose of this study was to investigate the incidence and prognostic relevance of viable CTC in a large cohort of metastatic breast cancer (MBC) patients.

METHODS

A total of 254 MBC patients were enrolled in a prospective multicenter study at first diagnosis of metastatic disease or disease progression (before the start of a new treatment regimen). After EpCAM-independent enrichment, viable CTC releasing cytokeratin-19 as an epithelial cell marker were detected in the peripheral blood by an EPISPOT assay, and the Food and Drug Administration cleared CellSearch was used as the reference method.

RESULTS

Using the EPISPOT assay, CTC were detected in 59% of MBC patients. The overall survival (OS) was linked with the CTC status measured by EPISPOT (P = 0.0191), which allowed stratification of MBC patients in low- and high-risk groups. This stratification could be improved by addition of the CTC status assessed by the CellSearch system. In multivariate Cox proportional-hazards regression analysis, the 3 methods used to determine the level of CTC (EPISPOT, CellSearch, and combination of EPISPOT/CellSearch) were compared by the Bayesian information criterion method. Interestingly, the combination of the EPISPOT and CellSearch assays was the strongest predictor of OS (hazard ratio, 22.6; 95% CI, 2.8–184.08).

CONCLUSIONS

This is the first study in which CTC detection using the EPISPOT assay was evaluated on a large cohort of MBC patients, showing prognostic relevance of the presence of viable CTC.
Gene functional dynamics: environment as a trigger?
Authors: Stoupel Eliyahu G.
Published: November 2013

Recent decades have seen the deciphering of the human genome and, also, progress in studies related to the effects of space-weather on humans. The progress in genetics allows us to connect many human pathologies with specific gene abnormalities. Concomitantly it has been shown that many congenital and adherent diseases, and the timing of death are connected with space factors such as solar activity (SA), geomagnetic activity (GMA), cosmic ray activity (CRA), and space neutron and proton flux. Here arises the question to what extent gene expression is affected by the aforementioned space physical activity parameters. This is the motto of this hypothetical paper. In conclusion, the space-weather-related timing of many medical events invites presumption that gene activity is a changing phenomenon and space weather components may be playing a regulatory role in these changes.
Multiobjective optimization of composite cylindrical shells for strength and frequency using genetic algorithm and neural networks
Authors: Garmsiri Karim , Jalal Mostafa
Published: November 2013

In this paper, the optimal fiber orientations relative to the principle axis of composite cylindrical shell composed of four and six layers were determined so that the natural frequency and strength of the shell are optimized. For this purpose, first, the free vibration analysis of the shell was carried out based on 3D elasticity. Then, for calculation of the strength objective function, the inverse form of Tsai-Hill yield criteria was used and the functions of strength and frequency were developed in terms of fiber orientation. Once the correctness of the above solutions was ensured, the objective functions were modeled with artificial neural network (ANN). The model made was then introduced into genetic algorithm (GA) and the maximum fitness function and optimal staking sequence of the layers with respect to the fibers angles were obtained. Optimal solutions obtained by combination of ANN and GA are compared to the solutions obtained by analytical solution and GA; eventually, the tables and diagrams are presented and different fiber orientations as optimization solutions are presented as the final results of the composite shell analysis.
Astrocytes in the Rat Nucleus Tractus Solitarii Are Critical for Cardiovascular Reflex Control
Authors: Lin Li-Hsien , Moore Steven A. , Jones Susan Y. , McGlashon Jacob , Talman William T.
Published: November 2013

We have shown that an antibody to dopamine-β-hydroxylase conjugated with saporin (anti-DBH-SAP) damages catecholamine neurons in the nucleus tractus solitarii (NTS) of rat, attenuates arterial baroreflexes, and leads to lability of arterial blood pressure, damage to cardiac myocytes, and, in some animals, sudden death. However, others have shown that injection of 6-hydroxydopamine (6-OHDA), a toxin devoid of saporin, also damaged NTS catecholamine neurons but did not lead to these cardiovascular changes. We found similar cardiovascular changes after injecting a different SAP conjugate to target NTS neurons with neurokinin (NK1) receptors. Because ribosome-inactivating proteins may be toxic to glia, we hypothesized that SAP, a ribosome-inactivating protein, might target glia whose loss could account for physiological changes. We tested this hypothesis by assessing effects on select neurons and on glia in the NTS after exposure to SAP, targeted SAP conjugates, or 6-OHDA. SAP and all SAP conjugates led to loss of immunoreactivity for glial fibrillary acidic protein, a marker for astrocytes, in the NTS while 6-OHDA did not. As reported previously, anti-DBH-SAP selectively killed noradrenergic neurons in the NTS while SAP conjugated to stabilized substance P (SSP-SAP) selectively killed neurons with NK1 receptors. In contrast, SAP produced no demonstrable neuronal damage. All injections led to activation of microglia in the NTS; however, only SAP and its conjugates attenuated cardiovascular reflexes while also producing lability of arterial pressure, damage to cardiac myocytes, and in some animals, sudden death. Thus, NTS astrocytes may play a role in mediating cardiovascular reflex transmission through the NTS.
New records of Paracrias Ashmead (Hymenoptera, Eulophidae) as parasitoids on weevil larvae (Coleoptera, Curculionidae) in Brazil, with the description of a new species
Authors: Palmieri Luciano , Farache Fernando H. A. , Pereira Rodrigo A. S. , Hansson Christer
Published: November 2013

Paracrias strii Schauff, 1985 and P. ceratophaga Palmieri & Hansson sp. nov. are first record in Brazil and both are associated with Ceratopus Schoenherr larvae (Coleoptera, Curculionidae) reared from syconia of two species of fig-trees. Both Paracrias species are diagnosed and illustrated. Males of P. ceratophaga sp. nov. are described. The association of Paracrias with weevil larvae is briefly discussed.