bluuebunny/crossref_metadata_2025 huggingface dataset:
The Psychology of Change: Self-Affirmation and Social Psychological Intervention
Authors: Cohen Geoffrey L. , Sherman David K.
Published: January 2014

People have a basic need to maintain the integrity of the self, a global sense of personal adequacy. Events that threaten self-integrity arouse stress and self-protective defenses that can hamper performance and growth. However, an intervention known as self-affirmation can curb these negative outcomes. Self-affirmation interventions typically have people write about core personal values. The interventions bring about a more expansive view of the self and its resources, weakening the implications of a threat for personal integrity. Timely affirmations have been shown to improve education, health, and relationship outcomes, with benefits that sometimes persist for months and years. Like other interventions and experiences, self-affirmations can have lasting benefits when they touch off a cycle of adaptive potential, a positive feedback loop between the self-system and the social system that propagates adaptive outcomes over time. The present review highlights both connections with other disciplines and lessons for a social psychological understanding of intervention and change.
High-Dimensional Statistics with a View Toward Applications in Biology
Authors: Bühlmann Peter , Kalisch Markus , Meier Lukas
Published: January 2014

We review statistical methods for high-dimensional data analysis and pay particular attention to recent developments for assessing uncertainties in terms of controlling false positive statements (type I error) and p-values. The main focus is on regression models, but we also discuss graphical modeling and causal inference based on observational data. We illustrate the concepts and methods with various packages from the statistical software [Formula: see text] using a high-throughput genomic data set about riboflavin production with Bacillus subtilis, which we make publicly available for the first time.
Build, Compute, Critique, Repeat: Data Analysis with Latent Variable Models
Authors: Blei David M.
Published: January 2014

We survey latent variable models for solving data-analysis problems. A latent variable model is a probabilistic model that encodes hidden patterns in the data. We uncover these patterns from their conditional distribution and use them to summarize data and form predictions. Latent variable models are important in many fields, including computational biology, natural language processing, and social network analysis. Our perspective is that models are developed iteratively: We build a model, use it to analyze data, assess how it succeeds and fails, revise it, and repeat. We describe how new research has transformed these essential activities. First, we describe probabilistic graphical models, a language for formulating latent variable models. Second, we describe mean field variational inference, a generic algorithm for approximating conditional distributions. Third, we describe how to use our analyses to solve problems: exploring the data, forming predictions, and pointing us in the direction of improved models.
The phase of prestimulus alpha oscillations affects tactile perception
Authors: Ai Lei , Ro Tony
Published: December 2013

Previous studies have shown that neural oscillations in the 8- to 12-Hz range influence sensory perception. In the current study, we examined whether both the power and phase of these mu/alpha oscillations predict successful conscious tactile perception. Near-threshold tactile stimuli were applied to the left hand while electroencephalographic (EEG) activity was recorded over the contralateral right somatosensory cortex. We found a significant inverted U-shaped relationship between prestimulus mu/alpha power and detection rate, suggesting that there is an intermediate level of alpha power that is optimal for tactile perception. We also found a significant difference in phase angle concentration at stimulus onset that predicted whether the upcoming tactile stimulus was perceived or missed. As has been shown in the visual system, these findings suggest that these mu/alpha oscillations measured over somatosensory areas exert a strong inhibitory control on tactile perception and that pulsed inhibition by these oscillations shapes the state of brain activity necessary for conscious perception. They further suggest that these common phasic processing mechanisms across different sensory modalities and brain regions may reflect a common underlying encoding principle in perceptual processing that leads to momentary windows of perceptual awareness.
Role of amino terminus in voltage gating and junctional rectification of Shaking B innexins
Authors: Marks William D. , Skerrett I. Martha
Published: December 2013

Rectifying electrical synapses are rare gap junctions that favor transmission of signals in one direction. Such synapses have been identified in neural systems, including those mediating rapid escape responses of arthropods. In the Drosophila giant fiber system, adjacent cells express and contribute different transcript variants of the innexin Shaking B, resulting in heterotypic gap junctions with rectifying properties. When expressed exogenously, variants Shaking B Lethal (ShakBL) and Shaking B neural + 16 (ShakBN16) form heterotypic junctions that gate asymmetrically in response to transjunctional voltage. To determine whether the amino terminus confers properties of gating and rectification, amino-terminal domains were exchanged between ShakBL and ShakBN16, creating chimeric proteins SBL NTN16 and SBN16 NTL. The properties were analyzed in paired Xenopus oocytes. Our results suggest that the amino terminus plays an important role in establishing rectifying properties inherent to heterotypic junctions composed of ShakBL and ShakBN16. ShakBL/SBL NTN16 junctions behaved similarly to ShakBL/ShakBN16 junctions, gating in response to transjunctional voltage of one polarity and inducing a highly asymmetric conductance-voltage relationship. However, the amino terminus did not act independently to confer sensitivity to transjunctional voltage. The complementary pairing ShakBN16/SBN16 NTL displayed little sensitivity to voltage of either polarity, and in homotypic pairings SBL NTN16 was strongly gated by transjunctional voltage. We propose a model in which the amino terminus induces gating only when matched with an accommodating innexin body.
A Three-Dimensional Model of the Effective Electromechanical Impedance for an Embedded PZT Transducer
Authors: Zuo Chunyuan , Feng Xin , Zhou Jing
Published: December 2013

A three-dimensional model of the effective electromechanical impedance for an embedded PZT transducer is proposed by considering the interaction between a PZT patch and a host structure. By introducing an effective mechanical impedance, the coupled electromechanical admittance formulations are derived using the piezoelectric constitutive equations. Then, a modified methodology for monitoring structure changes using an electromechanical impedance (EMI) technique is proposed. In the proposed method, the changes in the host structure are monitored by using the “active” part associated with the structural mechanical impedance, which is extracted from the measured raw admittance signatures. The strength gain of a concrete beam with embedded PZT transducers during the curing age was monitored with the proposed methodology. The experimental results demonstrate that the use of the “active” part is more sensitive as opposed to the raw admittance signatures for structural health monitoring (SHM).
Effect of Brief Daily Resistance Training on Occupational Neck/Shoulder Muscle Activity in Office Workers with Chronic Pain: Randomized Controlled Trial
Authors: Lidegaard Mark , Jensen Rene B. , Andersen Christoffer H. , Zebis Mette K. , Colado Juan C. , Wang Yuling , Heilskov-Hansen Thomas , Andersen Lars L.
Published: December 2013

Purpose. This study investigates the acute and longitudinal effects of resistance training on occupational muscle activity in office workers with chronic pain.Methods. 30 female office workers with chronic neck and shoulder pain participated for 10 weeks in high-intensity elastic resistance training for 2 minutes per day (n=15) or in control receiving weekly email-based information on general health (n=15). Electromyography (EMG) from the splenius and upper trapezius was recorded during a normal workday.Results. Adherence to training and control interventions were 86% and 89%, respectively. Compared with control, training increased isometric muscle strength 6% (P<0.05) and decreased neck/shoulder pain intensity by 40% (P<0.01). The frequency of periods with complete motor unit relaxation (EMG gaps) decreased acutely in the hours after training. By contrast, at 10-week follow-up, training increased average duration of EMG gaps by 71%, EMG gap frequency by 296% and percentage time below 0.5%, and 1.0% EMGmax by 578% and 242%, respectively, during the workday in m. splenius.Conclusion. While resistance training acutely generates a more tense muscle activity pattern, the longitudinal changes are beneficial in terms of longer and more frequent periods of complete muscular relaxation and reduced pain.
Effect of Mechanism Error on Input Torque of Scroll Compressor
Authors: Zhao Man , Yu Shurong , Li Chao , Yu Yang
Published: December 2013

Based on the fundamental principle of plane four-bar mechanism, the force on the equivalent parallel four-bar mechanism was analyzed for scroll compressor with mini-crank antirotation, and the formula of input torque was proposed. The change of input torque caused by the mechanism size error was analyzed and verified with an example. The calculation results show that the mechanism size error will cause large fluctuation in input torque at the drive rod and connecting rod collinear and the fluctuation extreme value increases with rotational speed. Decreasing of the crankshaft eccentricity errors is helpful for reducing the effects of dimension error on input torque but will increase the friction loss of orbiting and fixed scroll wrap. The influence of size error should be considered in design in order to select suitable machining accuracy and reduce the adverse effect caused by size error.
Efficiency of Hysteresis Rods in Small Spacecraft Attitude Stabilization
Authors: Farrahi Assal , Sanz-Andrés Ángel
Published: December 2013

A semiempirical method for predicting the damping efficiency of hysteresis rods on‐board small satellites is presented. It is based on the evaluation of dissipating energy variation of different ferromagnetic materials for two different rod shapes: thin film and circular cross‐section rods, as a function of their elongation. Based on this formulation, an optimum design considering the size of hysteresis rods, their cross section shape, and layout has been proposed. Finally, the formulation developed was applied to the case of four existing small satellites, whose corresponding in‐flight data are published. A good agreement between the estimated rotational speed decay time and the in‐flight data has been observed.
Analysis of Size Correlations for Microdroplets Produced by Ultrasonic Atomization
Authors: Dalmoro Annalisa , Barba Anna Angela , d’Amore Matteo
Published: December 2013

Microencapsulation techniques are widely applied in the field of pharmaceutical production to control drugs release in time and in physiological environments. Ultrasonic‐assisted atomization is a new technique to produce microencapsulated systems by a mechanical approach. Interest in this technique is due to the advantages evidenceable (low level of mechanical stress in materials, reduced energy request, reduced apparatuses size) when comparing it to more conventional techniques. In this paper, the groundwork of atomization is introduced, the role of relevant parameters in ultrasonic atomization mechanism is discussed, and correlations to predict droplets size starting from process parameters and material properties are presented and tested.
Status of the GERDA Experiment at the Laboratori Nazionali del Gran Sasso
Authors: Brugnera R. , Garfagnini A.
Published: December 2013

The Germanium Detector Array (Gerda) is a low background experiment at the Laboratori Nazionali del Gran Sasso (LNGS) of the INFN designed to search for the rare neutrinoless double beta decay (0νββ) of76Ge. In its first phase, high purity germanium diodes inherited from the former Heidelberg-Moscow and Igexexperiments are operated “bare” and immersed in liquid argon, with an overall background environment of 10−2 cts/(keV·kg·yr), a factor of ten better than its predecessors. Measurements on two-neutrino double beta decay (2νββ) givingT1/22ν=(1.88±0.10)×1021 yrand recently published background model and pulse shape performances of the detectors are discussed in the paper. A new result on0νββhas been recently published with a half-life limit on0νββdecayT1/20ν>2.1×1025 yr(90% C.L.). A second phase of the experiment is scheduled to start during the year 2014, after a major upgrade shutdown. Thanks to the increased detector mass with new designed diodes and to the introduction of liquid argon instrumentation techniques, the experiment aims to reduce further the expected background to about 10−3 cts/(keV·kg·yr) and to improve the0νββsensitivity to aboutT1/20ν>1.5×1026 yr(90% C.L.).
Marine Invertebrate Natural Products for Anti-Inflammatory and Chronic Diseases
Authors: Senthilkumar Kalimuthu , Kim Se-Kwon
Published: December 2013

The marine environment represents a relatively available source of functional ingredients that can be applied to various aspects of food processing, storage, and fortification. Moreover, numerous marine invertebrates based compounds have biological activities and also interfere with the pathogenesis of diseases. Isolated compounds from marine invertebrates have been shown to pharmacological activities and are helpful for the invention and discovery of bioactive compounds, primarily for deadly diseases like cancer, acquired immunodeficiency syndrome (AIDS), osteoporosis, and so forth. Extensive research within the last decade has revealed that most chronic illnesses such as cancer, neurological diseases, diabetes, and autoimmune diseases exhibit dysregulation of multiple cell signaling pathways that have been linked to inflammation. On the basis of their bioactive properties, this review focuses on the potential use of marine invertebrate derived compounds on anti-inflammatory and some chronic diseases such as cardiovascular disease, osteoporosis, diabetes, HIV, and cancer.
Design and Implementation of Fuzzy Logic Controller for Online Computer Controlled Steering System for Navigation of a Teleoperated Agricultural Vehicle
Authors: Kannan Prema , Natarajan Senthil Kumar , Dash Subhransu Sekhar
Published: December 2013

This paper describes design, modeling, simulation, control, and implementation of teleoperated agricultural vehicle using intelligent technique. This vehicle can be used for ploughing, sowing, and soil moisture sensing. Online computer controlled steering system for a vehicle utilizing two independent drive wheels can be used to avoid obstacles and to improve the ability to resist external side forces. To control the steer angles of the nondriven wheels, the mathematical relationships between the drive wheel speeds and the steer angles of the nondriven wheels are used. A fuzzy logic controller is designed to change the drive wheel speeds and to achieve the desired steer angles. Online control of the agricultural vehicle is achieved from a remote place by means of Web Publishing Tool in LabVIEW. IR sensors in the vehicle are used to detect and to avoid the obstacles around. The developed steering angle control algorithm and fuzzy logic controller have been implemented in an agricultural vehicle which depicts that the vehicle performs its operation efficiently and reduces the manpower and becomes advantageous.
New BraidedT-Categories over Weak Crossed Hopf Group Coalgebras
Authors: Zhou Xuan , Yang Tao
Published: December 2013

LetHbe a weak crossed Hopf group coalgebra over groupπ; we first introduce a kind of newα-Yetter-Drinfel’d module categories𝒲𝒴𝒟α(H)forα∈πand use it to construct a braidedT-category𝒲𝒴𝒟(H). As an application, we give the concept of a Long dimodule categoryH𝒲ℒHfor a weak crossed Hopf group coalgebraHwith quasitriangular and coquasitriangular structures and obtain thatH𝒲ℒHis a braidedT-category by translating it into a weak Yetter-Drinfel'd module subcategory𝒲𝒴𝒟(H⊗H).
Nonlinear Pulse Vaccination in an SIR Epidemic Model with Resource Limitation
Authors: Qin Wenjie , Tang Sanyi , Cheke Robert A.
Published: December 2013

Mathematical models can assist in the design and understanding of vaccination strategies when resources are limited. Here we propose and analyse an SIR epidemic model with a nonlinear pulse vaccination to examine how a limited vaccine resource affects the transmission and control of infectious diseases, in particular emerging infectious diseases. The threshold condition for the stability of the disease free steady state is given. Latin Hypercube Sampling/Partial Rank Correlation Coefficient uncertainty and sensitivity analysis techniques were employed to determine the key factors which are most significantly related to the threshold value. Comparing this threshold value with that without resource limitation, our results indicate that if resources become limited pulse vaccination should be carried out more frequently than when sufficient resources are available to eradicate an infectious disease. Once the threshold value exceeds a critical level, both susceptible and infected populations can oscillate periodically. Furthermore, when the pulse vaccination period is chosen as a bifurcation parameter, the SIR model with nonlinear pulse vaccination reveals complex dynamics including period doubling, chaotic solutions, and coexistence of multiple attractors. The implications of our findings with respect to disease control are discussed.
Exact CS Reconstruction Condition of Undersampled Spectrum-Sparse Signals
Authors: Luo Ying , Zhang Qun , Wang Guozheng , Bai Youqing
Published: December 2013

Compressive sensing (CS) reconstruction of a spectrum-sparse signal from undersampled data is, in fact, an ill-posed problem. In this paper, we mathematically prove that, in certain cases, the exact CS reconstruction of a spectrum-sparse signal from undersampled data is impossible. Then we present the exact CS reconstruction condition of undersampled spectrum-sparse signals, which is valuable for digital signal compression.
Enhanced Water Splitting by Fe2O3‐TiO2‐FTO Photoanode with Modified Energy Band Structure
Authors: Noh Eul , Noh Kyung-Jong , Yun Kang-Seop , Kim Bo-Ra , Jeong Hee-June , Oh Hyo-Jin , Jung Sang-Chul , Kang Woo-Seung , Kim Sun-Jae
Published: December 2013

The effect of TiO2 layer applied to the conventional Fe2O3/FTO photoanode to improve the photoelectrochemical performance was assessed from the viewpoint of the microstructure and energy band structure. Regardless of the location of the TiO2 layer in the photoanodes, that is, Fe2O3/TiO2/FTO or TiO2/Fe2O3/FTO, high performance was obtained when α‐Fe2O3 and H‐TiNT/anatase‐TiO2 phases existed in the constituent Fe2O3 and TiO2 layers after optimized heat treatments. The presence of the Fe2O3 nanoparticles with high uniformity in the each layer of the Fe2O3/TiO2/FTO photoanode achieved by a simple dipping process seemed to positively affect the performance improvement by modifying the energy band structure to a more favorable one for efficient electrons transfer. Our current study suggests that the application of the TiO2 interlayer, together with α‐Fe2O3 nanoparticles present in the each constituent layers, could significantly contribute to the performance improvement of the conventional Fe2O3 photoanode.
All Terrain Vehicle Flexible Multibody Dynamic Simulation for Fatigue Prediction
Authors: Chen Jia-Shiun , Hwang Hsiu-Ying
Published: December 2013

This study presents the flexible-body dynamic analysis and simulated stress recovery of vehicle components to predict their lifetime when maneuvering on an uneven random road. The subject of this study was an all-terrain vehicle (ATV). The body frame and suspension system were modeled as flexible elements for multibody dynamic simulation. The simulations in this study revealed the stress from the flexible elements and predicted the component fatigue life using the retrieved stresses. This approach considers the interaction between dynamic forces and structure deformation and achieves more accurate structure stress prediction and fatigue life prediction.
The Pathways to the First Contact with Mental Health Services among Patients with Schizophrenia in Lagos, Nigeria
Authors: Adeosun Increase Ibukun , Adegbohun Abosede Adekeji , Adewumi Tomilola Adejoke , Jeje Oyetayo O.
Published: December 2013

There is increasing evidence that delay in the commencement of treatment, following the onset of schizophrenia, may be related to the pathways patients navigate before accessing mental health care. Therefore, insight into the pattern and correlates of pathways to mental care of patients with schizophrenia may inform interventions that could fast track their contact with mental health professionals and reduce the duration of untreated psychosis. This study assessed the pathways to mental health care among patients with schizophrenia (n=138), at their first contact with mental health services at the Federal Neuro-Psychiatric Hospital Yaba Lagos, Nigeria. Traditional and religious healers were the first contact for the majority (69%) of the patients. Service users who first contacted nonorthodox healers made a greater number of contacts in the course of seeking help, eventuating in a longer duration of untreated psychosis (P<0.001). However, the delay between the onset of psychosis and contact with the first point of care was shorter in patients who patronized nonorthodox practitioners. The findings suggest that collaboration between orthodox and nonorthodox health services could facilitate the contact of patients with schizophrenia with appropriate treatment, thereby reducing the duration of untreated psychosis. The need for public mental health education is also indicated.
NHCs Catalyzed Hydrophosphonylation of α‐Ketoesters and α‐Trifluoromethyl Ketones
Authors: He Lin , Cai Zhi-Hua , Pian Ji-Xin , Du Guang-Fen
Published: December 2013

N‐Heterocyclic carbenes catalyzed hydrophosphonylation reaction of α‐ketoesters and α‐trifluoromethyl ketones was developed. Under the catalysis of 10 mol% IPr, α‐ketoesters or α‐trifluoromethyl ketones reacted with dialkyl phosphites to provide quaternary α‐hydroxyphosphonates in good to excellent yield.
Newton-Kantorovich and Smale Uniform Type Convergence Theorem for a Deformed Newton Method in Banach Spaces
Authors: Lin Rongfei , Zhao Yueqing , Šmarda Zdeněk , Khan Yasir , Wu Qingbiao
Published: December 2013

Newton-Kantorovich and Smale uniform type of convergence theorem of a deformed Newton method having the third-order convergence is established in a Banach space for solving nonlinear equations. The error estimate is determined to demonstrate the efficiency of our approach. The obtained results are illustrated with three examples.
Unbiased Compound Screening Identifies Unexpected Drug Sensitivities and Novel Treatment Options for Gastrointestinal Stromal Tumors
Authors: Boichuk Sergei , Lee Derek J. , Mehalek Keith R. , Makielski Kathleen R. , Wozniak Agnieszka , Seneviratne Danushka S. , Korzeniewski Nina , Cuevas Rolando , Parry Joshua A. , Brown Matthew F. , Zewe James , Taguchi Takahiro , Kuan Shin-Fan , Schöffski Patrick , Debiec-Rychter Maria , Duensing Anette
Published: January 2014

Most gastrointestinal stromal tumors (GIST) are caused by oncogenic KIT or platelet-derived growth factor receptor activation, and the small molecule kinase inhibitor imatinib mesylate is an effective first-line therapy for metastatic or unresectable GIST. However, complete remissions are rare and most patients ultimately develop resistance, mostly because of secondary mutations in the driver oncogenic kinase. Hence, there is a need for novel treatment options to delay failure of primary treatment and restore tumor control in patients who progress under therapy with targeted agents. Historic data suggest that GISTs do not respond to classical chemotherapy, but systematic unbiased screening has not been performed. In screening a compound library enriched for U.S. Food and Drug Administration (FDA)–approved chemotherapeutic agents (NCI Approved Oncology Drugs Set II), we discovered that GIST cells display high sensitivity to transcriptional inhibitors and topoisomerase II inhibitors. Mechanistically, these compounds exploited the cells' dependency on continuous KIT expression and/or intrinsic DNA damage response defects, explaining their activity in GIST. Mithramycin A, an indirect inhibitor of the SP1 transcription factor, and mitoxantrone, a topoisomerase II inhibitor, exerted significant antitumor effects in mouse xenograft models of human GIST. Moreover, these compounds were active in patient-derived imatinib-resistant primary GIST cells, achieving efficacy at clinically relevant concentrations. Taken together, our findings reveal that GIST cells have an unexpectedly high and specific sensitivity to certain types of FDA-approved chemotherapeutic agents, with immediate implications for encouraging their clinical exploration. Cancer Res; 74(4); 1200–13. ©2014 AACR.
Associação de alelos do complexo principal de histocompatibilidade de classe II com a doença de graves, em pacientes brasileiros
Authors: Maciel Léa M.Z. , Rodrigues Sandra S. , Dibbern Ralph S. , Navarro Paula A.A. , Donadi Eduardo A.
Published: December 2013

A Doença de Graves (DG) é a causa mais freqüente de hipertireoidismo. Sua origem é multifatorial, complexa, na qual a susceptibilidade genética interage com o meio ambiente e fatores endógenos para causar a doença. Os alelos do Complexo Principal de Histocompatibilidade (CPH) de classe II têm sido associados com a DG, em populações de diferentes etnias e muitas evidências apontam para a associação do antígeno HLA-DR3 em caucasianos. O envolvimento dos alelos do CPH na nossa população, altamente miscigenada, foi estudado em pacientes com a DG e em indivíduos-controle da mesma área geográfica, utilizando-se DNA genômico amplificado e hibridado com iniciadores de seqüência específica (SSP). O alelo HLADRB1* 0301 esteve presente com maior freqüência (44,7%) em pacientes com DG, relativamente à população-controle (22,3%, pc=0,0068), conferindo Risco Relativo (RR) de 2,8 e uma Fração Etiológica de 28,7, enquanto o alelo HLA-DQB1*0602 esteve, significantemente, diminuído nesses pacientes (8%) em relação aos pacientes-controle (31,9%, pc=0,00062), conferindo RR de 1,8 e uma Fração Preventiva de 26,7. Apesar de a população brasileira ser altamente miscigenada, a confirmação do alelo HLA-DRB1*0301, conferindo susceptibilidade à doença, aponta esse alelo com um marcador importante na predisposição à doença. Em contraste, a proteção conferida pelo alelo HLA-DQB1*0602 parece ser peculiar aos pacientes brasileiros.
Como entender a nomenclatura e os mecanismos de associação entre os antígenos e os alelos de histocompatibildade com as doenças
Authors: Donadi Eduardo A.
Published: December 2013

Devido ao elevado grau de polimorfismo das moléculas e genes do Complexo Principal de Histocompatibilidade e às grandes mudanças ocorridas, recentemente, nos métodos de tipificação desses marcadores, tem havido muita confusão para o não especialista, em relação ao entendimento da nomenclatura do sistema. Além disso, devido ao crescente conhecimento acerca do papel das moléculas de histocompatibilidade na função imune, os mecanismos de associação das moléculas HLA com as doenças ainda constituem tópicos bastante complexos. Esta revisão abrange esses aspectos, tentando facilitar o entendimento da nomenclatura e a relevância desses marcadores imunogenéticos na determinação de susceptibilidade ou resistência às doenças.
Atendimento multiprofissional ao paciente com diabetes mellitus no ambulatório de diabetes do HCFMRP-USP
Authors: Ferraz Ana Emilia P. , Zanetti Maria Lúcia , Brandão Edith C.M. , Romeu Lídia C. , Foss Milton Cesar , Paccola Glória Maria G.F. , Paula Francisco José A. , Gouveia Leonor Maria F.B. , Montenegro Jr Renan
Published: December 2013

O presente estudo descreve o fluxo de atendimento e as atividades desenvolvidas pela equipe multiprofissional de saúde do Ambulatório de Endocrinologia e Metabologia do HCFMRPUSP, junto aos pacientes com diabetes mellitus. Este programa, em consonância aos propósitos da Declaração das Américas sobre Diabetes, visa assegurar que os pacientes com diabetes estejam em condições de adquirir conhecimentos e aptidões para o autocuidado.
Transplante de medula óssea
Authors: Thomas E. Donnall
Published: December 2013

O transplante de medula óssea evoluiu bastante nos últimos 50 anos. Observações laboratoriais e estudos experimentais definiram os elementos essenciais da biologia dos transplantes. As primeiras tentativas para replicar esses estudos em pacientes tiveram pouco sucesso. A definição de complexidade do sistema HLA humano tornou possível selecionar, como doadores, irmãos compativeis e, mais recentemente, doadores não relacionados. Transplantes de celulas tronco hematopoéticas da medula óssea, sangue periférico ou cordão umbilical são, agora, o tratamento de escolha para várias doenças hematológicas e genéticas. Transplantes usando regimes de condicionamento menos tóxicos para induzir quimerismo misto tornaram possível sua aplicação em doenças auto-imunes. Investigações clínicas e laboratoriais dirigidas à indução de tolerância imunologica e eliminação de células malignas abrem caminho para aplicações mais amplas do transplante de células tronco hematopoéticas na próxima década.
Efficacy and Safety of ETC-1002, a Novel Investigational Low-Density Lipoprotein-Cholesterol–Lowering Therapy for the Treatment of Patients With Hypercholesterolemia and Type 2 Diabetes Mellitus
Authors: Gutierrez Maria J. , Rosenberg Noah L. , MacDougall Diane E. , Hanselman Jeffrey C. , Margulies Janice R. , Strange Poul , Milad Mark A. , McBride Scott J. , Newton Roger S.
Published: January 2014

Objective—

8-Hydroxy-2,2,14,14-tetramethylpentadecanedioic acid (ETC-1002) is a small molecule with a unique mechanism of action shown in nonclinical studies to modulate pathways of cholesterol, fatty acid, and carbohydrate metabolism. In previous phase 2 clinical trials, once daily oral treatment with ETC-1002 significantly reduced low-density lipoprotein-cholesterol in patients with hypercholesterolemia. In this trial, the lipid-lowering efficacy of ETC-1002 was evaluated in patients with type 2 diabetes mellitus and hypercholesterolemia. Additional cardiometabolic biomarkers, including glycemic measures, were also assessed.

Approach and Results—

A single-center, double-blind, placebo-controlled trial evaluated 60 patients with type 2 diabetes mellitus and elevated low-density lipoprotein-cholesterol. Patients discontinued all diabetes mellitus and lipid-regulating drugs and were randomized to receive ETC-1002 80 mg QD for 2 weeks followed by 120 mg QD for 2 weeks or placebo for 4 weeks. ETC-1002 lowered low-density lipoprotein-cholesterol levels by 43±2.6% (least squares mean±SE), compared with a reduction of 4±2.5% by placebo at day 29 (
P
<0.0001; primary end point). Non–high-density lipoprotein-cholesterol and total cholesterol were also significantly lowered by ETC-1002 compared with placebo (
P
<0.0001). High-sensitivity C-reactive protein was reduced by 41% (median) compared with a placebo reduction of 11% (
P
=0.0011). No clinically meaningful safety findings were observed.

Conclusions—

ETC-1002 lowered low-density lipoprotein-cholesterol and other lipids and demonstrated improvement in high-sensitivity C-reactive protein in patients with type 2 diabetes mellitus and hypercholesterolemia without worsening glycemic control. ETC-1002 was well tolerated in this population.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT# 01607294.
Rho-Associated Kinase Activity Is a Predictor of Cardiovascular Outcomes
Authors: Kajikawa Masato , Noma Kensuke , Maruhashi Tatsuya , Mikami Shinsuke , Iwamoto Yumiko , Iwamoto Akimichi , Matsumoto Takeshi , Hidaka Takayuki , Kihara Yasuki , Chayama Kazuaki , Nakashima Ayumu , Goto Chikara , Liao James K. , Higashi Yukihito
Published: December 2013

Cardiovascular diseases are associated with chronic activation of Rho-associated kinase. Rho-associated kinase activity is significantly correlated with endothelial function and Framingham risk score. However, there is no information on the prognostic value of Rho-associated kinase activity. We evaluated Rho-associated kinase activity in peripheral leukocytes by Western blot analysis in 633 subjects who underwent health-screening examination at Hiroshima University Hospital. We assessed the associations between Rho-associated kinase activity and first major cardiovascular events (death from cardiovascular causes, myocardial infarction, and stroke), death from cardiovascular causes, acute myocardial infarction, stroke, revascularization (percutaneous coronary intervention, coronary artery bypass grafting), and hospitalization for heart failure. During a median period of 42.0 months (interquartile range, 24.4–56.6 months) of follow-up, 29 subjects died (10 from cardiovascular causes), 2 myocardial infarction, 20 revascularization, 15 stroke, and 17 hospitalization for heart failure. After adjustment for age, sex, cardiovascular risk factors, and other relevant variables, Rho-associated kinase activity remained a strong independent indicator of first major cardiovascular events (hazard ratio, 2.19; 95% confidence interval, 1.35–3.70;
P
=0.002), death from cardiovascular disease (hazard ratio, 2.57; 95% confidence interval, 1.18–6.60;
P
=0.002), stroke (hazard ratio, 2.14; 95% confidence interval, 1.24–3.86;
P
=0.006), and revascularization (hazard ratio, 2.68; 95% confidence interval, 1.60–4.66;
P
<0.001). Leukocyte Rho-associated kinase activity may be a new biomarker of cardiovascular events. These findings suggest that inhibition of Rho-associated kinase activity may be a therapeutic target for prevention of cardiovascular events.
NFAT5 Is Protective Against Ischemic Acute Kidney Injury
Authors: Hao Shoujin , Bellner Lars , Zhao Hong , Ratliff Brian B. , Darzynkiewicz Zbigniew , Vio Carlos P. , Ferreri Nicholas R.
Published: December 2013

NFAT5 is a transcription factor that protects the kidney from hypertonic stress and also is activated by hypoxia. We hypothesized that NFAT5 mitigates the extent of renal damage induced by ischemia–reperfusion injury (IRI). Mice were subjected to IRI by unilateral clamping of the left renal pedicle for 30 minutes followed by reperfusion. After 3 hours of reperfusion, the level of NFAT5 mRNA was similar in contralateral and clamped kidneys. However, after 48 hours, NFAT5 mRNA accumulation increased ≈3-fold in both outer medulla and medullary thick ascending limb tubules. NFAT1 levels were elevated at 3 hours but did not increase further at 48 hours. Mice were then either pretreated for 72 hours with an intrarenal injection of a lentivirus short-hairpin RNA construct to silence NFAT5 (enhanced green fluorescent protein-U6-N5-ex8) or a control vector (enhanced green fluorescent protein-U6) before induction of IRI. Neutrophil gelatinase–associated lipocalin and kidney ischemia molecule-1 mRNA levels increased after IRI and further increased after knockdown of NFAT5, suggesting that silencing of NFAT5 exacerbates renal damage during IRI. In contrast, silencing of NFAT1 had no effect on the levels of neutrophil gelatinase–associated lipocalin or kidney ischemia molecule-1 mRNA. Hematoxylin and eosin staining revealed patchy denudation of renal epithelial cells and tubular dilation when NFAT5 was silenced. The number of TUNEL-positive cells in the outer and inner medulla of the clamped kidney increased nearly 2-fold after knockdown of NFAT5 and was associated with an increase in the number of caspase-3–positive cells. Collectively, the data suggest that NFAT5 is part of a protective mechanism that limits renal damage induced by IRI.
Synergistic Effects of High Blood Cholesterol and Hypertension on Leukocyte and Platelet Recruitment in the Cerebral Microcirculation
Authors: Rodrigues Stephen F. , Almeida-Paula Lidiana D. , Granger Daniel N.
Published: December 2013

Hypertension or hypercholesterolemia can induce a proinflammatory and prothrombogenic phenotype in the microcirculation of the brain; however, less is known about how the combination of these risk factors affects the vasculature. We recently reported that a moderate (60%) increase in plasma cholesterol blunts the recruitment of leukocytes and platelets in the cerebral microvessels elicited by hypertension. In this study, we examined whether larger increments in blood cholesterol (4-fold) exerts a similar modulating influence on the vasculature in the presence of hypertension. Apolipoprotein E–knockout mice with deoxycorticosterone acetate salt–induced hypertension were placed on a high-cholesterol diet and exhibited exaggerated leukocyte and platelet adhesion responses in cerebral microvessels. Intermittent feeding (every fourth day) with high-cholesterol diet yielded similar phenotypic changes in the vasculature. Once the mice were placed on high-cholesterol diet, 4 days on normal diet (ND) were needed to revert to a normal vascular phenotype. Angiotensin II type 1 receptors and reactive oxygen species seem to contribute to the vascular responses induced by hypercholesterolemia and hypertension. Our findings indicate that the combination of hypertension and large increases in plasma cholesterol concentration results in a severe, but reversible, inflammatory and thrombogenic phenotype in the cerebral microvasculature.
d
‐Dimer Levels Over Time and the Risk of Recurrent Venous Thromboembolism: An Update of the Vienna Prediction Model
Authors: Eichinger Sabine , Heinze Georg , Kyrle Paul A.
Published: January 2014

Background

Patients with unprovoked venous thromboembolism (
VTE
) can be stratified according to their recurrence risk based on their sex, the
VTE
location, and
d
‐dimer measured 3 weeks after anticoagulation by the
V
ienna Prediction Model. We aimed to expand the model to also assess the recurrence risk from later points on.

Methods and Results

Five hundred and fifty‐three patients with a first
VTE
were followed for a median of 68 months. We excluded patients with
VTE
provoked by a transient risk factor or female hormone intake, with a natural inhibitor deficiency, the lupus anticoagulant, or cancer. The study end point was recurrent
VTE
, which occurred in 150 patients.
d
‐Dimer levels did not substantially increase over time. Subdistribution hazard ratios (95% confidence intervals) dynamically changed from 2.43 (1.57 to 3.77) at 3 weeks to 2.27 (1.48 to 3.48), 1.98 (1.30 to 3.02) , and 1.73 (1.11 to 2.69) at 3, 9, and 15 months in men versus women, from 1.84 (1.00 to 3.43) to 1.68 (0.91 to 3.10), 1.49 (0.79 to 2.81) , and 1.44 (0.76 to 2.72) in patients with proximal deep vein thrombosis or pulmonary embolism compared with calf vein thrombosis, and from 1.30 (1.07 to 1.58) to 1.27 (1.06 to 1.51), 1.20 (1.02 to 1.41), and 1.13 (0.95 to 1.36) per doubling
d
‐dimer. Using a dynamic landmark competing risks regression approach, we generated nomograms and a web‐based calculator to calculate risk scores and recurrence rates from multiple times after anticoagulation.

Conclusions

Risk of recurrent
VTE
after discontinuation of anticoagulation can be predicted from multiple random time points by integrating the patient's sex, location of first
VTE
, and serial
d
‐dimer measurements.
“Not the ‘Grim Reaper Service’”: An Assessment of Provider Knowledge, Attitudes, and Perceptions Regarding Palliative Care Referral Barriers in Heart Failure
Authors: Kavalieratos Dio , Mitchell Emma M. , Carey Timothy S. , Dev Sandesh , Biddle Andrea K. , Reeve Bryce B. , Abernethy Amy P. , Weinberger Morris
Published: January 2014

Background

Although similar to cancer patients regarding symptom burden and prognosis, patients with heart failure (
HF
) tend to receive palliative care far less frequently. We sought to explore factors perceived by cardiology, primary care, and palliative care providers to impede palliative care referral for
HF
patients.

Methods and Results

We conducted semistructured interviews regarding (1) perceived needs of patients with advanced
HF
; (2) knowledge, attitudes, and experiences with specialist palliative care; (3) perceived indications for and optimal timing of palliative care referral in
HF
; and (4) perceived barriers to palliative care referral. Two investigators analyzed data using template analysis, a qualitative technique. We interviewed 18 physician, nurse practitioner, and physician assistant providers from 3 specialties: cardiology, primary care, and palliative care. Providers had limited knowledge regarding what palliative care is, and how it can complement traditional
HF
therapy to decrease
HF
‐related suffering. Interviews identified several potential barriers: the unpredictable course of
HF
; lack of clear referral triggers across the
HF
trajectory; and ambiguity regarding what differentiates standard
HF
therapy from palliative care. Nevertheless, providers expressed interest for integrating palliative care into traditional
HF
care, but were unsure of how to initiate collaboration.

Conclusions

Palliative care referral for
HF
patients may be suboptimal due to limited provider knowledge and misperceptions of palliative care as a service reserved for those near death. These factors represent potentially modifiable targets for provider education, which may help to improve palliative care referral for
HF
patients with unresolved disease‐related burden.
Systematic Review and Meta-Analysis of Interventions Tested in Animal Models of Lacunar Stroke
Authors: Pedder Hugo , Vesterinen Hanna M. , Macleod Malcolm R. , Wardlaw Joanna M.
Published: January 2014

Background and Purpose—

A total of 25% of strokes are lacunar, and these are pathophysiologically different from large artery strokes. Despite emerging evidence of a substantial impact on physical disability and dementia, little attention has been paid to the development of specific treatments. The optimal use of the animal models of lacunar stroke used to test candidate interventions is not known.

Methods—

We conducted a systematic review and meta-analysis of studies testing candidate interventions in animal models of lacunar stroke. We used random-effects meta-analysis to assess the impact of study characteristics and trim and fill to seek evidence of publication bias.

Results—

The efficacy of 43 distinct interventions was described in 57 publications. The median number of quality checklist items scored was 3 of 8 (interquartile range, 2–4). Many models reflected mechanisms of limited relevance to lacunar stroke. Meta-analysis of results from 27 studies showed that on average, infarct size and neurobehavioral outcome were improved by 34.2% (24.1–44.2) and 0.82 standardized mean difference (0.51–1.14), respectively. Four interventions improved both infarct size and neurobehavioral outcome but there were insufficient data for this finding to be considered robust. For infarct size, efficacy was lower in studies reporting blinding and higher in studies reporting randomization. For neurobehavior, efficacy was lower in randomized studies. For infarct size there was evidence of publication bias.

Conclusions—

No intervention has yet been tested in sufficient range and depth to support translation to clinical trial. There is limited reporting of measures to reduce the risk of bias and evidence for a substantial publications bias.
Cost-Effectiveness of Optimizing Acute Stroke Care Services for Thrombolysis
Authors: Penaloza-Ramos Maria Cristina , Sheppard James P. , Jowett Sue , Barton Pelham , Mant Jonathan , Quinn Tom , Mellor Ruth M. , Sims Don , Sandler David , McManus Richard J. ,   Birmingham and Black Country Collaborations for Leadership in Applied Health Research and Care investigators include:, Carr Peter , Greenfield Sheila , Helliwell Brin , Nand Cristina , Phillips Norman , Scott Rob , Singh Satinder , Ward Matthew
Published: January 2014

Background and Purpose—

Thrombolysis in acute stroke is effective up to 4.5 hours after symptom onset but relies on early recognition, prompt arrival in hospital, and timely brain scanning. This study aimed to establish the cost-effectiveness of increasing thrombolysis rates through a series of hypothetical change strategies designed to optimize the acute care pathway for stroke.

Methods—

A decision-tree model was constructed, which relates the acute management of patients with suspected stroke from symptom onset to outcome. Current practice was modeled and compared with 7 change strategies designed to facilitate wider eligibility for thrombolysis. The model basecase consisted of data from consenting patients following the acute stroke pathway recruited in participating hospitals with data on effectiveness of treatment and costs from published sources.

Results—

All change strategies were cost saving while increasing quality-adjusted life years gained. Using realistic estimates of effectiveness, the change strategy with the largest potential benefit was that of better recording of onset time, which resulted in 3.3 additional quality-adjusted life years and a cost saving of US $46 000 per 100 000 population. All strategies increased the number of thrombolysed patients and the number requiring urgent brain imaging (by 9% to 21% dependent on the scenario). Assuming a willingness-to-pay of US $30 000 per quality-adjusted life year gained, the potential budget available to deliver the interventions in each strategy ranged from US $50 000 to US $144 000.

Conclusions—

These results suggest that any strategy that increases thrombolysis rates will result in cost savings and improved patient quality of life. Healthcare commissioners could consider this model when planning improvements in stroke care.
Revision of Chinese Dilaridae (Insecta: Neuroptera) (Part I): Species of the genus Dilar Rambur from northern China
Authors: ZHANG WEI , LIU XINGYUE , ASPöCK HORST , ASPÖCK ULRIKE
Published: January 2014

The pleasing lacewing genus Dilar Rambur is a dominant group of the family Dilaridae in Asia and is diverse in China with 18 described species. Herein we record five species of Dilar. Three species, i.e. Dilar hastatus sp.nov., Dilar spectabilis sp.nov. and Dilar taibaishanus sp.nov. are described as new to science. Dilar sinicus Nakahara and Dilar septentrionalis Navás are also redescribed. A key to the species of Dilar from northern China is given.