bluuebunny/crossref_metadata_2025 huggingface dataset:
Republished curriculum based clinical review: IBD: reproductive health, pregnancy and lactation
Authors: Hendy Philip , Chadwick Georgina , Hart Ailsa
Published: April 2015

The peak incidence of inflammatory bowel diseases (IBD) occurs during the child-bearing years, and so questions about fertility, pregnancy and breast feeding are often asked by patients. It is known that patients with IBD receive twice as much information about pregnancy-related issues from gastroenterologists as from any other source (including the internet). Therefore, the role of the gastroenterologist in correctly educating patients to avoid misconceptions is paramount, and this should be done proactively prior to planning pregnancy so that the patient's health and medications can be optimised. A clear understanding of medication safety during pregnancy and lactation will improve clinical management.
Adinkras, 0-branes, holoraumy and the SUSY QFT/QM correspondence
Authors: Calkins Mathew , Gates D. E. A. , Gates S. James , Stiffler Kory
Published: April 2015

We propose the recently defined "Holoraumy Tensor" to play a critical role in defining a metric to establish a correspondence between 4D, [Formula: see text]-extended 0-brane-based valise supermultiplet representations and, correspondingly via "SUSY Holography," on the space of 1D, N-extended network-based adinkras. Using an analogy with the su(3) algebra, it is argued the 0-brane holoraumy tensors play the role of the " d -coefficients" and provide a newly established tool for investigating supersymmetric representation theory.
Visual Stimulus Background Effects on SSVEP-Based BCI Towards a Practical Robot Car Control
Authors: Shu Xiaokang , Yao Lin , Meng Jianjun , Sheng Xinjun , Zhu Xiangyang
Published: April 2015

Flickering source is an indispensable component in steady-state visual evoked potentials (SSVEPs)-based brain–computer interface (BCI), and its background severely influences the potentials evoked by the repetitive stimuli. In this paper, we investigated the problem under three different backgrounds in the context of the SSVEP-BCI-based robot car control, including black screen, static scene and dynamic scene of the environment. In the ten subjects experiment, we found significant decrease in SSVEP amplitude in dynamic scene condition compared to the reference condition black screen (p < 0.05), which resulted in classification accuracy decrease as evaluated by 10-fold cross validation. However, our proposed experiment paradigm has shown that training with static scene or dynamic scene condition could well compensate this performance drop and improve the online robot car control with real-time video feedback. The addressed problem in our application would provide some valuable suggestions when translating the SSVEP-BCI from laboratory exploration into practical usages.
Chronic ethanol consumption disrupts diurnal rhythms of hepatic glycogen metabolism in mice
Authors: Udoh Uduak S. , Swain Telisha M. , Filiano Ashley N. , Gamble Karen L. , Young Martin E. , Bailey Shannon M.
Published: April 2015

Chronic ethanol consumption has been shown to significantly decrease hepatic glycogen content; however, the mechanisms responsible for this adverse metabolic effect are unknown. In this study, we examined the impact chronic ethanol consumption has on time-of-day-dependent oscillations (rhythms) in glycogen metabolism processes in the liver. For this, male C57BL/6J mice were fed either a control or ethanol-containing liquid diet for 5 wk, and livers were collected every 4 h for 24 h and analyzed for changes in various genes and proteins involved in hepatic glycogen metabolism. Glycogen displayed a robust diurnal rhythm in the livers of mice fed the control diet, with the peak occurring during the active (dark) period of the day. The diurnal glycogen rhythm was significantly altered in livers of ethanol-fed mice, with the glycogen peak shifted into the inactive (light) period and the overall content of glycogen decreased compared with controls. Chronic ethanol consumption further disrupted diurnal rhythms in gene expression (glycogen synthase 1 and 2, glycogenin, glucokinase, protein targeting to glycogen, and pyruvate kinase), total and phosphorylated glycogen synthase protein, and enzyme activities of glycogen synthase and glycogen phosphorylase, the rate-limiting enzymes of glycogen metabolism. In summary, these results show for the first time that chronic ethanol consumption disrupts diurnal rhythms in hepatic glycogen metabolism at the gene and protein level. Chronic ethanol-induced disruption in these daily rhythms likely contributes to glycogen depletion and disruption of hepatic energy homeostasis, a recognized risk factor in the etiology of alcoholic liver disease.
Echocardiography and invasive hemodynamics during stress testing for diagnosis of heart failure with preserved ejection fraction: an experimental study
Authors: Leite Sara , Oliveira-Pinto José , Tavares-Silva Marta , Abdellatif Mahmoud , Fontoura Dulce , Falcão-Pires Inês , Leite-Moreira Adelino F. , Lourenço André P.
Published: April 2015

Inclusion of exercise testing in diagnostic guidelines for heart failure with preserved ejection fraction (HFpEF) has been advocated, but the target population, technical challenges, and underlying pathophysiological complexity raise difficulties to implementation. Hemodynamic stress tests may be feasible alternatives. Our aim was to test Trendelenburg positioning, phenylephrine, and dobutamine in the ZSF1 obese rat model to find echocardiographic surrogates for end-diastolic pressure (EDP) elevation and HFpEF. Seventeen-week-old Wistar-Kyoto, ZSF1 lean, and obese rats ( n = 7 each) randomly and sequentially underwent (crossover) Trendelenburg (30°), 5 μg·Kg−1·min−1 dobutamine, and 7.5 μg·Kg−1·min−1 phenylephrine with simultaneous left ventricular (LV) pressure-volume loop and echocardiography evaluation under halogenate anesthesia. Effort testing with maximum O2 consumption (V̇o2 max) determination was performed 1 wk later. Obese ZSF1 showed lower effort tolerance and V̇o2 max along with higher resting EDP. Both Trendelenburg and phenylephrine increased EDP, whereas dobutamine decreased it. Significant correlations were found between EDP and 1) peak early filling Doppler velocity of transmitral flow (E) to corresponding myocardial tissue Doppler velocity (E′) ratio, 2) E to E-wave deceleration time (E/DT) ratio, and 3) left atrial area (LAA). Diagnostic efficiency of E/DT*LAA by receiver-operating characteristic curve analysis for elevation of EDP above a cut-off of 13 mmHg during hemodynamic stress was high (area under curve, AUC = 0.95) but not higher than that of E/E′ (AUC = 0.77, P = 0.15). Results in ZSF1 obese rats suggest that noninvasive echocardiography after hemodynamic stress induced by phenylephrine or Trendelenburg can enhance diagnosis of stable HFpEF and constitute an alternative to effort testing.
The matrikine PGP as a potential biomarker in COPD
Authors: Abdul Roda Mojtaba , Fernstrand Amanda M. , Redegeld Frank A. , Blalock J. Edwin , Gaggar Amit , Folkerts Gert
Published: April 2015

The lack of a well-characterized biomarker for the diagnosis of chronic obstructive pulmonary disease (COPD) has increased interest toward finding one, because this would provide potential insight into disease pathogenesis and progression. Since persistent neutrophilia is an important hallmark in COPD Pro-Gly-Pro (PGP), an extracellular matrix-derived neutrophil chemoattractant, has been suggested to be a potential biomarker in COPD. The purpose of this review is to critically examine both biological and clinical data related to the role of PGP in COPD, with particular focus on its role as a clinical biomarker and potential therapeutic target in disease. The data provided in this review will offer insight into the potential use of PGP as end point for future clinical studies in COPD lung disease. Following PGP levels during disease might serve as a guide for the progression of lung disorders.
Remodeling of alveolar septa after murine pneumonectomy
Authors: Ysasi Alexandra B. , Wagner Willi L. , Bennett Robert D. , Ackermann Maximilian , Valenzuela Cristian D. , Belle Janeil , Tsuda Akira , Konerding Moritz A. , Mentzer Steven J.
Published: April 2015

In most mammals, removing one lung (pneumonectomy) results in the compensatory growth of the remaining lung. In mice, stereological observations have demonstrated an increase in the number of mature alveoli; however, anatomic evidence of the early phases of alveolar growth has remained elusive. To identify changes in the lung microstructure associated with neoalveolarization, we used tissue histology, electron microscopy, and synchrotron imaging to examine the configuration of the alveolar duct after murine pneumonectomy. Systematic histological examination of the cardiac lobe demonstrated no change in the relative frequency of dihedral angle components (Ends, Bends, and Junctions) ( P > 0.05), but a significant decrease in the length of a subset of septal ends (“E”). Septal retraction, observed in 20–30% of the alveolar ducts, was maximal on day 3 after pneumonectomy ( P < 0.01) and returned to baseline levels within 3 wk. Consistent with septal retraction, the postpneumonectomy alveolar duct diameter ratio (Dout:Din) was significantly lower 3 days after pneumonectomy compared to all controls except for the detergent-treated lung ( P < 0.001). To identify clumped capillaries predicted by septal retraction, vascular casting, analyzed by both scanning electron microscopy and synchrotron imaging, demonstrated matted capillaries that were most prominent 3 days after pneumonectomy. Numerical simulations suggested that septal retraction could reflect increased surface tension within the alveolar duct, resulting in a new equilibrium at a higher total energy and lower surface area. The spatial and temporal association of these microstructural changes with postpneumonectomy lung growth suggests that these changes represent an early phase of alveolar duct remodeling.
Adapted approach to profile genes while reconciling Vegf-a mRNA expression in the developing and injured lung
Authors: Lee Daniel D. , Schwarz Margaret A.
Published: April 2015

During lung development and injury, messenger RNA (mRNA) transcript levels of genes fluctuate over both space and time. Quantitative PCR (qPCR) is a highly sensitive, widely used technique to measure the mRNA levels. The sensitivity of this technique can be disadvantageous and errors amplified when each qPCR assay is not validated. In contrast to other organs, lungs have high RNase activity, resulting in less than optimal RNA integrity. We implemented a strategy to address these limitations in developing and injured lungs. Parameters were established and a filter designed that optimized amplicon length and included or excluded samples based on RNA integrity. This approach was illustrated and validated by measuring mRNA levels including Vegf-a in newborn mouse lungs that were injured by 85% oxygen (hyperoxia) for 12 days and compared with control (normoxia). We demonstrate that, in contrast to contradictory Vegf-a expression when normalized to the least suitable housekeeping genes, application of this filter and normalization to most suitable three housekeeping genes, Hprt, Eef2, and Rpl13a, gave reproducible Vegf-a expression, thus corroborating the sample filter. Accordingly, both short amplicon length and proper normalization to ranked, evaluated genes minimized erroneous fluctuation and qPCR amplification issues associated with nonideal RNA integrity in injured and developing lungs. Furthermore, our work uncovers how RNA integrity, purity, amplicon length, and discovery of stable candidate reference genes enhance precision of qPCR results and utilizes the advantages of qPCR in developmental studies.
Role of calcium ions in the positive interaction between TRPA1 and TRPV1 channels in bronchopulmonary sensory neurons
Authors: Hsu Chun-Chun , Lee Lu-Yuan
Published: April 2015

Both transient receptor potential ankyrin 1 (TRPA1) and vanilloid 1 (TRPV1) receptors are abundantly expressed in bronchopulmonary C-fiber sensory nerves and can be activated by a number of endogenous inflammatory mediators. A recent study has reported a synergistic effect of simultaneous TRPA1 and TRPV1 activations in vagal pulmonary C-fiber afferents in anesthetized rats, but its underlying mechanism was not known. This study aimed to characterize a possible interaction between these two TRP channels and to investigate the potential role of Ca2+as a mediator of this interaction in isolated rat vagal pulmonary sensory neurons. Using the perforated patch-clamp recording technique, our study demonstrated a distinct positive interaction occurring abruptly between TRPA1 and TRPV1 when they were activated simultaneously by their respective agonists, capsaicin (Cap) and allyl isothiocyanate (AITC), at near-threshold concentrations in these neurons. AITC at this low concentration evoked only minimal or undetectable responses, but it markedly amplified the Cap-evoked current in the same neurons. This potentiating effect was eliminated when either AITC or Cap was replaced by non-TRPA1 and non-TRPV1 chemical activators of these neurons, demonstrating the selectivity of the interaction between these two TRP channels. Furthermore, when Ca2+was removed from the extracellular solution, the synergistic effect of Cap and AITC on pulmonary sensory neurons was completely abrogated, clearly indicating a critical role of Ca2+in mediating the action. These results suggest that this TRPA1-TRPV1 interaction may play a part in regulating the sensitivity of pulmonary sensory neurons during airway inflammatory reaction.
Selective optogenetic stimulation of the retrotrapezoid nucleus in sleeping rats activates breathing without changing blood pressure or causing arousal or sighs
Authors: Burke Peter G. R. , Kanbar Roy , Viar Kenneth E. , Stornetta Ruth L. , Guyenet Patrice G.
Published: April 2015

Combined optogenetic activation of the retrotrapezoid nucleus (RTN; a CO2/proton-activated brainstem nucleus) with nearby catecholaminergic neurons (C1 and A5), or selective C1 neuron stimulation, increases blood pressure (BP) and breathing, causes arousal from non-rapid eye movement (non-REM) sleep, and triggers sighs. Here we wished to determine which of these physiological responses are elicited when RTN neurons are selectively activated. The left rostral RTN and nearby A5 neurons were transduced with channelrhodopsin-2 (ChR2+) using a lentiviral vector. Very few C1 cells were transduced. BP, breathing, EEG, and neck EMG were monitored. During non-REM sleep, photostimulation of ChR2+neurons (20s, 2-20 Hz) instantly increased V̇e without changing BP (13 rats). V̇e and BP were unaffected by light in nine control (ChR2−) rats. Photostimulation produced no sighs and caused arousal (EEG desynchronization) more frequently in ChR2+than ChR2−rats (62 ± 5% of trials vs. 25 ± 2%; P < 0.0001). Six ChR2+rats then received spinal injections of a saporin-based toxin that spared RTN neurons but destroyed surrounding catecholaminergic neurons. Photostimulation of the ChR2+neurons produced the same ventilatory stimulation before and after lesion, but arousal was no longer elicited. Overall (all ChR2+rats combined), ΔV̇e correlated with the number of ChR2+RTN neurons whereas arousal probability correlated with the number of ChR2+catecholaminergic neurons. In conclusion, RTN neurons activate breathing powerfully and, unlike the C1 cells, have minimal effects on BP and have a weak arousal capability at best. A5 neuron stimulation produces little effect on breathing and BP but does appear to facilitate arousal.
TGFβ Is a Master Regulator of Radiation Therapy-Induced Antitumor Immunity
Authors: Vanpouille-Box Claire , Diamond Julie M. , Pilones Karsten A. , Zavadil Jiri , Babb James S. , Formenti Silvia C. , Barcellos-Hoff Mary Helen , Demaria Sandra
Published: April 2015

T cells directed to endogenous tumor antigens are powerful mediators of tumor regression. Recent immunotherapy advances have identified effective interventions to unleash tumor-specific T-cell activity in patients who naturally develop them. Eliciting T-cell responses to a patient's individual tumor remains a major challenge. Radiation therapy can induce immune responses to model antigens expressed by tumors, but it remains unclear whether it can effectively prime T cells specific for endogenous antigens expressed by poorly immunogenic tumors. We hypothesized that TGFβ activity is a major obstacle hindering the ability of radiation to generate an in situ tumor vaccine. Here, we show that antibody-mediated TGFβ neutralization during radiation therapy effectively generates CD8+ T-cell responses to multiple endogenous tumor antigens in poorly immunogenic mouse carcinomas. Generated T cells were effective at causing regression of irradiated tumors and nonirradiated lung metastases or synchronous tumors (abscopal effect). Gene signatures associated with IFNγ and immune-mediated rejection were detected in tumors treated with radiation therapy and TGFβ blockade in combination but not as single agents. Upregulation of programmed death (PD) ligand-1 and -2 in neoplastic and myeloid cells and PD-1 on intratumoral T cells limited tumor rejection, resulting in rapid recurrence. Addition of anti–PD-1 antibodies extended survival achieved with radiation and TGFβ blockade. Thus, TGFβ is a fundamental regulator of radiation therapy's ability to generate an in situ tumor vaccine. The combination of local radiation therapy with TGFβ neutralization offers a novel individualized strategy for vaccinating patients against their tumors. Cancer Res; 75(11); 2232–42. ©2015 AACR.
Sintomas mentais em homeopatia versus neurociência em medicina veterinária
Authors: Prada Irvenia Luiza de Santis , Prada Marcela De Santis
Published: April 2015

O objetivo deste estudo foi o de conhecer a devida correspondência entre os sintomas mentais considerados na homeopatia e as várias regiões e estruturas identificáveis no encéfalo dos animais. Os resultados obtidos mostraram que as sensações e emoções muito primitivas, como medos e fobias, interagem pontualmente com regiões evolutivamente também muito primitivas do cérebro (como amígdala e núcleos septais), enquanto sentimentos “nobres” como afeto e lealdade interagem holisticamente com várias estruturas cerebrais evolutivamente mais recentes, tais como as áreas neocorticais terciárias associativas (área pré-frontal e temporal). No primeiro caso, as manifestações orgânicas são mediadas pelo sistema nervoso autônomo com sinais fisiológicos de taquicardia, elevação da pressão arterial, vasoconstrição periférica, eriçamento de pelos, midríase e secreção de hormônios como adrenalina e cortisol (disfluência comportamental), enquanto na outra situação apontada, eventuais manifestações orgânicas são harmoniosas e serenas (fluência comportamental). O conteúdo de todo o texto do trabalho é indicativo do interesse prático dos dados obtidos para o clínico veterinário homeopata, ressaltando-se nesse contexto a validação do uso de repertórios homeopáticos humanos na clínica veterinária, evidentemente com as devidas precauções sempre balizadas pelo bom senso do profissional.
“Breves notas sobre a responsabilidade civil nas cirurgias plásticas reparadora, estética e de transgenitalização e nos tratamentos dermatológicos. Análise da jurisprudência”
Authors: Gonçalves Camila de Jesus Mello
Published: April 2015

A responsabilidade civil é um dos institutos do direito privado que mais permite a criatividade do jurista. Na regulamentação da matéria, a lei estabelece o dever de indenizar, mas deixa a cargo do profissional do direito a verificação da existência do ilícito no caso concreto. Essa abertura torna fértil o campo da doutrina e da jurisprudência, na construção dogmática do conteúdo e dos limites da responsabilidade civil.
 No caso do cirurgião plástico, a responsabilidade civil envolve importantes questões. As mais relevantes são a origem da responsabilidade, se contratual ou extracontratual; a natureza da responsabilidade, se subjetiva ou objetiva; a natureza da obrigação, se de meio ou de resultado; e a classificação da atividade médica como de risco ou-não. Por se tratar de relação de consumo, as particularidades da relação médico-paciente sob o enfoque do dever de informação igualmente são relevantes.
 Neste artigo, pretendeu-se tratar cada um desses temas, a partir das especificidades das diversas cirurgias plásticas, inclusive da operação de mudança de sexo do transexual, denominada cirurgia de transgenitalização e dos tratamentos dermatológicos. Além da doutrina nacional e estrangeira, foram trazidas decisões judiciais em diferentes sentidos, com vistas a ilustrar a complexidade do tema e a necessidade de aprofundamento da reflexão.
 Pela análise do Código Civil, do Código de Defesa do Consumidor e de normas do Conselho Federal de Medicina procurou-se estabelecer pontos de contato e enfrentar as aparentes contradições, na tentativa de contribuir para a construção dogmática da responsabilidade civil do médico na cirurgia plástica.
Juridicidade: uma abordagem crítica à monolatria jurídica enquanto obstáculo epistemológico
Authors: Villas Bôas Filho Orlando
Published: April 2015

Este artigo analisa a obra de Étienne Le Roy e, em especial, sua crítica à tendência dos juristas em atribuir uma universalidade ao direito ocidental. Para tanto, centrase na noção de juridicidade, proposta pelo autor, a fim de mostrar que o direito ocidental nada mais seria que um subproduto de um fenômeno mais amplo de regulação. Assim, por meio do resgate da articulação entre direito e juridicidade no pensamento de Étienne Le Roy, procura-se demonstrar que a concepção de direito construída no Ocidente estaria atrelada a uma visão de mundo marcada pela monolatria que, como consequência, geraria uma representação do direito naturalmente vocacionada ao monismo. Ao ressaltar que o direito ocidental consiste apenas em uma forma particular de expressão da juridicidade, o artigo procura apresentar a tese do multijuridismo sugerida pelo autor, indicando sua afinidade com a discussão relativa ao pluralismo jurídico e sua incompatibilidade com o pressuposto monólatra que orienta a visão tradicional do direito construída no Ocidente moderno. Finalmente, são feitas uma breve análise da noção de transmodernidade e uma indicação ilustrativa de alguns temas em curso no debate brasileiro para os quais a teoria do autor pode fornecer um aporte frutífero.
Carta dos Direitos Fundamentais da União Europeia e Declaração Sociolaboral do Mercosul: origem, natureza jurídica e aplicabilidade
Authors: Silva Walküre Lopes Ribeiro da
Published: April 2015

Este artigo analisa, comparativamente, a Carta dos Direitos Fundamentais da União Europeia e a Declaração Sociolaboral do Mercosul, quanto à origem, natureza jurídica e aplicabilidade.
Contratualismo, utilitarismo, a emergência do indivíduo e da cooperação I: os fundamentos metodológicos e metafísicos das instituições do Estado e do Mercado
Authors: Chiappin José Raymundo Novaes , Leister Carolina
Published: April 2015

O escopo deste artigo é proceder a uma aplicação do programa racionalista na solução de problemas políticos, jurídicos e econômicos: o problema da emergência da cooperação entre indivíduos interagentes. Esse problema emerge com o estabelecimento por Descartes do núcleo central do programa racionalista com a tese ontológica do indivíduo como agente racional e autônomo e da geometria como modelo da ciência. O modelo de escolha racional composto das faculdades do entendimento e da vontade transforma o indivíduo em agente responsável e no fundamento, com Hobbes, do Direito Civil e Penal. Hobbes aplica o programa racionalista para construir o programa contratualista, e, com este, uma nova imagem do mundo político e econômico rompendo com a metafísica do mundo aristotélico. O estado é a solução de Hobbes para a cooperação. O programa racionalista clássico é substituído pelo do racionalismo neoclássico com Hume que o aplica na construção do programa utilitarista em substituição ao contratualismo. O mercado, e sua combinação com o Estado, é a solução do utilitarismo para a cooperação. A compreensão da construção e desenvolvimento dos programas contratualista e utilitarista na solução de problemas sociais depende da compreensão da relação entre a metafísica e da metodologia da nova imagem do mundo com a política, o direito, e a economia como ciência, os instrumentos da construção da nova imagem do mundo.
Exercícios gramaticais no ensino de paisagismo experiências didáticas em diferentes contextos: UFU/Uberlância e UNIFOR/Fortaleza
Authors: Cocozza Glauco de Paula , Rocha Fernanda Cláudia Lacerda
Published: April 2015

Este artigo apresenta alguns exercícios gramaticais aplicados na disciplina de Paisagismo da Universidade Federal de Uberlândia e da Universidade de Fortaleza, apresentando a metodologia aplicada, os temas sugeridos para os exercícios, a sua relação com a ementa da disciplina, os reflexos no aprendizado, e como eles possibilitam uma interpretação dos conceitos e práticas que o paisagismo propicia. Essa temática não é recente, alguns professores adotam metodologias semelhantes, variando o tema, a articulação com conteúdos ministrados e a forma de abordagens. O objetivo deste trabalho é apresentar como os exercícios são pensados na disciplina, como são executados e de que modo se relacionam ao trabalho final entregue como síntese da disciplina de Paisagismo.
Dimethylarginine Dimethylaminohydrolase 2 Regulates Nitric Oxide Synthesis and Hemodynamics and Determines Outcome in Polymicrobial Sepsis
Authors: Lambden Simon , Kelly Peter , Ahmetaj-Shala Blerina , Wang Zhen , Lee Benjamin , Nandi Manasi , Torondel Belen , Delahaye Matthew , Dowsett Laura , Piper Sophie , Tomlinson James , Caplin Ben , Colman Lucy , Boruc Olga , Slaviero Anna , Zhao Lan , Oliver Eduardo , Khadayate Sanjay , Singer Mervyn , Arrigoni Francesca , Leiper James
Published: April 2015

Objective—

Nitric oxide is a key to numerous physiological and pathophysiological processes. Nitric oxide production is regulated endogenously by 2 methylarginines, asymmetric dimethylarginine (ADMA) and monomethyl-
l
-arginine. The enzyme that specifically metabolizes asymmetric dimethylarginine and monomethyl-
l
-arginine is dimethylarginine dimethylaminohydrolase (DDAH). The first isoform dimethylarginine dimethylaminohydrolase 1 has previously been shown to be an important regulator of methylarginines in both health and disease. This study explores for the first time the role of endogenous dimethylarginine dimethylaminohydrolase 2 in regulating cardiovascular physiology and also determines the functional impact of dimethylarginine dimethylaminohydrolase 2 deletion on outcome and immune function in sepsis.

Approach and Results—

Mice, globally deficient in Ddah2, were compared with their wild-type littermates to determine the physiological role of Ddah2 using in vivo and ex vivo assessments of vascular function. We show that global knockout of Ddah2 results in elevated blood pressure during periods of activity (mean [SEM], 118.5 [1.3] versus 112.7 [1.1] mm Hg;
P
=0.025) and changes in vascular responsiveness mediated by changes in methylarginine concentration, mean myocardial tissue asymmetric dimethylarginine (SEM) was 0.89 (0.06) versus 0.67 (0.05) μmol/L (
P
=0.02) and systemic nitric oxide concentrations. In a model of severe polymicrobial sepsis, Ddah2 knockout affects outcome (120-hour survival was 12% in Ddah2 knockouts versus 53% in wild-type animals;
P
<0.001). Monocyte-specific deletion of Ddah2 results in a similar pattern of increased severity to that seen in globally deficient animals.

Conclusions—

Ddah2 has a regulatory role both in normal physiology and in determining outcome of severe polymicrobial sepsis. Elucidation of this role identifies a mechanism for the observed relationship between Ddah2 polymorphisms, cardiovascular disease, and outcome in sepsis.
Enhanced Pulmonary Vasodilator Reserve and Abnormal Right Ventricular
Authors: Andersen Mads J. , Hwang Seok-Jae , Kane Garvan C. , Melenovsky Vojtech , Olson Thomas P. , Fetterly Kenneth , Borlaug Barry A.
Published: April 2015

Background—

Pulmonary hypertension and right ventricular (RV) dysfunction are common in patients with advanced heart failure with preserved ejection fraction (HFpEF), yet their underlying mechanisms remain poorly understood. We sought to examine RV–pulmonary artery (PA) functional reserve responses and RV–PA coupling at rest and during β-adrenergic stimulation in subjects with earlier stage HFpEF.

Methods and Results—

In a prospective trial, subjects with HFpEF (n=39) and controls (n=18) underwent comprehensive invasive and noninvasive hemodynamic assessment using high fidelity micromanometer catheters, echocardiography, and expired gas analysis at rest and during dobutamine infusion. HFpEF subjects displayed similar RV structure but significantly impaired RV systolic (lower RV d
P
/d
t
max
/IP and s′) and diastolic function (higher RV τ) coupled with more severe pulmonary vascular disease, manifest by higher PA pressures, higher PA resistance, and lower PA compliance compared with controls. Dobutamine infusion caused greater pulmonary vasodilation in HFpEF compared with controls, with enhanced reductions in PA resistance, greater increase in PA compliance, and a more negative slope in the PA pressure–flow relationship when compared with controls (all
P
<0.001). RV–PA coupling analysis revealed that dobutamine improved RV ejection in HFpEF subjects through afterload reduction alone, rather than through enhanced contractility, indicating RV systolic reserve dysfunction.

Conclusions—

Pulmonary hypertension in early stage HFpEF is related to partially reversible pulmonary vasoconstriction coupled with RV systolic and diastolic dysfunction, even in the absence of RV structural remodeling. Pulmonary vascular tone is more favorably responsive to β-adrenergic stimulation in HFpEF than controls, suggesting a potential role for β-agonists in the treatment of patients with HFpEF and pulmonary hypertension.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT01418248.
Cerebrovascular Events After a Primary Percutaneous Coronary Intervention Strategy for Acute ST-Segment– Elevation Myocardial Infarction
Authors: Nikolsky Eugenia , Mehran Roxana , Dangas George D. , Xu Ke , Parvataneni Rupa , Witzenbichler Bernhard , Guagliumi Giulio , Kornowski Ran , Généreux Philippe , Brener Sorin J. , Stone Gregg W.
Published: April 2015

Background—

Patients with ST-segment–elevation myocardial infarction are at increased risk of cerebrovascular events. We assessed the incidence, predictors, and implications of cerebrovascular events in patients with ST-segment–elevation myocardial infarction managed with a primary percutaneous coronary intervention strategy.

Methods and Results—

In the Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction (HORIZONS-AMI) trial, 72 of 3602 patients (2.0%) experienced at least 1 cerebrovascular event (stroke: 63 patients; transient ischemic attack: 12 patients) during the 3-year follow-up (40.3% within 30 days, 20.8% between 30 days and 1 year, and 38.9% between 1 and 3 years). Stroke was ischemic in 58 (92.1%) patients and hemorrhagic in 5 (7.9%) patients. More than half of all strokes (52.3%) were disabling. By principal management strategy, cerebrovascular events developed in 2.0%, 14.9%, and 1.9% of patients triaged to primary percutaneous coronary intervention, coronary artery bypass grafting, and medical therapy, respectively (
P
<0.0001). Cerebrovascular events were independently predicted by older age, creatinine clearance <60 mL/min, treatment with coronary artery bypass grafting, anemia, and diabetes mellitus. Cerebrovascular events were associated with significantly increased rates of 3-year mortality (20.5% versus 6.5%;
P
<0.0001), as well as reinfarction (14.3% versus 3.8%;
P
=0.0007), ischemia-driven target vessel revascularization (22.8% versus 13.0%;
P
=0.006), and major bleeding (23.5% versus 8.4%;
P
<0.0001).

Conclusions—

In HORIZONS-AMI, cerebrovascular events within 3 years after ST-segment–elevation myocardial infarction in patients undergoing a primary percutaneous coronary intervention management strategy occurred in 2.0% of patients and were most frequent after coronary artery bypass grafting. Cerebrovascular events were often disabling and were strongly associated with high rates of death, reinfarction, recurrent ischemia, and major bleeding.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00433966.
Adverse Childhood Experiences and Blood Pressure Trajectories From Childhood to Young Adulthood
Authors: Su Shaoyong , Wang Xiaoling , Pollock Jennifer S. , Treiber Frank A. , Xu Xiaojing , Snieder Harold , McCall W. Vaughn , Stefanek Michael , Harshfield Gregory A.
Published: April 2015

Background—

The purposes of this study were to assess the long-term effect of adverse childhood experiences (ACEs) on blood pressure (BP) trajectories from childhood to young adulthood and to examine whether this relation is explained by childhood socioeconomic status (SES) or risk behaviors that are associated with ACEs.

Methods and Results—

Systolic and diastolic BPs were measured up to 16 times (13 times on average) over a 23-year period in 213 African Americans and 181 European Americans 5 to 38 years of age. Retrospective data on traumatic experiences before 18 years of age were collected, including abuse, neglect, and household dysfunction. Individual growth curve modeling within a multilevel framework was used to examine the relation between exposure to ACEs and BP development. No main effect of ACEs on average BP levels was found. However, a significant interaction of ACE score with age
3
was observed (systolic BP,
P
=0.033; diastolic BP,
P
=0.017). Subjects who experienced multiple traumatic events during childhood showed a faster rise in BP levels after 30 years of age than those without ACEs. As expected, a graded association of ACEs with childhood socioeconomic status and negative health behaviors was observed (
P
<0.001). The ACE–systolic BP relation was not explained by these factors, whereas the ACE–diastolic BP relation was partially mediated by illicit drug use.

Conclusion—

In this novel longitudinal study, we observed that participants who were exposed to multiple ACEs displayed a greater increase in BP levels in young adulthood compared with their counterparts without ACEs.
Hemorrhage Rates From Brain Arteriovenous Malformation in Patients With Hereditary Hemorrhagic Telangiectasia
Authors: Kim Helen , Nelson Jeffrey , Krings Timo , terBrugge Karel G. , McCulloch Charles E. , Lawton Michael T. , Young William L. , Faughnan Marie E. ,   BVMC HHT Investigator Group, Chakinala Murali , Gossage James R. , Henderson Katharine , Iyer Vivek , Kasthuri Raj , Lin Doris , Mager Johannes Jurgen , McWilliams Justin , McDonald Jamie , Pawlikowska Ludmila , Pollak Jeffrey , Ratjen Felix , Swanson Karen , Vethanayagam Dilini , White Andrew , White Robert I. , Wilcox Pearce
Published: April 2015

Background and Purpose—

Hereditary hemorrhagic telangiectasia (HHT) is a systemic disease characterized by mucocutaneous telangiectasias, epistaxis, and arteriovenous malformations (AVMs). Intracranial hemorrhage (ICH) rates in this population are not well described. We report ICH rates and characteristics in HHT patients with brain AVMs (HHT-BAVMs).

Methods—

We studied the first 153 HHT-BAVM patients with follow-up data enrolled in the Brain Vascular Malformation Consortium HHT Project. We estimated ICH rates after BAVM diagnosis.

Results—

The majority of patients were women (58%) and white (98%). The mean age at BAVM diagnosis was 31±19 years (range, 0–70), with 61% of cases diagnosed on asymptomatic screening. Overall, 14% presented with ICH; among symptomatic cases, 37% presented ruptured. During 493 patient-years of follow-up, 5 ICH events occurred yielding a rate of 1.02% per year (95% confidence interval, 0.42–2.44%). ICH-free survival differed significantly by ICH presentation (
P
=0.003); ruptured cases had a higher ICH rate (10.07%; 95% confidence interval, 3.25–31.21%) than unruptured cases (0.43%; 95% confidence interval, 0.11–1.73%).

Conclusions—

Patients with HHT-BAVM who present with hemorrhage are at a higher risk for rehemorrhage compared with patients with BAVM detected presymptomatically.
Twelve-Month Clinical and Quality-of-Life Outcomes in the Interventional Management of Stroke III Trial
Authors: Palesch Yuko Y. , Yeatts Sharon D. , Tomsick Thomas A. , Foster Lydia D. , Demchuk Andrew M. , Khatri Pooja , Hill Michael D. , Jauch Edward C. , Jovin Tudor G. , Yan Bernard , von Kummer Rüdiger , Molina Carlos A. , Goyal Mayank , Schonewille Wouter J. , Mazighi Mikael , Engelter Stefan T. , Anderson Craig , Spilker Judith , Carrozzella Janice , Ryckborst Karla J. , Janis L. Scott , Simpson Annie , Simpson Kit N. , Broderick Joseph P.
Published: April 2015

Background and Purpose—

Randomized trials have indicated a benefit for endovascular therapy in appropriately selected stroke patients at 3 months, but data regarding outcomes at 12 months are currently lacking.

Methods—

We compared functional and quality-of-life outcomes at 12 months overall and by stroke severity in stroke patients treated with intravenous tissue-type plasminogen activator followed by endovascular treatment as compared with intravenous tissue-type plasminogen activator alone in the Interventional Management of Stroke III Trial. The key outcome measures were a modified Rankin Scale score ≤2 (functional independence) and the Euro-QoL EQ-5D, a health-related quality-of-life measure.

Results—

656 subjects with moderate-to-severe stroke (National Institutes of Health Stroke Scale ≥8) were enrolled at 58 centers in the United States (41 sites), Canada (7), Australia (4), and Europe (6). There was an interaction between treatment group and stroke severity in the repeated measures analysis of modified Rankin Scale ≤2 outcome (
P
=0.039). In the 204 participants with severe stroke (National Institutes of Health Stroke Scale ≥20), a greater proportion of the endovascular group had a modified Rankin Scale ≤2 (32.5%) at 12 months as compared with the intravenous tissue-type plasminogen activator group (18.6%,
P
=0.037); no difference was seen for the 452 participants with moderately severe strokes (55.6% versus 57.7%). In participants with severe stroke, the endovascular group had 35.2 (95% confidence interval: 2.1, 73.3) more quality-adjusted-days over 12 months as compared with intravenous tissue-type plasminogen activator alone.

Conclusions—

Endovascular therapy improves functional outcome and health-related quality-of-life at 12 months after severe ischemic stroke.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00359424.
On the Time of the Intellect: The Interpretation of De Anima 3.6 (430b 7–20) in Renaissance and Early Modern Italian Philosophy
Authors: Dubouclez Olivier
Published: April 2015

This article argues that an original debate over the relationship between time and the intellect took place in Northern Italy in the second half of the sixteenth century, which was part of a broader reflection on the temporality of human mental acts. While human intellectual activity was said to be ‘above time’ during the Middle Ages, Renaissance scholars such as Marcantonio Genua (1491–1563), Giulio Castellani (1528–1586), Antonio Montecatini (1537–1599) and Francesco Piccolomini (1520–1604), greatly influenced by the Simplician and Alexandrist interpretations of Aristotle’s works, proposed alternative conceptions based on the interpretation of De anima 3.6 (430b 7–20) according to which intellectual acts happen in a both ‘undivided’ and ‘divisible time’. In order to explain Aristotle’s puzzling claim, they were led to conceive of intellectual activity as a process similar to sensation, corresponding to a certain lapse of time (Castellani), an instant (Montecatini), or a mix of instantaneousness and concrete duration (Picco­lomini), depending on their theoretical options.
Anthurium carrasquillanum (Araceae), a new species of section Decurrentia from Panama
Authors: Ortiz Orlando Oriel , Croat Thomas
Published: April 2015

Anthurium Schott (1829: 828) is a monophyletic and neotropical genus, which is present from Mexico to Argentina (Croat 1986, Carlsen & Croat 2013). The genus is estimated by ca. 1500 species in the Neotropics (Boyce & Croat 2012), including 250 that are present in Central America, where the greatest diversity is found in Panama and Costa Rica (Croat 1986). In the Revision of Anthurium for Panama (Croat 1986), 16 sections are recognized. Croat et al. (2005) described a new section of the genus, called Decurrentia Croat (2005: 14), which includes A. decurrens Poeppig & Endlicher (1845: 83) and A. pittieri Engler (1898: 372). The latter species are present in Panama and Costa Rica (Croat 1986) and were previously classified within Section Oxycarpium Schott (1860: 450) based on the work of Schott (1860) and Engler (1905). The Decurrentia section is mainly characterized by short internodes, elongate petioles and epunctate leaf blades with an acute base. There are currently 46 species in section Decurrentia but some of the species are as yet unpublished.
Species of Lissothrips and Williamsiella from mosses and lichens in Australia and New Zealand (Thysanoptera, Phlaeothripinae)
Authors: MOUND LAURENCE A. , TREE DESLEY J.
Published: April 2015

Species of Lissothrips and Williamsiella live in association with mosses and lichens. Their gut contents are commonly blue-green, suggesting that they possibly feed on blue-green algae. Three species of Lissothrips are known from New Zealand, of which two are here recorded from Australia together with six new species. Williamsiella is recorded from Australia for the first time, with one new species.
Saturnia jonasii Butler, 1877 on Jejudo Island, a new saturnid moth of South Korea with DNA data and morphology (Lepidoptera: Saturniidae)
Authors: KIM MIN JEE , CHOI SEI-WOONG , KIM IKSOO
Published: April 2015

Saturnia (Rinaca) jonasii Butler, 1877 is distributed in Japan, including Tsushima Island and Taiwan, whereas S. boisduvalii Eversmann, 1846 is distributed in northern areas, such as China, Russia, and South Korea. In the present study we found that the specimens from Mt. Hallasan on Jejudo, a southern remote offshore island, were S. jonasii, rather than S. boisduvalii based on morphology, DNA barcode, and nuclear elongation factor 1 alpha (EF-1α) sequences. The major morphological differences between the two species included the shape of wing pattern elements of fore- and hindwings and male and female genitalia. A DNA barcode analysis of the sequences of the Jejudo specimens and S. boisduvalii, along with those of Saturnia species obtained from a public database showed a minimum sequence divergence of 4.26% (28 bp). A phylogenetic analysis also showed clustering of the Jejudo specimens with S. jonasii, separating S. boisduvalii (Bayesian posterior probability = 0.99). The EF-1α-based sequence and phylogenetic analyses of the two species from Jejudo Island and the Korean mainland showed the uniqueness of the Jejudo specimens from S. boisduvalii collected on the Korean mainland, indicating distribution of S. jonasii on Jejudo Island in South Korea, instead of S. boisduvalii.
Signals of Public Opinion in Online Communication
Authors: González-Bailón Sandra , Paltoglou Georgios
Published: April 2015

This study offers a systematic comparison of automated content analysis tools. The ability of different lexicons to correctly identify affective tone (e.g., positive vs. negative) is assessed in different social media environments. Our comparisons examine the reliability and validity of publicly available, off-the-shelf classifiers. We use datasets from a range of online sources that vary in the diversity and formality of the language used, and we apply different classifiers to extract information about the affective tone in these datasets. We first measure agreement (reliability test) and then compare their classifications with the benchmark of human coding (validity test). Our analyses show that validity and reliability vary with the formality and diversity of the text; we also show that ready-to-use methods leave much space for improvement when analyzing domain-specific content and that a machine-learning approach offers more accurate predictions across communication domains.
The Power of Television Images in a Social Media Age
Authors: Shah Dhavan V. , Hanna Alex , Bucy Erik P. , Wells Chris , Quevedo Vidal
Published: April 2015

There is considerable controversy surrounding the study of presidential debates, particularly efforts to connect their content and impact. Research has long debated whether the citizenry reacts to what candidates say, how they say it, or simply how they appear. This study uses detailed coding of the first 2012 debate between Barack Obama and Mitt Romney to test the relative influence of the candidates’ verbal persuasiveness and nonverbal features on viewers’ “second screen” behavior—their use of computers, tablets, and mobile phones to enhance or extend the televised viewing experience. To examine these relationships, we merged two datasets: (1) a shot-by-shot content analysis coded for functional, tonal, and visual elements of both candidates’ communication behavior during the debate; and (2) corresponding real-time measures, synched and lagged, of the volume and sentiment of Twitter expression about Obama and Romney. We find the candidates’ facial expressions and physical gestures to be more consistent and robust predictors of the volume and valence of Twitter expression than candidates’ persuasive strategies, verbal utterances, and voice tone during the debate.
Big Data under the Microscope and Brains in Social Context
Authors: O’Donnell Matthew Brook , Falk Emily B.
Published: April 2015

Methods for analyzing neural and computational social science data are usually used by different types of scientists and generally seen as distinct, but they strongly complement one another. Computational social science methodologies can strengthen and contextualize individual-level analysis, specifically our understanding of the brain. Neuroscience can help to unpack the mechanisms that lead from micro- through meso- to macro-level observations. Integrating levels of analysis is essential to unified progress in social research. We present two example areas that illustrate this integration. First, combining egocentric social network data with neural variables from the “egos” provides insight about why and for whom certain types of antismoking messages may be more or less effective. Second, combining tools from natural language processing with neuroimaging reveals mechanisms involved in successful message propagation, and suggests links from microscopic to macroscopic scales.
What Social Media Data We Are Missing and How to Get It
Authors: Resnick Paul , Adar Eytan , Lampe Cliff
Published: April 2015

Most electronic behavior traces available to social scientists offer a site-centric view of behavior. We argue that to understand patterns of interpersonal communication and media consumption, a more person-centric view is needed. The ideal research platform would capture reading as well as writing and friending, behavior across multiple sites, and demographic and psychographic variables. It would also offer opportunities for researchers to make interventions that make changes and additions to the information presented to people in social media interfaces. Any attempt to create such an ideal platform will have to make compromises because of engineering and privacy constraints. We describe one attempt to navigate those tensions: the MTogether project will recruit a panel of participants who will install a browser extension and mobile app that enable limited data collection and interventions.