bluuebunny/crossref_metadata_2025 huggingface dataset:
Computing the Reverse Eccentric Connectivity Index for Certain Family of Nanocone and Fullerene Structures
Authors: Gao Wei , Farahani Mohammad Reza
Published: March 2016

A large number of previous works reveal that there exist strong connections between the chemical characteristics of chemical compounds and drugs (e.g., melting point and boiling point) and their topological structures. Chemical indices introduced on these molecular topological structures can help chemists and material and medical scientists to grasp its chemical reactivity, biological activity, and physical features better. Hence, the study of the topological indices on the material structure can make up the defect of experiments and provide the theoretical evidence in material engineering. In this paper, we determine the reverse eccentric connectivity index of one family of pentagonal carbon nanoconesPCN5[n]and three infinite families of fullerenesC12n+2,  C12n+4, andC18n+10based on graph analysis and computation derivation, and these results can offer the theoretical basis for material properties.
Stator Fault Detection in Induction Motors by Autoregressive Modeling
Authors: Garcia-Guevara Francisco M. , Villalobos-Piña Francisco J. , Alvarez-Salas Ricardo , Cabal-Yepez Eduardo , Gonzalez-Garcia Mario A.
Published: March 2016

This study introduces a novel methodology for early detection of stator short circuit faults in induction motors by using autoregressive (AR) model. The proposed algorithm is based on instantaneous space phasor (ISP) module of stator currents, which are mapped toα-βstator-fixed reference frame; then, the module is obtained, and the coefficients of the AR model for such module are estimated and evaluated by order selection criterion, which is used as fault signature. For comparative purposes, a spectral analysis of the ISP module by Discrete Fourier Transform (DFT) is performed; a comparison of both methodologies is obtained. To demonstrate the suitability of the proposed methodology for detecting and quantifying incipient short circuit stator faults, an induction motor was altered to induce different-degree fault scenarios during experimentation.
Multivariate Statistics and Supervised Learning for Predictive Detection of Unintentional Islanding in Grid-Tied Solar PV Systems
Authors: Vyas Shashank , Kumar Rajesh , Kavasseri Rajesh
Published: March 2016

Integration of solar photovoltaic (PV) generation with power distribution networks leads to many operational challenges and complexities. Unintentional islanding is one of them which is of rising concern given the steady increase in grid-connected PV power. This paper builds up on an exploratory study of unintentional islanding on a modeled radial feeder having large PV penetration. Dynamic simulations, also run in real time, resulted in exploration of unique potential causes of creation of accidental islands. The resulting voltage and current data underwent dimensionality reduction using principal component analysis (PCA) which formed the basis for the application ofQstatistic control charts for detecting the anomalous currents that could island the system. For reducing the false alarm rate of anomaly detection, Kullback-Leibler (K-L) divergence was applied on the principal component projections which concluded thatQstatistic based approach alone is not reliable for detection of the symptoms liable to cause unintentional islanding. The obtained data was labeled and aK-nearest neighbor (K-NN) binomial classifier was then trained for identification and classification of potential islanding precursors from other power system transients. The three-phase short-circuit fault case was successfully identified as statistically different from islanding symptoms.
Does Unilateral Oocyte Retrieval due to Transvaginally Inaccessible Ovaries, Contrary to Common Beliefs, Affect IVF/ICSI Treatment Outcomes That Much?
Authors: Olgan Safak , Mumusoglu Sezcan , Bozdag Gurkan
Published: March 2016

Objective. To investigate in vitro fertilization (IVF) treatment outcomes of unilateral oocyte retrieval in patients with transvaginally inaccessible ovaries.Study Design. Ninety-two women who underwent unilateral oocyte retrieval were retrospectively matched for age, antral follicle count, and body mass index with 184 women who underwent bilateral oocyte retrieval. Each patient in bilateral oocyte retrieval group had the same number of cumulus oophorus complexes (COCs) from single ovary and had comparable number of follicles (±2) on contralateral site where follicular aspiration was performed.Results. The number of COCs, metaphase-2 oocytes, 2-pronuclei, and top-quality embryos was significantly lower in unilateral oocyte retrieval group. However, proportion of patients with an embryo transfer of at least one top-quality embryo was found to be comparable between unilateral and bilateral oocyte retrieval. Subsequently, clinical pregnancy and live birth rates were found to be similar between the groups. The ROC curve analysis revealed (AUC = 0.74, 95% CI 0.63–0.86,p=0.001) that retrieved COCs ≥ 5 from single ovary had sensitivity of 76.0% and specificity of 64.2% for occurrence of a clinical pregnancy.Conclusion. The patients with unilateral oocyte retrieval have reasonable chance of success with IVF. The retrieval of ≥5 COCs from accessible ovary might result in better treatment outcomes among these patients.
Multidrug Resistant CTX-M-ProducingEscherichia coli: A Growing Threat among HIV Patients in India
Authors: Padmavathy Kesavaram , Padma Krishnan , Rajasekaran Sikhamani
Published: March 2016

Extended Spectrumβ-Lactamases (ESBLs) confer resistance to third-generation cephalosporins and CTX-M types have emerged as the most prominent ESBLs worldwide. This study was designed to determine the prevalence of CTX-M positive ESBL-producing urinaryE. coliisolates from HIV patients and to establish the association of multidrug resistance, phylogeny, and virulence profile with CTX-M production. A total of 57 ESBL producers identified among 76E. colistrains isolated from HIV patients from South India were screened forblaCTX-M, AmpC production, multidrug resistance, and nine virulence associated genes (VAGs),fimH,pap,afa/dra,sfa/foc,iutA,fyuA,iroN,usp,andkpsMII.The majority (70.2%) of the ESBL producers harboredblaCTX-Mand were AmpC coproducers. Among the CTX-M producers, 47.5% were found to be UPEC, 10% harbored as many as 7 VAGs, and 45% possessedkpsMII. Multidrug resistance (CIPRSXTRGENR) was significantly more common among the CTX-M producers compared to the nonproducers (70% versus 41.2%). However, 71.4% of the multidrug resistant CTX-M producers exhibited susceptibility to nitrofurantoin thereby making it an effective alternative to cephalosporins/fluoroquinolones. The emergence of CTX-M-producing highly virulent, multidrug resistant uropathogenicE. coliis of significant public health concern in countries like India with a high burden of HIV/AIDS.
Sociodemographic Correlates of Tobacco Consumption in Rural Gujarat, India
Authors: Kahar Payal , Misra Ranjita , Patel Thakor G.
Published: March 2016

Background.The purpose of this study was to examine occupation-, education-, and gender-specific patterns of tobacco use and knowledge of its health effects among 23,953 rural Asian Indians ≥18 years in Gujarat.Methodology.A statewide, community-based, cross-sectional survey was conducted in 26 districts of Gujarat (December 2010–May 2015), using face-to-face interviews by trained community health workers called SEVAKS.Results.Mean age was 39.8 ± 15.2 years. Eighteen percent of respondents used tobacco in various forms. Tobacco consumption was significantly higher among males (32%), 18–34 years’ age group (35%), those who were self-employed (72%), and those with elementary education (40%). The prevalence was 11 times higher among males than females (95% CI = 9.78, 13.13). Adjusted ORs for tobacco use showed strong gradient by age and educational level; consumption was lower among the illiterates and higher for older participants (≥55 years). Tobacco consumption also varied by occupation; that is, those who were self-employed and employed for wages were more likely to use tobacco than those who were unemployed. Knowledge of health effects of tobacco lowered the odds of consumption by 30–40%.Conclusions.Effective educational programs should be tailored by gender, to improve knowledge of health risks and dispel myths on perceived benefits of tobacco.
Research on Price of Railway Freight Based on Low-Carbon Economy
Authors: Feng Fenling , Liu Chengguang , Liu Haihong , Ji Zhizhou
Published: March 2016

Transportation is one of the major energy consumption and carbon emission industries. Railway transport is a typical low-carbon transport. To accelerate the green low-carbon transportation development and improve the railway market share, this paper defines the concept of carbon saving profit to study the price of railway freight after the government functions were separated from railway enterprise management. First, taking full account of market factors and on the principle of utility maximization and maximum likelihood method, the sharing ratio model of transportation modes is established. Then consideration is given to both the profit of railway enterprises and social benefits, and income maximization model of railway freight based on low-carbon economy is established. The model can scientifically guide the transportation users who prefer to use resource-saving and environmental-friendly transportation modes, optimize transportation structure, and comprehensively improve the efficiency of transportation system. Finally, case analysis is conducted to verify the rationality and validity of the model, and reference for the rail freight pricing is provided.
Zinc Chelation Mediates the Lysosomal Disruption without Intracellular ROS Generation
Authors: Matias Andreza Cândido , Manieri Tânia Maria , Cerchiaro Giselle
Published: March 2016

We report the molecular mechanism for zinc depletion caused by TPEN (N,N,N′,N′‐Tetrakis(2‐pyridylmethyl)ethylenediamine) in neuroblastoma cells. The activation of p38 MAP kinase and subsequently caspase 3 is not due to or followed by redox imbalance or ROS generation, though these are commonly observed in literature. We found that TPEN is not responsible for ROS generation and the mechanism involves essentially lysosomal disruption caused by intracellular zinc depletion. We also observed a modest activation of Bax and no changes in the Bcl‐2 proteins. As a result, we suggest that TPEN causes intracellular zinc depletion which can influence the breakdown of lysosomes and cell death without ROS generation.
Case Report of Necrotizing Fasciitis Associated withStreptococcus pneumoniae
Authors: Jiao Lei , Chagla Zain , Kaki Reham Mohammedsaeed , Gohla Gabriela , Smieja Marek
Published: March 2016

Necrotizing fasciitis, caused byStreptococcus pneumoniae, is an extremely rare and life-threatening bacterial soft tissue infection. We report a case of early necrotizing fasciitis associated withStreptococcus pneumoniaeinfection in a 26-year-old man who was immunocompromised with mixed connective tissue disease. The patient presented with acute, painful, erythematous, and edematous skin lesions of his right lower back, which rapidly progressed to the right knee. The patient underwent surgical exploration, and a diagnosis of necrotizing fasciitis was confirmed by pathological evidence of necrosis of the fascia and neutrophil infiltration in tissue biopsies. Cultures of fascial tissue biopsies and blood samples were positive forStreptococcus pneumoniae. To our knowledge, this is the first report of necrotizing fasciitis resulting fromStreptococcus pneumoniaediagnosed at early phase; the patient recovered well without surgical debridement.
Evaluating Emotional Well‐Being after a Short‐Term Traditional Yoga Practice Approach in Yoga Practitioners with an Existing Western‐Type Yoga Practice
Authors: Meissner Maxi , Cantell Marja H. , Steiner Ronald , Sanchez Xavier
Published: March 2016

The purpose of the present study was to examine the influence of a traditional yoga practice approach (morning daily practice, TY) compared to that of a Western yoga practice approach (once‐twice weekly, evening practice, WY) on determinants of emotional well‐being. To that end, in a pre/posttest between‐subject design, measures of positive (PA) and negative affect (NA), mindfulness, perceived stress, and arousal states were taken in 24 healthy participants (20 women; mean age: 30.5, SD = 8.1 years) with an already existing WY practice, who either maintained WY or underwent a 2‐week, five‐times‐per‐week morning practice (TY). While WY participants maintained baseline values for all measures taken, TY participants showed significant beneficial changes for PA, NA, and mindfulness and a trend for improved ability to cope with stress at the completion of the intervention. Furthermore, TY participants displayed decreased subjective energy and energetic arousal. Altogether, findings indicate that the 2‐week TY is beneficial over WY for improving perceived emotional well‐being. The present findings (1) undermine and inspire a careful consideration and utilization of yoga practice approach to elicit the best benefits for emotional well‐being and (2) support yoga as an evidence‐based practice among healthy yoga practitioners.
Diagnostic Laparoscopy with Ultrasound Still Has a Role in the Staging of Pancreatic Cancer: A Systematic Review of the Literature
Authors: Levy Jordan , Tahiri Mehdi , Vanounou Tsafrir , Maimon Geva , Bergman Simon
Published: March 2016

Background. The reported incidence of noncurative laparotomies for pancreatic cancer using standard imaging (SI) techniques for staging remains high. The objectives of this study are to determine the diagnostic accuracy of diagnostic laparoscopy with ultrasound (DLUS) in assessing resectability of pancreatic tumors.Study Design. We systematically searched the literature for prospective studies investigating the accuracy of DLUS in determining resectability of pancreatic tumors.Results. 104 studies were initially identified and 19 prospective studies (1,573 patients) were included. DLUS correctly predicted resectability in 79% compared to 55% for SI. DLUS prevented noncurative laparotomies in 33%. Of those, the most frequent DLUS findings precluding resection were liver metastases, vascular involvement, and peritoneal metastases. DLUS had a morbidity rate of 0.8% with no mortalities. DLUS remained superior to SI when analyzing studies published only in the last five years (100% versus 81%), enrolling patients after the year 2000 (74% versus 58%), or comparing DLUS to modern multidimensional CT (100% versus 78%).Conclusion. DLUS seems to still have a role in the preoperative staging of pancreatic cancer. With its ability to detect liver metastases, vascular involvement, and peritoneal metastases, the use of DLUS leads to less noncurative laparotomies.
An Optimal Treatment Control of TB-HIV Coinfection
Authors: Fatmawati  , Tasman Hengki
Published: March 2016

An optimal control on the treatment of the transmission of tuberculosis-HIV coinfection model is proposed in this paper. We use two treatments, that is, anti-TB and antiretroviral, to control the spread of TB and HIV infections, respectively. We first present an uncontrolled TB-HIV coinfection model. The model exhibits four equilibria, namely, the disease-free, the HIV-free, the TB-free, and the coinfection equilibria. We further obtain two basic reproduction ratios corresponding to TB and HIV infections. These ratios determine the existence and stability of the equilibria of the model. The optimal control theory is then derived analytically by applying the Pontryagin Maximum Principle. The optimality system is performed numerically to illustrate the effectiveness of the treatments.
p53 Loss in MYC-Driven Neuroblastoma Leads to Metabolic Adaptations Supporting Radioresistance
Authors: Yogev Orli , Barker Karen , Sikka Arti , Almeida Gilberto S. , Hallsworth Albert , Smith Laura M. , Jamin Yann , Ruddle Ruth , Koers Alexander , Webber Hannah T. , Raynaud Florence I. , Popov Sergey , Jones Chris , Petrie Kevin , Robinson Simon P. , Keun Hector C. , Chesler Louis
Published: March 2016

Neuroblastoma is the most common childhood extracranial solid tumor. In high-risk cases, many of which are characterized by amplification of MYCN, outcome remains poor. Mutations in the p53 (TP53) tumor suppressor are rare at diagnosis, but evidence suggests that p53 function is often impaired in relapsed, treatment-resistant disease. To address the role of p53 loss of function in the development and pathogenesis of high-risk neuroblastoma, we generated a MYCN-driven genetically engineered mouse model in which the tamoxifen-inducible p53ERTAM fusion protein was expressed from a knock-in allele (Th-MYCN/Trp53KI). We observed no significant differences in tumor-free survival between Th-MYCN mice heterozygous for Trp53KI (n = 188) and Th-MYCN mice with wild-type p53 (n = 101). Conversely, the survival of Th-MYCN/Trp53KI/KI mice lacking functional p53 (n = 60) was greatly reduced. We found that Th-MYCN/Trp53KI/KI tumors were resistant to ionizing radiation (IR), as expected. However, restoration of functional p53ERTAM reinstated sensitivity to IR in only 50% of Th-MYCN/Trp53KI/KI tumors, indicating the acquisition of additional resistance mechanisms. Gene expression and metabolic analyses indicated that the principal acquired mechanism of resistance to IR in the absence of functional p53 was metabolic adaptation in response to chronic oxidative stress. Tumors exhibited increased antioxidant metabolites and upregulation of glutathione S-transferase pathway genes, including Gstp1 and Gstz1, which are associated with poor outcome in human neuroblastoma. Accordingly, glutathione depletion by buthionine sulfoximine together with restoration of p53 activity resensitized tumors to IR. Our findings highlight the complex pathways operating in relapsed neuroblastomas and the need for combination therapies that target the diverse resistance mechanisms at play. Cancer Res; 76(10); 3025–35. ©2016 AACR.
A CDK4/6-Dependent Epigenetic Mechanism Protects Cancer Cells from PML-induced Senescence
Authors: Acevedo Mariana , Vernier Mathieu , Mignacca Lian , Lessard Frédéric , Huot Geneviève , Moiseeva Olga , Bourdeau Véronique , Ferbeyre Gerardo
Published: March 2016

Promyelocytic leukemia (PML) plays a tumor suppressive role by inducing cellular senescence in response to oncogenic stress. However, tumor cell lines fail to engage in complete senescence upon PML activation. In this study, we investigated the mechanisms underlying resistance to PML-induced senescence. Here, we report that activation of the cyclin-dependent kinases CDK4 and CDK6 are essential and sufficient to impair senescence induced by PML expression. Disrupting CDK function by RNA interference or pharmacological inhibition restored senescence in tumor cells and diminished their tumorigenic potential in mouse xenograft models. Complete senescence correlated with an increase in autophagy, repression of E2F target genes, and an gene expression signature of blocked DNA methylation. Accordingly, treatment of tumor cells with inhibitors of DNA methylation reversed resistance to PML-induced senescence. Further, CDK inhibition with palbociclib promoted autophagy-dependent degradation of the DNA methyltransferase DNMT1. Lastly, we found that CDK4 interacted with and phosphorylated DNMT1 in vitro, suggesting that CDK activity is required for its stabilization. Taken together, our findings highlight a potentially valuable feature of CDK4/6 inhibitors as epigenetic modulators to facilitate activation of senescence programs in tumor cells. Cancer Res; 76(11); 3252–64. ©2016 AACR.
Membrane IL1α Inhibits the Development of Hepatocellular Carcinoma via Promoting T- and NK-cell Activation
Authors: Lin Dandan , Lei Lei , Liu Yonghao , Zhang Yinsheng , Hu Bo , Bao Guangming , Song Yuan , Jin Ziqi , Liu Chunliang , Mei Yu , Sandikin Dedy , Wu Yan , Zhao Lixiang , Yu Xiao , Liu Haiyan
Published: March 2016

Hepatocellular carcinoma is a worldwide health problem with limited treatment options and poor prognosis. Inflammation associated with liver injury and hepatocyte regeneration can lead to fibrosis, cirrhosis, and eventually, hepatocellular carcinoma. IL1α is one of the most important inflammatory cytokines involved in inflammation and tumor development. IL1α presents as multiple forms in vivo, including precursor, propiece, membrane, and secreted forms, and their functions have been thought to be different. The role of membrane IL1α in hepatocellular carcinoma tumorigenesis is still not clear. Here, we examined the functions of membrane IL1α in murine hepatocellular carcinoma models. We found that membrane IL1α potently inhibited hepatocellular carcinoma tumor growth. Further studies showed that membrane IL1α promoted T- and natural killer (NK)–cell activation in vivo. IFNγ production by CD8+ T and NK cells was also increased as a result of membrane IL1α expression. Moreover, the cytotoxicity of the CTL and NK cells was also enhanced by membrane IL1α expression. Furthermore, in vitro studies demonstrated that membrane IL1α could directly activate T cells and NK cells in a cell contact–dependent manner. Conversely, depletion of both CD8+ T and NK cells suppressed the antitumor activity of membrane IL1α. Our studies demonstrated that membrane IL1α could promote antitumor immune responses through activation of T and NK cells. Thus, our findings provide new insights of IL1α functions during hepatocellular carcinoma development. Cancer Res; 76(11); 3179–88. ©2016 AACR.
Trastuzumab, but Not Pertuzumab, Dysregulates HER2 Signaling to Mediate Inhibition of Autophagy and Increase in Reactive Oxygen Species Production in Human Cardiomyocytes
Authors: Mohan Nishant , Shen Yi , Endo Yukinori , ElZarrad M. Khair , Wu Wen Jin
Published: March 2016

Dysregulation of autophagy has been implicated in various cardiovascular diseases. Trastuzumab, a humanized monoclonal antibody, binds to HER2 domain IV and is approved for the treatment of HER2-positive breast cancer. Trastuzumab therapy is associated with considerable cardiotoxicity, the mechanism of which remains unclear. HER2 signaling plays a pivotal role in cardiomyocyte development and survival and is essential for the prevention of cardiomyopathy. However, a direct link has not been confirmed between trastuzumab-induced cardiomyopathy and impaired HER2 signaling. Our data reveal a novel mechanism by which trastuzumab dysregulates HER2 signaling and impairs basal autophagic process in human primary cardiomyocytes. Specifically, trastuzumab treatment leads to the phosphorylation of HER1-Y845 and HER2-Y1248 and the activation of Erk. This in turn results in upregulation of mTOR signaling pathway and subsequently inhibition of autophagy in primary cardiomyocytes and C57BL/6 mice. Trastuzumab-induced downregulation of autophagy is further supported by the fact that trastuzumab treatment reduces protein levels of autophagosome-associated signaling molecules such as Atg 5-12, Atg 7, Atg 14, and Beclin 1. We further demonstrated that trastuzumab-mediated inhibition of autophagy resulted in the increased production of reactive oxygen species (ROS) in cardiomyocytes. Pertuzumab, another anti-HER2 therapeutic mAb binding to HER2 domain II, fails to modulate HER2 signaling and is unable to inhibit autophagy and to increase ROS production in cardiomyocytes. This study provides novel mechanistic insights into trastuzumab-induced cardiotoxicity, which may assist in formulating novel approaches for clinical management of trastuzumab-induced cardiomyopathy. Mol Cancer Ther; 15(6); 1321–31. ©2016 AACR.
Short-Term Effects of Phenobarbitone on Electrographic Seizures in Neonates
Authors: Low Evonne , Stevenson Nathan J. , Mathieson Sean R. , Livingstone Vicki , Ryan Anthony C. , Rennie Janet M. , Boylan Geraldine B.
Published: March 2016

Background: Phenobarbitone is the most common first-line anti-seizure drug and is effective in approximately 50% of all neonatal seizures. Objective: To describe the response of electrographic seizures to the administration of intravenous phenobarbitone in neonates using seizure burden analysis techniques. Methods: Multi-channel conventional EEG, reviewed by experts, was used to determine the electrographic seizure burden in hourly epochs. The maximum seizure burden evaluated 1 h before each phenobarbitone dose (T-1) was compared to seizure burden in periods of increasing duration after each phenobarbitone dose had been administered (T+1, T+2 to seizure offset). Differences were analysed using linear mixed models and summarized as means and 95% CI. Results: Nineteen neonates had electrographic seizures and met the inclusion criteria for the study. Thirty-one doses were studied. The maximum seizure burden was significantly reduced 1 h after the administration of phenobarbitone (T+1) [-14.0 min/h (95% CI: -19.6, -8.5); p < 0.001]. The percentage reduction was 74% (IQR: 36-100). This reduction was temporary and not significant within 4 h of administrating phenobarbitone. Subgroup analysis showed that only phenobarbitone doses at 20 mg/kg resulted in a significant reduction in the maximum seizure burden from T-1 to T+1 (p = 0.002). Conclusions: Phenobarbitone significantly reduced seizures within 1 h of administration as assessed with continuous multi-channel EEG monitoring in neonates. The reduction was not permanent and seizures were likely to return within 4 h of treatment.
Prevalence of Masked Hypertension and Its Association With Subclinical Cardiovascular Disease in African Americans: Results From the Jackson Heart Study
Authors: Redmond Nicole , Booth John N. , Tanner Rikki M. , Diaz Keith M. , Abdalla Marwah , Sims Mario , Muntner Paul , Shimbo Daichi
Published: March 2016

Background

Studies consisting mostly of whites have shown that the prevalence of masked hypertension differs by prehypertension status. Using data from the Jackson Heart Study, an exclusively African American population‐based cohort, we evaluated the association of masked hypertension and prehypertension with left ventricular mass index and common carotid intima media thickness.

Methods and Results

At the baseline visit, clinic blood pressure (
CBP
) measurement and 24‐hour ambulatory blood pressure monitoring were performed. Masked hypertension was defined as mean systolic/diastolic
CBP
<140/90 mm Hg and mean daytime systolic/diastolic ambulatory blood pressure ≥135/85 mm Hg. Clinic hypertension was defined as mean systolic/diastolic
CBP
≥140/90 mm Hg. Normal
CBP
was defined as mean systolic/diastolic
CBP
<120/80 mm Hg and prehypertension as mean systolic/diastolic
CBP
120 to 139/80 to 89 mm Hg. The analytic sample included 909 participants. Among participants with systolic/diastolic
CBP
<140/90 mm Hg, the prevalence of masked hypertension and prehypertension was 27.5% and 62.4%, respectively. The prevalence of masked hypertension among those with normal
CBP
and prehypertension was 12.9% and 36.3%, respectively. In a fully adjusted model, which included prehypertension status and antihypertensive medication use as covariates, left ventricular mass index was 7.94 g/m
2
lower among those without masked hypertension compared to participants with masked hypertension (
P
<0.001). Left ventricular mass index was also 4.77 g/m
2
lower among those with clinic hypertension, but this difference was not statistically significant (
P
=0.068). There were no significant differences in left ventricular mass index between participants with and without masked hypertension, or clinic hypertension.

Conclusions

Masked hypertension was common among African Americans with prehypertension and also normal
CBP
, and was associated with subclinical cardiovascular disease.
Diastolic Left Ventricular Function in Relation to Circulating Metabolic Biomarkers in a General Population
Authors: Zhang Zhen‐Yu , Marrachelli Vannina G. , Thijs Lutgarde , Yang Wen‐Yi , Wei Fang‐Fei , Monleon Daniel , Jacobs Lotte , Nawrot Tim , Verhamme Peter , Voigt Jens‐Uwe , Kuznetsova Tatiana , Redón Josep , Staessen Jan A.
Published: March 2016

Background

The metabolic signature associated with subclinical diastolic left ventricular (
LV
) dysfunction in the population remains ill defined.

Methods and Results

In 711 randomly recruited Flemish (50.8% women; mean age, 50.8 years), we assessed echocardiographic Doppler indexes of diastolic
LV
function in relation to 44 circulating metabolites determined by nuclear magnetic resonance spectroscopy. In multivariable‐adjusted regression analysis with Bonferroni correction of significance levels applied, peak a’ decreased (
P
≤0.048) and e’/a’ increased (
P
≤0.044) with circulating tyrosine, high‐density lipoprotein apolipoproteins, glucose+glutamine, and an unidentified molecule. Effect sizes expressed per 1‐
SD
increment in the metabolite ranged from −0.277 to −0.203 cm/s for peak a’ and from +0.047 to +0.054 for e’/a’. In addition, peak a’ decreased (
P
≤0.031) with glucose+2‐aminobutyrate (−0.261 cm/s) and glucose+2‐phosphoglycerate (−0.209 cm/s). In partial least square discriminant analysis (
PLS
‐
DA
), metabolites associated with normal diastolic
LV
function (n=538) included glucose+glutamine, glucose+2‐aminobutyrate, and glucose+2‐phosphoglycerate, whereas those siding with abnormal function encompassed 4‐aminobutyrate, 4‐hydroxybutyrate, creatinine, and phosphocholine. In receiver operating characteristics plots, adding 3 latent factors identified by
PLS
‐
DA
to prohormone brain natriuretic peptide increased (
P
<0.0001) the area under the curve from 0.64 (95%
CI
, 0.58–0.68) to 0.73 (0.68–0.78).

Conclusions

In a general population, circulating metabolites indicative of energy substrate utilization and protection against oxidative stress differentiated normal from abnormal diastolic
LV
function. These findings improve our understanding of the pathophysiology underlying deterioration of diastolic
LV
function and potentially point to new targets for prevention and treatment of this condition.
Comparative Effectiveness of Personalized Lifestyle Management Strategies for Cardiovascular Disease Risk Reduction
Authors: Chu Paula , Pandya Ankur , Salomon Joshua A. , Goldie Sue J. , Hunink M. G. Myriam
Published: March 2016

Background

Evidence shows that healthy diet, exercise, smoking interventions, and stress reduction reduce cardiovascular disease risk. We aimed to compare the effectiveness of these lifestyle interventions for individual risk profiles and determine their rank order in reducing 10‐year cardiovascular disease risk.

Methods and Results

We computed risks using the American College of Cardiology/American Heart Association Pooled Cohort Equations for a variety of individual profiles. Using published literature on risk factor reductions through diverse lifestyle interventions—group therapy for stopping smoking, Mediterranean diet, aerobic exercise (walking), and yoga—we calculated the risk reduction through each of these interventions to determine the strategy associated with the maximum benefit for each profile. Sensitivity analyses were conducted to test the robustness of the results. In the base‐case analysis, yoga was associated with the largest 10‐year cardiovascular disease risk reductions (maximum absolute reduction 16.7% for the highest‐risk individuals). Walking generally ranked second (max 11.4%), followed by Mediterranean diet (max 9.2%), and group therapy for smoking (max 1.6%). If the individual was a current smoker and successfully quit smoking (ie, achieved complete smoking cessation), then stopping smoking yielded the largest reduction. Probabilistic and 1‐way sensitivity analysis confirmed the demonstrated trend.

Conclusions

This study reports the comparative effectiveness of several forms of lifestyle modifications and found smoking cessation and yoga to be the most effective forms of cardiovascular disease prevention. Future research should focus on patient adherence to personalized therapies, cost‐effectiveness of these strategies, and the potential for enhanced benefit when interventions are performed simultaneously rather than as single measures.
TRAF3
Epigenetic Regulation Is Associated With Vascular Recurrence in Patients With Ischemic Stroke
Authors: Gallego-Fabrega Cristina , Carrera Caty , Reny Jean-Luc , Fontana Pierre , Slowik Agnieszka , Pera Joanna , Pezzini Alessandro , Serrano-Heras Gemma , Segura Tomás , Martí-Fàbregas Joan , Muiño Elena , Cullell Natalia , Montaner Joan , Krupinski Jerzy , Fernandez-Cadenas Israel
Published: March 2016

Background and Purpose—

Clopidogrel is one of the most used antiplatelet drugs in patients with cardiovascular disease. However, 16% to 50% of patients have a high on-clopidogrel platelet reactivity and an increased risk of ischemic events. The pathogenesis of high on-treatment platelet reactivity in patients with stroke is only partially explained by genetic variations. This study aims to find differentially methylated sites across the genome associated with vascular recurrence in ischemic stroke patients treated with clopidogrel.

Methods—

From a cohort of 1900 patients with ischemic stroke, we selected 42 patients treated with clopidogrel, including 21 with a recurrent vascular event and 21 without vascular recurrence during the first year of follow-up. Over 480 000 DNA methylation sites were analyzed across the genome. Differentially methylated CpG sites were identified by nonparametric testing using R. Replication analysis was performed in a new cohort of 191 subjects and results were correlated with platelet reactivity in a subset of 90 subjects using light transmission aggregometry.

Results—

A total of 73 differentially methylated CpG sites (
P
<1×10
−05
) were identified; 3 of them were selected for further replication: cg03548645 (
P
=1.42×10
−05
,
TRAF3
), cg09533145 (
P
=7.81×10
−06
,
ADAMTS2
), and cg15107336 (
P
=1.89×10
−05
,
XRCC1
). The cg03548645 CpG remained significant in the replication study (
P
=0.034), a deep analysis of this region revealed another methylation site associated with vascular recurrence,
P
=0.037. Lower cg03548645 (
TRAF3
) DNA methylation levels were correlated with an increased platelet aggregation (ρ=−0.29,
P
=0.0075).

Conclusions—

This study suggests for the first time that epigenetics may significantly contribute to the variability of clopidogrel response and recurrence of ischemic events in patients with stroke.
De Novo Aneurysm Formation in Carriers of Saccular Intracranial Aneurysm Disease in Eastern Finland
Authors: Lindgren Antti E. , Räisänen Sari , Björkman Joel , Tattari Hanna , Huttunen Jukka , Huttunen Terhi , Kurki Mitja I. , Frösen Juhana , Koivisto Timo , Jääskeläinen Juha E. , von und zu Fraunberg Mikael
Published: March 2016

Background and Purpose—

Formation of new (de novo) aneurysms in patients carrying saccular intracranial aneurysm (sIA) disease has been published, but data from population-based cohorts are scarce.

Methods—

Kuopio sIA database (
http://www.uef.fi/ns
) contains all unruptured and ruptured sIA patients admitted to Kuopio University Hospital from its Eastern Finnish catchment population. We studied the incidence and risk factors for de novo sIA formation in 1419 sIA patients with ≥5 years of angiographic follow-up, a total follow-up of 18 526 patient-years.

Results—

There were 42 patients with a total of 56 de novo sIAs, diagnosed in a median of 11.7 years after the first sIA diagnosis. The cumulative incidence of de novo sIAs was 0.23% per patient-year and that of subarachnoid hemorrhage from a ruptured de novo sIA 0.05% per patient-year. The risk of de novo sIA discovery per patient-year increased with younger age at the first sIA diagnosis: 2.2% in the patients aged <20 years and 0.46% in the patients aged between 20 and 39 years. In Cox regression analysis, smoking history and younger age at the first sIA diagnosis significantly associated with de novo sIA formation, but female sex, multiple sIAs, and sIA family did not.

Conclusions—

Patients aged < 40 years at the first sIA diagnosis are in a significant risk of developing de novo sIAs, and they should be scheduled for long-term angiographic follow-up. Smoking increases the risk of de novo sIA formation, suggesting long-term follow-up for smokers. Antismoking efforts are highly recommended for sIA patients.
RNA Sequencing Analysis of Intracranial Aneurysm Walls Reveals Involvement of Lysosomes and Immunoglobulins in Rupture
Authors: Kleinloog Rachel , Verweij Bon H. , van der Vlies Pieter , Deelen Patrick , Swertz Morris A. , de Muynck Louis , Van Damme Philip , Giuliani Fabrizio , Regli Luca , van der Zwan Albert , Berkelbach van der Sprenkel Jan W. , Han K. Sen , Gosselaar Peter , van Rijen Peter C. , Korkmaz Emine , Post Jan A. , Rinkel Gabriel J.E. , Veldink Jan H. , Ruigrok Ynte M.
Published: March 2016

Background and Purpose—

Analyzing genes involved in development and rupture of intracranial aneurysms can enhance knowledge about the pathogenesis of aneurysms, and identify new treatment strategies. We compared gene expression between ruptured and unruptured aneurysms and control intracranial arteries.

Methods—

We determined expression levels with RNA sequencing. Applying a multivariate negative binomial model, we identified genes that were differentially expressed between 44 aneurysms and 16 control arteries, and between 22 ruptured and 21 unruptured aneurysms. The differential expression of 8 relevant and highly significant genes was validated using digital polymerase chain reaction. Pathway analysis was used to identify enriched pathways. We also analyzed genes with an extreme pattern of differential expression: only expressed in 1 condition without any expression in the other.

Results—

We found 229 differentially expressed genes in aneurysms versus controls and 1489 in ruptured versus unruptured aneurysms. The differential expression of all 8 genes selected for digital polymerase chain reaction validation was confirmed. Extracellular matrix pathways were enriched in aneurysms versus controls, whereas pathways involved in immune response and the lysosome pathway were enriched in ruptured versus unruptured aneurysms. Immunoglobulin genes were expressed in aneurysms, but showed no expression in controls.

Conclusions—

For rupture of intracranial aneurysms, we identified the lysosome pathway as a new pathway and found further evidence for the role of the immune response. Our results also point toward a role for immunoglobulins in the pathogenesis of aneurysms. Immune-modifying drugs are, therefore, interesting candidate treatment strategies in the prevention of aneurysm development and rupture.
Timing of Occurrence Is the Most Important Characteristic of Spot Sign
Authors: Wang Binli , Yan Shenqiang , Xu Mengjun , Zhang Sheng , Liu Keqin , Hu Haitao , Selim Magdy , Lou Min
Published: March 2016

Background and Purpose—

Most previous studies have used single-phase computed tomographic angiography to detect the spot sign, a marker for hematoma expansion (HE) in spontaneous intracerebral hemorrhage. We investigated whether defining the spot sign based on timing on perfusion computed tomography (CTP) would improve its specificity for predicting HE.

Methods—

We prospectively enrolled supratentorial spontaneous intracerebral hemorrhage patients who underwent CTP within 6 hours of onset. Logistic regression was performed to assess the risk factors for HE and poor outcome. Predictive performance of individual CTP spot sign characteristics were examined with receiver operating characteristic analysis.

Results—

Sixty-two men and 21 women with spontaneous intracerebral hemorrhage were included in this analysis. Spot sign was detected in 46% (38/83) of patients. Receiver operating characteristic analysis indicated that the timing of spot sign occurrence on CTP had the greatest area under receiver operating characteristic curve for HE (0.794; 95% confidence interval, 0.630–0.958;
P
=0.007); the cutoff time was 23.13 seconds. On multivariable analysis, the presence of early-occurring spot sign (ie, spot sign before 23.13 seconds) was an independent predictor not only of HE (odds ratio=28.835; 95% confidence interval, 6.960–119.458;
P
<0.001), but also of mortality at 3 months (odds ratio =22.377; 95% confidence interval, 1.773–282.334;
P
=0.016). Moreover, the predictive performance showed that the redefined early-occurring spot sign maintained a higher specificity for HE compared with spot sign (91% versus 74%).

Conclusions—

Redefining the spot sign based on timing of contrast leakage on CTP to determine early-occurring spot sign improves the specificity for predicting HE and 3-month mortality. The use of early-occurring spot sign could improve the selection of ICH patients for potential hemostatic therapy.
Frontal and Parietal Cortices Show Different Spatiotemporal Dynamics across Problem-solving Stages
Authors: Tschentscher Nadja , Hauk Olaf
Published: March 2016

Arithmetic problem-solving can be conceptualized as a multistage process ranging from task encoding over rule and strategy selection to step-wise task execution. Previous fMRI research suggested a frontal–parietal network involved in the execution of complex numerical and nonnumerical tasks, but evidence is lacking on the particular contributions of frontal and parietal cortices across time. In an arithmetic task paradigm, we evaluated individual participants' “retrieval” and “multistep procedural” strategies on a trial-by-trial basis and contrasted those in time-resolved analyses using combined EEG and MEG. Retrieval strategies relied on direct retrieval of arithmetic facts (e.g., 2 + 3 = 5). Procedural strategies required multiple solution steps (e.g., 12 + 23 = 12 + 20 + 3 or 23 + 10 + 2). Evoked source analyses revealed independent activation dynamics within the first second of problem-solving in brain areas previously described as one network, such as the frontal–parietal cognitive control network: The right frontal cortex showed earliest effects of strategy selection for multistep procedural strategies around 300 msec, before parietal cortex activated around 700 msec. In time–frequency source power analyses, memory retrieval and multistep procedural strategies were differentially reflected in theta, alpha, and beta frequencies: Stronger beta and alpha desynchronizations emerged for procedural strategies in right frontal, parietal, and temporal regions as function of executive demands. Arithmetic fact retrieval was reflected in right prefrontal increases in theta power. Our results demonstrate differential brain dynamics within frontal–parietal networks across the time course of a problem-solving process, and analyses of different frequency bands allowed us to disentangle cortical regions supporting the underlying memory and executive functions.
Physically Based Stochastic Perturbations (PSP) in the Boundary Layer to Represent Uncertainty in Convective Initiation
Authors: Kober Kirstin , Craig George C.
Published: March 2016

Stochastic perturbations allow for the representation of small-scale variability due to unresolved physical processes. However, the properties of this variability depend on model resolution and weather regime. A physically based method is presented for introducing stochastic perturbations into kilometer-scale atmospheric models that explicitly account for these dependencies. The amplitude of the perturbations is based on information obtained from the model’s subgrid turbulence parameterization, while the spatial and temporal correlations are based on physical length and time scales of the turbulent motions. The stochastic perturbations lead to triggering of additional convective cells and improved precipitation amounts in simulations of two days with weak synoptic forcing of convection but different amounts of precipitation. The perturbations had little impact in a third case study, where precipitation was mainly associated with a cold front. In contrast, an unphysical version of the scheme with constant perturbation amplitude performed poorly since there was no perturbation amplitude that would give improved amounts of precipitation during the day without generating spurious convection at other times.
Internal Tide Generation Using Green Function Analysis: To WKB or Not to WKB?
Authors: Mathur Manikandan , Carter Glenn S. , Peacock Thomas
Published: March 2016

An established analytical technique for modeling internal tide generation by barotropic flow over bottom topography in the ocean is the Green function–based approach. To date, however, for realistic ocean studies this method has relied on the WKB approximation. In this paper, the complete Green function method, without the WKB approximation, is developed and tested, and in the process, the accuracy of the WKB approximation for realistic ridge geometries and ocean stratifications is considered. For isolated Gaussian topography, the complete Green function approach is shown to be accurate via close agreement with the results of numerical simulations for a wide range of height ratios and criticality; in contrast, the WKB approach is found to be inaccurate for small height ratios in the subcritical regime and all tall topography that impinges on the pycnocline. Two ocean systems are studied, the Kaena and Wyville Thomson Ridges, for which there is again excellent agreement between the complete Green function approach and numerical simulations, and the WKB approximate solutions have substantial errors. This study concludes that the complete Green function approach, which is typically only modestly more computationally expensive than the WKB approach, should be the go-to analytical method to model internal tide generation for realistic ocean ridge scenarios.
Contribution of Monthly and Regional Rainfall to the Strength of Indian Summer Monsoon
Authors: Zheng Yangxing , Ali M. M. , Bourassa Mark A.
Published: March 2016

Indian summer monsoon rainfall (ISMR; June–September) has both temporal and spatial variability causing floods and droughts in different seasons and locations, leading to a strong or weak monsoon. Here, the authors present the contribution of all-India monthly, seasonal, and regional rainfall to the ISMR, with an emphasis on the strong and weak monsoons. Here, regional rainfall is restricted to the seasonal rainfall over four regions defined by the India Meteorological Department (IMD) primarily for the purpose of forecasting regional rainfall: northwest India (NWI), northeast India (NEI), central India (CI), and south peninsula India (SPIN). In this study, two rainfall datasets provided by IMD are used: 1) all-India monthly and seasonal (June–September) rainfall series for the entire Indian subcontinent as well as seasonal rainfall series for the four homogeneous regions for the period 1901–2013 and 2) the latest daily gridded rainfall data for the period 1951–2014, which is used for assessment at the extent to which the four regions are appropriate for the intended purpose. Rainfall during July–August contributes the most to the total seasonal rainfall, regardless of whether it is a strong or weak monsoon. Although NEI has the maximum area-weighted rainfall, its contribution is the least toward determining a strong or weak monsoon. It is the rainfall in the remaining three regions (NWI, CI, and SPIN) that controls whether an ISMR is strong or weak. Compared to monthly rainfall, regional rainfall dominates the strong or weak rainfall periods.