bluuebunny/crossref_metadata_2025 huggingface dataset:
Genomic in situ hybridization reveals both auto- and allopolyploid origins of different North and Central American hexaploid potato (Solanum sect. Petota) species
Authors: Pendinen Galina , Spooner David M. , Jiang Jiming , Gavrilenko Tatjana
Published: June 2012

Wild potato ( Solanum L. sect. Petota Dumort.) species contain diploids (2n = 2x = 24) to hexaploids (2n = 6x = 72). J.G. Hawkes classified all hexaploid Mexican species in series Demissa Bukasov and, according to a classic five-genome hypothesis of M. Matsubayashi in 1991, all members of series Demissa are allopolyploids. We investigated the genome composition of members of Hawkes’s series Demissa with genomic in situ hybridization (GISH), using labeled DNA of their putative progenitors having diploid AA, BB, or PP genome species or with DNA of tetraploid species having AABB or AAAaAa genomes. GISH analyses support S. hougasii Correll as an allopolyploid with one AA component genome and another BB component genome. Our results also indicate that the third genome of S. hougasii is more closely related to P or a P genome-related species. Solanum demissum Lindl., in contrast, has all three chromosome sets related to the basic A genome, similar to the GISH results of polyploid species of series Acaulia Juz. Our results support a more recent taxonomic division of the Mexican hexaploid species into two groups: the allopolyploid Iopetala group containing S. hougasii, and an autopolyploid Acaulia group containing S. demissum with South American species S. acaule Bitter and S. albicans (Ochoa) Ochoa.
Confirmation of hybridity using GISH and determination of 18S rDNA copy number using FISH in interspecific F1hybrids ofTecoma(Bignoniaceae)
Authors: Contreras Ryan N. , Ruter John M. , Conner Joann , Zeng Yajuan , Ozias-Akins Peggy
Published: June 2012

Interspecific hybridization in Tecoma Juss. was conducted to develop novel forms for the nursery industry. We report fertile hybrids from the cross T. garrocha Hieron. (pistillate parent) × T. stans (L.) Juss. ex Kunth. Leaf morphology of the F1hybrids of T. garrocha × T. stans was intermediate between the parents. GISH also confirmed hybridity. The F1hybrids were successfully backcrossed to both parents and self-pollinated to produce BC and F2progeny. Tecoma garrocha , T. stans, and T. guarume A. DC. ‘Tangelo’ were self-fertile. The F1hybrids also were crossed with T. capensis (Thunb.) Lindl. and T. guarume ‘Tangelo’, resulting in three-species hybrids. FISH conducted on F1hybrids identified four copies of the 18S internal transcribed spacer region. Further analysis using FISH has the potential to provide information on the evolution of Bignoniaceae and the potential role of polyploidy.
Integrated cytogenetic, ecological, and DNA barcode study reveals cryptic diversity inSimulium(Gomphostilbia)angulistylum(Diptera: Simuliidae)
Authors: Pramual Pairot , Kuvangkadilok Chaliow
Published: June 2012

An integrated approach based on cytogenetics, molecular genetics, and ecology was used to examine diversity in the black fly Simulium angulistylum Takaoka & Davies in Thailand. Cytological analysis revealed three cytoforms (A, B, and C) of S. angulistylum differentiated by fixed chromosome inversions. Distributions of these cytoforms were associated with ecology. Cytoforms A and B were found in low-altitude habitats (<600 m above sea level), whereas cytoform C occurred at high altitudes (>1000 m above sea level). Mitochondrial DNA sequences of the cytochrome oxidase subunit I barcoding region revealed significant genetic differentiation among the cytoforms. The mitochondrial DNA haplotype network revealed divergent lineages within cytoforms, indicating additional hidden diversity. Therefore, integrated approaches are necessary for fully understanding black fly biodiversity. Population genetic analysis revealed high genetic structuring that could be due to the habitat preferences of S. angulistylum. Phylogeographic analyses indicated population demographic expansion at the mid-Pleistocene (900 000 years ago), which is older than for other black flies and insects in the Southeast Asian mainland. The high level of genetic structure and diversity, therefore, could also be due to the long demographic history of S. angulistylum.
Book Review: 'The Gamification of Learning and Instruction: Game-Based Methods and Strategies For Training And Education' by Karl Kapp
Authors: Malamed Connie
Published: June 2012

Connie Malamed, the eLearning Coach, reviews Karl Kapp's latest book in which he skillfully explores the depth and breadth of gamification.
Temperature and Safety Profiles of Needle-Warming Techniques in Acupuncture and Moxibustion
Authors: Gao X. Y. , Chong C. Y. , Zhang S. P. , Cheng K. W. E. , Zhu B.
Published: June 2012

The needle-warming technique combines acupuncture and moxibustion, and it is commonly practised in China to relieve pain conditions. However, burning of moxa has many disadvantages. This study examined the temperature and safety profiles of such technique. First, skin temperature changes during needle-warming were examined in anesthetized animals to determine the safe distance for needle-warming moxibustion in human subjects. Then, the practical distance for needle-warming in human subjects were verified. Finally, the temperature profiles of the needle during needle-warming moxibustion were examined using an infrared camera. Our results show that during needle-warming moxibustion there is little heat being conducted into deep tissue via the shaft of the needle, and that the effective heating time to the acupoint is rather short compared to the period of moxibustion. These findings suggest that the needle-warming technique is an inefficient way of acupoint thermal stimulation and should be modified and improved using new technologies.
Authentication and Integrity in the Smart Grid: An Empirical Study in Substation Automation Systems
Authors: Lu Xiang , Wang Wenye , Ma Jianfeng
Published: June 2012

The smart grid is an emerging technology that integrates power infrastructures with information technologies to enable intelligent energy managements. As one of the most important facilities of power infrastructures, electrical substations undertake responsibilities of energy transmissions and distributions by operating interconnected electrical devices in a coordinated manner. Accordingly, it imposes a great challenge on information security, since any falsifications may trigger mal-operations, and result in damages to power usage. In this paper, we aim at authentication and integrity protections in substation automation systems (SAS), by an experimental approach on a small scale SAS prototype, in which messages are transmitted with commonly-used data origin authentication schemes, such as RSA, Message Authentication Code, and One-Time Signature. Through experimental results, we find that, current security solutions cannot be applied directly into the SAS due to insufficient performance considerations in response to application constraints, including limited device computation capabilities, stringent timing requirements and high data sampling rates. Moreover, intrinsic limitations of security schemes, such as complicated computations, shorter key valid time and limited key supplies, can easily be hijacked by malicious attackers, to undermine message deliveries, thus becoming security vulnerabilities. Our experimental results demonstrate guidelines in design of novel security schemes for the smart grid.
A New Approach to Black Hole Quasinormal Modes: A Review of the Asymptotic Iteration Method
Authors: Cho H. T. , Cornell A. S. , Doukas Jason , Huang T.-R. , Naylor Wade
Published: June 2012

We discuss how to obtain black hole quasinormal modes (QNMs) using the asymptotic iteration method (AIM), initially developed to solve second-order ordinary differential equations. We introduce the standard version of this method and present an improvement more suitable for numerical implementation. We demonstrate that the AIM can be used to find radial QNMs for Schwarzschild, Reissner-Nordström (RN), and Kerr black holes in a unified way. We discuss some advantages of the AIM over the continued fractions method (CFM). This paper presents for the first time the spin 0, 1/2 and 2 QNMs of a Kerr black hole and the gravitational and electromagnetic QNMs of the RN black hole calculated via the AIM and confirms results previously obtained using the CFM. We also present some new results comparing the AIM to the WKB method. Finally we emphasize that the AIM is well suited to higher-dimensional generalizations and we give an example of doubly rotating black holes.
Durability Index Performance of High Strength Concretes Made Based on Different Standard Portland Cements
Authors: Ekolu Stephen O. , Murugan Sheena
Published: June 2012

A consortium of three durability index test methods consisting of oxygen permeability, sorptivity and chloride conductivity were used to evaluate the potential influence of four (4) common SANS 10197 cements on strength and durability of concrete. Twenty four (24) concrete mixtures of water-cement ratios (w/c's) = 0.4, 0.5, 0.65 were cast using the cement types CEM I 42.5N, CEM II/A-M (V-L) 42.5N, CEM IV/B 32.5R and CEM II/A-V 52.5N. The concretes investigated fall in the range of normal strength, medium strength and high strength concretes. It was found that the marked differences in oxygen permeability and sorptivity results observed at normal and medium strengths tended to vanish at high concrete strengths. Also, the durability effects attributed to use of different cement types appear to diminish at high strengths. Cements of low strength and/or that contained no extenders (CEM 32.5R, CEM I 42.5N) showed greater sensitivity to sorptivity, relative to other cement types. Results also show that while concrete resistance to chlorides generally improves with increase in strength, adequately high chloride resistance may not be achieved based on high strength alone, and appropriate incorporation of extenders may be necessary.
Single-Walled Carbon Nanotube Network Field Effect Transistor as a Humidity Sensor
Authors: Mudimela Prasantha R. , Grigoras Kestutis , Anoshkin Ilya V. , Varpula Aapo , Ermolov Vladimir , Anisimov Anton S. , Nasibulin Albert G. , Novikov Sergey , Kauppinen Esko I.
Published: June 2012

Single-walled carbon nanotube network field effect transistors were fabricated and studied as humidity sensors. Sensing responses were altered by changing the gate voltage. At the open channel state (negative gate voltage), humidity pulse resulted in the decrease of the source-drain current, and,vice versa, the increase in the source-drain current was observed at the positive gate voltage. This effect was explained by the electron-donating nature of water molecules. The operation speed and signal intensity was found to be dependent on the gate voltage polarity. The positive or negative change in current with humidity pulse at zero-gate voltage was found to depend on the previous state of the gate electrode (positive or negative voltage, respectively). Those characteristics were explained by the charge traps in the gate dielectric altering the effective gate voltage, which influenced the operation of field effect transistor.
The Usefulness of Homeostatic Measurement Assessment-Insulin Resistance (HOMA-IR) for Detection of Glucose Intolerance in Thai Women of Reproductive Age with Polycystic Ovary Syndrome
Authors: Wongwananuruk Thanyarat , Rattanachaiyanont Manee , Leerasiri Pichai , Indhavivadhana Suchada , Techatraisak Kitirat , Angsuwathana Surasak , Tanmahasamut Prasong , Dangrat Chongdee
Published: June 2012

Objectives. To study the cut-off point of Homeostatic Measurement Assessment-Insulin Resistance (HOMA-IR) as a screening test for detection of glucose intolerance in Thai women with polycystic ovary syndrome (PCOS).Study Design. Cross-sectional study.Setting. Department of Obstetrics and Gynecology, Faculty of Medicine Siriraj Hospital.Subject. Two hundred and fifty Thai PCOS women who attended the Gynecologic Endocrinology Unit, during May 2007 to January 2009.Materials and Methods. The paitents were interviewed and examined for weight, height, waist circumference, and blood pressure. Venous blood samples were drawn twice, one at 12-hour fasting and the other at 2 hours after glucose loading.Results. The prevalence of glucose intolerance in Thai PCOS women was 20.0%. The mean of HOMA-IR was 3.53  ±  7.7. Area under an ROC curve for HOMA-IR for detecting glucose intolerance was 0.82. Using the cut-off value of HOMA-IR >2.0, there was sensitivity at 84.0%, specificity at 61.0%, positive predictive value at 35.0%, negative predictive value at 93.8%, and accuracy at 65.6%.Conclusion. HOMA-IR >2.0 was used for screening test for glucose intolerance in Thai PCOS women. If the result was positive, a specific test should be done to prove the diagnosis.
Modelling Marten (Martes americana) Movement Costs in a Boreal Forest: Effects of Grain Size and Thematic Resolution
Authors: Planckaert Ophélie , Desrochers André
Published: June 2012

We investigated landscape resistance to movements of American marten (Martes americana) based on snow-tracking data. We generated movement cost maps of the study area with different grain size, thematic resolution, and habitat-specific resistance to movements. We compared simulated tracks obtained from resistance maps to real tracks plotted along transects that we surveyed in winters 2004 to 2008 at the Montmorency Forest, Quebec, Canada. Simulated tracks were located at the intersection between least-cost paths simulated across the study area and transects. We used nearest-neighbour distances between simulated and real tracks to assess the performance of resistance maps and estimate landscape resistance parameters. Simulations with specified costs to movement for open areas, young forest, and mature forest performed better than simpler resistance scenarios, suggesting that resistance to marten movements differed among those landscape attributes that were considered. Simulations with a map grain size of 100 m performed significantly better than 5, 25, and 300 m, possibly because of gap crossing avoidance. Model performance (compared to null model) was maximal when resistance to movement in open habitat was set to 20 times higher than in mature forest, but uncertainty around this estimate was large. This research demonstrates that presence-only (point) data can be used to parameterize movements using spatially explicit modelling.
3D Finite Volume Modeling of ENDE Using ElectromagneticT-Formulation
Authors: Li Yue , Berthiau Gérard , Feliachi Mouloud , Cheriet Ahmed
Published: June 2012

An improved method which can analyze the eddy current density in conductor materials using finite volume method is proposed on the basis of Maxwell equations andT-formulation. The algorithm is applied to solve 3D electromagnetic nondestructive evaluation (E’NDE) benchmark problems. The computing code is applied to study an Inconel 600 work piece with holes or cracks. The impedance change due to the presence of the crack is evaluated and compared with the experimental data of benchmark problems No. 1 and No. 2. The results show a good agreement between both calculated and measured data.
Genetic Overlap between Holoprosencephaly and Kallmann Syndrome
Authors: Vaaralahti K. , Raivio T. , Koivu R. , Valanne L. , Laitinen E.-M. , Tommiska J.
Published: June 2012

Patients with Kallmann syndrome (KS; congenital hypogonadotropic hypogonadism and decreased/absent sense of smell), septo-optic dysplasia (SOD), or holoprosencephaly (HPE) reportedly have midline defects. In this study, we investigate a genetic overlap between KS, SOD, and HPE. Nineteen subjects (18 males, 1 female) with KS and without mutations in the known KS genes were screened for mutations in SOX2, SHH, SIX3,TGIF1,TDGF1,FOXH1,GLI2, and GLI3. One male carried 2 heterozygous missense changes, one in SIX3 (c.428G>A, p.G143D) and the other in GLI2 (c.2509G>A, p.E837K). Both of these genes have been implicated in the etiology of HPE and neither of these changes were present in 200 control subjects. Other variants found among the subjects were known polymorphisms. KS and HPE may display a genetic overlap. The involvement of genes implicated in the etiology of midline defects in patients with KS warrants further studies.
Radionuclide Detection of Multiple Soft Tissue Metastases of Osteosarcoma Masquerading as Bone Metastasis
Authors: Takesh Mustafa , Zoller Henry , Ghazi Husam , Zein Majdi , Sahli Hussam
Published: June 2012

Objective: The aim of this work was to report an unusual case of multiple soft tissue metastases of osteosarcoma detected using bone scan and confirmed by CT scan. Clinical Presentation and Intervention: A 15-year-old patient with a history of osteogenic sarcoma presented with fatigue and loss of appetite in addition to a painless swelling of the distal left lower extremity. Bone scan and chest CT scan were performed for restaging purposes. The bone scan revealed multiple bone metastases and suspected tumor recurrence in the left lower extremity in addition to multiple extraosseous hot spots. The latter findings were assessed as ossified soft tissue metastases after considering the performed CT scan. Conclusion: This case showed the double role of bone scan in osteosarcoma in simultaneously assessing the bone status and tumor spread in soft tissue. The benefit of a comparison of bone scan findings with other modalities was also demonstrated.
Platelets selectively enhance lymphocyte adhesion on subendothelial matrix under arterial flow conditions
Authors: Ersoy Maria , Hjemdahl Paul , Savion Naphtali , Varon David , Spectre Galia , Zhu Linjing , Li Nailin
Published: June 2012

Platelet adhesion at sites of cardiovascular injury may facilitate leukocyte deposition. We asked if and how platelets enhance lymphocyte adhesion on different subendothelial matrix protein (SEMP)-coated surface at arterial shear stress. Hirudinised whole blood was subjected to an arterial shear rate (500 s−1) in a Cone and Plate(let) analyser (CPA) for 5 minutes using plates coated with bovine serum albumin (BSA), collagen, fibrinogen, von Willebrand factor (vWF), or fibronectin. Platelet and lymphocyte adhesion were monitored by CPA and flow cytometry. Exposure of blood to collagen, fibrinogen, and vWF-coated surfaces induced platelet activation. The most marked effect was seen with collagen-coating, which markedly enhanced the adhesion of all lymphocyte subpopulations compared to BSA-coating. Fibrinogen-coating supported both T and NK cell adhesion, while vWF-coated surface only enhanced NK cell deposition. In contrast, fibronectin enhanced neither platelet activation nor lymphocyte adhesion. Moreover, platelets preferentially facilitated adhesion of large CD4+ and CD8+ T cells and NK cells, and of small B cells. Enhanced cell adhesion of larger lymphocytes was associated with elevated platelet conjugation and higher lymphocyte expression of PSGL-1, Mac-1, and CD40L. The enhancement of lymphocyte adhesion was totally platelet-dependent, and was abolished in platelet-depleted blood. Moreover, blockade of the platelet adhesion molecules P-selectin, GPIIb/IIIa, and CD40L attenuated platelet-dependent lymphocyte deposition. In conclusion, platelets support lymphocyte adhesion on SEMP-coated surfaces under arterial shear. The enhancement is selective for large T and NK cells and small B cells.
Relationship Between Delay in Performing Direct Coronary Angioplasty and Early Clinical Outcome in Patients With Acute Myocardial Infarction
Authors: Berger Peter B. , Ellis Stephen G. , Holmes David R. , Granger Christopher B. , Criger Douglas A. , Betriu Amadeo , Topol Eric J. , Califf Robert M.
Published: June 2012

Background
—Time to treatment with thrombolytic therapy is a critical determinant of mortality in acute myocardial infarction. Little is known about the relationship between the time to treatment with direct coronary angioplasty and clinical outcome. The objectives of this study were to determine both the time required to perform direct coronary angioplasty in the Global Use of Strategies to Open Occluded Arteries in Acute Coronary Syndromes (GUSTO-IIb) trial and its relationship to clinical outcome.

Methods and Results
—Patients randomized to direct coronary angioplasty (n=565) were divided into groups based on the time between study enrollment and first balloon inflation. Patients randomized to angioplasty who did not undergo the procedure were also analyzed. The median time from study enrollment to first balloon inflation was 76 minutes; 19% of patients assigned to angioplasty did not undergo an angioplasty procedure. The 30-day mortality rate of patients who underwent balloon inflation ≤60 minutes after study enrollment was 1.0%; 61 to 75 minutes after enrollment, 3.7%; 76 to 90 minutes after enrollment, 4.0%; and ≥91 minutes after enrollment, 6.4%. The mortality rate of patients assigned to angioplasty who never underwent the procedure was 14.1% (
P
=0.001). Logistic regression analysis revealed that the time from enrollment to first balloon inflation was a significant predictor of mortality within 30 days; after adjustment for differences in baseline characteristics, the odds of death increased 1.6 times (
P
=0.008) for a movement from each time interval to the next.

Conclusions
—The time to treatment with direct PTCA, as with thrombolytic therapy, is a critical determinant of mortality.
Muscle Metaboreflex Contribution to Sinus Node Regulation During Static Exercise
Authors: Iellamo Ferdinando , Pizzinelli Paolo , Massaro Michele , Raimondi Gianfranco , Peruzzi Giuseppe , Legramante Jacopo Maria
Published: June 2012

Background
—It is currently assumed that during static exercise, central command increases heart rate (HR) through a decrease in parasympathetic activity, whereas the muscle metaboreflex raises blood pressure (BP) only through an increase in sympathetic outflow to blood vessels, because when the metaboreflex activation is maintained during postexercise muscle ischemia, BP remains elevated while HR recovers. We tested the hypotheses that the muscle metaboreflex contributes to HR regulation during static exercise via sympathetic activation and that the arterial baroreflex is involved in the HR recovery of postexercise muscle ischemia.

Methods and Results
—Eleven healthy male volunteers performed 4-minute static leg extension (SLE) at 30% of maximal voluntary contraction, followed by 4-minute arrested leg circulation (ALC). Autonomic regulation of HR was investigated by spectral analysis of HR variability (HRV), and baroreflex control of heart period was assessed by the spontaneous baroreflex method. SLE resulted in a significant increase in the low-frequency component of HRV that remained elevated during ALC. The normalized high-frequency component of HRV was reduced during SLE and returned to control levels during ALC. Baroreflex sensitivity was significantly reduced during SLE and returned to control levels during ALC when BP was kept elevated above the resting level while HR recovered.

Conclusions
—The muscle metaboreflex contributes to HR regulation during static exercise via a sympathetic activation. The bradycardia that occurs during postexercise muscle ischemia despite the maintained sympathetic stimulus may be explained by a baroreflex-mediated increase in parasympathetic outflow to the sinoatrial node that overpowers the metaboreflex-induced cardiac sympathetic activation.
Endothelin-1 Potentiates Human Smooth Muscle Cell Growth to PDGF
Authors: Yang Zhihong , Krasnici Nazmi , Lüscher Thomas F.
Published: June 2012

Background
—Endothelin-1 (ET-1) is a potent vasoconstrictor. However, its mitogenic effects on vascular smooth muscle cells (SMCs) remain controversial. We investigated the role of ET-1 in human SMC growth and its synergistic effect with platelet-derived growth factor (PDGF).

Methods and Results
—Human aortic SMCs were cultured and cell proliferation was assayed by [
3
H]thymidine incorporation. PDGF receptor expression, activation of mitogen-activated protein kinase (MAPK), cell cycle regulators such as cyclin-dependent kinase 2 (Cdk2), Cdk inhibitor (p27
Kip1
), and retinoblastoma protein (pRb) were analyzed by immunoblotting. ET-1 on its own was unable to stimulate [
3
H]thymidine incorporation but dramatically potentiated the effect of PDGF-BB up to 6-fold (
P
<0.001). Most of the potentiating effects (88%) were blocked by the ET
A
receptor antagonist LU135252 and slightly further blocked by the ET
A/B
receptor antagonist bosentan (
P
<0.05). ET-1 stimulated MAPK, but it neither potentiated PDGF-induced MAPK activation nor overexpressed PDGF receptors. In contrast to PDGF-BB, ET-1 had no regulatory effects on Cdk2, p27
Kip1
, and pRb.

Conclusions
—In human SMCs, ET-1 activates MAPK but has no mitogenic effects on its own. However, ET-1 markedly potentiates proliferation to PDGF, mainly via ET
A
receptors. This may represent an important function of ET-1 for vascular structural changes in patients and provide new therapeutic opportunities for ET-1 receptor antagonists.
C-Reactive Protein as a Cardiovascular Risk Factor
Authors: Lagrand Wim K. , Visser Cees A. , Hermens Willem T. , Niessen Hans W. M. , Verheugt Freek W. A. , Wolbink Gert-Jan , Hack C. Erik
Published: June 2012

Background
—Circulating levels of C-reactive protein (CRP) may constitute an independent risk factor for cardiovascular disease. How CRP as a risk factor is involved in cardiovascular disease is still unclear.

Methods and Results
—By reviewing available studies, we discuss explanations for the associations between CRP and cardiovascular disease. CRP levels within the upper quartile/quintile of the normal range constitute an increased risk for cardiovascular events, both in apparently healthy persons and in persons with preexisting angina pectoris. High CRP responses after acute myocardial infarction indicate an unfavorable outcome, even after correction for other risk factors. This link between CRP and cardiovascular disease has been considered to reflect the response of the body to the inflammatory reactions in the atherosclerotic (coronary) vessels and adjacent myocardium. However, because CRP localizes in infarcted myocardium (with colocalization of activated complement), we hypothesize that CRP may directly interact with atherosclerotic vessels or ischemic myocardium by activation of the complement system, thereby promoting inflammation and thrombosis.

Conclusions
—CRP constitutes an independent cardiovascular risk factor. Unraveling the molecular background of this association may provide new directions for prevention of cardiovascular events.
Derivation and Prospective Validation of a Simple Index for Prediction of Cardiac Risk of Major Noncardiac Surgery
Authors: Lee Thomas H. , Marcantonio Edward R. , Mangione Carol M. , Thomas Eric J. , Polanczyk Carisi A. , Cook E. Francis , Sugarbaker David J. , Donaldson Magruder C. , Poss Robert , Ho Kalon K. L. , Ludwig Lynn E. , Pedan Alex , Goldman Lee
Published: June 2012

Background
—Cardiac complications are important causes of morbidity after noncardiac surgery. The purpose of this prospective cohort study was to develop and validate an index for risk of cardiac complications.

Methods and Results
—We studied 4315 patients aged ≥50 years undergoing elective major noncardiac procedures in a tertiary-care teaching hospital. The main outcome measures were major cardiac complications. Major cardiac complications occurred in 56 (2%) of 2893 patients assigned to the derivation cohort. Six independent predictors of complications were identified and included in a Revised Cardiac Risk Index: high-risk type of surgery, history of ischemic heart disease, history of congestive heart failure, history of cerebrovascular disease, preoperative treatment with insulin, and preoperative serum creatinine >2.0 mg/dL. Rates of major cardiac complication with 0, 1, 2, or ≥3 of these factors were 0.5%, 1.3%, 4%, and 9%, respectively, in the derivation cohort and 0.4%, 0.9%, 7%, and 11%, respectively, among 1422 patients in the validation cohort. Receiver operating characteristic curve analysis in the validation cohort indicated that the diagnostic performance of the Revised Cardiac Risk Index was superior to other published risk-prediction indexes.

Conclusions
—In stable patients undergoing nonurgent major noncardiac surgery, this index can identify patients at higher risk for complications. This index may be useful for identification of candidates for further risk stratification with noninvasive technologies or other management strategies, as well as low-risk patients in whom additional evaluation is unlikely to be helpful.
Purple Grape Juice Improves Endothelial Function and Reduces the Susceptibility of LDL Cholesterol to Oxidation in Patients With Coronary Artery Disease
Authors: Stein James H. , Keevil Jon G. , Wiebe Donald A. , Aeschlimann Susan , Folts John D.
Published: June 2012

Background
—In vitro, the flavonoid components of red wine and purple grape juice are powerful antioxidants that induce endothelium-dependent vasodilation of vascular rings derived from rat aortas and human coronary arteries. Although improved endothelial function and inhibition of LDL oxidation may be potential mechanisms by which red wine and flavonoids reduce cardiovascular risk, the in vivo effects of grape products on endothelial function and LDL oxidation have not been investigated. This study assessed the effects of ingesting purple grape juice on endothelial function and LDL susceptibility to oxidation in patients with coronary artery disease (CAD).

Methods and Results
—Fifteen adults with angiographically documented CAD ingested 7.7±1.2 mL · kg
−1
· d
−1
of purple grape juice for 14 days. Flow-mediated vasodilation (FMD) was measured using high-resolution brachial artery ultrasonography. Susceptibility of LDL particles to oxidation was determined from the rate of conjugated diene formation after exposure to copper chloride. At baseline, FMD was impaired (2.2±2.9%). After ingestion of grape juice, FMD increased to 6.4±4.7% (
P
=0.003). In a linear regression model that included age, artery diameter, lipid values, and use of lipid-lowering and antioxidant therapies, the effect of grape juice on FMD remained significant (mean change 4.2±4.4%,
P
<0.001). After ingestion of grape juice, lag time increased by 34.5% (
P
=0.015).

Conclusions
—Short-term ingestion of purple grape juice improves FMD and reduces LDL susceptibility to oxidation in CAD patients. Improved endothelium-dependent vasodilation and prevention of LDL oxidation are potential mechanisms by which flavonoids in purple grape products may prevent cardiovascular events, independent of alcohol content.
Origin of Oscillatory Kinetics of Respiratory Gas Exchange in Chronic Heart Failure
Authors: Francis Darrel P. , Davies L. Ceri , Piepoli Massimo , Rauchhaus Mathias , Ponikowski Piotr , Coats Andrew J. S.
Published: June 2012

Background
—Respiratory gas exchange measurements in patients with chronic heart failure (CHF) at rest and during exercise commonly reveal prominent slow oscillations in ventilation (V̇
E
), measured oxygen uptake (V̇
o
2
), and carbon dioxide production (V̇
co
2
), whose origin is not clear. Voluntary simulation of periodic breathing (PB) in normals has been reported to generate a different pattern of oscillations in gas exchange from that seen in spontaneous PB. This necessitates hypothesizing that PB is caused by a primary oscillation in tissue metabolism or in cardiac output.

Methods and Results
—We developed an automated method by which normal controls could be guided to breathe according to a PB pattern. The resultant metabolic oscillations closely matched those seen in spontaneous PB and had several interesting properties. At low workloads (including rest), the oscillations in V̇
o
2
were as prominent as those in V̇
E
in both spontaneous PB (α
VO2
/α
VE
=0.92±0.04) and voluntary PB (0.93±0.07). However, at increased workload, the oscillations in V̇
o
2
because less prominent than those in V̇
E
in spontaneous PB (intermediate workload 0.63±0.05, high workload 0.57±0.04;
P
<0.001) and voluntary PB (intermediate 0.66±0.03, high 0.48±0.03;
P
<0.001). There was no difference in the relative size of metabolic oscillations between voluntary and spontaneous PB at matched workloads (
P
>0.05 at low, intermediate, and high workloads). Furthermore, V̇
o
2
peaked before V̇
E
in both spontaneous and voluntary PB. This time delay varied from 6.4±0.4 s at low ventilation, to 11.3±0.9 s at high ventilation (
P
<0.0001).

Conclusions
—The magnitude and phase pattern of oscillations in gas exchange of spontaneous PB can be obtained by adequately matched voluntary PB. Therefore, the gas exchange features of PB are explicable by primary ventilatory oscillation.
Association of Serum Antibodies to Heat-Shock Protein 65 With Carotid Atherosclerosis
Authors: Xu Qingbo , Kiechl Stefan , Mayr Manuel , Metzler Bernhard , Egger Georg , Oberhollenzer Friedrich , Willeit Johann , Wick Georg
Published: June 2012

Background
—Previous work has proved that increased titers of antibodies against heat-shock protein (hsp) 65 are associated with atherosclerotic lesions independently of other established risk factors. The present follow-up study was designed to further scrutinize the association of hsp antibodies and atherosclerosis and evaluate the possible predictive value of these antibodies for the development and/or progression of lesions in the same population.

Methods and Results
—A total of 750 subjects 45 to 74 years old were recruited, and the rate of participation was 93.6%; 58 subjects died between 1990 and 1995. All participants were subjected to determination of serum antibodies against hsp65 and sonography to assess carotid atherosclerotic lesions and evaluate other risk factors, ie, age, sex, body mass index, blood cholesterol, apolipoprotein B, apolipoprotein A, triglycerides, lipoprotein(a), fibrinogen, leukocyte number, antithrombin III, ESR, ferritin, hypertension, smoking, and diabetes mellitus. Our data show that hsp65 antibody titers in the population emerged as highly consistent over a 5-year observation period (
r
=0.78,
P
<0.0001). Titers were significantly elevated in subjects with progressive carotid atherosclerosis and correlated with intima/media thickness. Multiple linear regression analysis documented these associations to be independent of age, sex, and other risk factors. Subanalyses revealed a preferential association of hsp65 antibody titers with advanced lesions (odds ratio, 1.42; 95% CI, 1.02 to 1.98;
P
=0.039). Other risk factors neither confounded nor modified this association. Finally, hsp65 antibody titers significantly predicted the 5-year mortality (hazard ratio, 1.52; 95% CI, 1.14 to 2.03;
P
<0.001).

Conclusions
—These findings indicate a sustained existence of anti-hsp65 antibodies in subjects with severe atherosclerosis, which is predictive for mortality.
Impairment of Endothelium-Dependent Arterial Relaxation By High-Fat Feeding in ApoE-Deficient Mice
Authors: Deckert Valérie , Lizard Gérard , Duverger Nicolas , Athias Anne , Palleau Viviane , Emmanuel Florence , Moisant Maryvonne , Gambert Philippe , Lallemant Christian , Lagrost Laurent
Published: June 2012

Background
—Atherogenic lipoproteins can impair the endothelium-dependent arterial relaxation, and circumstantial evidence suggests a beneficial role of plasma high density lipoproteins and apolipoprotein (apo) A-I in counteracting the endothelium dysfunction. In the present study, vascular reactivity was determined in control, apoE-deficient mice (apoE-KO mice), and apoE-deficient mice expressing human apoA-I (apoE-KO/HuAITg mice).

Methods and Results
—In the first part of the study, control and apoE-KO mice were fed a low-fat or a high-fat diet for 23 weeks, and the vasoactive responses of isolated thoracic aortic segments to norepinephrine, sodium nitroprusside, and acetylcholine (ACh) were determined. Whereas norepinephrine, sodium nitroprusside, and ACh evoked similar vascular responses in control and apoE-KO mice fed the low-fat diet, high-fat feeding in apoE-KO mice produced a significant 3-fold increase in the mean concentration required to produce a half-maximal relaxing effect (EC
50
) of ACh as compared with control mice. This reflects a weaker sensitivity to ACh of the aortic segments from the apoE-deficient animals. In the second part of the study, the mean EC
50
for ACh after high-fat feeding was found to be 4.4-fold lower in apoE-KO/HuAITg mice than in apoE-KO mice, indicating that the reduced sensitivity to ACh of the thoracic aorta from the apoE-KO mice fed the high-fat diet is improved by the expression of human apoA-I.

Conclusions
—The present study demonstrates that the endothelium-dependent arterial relaxation is impaired in apoE-KO mice fed the high-fat diet. The endothelium dysfunction tends to be normalized by human apoA-I expression.
Heterozygosity for a Hereditary Hemochromatosis Gene Is Associated With Cardiovascular Death in Women
Authors: Roest Mark , van der Schouw Yvonne T. , de Valk Bart , Marx Jo J. M. , Tempelman Mariëlle J. , de Groot Philip G. , Sixma Jan J. , Banga Jan Dirk
Published: June 2012

Background
—The genetic background of hereditary hemochromatosis (
HH
) is homozygosity for a cysteine-to-tyrosine transition at position 282 in the
HFE
gene. Heterozygosity for
HH
is associated with moderately increased iron levels and could be a risk factor for cardiovascular death.

Methods and Results
—We studied the relation between
HH
heterozygosity and cardiovascular death in a cohort study among 12 239 women 51 to 69 years of age residing in Utrecht, the Netherlands. Women were followed for 16 to 18 years (182 976 follow-up years). The allele prevalence of the
HH
gene in the reference group was 4.0 (95% CI 2.9 to 5.4). The mortality rate ratios for
HH
heterozygotes compared with wild types was 1.5 (95% CI 0.9 to 2.5) for myocardial infarction (n=242), 2.4 (95% CI 1.3 to 3.5) for cerebrovascular disease (n=118), and 1.6 (95% CI 1.1 to 2.4) for total cardiovascular disease (n=530). The population-attributable risks of
HH
heterozygosity for myocardial infarction and cerebrovascular and total cardiovascular death were 3.3%, 8.8%, and 4.0%, respectively. In addition, we found evidence for effect modification by hypertension and smoking.

Conclusions
—We found important evidence that inherited variation in iron metabolism is involved in cardiovascular death in postmenopausal women, especially in women already carrying classic risk factors.
Increased Risk of Acute Myocardial Infarction in Carriers of the Hemochromatosis Gene Cys282Tyr Mutation
Authors: Tuomainen Tomi-Pekka , Kontula Kimmo , Nyyssönen Kristiina , Lakka Timo A. , Heliö Tiina , Salonen Jukka T.
Published: June 2012

Background
—Homozygosity for a relatively common Cys282Tyr mutation of the human hemochromatosis-associated (
HFE
) gene was recently found to account for most cases of hereditary hemochromatosis. Because excess iron has been postulated to enhance risk of vascular disease, we studied whether occurrence of this mutation was associated with increased risk of first acute myocardial infarction in healthy middle-aged men in a prospective cohort study.

Methods and Results
—Study subjects were the 1150 participants in the population-based Kuopio Ischemic Heart Disease Risk Factor Study (KIHD), aged 42, 48, 54, or 60 years at baseline, who had no coronary heart disease at baseline and for whom a DNA sample was available. Information about myocardial infarctions was collected prospectively by use of FINMONICA (FINnish MONItoring of trends and determinants in CArdiovascular disease study) and hospital data. Events were classified by MONICA (MONItoring of trends and determinants in CArdiovascular disease study) diagnostic criteria. The
HFE
Cys282Tyr mutation was assayed by a solid-phase minisequencing technique. One subject was homozygous and 76 individuals were heterozygous for the
HFE
Cys282Tyr mutation (6.7%). During a mean follow-up of 9 years, 8 (10.4%) of 77 carriers and 60 (5.6%) of 1073 noncarriers experienced an acute myocardial infarction. In a Cox proportional hazards model allowing for the other strongest risk factors, the carriers had a 2.3-fold (95% CI 1.1 to 4.8;
P
=0.03) risk of acute myocardial infarction compared with noncarriers.

Conclusions
—Male carriers of the common hemochromatosis gene mutation are at 2-fold risk for first acute myocardial infarction compared with noncarriers.
Nitric Oxide Modulates Mitochondrial Respiration in Failing Human Heart
Authors: Loke Kit E. , Laycock Sarra K. , Mital Seema , Wolin Michael S. , Bernstein Robert , Oz Mehmet , Addonizio Linda , Kaley Gabor , Hintze Thomas H.
Published: June 2012

Background
—Our objective for this study was to investigate whether nitric oxide (NO) modulates tissue respiration in the failing human myocardium.

Methods and Results
—Left ventricular free wall and right ventricular tissue samples were taken from 14 failing explanted human hearts at the time of transplantation. Tissue oxygen consumption was measured with a Clark-type oxygen electrode in an airtight stirred bath containing Krebs solution buffered with HEPES at 37°C (pH 7.4). Rate of decrease in oxygen concentration was expressed as a percentage of the baseline, and results of the highest dose are indicated. Bradykinin (10
−4
mol/L, −21±5%), amlodipine (10
−5
mol/L, −14±5%), the ACE inhibitor ramiprilat (10
−4
mol/L, −21±2%), and the neutral endopeptidase inhibitor thiorphan (10
−4
mol/L, −16±5%) all caused concentration-dependent decreases in tissue oxygen consumption. Responses to bradykinin (−2±6%), amlodipine (−2±4%), ramiprilat (−5±6%), and thiorphan (−4±7%) were significantly attenuated after NO synthase blockade with
N
-nitro-
l
-arginine methyl ester (10
−4
mol/L; all
P
<0.05). NO-releasing compounds
S
-nitroso-
N
-acetyl-penicillamine (10
−4
mol/L, −34±5%) and nitroglycerin (10
−4
mol/L, −21±5%), also decreased tissue oxygen consumption in a concentration-dependent manner. However, the reduction in tissue oxygen consumption in response to
S
-nitroso-
N
-acetyl-penicillamine (−35±7%) or nitroglycerin (−16±5%) was not significantly affected by
N
-nitro-
l
-arginine methyl ester.

Conclusions
—These results indicate that the modulation of oxygen consumption by both endogenous and exogenous NO is preserved in the failing human myocardium and that the inhibition of kinin degradation plays an important role in the regulation of mitochondrial respiration.
Evidence for Prothrombotic Effects of Exercise and Limited Protection by Aspirin
Authors: Li Nailin , Wallén N. Håkan , Hjemdahl Paul
Published: June 2012

Background
—Exercise may activate platelets and leukocytes and promote thrombosis. The effects of aspirin treatment on the prothrombotic effects of exercise have not been established.

Methods and Results
—A total of 15 healthy men performed exhaustive exercise without and with 1 week of pretreatment with aspirin (500 mg/day). Before and immediately after exercise, platelet aggregability ex vivo was measured by filtragometry, and venous blood samples were obtained. Whole-blood flow cytometry was used to determine platelet and leukocyte activation and platelet-leukocyte aggregates. Exercise increased platelet P-selectin expression, CD11b expression in neutrophils and lymphocytes, and platelet and leukocyte responses to thrombin, ADP, platelet activating factor, and N-formyl-methionyl-leucyl-phenylalanine (fMLP) in vitro. Consistent with enhanced platelet and leukocyte activation, more circulating platelet-platelet and platelet-leukocyte aggregates were detected after exercise (
P
<0.001 for both). Filtragometry readings were shortened, and plasma soluble P-selectin and prothrombin fragment 1+2 were elevated. Aspirin markedly reduced the urinary excretion of 11-dehydrothromboxane B
2
, decreased P-selectin expression in single platelets at rest (
P
<0.05), and inhibited fMLP-induced neutrophil CD11b expression, but it did not attenuate exercise-induced increases in platelet aggregability, platelet P-selectin expression, leukocyte CD11b expression, platelet-leukocyte aggregate formation, soluble P-selectin, or prothrombin fragment 1+2.

Conclusions
—Exercise induced platelet and leukocyte activation and platelet-leukocyte aggregation in vivo, and it increased platelet and leukocyte responsiveness to in vitro stimulation. Aspirin treatment attenuated certain signs of platelet activity in vivo at rest and fMLP-induced neutrophil activation in vitro, but it did not attenuate the prothrombotic effects of exercise.
Association Between Local Pulse Pressure, Mean Blood Pressure, and Large-Artery Remodeling
Authors: Boutouyrie Pierre , Bussy Caroline , Lacolley Patrick , Girerd Xavier , Laloux Brigitte , Laurent Stéphane
Published: June 2012

Background
—The aim of the present study was to determine the respective influences of local pulse pressure and mean blood pressure on arterial remodeling in humans at 2 arterial sites: a central, predominantly elastic artery (the common carotid artery) and a peripheral muscular artery (the radial artery).

Methods and Results
—Forty-three healthy subjects and 124 never-treated hypertensive patients were included in the study. Intima-media thickness and internal diameter of the carotid and radial arteries were noninvasively determined with high-definition echo-tracking devices. Pulse pressure was measured locally with applanation tonometry. Multivariate regression models including mean blood pressure and local pulse pressure were established in the whole population. Carotid internal diameter and intima-media thickness were strongly influenced (
P
<0.0001) by carotid pulse pressure but not by mean blood pressure or brachial pulse pressure, independently of age and sex. Radial artery internal diameter was correlated with age but not with mean blood pressure or radial pulse pressure. Radial artery intima-media thickness was correlated with mean blood pressure (
P
<0.001) but not with radial pulse pressure.

Conclusions
—Carotid pulse pressure was a strong independent determinant of carotid artery enlargement and wall thickening, whereas mean blood pressure and brachial pulse pressure were not, indicating the prominent influence of local pulsatile mechanical load on arterial remodeling. These relationships were observed at the site of an elastic artery but not at the site of a muscular artery, suggesting the contribution of cyclic stretching to the pulse pressure–induced arterial remodeling.