bluuebunny/crossref_metadata_2025 huggingface dataset:
Are there differences in injury mortality among refugees and immigrants compared with native-born?
Authors: Norredam Marie , Olsbjerg Maja , Petersen Jorgen H , Laursen Bjarne , Krasnik Allan
Published: May 2012

Background

The authors studied injury mortality in Denmark among refugees and immigrants compared with that among native Danes.

Method

A register-based, historical prospective cohort design. All refugees (n=29 139) and family reunited immigrants (n=27 134) who between 1 January 1993 and 31 December 1999 received residence permission were included and matched 1:4 on age and sex with native Danes. Civil registration numbers were cross-linked to the Register of Causes of Death, and fatalities due to unintentional and intentional injuries were identified based on ICD-10 diagnosis. Sex-specific mortality ratios were estimated by migrant status and region of birth, adjusting for age and income and using a Cox regression model after a median follow-up of 11–12 years.

Results

Compared with native Danes, both female (RR=0.44; 95% CI 0.23 to 0.83) and male (RR=0.40; 95% CI 0.29 to 0.56) refugees as well as female (RR=0.40; 95% CI 0.21 to 0.76) and male (RR=0.22; 95% CI 0.12 to 0.42) immigrants had significantly lower mortality from unintentional injuries. Suicide rates were significantly lower for male refugees (RR=0.38; 95% CI 0.24 to 0.61) and male immigrants (RR=0.24; 95% CI 0.10 to 0.59), whereas their female counterparts showed no significant differences. Only immigrant women had a significantly higher homicide rate (RR=3.09; 95% CI 1.11 to 8.60) compared with native Danes.

Conclusions

Overall results were advantageous to migrant groups. Research efforts should concentrate on investigating protective factors among migrants, which may benefit injury prevention in the majority population.
Sickle cell disease is associated with decreased HIV but higher HBV and HCV comorbidities in US hospital discharge records: a cross-sectional study
Authors: Nouraie Mehdi , Nekhai Sergei , Gordeuk Victor R
Published: May 2012

Objective

Some studies suggest that HIV infection progresses slowly in patients with sickle cell disease (SCD). The authors aimed to determine the relationships between SCD and HIV infection.

Methods

National Hospital Discharge Survey data from adult African–Americans in the period of 1997–2009 were analysed. The comorbidities of SCD with HIV infections in hospital discharges were analysed. Multiple logistic regression was used to test the association between SCD and HIV. For comparative purposes, the relationships of SCD with hepatitis B virus (HBV) and hepatitis C virus (HCV) were also assessed.

Results

423 431 records were divided into two time periods 1997–2003 (53% of records) and 2004–2009 (47% of records). The frequency of HIV diagnosis was lower in patients with SCD (1.5% vs 3.3% in patients without SCD). In logistic regression, SCD diagnosis was associated with an OR of 0.24 (95% CI 0.18 to 0.32) for HIV diagnosis in the first period and with an OR of 0.31 (95% CI 0.22 to 0.42) in the second period. In contrast, SCD was associated with higher risk of HCV (OR=2.01, 95% CI 1.56 to 2.59 in the first period and OR=2.12, 95% CI 1.71 to 2.63 in the second period). SCD was also associated with a higher risk of HBV (OR=1.15, 95% CI 0.72 to 1.83 in the first period and OR=1.82, 95% CI 1.24 to 2.68 in the second period).

Conclusions

The lower risk of HIV comorbidity, but not HCV and HBV, with SCD is consistent with the possibility that SCD has a unique effect in altering the risk of HIV infection or progression. Investigation of how the haemolytic and immunological changes of SCD influence HIV might lead to new therapeutic or preventive approaches.
Effect of Gate Length on Device Performances of AlSb/InAs High Electron Mobility Transistors Fabricated Using BCl3 Dry Etching
Authors: Kuo Chien-I , Hsu Heng-Tung , Hsu Ching-Yi , Yu Chia-Hui , Ho Han-Chieh , Chang Edward Yi , Chyi Jen-Inn
Published: May 2012

In this paper, we present the development of a mesa isolation process for AlSb/InAs high electron mobility transistors (HEMTs) using inductively coupled plasma (ICP) etching with BCl3 gas. Devices with different gate lengths (L
g: 60, 100, and 200 nm) fabricated by this dry etching technique show good DC and RF performances. With an appropriate L
g/gate-channel distance ratio, the 200-nm-gate has very high peak transconductances of 781 mS/mm at V
DS = 0.1 V and 2000 mS/mm at V
DS = 0.5 V. Moreover, an extrinsic current gain cutoff frequency of 137 GHz and maximum oscillation frequency of 97 GHz were achieved at a drain bias voltage V
DS = 0.3 V, indicating the great potential for such a device operating at high frequency with extremely low DC power consumption.
Carrier Transport Mechanism of a Low Resistance Ti/Al Ohmic Contact on (112̄2) Semipolar n-Type GaN
Authors: Jung Sungmin , Lee Sung-Nam , Ahn Kwang-Soon , Kim Hyunsoo
Published: May 2012

The carrier transport mechanism of a low resistance Ti/Al Ohmic contact to (112̄2) semipolar n-type GaN grown on m-plane sapphire substrate was investigated. Thermal annealing led to an excellent Ohmic contact with a specific contact resistance of 3.2 ×10-4 Ω cm2. Current–voltage–temperature measurements revealed insignificant changes in the specific contact resistance with respect to temperature, which is evidence of a tunneling transport. Based on the thermionic field emission model, a very low Schottky barrier height of 3 meV and barrier width of 1 nm were obtained due to increased interfacial carriers of 9.2 ×1018 cm-3, resulting in excellent Ohmic contact to semipolar n-type GaN.
Filterless Ultraviolet Detector Based on Cerium Fluoride Thin Film Grown by Pulsed Laser Deposition
Authors: Ieda Mirai , Ishimaru Tatsuya , Ono Shingo , Kawaguchi Noriaki , Fukuda Kentaro , Suyama Toshihisa , Yokota Yuui , Yanagida Takayuki , Yoshikawa Akira
Published: May 2012

We report on an ultraviolet photoconductive detector based on cerium fluoride (CeF3) thin films. CeF3 thin films were grown on quartz glass substrates by the pulsed laser deposition (PLD) method. Optimization of the substrate temperature using the PLD method successfully increased the photocurrent of the CeF3 detector. The photocurrent increases linearly up to at least 600 V. The sample grown at 670 K shows the highest crystallinity and orientation. This sample shows a response in the wavelength range below 310 nm without any filters. Additionally, the measured dielectric-breakdown field of this detector exceeded 15 kV/cm.
X-ray Absorption Fine Structure Analysis of Valence State of Ce in Y3Al5O12:Ce Phosphor Synthesized by Coprecipitation Method
Authors: Okura Hiroshi , Murakawa Takuro , Miyamoto Yoshinobu , Honma Tetsuo , Ohmi Koutoku
Published: May 2012

To clarify the activation procedure of Ce through the synthesis of Y3Al5O12:Ce (YAG:Ce) phosphor by a coprecipitation method, the valence state of Ce has been studied by X-ray absorption fine structure (XAFS) analysis. A linear combination of reference spectra was fit to the X-ray absorption near-edge structure (XANES) and the extended XAFS (EXAFS) oscillation curves of the oxidized samples. It was found that YAG and CeO2 are formed above 1000 °C. The fitting result indicates that Ce atoms with a concentration of about 0.6 mol % are directly incorporated into the YAG lattice upon oxidation at above 1000 °C without their segregation as CeO2. The incorporated Ce3+ ions are considered to be uniformly distributed in the YAG particles and act as efficient luminescent centers.
Numerical Simulation of Nonlinear Optical Effects in Frequency-Modulation Mode-Locked Semiconductor Laser Diodes
Authors: Kuwatsuka Haruhiko , Hasama Toshifumi , Ishikawa Hiroshi
Published: May 2012

The nonlinear optical effects in frequency-modulation mode-locked semiconductor laser diodes have been examined. The numerical simulation carried out in the frequency domain showed that the asymmetric nonlinear optical gain, which causes mode instability in mode-locked lasers, can be compensated for by an additional phase modulator. The stabilization of multimode oscillation was experimentally confirmed by applying phase modulation to the grating coupled laser diode.
SnS2 Thin Film Deposition by Spray Pyrolysis
Authors: Jaber Abdallah Yahia , Alamri Saleh Noaiman , Aida Mohammed Salah
Published: May 2012

Tin disulfide (SnS2) thin films have been synthesized using a simplified spray pyrolysis technique using a perfume atomizer. The films were deposited using two different solutions prepared by the dilution of SnCl2 and thiourea in distilled water and in methanol. The obtained films have a microcrystalline structure. The film deposited using methanol as the solvent is nearly stochiometric SnS2 with a spinel phase having a (001) preferential orientation. The film prepared with an aqueous solution is Sn-rich. Scanning electronic microscopy (SEM) images reveal that the film deposited with the aqueous solution is rough and is formed with large wires. However, the film deposited with methanol is dense and smooth. Conductivity measurements indicate that the aqueous solution leads to an n-type semiconductor, while methanol leads to a p-type semiconductor.
Fluid–Particle Separation of Magnetorheological Fluid in Squeeze Mode
Authors: Ismail Izwan , Mazlan Saiful A. , Zamzuri Hairi , Olabi Abdul G.
Published: May 2012

In squeeze mode, magnetorheological (MR) fluids exhibit a unique behaviour when compression load is applied. The MR fluids were assumed to experience fluid–particle separation phenomenon, where magnetic particles and carrier fluid were separated at some extent of compression. In this study, the establishment of this phenomenon has been carried out. A cyclic compression test was performed on hydrocarbon-based MR fluid, where a video camera was used to record the expelling fluid. Solidified samples of epoxy-based MR fluid were then prepared and the cured samples were sectioned, mounted and prepared for metallographic study. Images extracted from the recorded video have shown that there was a separation of carrier fluid during compression where a brighter colour of fluid was observed expelling from the testing region. Furthermore, analyses of the micrographs demonstrated the increment of the particle distribution along compression process. The separation process was responsible for the variability of particle volume fraction in order to achieve desirable stresses.
Upper airway collapsibility and patterns of flow limitation at constant end-expiratory lung volume
Authors: Owens Robert L. , Edwards Bradley A. , Sands Scott A. , Butler James P. , Eckert Danny J. , White David P. , Malhotra Atul , Wellman Andrew
Published: May 2012

The passive pharyngeal critical closing pressure (Pcrit) is measured using a series of pressure drops. However, pressure drops also lower end-expiratory lung volume (EELV), which independently affects Pcrit. We describe a technique to measure Pcrit at a constant EELV. Continuous positive airway pressure (CPAP)-treated obstructive sleep apnea (OSA) patients and controls were instrumented with an epiglottic catheter, magnetometers (to measure change in EELV), and nasal mask/pneumotachograph and slept supine on nasal CPAP. Pcrit was measured in standard fashion and using our novel “biphasic technique” in which expiratory pressure only was lowered for 1 min before the inspiratory pressure was dropped; this allowed EELV to decrease to the drop level before performing the pressure drop. Seven OSA and three controls were studied. The biphasic technique successfully lowered EELV before the inspiratory pressure drop. Pcrit was similar between the standard and biphasic techniques (−0.4 ± 2.6 vs. −0.6 ± 2.3 cmH2O, respectively, P = 0.84). Interestingly, we noted three different patterns of flow limitation: 1) classic Starling resistor type: flow fixed and independent of downstream pressure; 2) negative effort dependence within breaths: substantial decrease in flow, sometimes with complete collapse, as downstream pressure decreased; and 3) and negative effort dependence across breaths: progressive reductions in peak flow as respiratory effort on successive breaths increased. Overall, EELV changes do not influence standard passive Pcrit measurements if breaths 3–5 of pressure drops are used. These results also highlight the importance of inspiratory collapse in OSA pathogenesis. The cause of negative effort dependence within and across breaths is not known and requires further study.
Low muscle glycogen concentration does not suppress the anabolic response to resistance exercise
Authors: Camera Donny M. , West Daniel W. D. , Burd Nicholas A. , Phillips Stuart M. , Garnham Andrew P. , Hawley John A. , Coffey Vernon G.
Published: May 2012

We determined the effect of muscle glycogen concentration and postexercise nutrition on anabolic signaling and rates of myofibrillar protein synthesis after resistance exercise (REX). Sixteen young, healthy men matched for age, body mass, peak oxygen uptake (V̇o2peak) and strength (one repetition maximum; 1RM) were randomly assigned to either a nutrient or placebo group. After 48 h diet and exercise control, subjects undertook a glycogen-depletion protocol consisting of one-leg cycling to fatigue (LOW), whereas the other leg rested (NORM). The next morning following an overnight fast, a primed, constant infusion of l-[ ring-13C6] phenylalanine was commenced and subjects completed 8 sets of 5 unilateral leg press repetitions at 80% 1RM. Immediately after REX and 2 h later, subjects consumed a 500 ml bolus of a protein/CHO (20 g whey + 40 g maltodextrin) or placebo beverage. Muscle biopsies from the vastus lateralis of both legs were taken at rest and 1 and 4 h after REX. Muscle glycogen concentration was higher in the NORM than LOW at all time points in both nutrient and placebo groups ( P < 0.05). Postexercise Akt-p70S6K-rpS6 phosphorylation increased in both groups with no differences between legs ( P < 0.05). mTORSer2448 phosphorylation in placebo increased 1 h after exercise in NORM ( P < 0.05), whereas mTOR increased ∼4-fold in LOW ( P < 0.01) and ∼11 fold in NORM with nutrient ( P < 0.01; different between legs P < 0.05). Post-exercise rates of MPS were not different between NORM and LOW in nutrient (0.070 ± 0.022 vs. 0.068 ± 0.018 %/h) or placebo (0.045 ± 0.021 vs. 0.049 ± 0.017 %/h). We conclude that commencing high-intensity REX with low muscle glycogen availability does not compromise the anabolic signal and subsequent rates of MPS, at least during the early (4 h) postexercise recovery period.
Glutathione enhances endothelium-mediated control of coronary vascular resistance via a ROS- and NO intermediate-dependent mechanism
Authors: Levy Andrew S. , Vigna Chris , Rush James W. E.
Published: May 2012

The purpose of this investigation was to determine the effects of acute physiological GSH administration on endothelium-mediated reduction in coronary vascular resistance (CVR) using isolated perfused Sprague-Dawley rat hearts. A dose-response curve to GSH was conducted to determine a threshold concentration of GSH. We demonstrate that 30 μM GSH was sufficient to reduce CVR, and maximal dilation was achieved with 1 mM. In subsequent experiments, GSH was administered at concentrations of 0 [control (CON)], 1 μM, or 10 μM (GSH10), and dose-response curves to the endothelial agonist bradykinin (BK) were constructed. These GSH concentrations were chosen because of the physiological relevance and because the effects of GSH on BK action could be assessed independent of baseline differences in CVR. Sensitivity to BK (EC50) was enhanced in GSH10 vs. CON ( P < 0.05). This enhancement remained in the presence of nitric oxide (NO) synthase inhibition l-ωnitro-l-arginine (lNAME) and/or soluble guanylate cyclase (sGC) inhibition. Treatment with 4-hydroxy (2,2,6,6-tetramethylpiperidin-1-yl)oxyl (TEMPOL) enhanced the sensitivity to BK in CON, similar to the effects of GSH10 and GSH10 + TEMPOL. However, the GSH10-dependent enhancement of EC50 observed in the presence of lNAME did not occur in the presence of lNAME + TEMPOL or in the presence of lNAME + sGC inhibition and NO scavenging. Collectively, these results suggest that GSH enhances BK-mediated dilation and reduction in CVR through an antioxidant-dependent mechanism that involves a NO intermediate but is unrelated to acute production of NO and GC-dependent effects of NO. These results suggest a mechanism whereby physiologically relevant levels of GSH modulate the endogenous reactive oxygen species and NO control of endothelium-dependent coronary vascular function.
CD27 Signaling Increases the Frequency of Regulatory T Cells and Promotes Tumor Growth
Authors: Claus Christina , Riether Carsten , Schürch Christian , Matter Matthias S. , Hilmenyuk Tamara , Ochsenbein Adrian F.
Published: May 2012

Signaling of the TNF receptor superfamily member CD27 activates costimulatory pathways to elicit T- and B-cell responses. CD27 signaling is regulated by the expression of its ligand CD70 on subsets of dendritic cells and lymphocytes. Here, we analyzed the role of the CD27–CD70 interaction in the immunologic control of solid tumors in Cd27-deficient mice. In tumor-bearing wild-type mice, the CD27–CD70 interaction increased the frequency of regulatory T cells (Tregs), reduced tumor-specific T-cell responses, increased angiogenesis, and promoted tumor growth. CD27 signaling reduced apoptosis of Tregs in vivo and induced CD4+ effector T cells (Teffs) to produce interleukin-2, a key survival factor for Tregs. Consequently, the frequency of Tregs and growth of solid tumors were reduced in Cd27-deficient mice or in wild-type mice treated with monoclonal antibody to block CD27 signaling. Our findings, therefore, provide a novel mechanism by which the adaptive immune system enhances tumor growth and may offer an attractive strategy to treat solid tumors. Cancer Res; 72(14); 3664–76. ©2012 AACR.
Myocardial Strain Abnormalities in Fetal Congenital Heart Disease Assessed by Speckle Tracking Echocardiography
Authors: Germanakis Ioannis , Matsui Hikoro , Gardiner Helena M.
Published: May 2012

Objectives: To compare myocardial deformation patterns in fetuses with congenital heart disease (CHD) with our reference range using speckle tracking echocardiography. Methods: We prospectively stored and analyzed 4-chamber loops of 28 fetuses with CHD (median gestation 27 weeks, range 20.9–37.0). The peak longitudinal left (LVs) and right (RVs) ventricular free wall Lagrangian strain and LV/RV strain ratio were measured from Syngo VVI software- (Siemens) derived original coordinates. Strain values from the first examination were compared with normative data from the same population using ANOVA with post hoc tests and serial examinations described in 14 fetuses. Results: Simple shunt lesions (0.82) and shunts with pulmonary stenosis or atresia (0.93) had reduced mean LV/RV strain ratios compared to normal fetuses (1.01; 95% CI 0.97–1.05). Fetuses with hypoplastic left heart had the lowest (0.29), and those with Ebstein the highest (1.55), LV:RV ratio. Serial measurements showed increased LVs in aortic coarctation and aortic stenosis, but not in one developing important mitral regurgitation. Increased right ventricular loading in a fetus developing pulmonary regurgitation was associated with increasing RVs. Conclusions: Myocardial strain reflects the changing physiology of fetal CHD. Speckle tracking might be a useful tool to study the progress of myocardial function in affected fetuses.
Influence of Antipsychotic Agents on Heart Rate Variability in Male WKY Rats: Implications for Cardiovascular Safety
Authors: Wang Ying-Chieh , Chen Chun-Yu , Kuo Terry B.J. , Lai Ching-Jung , Yang Cheryl C.H.
Published: May 2012

Background: Sudden cardiac death is higher among schizophrenic patients and is associated with parasympathetic hypoactivity. Antipsychotic agents are highly suspected to be a precipitating factor. Thus, we aimed to test if the antipsychotics haloperidol, risperidone and clozapine affect cardiac autonomic function, excluding the confounding effect of altered sleep structure by the drugs. Methods: In this study, haloperidol, risperidone and clozapine were given separately by intraperitoneal injection to male Wistar-Kyoto rats for 5 days. Electroencephalogram (EEG), electromyogram (EMG) and electrocardiographic signals were recorded at baseline and 5 days after drug treatments. Sleep scoring was based on EEG and EMG signals. Cardiac autonomic function was assessed using heart rate variability analysis. Results: Clozapine increased heart rate and suppressed cardiac sympathetic and parasympathetic activity. Cardiac acceleration was more severe during sleep. Haloperidol tended to decrease heart rate while risperidone mildly increased heart rate; however, their effects were less obvious than those of clozapine. There was a significant drug-by-stage interaction on several heart rate variability measures. Conclusion: Taking this evidence as a whole, we conclude that haloperidol has a better level of cardiovascular safety than either risperidone or clozapine. Application of this approach to other psychotropic agents in the future will be a useful and helpful way to evaluate the cardiovascular safety of the various psychotropic medications that are in clinical use.
Activation of MAPK/PI3K/SMAD Pathways by TGF-β1 Controls Differentiation of Radial Glia into Astrocytes in vitro
Authors: Stipursky Joice , Francis Daniel , Gomes Flávia Carvalho Alcantara
Published: May 2012

The major neural stem cell population in the developing cerebral cortex is the radial glia cells, which generate neurons and glial cells. The mechanisms that modulate the maintenance of the radial glia stem cell phenotype, or its differentiation, are not completely elucidated. We previously demonstrated that transforming growth factor-β1 (TGF-β1) promotes radial glia differentiation into astrocytes in vitro [Glia 2007;55:1023–1033]. Here we investigated the intracellular signaling pathways involved in the TGF-β1-induced radial glia fate commitment. We demonstrate that the mechanisms underlying the TGF-β1 effect on radial glia cell differentiation or progenitor potential maintenance diverge. Whereas radial glia differentiation into astrocytes is mediated by the activation of the MAPK signaling pathway, neurogenesis is modulated by different levels of PI3K and SMAD2/3 activity. Our work demonstrates that radial glia cells are a heterogeneous population and a potential target of TGF-β1, and suggests that its effect on radial glia fate commitment is mediated by the recruitment of a complex multipathway mechanism that controls astrocyte and neuronal generation in the developing cerebral cortex.
Blood Transfusion Practice in Critically Ill Patients: A Single Institutional Experience
Authors: Al-Faris Lama , Al-Fares Abdul Rahman , Abdul Malek Kefaya , Omran Alaa , Al-Humood Salah
Published: May 2012

Objectives: To assess the transfusion practice in the intensive care unit (ICU) in a general hospital in Kuwait relative to indications, pretransfusion hemoglobin, red blood cell (RBC) use and outcome. Subjects and Methods: 475 patients were admitted to the ICU during the study period (January 2009 to February 2010). Ninety-nine received RBC transfusion. Demographic, clinical and transfusion data were prospectively collected for the 99 patients who were followed up for 30 days, until hospital discharge, or death, whichever occurred first. Indications for RBC transfusion included hemorrhage in 39 patients, improving oxygen-carrying capacity in 55, and hemolysis in 5. Results: Of the 99 transfused patients, 22 (22.22%) were also transfused after discharge from the ICU. Transfusions were more frequent in patients admitted with respiratory failure (30, 30.3%), hemorrhagic shock (24, 24.2%), and septic shock (18, 18.4%). The mean pretransfusion hemoglobin in ICU transfusions was statistically different (70.9 ± 12.7 g/l) from transfusions after discharge (79.7 ± 9.4 g/l) (p < 0.001). Longer ICU stay was associated with more RBC units transfused per transfusion episode per patient (p < 0.001). The Sequential Organ Failure Assessment (SOFA) score was significantly associated with the number of RBC units transfused per patient (p = 0.006). Mortality was significantly associated with Acute Physiology and Chronic Health Evaluation II and SOFA scores, the need and duration for mechanical ventilation, and the length of stay in hospital. Conclusion: Intensivists in our center followed a restrictive transfusion practice, by adopting a low pretransfusion hemoglobin threshold. Decisions on RBC transfusions seemed in most cases to be based on a ‘transfusion trigger’ rather than a physiologic need.
Short- and Long-Term Effects of Alkali Therapy in Chronic Kidney Disease: A Systematic Review
Authors: Susantitaphong Paweena , Sewaralthahab Kamal , Balk Ethan M. , Jaber Bertrand L. , Madias Nicolaos E.
Published: May 2012

Background: Clinical practice guidelines recommend alkali therapy in patients with non-dialysis-dependent chronic kidney disease (CKD) and metabolic acidosis to prevent complications from metabolic acidosis. We systematically reviewed the effect of sodium bicarbonate on benefits and harms in patients with CKD. Methods: We searched for randomized controlled trials in MEDLINE (through July 2011), Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, and scientific abstracts. We included trials that compared sodium bicarbonate to standard-of-care therapy or placebo that reported on kidney-related outcomes. We performed random-effects model meta-analyses to compute net changes (for continuous variables) and risk ratios (for binary variables). Results: Two short-term (≤7 days) crossover trials and 4 long-term (≥2 months) parallel-design randomized controlled trials met eligibility (312 patients). All 6 trials prescribed sodium bicarbonate in the alkali-treated group. In the long-term studies, alkali therapy was associated with a net decrease in serum creatinine (–0.07 mg/dl, 95% CI –0.09, –0.05; p < 0.001; I2 = 0), a net improvement in GFR (3.2 ml/min/1.73 m2, 95% CI 1.6, 4.7; p < 0.001; I2 = 0), and a lower incidence of dialysis initiation (risk ratio 0.21, 95% CI 0.08, 0.54; p = 0.001; I2 = 0). No benefit was observed on the serum creatinine or GFR in short-term studies. Alkali therapy was not associated with a higher likelihood of initiating or escalating anti-hypertensive medications. Conclusions: Alkali therapy is associated with an improvement in kidney function, which may afford a long-term benefit in slowing the progression of CKD. However, differences in study protocols and small sample sizes preclude definitive conclusions.
Farnesyl pyrophosphate is an endogenous antagonist to ADP-stimulated P2Y12 receptor-mediated platelet aggregation
Authors: Högberg Carl , Gidlöf Olof , Deflorian Francesca , Jacobson Kenneth , Abdelrahman Aliaa , Müller Christa , Olde Björn , Erlinge David
Published: May 2012

Farnesyl pyrophosphate (FPP) is an intermediate in cholesterol biosynthesis, and it has also been reported to activate platelet LPA (lysophos-phatidic acid) receptors. The aim of this study was to investigate the role of extracellular FPP in platelet aggregation. Human platelets were studied with light transmission aggregometry, flow cytometry and [35S]GTPγS binding assays. As shown previously, FPP could potentiate LPA-stimulated shape change. Surprisingly, FPP also acted as a selective insurmountable antagonist to ADP-induced platelet aggregation. FPP inhibited ADP-induced expression of P-selectin and the activated glycoprotein (Gp)IIb/IIIa receptor. FPP blocked ADP-induced inhibition of cAMP accumulation and [35S]GTPγS binding in platelets. In Chinese hamster ovary cells expressing the P2Y12 receptor, FPP caused a right-ward shift of the [35S]GTPγS binding curve. In Sf9 insect cells expressing the human P2Y12 receptor, FPP showed a concentration-dependent, although incomplete inhibition of [3H]PSB-0413 binding. Docking of FPP in a P2Y12 receptor model revealed molecular similarities with ADP and a good fit into the binding pocket for ADP. In conclusion, FPP is an insurmountable antagonist of ADP-induced platelet aggregation mediated by the P2Y12 receptor. It could be an endogenous antithrombotic factor modulating the strong platelet aggregatory effects of ADP in a manner similar to the use of clopidogrel, prasugrel or ticagrelor in the treatment of ischaemic heart disease.
Changes in von Willebrand factor-cleaving protease (ADAMTS-13) in patients with aortic stenosis undergoing valve replacement or balloon valvuloplasty
Authors: Elmariah Sammy , Aledort Louis , Dlott Jeffrey , Stelzer Paul , Halperin Jonathan , Kini Annapoorna , Sharma Samin , Bander Jeffrey
Published: May 2012

It was the objective of this study to determine whether reduced cleavage of von Willebrand factor (VWF) multimers following aortic valve replacement (AVR) is a consequence of reduced shear stress or postoperative changes in VWF cleavage protease (ADAMTS-13) activity. Aortic stenosis (AS) may be complicated by acquired von Willebrand disease. Aortic valve replacement (AVR) corrects the associated haematologic abnormalities. We enrolled 114 patients with severe AS scheduled for either balloon aortic valvuloplasty (BAV; n=64) or AVR (n=50). Haematologic assessments of VWF levels and activity and ADAMTS-13 were performed before and 24 hours after valve intervention. The VWF:RCo to VWF:Ag ratio, a surrogate for large VWF multimer activity, increased by 37% (p < 0.0001) after AVR and by 10% (p = 0.0002) after BAV. ADAMTS-13 activity significantly decreased after AVR (579 ± 127 to 468 ± 135 ng/ml; p<0.0001), but not after BAV (484 ± 153 to 529 ± 185 ng/ml; p = 0.10). By multivariable analysis, the change in VWF:RCo ratio after AVR was more strongly associated with the fall in ADAMTS-13 than with reduction of valve gradient; whereas the change in gradient better predicted the rise in VWF:RCo after BAV. In conclusion, both BAV and AVR reverse the haematological abnormalities of the acquired von Willebrand syndrome of AS and ADAMTS-13 levels decrease after AVR. These findings suggest that a portion of the haematologic benefit of AVR may be due to a postoperative decline in ADAMTS-13 rather than solely to relief of AS as previously thought.
Roles of Purinergic Receptor P2Y, G Protein–Coupled 12 in the Development of Atherosclerosis in Apolipoprotein E–Deficient Mice
Authors: Li Ding , Wang Yanhua , Zhang Lin , Luo Xinping , Li Jian , Chen Xuejin , Niu Haixia , Wang Kemin , Sun Yueping , Wang Xuefeng , Yan Yan , Chai Weiran , Gartner T. Kent , Liu Junling
Published: May 2012

Objective—

The aim of the study was to evaluate the role of purinergic receptor P2Y, G protein–coupled 12 (P2Y12), an ADP receptor, in the development of atherosclerotic lesions.

Methods and Results—

Apolipoprotein E–null mice were crossed with
P2y12
−/−
mice to generate double knockout mice. The double knockout mice and the control apolipoprotein E–null mice were fed a high-fat diet for 20 weeks. Assessment of the atherosclerotic lesions in the control and double knockout mice demonstrated that P2Y12 deficiency caused a diminished lesion area, an increased fibrous content at the plaque site, and decreased monocyte/macrophage infiltration of the lesions. Polymerase chain reaction studies revealed that white blood cells do not express significant levels of P2Y12. Bone marrow transplantation experiments confirmed that P2Y12 expressed on platelets is a key factor responsible for atherosclerosis, but do not exclude a role of smooth muscle cell P2Y12. Supernatant fluid from activated
P2y12
+/+
but not
P2y12
−/−
platelets was capable of causing monocyte migration. In vitro studies showed that platelet P2Y12 deficiency suppressed platelet factor 4 secretion and P-selectin expression. Further work demonstrated that platelet P2Y12, through inhibition of the cAMP/protein kinase A pathway, critically regulates the release of platelet factor 4, and thereby affects monocyte recruitment and infiltration.

Conclusion—

These results demonstrate that P2Y12 modulates atherogenesis, at least in part by augmenting inflammatory cell recruitment via regulation of platelet α-granule release.
ABO Blood Group and von Willebrand Factor Levels Partially Explained the Incomplete Penetrance of Congenital Thrombophilia
Authors: Cohen William , Castelli Christel , Alessi Marie-Christine , Aillaud Marie-Françoise , Bouvet Sophie , Saut Noémie , Brunet Dominique , Barthet Marie-Christine , Tregouet David-Alexandre , Lavigne Géraldine , Morange Pierre-Emmanuel
Published: May 2012

Objective—

We aimed to study the association among ABO blood group, von Willebrand factor, factor VIII plasma levels, and the risk of venous thrombosis (VT) in a cohort of 1774 relatives from 500 families with inherited thrombophilia.

Methods and Results—

One hundred sixty-one of the 1774 relatives had a VT. Different risk groups were formed: no, low-(factor V Leiden or F2G20210A heterozygous carriers), and high-risk thrombophilia (antithrombin, protein C, protein S, factor V Leiden, or F2G20210A homozygous carriers and combined defects). Compared with group O, AB blood group was associated with increased risk of VT: hazard ratio (HR)=3.8 (2.0–7.2). The effect of blood group A and B was milder (HR=1.6 [1.1–2.5] and 1.8 [1.0–3.3], respectively). An increased risk of VT was observed with increasing levels of von Willebrand factor and factor VIII plasma levels (HR=2.96 [1.92–4.56] and HR=2.60 [1.92–4.56] for third versus first tertile of von Willebrand factor and factor VIII plasma levels, respectively). In multivariate analysis, AB group (HR=2.3 [1.1–4.8]), high-risk thrombophilia (HR=2.8 [1.6–4.6]), and high von Willebrand factor levels (HR=2.3 [1.3–4.0]) were significantly associated with increased risk of VT. The risk of VT in individuals with high-risk thrombophilia and AB group was 14.4× higher than in those without thrombophilia and O group (5.0–41.4).

Conclusion—

ABO blood group modifies the risk of VT in families with hereditary thrombophilia. Phenotyping of the ABO blood group should be performed to better assess the risk of VT in asymptomatic individuals from thrombophilic families.
Endoluminal Gingival Fibroblast Transfer Reduces the Size of Rabbit Carotid Aneurisms via Elastin Repair
Authors: Durand Eric , Fournier Benjamin , Couty Ludovic , Lemitre Mathilde , Achouh Paul , Julia Pierre , Trinquart Ludovic , Fabiani Jean Noel , Seguier Sylvie , Gogly Bruno , Coulomb Bernard , Lafont Antoine
Published: May 2012

Objective—

Matrix metalloproteinase-9 is considered to play a pivotal role in aneurismal formation. We showed that gingival fibroblasts (GF) in vitro reduced matrix metalloproteinase-9 activity via increased secretion of tissue inhibitor of metalloproteinase 1. We aimed to evaluate in vivo the efficacy of GF transplantation to reduce aneurism development in a rabbit model.

Methods and Results—

Seventy rabbit carotid aneurisms were induced by elastase infusion. Four weeks later, GF, dermal fibroblast, or culture medium (DMEM) were infused into established aneurisms. Viable GF were abundantly detected in the transplanted arteries 3 months after seeding. GF engraftment resulted in a significant reduction of carotid aneurisms (decrease of 23.3% [
P
<0.001] and 17.6% [
P
=0.01] of vessel diameter in GF-treated arteries, 1 and 3 months after cell therapy, respectively), whereas vessel diameter of control DMEM and dermal fibroblast–treated arteries increased. GF inhibited matrix metalloproteinase-9 activity by tissue inhibitor of metalloproteinase 1 overexpression and matrix metalloproteinase-9/tissue inhibitor of metalloproteinase 1 complex formation, induced elastin repair, and increased elastin density in the media compared with DMEM-treated arteries (38.2 versus 18.0%;
P
=0.02). Elastin network GF-induced repair was inhibited by tissue inhibitor of metalloproteinase 1 blocking peptide.

Conclusion—

Our results demonstrate that GF transplantation results in significant aneurism reduction and elastin repair. This strategy may be attractive because GF are accessible and remain viable within the grafted tissue.
Magnetic Versus Manual Catheter Navigation for Ablation of Free Wall Accessory Pathways in Children
Authors: Kim Jeffrey J. , Macicek Scott L. , Decker Jamie A. , Kertesz Naomi J. , Friedman Richard A. , Cannon Bryan C.
Published: May 2012

Background—

Transcatheter ablation of accessory pathway (AP)–mediated tachycardia is routinely performed in children. Little data exist regarding the use of magnetic navigation (MN) and its potential benefits for ablation of AP-mediated tachycardia in this population.

Methods and Results—

We performed a retrospective review of prospectively gathered data in children undergoing radiofrequency ablation at our institution since the installation of MN (Stereotaxis Inc, St. Louis, MO) in March 2009. The efficacy and safety between an MN-guided approach and standard manual techniques for mapping and ablation of AP-mediated tachycardia were compared. During the 26-month study period, 145 patients underwent radiofrequency ablation for AP-mediated tachycardia. Seventy-three patients were ablated with MN and 72 with a standard manual approach. There were no significant differences in demographic factors between the 2 groups with a mean cohort age of 13.1±4.0 years. Acute success rates were equivalent with 68 of 73 (93.2%) patients in the MN group being successfully ablated versus 68 of 72 (94.4%) patients in the manual group (
P
=0.889). During a median follow-up of 21.4 months, there were no recurrences in the MN group and 2 recurrences in the manual group (
P
=0.388). There were no differences in time to effect, number of lesions delivered, or average ablation power. There was also no difference in total procedure time, but fluoroscopy time was significantly reduced in the MN group at 14.0 (interquartile range, 3.8–23.9) minutes compared with the manual group at 28.1 (interquartile range, 15.3–47.3) minutes (
P
<0.001). There were no complications in either group.

Conclusions—

MN is a safe and effective approach to ablate AP-mediated tachycardia in children.
Low Dietary Vitamin D Predicts 34-Year Incident Stroke
Authors: Kojima Gotaro , Bell Christina , Abbott Robert D. , Launer Lenore , Chen Randi , Motonaga Heather , Ross G. Webster , Curb J. David , Masaki Kamal
Published: May 2012

Background and Purpose—

Vitamin D deficiency has been reported to contribute to the risk of cardiovascular disease, especially stroke. We examined the relationship between dietary vitamin D intake and 34-year incident stroke.

Methods—

The Honolulu Heart Program is a prospective population-based cohort study of 8006 Japanese-American men in Hawaii who were 45 to 68 years old at the baseline examination in 1965 to 1968. Dietary vitamin D intake was calculated using the Nutritionist IV Version 3 software from a 24-hour dietary recall. Subjects with prevalent stroke were excluded, leaving 7385 men followed through 1999 for incident stroke. Subjects were divided into quartiles of dietary vitamin D for analyses.

Results—

During 34 years of follow-up, 960 subjects developed stroke. Age-adjusted rates of incident stroke were significantly higher in the lowest dietary vitamin D quartile compared with the highest (all stroke: 6.38 versus 5.14 per 1000 person-years follow-up,
P
=0.030; thromboembolic stroke: 4.36 versus 3.30,
P
=0.033). Using Cox regression, adjusting for age, total kilocalories, body mass index, hypertension, diabetes mellitus, pack-years smoking, physical activity index, serum cholesterol, and alcohol intake, those in the lowest quartile had a significantly increased risk of incident stroke (all stroke hazard ratio, 1.22; 95% CI, 1.01–1.47;
P
=0.038; thromboembolic stroke hazard ratio, 1.27; 95% CI, 1.01–1.59;
P
=0.044) with the highest as the reference. We found no significant associations between dietary vitamin D and hemorrhagic stroke.

Conclusions—

Low dietary vitamin D intake was an independent risk factor for 34-year incidence of all stroke and thromboembolic stroke in Japanese-American men. Additional research is needed on vitamin D supplementation to prevent stroke.
Multiple Cognitive Abilities from a Single Cortical Algorithm
Authors: Forwood Suzanna E. , Cowell Rosemary A. , Bussey Timothy J. , Saksida Lisa M.
Published: May 2012

One strong claim made by the representational–hierarchical account of cortical function in the ventral visual stream (VVS) is that the VVS is a functional continuum: The basic computations carried out in service of a given cognitive function, such as recognition memory or visual discrimination, might be the same at all points along the VVS. Here, we use a single-layer computational model with a fixed learning mechanism and set of parameters to simulate a variety of cognitive phenomena from different parts of the functional continuum of the VVS: recognition memory, categorization of perceptually related stimuli, perceptual learning of highly similar stimuli, and development of retinotopy and orientation selectivity. The simulation results indicate—consistent with the representational–hierarchical view—that the simple existence of different levels of representational complexity in different parts of the VVS is sufficient to drive the emergence of distinct regions that appear to be specialized for solving a particular task, when a common neurocomputational learning algorithm is assumed across all regions. Thus, our data suggest that it is not necessary to invoke computational differences to understand how different cortical regions can appear to be specialized for what are considered to be very different psychological functions.
Local Climate Zones for Urban Temperature Studies
Authors: Stewart I. D. , Oke T. R.
Published: May 2012

The effect of urban development on local thermal climate is widely documented in scientific literature. Observations of urban–rural air temperature differences—or urban heat islands (UHIs)—have been reported for cities and regions worldwide, often with local field sites that are extremely diverse in their physical and climatological characteristics. These sites are usually described only as “urban” or “rural,” leaving much uncertainty about the actual exposure and land cover of the sites. To address the inadequacies of urban–rural description, the “local climate zone” (LCZ) classification system has been developed. The LCZ system comprises 17 zone types at the local scale (102 to 104 m). Each type is unique in its combination of surface structure, cover, and human activity. Classification of sites into appropriate LCZs requires basic metadata and surface characterization. The zone definitions provide a standard framework for reporting and comparing field sites and their temperature observations. The LCZ system is designed primarily for urban heat island researchers, but it has derivative uses for city planners, landscape ecologists, and global climate change investigators.
Unified Modeling and Prediction of Weather and Climate: A 25-Year Journey
Authors: Brown Andrew , Milton Sean , Cullen Mike , Golding Brian , Mitchell John , Shelly Ann
Published: May 2012

In recent years there has been a growing appreciation of the potential advantages of using a seamless approach to weather and climate prediction. However, what exactly should this mean in practice? To help address this question, we document some of the experiences already gathered over 25 years of developing and using the Met Office Unified Model (MetUM) for both weather and climate prediction. Overall, taking a unified approach has given enormous benefits, both scientific and in terms of efficiency, but we also detail some of the challenges it has presented and the approaches taken to overcome them.
A High-Resolution Simulation of the Year 2003 for Germany Using the Regional Model COSMO
Authors: Kücken Martin , Hauffe Detlef , Österle Hermann
Published: May 2012

In this article, the authors examine the effect of a high-resolution grid (grid resolution lower than 3 km) in the context of a realistic climate simulation. For this purpose global simulation results of the German Weather Service were dynamically downscaled in a one-way nesting approach to 2.8 km using the regional forecast model of the Consortium for Small-Scale Modeling (COSMO) of the German Weather Service. The simulations were performed for the region of central Europe in 2003. In particular, the authors investigate whether COSMO adequately handles extreme events such as the persistent drought and heat of the summer of 2003. Comparisons of the simulated atmospheric conditions in terms of 2-m temperature, mean sea level pressure, and precipitation demonstrated a good correspondence to their associated observational data. Simulation results and observed data are both given as time series at locations such as grid cells or station locations. By cluster analysis a representation of the spatial structure for observation data and simulation results is found. The kappa statistic evaluates how well the two spatial structures correspond to each other. The different kappa variants are helpful to diagnose where shortcomings of the simulation results are located.
3DVAR versus Traditional Dual-Doppler Wind Retrievals of a Simulated Supercell Thunderstorm
Authors: Potvin Corey K. , Betten Daniel , Wicker Louis J. , Elmore Kimberly L. , Biggerstaff Michael I.
Published: May 2012

Use of the three-dimensional variational data assimilation (3DVAR) framework in dual-Doppler wind analysis (DDA) offers several advantages over traditional techniques. Perhaps the most important is that the errors that result from explicit integration of the mass continuity equation in traditional methods are avoided. In this study, observing system simulation experiments (OSSEs) are used to compare supercell thunderstorm wind retrievals from a 3DVAR DDA technique and three traditional DDA methods. The 3DVAR technique produces better wind retrievals near the top of the storm than the traditional methods in the experiments. This is largely attributed to the occurrence of severe errors aloft in the traditional retrievals whether the continuity equation integration proceeds upward (due to vertically accumulating errors), downward (due to severe boundary condition errors arising from uncertainty in the horizontal divergence field aloft), or in both directions. Smaller, but statistically significant, improvement occurs near the ground using the 3DVAR method. When lack of upper-level observations prevents application of a top boundary condition in the traditional DDA framework, the 3DVAR approach produces better analyses at all levels. These results strongly suggest the 3DVAR DDA framework is generally preferable to traditional formulations.