bluuebunny/crossref_metadata_2025 huggingface dataset:
A Comparison of the Diagnostic Sensitivity of MRI, CBF-SPECT, FDG-PET and Cerebrospinal Fluid Biomarkers for Detecting Alzheimer’s Disease in a Memory Clinic
Authors: Morinaga Akiyoshi , Ono Kenjiro , Ikeda Tokuhei , Ikeda Yoshihisa , Shima Keisuke , Noguchi-Shinohara Moeko , Samuraki Miharu , Yanase Daisuke , Yoshita Mitsuhiro , Iwasa Kazuo , Mastunari Ichiro , Yamada Masahito
Published: September 2010

Background/Aim: Magnetic resonance imaging (MRI), cerebral blood flow single photon emission computed tomography (CBF-SPECT), fluorodeoxyglucose-positron emission tomography (FDG-PET) and cerebrospinal fluid (CSF) biomarkers are used for the diagnosis of Alzheimer’s disease (AD). We aimed to reveal the relative sensitivity of these tools in a memory clinic setting. Methods: In 207 patients with probable AD in our memory clinic, medial temporal lobe atrophy on MRI, hypoperfusion/hypometabolism of the parietotemporal lobe and posterior cingulate gyrus in ethylcysteinate dimer-CBF-SPECT/FDG-PET, and abnormalities of CSF amyloid β-protein 1–42, total tau and phosphorylated tau were evaluated as findings characteristic of AD. Results: The AD findings were observed in 77.4% of all AD patients with MRI, 81.6% with CBF-SPECT, 93.1% with FDG-PET and 94.0% with CSF biomarkers. At the stage of Clinical Dementia Rating (CDR) 0.5, CSF biomarkers were the most sensitive (90.0%); at the stage of CDR 1, FDG-PET (96.7%) and CSF biomarkers (95.5%) were highly sensitive. At the stage of CDR 2, all tools showed high positive percentages. Conclusion: The diagnosis of AD was most often supported by CSF biomarkers and FDG-PET at the early stage of dementia (CDR 1) and by CSF biomarkers at the earlier stage (CDR 0.5).
The Role of Tumor Necrosis Factor-α Converting Enzyme in Renal Transplant Rejection
Authors: Wang Jun , Li Zilong , Al-Lamki Rafia , Wang Juan , Zuo Nan , Bradley John R. , Wang Lining
Published: September 2010

Background: Tumor necrosis factor receptors (TNFR) are differentially regulated in human rejecting renal transplants. The TNF-α converting enzyme (TACE) regulates the membrane shedding of both receptors and TNF itself. We analyzed the expression and regulation of TACE in human rejecting renal transplants. Methods: Samples from normal renal tissue or renal transplant undergoing severe acute rejection were immunostained for TACE using antibodies from different species. Human kidney epithelial cells were cultured and TACE plasmid was transfected to upregulate TACE expression. Cells were fractionated and immunoblotted for TACE, and ELISA was performed to test soluble TNFR2. Results: We showed that TACE was upregulated mainly in tubular epithelial cells in acute rejecting kidney, where it colocalized with TNFR2. Epithelial cells with increased levels of TACE shed more soluble TNFR2 into culture media and even more after TACE activation by phorbol-12-myristate-13-acetate stimulation. The shedding could be completely blocked by the TACE inhibitor TNF-α protease inhibitor. Conclusion: Upregulation of TACE in epithelial cells in acute rejecting kidney could lead to more TNFR2 shedding and, hence, antagonize the proinflammatory effect of local TNF.
Allergenicity of Ascaris lumbricoides Tropomyosin and IgE Sensitization among Asthmatic Patients in a Tropical Environment
Authors: Acevedo N. , Erler A. , Briza P. , Puccio F. , Ferreira F. , Caraballo L.
Published: September 2010

Background:Ascaris lumbricoides induces a Th2 response and specific IgE synthesis in humans. This confers antiparasite immunity but could modify the natural history of allergic diseases in the tropics, justifying the study of its allergenic composition. We analyzed the allergenic properties of Ascaris tropomyosin and the frequency of sensitization in subjects exposed to the parasite. Methods: cDNA was obtained by reverse transcription PCR, cloned into pQE30-UA and purified as a 6× His-tagged protein. Equivalence with its natural counterpart was analyzed by cross-inhibition and liquid chromatography-tandem mass spectrometry. Specific IgE was measured by ELISA in 175 asthmatics and 170 nonasthmatics naturally exposed to the parasite and sensitized to the Ascaris extract. Results: The cDNA encoded 287 residues with high sequence identity with other invertebrate tropomyosins. The 40-kDa protein was recognized by human serum and affinity-purified anti-rBlo t 10 IgE. Specific IgE to tropomyosin could represent approximately 50% of the total IgE response to the extract. Ascaris tropomyosin induced wheal and flare in skin prick tests and histamine release from basophils. Although the prevalence of IgE to Ascaris tropomyosin was higher in asthmatic patients, logistic regression analysis suggested that this result was biased by sensitization to mites. Conclusions:A. lumbricoides tropomyosin (Asc l 3) is a new allergen that binds specific IgE, induces mediator release from effector cells and is cross-reactive to mite tropomyosins. IgE reactivity to this allergen is very frequent in both asthmatic and normal subjects sensitized to Ascaris extract. The potential role of Ascaris tropomyosin in asthma pathogenesis in tropical regions should be further investigated.
Recombinant Adeno-Associated Virus Vector-Mediated Delivery of Antisense Interleukin-5 Gene Attenuates Airway Remodeling in Allergic Rats
Authors: Zeng Daxiong , Cao Yong , Song Qingfeng , Cao Chao , Xie Min , Liu Xiansheng , Xiong Shengdao , Xu Yongjian , Xiong Weining
Published: September 2010

Background: Increasing evidence indicates that eosinophils contribute greatly to airway remodeling in asthma. Since interleukin-5 (IL-5) plays a critical role in the regulation of eosinophils in asthma, anti-IL-5 therapy may be a novel approach to inhibit airway remodeling in asthma. Objectives: In this study, we applied a recombinant adeno-associated virus vector-mediated antisense IL-5 gene delivery (rAAV-ASIL-5) system to investigate its effect on airway remodeling in ovalbumin (OVA)-sensitized and -challenged rats. Methods: rAAV-ASIL-5 was used to infect OVA-sensitized and -challenged rats. IL-5 protein in bronchoalveolar lavage fluid (BALF) was detected by ELISA. The eosinophils in BALF were counted. Transforming growth factor (TGF)-β1- and TGF-β2-positive cells in the peribronchial space were detected by immunohistochemical staining. Lung tissue was collected for Sirius red staining and histological analysis. Results: rAAV-ASIL-5 significantly decreased the level of IL-5 protein, the number of eosinophils in BALF and the numbers of TGF-β1- and TGF-β2-positive cells in the peribronchial space. The area of Sirius red staining in airways was also decreased. Moreover, the rAAV-ASIL-5 treatment inhibited the increase in total bronchial wall area and airway smooth muscle area. Conclusion: These results suggest that rAAV-ASIL-5-based gene therapy could be used to inhibit airway remodeling in allergic rats.
A Novel Immunoassay Using Recombinant Allergens Simplifies Peanut Allergy Diagnosis
Authors: Codreanu F. , Collignon O. , Roitel O. , Thouvenot B. , Sauvage C. , Vilain A.-C. , Cousin M.-O. , Decoster A. , Renaudin J.-M. , Astier C. , Monnez J.-M. , Vallois P. , Morisset M. , Moneret-Vautrin D.-A. , Brulliard M. , Ogier V. , Castelain M.-C. , Kanny G. , Bihain B.E. , Jacquenet S.
Published: September 2010

Background: Double-blind placebo-controlled food challenge (DBPCFC) is currently considered the gold standard for peanut allergy diagnosis. However, this procedure that requires the hospitalization of patients, mostly children, in specialized centers for oral exposure to allergens may cause severe reactions requiring emergency measures. Thus, a simpler and safer diagnosis procedure is needed. The aim of this study was to evaluate the diagnostic performance of a new set of in vitro blood tests for peanut allergy. Methods: The levels of IgE directed towards peanut extract and recombinant peanut allergens Ara h 1, Ara h 2, Ara h 3, Ara h 6, Ara h 7, and Ara h 8 were measured in 3 groups of patients enrolled at 2 independent centers: patients with proven peanut allergy (n = 166); pollen-sensitized subjects without peanut allergy (n = 61), and control subjects without allergic disease (n = 10). Results: Seventy-nine percent of the pollen-sensitized patients showed IgE binding to peanut, despite their tolerance to peanut. In contrast, combining the results of specific IgE to peanut extract and to recombinant Ara h 2 and Ara h 6 yielded a peanut allergy diagnosis with a 98% sensitivity and an 85% specificity at a positivity threshold of 0.10 kU/l. Use of a threshold of 0.23 kU/l for recombinant Ara h 2 increased specificity (96%) at the cost of sensitivity (93%). Conclusion: A simple blood test can be used to diagnose peanut allergy with a high level of precision. However, DBPCFC will remain useful for the few cases where immunological and clinical observations yield conflicting results.
Enhancement of Mast Cell IL-6 Production by Combined Toll-Like and Nucleotide-Binding Oligomerization Domain-Like Receptor Activation
Authors: Haidl Ian D. , McAlpine Sarah M. , Marshall Jean S.
Published: September 2010

Background: Mast cells respond to bacterial infection by producing mediators that recruit and activate leukocytes, mediate vasodilation and induce bronchoconstriction. These mast cell-driven responses play a crucial role in protective immunity against bacterial infection, but may contribute to bacterial exacerbation of allergic diseases. Bacterial components including peptidoglycan (PGN) and lipopeptides are known to activate receptors such as Toll-like receptors (TLR) and nucleotide-binding oligomerization domain-like receptors (NLR). Since the consequences of mast cell activation by individual or combinations of bacterial components have not been fully characterized, we determined the effects of TLR2 and NLR activation, alone or in combination, on human mast cell mediator production. Methods: Cord blood-derived human mast cells were activated by bacterial PGN, the lipopeptide Pam3CSK4 and NLR agonists alone or in combination. Mast cell degranulation, LTC4 production and the production of cytokines were assessed. Results:PGN and the lipopeptide Pam3CSK4 induced human mast cells to produce the pro-inflammatory mediators IL-1β, IL-6, CXCL8 and LTC4 in addition to anti-inflammatory IL-10. NLR agonists alone did not induce these responses, but significantly and selectively increased Pam3CSK4-mediated mast cell IL-6 production. PGN- and Pam3CSK4-induced mast cell IL-6, but not IL-1β, production was dependent on adenylyl cyclase activity and could be partially inhibited by the cyclooxygenase inhibitor naproxen. Conclusions: Increased mast cell IL-6 production in response to combined TLR2 and NLR activation could play a role in the protection against bacterial infection, but potentially exacerbate inflammation-dependent conditions. In addition, mast cell IL-6 production is dependent on adenylyl cyclase activity.
Effects of Oral Administration of Lactobacillus acidophilus L-92 on the Symptoms and Serum Markers of Atopic Dermatitis in Children
Authors: Torii Shinpei , Torii Akiko , Itoh Komei , Urisu Atsuo , Terada Akihiko , Fujisawa Takao , Yamada Kazue , Suzuki Hiromi , Ishida Yu , Nakamura Futoshi , Kanzato Hiroki , Sawada Daisuke , Nonaka Atsuko , Hatanaka Misaki , Fujiwara Shigeru
Published: September 2010

Background: Few studies have investigated the complementary effects of long-term oral administration of Lactobacillus acidophilus on traditional medical therapy in the treatment of patients with atopic dermatitis (AD). Methods: The Atopic Dermatitis Area and Severity Index was used to evaluate AD severity. Symptom severity was assessed using the symptom score. The effect of medical therapy was evaluated by adding the medication score, calculated as the sum of each product of the amount of steroid ointment used for therapy and its designated strength graded on a 4-point scale, to the symptom score. The complementary effect of long-term oral administration of L. acidophilus strain L-92 (L-92) as a probiotic or biogenic strain in patients with AD was evaluated using the symptom-medication score, which was calculated as the sum of the symptom score and medication score. Both a preliminary casuistic study and a double-blinded, placebo-controlled study were performed to evaluate the effects of L-92 on the symptoms of AD in children. Results: Orally administered L-92 significantly ameliorated the symptoms of AD in Japanese children. L-92 also affected the serum concentrations of thymus and activation-regulated chemokine in a time-dependent manner.Conclusions: The results of the preliminary trial and the double-blinded, placebo-controlled study revealed a complementary effect of oral L-92 on the standard medical therapy (topical application of a steroid ointment) in patients with AD that was mediated, at least in part, by alterations in the Th1/Th2 balance.
Patterns of Psychosocial Adaptation and Allergic Disorders in Korean Schoolchildren
Authors: Park JinAh , Kim Byoung-Ju , Kwon Ji-Won , Song Young Hwa , Yu Jinho , Kim Hyo-Bin , Lee So-Yeon , Kim Woo Kyung , Jee Hye Mi , Kim Kyung Won , Kim Kyu-Earn , Hong Soo-Jong , Shin Yee-Jin
Published: September 2010

Background: To date, there is little evidence to support an association between symptoms of pediatric allergic disorders and psychosocial factors in the general population, particularly in Asian countries. The current study aims to investigate the relationship between psychosocial factors and symptoms of allergic disorders and to investigate the association between behavior problems and biomarkers of atopy. Methods: A cross-sectional survey of parental responses to the International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire and the Korean version of the Child Behavior Checklist (CBCL) was conducted from one elementary school in Seoul, Korea. Skin prick tests for 18 major allergens were also performed. Results: A total of 780 children with valid CBCL surveys were included in the study. Externalizing problems were significantly larger in children with asthmatic symptoms, while internalizing problems were significantly larger in children with symptoms of both asthma and allergic rhinitis. Social adaptations were significantly lower in children with symptoms of allergic rhinitis and atopic dermatitis. Boys with more positive allergens via the skin prick tests showed larger internalizing problems. Conclusions: While school children with allergic symptoms have been reported to have more difficulties with psychosocial adaptation, the patterns of psychosocial problems varied somewhat according to the types of atopic disorder. There was a positive relationship between atopy and behavior problems, especially in boys.
Skin Prick Test Extracts for Dog Allergy Diagnosis Show Considerable Variations Regarding the Content of Major and Minor Dog Allergens
Authors: Curin Mirela , Reininger Renate , Swoboda Ines , Focke Margit , Valenta Rudolf , Spitzauer Susanne
Published: September 2010

Background: Commercial skin prick test (SPT) extracts used for the diagnosis of dog allergy are prepared by extracting allergens from natural sources, e.g. dog hair and dander. Due to different starting material and extraction methods used, it is likely that extracts differ regarding their allergen contents. Methods: The total protein content and composition of dog SPT extracts from 5 European manufacturers were compared by silver-stained SDS-PAGE. Specific antibody probes were generated to detect major and minor allergens in each extract by immunoblotting. Additionally, sera of patients suffering from dog allergy were used to detect dog allergens in SPT extracts. Results: SPT extracts showed a 20-fold variation regarding the total protein content. The contents of the major dog allergen Can f 1 and of Can f 2 varied considerably between the extracts. In one of the extracts, neither Can f 1 nor Can f 2 could be detected by immunoblotting. The contents of the minor dog allergen Can f 3, albumin, also showed great variability. In one of the dog SPT extracts, the presence of human serum albumin (HSA) was detected with HSA-specific antibodies. Conclusion: The observed variability of commercial dog SPT extracts regarding their allergen contents likely has a negative influence on the accuracy of diagnosis of dog allergy.
Recombinant Activated Factor VII Is Reabsorbed in Renal Proximal Tubules and Is a Ligand to Megalin and Cubilin
Authors: Seested Torben , Appa Rupa Shree , Jacobsen Christian , Christensen Erik Ilso
Published: September 2010

Background/Aims: Recombinant activated factor VIIa (rFVIIa) is used for treatment of haemophilia patients with inhibitors. Tissue distribution studies in rats have shown that injected 125I-rFVIIa accumulates in organs such as the liver and the kidneys. In this study, we explored which mechanism could be involved in renal clearance of rFVIIa. Methods: Immunohistochemistry was used for examination of the renal distribution in detail after injection of rFVIIa to mice and rats. Surface plasmon resonance evaluated specific binding of rFVIIa to megalin and cubilin. The biological function of megalin and cubilin in rFVIIa endocytosis was explored in opossum kidney (OK) cells. Results: Staining of rFVIIa was observed only in endosomes and lysosomes within proximal convoluted tubules from renal cortex of mice and rats. Specific binding of rFVIIa to megalin and cubilin was in the presence of receptor-associated protein (RAP) obliterated and reduced by approximately 50%, respectively. Immunofluorescence microscopy and a quantitative cellular endocytosis showed uptake in OK cells of either rFVIIa or 125I-rFVIIa, and this uptake was significantly decreased in the presence of RAP. Conclusion: We suggest that the renal cortex plays a significant role in clearance of injected rFVIIa and that endocytosis and degradation of rFVIIa in proximal tubule cells is mediated via binding to megalin and cubilin.
Serum Osteoprotegerin Is a Predictor of Progression of Atherosclerosis and Coronary Calcification in Hemodialysis Patients
Authors: Kurnatowska Ilona , Grzelak Piotr , Kaczmarska Magdalena , Stefańczyk Ludomir , Nowicki Michał
Published: September 2010

Background: The aim of this prospective cohort study was to evaluate the progression of coronary artery calcification (CAC), and atherosclerosis in hemodialysis (HD) patients and to relate them to novel biomarkers, i.e. serum osteoprotegerin (OPG) and fibroblast growth factor 23 (FGF-23). Material and Methods: Forty-seven HD patients were followed up for 30 months or until death. Intima media thickness (CCA-IMT), atherosclerotic plaques and CAC were assessed at baseline and after 30 months. Serum mineral parameters, lipids, OPG and plasma FGF-23 were also measured. Results: At baseline, 70% HD patients presented detectable CAC. The patients without calcification at baseline remained calcification free at 30 months and presented lower serum OPG and FGF-23 than those with CAC. A 64.4% progression of CAC was observed in all patients with CAC at baseline. In parallel, a 13% increase in CCA-IMT was found. Both ΔCAC and ΔCCA-IMT correlated positively with baseline and follow-up serum OPG. The patients who died had significantly higher baseline CAC and serum OPG. Conclusion: The plasma level of OPG could serve as a surrogate marker of progression of atherosclerosis and calcification in patients with end-stage renal disease. Therefore, the serum OPG may be a candidate biomarker of cardiovascular complications and poor outcome among dialysis patients.
Prevalence of Acute Kidney Injury following Cardiac Surgery and Related Risk Factors in Chinese Patients
Authors: Che Miaolin , Li Yi , Liang Xinyue , Xie Bo , Xue Song , Qian Jiaqi , Ni Zhaohui , Axelsson Jonas , Yan Yucheng
Published: September 2010

Background/Aims: Acute kidney injury (AKI) following surgery is a major complication, but the prevalence and risk factors in the Asian population are unclear. Recently, a consensus definition of AKI (AKIN) was proposed. We studied a cohort of cardiac surgery patients and identified AKI by AKIN and associated risk factors. Methods: We retrospectively evaluated 1,056 consecutive patients undergoing cardiac surgery in Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China from January 1, 2004 to June 30, 2007. We recorded AKIN stage, clinical characteristics, perioperative variables and complications, as well as clinical outcomes. Univariate and multivariate regression as well as survival analysis was performed. Results: AKI occurred in 328 (31.1%) patients, stage 1 in 21.1%, stage 2 in 6.3% and stage 3 in 3.7%. Patients with AKI were older (65.8 vs. 53.5 years, p < 0.001), more often male (66.8 vs. 54.1%, p < 0.001), and had higher Charlson Comorbidity Index (CCI) (CCI >2: 22.6 vs. 7.8%, p < 0.001). In logistic regression, advanced age (OR 1.48 per decade, 95% CI 1.32–1.67), CCI >2 (OR 2.82, 95% CI 1.80–4.41), hypertension (OR 2.13, 95% CI 1.47–3.09), left ventricular ejection fraction (LVEF) <45% (OR 1.97, 95% CI 1.14–3.40), postoperative central venous pressure (CVP) <6 cm H2O (OR 13.28, 95% CI 8.72–20.14) and postoperative use of ACEI/ARB (OR 1.90, 95% CI 1.27–2.85) were risk factors of AKI. Mortality rose progressively with increased AKIN stage (non-AKI 0.7%, stage 1 4.9%, stage 2 12.1% and stage 3 48.7%). In ROC analysis, AKIN classification was identified to be associated with in-hospital mortality with an AUC of 0.865 (95% CI 0.801–0.929, sensitivity 0.884, specificity 0.714, p < 0.001). Finally, in a Cox proportional hazards model, AKIN stage (HR 2.40, p < 0.001), re-exploration (HR 6.30, p = 0.002) and multiple organ dysfunction syndrome (MODS) (HR 4.42, p = 0.001) were associated risk factors for in-hospital mortality. Conclusion: We evaluated AKIN as a marker of AKI and mortality risk in a large, unselected Chinese cohort of incident patients undergoing cardiac surgery. AKI following cardiac surgery was diagnosed by AKIN criteria in around one third of the patients, and AKI may be associated with outcome. The value of preventative strategies to reduce AKI and their effect on in-hospital mortality should be studied.
Fine Mapping of the Insulin-Induced Gene 2 Identifies a Variant Associated With LDL Cholesterol and Total Apolipoprotein B Levels
Authors: Do Ron , Bailey Swneke D. , Paré Guillaume , Montpetit Alexandre , Desbiens Katia , Hudson Thomas J. , Yusuf Salim , Bouchard Claude , Gaudet Daniel , Pérusse Louis , Anand Sonia , Vohl Marie-Claude , Pastinen Tomi , Engert James C.
Published: September 2010

Background—

In a whole-genome scan, a single nucleotide polymorphism (SNP) (rs7566605) upstream of the insulin-induced gene 2 (
INSIG2
) was shown to influence body mass index and obesity in the Framingham Heart Study, with replication of these results in an additional 4 of 5 studies. However, other studies could not replicate the association. Because
INSIG2
plays an important role in cholesterol biosynthesis, we hypothesized that human
INSIG2
variants might play a role in the regulation of plasma lipid and lipoprotein levels.

Methods and Results—

We selected tagging SNPs spanning >100 kb of
INSIG2
locus and sequenced 18 434 base pairs to discover novel SNPs. Thirty-two SNPs were genotyped in 645 individuals from the Quebec Family Study. Two SNPs (rs10490626 and rs12464355) were associated with plasma low-density lipoprotein cholesterol (LDL-C) (
P
<0.0015) and total apolipoprotein B (apoB) levels (
P
<0.014), whereas no association was found between any SNP and body mass index. We replicated the finding of rs10490626 for both LDL-C and total apoB in additional study samples, including 758 individuals from Saguenay–Lac St. Jean, Quebec (
P
=0.040 for LDL-C,
P
=0.044 for apoB), 3247 Europeans (
P
=0.028 for LDL-C,
P
=0.030 for apoB), and 1695 South Asians (
P
=0.0036 for LDL-C,
P
=0.034 for apoB) from the INTERHEART study (for LDL-C, the combined 2-sided
P
=6.2×10
−5
and for total apoB,
P
=0.0011). Furthermore, we identified a variant in the human sorbin and SH
3
-domain–containing-1 gene that was associated with
INSIG2
mRNA levels, and this SNP was shown to act in combination with rs10490626 to affect LDL-C (
P
=0.022) in the Quebec Family Study and in INTERHEART South Asians (
P
=0.019) and Europeans (
P
=0.052).

Conclusion—

These results suggest that
INSIG2
genetic variants may have a more direct role in lipid and lipoprotein metabolism than in obesity.
The Association of Patent Foramen Ovale Morphology and Stroke Size in Patients With Paradoxical Embolism
Authors: Akhondi Andre , Gevorgyan Rubine , Tseng Chi-Hong , Slavin Leo , Dao Catherine , Liebeskind David S. , Tobis Jonathan M.
Published: September 2010

Background—

Patent foramen ovale (PFO) has been implicated in the pathogenesis of cryptogenic stroke through paradoxical embolization to the cerebral circulation. This study evaluated the relationship between the morphological and functional size of the PFO by echocardiography compared with cerebral infarct volume identified on MRI.

Methods and Results—

Patients who were referred to interventional cardiology with the diagnosis of cryptogenic stroke were included and had either a transesophageal echocardiogram or an intracardiac echo and a brain MRI at the time of stroke. Transesophageal echocardiogram or intracardiac echo was used to obtain PFO measurements. MRI of the brain with 3 sequences (T2, diffusion-weighted imaging, and fluid-attenuated inversion recovery) was used to diagnose acute stroke and measure the infarct volume. In the 72 patients studied, the median measured stroke volume was 4.3 cm
3
on diffusion-weighted imaging, 4.1 cm
3
on T2, and 3.5 cm
3
on fluid-attenuated inversion recovery. There was no significant correlation between the PFO height, length, septum secundum thickness, or echo bubble grade and the infarct volume measured from the 3 MRI sequences. There was a significant correlation between septal excursion distance and infarct volume (
r
=0.35;
P
=0.005), but the 12 patients with atrial septal aneurysm did not have the largest strokes.

Conclusions—

This analysis revealed that septal excursion distance correlates with stroke size by MRI. However, smaller PFO size without the presence of atrial septal aneurysm may still be associated with significant strokes. There was no significant association between PFO height, length by echo, or shunt grade by transcranial Doppler study and brain infarct volume. Therefore, PFO size or morphology should not be the only criteria to decide whether a PFO should be closed.
A Model for Predicting Mortality in Acute ST-Segment Elevation Myocardial Infarction Treated With Primary Percutaneous Coronary Intervention
Authors: Stebbins Amanda , Mehta Rajendra H. , Armstrong Paul W. , Lee Kerry L. , Hamm Christian , Van de Werf Frans , James Stefan , Toftegaard-Nielsen Torsten , Seabra-Gomes Ricardo , White Harvey D. , Granger Christopher B. ,   for the Assessment of Pexelizumab in Acute Myocardial Infarction (APEX AMI Investigators)
Published: September 2010

Background—

Accurate models to predict mortality are needed for risk stratification in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI).

Methods and Results—

We examined 5745 patients with STEMI undergoing primary PCI in the Assessment of Pexelizumab in Acute Myocardial Infarction Trial within 6 hours of symptom onset. A Cox proportional hazards model incorporating regression splines to accommodate nonlinearity in the log hazard ratio (HR) scale was used to determine baseline independent predictors of 90-day mortality. At 90 days, 271 (4.7%) of 5745 patients died. Independent correlates of 90-day mortality were (in descending order of statistical significance) age (HR, 2.03/10-y increments; 95% CI, 1.80 to 2.29), systolic blood pressure (HR, 0.86/10-mm Hg increments; 95% CI, 0.82 to 0.90), Killip class (class 3 or 4 versus 1 or 2) (HR, 4.24; 95% CI, 2.97 to 6.08), heart rate (>70 beats per minute) (HR, 1.45/10-beat increments; 95% CI, 1.31 to 1.59), creatinine (HR, 1.23/10-μmol/L increments >90 μmol/L; 95% CI, 1.13 to 1.34), sum of ST-segment deviations (HR, 1.25/10-mm increments; 95% CI, 1.11 to 1.40), and anterior STEMI location (HR, 1.47; 95% CI, 1.12 to 1.93) (c-index, 0.82). Internal validation with bootstrapping confirmed minimal overoptimism (c-index, 0.81).

Conclusions—

Our study provides a practical method to assess intermediate-term prognosis of patients with STEMI undergoing primary PCI, using baseline clinical and ECG variables. This model identifies key factors affecting prognosis and enables quantitative risk stratification that may be helpful in guiding clinical care and for risk adjustment for observational analyses.
Pharmacodynamic Effects of Concomitant Versus Staggered Clopidogrel and Omeprazole Intake
Authors: Ferreiro José L. , Ueno Masafumi , Capodanno Davide , Desai Bhaloo , Dharmashankar Kodlipet , Darlington Andrew , Charlton Ronald K. , Bass Theodore A. , Angiolillo Dominick J.
Published: September 2010

Background—

A drug interaction between clopidogrel and omeprazole resulting in impaired platelet inhibition has been reported. It has been suggested that staggering administration of clopidogrel and omeprazole may overcome this pharmacodynamic (PD) interaction.

Methods and Results—

This prospective, open-label, 3-period, randomized crossover study was performed in 20 healthy volunteers. Subjects were randomly selected to receive omeprazole (40 mg daily) concomitantly (CONC) or staggered by 8 to 12 hours (STAG) for 1 week on a background of clopidogrel therapy in a crossover fashion, with a 2- to 4-week washout period between treatments. After another 2- to 4-week washout period, all subjects were treated for 1 week with clopidogrel alone. Clopidogrel was administered as a 600-mg loading dose followed by a 75-mg maintenance dose during all phases. PD effects were assessed by vasodilator-stimulated phosphoprotein phosphorylation assay, VerifyNow P2Y
12
system, and light transmittance aggregometry at baseline, 24 hours, and 1 week. The primary end point was the comparison of P2Y
12
reactivity index assessed by vasodilator-stimulated phosphoprotein phosphorylation assay at 1 week between CONC and STAG regimens. No significant difference in the primary end point was observed (least squares mean±SEM, 56.1±3.5% for CONC versus 61.6±3.4% for STAG;
P
=0.08). P2Y
12
reactivity index values were significantly lower in the clopidogrel regimen (48.8±3.4%) than in the CONC (
P
=0.02) and STAG (
P
=0.001) regimens. No PD differences were observed between regimens at baseline and 24 hours. Concordant results were obtained by P2Y
12
-specific assessments using VerifyNow but not with light transmittance aggregometry.

Conclusions—

Omeprazole impairs clopidogrel-induced antiplatelet effects in the maintenance phase of treatment irrespective of timing of their administration.
DTCA of Prescription Medicines in the European Union: Is There Still a Need for a Ban?
Authors: Poser Mareen
Published: September 2010

The pharmaceutical sector is one of the main markets in the European Union. The consumption of medicines is high and steadily increasing. However, the pharmaceutical market is subject to a wider range of restrictions than almost any other sector. The restrictions mainly apply to information provision and advertising practice within the community. One of the main features in pharmaceutical regulation is the ban on direct-to-consumer advertising (DTCA) of prescription medicines. However, an abolition of the ban is controversial in the European Community, especially as the pharmaceutical industry keeps pleading for its ability to use the highly effective marketing strategy of DTCA to promote prescription medicines to the general public. Such advertising is only allowed in two jurisdictions in the world, New Zealand and the United States. In both systems the impact of DTCA on the consumer and the economy has been subject to research. The outcome of these studies is outlined in this article. Since the European Commission has provided a new proposal to amend the current information practice regarding prescription medicines in 2008 (European Commission, Proposal for a Directive of the European Parliament and of the Council Amending, as Regards Information to the General Public on Medicinal Products Subject to Medical Prescription, Directive 2001/83/EC on the Community Code Relating to Medicinal Products for Human Use, COM/2008/0663 final) it is time to examine different options to regulate the provision of information and discuss the need for a ban of DTCA.
End of Life Decisions and Pregnant Women: Do Pregnant Women Have the Right to Refuse Life Preserving Medical Treatment? A Comparative Study
Authors: Lemmens Christophe
Published: September 2010

In this article the practice of end of life decisions is applied to pregnant women. This is not an easy task as shown by the extensive case law and literature on the subject. The main conclusion of the article is that the pregnant woman's wishes should always be respected whatever the consequences for the foetus may be. Another position would unjustly sacrifice the woman's fundamental rights to bodily integrity and self-determination for the benefit of a non-person. The result is repeated in the situation where the woman is found to be incompetent or brain dead.
Estimating Climatically Relevant Singular Vectors for Decadal Predictions of the Atlantic Ocean
Authors: Hawkins Ed , Sutton Rowan
Published: September 2010

A key aspect in designing an efficient decadal prediction system is ensuring that the uncertainty in the ocean initial conditions is sampled optimally. Here one strategy for addressing this issue is considered by investigating the growth of optimal perturbations in the third climate configuration of the Met Office Unified Model (HadCM3) global climate model (GCM). More specifically, climatically relevant singular vectors (CSVs)—the small perturbations of which grow most rapidly for a specific set of initial conditions—are estimated for decadal time scales in the Atlantic Ocean. It is found that reliable CSVs can be estimated by running a large ensemble of integrations of the GCM. Amplification of the optimal perturbations occurs for more than 10 yr, and possibly up to 40 yr. The identified regions for growing perturbations are found to be in the far North Atlantic, and these perturbations cause amplification through an anomalous meridional overturning circulation response. Additionally, this type of analysis potentially informs the design of future ocean observing systems by identifying the sensitive regions where small uncertainties in the ocean state can grow maximally. Although these CSVs are expensive to compute, ways in which the process could be made more efficient in the future are identified.
An Atmospheric Teleconnection Linking ENSO and Southwestern European Precipitation
Authors: Shaman Jeffrey , Tziperman Eli
Published: September 2010

Numerous studies have demonstrated statistical associations between the El Niño–Southern Oscillation (ENSO) and precipitation in the Mediterranean basin. The dynamical bases for these teleconnections have yet to be fully identified. Here, observational analyses and model simulations are used to show how ENSO variability affects rainfall over southwestern Europe (Iberia, Southern France, and Italy). A precipitation index for the region, named southwestern European Precipitation (SWEP), is used. The observational analyses show that ENSO modulates SWEP during the September–December wet season. These precipitation anomalies are associated with changes in large-scale atmospheric fields to the west of Iberia that alter low-level westerly winds and onshore moisture advection from the Atlantic.

The vorticity anomalies associated with SWEP variability are linked to ENSO through a stationary barotropic Rossby wave train that emanates from the eastern equatorial Pacific and propagates eastward to the Atlantic and Mediterranean. Solutions of the linearized barotropic vorticity equation produce such eastward-propagating Rossby waves with trajectories that traverse the region of observed ENSO-related anomalies. In addition, these linearized barotropic vorticity equation solutions produce a dipole of positive and negative vorticity anomalies to the west of Iberia that matches observations and is consistent with the onshore advection of moisture. Thus, interannual variability of fall and early winter precipitation over southwestern Europe is linked to ENSO variability in the eastern Pacific via an eastward-propagating atmospheric stationary barotropic Rossby wave train.
Optimal Excitation of Interannual Atlantic Meridional Overturning Circulation Variability
Authors: Zanna Laure , Heimbach Patrick , Moore Andrew M. , Tziperman Eli
Published: September 2010

The optimal excitation of Atlantic meridional overturning circulation (MOC) anomalies is investigated in an ocean general circulation model with an idealized configuration. The optimal three-dimensional spatial structure of temperature and salinity perturbations, defined as the leading singular vector and generating the maximum amplification of MOC anomalies, is evaluated by solving a generalized eigenvalue problem using tangent linear and adjoint models. Despite the stable linearized dynamics, a large amplification of MOC anomalies, mostly due to the interference of nonnormal modes, is initiated by the optimal perturbations.

The largest amplification of MOC anomalies, found to be excited by high-latitude deep density perturbations in the northern part of the basin, is achieved after about 7.5 years. The anomalies grow as a result of a conversion of mean available potential energy into potential and kinetic energy of the perturbations, reminiscent of baroclinic instability. The time scale of growth of MOC anomalies can be understood by examining the time evolution of deep zonal density gradients, which are related to the MOC via the thermal wind relation. The velocity of propagation of the density anomalies, found to depend on the horizontal component of the mean flow velocity and the mean density gradient, determines the growth time scale of the MOC anomalies and therefore provides an upper bound on the MOC predictability time.

The results suggest that the nonnormal linearized ocean dynamics can give rise to enhanced MOC variability if, for instance, overflows, eddies, and/or deep convection can excite high-latitude density anomalies in the ocean interior with a structure resembling that of the optimal perturbations found in this study. The findings also indicate that errors in ocean initial conditions or in model parameterizations or processes, particularly at depth, may significantly reduce the Atlantic MOC predictability time to less than a decade.
Characteristics of the Beaufort Sea High
Authors: Serreze Mark C. , Barrett Andrew P.
Published: September 2010

Characteristics of the Arctic Ocean’s Beaufort Sea high are examined using fields from the NCEP–NCAR reanalysis. At a 2-hPa contour interval, the Beaufort Sea high appears as a closed anticyclone in the long-term annual mean sea level pressure field and in spring. In winter, the Beaufort Sea region is influenced by a pressure ridge at sea level extending from the Siberian high to the Yukon high over northwestern Canada. As assessed from 6-hourly surface winds, the mean frequency of anticyclonic surface winds over the Beaufort Sea region is fairly constant through the year. While for all seasons a strong closed high can be interpreted as the surface expression of an amplified western North American ridge at 500 hPa, there is some suggestion of a split flow, where the ridge linked to the surface high is separated from the ridge to the south that lies within the main belt of westerlies. The Aleutian low in the North Pacific tends to be deeper than normal when there is a strong Beaufort Sea high. In all seasons but autumn, a strong Beaufort Sea high is associated with positive lower-tropospheric temperature anomalies covering much of the Arctic Ocean; positive anomalies are especially pronounced in spring. Seasons with a weak anticyclone show broadly opposing anomalies. A strong high is found to be a feature of the negative phase of the summer northern annular mode, the positive phase of the Pacific–North American wave train, and, to a weaker extent, the positive phase of the summer Arctic dipole anomaly and Pacific decadal oscillation. The unifying theme is that, to varying degrees, the high-latitude 500-hPa ridge associated with the Beaufort Sea high represents a center of action in each teleconnection pattern.
Scale Interaction of the Diurnal Cycle of Rainfall over the Maritime Continent and Australia: Influence of the MJO
Authors: Rauniyar Surendra P. , Walsh Kevin J. E.
Published: September 2010

The influence of the MJO on the phase and amplitude of the diurnal cycle of rainfall during Australian summer [December–February (DJF)] over the Maritime Continent (MC) and northern Australia is investigated using the Tropical Rainfall Measuring Mission (TRMM) 3B42 and 3G68 datasets. The gridded rainfall was partitioned into MJO categories (active, suppressed, and weak) based on their longitudinal position and by utilizing the real-time multivariate MJO (RMM) index of Wheeler and Hendon. The diurnal cycles were composited and an empirical orthogonal function (EOF) analysis was applied to extract the spatial and temporal variability.

Distinct variations in the rainfall distribution pattern among categories of the MJO over land and ocean are seen. The result of the composite-mean rainfall distribution shows that the average daily rainfall rate over islands is higher during suppressed MJO days, while for surrounding oceans and northern regions of Australia, more rainfall occurs during MJO active days. The normalized relative amplitude (NRA) of the diurnal cycle of rainfall shows that morning rainfall near coastal areas during active days of the MJO is 1.5 times greater than the climatological-mean rainfall but is less than or equal to the climatological mean during other phases of the MJO. Similarly, during the suppressed phase of the MJO evening rainfall is greater over the islands than in other MJO phases. The first two modes of the EOF alone explain more than 88% (65%) of the variance for the 3B42 (3G68) rainfall, and the corresponding principal component time series show a marked diurnal cycle. The results show that both the amplitude and phase of the diurnal cycle of rainfall are modulated by the categories of the MJO. In general, the peak in the diurnal cycle for active (suppressed/weak) days of the MJO lags (leads) the peak in the diurnal cycle for total rainfall by 2 h. Over Darwin and its adjacent regions, the active phase of the MJO is responsible for the occurrence of maximum rainfall after midnight, which is unusual in this region.
Persistence and Inherent Predictability of Arctic Sea Ice in a GCM Ensemble and Observations
Authors: Blanchard-Wrigglesworth Edward , Armour Kyle C. , Bitz Cecilia M. , DeWeaver Eric
Published: September 2010

The temporal characteristics of Arctic sea ice extent and area are analyzed in terms of their lagged correlation in observations and a GCM ensemble. Observations and model output generally match, exhibiting a red-noise spectrum, where significant correlation (or memory) is lost within 2–5 months. September sea ice extent is significantly correlated with extent of the previous August and July, and thus these months show a predictive skill of the summer minimum extent. Beyond this initial loss of memory, there is an increase in correlation—a reemergence of memory—that is more ubiquitous in the model than observations. There are two distinct modes of memory reemergence in the model. The first, a summer-to-summer reemergence arises within the model from the persistence of thickness anomalies and their influence on ice area. The second, which is also seen in observations, is associated with anomalies in the growth season that originate in the melt season. This reemergence stems from the several-month persistence of SSTs. In the model memory reemergence is enhanced by the sea ice albedo feedback. The same mechanisms that give rise to reemergence also enhance the 1-month lagged correlation during summer and winter. The study finds the least correlation between successive months when the sea ice is most rapidly advancing or retreating.
Diagnosis of Local Land–Atmosphere Feedbacks in India
Authors: Tuinenburg O. A. , Hutjes R. W. A. , Jacobs C. M. J. , Kabat P.
Published: September 2010

Following the convective triggering potential (CTP)–humidity index (HIlow) framework by Findell and Eltahir, the sensitivity of atmospheric convection to soil moisture conditions is studied for India. Using the same slab model as Findell and Eltahir, atmospheric conditions in which the land surface state affects convective precipitation are determined. For India, CTP–HIlow thresholds for land surface–atmosphere feedbacks are shown to be slightly different than for the United States.

Using atmospheric sounding data from 1975 to 2009, the seasonal and spatial variations in feedback strength have been assessed. The patterns of feedback strengths thus obtained have been analyzed in relation to the monsoon timing. During the monsoon season, atmospheric conditions where soil moisture positively influences precipitation are present about 25% of the time. During onset and retreat of the monsoon, the south and east of India show more potential for feedbacks than the north. These feedbacks suggest that large-scale irrigation in the south and east may increase local precipitation.

To test this, precipitation data (from 1960 to 2004) for the period about three weeks just before the monsoon onset date have been studied. A positive trend in the precipitation just before the monsoon onset is found for irrigated stations. It is shown that for irrigated stations, the trend in the precipitation just before the monsoon onset is positive for the period 1960–2004. For nonirrigated stations, there is no such upward trend in this period. The precipitation trend for irrigated areas might be due to a positive trend in the extent of irrigated areas, with land–atmosphere feedbacks inducing increased precipitation.
Wave- and Anemometer-Based Sea Surface Wind (WASWind) for Climate Change Analysis*
Authors: Tokinaga Hiroki , Xie Shang-Ping
Published: September 2010

Ship-based measurements of sea surface wind speed display a spurious upward trend due to increases in anemometer height. To correct this bias, the authors constructed a new sea surface wind dataset from ship observations of wind speed and wind wave height archived in the International Comprehensive Ocean–Atmosphere Data Set (ICOADS). The Wave- and Anemometer-based Sea surface Wind (WASWind) dataset is available for wind velocity and scalar speed at monthly resolution on a 4° × 4° longitude–latitude grid from 1950 to 2008. It substantially reduces the upward trend in wind speed through height correction for anemometer-measured winds, rejection of spurious Beaufort winds, and use of estimated winds from wind wave height. The reduced global upward trend is smallest among the existing global datasets of in situ observations and comparable with those of reanalysis products. Despite the significant reduction of globally averaged wind speed trend, WASWind features rich spatial structures in trend pattern, making it a valuable dataset for studies of climate changes on regional scales. Not only does the combination of ship winds and wind wave height successfully reproduce major modes of seasonal-to-decadal variability; its trend patterns are also physically consistent with sea level pressure (SLP) measurements. WASWind is in close agreement with wind changes in satellite measurements by the Special Sensor Microwave Imagers (SSM/Is) for the recent two decades. The agreement in trend pattern with such independent observations illustrates the utility of WASWind for climate trend analysis. An application to the South Asian summer monsoon is presented.