bluuebunny/crossref_metadata_2025 huggingface dataset:
A Prospective Study of Dietary Acrylamide Intake and the Risk of Endometrial, Ovarian, and Breast Cancer
Authors: Hogervorst Janneke G. , Schouten Leo J. , Konings Erik J. , Goldbohm R. Alexandra , van den Brandt Piet A.
Published: November 2007

Background: Acrylamide, a probable human carcinogen, was detected in various heat-treated carbohydrate-rich foods in 2002. The few epidemiologic studies done thus far have not shown a relationship with cancer. Our aim was to investigate the association between acrylamide intake and endometrial, ovarian, and breast cancer risk.

Methods: The Netherlands Cohort Study on diet and cancer includes 62,573 women, aged 55-69 years. At baseline (1986), a random subcohort of 2,589 women was selected using a case cohort analysis approach for analysis. The acrylamide intake of subcohort members and cases was assessed with a food frequency questionnaire and was based on chemical analysis of all relevant Dutch foods. Subgroup analyses were done for never-smokers to eliminate the influence of smoking; an important source of acrylamide.

Results: After 11.3 years of follow-up, 327, 300, and 1,835 cases of endometrial, ovarian, and breast cancer, respectively, were documented. Compared with the lowest quintile of acrylamide intake (mean intake, 8.9 μg/day), multivariable-adjusted hazard rate ratios (HR) for endometrial, ovarian, and breast cancer in the highest quintile (mean intake, 40.2 μg/day) were 1.29 [95% confidence interval (95% CI), 0.81-2.07; Ptrend = 0.18], 1.78 (95% CI, 1.10-2.88; Ptrend = 0.02), and 0.93 (95% CI, 0.73-1.19; Ptrend = 0.79), respectively. For never-smokers, the corresponding HRs were 1.99 (95% CI, 1.12-3.52; Ptrend = 0.03), 2.22 (95% CI, 1.20-4.08; Ptrend = 0.01), and 1.10 (95% CI, 0.80-1.52; Ptrend = 0.55).

Conclusions: We observed increased risks of postmenopausal endometrial and ovarian cancer with increasing dietary acrylamide intake, particularly among never-smokers. Risk of breast cancer was not associated with acrylamide intake. (Cancer Epidemiol Biomarkers Prev 2007;16(11):2304–13)
CYP17Genetic Variation and Risk of Breast and Prostate Cancer from the National Cancer Institute Breast and Prostate Cancer Cohort Consortium (BPC3)
Authors: Setiawan Veronica Wendy , Schumacher Fredrick R. , Haiman Christopher A. , Stram Daniel O. , Albanes Demetrius , Altshuler David , Berglund Göran , Buring Julie , Calle Eugenia E. , Clavel-Chapelon Françoise , Cox David G. , Gaziano J. Michael , Hankinson Susan E. , Hayes Richard B. , Henderson Brian E. , Hirschhorn Joel N. , Hoover Robert , Hunter David J. , Kaaks Rudolf , Kolonel Laurence N. , Kraft Peter , Ma Jing , Le Marchand Loïc , Linseisen Jakob , Lund Eiliv , Navarro Carmen , Overvad Kim , Palli Domenico , Peeters Petra H.M. , Pike Malcolm C. , Riboli Elio , Stampfer Meir J. , Thun Michael J. , Travis Ruth C. , Trichopoulos Dimitrios , Yeager Meredith , Ziegler Regina G. , Feigelson Heather Spencer , Chanock Stephen J.
Published: November 2007

CYP17 encodes cytochrome p450c17α, which mediates activities essential for the production of sex steroids. Common germ line variation in the CYP17 gene has been related to inconsistent results in breast and prostate cancer, with most studies focusing on the nonsynonymous single nucleotide polymorphism (SNP) T27C (rs743572). We comprehensively characterized variation in CYP17 by direct sequencing of exons followed by dense genotyping across the 58 kb region around CYP17 in five racial/ethnic populations. Two blocks of strong linkage disequilibrium were identified and nine haplotype-tagging SNPs, including T27C, were chosen to predict common haplotypes (Rh2 ≥ 0.85). These haplotype-tagging SNPs were genotyped in 8,138 prostate cancer cases and 9,033 controls, and 5,333 breast cancer cases and 7,069 controls from the Breast and Prostate Cancer Cohort Consortium. We observed borderline significant associations with prostate cancer for rs2486758 [TC versus TT, odds ratios (OR), 1.07; 95% confidence intervals (95% CI), 1.00-1.14; CC versus TT, OR, 1.09; 95% CI, 0.95-1.26; P trend = 0.04] and rs6892 (AG versus AA, OR, 1.08; 95% CI, 1.00-1.15; GG versus AA, OR, 1.11; 95% CI, 0.95-1.30; P trend = 0.03). We also observed marginally significant associations with breast cancer for rs4919687 (GA versus GG, OR, 1.04; 95% CI, 0.97-1.12, AA versus GG, OR, 1.17; 95% CI, 1.03-1.34; P trend = 0.03) and rs4919682 (CT versus CC, OR, 1.04; 95% CI, 0.97-1.12; TT versus CC, OR, 1.16; 95% CI, 1.01-1.33; P trend = 0.04). Common variation at CYP17 was not associated with circulating sex steroid hormones in men or postmenopausal women. Our findings do not support the hypothesis that common germ line variation in CYP17 makes a substantial contribution to postmenopausal breast or prostate cancer susceptibility. (Cancer Epidemiol Biomarkers Prev 2007;16(11):2237–46)
Fugu (Takifugu rubripes) Sexual Differentiation: CYP19 Regulation and Aromatase Inhibitor Induced Testicular Development
Authors: Rashid H. , Kitano H. , Hoon Lee K. , Nii S. , Shigematsu T. , Kadomura K. , Yamaguchi A. , Matsuyama M.
Published: November 2007

In order to assess the involvement of aromatase CYP19 isoforms and endogenous sex steroids in gonadal sex differentiation and development of the Japanese fugu (Takifugu rubripes), an aromatase inhibitor (AI, fadrozole) was administered to developing fishes from the ‘first feeding’ till the 100th day after hatching. It was observed that ovarian cavity formation was inhibited by fadrozole at doses of 500 and 1000 µg/g diet, which was followed by testicular differentiation in all treated fugu. In the non-treated fugu, CYP19A was predominantly expressed in the ovary and CYP19B in the brain (in both sexes), although both were expressed interchangeably at low levels. An exceptionally high expression of CYP19B was also evident in testis throughout the study period. Both forms of CYP19 mRNA showed low levels of expression in brain and gonad with no significant differences between the two AI treatments. AI treatment inhibited CYP19A mRNA in trunk during the crucial period of ovarian cavity formation and CYP19B in gonad and brain by the end of gonadal sex differentiation. An elevation of testosterone and 11-ketotestosterone was observed which can be associated with the down-regulation of the circulating 17β-estradiol production during the AI treatment period. After stopping AI treatment, both circulating estrogen and androgen were normalized. The current results suggest that suppression of CYP19A before and during morphological sex differentiation inhibits ovarian cavity formation in fugu. Furthermore, non-detectable limits of 17β-estradiol and high testosterone levels by the end of the gonadal differentiation period can be ascribed to inhibition of CYP19B, suggesting that conversion of 17β-estradiol from testosterone is plausibly regulated by CYP19B, and that this factor (CYP19B) may play an important role in AI-induced testicular development after gonadal sex differentiation through regulation of the testosterone–17β-estradiol balance in fugu.
Pattern and Progression of Cognitive Decline in Alzheimer’s Disease: Role of Premorbid Intelligence and ApoE Genotype
Authors: Bracco Laura , Piccini Carolina , Baccini Michela , Bessi Valentina , Biancucci Federica , Nacmias Benedetta , Bagnoli Silvia , Sorbi Sandro
Published: November 2007

Background/Aims: Because of controversial results across studies, we evaluated the predictive value of premorbid intelligence and the apolipoprotein E (ApoE) genotype on baseline and progression of cognitive performance in Alzheimer’s disease (AD). Methods: Eighty-five mild AD cases, ApoE genotyped and included in a longitudinal cliniconeuropsychological-genetic study, underwent a premorbid intelligence test and up to 11 (average 5) neuropsychological assessments. We applied linear- and logistic-regression models for cross-sectional data and mixed models for longitudinal ones. Results: Higher premorbid intelligence was associated with higher global, executive and memory performance, while the ApoE Ε4 allele was specifically related to poorer memory performance. The premorbid intelligence-ApoE Ε4/Ε4 interaction was significant, with higher premorbid intelligence scores reducing the detrimental effect of ApoE Ε4 homozygosity on memory performance. Higher premorbid intelligence, but not the ApoE Ε4 allele, was related to faster memory deficit progression. Conclusion: The association of higher premorbid intelligence with better baseline cognitive performance and faster memory decline, as well as its interaction with the ApoE genotype, strengthens the role of cognitive reserve in shaping the disease’s clinical expression. Our findings confirm that the Ε4 allele affects memory deficit at baseline but does not exert any influence on the rate of cognitive decline.
Consistency of Neuropsychiatric Syndromes across Dementias: Results from the European Alzheimer Disease Consortium
Authors: Aalten Pauline , Verhey Frans R.J. , Boziki Marina , Brugnolo Andrea , Bullock Roger , Byrne Eleanor Jane , Camus Vincent , Caputo Miriam , Collins Debby , De Deyn Peter Paul , Elina Kazi , Frisoni Giovanni , Holmes Clive , Hurt Catherine , Marriott Anna , Mecocci Patrizia , Nobili Flavio , Ousset Pierre Jean , Reynish Emma , Salmon Eric , Tsolaki Magda , Vellas Bruno , Robert Philippe H.
Published: November 2007

Background/Aims: The aim of this study was to determine the consistency of neuropsychiatric subsyndromes of the Neuropsychiatric Inventory across several clinical and demographic subgroups (e.g. dementia subtypes, dementia severity, medication use, age and gender) in a large sample of outpatients with dementia. Methods: Cross-sectional data of 2,808 patients with dementia from 12 centres from the European Alzheimer’s Disease Consortium were collected. Principal component analysis was used for factor analysis. Subanalyses were performed for dementia subtypes, dementia severity, medication use, age and gender. Results: The results showed the relatively consistent presence of the 4 neuropsychiatric subsyndromes ‘hyperactivity’, ‘psychosis’, ‘affective symptoms’ and ‘apathy’ across the subanalyses. The factor structure was not dependent on dementia subtypes, age and gender but was dependent on dementia severity and cholinesterase use. The factors hyperactivity and affective symptoms were present in all subanalyses, but the presence of the factors apathy and psychosis was dependent on use of cholinesterase inhibitors and dementia severity, respectively. Conclusion: The present study provided evidence of the relative consistency of neuropsychiatric subsyndromes across dementia subtypes, age and gender, thereby stressing the importance of thinking about neuropsychiatric subsyndromes instead of separate symptoms. However, the subsyndromes apathy and psychosis were dependent on use of cholinesterase inhibitors and dementia severity.
An Unusual Neonatal Presentation of Anomalous Origin of the Left Coronary Artery Arising from the Pulmonary Artery
Authors: Garty Y. , Guri A. , Shinwell E.S. , Matitiau A.
Published: November 2007

We describe a previously unreported neonatal presentation of an anomalous origin of the left coronary artery arising from the pulmonary artery. This is a full-term female infant after normal pregnancy and delivery. The baby was diagnosed at 2 days of age due to weak femoral pulses noted on the routine nursery discharge examination. The cardiac examination revealed weak pulses everywhere and mild tachypnea and tachycardia. An electrocardiogram showed clear signs of ischemia. Echocardiography demonstrated an anomalous origin of the left coronary artery arising from the pulmonary artery with bidirectional blood flow. There was a severely depressed left ventricular function and mild mitral valve regurgitation. At 4 days of age, the infant underwent complete successful surgical repair with reimplantation of the anomalous coronary artery to the aorta. She recovered slowly but well. Fifteen months later she is doing well with no cardiac residua. A neonatal presentation is very unusual due to protective high pulmonary resistance after birth, with gradual decline in pressure and gradual onset of heart failure. This case may be related to an unusually rapid drop in pulmonary vascular resistance causing very early cardiac ischemia.
Cetuximab plus Gemcitabine-Oxaliplatin (GEMOX) in Patients with Refractory Advanced Intrahepatic Cholangiocarcinomas
Authors: Paule Bernard , Herelle Marie-Olga , Rage Estelle , Ducreux Michel , Adam René , Guettier Catherine , Bralet Marie-Pierre
Published: November 2007

Objectives: To assess the efficacy and safety of cetuximab in the palliative treatment of patients with intrahepatic cholangiocarcinomas (CCA) unresponsive to first-line gemcitabine-oxaliplatin (GEMOX) pretreatment. Methods: Nine patients (mean age: 54 years) with recurrent or unresectable CCA (6 peripheral and 3 hilar CCA, histologically proven) resistant to GEMOX received cetuximab 400 mg/m2 on day 1 then 250 mg/m2 weekly combined with gemcitabine 1,000 mg/m2 on day 1 and oxaliplatin 85 mg/m2 on day 2, every 3 weeks. Immunohistochemical detection of epidermal growth factor receptor (EGFR) and erbB-2, as well as EGFR gene copy number were assessed. Tumor response was measured using RECIST. Results: A total of 43 cycles were given (3–8 per patient). After 6 months, CT scans revealed 1 complete response, 1 partial response, 1 stable disease and 6 patients with disease progression. Median time to tumor progression and overall survival were 4 and 7 months, respectively. All patients relapsed (mean follow-up: 17 months). In 6 patients, death was not related to treatment. Toxicity included grade 3 neutropenia (n = 1) and acne-like rash (n = 7). In 7 of the 9 patients, EGFR was highly expressed in all tumor cells without gene amplification. No expression of erbB-2 was noted. Conclusion: Even in the absence of EGFR gene amplification, cetuximab + GEMOX is a well-tolerated palliative treatment in patients with advanced CCA. Adding cetuximab circumvents tumor resistance to GEMOX.
Vascular Endothelial Growth Factor, Hypoxia-Inducible Factor 1 Alpha and CD34 Expressions in Early-Stage Gastric Tumors: Relationship with Pathological Factors and Prognostic Impact on Survival
Authors: Cabuk Devrim , Basaran Gul , Celikel Cigdem , Dane Faysal , Yumuk P. Fulden , Iyikesici M. Salih , Ekenel Meltem , Turhal N. Serdar
Published: November 2007

Background: Angiogenesis is one of the key steps in solid tumor growth and metastasis. We planned to investigate the prognostic significance of vascular endothelial growth factor (VEGF), hypoxia-inducible factor 1α (HIF-1α) and CD34 expressions as markers of angiogenesis in gastric cancer. Patients and Methods: We retrospectively reviewed the medical records of 51 gastric cancer patients who had total or subtotal gastrectomy at Marmara University Hospital from 1990 to 2004 and evaluated the expression of VEGF, HIF-1α and CD34 by immunohistochemistry in their archival tumor tissues. We recorded the clinical and pathological characteristics of these patients and analyzed their survival outcome. Results: Thirty out of 51 patients were males. The median age was 63 years (range 34–81). The median follow-up was 17 months. Thirty-six patients had node-positive disease. The majority of patients (n = 43) had T2 and T3 disease. Vascular and lymphatic invasions were present in 57 and 77% of tumors, respectively. VEGF and HIF-1α were positive in 65 and 71% of tumors. The median CD34 staining score was 19 (3–68). VEGF, HIF-1α and CD34 expressions were more frequent in tumors without serosal invasion (p = 0.01, p = 0.01 and p = 0.003, respectively). CD34 expression was significantly more frequent in tumors with VEGF and HIF-1α expression (p = 0.00, p = 0.00). HIF-1α expression was more frequent in tumors with VEGF expression (p = 0.00). The 5-year overall survival was 45%. VEGF, HIF-1α, CD34 expressions and other pathological characteristics were found to have no impact on survival. Conclusion: VEGF, HIF-1α and CD34 expressions were more common in tumors without serosal invasion. As a future perspective, biological agents targeting VEGF and HIF-1α might be more effective at earlier stages of gastric cancer.
Placebo-Controlled, Double-Blind, Randomized, Prospective Study of a Glycerol-Based Emollient on Eczematous Skin in Atopic Dermatitis: Biophysical and Clinical Evaluation
Authors: Breternitz M. , Kowatzki D. , Langenauer M. , Elsner P. , Fluhr J.W.
Published: November 2007

Background/Aims: Atopic dermatitis (AD) is a frequent, chronic inflammatory disease influenced by local, immunological, genetic and environmental factors. Important symptoms of AD are dry skin, intense pruritus and impaired epidermal barrier function. The therapeutic management of AD is difficult and needs individualized concepts. Moisturizing creams and emollients are useful and important treatment adjuncts for the daily skin care of patients with dry and inflamed skin, e.g. AD. Glycerol is known to increase stratum corneum (SC) hydration, improve epidermal barrier function and decrease clinical signs of inflammation. However, no controlled study on the efficacy of glycerol on barrier function and SC hydration in AD has been published. In the present study, a topical 20% glycerol preparation was compared with its vehicle in patients with AD. The aim of the present study was to evaluate the effect of a single emollient ingredient in AD within the full frame of a phase III drug study. Methods: 24 patients with AD were treated for 4 weeks twice daily with a glycerol-based emollient in a randomized, double-blind study. Transepidermal water loss, skin capacitance, erythema and skin surface pH were assessed with biophysical, non-invasive instruments. The SCORAD and a local severity score were evaluated. After a wash-out period of 2 weeks, these parameters were assessed in order to quantify the sustained effect of this treatment. Results: SC hydration was significantly improved, and epidermal barrier function was restored under treatment with glycerol-containing cream compared to the glycerol-free placebo. No significant differences were detectable for erythema values, SCORAD and local severity between the glycerol-containing cream and placebo. However, an improvement over time was detectable in the assessed parameters in both groups indicating the importance of emollient treatment in AD. Conclusions: Glycerol-based emollients have a positive influence on the skin of patients with AD. They enhance the SC hydration. Furthermore, it was possible to evaluate skin care products with a protocol design for efficacy studies of fully registered drugs in a placebo-controlled study.
Simvastatin Reverses High Glucose-Induced Apoptosis of Mesangial Cells via Modulation of Wnt Signaling Pathway
Authors: Lin Chun-Liang , Cheng Ho , Tung Chun-Wu , Huang Wei-Jan , Chang Pey-Jium , Yang Jen-Tsung , Wang Jeng-Yi
Published: November 2007

Background/Aims: Disruption of Wnt/β-catenin signaling in mesangial cells is a pathogenic consequence of diabetic nephropathy. We examined the role of simvastatin (SIM) in modulation of Wnt/β-catenin signaling in the apoptosis of high glucose (HG)-stressed mesangial cells in vitro and in vivo. Methods: For in vitro studies, we cultured mesangial cells, with or without SIM pretreatment, in 35 mM glucose and then assayed Wnt activity and apoptosis. For in vivo studies, we administered SIM to streptozocin-induced diabetic rats for 28 days and then dissected renal tissues for immunohistological assessment of Wnt signal expression and apoptosis of glomerular cells. Results: SIM reduced the promotional effect of HG on caspase-3 expression, PARP activation, and cell apoptosis. HG significantly reduced Wnt4 and Wnt5a mRNA expression and SIM restored Wnt4 and Wnt5a mRNA expression to the level of controls. SIM also suppressed HG-mediated activation of GSK-3b and restored nuclear β-catenin levels and phospho-Akt expression. This suggests that SIM alters the stability of β-catenin, a critical element of mesangial cell survival. Exogenous SIM treatment blocked DNA fragmentation, increased the Wnt/β-catenin immunoreactivities of cells adjacent to renal glomeruli, and attenuated urinary protein secretion in diabetic rats. Conclusions: SIM reduces the detrimental effects of HG on diabetic renal glomeruli in vitro and in vivo. SIM prevents HG-induced downregulation of Wnt/β-catenin signaling and thereby blocks mesangial cell apoptosis.
Femoral Localization and Higher Ultrafiltration Rate but Not Concentration of Heparin Used for Canal Locking of Hemodialysis Catheter Are Negative Predictors for Its Malfunction
Authors: Brzosko Szymon , Hryszko Tomasz , Malyszko Jolanta , Malyszko Jacek Stanisław , Mazerska Maria , Myśliwiec Michal
Published: November 2007

Background/Aim: Non-tunneled, temporal hemodialysis (HD) catheters are commonly used as short-term vascular access for the HD procedure. One of their late complications is thrombotic occlusion of the catheter ensuing in their malfunction. A heparin lock is conventionally used for maintaining the patency of the catheter. The aim of the study was to evaluate the influence of heparin concentration used for locking the catheter canals (5,000 vs. 2,500 IU/ml) and some other clinical and laboratory variables at the time of temporal HD catheter functioning. Methods: Catheter malfunction was defined as the inability to attain and maintain a blood flow of at least 150 ml/min. 174 consecutive HD catheters inserted into jugular or femoral veins (114 patients) were followed up and remained in use for a total of 3,284 days. Results: Catheter thrombosis occurred in 53 cases (30.5%) during the study period, giving an overall rate of 16 episodes per 1,000 catheter-days at risk. In univariate Cox proportional hazard analysis, predictors of catheter dysfunction were: femoral localization (HR 4.92, 95% CI 4.30–5.50), acute renal failure (HR 1.75, 95% CI 1.18–2.32), higher mean ultrafiltration (UF) (HR 1.31, 95% CI 0.99–1.63) and higher concentration of hemoglobin (HR 1.15, 95% CI 0.99–1.33). The concentration of heparin used for canal locking did not influence the time of catheter functioning (HR 1.1, p = 0.7). In multivariate Cox proportional hazard analysis (χ2 = 38.5, d.f. = 4, p < 0.0001) the remaining statistically independent predictors of catheter malfunction were: femoral localization (HR 5.94, 95% CI 5.27–6.61, p < 0.0001) and higher UF (HR 1.60, 95% CI 1.24–1.94, p < 0.01). Conclusions: A lower concentration of heparin (2,500 IU/ml) prevents catheter thrombosis as effectively as a standard one (5,000 IU/ml). Femoral localization of HD catheters and higher UF during the HD procedure are the factors predisposing for catheter malfunction.
Combined Deletion of Macrophage ABCA1 and ABCG1 Leads to Massive Lipid Accumulation in Tissue Macrophages and Distinct Atherosclerosis at Relatively Low Plasma Cholesterol Levels
Authors: Out Ruud , Hoekstra Menno , Habets Kim , Meurs Illiana , de Waard Vivian , Hildebrand Reeni B. , Wang Yanan , Chimini Giovanna , Kuiper Johan , Van Berkel Theo J.C. , Van Eck Miranda
Published: November 2007

Objective—

The purpose of this study was to evaluate the effect of the combined deletion of ABCA1 and ABCG1 expression in macrophages on foam cell formation and atherosclerosis.

Methods and Results—

LDL receptor knockout (KO) mice were transplanted with bone marrow from ABCA1/ABCG1 double KO (dKO) mice. Plasma cholesterol levels after 6 weeks of Western-type diet (WTD) feeding were significantly lower in dKO transplanted mice than ABCA1 KO, ABCG1 KO, and control transplanted animals. Extreme foam cell formation was present in macrophages of various tissues and the peritoneal cavity of dKO transplanted animals. Furthermore, severe hypoplasia of the thymus and a significant decrease in CD4-positive T cells in blood was observed. Despite relatively low plasma cholesterol levels dKO transplanted animals developed lesion sizes of 156±19×10
3
μm
2
after only 6 weeks of WTD feeding. Lesions, however, were smaller than single ABCA1 KO transplanted animals (226±30×10
3
μm
2
;
P
<0.05) and not significantly different from single ABCG1 KO (117±22×10
3
μm
2
) and WT transplanted mice (112±15×10
3
μm
2
).

Conclusions—

Macrophage ABCA1 and ABCG1 play a crucial role in the prevention of macrophage foam cell formation, whereas combined deletion only modestly influences atherosclerosis which is associated with an attenuated increase in WTD-induced plasma cholesterol and decreased proinflammatory CD4-positive T cell counts.
The Role of Osteopontin in Recovery from Hind Limb Ischemia
Authors: Duvall Craig L. , Weiss Daiana , Robinson Scott T. , Alameddine Fadi M.F. , Guldberg Robert E. , Taylor W. Robert
Published: November 2007

Objective—

Osteopontin (OPN) is a highly phosphorylated extracellular matrix glycoprotein that is involved in a diversity of biological processes. In the vascular wall, OPN is produced by monocytes/macrophages, endothelial cells, and smooth muscle cells, and it is thought to mediate adhesion, migration, and survival of these cell types. In this study, we hypothesized that OPN plays a critical role in recovery from limb ischemia.

Methods and Results—

We induced hind limb ischemia in wild-type and OPN
−/−
mice. OPN
−/−
mice exhibited significantly delayed recovery of ischemic foot perfusion as determined by LDPI, impaired collateral vessel formation as measured using micro-CT, and diminished functional capacity of the ischemic limb. In the aortic ring assay, normal endothelial cell sprouting was found in OPN
−/−
mice. However, OPN
−/−
peritoneal monocytes/macrophages were found to possess significantly reduced migration in response to chemoattraction.

Conclusions—

This study provides evidence that a definitive biological role exists for OPN during ischemic limb revascularization, and we have suggested that this may be driven by impaired monocyte/macrophage migration in OPN
−/−
mice. These findings provide the first in vivo evidence that OPN may be a key regulator in postnatal vascular growth.
Toll-Like Receptor 4 Mediates Maladaptive Left Ventricular Remodeling and Impairs Cardiac Function After Myocardial Infarction
Authors: Timmers Leo , Sluijter Joost P.G. , van Keulen J. Karlijn , Hoefer Imo E. , Nederhoff Marcel G.J. , Goumans Marie-Jose , Doevendans Pieter A. , van Echteld Cees J.A. , Joles Jaap A. , Quax Paul H. , Piek Jan J. , Pasterkamp Gerard , de Kleijn Dominique P.V.
Published: November 2007

Left ventricular (LV) remodeling leads to congestive heart failure and is a main determinant of morbidity and mortality following myocardial infarction. Therapeutic options to prevent LV remodeling are limited, which necessitates the exploration of alternative therapeutic targets. Toll-like receptors (TLRs) serve as pattern recognition receptors within the innate immune system. Activation of TLR4 results in an inflammatory response and is involved in extracellular matrix degradation, both key processes of LV remodeling following myocardial infarction. To establish the role of TLR4 in postinfarct LV remodeling, myocardial infarction was induced in wild-type BALB/c mice and TLR4-defective C3H-
Tlr4

LPS−d

mice. Without affecting infarct size, TLR4 defectiveness reduced the extent of LV remodeling (end-diastolic volume: 103.7±6.8 μL versus 128.5±5.7 μL;
P
<0.01) and preserved systolic function (ejection fraction: 28.2±3.1% versus 16.6±1.3%;
P
<0.01), as assessed by MRI. In the noninfarcted area, interstitial fibrosis, and myocardial hypertrophy were reduced in C3H-
Tlr4

LPS−d

mice. In the infarcted area, however, collagen density was increased, which was accompanied by fewer macrophages, reduced inflammation regulating cytokine expression levels (interleukin [IL]-1α, IL-2, IL-4, IL-5, IL-6, IL-10, IL-17, tumor necrosis factor-α, interferon-γ, granulocyte/macrophage colony-stimulating factor), and reduced matrix metalloproteinase-2 (4684±515 versus 7573±611;
P
=0.002) and matrix metalloproteinase-9 activity (76.0±14.3 versus 168.0±36.2;
P
=0.027). These data provide direct evidence for a causal role of TLR4 in postinfarct maladaptive LV remodeling, probably via inflammatory cytokine production and matrix degradation. TLR4 may therefore constitute a novel target in the treatment of ischemic heart failure.
Reduced Phospholamban Phosphorylation Is Associated With Impaired Relaxation in Left Ventricular Myocytes From Neuronal NO Synthase–Deficient Mice
Authors: Zhang Yin Hua , Zhang Mei Hua , Sears Claire E. , Emanuel Krzysztof , Redwood Charles , El-Armouche Ali , Kranias Evangelia G. , Casadei Barbara
Published: November 2007

Stimulation of nitric oxide (NO) release from the coronary endothelium facilitates myocardial relaxation via a cGMP-dependent reduction in myofilament Ca
2+
sensitivity. Recent evidence suggests that NO released by a neuronal NO synthase (nNOS) in the myocardium can also hasten left ventricular relaxation; however, the mechanism underlying these findings is uncertain. Here we show that both relaxation (TR
50
) and the rate of [Ca
2+
]
i
transient decay (tau) are significantly prolonged in field-stimulated or voltage-clamped left ventricular myocytes from nNOS
−/−
mice and in wild-type myocytes (nNOS
+/+
) after acute nNOS inhibition. Disabling the sarcoplasmic reticulum abolished the differences in TR
50
and tau, suggesting that impaired sarcoplasmic reticulum Ca
2+
reuptake may account for the slower relaxation in nNOS
−/−
mice. In line with these findings, disruption of nNOS (but not of endothelial NOS) decreased phospholamban phosphorylation (P-Ser
16
PLN), whereas nNOS inhibition had no effect on TR
50
or tau in PLN
−/−
myocytes. Inhibition of cGMP signaling had no effect on relaxation in either group whereas protein kinase A inhibition abolished the difference in relaxation and PLN phosphorylation by decreasing P-Ser
16
PLN and prolonging TR
50
in nNOS
+/+
myocytes. Conversely, inhibition of type 1 or 2A protein phosphatases shortened TR
50
and increased P-Ser
16
PLN in nNOS
−/−
but not in nNOS
+/+
myocytes, in agreement with data showing increased protein phosphatase activity in nNOS
−/−
hearts. Taken together, our findings identify a novel mechanism by which myocardial nNOS promotes left ventricular relaxation by regulating the protein kinase A–mediated phosphorylation of PLN and the rate of sarcoplasmic reticulum Ca
2+
reuptake via a cGMP-independent effect on protein phosphatase activity.
Prestroke Cognitive Performance, Incident Stroke, and Risk of Dementia
Authors: Reitz Christiane , Bos Michiel J. , Hofman Albert , Koudstaal Peter J. , Breteler Monique M.B.
Published: November 2007

Background and Purpose—

Several studies indicate that stroke increases the risk of dementia. Most of these studies lacked the ability to take accurately assessed prestroke cognitive function into account. Whether the effects of stroke merely unravel an ongoing underlying dementing process or in fact cause the dementia has implications for the prevention of dementia in persons with cerebrovascular disease. We explored in a prospective cohort study whether stroke occurrence was related to a higher risk of subsequent dementia and whether this association was dependent on prestroke slope of cognitive function.

Methods—

Cox proportional hazard models were used to relate incident stroke as a time-varying exposure with the risk of dementia in 6724 participants of the Rotterdam Study without dementia or stroke at baseline (49 361 person years of follow-up). Subsequently Cox proportional hazard models were performed to assess whether this association was dependent on slope of prestroke cognitive performance and other risk factors for cognitive decline.

Results—

Independent of both level and the rate of change of prestroke cognitive performance and other risk factors for cognitive decline, incident stroke was associated with a more than doubled risk of subsequent dementia (hazard ratio, 2.1; 95% CI, 1.55 to 2.81).

Conclusions—

Prestroke cognitive function is not a major determinant of the effect of stroke on the risk of poststroke dementia.
Ultrasound Diagnosis of Spontaneous Carotid Dissection With Isolated Horner Syndrome
Authors: Arnold Marcel , Baumgartner Ralf W. , Stapf Christian , Nedeltchev Krassen , Buffon Frédérique , Benninger David , Georgiadis Dimitrios , Sturzenegger Matthias , Mattle Heinrich P. , Bousser Marie-Germaine
Published: November 2007

Background and Purpose—

Isolated Horner syndrome without associated cranial nerve palsies or ischemic symptoms is an important presentation of spontaneous internal carotid artery dissection (sICAD). Ultrasound is often used as a screening method in these patients because cervical MRI is not always available on an emergency basis. Current knowledge on ultrasound findings in patients with sICAD presenting with isolated Horner syndrome is limited.

Methods—

Patients were recruited from prospective cervical artery dissection databases of 3 tertiary care centers. Diagnosis of sICAD was confirmed by cervical MRI and MR angiography or digital subtraction angiography in all patients. Data on Doppler sonography and color duplex sonography examinations performed within 30 days of symptom onset were analyzed.

Results—

We identified 88 patients with Horner syndrome as the only sign of sICAD. Initial ultrasound examination was performed in 72 patients after a mean time interval from symptom onset to examination of 11 (SD 8) days. The overall frequency of false-negative ultrasound findings was 31% (22 of 72 patients). It showed stenosis ≥80% or occlusion in 34 (47%) patients, and stenosis ≤80% in 16 (22%). It visualized mural hematoma in 7 patients and intimal flap in one. Patients with normal ultrasound were less frequently smokers (9% versus 28%,
P
=0.034), and had less frequently migraine without aura (9% versus 43%,
P
=0.012) or neck pain (18% versus 62%,
P
=0.003) than those with pathological ultrasound findings.

Conclusions—

Nearly one third of patients with Horner syndrome as the only sign of sICAD presented with normal ultrasound findings. These results indicate that ultrasound is not a reliable method to diagnose sICAD in patients with isolated Horner syndrome.
A Pilot Study of Randomized Clinical Controlled Trial of Gait Training in Subacute Stroke Patients With Partial Body-Weight Support Electromechanical Gait Trainer and Functional Electrical Stimulation
Authors: Ng Maple F.W. , Tong Raymond K.Y. , Li Leonard S.W.
Published: November 2007

Background and Purpose—

This study aimed to assess the effectiveness of gait training using an electromechanical gait trainer with or without functional electrical stimulation for people with subacute stroke.

Methods—

This was a nonblinded randomized controlled trial with a 6-month follow-up. Fifty-four subjects were recruited within 6 weeks after stroke onset and were randomly assigned to 1 of 3 gait intervention groups: conventional overground gait training treatment (CT, n=21), electromechanical gait trainer (GT, n=17) and, electromechanical gait trainer with functional electrical stimulation (GT-FES, n=16). All subjects were to undergo an assigned intervention program comprising a 20-minute session every weekday for 4 weeks. The outcome measures were Functional Independence Measure, Barthel Index, Motricity Index leg subscale, Elderly Mobility Scale (EMS), Berg Balance Scale, Functional Ambulatory Category (FAC), and 5-meter walking speed test. Assessments were made at baseline, at the end of the 4-week intervention program, and 6 months after the program ended.

Results—

By intention-to-treat and multivariate analysis, statistically significant differences showed up in EMS (Wilks’ λ=0.743,
P
=0.005), FAC (Wilks’ λ=0.744,
P
=0.005) and gait speed (Wilks’ λ=0.658,
P
<0.0001). Post hoc analysis (univariate 2-way ANCOVA) revealed that the GT and GT-FES groups showed significantly better improvement in comparison with the CT group at the end of the 4 weeks of training and in the 6-month follow-up.

Conclusions—

For the early stage after stroke, this study indicated a higher effectiveness in poststroke gait training that used an electromechanical gait trainer compared with conventional overground gait training. The training effect was sustained through to the 6-month follow-up after the intervention.
Pretty Paper Rolls: Experiments in Woven Circuits
Authors: Blasser Peter
Published: November 2007

The author presents a history of his efforts to design sustainable and economical circuit construction on paper, which he finds more akin to craft than industry. He focuses on a collection of modules called Rollz-5, which creates organic rhythms out of geometrical forms. A future application of this work will be to create radio devices based on the Platonic solids.
Big Fish and Small Fish Debate–An Examination of the Prosecutorial Discretion
Authors: Takemura Hitomi
Published: November 2007

It is widely known that the earlier practices of the International Criminal Tribunal for the Former Yugoslavia have been criticized for having dealt with comparably minor war criminals. The implications behind such a criticism may be that an ad hoc international or hybrid criminal tribunal should concentrate on those who were most responsible for the crimes and serious violations of international humanitarian law. The first part of this paper will thus focus on the logic of targeting big fish. Then the recent practices of the ad hoc International Criminal Tribunals and the Special Panels for Serious Crimes of East Timor have been addressed in this light. Irrespective of the institutional and practical demands of targeting big fish, the concern remains whether there is a normative demand for targeting only senior leaders of mass atrocities. Therefore, the last part of this paper would like to discuss the big fish versus small fish debate by examining the possibilities of a leadership element in ratione materiae of international criminal tribunals.
The Dynamic Response of the Winter Stratosphere to an Equable Climate Surface Temperature Gradient
Authors: Korty Robert L. , Emanuel Kerry A.
Published: November 2007

This work investigates the dynamic and thermal response of the winter stratosphere to the presence of a weak meridional surface temperature gradient. Previous work suggested that polar stratospheric clouds could have played a decisive role in maintaining high-latitude warmth, especially over continental interiors, during the polar nights of the late Paleocene and early Eocene epochs; both a chemical source of additional water vapor and a dynamical feedback between the surface climate and stratospheric temperatures have been proposed as mechanisms by which such clouds could form. A principal goal of this work is to investigate the latter problem using a general circulation model with stratospheric resolution that is forced with a very weak surface temperature gradient. It is found that temperatures in the lower stratosphere do not deviate significantly from the control run, which results from a robust flux of wave activity into the winter stratosphere. The strength of the stratosphere’s residual circulation increases slightly in the presence of the weak gradient, as wavenumber 3 begins to propagate to stratospheric altitudes. Changes in the zonal wind field that allow for the altered propagation are in balance with a weakened temperature gradient through the full depth of the troposphere. These simulations also suggest that the tropospheric thermal stratification could be maintained by moist convection at all latitudes in warm climate states with a weak temperature gradient.
Long-Term Performance of Aanderaa Optodes and Sea-Bird SBE-43 Dissolved-Oxygen Sensors Bottom Mounted at 32 m in Massachusetts Bay
Authors: Martini Marinna , Butman Bradford , Mickelson Michael J.
Published: November 2007

A field evaluation of two new dissolved-oxygen sensing technologies, the Aanderaa Instruments AS optode model 3830 and the Sea-Bird Electronics, Inc., model SBE43, was carried out at about 32-m water depth in western Massachusetts Bay. The optode is an optical sensor that measures fluorescence quenching by oxygen molecules, while the SBE43 is a Clark polarographic membrane sensor. Optodes were continuously deployed on bottom tripod frames by exchanging sensors every 4 months over a 19-month period. A Sea-Bird SBE43 was added during one 4-month deployment. These moored observations compared well with oxygen measurements from profiles collected during monthly shipboard surveys conducted by the Massachusetts Water Resources Authority. The mean correlation coefficient between the moored measurements and shipboard survey data was >0.9, the mean difference was 0.06 mL L−1, and the standard deviation of the difference was 0.15 mL L−1. The correlation coefficient between the optode and the SBE43 was >0.9 and the mean difference was 0.07 mL L−1. Optode measurements degraded when fouling was severe enough to block oxygen molecules from entering the sensing foil over a significant portion of the sensing window. Drift observed in two optodes beginning at about 225 and 390 days of deployment is attributed to degradation of the sensing foil. Flushing is necessary to equilibrate the Sea-Bird sensor. Power consumption by the SBE43 and required pump was 19.2 mWh per sample, and the optode consumed 0.9 mWh per sample, both within expected values based on manufacturers’ specifications.
Lightning Charge Retrievals: Dimensional Reduction, LDAR Constraints, and a First Comparison with LIS Satellite Data
Authors: Koshak W. J. , Krider E. P. , Murray N. , Boccippio D. J.
Published: November 2007

A “dimensional reduction” (“DR”) method is introduced for analyzing lightning field changes (ΔEs) whereby the number of unknowns in a discrete two-charge model is reduced from the standard eight (x, y, z, Q, x′, y′, z′, Q′) to just four (x, y, z, Q). The four unknowns (x, y, z, Q) are found by performing a numerical minimization of a chi-square function. At each step of the minimization, an overdetermined fixed matrix (OFM) method is used to immediately retrieve the best “residual source” (x′, y′, z′, Q′), given the values of (x, y, z, Q). In this way, all eight parameters (x, y, z, Q, x′, y′, z′, Q′) are found, yet a numerical search of only four parameters (x, y, z, Q) is required. The DR method has been used to analyze lightning-caused ΔEs derived from multiple ground-based electric field measurements at the NASA Kennedy Space Center (KSC) and U.S. Air Force Eastern Range (ER). The accuracy of the DR method has been assessed by comparing retrievals with data provided by the lightning detection and ranging (LDAR) system at the KSC-ER, and from least squares error estimation theory, and the method is shown to be a useful “stand alone” charge retrieval tool. Since more than one charge distribution describes a finite set of ΔEs (i.e., solutions are nonunique), and since there can be appreciable differences in the physical characteristics of these solutions, not all DR solutions are physically acceptable. Hence, an alternative and more accurate method of analysis is introduced that uses LDAR data to constrain the geometry of the charge solutions, thereby removing physically unacceptable retrievals. The charge solutions derived from this method are shown to compare well with independent satellite- and ground-based observations of lightning in several Florida storms.
Quantifying EOS Aqua and NOAA POES AMSU-A Brightness Temperature Biases for Weather and Climate Applications Utilizing the SNO Method
Authors: Iacovazzi Robert A. , Cao Changyong
Published: November 2007

Systematic biases between brightness temperature (Tb) measurements made from concurrently operational Advanced Microwave Sounding Unit-A (AMSU-A) instruments can introduce errors into weather and climate applications. For this reason, in this study the ability of the simultaneous nadir overpass (SNO) method to estimate relative Tb biases between operational Earth Observing System (EOS) Aqua and Polar-orbiting Operational Environmental Satellites (POES) NOAA-15, NOAA-16, and NOAA-18 AMSU-A instruments is evaluated.

From an analysis of SNO events occurring from 21 May 2005 to 31 July 2006, AMSU-A SNO-ensemble mean Tb biases could not be statistically determined for window channels, while significant bias detection to within about 0.02 K is accomplished in some low-noise sounding channels. These results are shown to be a consequence of the decrease of the earth-scene Tb variability with increasing atmospheric zenith opacity, which is a function of microwave frequency. Examination of SNO-ensemble mean Tb biases for two independent AMSU-A instrument components—AMSU-A1–1 and AMSU-A1–2—exposed a significant cold (warm) bias on the order of 0.4 K (0.2 K) in the AMSU-A1–1 unit on board the NOAA-18 (Aqua) satellite. This analysis also revealed on average a significant cold bias on the order of 0.1 K in the NOAA-16 AMSU-A1–2 component. Furthermore, the individual SNO mean Tb biases were often found to be a function of the SNO earth-scene average Tb, which is a manifestation of instrument calibration errors. On the other hand, it was found that determining the root cause of such errors is inhibited by the lack of postlaunch quality control of the AMSU-A calibration-related hardware.

Based on the results of this study, a need to reduce impacts of surface emissivity and temperature inhomogeneities on the SNO method in microwave radiometer window channels becomes evident. In addition, the unparalleled ability of the SNO method to isolate and quantify intersatellite, instrument-related Tb biases is demonstrated in most sounding channels, which is necessary to improve weather and climate applications.
The Accuracy of Sea Ice Drafts Measured from U.S. Navy Submarines
Authors: Rothrock D. A. , Wensnahan Mark
Published: November 2007

Navy submarines in the Arctic Ocean routinely obtain observations from an upward-looking sonar of the draft of the sea ice cover overhead. Draft data are now publicly available from some 40 cruises from 1975 to 2000 covering over 120 000 km of track in roughly the central half of the Arctic Ocean. To apply these observations to geophysics, error estimates are needed. This paper assesses how well the correction of the data during normal processing accounts for the major sources of error in the draft data from U.S. Navy submarines and what errors remain in the data. The error treated is the error for the average draft over tens of kilometers. The following sources of error are considered: measurement precision error; errors in identifying open water (as ice of zero draft); sound speed error; errors caused by variable sonar footprint size, by uncontrolled gain and thresholds, and by ship’s trim; and differences between data from analog charts and digitally recorded data. The bias with respect to the actual draft is +29 cm and is important both for knowing the actual ice draft and for comparing drafts from submarines with thicknesses in models and with draft, thickness, or freeboard estimated by other vehicles and technologies. The standard deviation is 25 cm. This number estimates the repeatability and comparability of draft measurements by U.S. Navy submarines and is important for examining the submarine data for regional and temporal variation. These errors are tolerable for an operational data source with a signal many meters in amplitude.
Adaptability of Just-in-time (JIT) Philosophy to Service Systems: A Case Study
Authors: Balci Deniz , Kesen Saadettin Erhan , Baykoç Ömer Faruk
Published: November 2007

Although a great deal of successful research has been carried out in just-in-time (JIT) philosophy, few researchers have focused on the adaptation of JIT philosophy in service systems. Despite the recent improvements in the service systems, few studies have been carried out which eXamine the effects of the JIT philosophy on service systems which have a different structure to production systems. As a result of the benefits obtained from successful application of the JIT philosophy in the production systems, we have adapted the JIT philosophy for the service systems and eXamined the obtainable benefits. For this purpose, observation and time-scaling studies were made in an Adult Emergency Service in Turkey. Within the framework of the data acquired in this study, the eXisting system was modeled. By analyzing the simulation results, an alternative system has been proposed which can be applied to the system. Results show that the proposed system under the principle of JIT philosophy outperforms the eXisting system.