bluuebunny/crossref_metadata_2025 huggingface dataset:
Predicting diameter distributions: a test of the stationary Markov model
Authors: Roberts Mark R. , Hruska Allan J.
Published: April 2010

We tested the null hypothesis that diameter class transitions over a 40-year period (1940–1980) in an even-aged mixed Pinusresinosa Ait. – Pinusstrobus L. stand represent a stationary Markov process. Transition probabilities were constructed from growth data on 202 trees ≥ 5.1 cm DBH in a 0.4-ha permanent plot. For each species, a diameter distribution in 1980 was predicted with the stationary Markov model using the 1940–1950 transition probability matrix. The predicted and observed 1980 distributions were significantly different for P. resinosa (χ2 = 31.67, p < 0.01), but not P. strobus (χ2 = 7.86, not significant). In P. resinosa, growth rates of trees in the same diameter class at different points in time declined with increasing stand age. This violates the assumption of stationarity. Growth did not decline in most diameter classes in P. strobus. The model also assumes that differences in the competitive histories of trees of the same size do not affect transition probabilities. The average growth rates of trees in different crown classes within two diameter classes were significantly different for P. resinosa, but not for P. strobus. Both assumptions of the model were violated in the case of P. resinosa. The.model was not rejected for P. strobus because it is a midtolerant species capable of relatively constant growth in the understory. However, this study included only the middle period of stand development when growth rates are relatively constant. These results indicate that more biologically realistic modelling approaches which incorporate growth declines with stand age and past competitive effects should be pursued.
Intraspecific variation in stem growth of western hemlock
Authors: Pollard D. F. W. , Portlock F. T.
Published: April 2010

Fifteen coastal provenances of western hemlock Tsugaheterophylla (Raf.) Sarg. were tested on four sites on Vancouver Island, B.C. Provenance origins and test sites lay within roughly 2° of latitude and at 0–580 m above mean sea level. Mean heights of provenances 10 years after planting varied from roughly 74 to 121% of the plantation mean at each site; plantation means varied from 388 to 493 cm. No interaction between provenance and test site was detected and rankings of provenances remained quite constant from site to site. A large proportion of provenance variation could not be accounted for by descriptors of provenance origin. Results show that for the geographic range tested, faster growing provenances could be planted without constraints imposed by elevation and latitude.
An FBG-Based Impact Event Detection System for Structural Health Monitoring
Authors: Shin C. S. , Chen B. L. , Liaw S. K.
Published: April 2010

Some structures are vulnerable to localized internal damages incurred by impact of small objects. An impact monitoring system using fiber Bragg grating (FBG) sensors has been established. Its ability to detect very low to medium energy impacts has been demonstrated on an aluminum plate and a 22 m long wind turbine blade. Previous analysis of this technique showed that the accuracy by which an impact position can be located is limited by equipment noises and angular insensitivity of the FBG. By employing two intensity demodulation schemes with different demodulation sensitivities and ranges, we try to differentiate the relative importance of the above limiting effects. Based on the results, directions for further improvement on impact source locating accuracy will be discussed and the implication of applying such systems on large-scale structures will be examined.
Almost Periodic Solutions of a Discrete Mutualism Model with Feedback Controls
Authors: Wang Zheng , Li Yongkun
Published: April 2010

We consider a discrete mutualism model with feedback controls. Assuming
that the coefficients in the system are almost periodic sequences, we obtain the
existence and uniqueness of the almost periodic solution which is uniformly asymptotically
stable.
Robotic Autonomous Observatories: A Historical Perspective
Authors: Castro-Tirado Alberto Javier
Published: April 2010

This paper presents a historical introduction to the field of Robotic Astronomy, from the point of view of a scientist working in this field for more than a decade. The author discusses the basic definitions, the differing telescope control operating systems, observatory managers, as well as a few current scientific applications.
New Examples of Einstein Metrics in Dimension Four
Authors: Ghanam Ryad
Published: April 2010

We construct new examples of four‐dimensional Einstein metrics with neutral signature and two‐dimensional holonomy Lie algebra.
Hepatitis B Response of Premature Infants after Primary and Booster Immunisation with a Diphtheria-Tetanus-Acellular Pertussis-Hepatitis B-Inactivated Poliovirus/Haemophilus InfluenzaeType B Vaccine
Authors: Omeñaca Felix , Garcia-Sicilia Jose , Boceta Reyes , García-Corbeira Pilar
Published: April 2010

A range of schedules are recommended for hepatitis B vaccination of premature infants. This open-label study (217744/083) compared the immune response of premature (N=94) and full-term infants (N=92) to hepatitis B antigen following primary administration of hexavalent DTPa-HBV-IPV/Hib vaccine at 2–4–6 months and a booster dose at 18 months. Anti-HBsAg antibodies were determined before and one month after primary and booster doses. There were no significant differences in postprimary seroprotection rates (anti-HBsAg >10 mIU/mL; preterm 93.4%; full-term 95.2%) or geometric mean concentrations (634 versus 867 mIU/ml), and neither appeared to be related to gestational length or birth weight. Prebooster seroprotection rates were 75 and 80.6%, respectively. Six premature infants did not respond to primary and booster doses. Primary and booster vaccinations with DTPa-HBV-IPV/Hib elicit satisfactory anti-HBsAg responses in preterm infants, which are not influenced by gestational age or birth weight. This schedule and vaccine will greatly facilitate the immunisation of premature infants.
Fluorogenic Membrane Overlays to Enumerate Total and FecalEscherichia coliand Total Vibrionaceae in Shellfish and Seawater
Authors: Richards Gary P. , Watson Michael A.
Published: April 2010

Three assays were developed to enumerate total and fecalEscherichia coliand total Vibrionaceae in shellfish, seawater, and other foods and environmental samples. Assays involve membrane overlays of overnight colonies on nonselective agar plates to detect -glucuronidase and lysyl aminopeptidase activities forE. coliand Vibrionaceae, respectively. Cellulose membranes containing the substrates 4-methylumbeferyl--D-glucuronide (MUG) produced a bright blue fluorescence when overlaid ontoE. coli, while L-lysyl-7-amino-4-trifluoromethylcoumarin produced green fluorescent foci when overlaid onto Vibrionaceae family members. A multiplex assay was also developed for simultaneously enumerating totalE. coliand total Vibrionaceae in oysters and seawater. Overall, 65% of overlaidE. coli(non-O157:H7) were MUG-positive, compared with 62% as determined by the most-probable-number-MUG assay. The overlays are rapid, simple, and cost effective for quantification purposes. This research provides practical alternatives for monitoring bacterial indicators and potential pathogens in complex samples, including molluscan shellfish.
Attenuated Neuroendocrine Response to Hypoglycemic Stress in Patients with Panic Disorder
Authors: Jezova Daniela , Vigas Milan , Hlavacova Natasa , Kukumberg Peter
Published: April 2010

Background/Aims: There is a lack of information on the effects of metabolic stress exposure on hormone release in patients with panic disorder. The aim of this study was to test the hypothesis that neuroendocrine activation during hypoglycemic stress is altered in panic disorder patients compared to healthy subjects. Methods: Hormone responses to an intravenous bolus of insulin (0.1 IU/kg) were evaluated in both fully remitted, medication-free panic disorder patients and healthy controls (n = 9/group). Blood samples for determination of cortisol, growth hormone, prolactin, adrenaline and noradrenaline concentrations were obtained at rest and over a 90-min period after insulin injection. Results: In patients with panic disorder, basal prestress hormone levels were comparable to those in healthy subjects with the exception of plasma adrenaline, which was higher in panic disorder patients compared to controls. The degree of hypoglycemia induced by insulin administration was similar in patients and healthy subjects. Hypoglycemia-induced increases in growth hormone, prolactin and cortisol concentrations were significantly attenuated in panic disorder patients compared to healthy individuals. No differences between patients and controls were observed in adrenalin release induced by hypoglycemia. Conclusions: The present data demonstrate that somatotropic, lactotropic and corticotropic activation during hypoglycemic stress is blunted in patients with panic disorder. It is suggested that in contrast to the effects of relatively mild stress conditions used in other studies published in the literature, intensive stressors inducing a broad spectrum of hormonal changes fail to provoke an adequate neuroendocrine response in patients with panic disorder.
Effect of Indomethacin Infused over 30 Minutes on Cerebral Fractional Tissue Oxygen Extraction in Preterm Newborns with a Patent Ductus Arteriosus
Authors: Keating Paul , Verhagen Elise , van Hoften Jacorina , ter Horst Henk , Bos Arend F.
Published: April 2010

Background: A significant patent ductus arteriosus (PDA) is a common finding in the first days of life and, if persistent, is associated with an increased morbidity and mortality in the preterm newborn. Objectives: Our aim was to investigate, using near-infrared spectroscopy, the effect of indomethacin on the fractional tissue (cerebral) oxygen extraction (FTcOE) in a group of preterm newborns undergoing medical treatment for a PDA. Methods: This is a prospective, observational study. A cohort of 18 preterm newborns (<32 weeks) undergoing treatment for a PDA with indomethacin were monitored continuously for mean arterial blood pressure, arterial oxygen saturation (SpO2) and regional cerebral oxygen saturation (rcSO2). Measurements were started 1 h before and continued for 4 h after the first indomethacin dose. A final measurement (1 h) was made within 24 h of completing the full course. FTcOE = [SpO2 – rcSO2]/SpO2 was then calculated. To analyze the data, we chose to average the measurements over 1-hour periods. Results: There was a significant increase in the FTcOE (0.06, 95% CI 0.04–0.09, p < 0.001) noticeable within the 1st hour after the start of indomethacin administration, which peaked in the 2nd hour (FTcOE increased by 0.08, 95% CI 0.04–0.11, p < 0.001) and lasted for the full 4-hour period measured. Conclusion: Indomethacin, infused over 30 min, significantly increased the FTcOE in the preterm newborn, the effect lasting at least 4 h. This may represent a protective response to the indomethacin-induced reduction in cerebral blood flow demonstrated by others and warrants further investigation.
Dexamethasone Treatment in the First Week of Life for Preventing Bronchopulmonary Dysplasia in Preterm Infants: A Systematic Review
Authors: Doyle Lex W. , Ehrenkranz Richard A. , Halliday Henry L.
Published: April 2010

Background: Dexamethasone treatment started soon after birth is controversial. Objectives: To determine if postnatal dexamethasone treatment during the first week of life is beneficial in preventing bronchopulmonary dysplasia (BPD) in preterm infants. Methods: Randomised controlled trials of postnatal dexamethasone therapy started in the first week of life in infants at risk of BPD were sought using methods of the Cochrane Collaboration. Data regarding clinical outcomes including mortality, BPD, death or BPD, complications during the primary hospitalisation, and long-term outcome were abstracted and analysed using RevMan 5. Results: 20 randomised controlled trials enrolling a total of 2,860 participants were eligible for inclusion. Meta-analysis of these trials demonstrated significant benefits as regards earlier extubation and decreased risks of BPD at both 28 days’ and 36 weeks’ postmenstrual age (PMA), death or BPD at 28 days’ and 36 weeks’ PMA, patent ductus arteriosus and severe retinopathy of prematurity. Gastrointestinal bleeding and intestinal perforation were important adverse effects, and the risks of hyperglycaemia and hypertension were also increased. In the seven trials (921 infants) that reported late outcomes, cerebral palsy and the combined outcome of death or cerebral palsy were significantly more common in those treated with dexamethasone. Conclusions: The benefits of early dexamethasone treatment (≤7 days) to prevent BPD do not outweigh the known or potential adverse effects of this treatment, and it cannot be recommended for routine clinical practice.
VEGF Secretion by Neuroendocrine Tumor Cells Is Inhibited by Octreotide and by Inhibitors of the PI3K/AKT/mTOR Pathway
Authors: Villaume Karine , Blanc Martine , Gouysse Géraldine , Walter Thomas , Couderc Christophe , Nejjari Mimoun , Vercherat Cécile , Cordier-Bussat Martine , Roche Colette , Scoazec Jean-Yves
Published: April 2010

Gastroenteropancreatic (GEP) endocrine tumors are hypervascular tumors able to synthesize and secrete high amounts of VEGF. We aimed to study the regulation of VEGF production in GEP endocrine tumors and to test whether some of the drugs currently used in their treatment, such as so- matostatin analogues and mTOR inhibitors, may interfere with VEGF secretion. We therefore analyzed the effects of the somatostatin analogue octreotide, the mTOR inhibitor rapamycin, the PI3K inhibitor LY294002, the MEK1 inhibitor PD98059 and the p38 inhibitor SB203850 on VEGF secretion, assessed by ELISA and Western blotting, in three murine endocrine cell lines, STC-1, INS-r3 and INS-r9. Octreotide and rapamycin induced a significant decrease in VEGF production by all three cell lines; LY294002 significantly inhibited VEGF production by STC-1 and INS-r3 only. We detected no effect of PD98059 whereas SB203850 significantly inhibited VEGF secretion in INS-r3 and INS-r9 cells only. By Western blotting analysis, we observed decreased intracellular levels of VEGF and HIF-1α under octreotide, rapamycin and LY294002. For rapamycin and LY294002, this effect was likely mediated by the inhibition of the mTOR/HIF-1/VEGF pathway. In addition to its well-known anti-secretory effects, octreotide may also act through the inhibition of the PI3K/Akt pathway, as suggested by the decrease in Akt phosphorylation detected in all three cell lines. In conclusion, our study points out to the complex regulation of VEGF synthesis and secretion in neoplastic GEP endocrine cells and suggests that the inhibition of VEGF production by octreotide and rapamycin may contribute to their therapeutic effects.
Rapid Detection and Identification of Probiotic Lactobacillus casei ATCC 393 by Multiplex PCR
Authors: Karapetsas Athanasios , Vavoulidis Eleftherios , Galanis Alex , Sandaltzopoulos Raphael , Kourkoutas Yiannis
Published: April 2010

Many functional foods containing probiotic strains have been developed recently. Lactobacillus casei ATCC 393 is one of the most frequently used cultures in probiotic products. The present study aimed to develop a method for the detection and identification of L. casei ATCC 393 based on genetic polymorphisms of the hsp60 gene. A multiplex polymerase chain reaction (PCR) assay was designed, utilizing two novel strain-specific primer sets that enable identification of L. casei ATCC 393.The accuracy of our method was further confirmed by successful identification of our strain in probiotic cheese. The method described is an easy to use, rapid, inexpensive and accurate tool that may be readily applied to food, fecal and intestinal samples.
A Phase II Study of Weekly Docetaxel in Combination with Capecitabine in Advanced Gastric and Gastroesophageal Adenocarcinomas
Authors: Lo Shelly S. , Khorana Alok A. , Javle Milind , Simon Sheryl , Kiefer Gauri , Rajasenan Kiran , Wang Hong , Hantel Alexander , Shayne Michelle , Hwang Jimmy , Schmotzer Amy , Ramanathan Ramesh K.
Published: April 2010

Objective: Docetaxel and capecitabine are active agents in advanced gastric and gastroesophageal (GE) carcinomas. This multi-institutional phase II trial evaluates the combination of docetaxel and capecitabine as first- or second-line treatment in patients with advanced gastric and GE adenocarcinomas. Methods: Patients who had received 1 or no prior chemotherapy regimens were eligible. The chemotherapy regimen consisted of a 21-day cycle with docetaxel 30 mg/m2 administered on days 1 and 8 and capecitabine 825 mg/m2 administered twice daily on days 1–14. The primary end point of the study was overall survival (OS). Results: Forty patients were enrolled in the study; 39 received treatment and were evaluable for response and toxicity. The median patient age was 61 years (range 21–84); 8 patients had received prior chemotherapy in the advanced or metastatic setting. Grade 3/4 adverse events occurred in 15 patients (38%), including diarrhea in 5 patients (13%) and hand-foot syndrome in 5 patients (13%). The overall response rate was 32% [95% confidence interval (CI) 16.7–51.4]. The median time to progression and OS were 3.4 months (95% CI 2.7–5.8) and 10.7 months (95% CI 6.1–12.1), respectively. Conclusions: The regimen of docetaxel and capecitabine is a well-tolerated, easily administered and active outpatient regimen for advanced gastric and GE adenocarcinoma.
Clinical Significance of PTEN and p-Akt Co-Expression in HER2-Positive Metastatic Breast Cancer Patients Treated with Trastuzumab-Based Therapies
Authors: Fabi A. , Metro G. , Di Benedetto A. , Nisticò C. , Vici P. , Melucci E. , Antoniani B. , Perracchio L. , Sperduti I. , Milella M. , Cognetti F. , Mottolese M.
Published: April 2010

Objective: The phosphatase and tensine homologue gene (PTEN) plays a crucial role in proliferation and survival of cancer cells by antagonizing the function of phosphatidylinositol 3′-kinase (PI3K), which, in turn, results in decreased Akt activity. We investigated the clinical impact of the expression of PTEN, p-Akt and PI3K in HER2-positive metastatic breast cancer (MBC) patients treated with trastuzumab-based therapies. Methods: Seventy-three patients treated with trastuzumab-based therapies were included and followed prospectively. PTEN, p-Akt and PI3K expression was determined by immunohistochemistry. Results: PTEN, p-Akt and PI3K resulted positive in 48%, 71% and 46.5% of patients, respectively. A significant correlation between PTEN and p-Akt (kappa 0.22, p = 0.03) and p-Akt and PI3K (kappa 0.20, p = 0.05) was observed. PTEN-positive patients had a progression-free survival (PFS) longer than PTEN-negative ones (p = 0.06). When grouped together, patients co-expressing PTEN and p-Akt had a statistically significant longer PFS as compared to the rest of patients (p = 0.01). At the multivariate analysis, PTEN and p-Akt co-expression was an independent predictor of lower risk of progression (hazard ratio 0.53, p = 0.05). Conclusion: In HER2-positive MBC, basal co-expression of PTEN and p-Akt might identify those patients who are more likely to benefit from trastuzumab-based therapies.
Reduced ADAMTS13 in children with severe meningococcal sepsis is associated with severity and outcome
Authors: Bongers Tamara , Emonts Marieke , de Maat Moniek , Groot Ronald de , Lisman Ton , Hazelzet Jan , Leebeek Frank
Published: April 2010

Multiple organ failure is a common feature of pediatric meningococcal sepsis and is associated with an imbalance of coagulation and fibrinolysis. This is partly due to an increased secretion of prothrombotic ultra-large von Willebrand factor (VWF) as the result of vascular endothelial damage. Another factor that may contribute is ADAMTS13, which converts VWF into smaller, less active, VWF multimers and thus influences VWF activity in plasma. We investigated the role of ADAMTS13 and VWF in the severity and outcome of sepsis. In 58 children with severe meningococcal sepsis we measured ADAMTS13 activity and antigen, VWF collagen binding activity (VWF:CB) and antigen levels (VWF:Ag), VWF propeptide and factor VIII at different time points during their stay in the paediatric intensive care unit. In the acute phase, both ADAMTS13 activity and antigen were decreased (median 23.4% and 33.7% of normal, respectively) and VWF:CB and VWF:Ag levels were strongly increased (325% and 348%, respectively.) ADAMTS13 antigen (23.9% vs. 34.6%; p=0.06) and VWF:CB (240% and 340% p<0.001) were lower in non-survivors than in survivors. ADAMTS13 activity and VWF:CB were both correlated with the severity of the disease, as indicated by the Pediatric Risk of Mortality score (Rs= –0.38 and Rs= –0.50, p=0.01, respectively, p<0.001). In the acute phase of severe sepsis decreased levels of ADAMTS13 and increased levels of VWF are observed, and the changes are related to severity of disease and outcome. This may contribute to the formation of microthrombi and the severity of thrombotic sequelae of sepsis.
Oral administration of a microencapsulated low-molecular-weight heparin to rabbits: Anti-Xa and anti-IIa profiles
Authors: Javot Lucie , Sapin Anne , Scala-Bertola Julien , Vigneron Claude , Lecompte Thomas , Maincent Philippe
Published: April 2010

The development of heparin oral form has been a subject of international research for a long time. Promising results have been obtained in vivo in terms of anti-Xa activity with different strategies and notably microparticles but studies concerning the anti-IIa activity and the anti-Xa/anti-IIa ratio have never been presented. Anti-Xa activities, anti-IIa activities and anti-Xa/anti-IIa ratios provided by nadroparin Eudragit→ RS and poly (D,L-lactic-co-glycolic acid) (PLGA) microparticles were determined in vitro and in vivo and an evaluation of their pharmacokinetic parameters compared to subcutaneous injection was performed. Nadroparin was encapsulated into microparticles prepared by the double emulsion method using Eudragit→ RS alone or in mixture with PLGA of two kinds, i.e. with (PLGA S) or without (PLGA H) esterification of the acid ending. Microparticles characterisation was performed (size, anti-Xa and anti-IIa activities entrapped and released) before their oral administration in rabbits. In vitro anti-Xa/anti-IIa ratios released from nadroparin microparticles were higher than the ratio of the commercial solution. After oral administration, whatever the formulation, sustained anti-Xa and anti-IIa activities were obtained compared to the subcutaneous injection with a peak concentration at 4 hours (up to 0.59 anti-Xa U/ml and 0.11 anti-IIa U/ml for PLGA S 50% / ERS 50% formulation). Anti-Xa and anti-IIa relative bioavailabilities were high, up to 40% (ERS 100% formulation). Anti-Xa/anti-IIa ratios were within range already obtained for subcutaneous injection, i.e. between 5 and 15. Nadroparin microparticles of nadroparin are promising oral dosage form performing sustained and well controlled anti-Xa, anti-IIa activities and anti-Xa/anti-IIa ratio.
Serum albumin and risk of venous thromboembolism
Authors: Lutsey Pamela L. , Heckbert Susan R. , Cushman Mary , Folsom Aaron R.
Published: April 2010

The incidence of venous thromboembolism (VTE) is increased in patients with albuminuria. However, whether a low serum albumin concentration is associated with increased risk of VTE has been a matter of controversy. We determined the association of serum albumin with VTE incidence in two large, prospective, population-based cohorts: the Atherosclerosis Risk in Communities (ARIC) Study (n = 15,300) and the Cardiovascular Health Study (CHS) (n = 5,400). Validated VTE occurrence (n = 462 in ARIC and n = 174 in CHS) was ascertained during follow-up. In both studies, after adjustment for age, sex, race, use of hormone replacement therapy, estimated glomerular filtration rate, history of cancer, and diabetes, serum albumin tended to be associated inversely with VTE. The adjusted hazard ratio per standard deviation lower albumin was 1.18 (95% confidence interval [CI] = 1.08, 1.31) in ARIC and 1.10 (95% CI = 0.94, 1.29) in CHS. The hazard ratio for albumin below (vs. above) the fifth percentile was 1.28 (95% CI = 0.90, 1.84) in ARIC and 1.80 (95% CI = 1.11, 2.93) in CHS. In conclusion, low serum albumin was a modest marker of increased VTE risk. The observed association likely does not reflect cause and effect, but rather that low serum albumin reflects a hyperinflammatory or hypercoagulable state. Whether this association has clinical relevance warrants further study.
Increasing Long-Term Major Vascular Events and Resource Consumption in Patients Receiving Off-Pump Coronary Artery Bypass
Authors: Hu Shengshou , Zheng Zhe , Yuan Xin , Wang Wei , Song Yunhu , Sun Hansong , Xu Jianping
Published: April 2010

Background—

Despite its widespread use and short-term efficacy, substantial uncertainty remains about the long-term outcomes and cost-effectiveness of off-pump coronary artery bypass (OPCAB).

Methods and Results—

A retrospective review of prospectively collected data was conducted of 6665 consecutive patients undergoing isolated coronary artery bypass graft (CABG) at our institution during 1999 to 2006. All patients were followed up until September 30, 2008. Short- and long-term outcomes were compared between OPCAB and conventional CABG. The 2 main long-term outcome measures were repeat revascularization and the composite outcome of major vascular events. Cost comparison at 2 years in a propensity-matched sample during follow-up was also a study interest. The overall mean baseline age was 60.3±8.6 years, and 17.0% were women. Compared with conventional CABG, patients who underwent OPCAB had lower rates of atrial fibrillation (
P
=0.003) and requirements for blood transfusion (
P
=0.03) and ventilation time >24 hours (
P
<0.001). After an average of 4.5 years of follow-up, the rates of repeat revascularization (adjusted hazard ratio, 1.40; 95% confidence interval, 1.03 to 1.89) and major vascular events (adjusted hazard ratio, 1.23; 95% confidence interval, 1.09 to 1.39) were significantly higher in the OPCAB than the conventional CABG group. At 2 years, OPCAB was associated with increased additional direct costs per patient compared with conventional CABG and had a similar survival rate.

Conclusions—

Compared with conventional CABG, OPCAB is associated with small short-term gain but increased long-term risks of repeat revascularization and major vascular events, especially among high-risk patients. Moreover, OPCAB consumes more resources and is less cost-effective in the long run.
Clinical Features and Outcomes of Women With Unstable Ischemic Heart Disease
Authors: Mega Jessica L. , Hochman Judith S. , Scirica Benjamin M. , Murphy Sabina A. , Sloan Sarah , McCabe Carolyn H. , Merlini Piera , Morrow David A.
Published: April 2010

Background—

The pathobiological basis of ischemic heart disease and thus the manifestations and response to therapy can differ between women and men. In prior studies, sex-based treatment differences have been observed with the antiischemic ranolazine, with a possibly diminished effect in women.

Methods and Results—

We conducted a prospectively planned analysis of the clinical, biomarker, angiographic, and continuous ECG features and 1-year outcomes of women with unstable ischemic heart disease randomized to ranolazine or placebo in Metabolic Efficiency With Ranolazine for Less Ischemia in Non–ST-Elevation Acute Coronary Syndromes–Thrombolysis in Myocardial Infarction 36 (MERLIN-TIMI 36). Compared with men (n=4269), women (n=2291) were older with more risk factors (
P
<0.001). On presentation, women were less likely than men to have significant epicardial coronary artery disease (no stenosis ≥50% on angiography, 19.4% versus 8.6%;
P
<0.001) or elevated troponin (57.1% versus 68.9%;
P
<0.001). Yet, women were more likely to have an elevated B-type natriuretic peptide (47.0% versus 40.2%;
P
<0.001), worse median angina frequency scores (80 versus 100;
P
<0.001), and an ischemic episode on continuous ECG administered during the first 7 days (22.5% versus 19.3%;
P
=0.0025). Women and men were at similar adjusted risk for the primary end point of cardiovascular death, myocardial infarction, or recurrent ischemia (adjusted hazard ratio, 1.11; 95% confidence interval, 0.96 to 1.29;
P
=0.15). Ranolazine was associated with a significant reduction in recurrent ischemia in women (13.0% versus 18.2%; hazard ratio, 0.71; 95% confidence interval, 0.57 to 0.88;
P
=0.002).

Conclusions—

Women with a clinical syndrome consistent with unstable ischemic heart disease, despite having less obstructive coronary artery disease, were more likely than men to report anginal episodes and had more recorded ischemic periods on continuous ECG. In this setting, ranolazine may be a particularly useful antiischemic agent in women.

Clinical Trial Registration—

URL: http://www.clinicaltrials.gov. Unique identifier: NCT00099788.
Transcatheter Valve-in-Valve Implantation for Failed Bioprosthetic Heart Valves
Authors: Webb John G. , Wood David A. , Ye Jian , Gurvitch Ronen , Masson Jean-Bernard , Rodés-Cabau Josep , Osten Mark , Horlick Eric , Wendler O. , Dumont Eric , Carere Ronald G. , Wijesinghe Namal , Nietlispach Fabian , Johnson Mark , Thompson Chrisopher R. , Moss Robert , Leipsic Jonathon , Munt Brad , Lichtenstein Samuel V. , Cheung Anson
Published: April 2010

Background—

The majority of prosthetic heart valves currently implanted are tissue valves that can be expected to degenerate with time and eventually fail. Repeat cardiac surgery to replace these valves is associated with significant morbidity and mortality. Transcatheter heart valve implantation within a failed bioprosthesis, a “valve-in-valve” procedure, may offer a less invasive alternative.

Methods and Results—

Valve-in-valve implantations were performed in 24 high-risk patients. Failed valves were aortic (n=10), mitral (n=7), pulmonary (n=6), or tricuspid (n=1) bioprostheses. Implantation was successful with immediate restoration of satisfactory valve function in all but 1 patient. No patient had more than mild regurgitation after implantation. No patients died during the procedure. Thirty-day mortality was 4.2%. Mortality was related primarily to learning-curve issues early in this high-risk experience. At baseline, 88% of patients were in New York Heart Association functional class III or IV; at the last follow-up, 88% of patients were in class I or II. At a median follow-up of 135 days (interquartile range, 46 to 254 days) and a maximum follow-up of 1045 days, 91.7% of patients remained alive with satisfactory valve function.

Conclusions—

Transcatheter valve-in-valve implantation is a reproducible option for the management of bioprosthetic valve failure. Aortic, pulmonary, mitral, and tricuspid tissue valves were amenable to this approach. This finding may have important implications with regard to valve replacement in high-risk patients.
Ribonucleic Acid Interference Knockdown of Interleukin 6 Attenuates Cold-Induced Hypertension
Authors: Crosswhite Patrick , Sun Zhongjie
Published: April 2010

The purpose of this study was to determine the role of the proinflammatory cytokine interleukin (IL) 6 in cold-induced hypertension. Four groups of male Sprague-Dawley rats were used (6 rats per group). After blood pressure was stabilized, 3 groups received intravenous delivery of adenoassociated virus carrying IL-6 small hairpin RNA (shRNA), adenoassociated virus carrying scrambled shRNA, and PBS, respectively, before exposure to a cold environment (5°C). The last group received PBS and was kept at room temperature (25°C, warm) as a control. Adenoassociated virus delivery of IL-6 shRNA significantly attenuated cold-induced elevation of systolic blood pressure and kept it at the control level for ≤7 weeks (length of the study). Chronic exposure to cold upregulated IL-6 expression in aorta, heart, and kidneys and increased macrophage and T-cell infiltration in kidneys, suggesting that cold exposure increases inflammation. IL-6 shRNA delivery abolished the cold-induced upregulation of IL-6, indicating effective silence of IL-6. Interestingly, RNA interference knockdown of IL-6 prevented cold-induced inflammation, as evidenced by a complete inhibition of tumor necrosis factor-α expression and leukocyte infiltration by IL-6 shRNA. RNA interference knockdown of IL-6 significantly decreased the cold-induced increase in vascular superoxide production. It is noted that IL-6 shRNA abolished the cold-induced increase in collagen deposition in the heart, suggesting that inflammation is involved in cold-induced cardiac remodeling. Cold exposure caused glomerular collapses, which could be prevented by knockdown of IL-6, suggesting an important role of inflammation in cold-induced renal damage. In conclusion, cold exposure increased IL-6 expression and inflammation, which play critical roles in the pathogenesis of cold-induced hypertension and cardiac and renal damage.
Hyperglycemia and Oxidative Stress Strengthen the Association Between Myeloperoxidase and Blood Pressure
Authors: Van der Zwan Leonard P. , Scheffer Peter G. , Dekker Jacqueline M. , Stehouwer Coen D.A. , Heine Robert J. , Teerlink Tom
Published: April 2010

Scavenging of the vasodilator nitric oxide by myeloperoxidase activity in the vasculature may contribute to hypertension. Because hydrogen peroxide is a cosubstrate of myeloperoxidase, hyperglycemia-induced oxidative stress may strengthen the relationship between myeloperoxidase and blood pressure. We investigated this relationship and its modification by hyperglycemia and oxidative stress in a population-based cohort of elderly subjects with normal glucose metabolism (n=267), impaired glucose metabolism (n=189), and type 2 diabetes (n=290). In an age- and sex-adjusted linear regression model, plasma myeloperoxidase was positively associated with systolic blood pressure (2.10 mm Hg per 1 SD increment of myeloperoxidase [95% CI: 0.66 to 3.54]), and this association was stronger at higher levels of fasting glucose (0.61 [−1.70 to 2.93], 1.33 [−1.43 to 4.10], and 3.42 [1.01 to 5.82] for increasing tertiles of glucose) and higher plasma levels of oxidized low-density lipoprotein (0.92 [−1.31 to 3.14], 2.00 [−0.71 to 4.70], and 3.58 [0.98 to 6.19] for increasing tertiles of oxidized low-density lipoprotein). Likewise, the relationship between myeloperoxidase and blood pressure was strongest under conditions associated with oxidative stress, like obesity, low high-density lipoprotein cholesterol, metabolic syndrome, and type 2 diabetes. The strength of these associations was only marginally attenuated by adjustment for other cardiovascular risk factors. Our data demonstrate that myeloperoxidase is positively and independently associated with blood pressure, and this association is strongest in subjects with (hyperglycemia-induced) oxidative stress. These observations, together with emerging evidence that myeloperoxidase-derived oxidants contribute to the initiation and propagation of cardiovascular disease, identify myeloperoxidase as a promising target for drug development.
Teratocarcinoma-Derived Growth Factor-1 Is Upregulated in Aldosterone-Producing Adenomas and Increases Aldosterone Secretion and Inhibits Apoptosis In Vitro
Authors: Williams Tracy A. , Monticone Silvia , Morello Fulvio , Liew Choong-Chin , Mengozzi Giulio , Pilon Catia , Asioli Sofia , Sapino Anna , Veglio Franco , Mulatero Paolo
Published: April 2010

Aldosterone-producing adenomas (APA) are a frequent cause of secondary hypertension characterized by autonomous hypersecretion of aldosterone. However, the molecular mechanisms involved in adrenal tumorigenesis and deregulated aldosterone secretion are currently unknown. To identify putative functional genes, a transcriptional screening was performed on 8 APA and 3 normal adrenals (NA) using oligonucleotide microarrays. Data were next validated on an expanded set of samples by real-time PCR (APA, n=19; NA, n=10). The epidermal growth factor–like teratocarcinoma-derived growth factor-1 (TDGF-1) was upregulated in APA compared with NA (14.7-fold and 21.4-fold by microarray and real-time PCR, respectively). In vitro studies and Western blot analysis using the NCI H295R adrenocortical cell line showed that TDGF-1 increased Akt phosphorylation on Thr308 and Ser473, consistent with activation of phosphatidylinositol 3-kinase/Akt signaling, and also demonstrated a concomitant inactivation of the Akt substrate glycogen synthesis kinase-3β via Ser9 phosphorylation. Furthermore, TDGF-1 mediated a 3.8±0.4-fold increase in aldosterone secretion (n=4) that was specifically blocked by the phosphatidylinositol 3-kinase inhibitors wortmannin (50 nmol/L) and LY294002 (20 μmol/L). Finally, TDGF-1 protected H295R cells from apoptosis induced by staurosporine, causing a decrease in caspase-3 activity, a reduction in the inactivation of poly(ADP-ribose) polymerase, and an inhibition of DNA fragmentation, detected by the TUNEL reaction and fluorescence microscopy that was blocked by LY294002. Taken together, our data suggest that TDGF-1, which is significantly upregulated in APA and mediates aldosterone hypersecretion and deregulated growth in adrenocortical cells in vitro, may represent a key player in the development and pathophysiology of primary aldosteronism.
Financial System Stability and Market Confidence
Authors: Nishimura Kiyohiko G.
Published: April 2010

This paper first explains why the financial crisis of 2007–08 started in the United States, in particular, in the sub-prime mortgage market, a periphery of their financial markets. Agency problems in complex securitization and investors' “responsibility avoidance” behavior are argued to be key factors in the sub-prime mortgage meltdown. It then examines the collapse of global financial markets and the erosion of market confidence that followed, and measures taken by governments and central banks to save the financial system. Finally, the paper explores possible safety nets that may prevent another financial crisis: private-sector capital insurance, public–private partnership capital insurance (a version of catastrophe insurance), and contingent capital.
Sotrastaurin and Tacrolimus Coadministration: Effects on Pharmacokinetics and Biomarker Responses
Authors: Kovarik John M. , Stitah Sylvie , Slade Alan , Vitaliti Alessandra , Straube Frank , Grenet Olivier , Winter Serge , Sfikas Nikolaos , Seiberling Michael
Published: April 2010

Sotrastaurin is an immunosuppressant that inhibits protein kinase C. In the prevention of acute rejection in organ transplantation, sotrastaurin might be combined with tacrolimus. A drug interaction study was performed in 18 healthy subjects who received single oral doses of sotrastaurin 400 mg, tacrolimus 7 mg, and the drug combination. Drug blood levels and lymphocyte activation and proliferation were measured. Tacrolimus did not alter the pharmacokinetics of sotrastaurin; however, sotrastaurin increased tacrolimus area under the concentration‐time curve by 2.0‐fold (90% confidence interval, 1.8–2.1). Production of interleukin‐2 and tumor necrosis factor by T cells activated via calcium‐independent pathways was inhibited by 75% ± 22% from baseline by sotrastaurin. Interleukin‐2 messenger RNA levels were decreased by 90% ± 9% from baseline by sotrastaurin. Addition of tacrolimus to sotrastaurin had minimal or no effect on these biomarkers, consistent with tacrolimus' mechanism of action. Lymphocyte proliferation induced via calcium‐dependent pathways was decreased from baseline by 82% ± 9% by sotrastaurin, 76% ± 11% by tacrolimus, and 96% ± 2% for the drug combination. How sotrastaurin and tacrolimus could be partnered in an immunosuppressive regimen will need to be established in the context of controlled clinical trials in organ transplant patients, taking into account the pharmacokinetic interaction on tacrolimus and the potentially enhanced immunosuppressive activity of this drug combination.
The Roles of Affect Dysregulation and Deficient Affect in Youth Violence
Authors: Penney Stephanie R. , Moretti Marlene M.
Published: April 2010

Children with high dysregulated affect experience a range of emotional and behavioral problems, including aggression, delinquency, and low levels of prosocial behavior. Alongside this research, the psychopathy literature suggests that abnormally low levels of affect and emotional reactivity are associated with aggression and violence. The current study builds on prior research in the fields of affect regulation and psychopathy by testing the effects of affect dysregulation and deficient affect in predicting aggression and antisociality in 179 high-risk youth. Using structural equation modeling, results suggest that affect dysregulation and deficient affect are separate risk factors for aggression, as both constructs contributed independently to aggression while showing marginal relations with one another. Features of deficient affect, but not dysregulation, were robust predictors of violent and nonviolent offending. We discuss the importance of recognizing that diverse risk factors may lead to similar outcomes and highlight the heterogeneity in risk factors underlying aggressive behaviors.
The ‘others’ in the Qur’an
Authors: Abu-Zayd Nasr
Published: April 2010

First, I argue for historical contextualization of the Qur’an as a given historical collection of discourses propagated by Muhammad as divine inspiration. Secondly, I argue for a distinction between the Qur’an and Islam, since the latter is the outcome of human efforts to construct their lives in accordance with what they understood to be the teachings of the Qur’an. The last point is to show how the role of Muhammad in his interaction with the communities of his time in Hijaz shaped the Qur’an. So, the article is organized as (1) introduction; (2) the Qur’an and lslam; (3) the Qur’an and history: open hermeneutics; (4) Muhammad and the Qur’an; (5) the divine—human communication; (6) Muhammad: the first recipient; (7) Muhammad in the Qur’an; and (8) the community of believers and the need for legal regulations; followed by (9) conclusion.
The specter haunting multiculturalism
Authors: Bernstein Richard J.
Published: April 2010

I argue that the specter haunting multiculturalism is incommensurability. In many discussions of multiculturalism there is a ‘picture’ that holds us captive — a picture of cultures, religious or ethnic groups that are self-contained and are radically incommensurable with each other. I explore and critique this concept of incommensurability. I trace the idea of incommensurability back to the discussion by Thomas Kuhn — and especially to the ways in which his views were received. Drawing on Gadamer’s understanding of hermeneutics, I argue that the very idea of radical incommensurability is incoherent. This does not entail an abstract universalism but rather sensitivity to the ways in which all languages and cultures are in principle open to the real possibility of enlarging one’s vision and mutually understanding.
Multicultural claims and equal respect
Authors: Galeotti Anna Elisabetta
Published: April 2010

In this article the author intends to provide general normative guidelines which ought to inform policies concerning the most controversial multicultural claims for a liberal democracy. In order to do that, she proposes a general reconsideration of the struggle of cultures and identities which makes up the stuff of multiculturalism. She suggests that instead of focusing on the issue of compatibility, the adequate viewpoint from which considering multicultural claims should be justice and, within justice, the principle of equal respect (ER). The reference to ER is widespread in the literature on multiculturalism, but it does not specify what should be the object of ER: persons and their dignity, or cultures/religions/identities and their members? The alternative is then examined and the author argues in favour of an interpretation of ER for persons which considers persons as they are, given their identities and differences. Finally, the author provides a typology of multicultural claims, ranked on a scale of different levels of disrespect, which consequently require different kinds of response. As a result, one is invited to reflect on the how beside the what, on the procedures and attitudes beside the benefits and measures, and not only for the pragmatic reasons of finding a relatively easy way out, but also for principled reasons of justice.
Faith in law?
Authors: Shachar Ayelet
Published: April 2010

This article evaluates demands for privatized diversity that destabilize traditional notions of separation of state and religion, by asking secular authorities to adopt a hands-off, non-interventionist approach, placing civil and family disputes with a religious or cultural aspect beyond the official realm of equal citizenship. This potential storm to come must be addressed head on because it mixes three inflammatory components in today’s political environment: religion; gender; and the rise of a neo-liberal state. The volatility of these issues is undisputed; they require a mere spark to ignite. The standard legal response to this challenge is to seek shelter behind a formidable ‘wall of separation’ between state and religion, even if this implies turning a blind eye to the concerns of religious women — especially those caught in the uncoordinated web of secular and religious marriage bonds. I will advance a different approach. By placing these once-ignored agents at the centre of analysis, this article explores the idea of permitting a degree of regulated interaction between religious and secular sources of identity and obligation, so long as the baseline of citizenship-guaranteed rights remains firmly in place.
The pathologies of Turkish republican laicism
Authors: Kadıoğlu Ayşe
Published: April 2010

This article reveals the pathologies of the Turkish republican project of laicism by focusing on the differences between the ideas of Ziya Gökalp and the leading architects of this project. Ziya Gökalp reasoned within the logic of the empire and envisioned a synthesis among Turkism, westernism and Islam. The logic of the republic à la Turca, on the other hand, was shaped by a radical break from Islam. The distaste that the architects of the republican laicist project had developed towards Islam became apparent during the years between 1920 and 1925. Accordingly, the republican project of laicism nurtured a highly visible control of the state over religion rather than a separation between the affairs of the state and religion. This article also discusses the possibilities of reforming the republican project of laicism that is congenial with democratization processes in Turkey.
Is a Muslim Gandhi possible?
Authors: Jahanbegloo Ramin
Published: April 2010

In the past decade, Islam has come to be associated more than ever with images of extremism and violence. Osama bin Laden and Saddam Hussein are stock characters in this association, in the aftermath of 11 September and the ‘war on terror’. Lost in all this is a long record of Muslim experience of non-violent change and peace-making. Yet Islam hardly glorifies violence — and does quite explicitly glorify its opposite. History offers much evidence of Muslim tolerance and civil engagement with other faith and cultural traditions. Non-violent Islam could give fresh life to secularism in Muslim societies. It may help steer public space away from state-dominated as well as other forms of political Islam, with their foolish utopias. Realizing the ideals of non-violence is a perennial struggle for Islamic communities around the world - and is part of the struggle for democratic life.