bluuebunny/crossref_metadata_2025 huggingface dataset:
Extreme Risk Analysis of Interdependent Economic and Infrastructure Sectors
Authors: Lian Chenyang , Santos Joost R. , Haimes Yacov Y.
Published: October 2007

Willful attacks or natural disasters pose extreme risks to sectors of the economy. An extreme‐event analysis extension is proposed for the Inoperability Input‐Output Model (IIM) and the Dynamic IIM (DIIM), which are analytical methodologies for assessing the propagated consequences of initial disruptions to a set of sectors. The article discusses two major risk categories that the economy typically experiences following extreme events: (i) significant changes in consumption patterns due to lingering public fear and (ii) adjustments to the production outputs of the interdependent economic sectors that are necessary to match prevailing consumption levels during the recovery period. Probability distributions associated with changes in the consumption of directly affected sectors are generated based on trends, forecasts, and expert evidence to assess the expected losses of the economy. Analytical formulations are derived to quantify the extreme risks associated with a set of initially affected sectors. In addition, Monte Carlo simulation is used to handle the more complex calculations required for a larger set of sectors and general types of probability distributions. A two‐sector example is provided at the end of the article to illustrate the proposed extreme risk model formulations.
Food Safety in the Domestic Environment: An Interdisciplinary Investigation of Microbial Hazards During Food Preparation
Authors: Fischer Arnout R. H. , De Jong Aarieke E. I. , Van Asselt Esther D. , De Jonge Rob , Frewer Lynn J. , Nauta Maarten J.
Published: October 2007

It has been established that, to a considerable extent, the domestic hygiene practices adopted by consumers can result in a greater or lesser microbial load in prepared meals. In the research presented here, an interdisciplinary study is reported in which interviews, observations of consumers preparing a recipe, and microbial contamination of the finished meals were compared. The results suggest that, while most consumers are knowledgeable about the importance of cross‐contamination and heating in preventing the occurrence of foodborne illness, this knowledge is not necessarily translated into behavior. The adoption of habitual cooking practices may also be important. Potentially risky behaviors were, indeed, observed in the domestic food preparation environment. Eighteen of the participants made errors in food preparation that could potentially result in cross‐contamination, and seven participants allowed raw meat juices to come in contact with the final meal. Using a tracer microorganism the log reduction as a result of consumer preparation was estimated at an average of log 4.1 cfu/salad. When combining these findings, it was found that cross‐contamination errors were a good predictor for log reduction. Procedural food safety knowledge (i.e., knowledge proffered after general open questions) was a better predictor of efficacious bacterial reduction than declarative food safety knowledge (i.e., knowledge proffered after formal questioning). This suggests that motivation to prepare safe food was a better indicator of actual behavior than knowledge about food safety per se.
Effects of Simultaneous and Optimized Sequential Cardiac Resynchronization Therapy on Myocardial Oxidative Metabolism and Efficiency
Authors: CHRISTENSON STUART D. , CHAREONTHAITAWEE PANITHAYA , BURNES JOHN E. , HILL MICHAEL R.S. , KEMP BRAD J. , KHANDHERIA BIJOY K. , HAYES DAVID L. , GIBBONS RAYMOND J.
Published: October 2007

Introduction: Cardiac resynchronization therapy (CRT) can improve left ventricular (LV) hemodynamics and function. Recent data suggest the energy cost of such improvement is favorable. The effects of sequential CRT on myocardial oxidative metabolism (MVO2) and efficiency have not been previously assessed.

Methods and Results: Eight patients with NYHA class III heart failure were studied 196 ± 180 days after CRT implant. Dynamic [11C]acetate positron emission tomography (PET) and echocardiography were performed after 1 hour of: 1) AAI pacing, 2) simultaneous CRT, and 3) sequential CRT. MVO2 was calculated using the monoexponential clearance rate of [11C]acetate (kmono). Myocardial efficiency was expressed in terms of the work metabolic index (WMI). P values represent overall significance from repeated measures analysis. Global LV and right ventricular (RV) MVO2 were not significantly different between pacing modes, but the septal/lateral MVO2 ratio differed significantly with the change in pacing mode (AAI pacing = 0.696 ± 0.094 min−1, simultaneous CRT = 0.975 ± 0.143 min−1, and sequential CRT = 0.938 ± 0.189 min−1; overall P = 0.001). Stroke volume index (SVI) (AAI pacing = 26.7 ± 10.4 mL/m2, simultaneous CRT = 30.6 ± 11.2 mL/m2, sequential CRT = 33.5 ± 12.2 mL/m2; overall P < 0.001) and WMI (AAI pacing = 3.29 ± 1.34 mmHg*mL/m2*106, simultaneous CRT = 4.29 ± 1.72 mmHg*mL/m2*106, sequential CRT = 4.79 ± 1.92 mmHg*mL/m2*106; overall P = 0.002) also differed between pacing modes. Compared with simultaneous CRT, additional changes in septal/lateral MVO2, SVI, and WMI with sequential CRT were not statistically significant on post hoc analysis.

Conclusion: In this small selected population, CRT increases LV SVI without increasing MVO2, resulting in improved myocardial efficiency. Additional improvements in LV work, oxidative metabolism, and efficiency from simultaneous to sequential CRT were not significant.
Dual‐Dye Optical Mapping after Myocardial Infarction: Does the Site of Ventricular Stimulation Alter the Properties of Electrical Propagation?
Authors: SABA SAMIR , MATHIER MICHAEL A. , MEHDI HAIDER , LIU TONG , CHOI BUM‐RAK , LONDON BARRY , SALAMA GUY
Published: October 2007

Introduction: Myocardial infarction (MI) disrupts electrical conduction in affected ventricular areas. We investigated the effect of MI on the regional voltage and calcium (Ca) signals and their propagation properties, with special attention to the effect of the site of ventricular pacing on these properties.

Methods: New Zealand White rabbits were divided into four study groups: sham‐operated (C, n = 6), MI with no pacing (MI, n = 7), MI with right ventricular pacing (MI + RV, n = 6), and MI with BIV pacing (MI + BIV, n = 7). At 4 weeks, hearts were excised, perfused, and optically mapped. As previously shown, systolic and diastolic dilation of the LV were prevented by BIV pacing, as was the reduction in LV fractional shortening.

Results: Four weeks after MI, optical mapping revealed markedly reduced action potential amplitudes and conduction velocities (CV) in MI zones, and these increased gradually in the border zone and normal myocardial areas. Also, Ca transients were absent in the infarcted areas and increased gradually 3–5 mm from the border of the normal zone. Neither BIV nor RV pacing affected these findings in any of the MI, border, or normal zones.

Conclusions: MI has profound effects on the regional electrical and Ca signals and on their propagation properties in this rabbit model. The absence of differences in these parameters by study group suggests that altering the properties of myocardial electrical conduction and Ca signaling are unlikely mechanisms by which BIV pacing confers its benefits. Further studies into the regional, cellular, and molecular benefits of BIV pacing are therefore warranted.
Correlation Between Atrial ZnT‐1 Expression and Atrial Fibrillation in Humans: A Pilot Study
Authors: ETZION YORAM , GANIEL AMIR , BEHARIER OFER , SHALEV ARYEH , NOVACK VICTOR , VOLVICH LIOBOV , ABRAHAMOV DAN , MATSA MENACHEM , SAHAR GIDEON , MORAN ARIE , KATZ AMOS
Published: October 2007

Background: Until recently, the membrane protein ZnT‐1 was studied mainly in the context of zinc homeostasis. However, new findings indicate that it acts as an inhibitor of L‐type calcium channels. We recently found that acute rapid pacing of the rat atria in vivo augments the expression of ZnT‐1, while knockdown of ZnT‐1 in culture can oppose the inhibition of L‐type calcium channels following rapid pacing. This pilot study, the first to assess cardiac ZnT‐1 in humans, was designed to look for possible correlation between the atrial expression of ZnT‐1 and atrial fibrillation.

Methods: Right atrial appendage tissue was collected from 39 patients (27 with sinus rhythm and 12 with atrial fibrillation; 6‐permanent, 6‐ paroxysmal or persistent) undergoing open‐heart surgery. The expression of ZnT‐1 was analyzed by Western blot utilizing β‐actin as an internal loading control and a standard rat heart sample (STD) for inter‐blot comparison.

Results: Overall atrial fibrillation patients (n = 12) had median ZnT‐1/β‐actin of 1.80 STD (inter‐quartile range 1.26 to 2.85) versus 0.73 STD (0.24 to 1.64) in the sinus rhythm group (P = 0.002). No association was found between ZnT‐1 level and most other clinical parameters tested. Multivariate analysis determined that atrial fibrillation and increased body mass index were the only independent variables clearly associated with higher ZnT‐1 levels (Standardized coefficients Beta = 0.62, 0.31; P = 0.002, P = 0.04, respectively).

Conclusions: This pilot study provides evidence for increased ZnT‐1 expression in the atria of patients with atrial fibrillation.
Improvement in Endothelium Dysfunction in Diabetics Treated with Statins: A Randomized Comparison of Atorvastatin 20 mg versus Rosuvastatin 10 mg
Authors: BRUNETTI NATALE DANIELE , MAULUCCI GUGLIELMO , CASAVECCHIA GRAZIA PIA , DISTASO CARLO , DE GENNARO LUISA , LUIGI PELLEGRINO PIER , DI BIASE MATTEO
Published: October 2007

Aim: To investigate the effect a 3‐month treatment with atorvastatin 20 mg compared with rosuvastatin 10 mg on endothelium dysfunction in subjects with diabetes.

Methods: A total of 22 consecutive subjects with diabetes who were not receiving statins were enrolled in the study. Endothelium function was assessed before treatment (T0), after 1 month (T1), and after 3 months of treatment (T2) with statins with brachial echo‐Doppler test. Patients were randomized to receive atorvastatin 20 mg or rosuvastatin 10 mg. Blood samples were drawn in the meantime in order to evaluate C‐reactive protein (CRP) plasmatic concentrations.

Results: A total of 82% of patients enrolled showed endothelium dysfunction (hyperemic reserve <5%). Treatment with statins significantly improved endothelium function in diabetics. Subjects with endothelium dysfunction decreased from 82% (T0) to 44% (T2): mean hyperemic reserve values increased from 2.64% (T0) to 3.23% (T1) and 4% (T2) in patients treated with rosuvastatin (ANOVA P < 0.01), and from 2.74% (T0) to 2.75% (T1) and 4.40% (T2) in those treated with atorvastatin (ANOVA P < 0.01); differences were significant only comparing T2 with T0. Relative increase in endothelium reserve was 51.51% with rosuvastatin versus 60.58% with atorvastatin (P N.S.). Both statins significantly reduced plasmatic levels of CRP (3.18 ± 2.43 mg/dL [T0] vs. 1.31 ± 1.67 mg/dL [T2] with rosuvastatin [P < 0.01], 7.53 ± 7.46 mg/dL [T0] vs. 2.92 ± 2.06 mg/dL [T2] with atorvastatin [P < 0.01]). Relative reduction of CRP levels was −50.57% with rosuvastatin versus −36.28% with atorvastatin (P N.S.).

Conclusion: A 3‐month treatment with either atorvastatin 20 mg or rosuvastatin 10 mg is effective in improving endothelium dysfunction in subjects with diabetes.
Varying Coefficients Model with Measurement Error
Authors: Li Liang , Greene Tom
Published: October 2007

SummaryWe propose a semiparametric partially varying coefficient model to study the relationship between serum creatinine concentration and the glomerular filtration rate (GFR) among kidney donors and patients with chronic kidney disease. A regression model is used to relate serum creatinine to GFR and demographic factors in which coefficient of GFR is expressed as a function of age to allow its effect to be age dependent. GFR measurements obtained from the clearance of a radioactively labeled isotope are assumed to be a surrogate for the true GFR, with the relationship between measured and true GFR expressed using an additive error model. We use locally corrected score equations to estimate parameters and coefficient functions, and propose an expected generalized cross‐validation (EGCV) method to select the kernel bandwidth. The performance of the proposed methods, which avoid distributional assumptions on the true GFR and residuals, is investigated by simulation. Accounting for measurement error using the proposed model reduced apparent inconsistencies in the relationship between serum creatinine and GFR among different clinical data sets derived from kidney donor and chronic kidney disease source populations.
Variable Selection for Model‐Based High‐Dimensional Clustering and Its Application to Microarray Data
Authors: Wang Sijian , Zhu Ji
Published: October 2007

SummaryVariable selection in high‐dimensional clustering analysis is an important yet challenging problem. In this article, we propose two methods that simultaneously separate data points into similar clusters and select informative variables that contribute to the clustering. Our methods are in the framework of penalized model‐based clustering. Unlike the classicalL1‐norm penalization, the penalty terms that we propose make use of the fact that parameters belonging to one variable should be treated as a natural “group.” Numerical results indicate that the two new methods tend to remove noninformative variables more effectively and provide better clustering results than theL1‐norm approach.
A Signed‐Rank Test for Clustered Data
Authors: Datta Somnath , Satten Glen A.
Published: October 2007

Summary We consider the problem of comparing two outcome measures when the pairs are clustered. Using the general principle of within‐cluster resampling, we obtain a novel signed‐rank test for clustered paired data. We show by a simple informative cluster size simulation model that only our test maintains the correct size under a null hypothesis of marginal symmetry compared to four other existing signed rank tests; further, our test has adequate power when cluster size is noninformative. In general, cluster size is informative if the distribution of pair‐wise differences within a cluster depends on the cluster size. An application of our method to testing radiation toxicity trend is presented.
Testing and Estimating Gene–Environment Interactions in Family‐Based Association Studies
Authors: Vansteelandt Stijn , DeMeo Dawn L. , Lasky‐Su Jessica , Smoller Jordan W. , Murphy Amy J. , McQueen Matt , Schneiter Kady , Celedon Juan C. , Weiss Scott T. , Silverman Edwin K. , Lange Christoph
Published: October 2007

Summary We propose robust and efficient tests and estimators for gene–environment/gene–drug interactions in family‐based association studies in which haplotypes, dichotomous/quantitative phenotypes, and complex exposure/treatment variables are analyzed. Using causal inference methodology, we show that the tests and estimators are robust against unmeasured confounding due to population admixture and stratification, provided that Mendel's law of segregation holds and that the considered exposure/treatment variable is not affected by the candidate gene under study. We illustrate the practical relevance of our approach by an application to a chronic obstructive pulmonary disease study. The data analysis suggests a gene–environment interaction between a single nucleotide polymorphism in the Serpine2 gene and smoking status/pack‐years of smoking. Simulation studies show that the proposed methodology is sufficiently powered for realistic sample sizes and that it provides valid tests and effect size estimators in the presence of admixture and stratification.
“Smooth” Semiparametric Regression Analysis for Arbitrarily Censored Time‐to‐Event Data
Authors: Zhang Min , Davidian Marie
Published: October 2007

SummaryA general framework for regression analysis of time‐to‐event data subject to arbitrary patterns of censoring is proposed. The approach is relevant when the analyst is willing to assume that distributions governing model components that are ordinarily left unspecified in popular semiparametric regression models, such as the baseline hazard function in the proportional hazards model, have densities satisfying mild “smoothness” conditions. Densities are approximated by a truncated series expansion that, for fixed degree of truncation, results in a “parametric” representation, which makes likelihood‐based inference coupled with adaptive choice of the degree of truncation, and hence flexibility of the model, computationally and conceptually straightforward with data subject to any pattern of censoring. The formulation allows popular models, such as the proportional hazards, proportional odds, and accelerated failure time models, to be placed in a common framework; provides a principled basis for choosing among them; and renders useful extensions of the models straightforward. The utility and performance of the methods are demonstrated via simulations and by application to data from time‐to‐event studies.
Augmentation of ECG QRS Complexes after Fluid Removal via a Mechanical Ultrafiltration Pump in Patients with Congestive Heart Failure
Authors: Madias John E. , Guglin Maya E.
Published: October 2007

Background: Augmentation of the amplitude of ECG QRS complexes, correlating with loss of weight or fluid volume removed, has been documented in patients with congestive heart failure (CHF).

Methods: We investigated the effect of an ultrafiltration (UF) pump on the fluid removal and the amplitude of ECG QRS complexes in patients with CHF. Nine patients aged 48.3 ± 10.4 years with CHF were treated with an UF system, and weights, fluid removed, and sums of the amplitude of QRS complexes (ΣQRS), were inter‐correlated.

Results: UF resulted in removal of 4.62 ± 1.82 L of fluid, 5.0 ± 2.9% decrease in the weights (P = 0.002) and 18.1 ± 16.8% increase in the ΣQRS (P = 0.012). There was a moderate correlation of % increase in the ΣQRS and net fluid volume losses (UF + urine − oral intake), (r = 0.67, P = 0.0471, and a poor correlation between % increase in the ΣQRS and % decrease in weights (r = 0.11, P = 0.77). Correlations of the change in weights after UF with the fluid removed by UF, or with the volume of total fluid loss (including insensible losses) were moderate but barely statistically significant (r = 0.65, P = 0.0559), and (r = 0.65, P = 0.0577), correspondingly.

Conclusion: Augmentation of the amplitude of QRS complexes correlates well with net fluid loss in response to UF in patients with CHF, and can be employed as an index of effectiveness of therapy. Also, a model of fluid losses in patients treated for CHF is being proposed.
Automatic P Wave Analysis Over 24 Hours in Patients with Paroxysmal or Persistent Atrial Fibrillation
Authors: Bitzen Alexander , Sternickel Karsten , Lewalter Thorsten , Schwab Jörg Otto , Yang Alexander , Schrickel Jan Wilko , Linhart Markus , Wolpert Christian , Jung Werner , David Peter , Lüderitz Berndt , Nickenig Georg , Lickfett Lars
Published: October 2007

Background: Patients with atrial fibrillation (AF) often exhibit abnormalities of P wave morphology during sinus rhythm. We examined a novel method for automatic P wave analysis in the 24‐hour‐Holter‐ECG of 60 patients with paroxysmal or persistent AF and 12 healthy subjects.

Methods: Recorded ECG signals were transferred to the analysis program where 5–10 P and R waves were manually marked. A wavelet transform performed a time‐frequency decomposition to train neural networks. Afterwards, the detected P waves were described using a Gauss function optimized to fit the individual morphology and providing amplitude and duration at half P wave height.

Results: >96% of P waves were detected, 47.4 ± 20.7% successfully analyzed afterwards. In the patient population, the mean amplitude was 0.073 ± 0.028 mV (mean variance 0.020 ± 0.008 mV2), the mean duration at half height 23.5 ± 2.7 ms (mean variance 4.2 ± 1.6 ms2). In the control group, the mean amplitude (0.105 ± 0.020 ms) was significantly higher (P < 0.0005), the mean variance of duration at half height (2.9 ± 0.6 ms2) significantly lower (P < 0.0085).

Conclusions: This method shows promise for identification of triggering factors of AF.
Acoustic Cardiography Augments Prolonged QRS Duration for Detecting Left Ventricular Dysfunction
Authors: Zuber Michel , Attenhofer Jost Christine H. , Kipfer Peter , Collins Sean P. , Michota Frank , Frank Peacock W.
Published: October 2007

Background: Prolonged QRS duration has been used as a marker for left ventricular (LV) systolic dysfunction (SD) and is used in the evaluation of patients presenting with known or suspected heart failure. The goal of this study was to compare the abilities of QRS duration and simultaneous digital ECG and heart sounds, that is acoustic cardiographic, parameters to identify patients with LV dysfunction.

Methods: Our learning population consisted of 171 patients with possible chronic compensated or mildly decompensated heart failure who presented to an ambulatory cardiology clinic for echocardiographic examination. We defined LVSD as a LV ejection fraction < 50%, and estimated LV filling pressures from diastolic measurements. These patients also had acoustic cardiographic recordings from which we obtained a variety of individual ECG and acoustic cardiographic parameters. We used the product of four of these parameters to obtain a diagnostic score for LV dysfunction. We then compared the diagnostic performances of QRS duration and the score on a test population of patients who presented to an emergency department with possible heart failure.

Results: In the learning population, the sensitivities/specificities of QRS duration ≥120 ms and the score for prediction of LVSD were 51%/92% and 77%/90%, respectively. In the test population, the score remained superior to QRS duration for detecting LVSD as well as acute decompensated heart failure.

Conclusions: Improved identification of LVSD and clinical heart failure can be achieved with a cost‐effective bedside screening tool with the simple combination of simultaneously acquired digital ECG and heart sound data.
Noninvasive Assessment of Atrial Substrate Change after Wide Area Circumferential Ablation: A Comparison with Segmental Pulmonary Vein Isolation
Authors: Redfearn Damian P. , Skanes Allan C. , Gula Lorne J. , Griffith Michael J. , Marshall Howard J. , Stafford Peter J. , Krahn Andrew D. , Yee Raymond , Klein George J.
Published: October 2007

Background: The wide area circumferential ablation (WACA) approach to atrial fibrillation is thought to result in ‘substrate modification’ perhaps related to autonomic denervation. We examined this prospectively by comparing WACA and segmental pulmonary vein isolation (PVI) using noninvasive surrogate markers.

Methods: Heart rate variability (HRV) and signal averaged P wave (SAPW) data were derived from high‐resolution (HR) recordings (‘SpiderView’ ELA Medical) made in sinus rhythm immediately before and 24 hours after ablation.

Results: Forty patients recruited (20 WACA; 20 PVI); cohorts were comparable. WACA caused marked SAPW change: P wave duration (PWD) (149[4.6] ms to 160[5.9] ms; P = 0.003), root mean square (RMS) (4.4[0.4]μV to 2.8[0.4]; P = 0.001) and energy content (30–150 Hz; 20.4 [3.6]μV2/s to 13.7[2.4]; P = 0.001). No significant change was seen after PVI. Heart rate increased after WACA and PVI (61.4 to 73.5 [P = 0.001]; 69.5 to 75.0 [P = 0.07], respectively). HRV was significantly influenced after WACA: low frequency power (LF) 5.7(0.4) to 3.6(0.4); P = 0.001), high‐frequency power (HF) 4.6(0.4)–3.4(0.3); P = 0.024, and after PVI: LF 5.4(0.3) to 4.3(0.3); P = 0.024. HF: 4.4(0.4) to3.0(0.4); P = 0.018).

Conclusions: HR recordings exhibit change in HRV after WACA and PVI. Marked change in both HRV and SAPW is observed after WACA. SAPW variables provide a measure of atrial substrate change after WACA unrelated to autonomic denervation.
Polymorphism in the Cholesteryl Ester Transfer Protein Gene and the Risk of Early Onset Myocardial Infarction among Cigarette Smokers
Authors: Goldenberg Ilan , Moss Arthur J. , Block Robert , Ryan Daniel , Corsetti James P. , McNitt Scott , Eberly Shirley W. , Zareba Wojciech
Published: October 2007

Background: Cigarette smoking and the common B1 allele of the TaqIB polymorphism have both been reported to be associated with increased cholesteryl ester transfer protein (CETP) activity and altered lipoprotein levels. Thus, it is possible that the combined presence of these two respective environmental and genetic factors may enhance cardiovascular risk. We hypothesized that susceptibility to early onset myocardial infarction (MI) among cigarette smokers may be related to the presence of TaqIB polymorphism in the CETP gene.

Methods: The age at onset of a first MI among current (n = 199), past (n = 345), and never (n = 270) smokers was related to the presence of the TaqIB1 and B2 alleles in a cohort of 814 first MI patients.

Results: Multivariate regression analysis demonstrated that cigarette smoking was associated with a significant increase in the risk for early onset MI only among carriers of the TaqIB1 allele: current smokers with the B1B1 and B1B2 genotypes displayed a respective 9.4 (P < 0.001) and 8.4 (P < 0.001) year reduction in the age at onset of a first MI compared with never smokers, and past smokers with these genotypes exhibited a respective 3.8 (P = 0.003) and 3.7 (P = 0.01) year reduction. By contrast, current and past smoking was not associated with a significant increase in the risk for early onset MI among B2B2 homozygotes (3.0 [P = 0.28] and 0.2 [P = 0.93] year reduction, respectively). The smoking x genotype interaction was statistically significant (P = 0.04).

Conclusions: The current findings suggest that genetic factors may modify susceptibility to early onset MI among cigarette smokers.
Electrical Storm in Patients with an Implanted Defibrillator: A Matter of Definition
Authors: Israel Carsten W. , Serge Barold S.
Published: October 2007

The term “electrical storm” (ES) indicates a state of cardiac electrical instability manifested by several episodes of ventricular tachyarrhythmias (VTs) within a short time. In patients with an implantable cardioverter defibrillator (ICD), ES is best defined as 3 appropriate VT detections in 24 h, treated by antitachycardia pacing, shock or eventually untreated but sustained in a VT monitoring zone. The number of shocks and inappropriate detections are irrelevant for the definition. ES occurs in approximately 25% of ICD patients within 3 years, with typically 5–55 individual VTs within one storm. Potential triggers can be found in approximately 66% of patients and include new/worsened heart failure, changes in antiarrhythmic medication, context with other illness, psychological stress, diarrhea, and hypokalemia. In most patients, ES consists of monomorphic VT indicating the presence of reentry while ventricular fibrillation indicating acute ischemia is rare. ES seems to have a low immediate mortality (1%) but frequently (50–80%) leads to hospitalization. Long‐term prognostic implications of ES are unclear. The key intervention in ES is reduction of the elevated sympathetic tone by beta blockers and frequently benzodiazepines. Amiodarone i.v. has also been successful and azimilide seems promising while class I antiarrhythmic drugs are usually unsuccessful. Substrate mapping and VT ablation may be useful in treatment and prevention of ES. Prevention of ES requires ICD programming systematically avoiding unnecessary shocks (long VT detection, antitachycardia pacing where ever possible) which otherwise can fuel the sympathetic tone and prolong ES.
Preparation of Aluminum Oxynitride and Nitride Spherical Powders Via Flame Synthesis Assisted by DC Arc Plasma
Authors: Takao Yasumasa , Shuzenji Kiyotaka , Tachibana Takeshi
Published: October 2007

Spherical powders of aluminum oxynitride/nitride are directly prepared by flame synthesis in which oxygen serves as an indispensable reactant. Nonoxide powders are commonly nonspherical, and the particle sizes of these powders are less than submicrometers. The major limiting factors for the synthesis are the free energy, reaction temperature, and reaction rate. The innovative issue related to this flame technology that is assisted by plasma is the ambivalence of the reducing gas atmosphere over 1500 K. The chemical equilibrium calculated indicates that the plasma heating compensates for the lack of reaction temperature under a low‐oxygen condition. This burner realizes a high‐speed reaction with the help of the reactive species in the arcs.
Predicting clinical and social outcome of patients attending ‘real world’ mental health services: a 6‐year multi‐wave follow‐up study
Authors: Lasalvia A. , Bonetto C. , Cristofalo D. , Tansella M. , Ruggeri M.
Published: October 2007

Objective:  The aims of this study were: i) to determine changes in symptoms and social disability, and ii) to explore predictors of clinical and social outcome in patients receiving community‐based mental health care.

Method:  A total of 354 patients treated in the South‐Verona Community Mental Health Service were followed up over 6 years (with assessments made at baseline, 2 and 6 years) by using a set of standardized measures exploring psychopathology (Brief Psychiatric Rating Scale) and social disability (Disability Assessment Schedule). Generalized linear latent and mixed models were used to explore longitudinal predictors of clinical and social outcome.

Results:  Psychotic patients displayed clinical and social outcome characterized by complex patterns of exacerbation and remission over time; however, a clear trend towards a deteriorating course was not found, thus challenging the notion that psychotics are fatally prone to a destiny of chronicity. Non‐psychotics reported a significant reduction in the core symptom of depression and in the observable physical and motor manifestations of tension and agitation, and a parallel increase in complaints about their physical health. Clinical and social dimensions of outcome are influenced by specific and different set of predictors.

Conclusion:  The results of this study confirm the need to implement naturalistic outcome studies conducted in the ‘real world’ services to inform decisions and strategies to be adopted in routine clinical practice.
Predictors of changes in needs for care in patients receiving community psychiatric treatment: a 4‐year follow‐up study
Authors: Lasalvia A. , Bonetto C. , Salvi G. , Bissoli S. , Tansella M. , Ruggeri M.
Published: October 2007

Objective:  This study aimed to investigate changes and predictors of change in needs for care, as assessed by both patients and mental health professionals, in a sample of subjects receiving community‐based psychiatric care.

Method:  The study was conducted using a 4‐year prospective longitudinal design. A cohort of patients from the South‐Verona Community Mental Health Service (CMHS) was assessed at baseline and follow‐up using the Camberwell Assessment of Need, both staff and patient versions. Predictors of changes in needs were explored using block‐stratified multiple regression analyses.

Results:  An overall stability for both patient‐rated and staff‐rated needs was found over time; however, significant changes in some specific need domains were found, such as self‐rated health needs (improvement), self‐rated social needs (deterioration) and staff‐rated health needs (deterioration). Changes over time in self‐rated and staff‐rated needs are influenced by different and specific set of predictors, thus indicating that the two measures are not overlapping and convey different types of information.

Conclusion:  Our data support the adoption of a negotiated approach in which both staff and users’ views should be given equal weight when planning and providing needs‐led mental health care.
Needs‐based cognitive‐behavioural family intervention for patients suffering from schizophrenia: 5‐year follow‐up of a randomized controlled effectiveness trial
Authors: Sellwood W. , Wittkowski A. , Tarrier N. , Barrowclough C.
Published: October 2007

Objective:  To determine whether a 24‐week, needs‐based cognitive‐behaviourally oriented family intervention for patients suffering from schizophrenia led to improved relapse profiles over a 5‐year follow‐up period.

Method:  The case notes of 60 patients who had participated in a randomized, controlled effectiveness trial were examined to determine relapse rates over a 5‐year period.

Results:  Patients were less likely to relapse over the 5‐year follow‐up when they received the needs‐based family intervention, especially in relation to exacerbations of symptoms not requiring inpatient admissions: 86.7% of control participants relapsed compared with 53.3% (P = 0.01). Survival analysis indicated that the relapse risk was 2.5 times higher for patients receiving routine care, compared with those receiving family intervention. A similar trend was observed for the final 4 years of follow‐up.

Conclusion:  The present study provides some tentative support for the long‐term effectiveness of family‐based interventions for the management of schizophrenia in general mental health services.
Contact sensitivity in patients with venous leg ulcers in Serbia: comparison with contact dermatitis patients and relationship to ulcer duration
Authors: Jankićević Jasmina , Vesić Sonja , Vukićević Jelica , Gajić Miodrag , Adamič Metka , Pavlović Miloš D.
Published: October 2007

Background: Contact hypersensitivity is a common occurrence in patients with chronic venous leg ulcers (CVLU) with allergen profiles depending upon the local treatment policies.

Objective: This study was to determine the frequency of contact sensitivity, prevalence of individual allergens, polyvalent sensitization, and/or their relationship to ulcers duration in the population of CVLU and contact dermatitis patients in Serbia.

Patients: 75 patients with CVLU and 82 patients with clinically suspected contact dermatitis were prospectively included in the study. The patients were patch tested with a series of 21 standard and 22 supplemental allergens.

Results: 73% (n = 55) of CVLU and 52% (n = 43) of control subjects had 1 or more positive patch test results (P < 0.01). Polysensitization was found in 53% of patients and 21% of controls (P < 0.01). CVLU patients run 2.5 and 4.3 higher risk for contact sensitization and polysensitization, respectively. The most common allergens were Balsam of Peru (21.3%), carba mix (18.7%), fusidic acid (17.3%), colophony (13.3%), paraben mix (12%), chloramphenicol (12%), silver nitrate (12%), and neomycin (10.7%). Polivalent sensitization and higher mean number of allergens were associated with ulcer duration >5 years.

Conclusions: The results confirm a high rate of contact (poly)sensitization in patients with CVLU and local variability in allergen prevalence.
The profile of patch test reactions to common contact allergens is related to sex
Authors: Brasch Jochen , Schnuch Axel , Uter Wolfgang ,   For the Information Network of Departments of Dermatology (IVDK) in Germanyand the German Contact Dermatitis Group (DKG)
Published: October 2007

Background:  Women are more often patch tested than men, and the reactivity to patch test allergens is dependent on sex. However, it is unclear whether the profiles of test reactions are also sex‐related.

Objective:  To compare the profiles of patch test reactions of men and women.

Methods:  Sex‐related reaction profiles of 16 common patch test allergens were analysed based on data of 47 626 patients filed by the Information Network of Departments of Dermatology in Germany. The proportions of weak positive reactions and of questionable and irritant reactions were evaluated by calculating the positivity ratio (PR) and the reaction index (RI) separately for men and women for each allergen.

Results:  Of the 16 allergens evaluated, 8 had a higher PR and a higher RI in women than in men. 4 allergens had a lower PR and another 4 had a lower RI in women than in men. For allergens with similar sensitization prevalence in men and women, female sex was associated with a higher PR and RI (P < 0.01).

Conclusions:  There is a marginal disparity in the reactivity of men and women to patch test allergens that is probably not of clinical relevance but constitutes a scientific challenge.
Heparin‐induced thrombocytopenia associated with interleukin‐8‐dependent platelet activation in a patient with antiphospholipid syndrome
Authors: Bounameaux Claire , Boehlen Françoise , Membré Aurélie , Genné Daniel , Pouplard Claire , Regnault Véronique , De Moerloose Philippe
Published: October 2007

Platelet factor 4 heparin enzyme immunoassay, platelet aggregation test, and serotonin release assay are commonly used to diagnose and confirm heparin‐induced thrombocytopenia. We describe a case of recurrent thrombocytopenia appearing in a few hours after each heparin administration and who tested negative for the three assays. Further analysis revealed anti‐interleukin (IL)‐8 antibodies and IL‐8‐dependent platelet activation facilitated by heparin, which may explain this unusual case of heparin‐induced thrombocytopenia.
Transforming growth factor‐beta1 affects interleukin‐10 production in the bone marrow of patients with chronic idiopathic neutropenia
Authors: Pyrovolaki Katerina , Mavroudi Irene , Papadantonakis Nicolas , Velegraki Maria , Ximeri Maria , Kalpadakis Christina , Gvazava Gilda , Klaus Mirjam , Eliopoulos George D. , Papadaki Helen A.
Published: October 2007

Background:  Chronic idiopathic neutropenia (CIN) is a bone marrow (BM) failure syndrome characterized by accelerated apoptosis of myeloid progenitor cells because of a local imbalance between pro‐inflammatory and anti‐inflammatory cytokines. In this study, we investigated the interplay among transforming growth factor‐beta1 (TGF‐β1), interleukin‐10 (IL‐10), and soluble flt‐3 ligand (sFL) within the BM of CIN patients and probed the role of these cytokines in the pathophysiology of CIN.

Design:  We used long‐term BM cultures (LTBMC) to evaluate TGF‐β1, IL‐10, and sFL levels in CIN patients (n = 70) and healthy subjects (n = 35). Cytokine levels in LTBMC supernatants were correlated with the number of circulating neutrophils and the proportion of BM CD34+/CD33+ myeloid progenitor cells.

Results:  CIN patients had increased TGF‐β1 and sFL levels in LTBMCs compared with controls and individual cytokine values were found to be correlated inversely with the number of neutrophils and the proportion of CD34+/CD33+ cells. Patients displayed low supernatant IL‐10 levels compared with controls and cytokine values were found to be correlated positively with the number of neutrophils and the proportion of CD34+/CD33+ cells. The levels of TGF‐β1 were found to be inversely correlated with IL‐10 and positively with sFL values in LTBMC, supernatants suggesting a possible interplay among these cytokines in CIN BM. Neutralization of TGF‐β1 in LTBMCs increased IL‐10 levels significantly in patients but not in controls, while neutralization had no effect on sFL levels.

Conclusion:  Excessive production of TGF‐β1 within the BM microenvironment of CIN patients results in downregulation of IL‐10 and reduction of myeloid progenitor cells. Overexpression of sFL probably represents a compensatory mechanism to the low myeloid progenitor cells.
Insulin sensitivity assessment with euglycemic insulin clamp in adult β‐thalassaemia major patients
Authors: Tsapas Apostolos , Vlachaki Efthymia , Christoforidis Athanasios , Sarigianni Maria , Bekiari Eleni , Perifanis Vassilis , Tsapas Vassilis , Paletas Konstantinos , Athanassiou‐Metaxa Miranda
Published: October 2007

Objective:  To assess insulin sensitivity in young adult normoglycemic β‐thalassaemia major patients.

Methods:  We measured insulin sensitivity with the euglycemic insulin clamp in 10 young adult (mean age 24.85 ± 2.45 yrs) normoglycemic β‐thalassaemia major patients and 10 sex‐ & age‐ matched controls. Liver iron accumulation was assessed by magnetic resonance imaging (MRI).

Results:  Glucose infusion rate (M) required to maintain euglycemia was significantly reduced in thalassaemic patients compared to controls (261.5 ± 63.5 mg/m2·min vs. 355.6 ± 35.3 mg/m2·min, P = 0.008). Consequently, significantly reduced in the thalassaemic group were also tissue sensitivity to insulin (M/Is‐s) and glucose metabolic clearance rate (M/Gs‐s). There was significant negative correlation between ferritin levels and glucose infusion rate (r = −0.918 P = 0.004). No significant correlations were observed between age, body mass index, daily transfusional iron accumulation, liver iron content and any of the euglycemic clamp parameters. Fasting insulin levels were significantly increased in patients with β‐thalassaemia major compared to controls (P = 0.01), and had significant negative correlation to MRI‐derived liver iron content (r = −0.733, P = 0.03).

Conclusions:  Our data indicate that reduced insulin sensitivity resulting in hyperinsulinaemia precedes the manifestation of glucose intolerance in patients with β‐thalassaemia major. Insulin resistance seems to correlate with increased serum ferritin levels.
Melatonin and the hair follicle
Authors: Fischer Tobias W. , Slominski Andrzej , Tobin Desmond J. , Paus Ralf
Published: October 2007

Abstract: Melatonin, the chief secretory product of the pineal gland, has long been known to modulate hair growth, pigmentation and/or molting in many species, presumably as a key neuroendocrine regulator that couples coat phenotype and function to photoperiod‐dependent environmental and reproductive changes. However, the detailed effects and mechanisms of this surprisingly pleiotropic indole on the hair follicle (HF) regarding growth control and pigmentation have not yet been completely understood. While unspecific melatonin binding sites have long been identified (e.g., in goat and mouse HFs), specific melatonin membrane MT2 receptor transcripts and both protein and mRNA expression for a specific nuclear melatonin binding site [retinoid‐related orphan receptor α (RORα)] have only recently been identified in murine HFs. MT1, known to be expressed in human skin cells, is not transcribed in mouse skin. After initial enzymologic data from hamster skin related to potential intracutaneous melatonin synthesis, it has recently been demonstrated that murine and human skin, namely human scalp HFs in anagen, are important sites of extrapineal melatonin synthesis. Moreover, HF melatonin production is enhanced by catecholamines (as it classically occurs in the pineal gland). Melatonin may also functionally play a role in hair‐cycle control, as it down‐regulates both apoptosis and estrogen receptor‐α expression, and modulates MT2 and RORα expression in murine skin in a hair‐cycle‐dependent manner. Because of melatonin′s additional potency as a free radical scavenger and DNA repair inducer, the metabolically and proliferatively highly active anagen hair bulb may also exploit melatonin synthesis in loco as a self‐cytoprotective strategy.
MT1 melatonin receptor internalization underlies melatonin‐induced morphologic changes in Chinese hamster ovary cells and these processes are dependent on Gi proteins, MEK 1/2 and microtubule modulation
Authors: Bondi C. Dominic , McKeon Raelene M. , Bennett Jennifer M. , Ignatius Paul F. , Brydon Lena , Jockers Ralf , Melan Melissa A. , Witt‐Enderby Paula A.
Published: October 2007

Abstract:  Melatonin induces cellular differentiation in numerous cell types. Data show that multiple mechanisms are involved in these processes that are cell‐type specific and may be receptor dependent or independent. The focus of this study was to specifically assess the role of human MT1 melatonin receptors in cellular differentiation using an MT1‐Chinese hamster ovary (CHO) model; one that reproducibly produces measurable morphologic changes in response to melatonin. Using multiple approaches, we show that melatonin induces MT1‐CHO cells to hyperelongate through a MEK 1/2, and ERK 1/2‐dependent mechanism that is dependent upon MT1 receptor internalization, Gi protein activation, and clathrin‐mediated endocytosis. Using immunoprecipitation analysis, we show that MT1 receptors form complexes with Giα 2,3, Gqα, β‐arrestin‐2, MEK 1/2, and ERK 1/2 in the presence of melatonin. We also show that MEK and ERK activity that is induced by melatonin is dependent on Gi protein activation, clathrin‐mediated endocytosis and is modulated by microtubules. We conclude from these studies that melatonin‐induced internalization of human MT1 melatonin receptors in CHO cells is responsible for activating both MEK 1/2 and ERK 1/2 to drive these morphologic changes. These events, as mediated by melatonin, require Gi protein activation and endocytosis mediated through clathrin, to form MT1 receptor complexes with β‐arrestin‐2/MEK 1/2 and ERK 1/2. The MT1‐CHO model is invaluable to mapping out signaling cascades as mediated through MT1 receptors especially because it separates out MEK/ERK 1/2 activation by MT1 receptors from that of receptor tyrosine kinases.
A Review of Molecular Contrasts Between Arresting and Viable Porcine Attachment Sites
Authors: Wessels Jocelyn M. , Linton Nicola F. , Croy B. Anne , Tayade Chandrakant
Published: October 2007

Significant spontaneous fetal loss of unknown cause occurs in North American commercial swine. About 30% of conceptuses, thought to be genetically normal, are lost during the peri‐attachment period. An additional 20% are lost at mid‐pregnancy. Littermate endometrial and trophoblast biopsies were studied by quantitative real‐time PCR for gene expression, and immunohistochemistry for protein expression at gestation day (gd)15–23 and 50. RNA analyses were also conducted on endometrial lymphocytes and arterial endothelial cells removed from biopsies by laser capture microdissection. Genes were selected for study from human literature and cloned as required. As in humans, angiogenic, cytokine, chemokine and chemokine decoy receptor gene expression occurs at the porcine maternal–fetal interface. In each tissue studied, distinct patterns of expression are found between early and mid‐pregnancy, as well as between viable and arresting conceptus attachment sites. These changes involve both endometrial lymphocytes and dendritic cells. Restriction in endometrial angiogenesis, reduction in expression of the chemokine decoy receptor D6, and reduction in dendritic cell numbers contribute to fetal arrest. In peri‐attachment loss, interferon‐γ is more abundantly transcribed than tumor necrosis factor‐α, but this ratio is reversed during midgestation failure. Further characterization of spontaneous fetal loss in pigs will identify targets for modification by hog producers and may provide a model for identification of antecedents to fetal loss in humans.
Evaluation of Serum and Urinary Angiogenic Factors in Patients with Endometriosis
Authors: Cho Si Hyun , Oh Yoon Jin , Nam Anna , Kim Hye Yeon , Park Joo Hyun , Kim Jae Hoon , Park Ki Hyun , Cho Dong Je , Lee Byung Seok
Published: October 2007

Problem  The aim of this study was to evaluate serum and urinary levels of vascular endothelial growth factors, tumor necrosis factor‐α (TNF‐α), and soluble fms‐like tyrosine kinase (sFlt‐1) in patients with endometriosis.

Method of study  During surgery for pelvic pain, pelvic mass or infertility, serum and urine were collected. Of 70 patients, 46 had histology‐proven endometriosis and 24 patients without endometriosis participated as controls.

Results  Serum TNF‐α levels and urinary sFlt‐1 levels corrected for creatinine excretion were significantly increased in the endometriosis group (P = 0.001 and P = 0.011 respectively). Serum sFlt‐1 levels and urinary sFlt‐1 levels corrected for creatinine were significantly higher in patients with minimal‐to‐mild disease (P = 0.014 and P = 0.015 respectively), where serum TNF‐α levels were increased in moderate‐to‐severe endometriosis (P < 0.001).

Conclusion  The pathogenesis of minimal‐to‐mild endometriosis and moderate‐to‐severe endometriosis seems to be different. Increased sFlt‐1 levels in serum and urine of minimal‐to‐mild disease indicate that sFlt‐1 may have an important role in inhibiting angiogenic process of the disease.