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AV
Terms modified by AV Selected AbstractsInterstellar extinction and polarization , a spheroidal dust grain approach perspectiveMONTHLY NOTICES OF THE ROYAL ASTRONOMICAL SOCIETY, Issue 1 2010H. K. Das ABSTRACT We extend and investigate the spheroidal model of interstellar dust grains used to simultaneously interpret the observed interstellar extinction and polarization curves. We compare our model with similar models recently suggested by other authors, study its properties and apply it to fit the normalized extinction A(,)/AV and the polarizing efficiency P(,)/A(,) measured in the near-infrared to far-ultraviolet region for several stars seen through one large cloud. We conclude that the model parameter , being the angle between the line of sight and the magnetic field direction can be more or less reliably determined from comparison of the theory and observations. This opens a way to study the spatial structure of interstellar magnetic fields by using multiwavelength photometric and polarimetric observations. [source] Differences in sino-atrial and atrio-ventricular function with age and sex attributable to the Scn5a+/, mutation in a murine cardiac modelACTA PHYSIOLOGICA, Issue 1 2010K. Jeevaratnam Abstract Aim:, To investigate the interacting effects of age and sex on electrocardiographic (ECG) features of Scn5a+/, mice modelling Brugada syndrome. Methods:, Recordings were performed on anaesthetized wild-type (WT) and Scn5a+/, mice and differences attributable to these risk factors statistically stratified. Results:,Scn5a+/, exerted sex-dependent effects upon sino-atrial function that only became apparent with age. RR intervals were greater in old male than in old female Scn5a+/,. Atrio-ventricular (AV) conduction was slower in young female mice, whether WT and Scn5a+/,, than the corresponding young male WT and Scn5a+/,. However, PR intervals lengthened with age in male but not in female Scn5a+/, giving the greatest PR intervals in old male Scn5a+/, compared with either old male WT or young male Scn5a+/, mice. In contrast, PR intervals were similar in old female Scn5a+/, and in old female WT. QTc was prolonged in Scn5a+/, compared with WT, and female Scn5a+/, compared with female WT. Age-dependent alterations in durations of ventricular repolarization relative to WT affected male but not female Scn5a+/,. Thus, T-wave durations were greater in old male Scn5a+/, compared with old male WT, but indistinguishable between old female Scn5a+/, and old female WT. Finally, analysis for combined interactions of genotype, age and sex demonstrated no effects on P wave and QRS durations and QTc intervals. Conclusion:, We demonstrate for the first time that age, sex and genotype exert both independent and interacting ECG effects. The latter suggest alterations in cardiac pacemaker function, atrio-ventricular conduction and ventricular repolarization greatest in ageing male Scn5a+/,. [source] Understanding heart development and congenital heart defects through developmental biology: A segmental approachCONGENITAL ANOMALIES, Issue 4 2005Masahide Sakabe ABSTRACT The heart is the first organ to form and function during development. In the pregastrula chick embryo, cells contributing to the heart are found in the postero-lateral epiblast. During the pregastrula stages, interaction between the posterior epiblast and hypoblast is required for the anterior lateral plate mesoderm (ALM) to form, from which the heart will later develop. This tissue interaction is replaced by an Activin-like signal in culture. During gastrulation, the ALM is committed to the heart lineage by endoderm-secreted BMP and subsequently differentiates into cardiomyocyte. The right and left precardiac mesoderms migrate toward the ventral midline to form the beating primitive heart tube. Then, the heart tube generates a right-side bend, and the d-loop and presumptive heart segments begin to appear segmentally: outflow tract (OT), right ventricle, left ventricle, atrioventricular (AV) canal, atrium and sinus venosus. T-box transcription factors are involved in the formation of the heart segments: Tbx5 identifies the left ventricle and Tbx20 the right ventricle. After the formation of the heart segments, endothelial cells in the OT and AV regions transform into mesenchyme and generate valvuloseptal endocardial cushion tissue. This phenomenon is called endocardial EMT (epithelial-mesenchymal transformation) and is regulated mainly by BMP and TGF,. Finally, heart septa that have developed in the OT, ventricle, AV canal and atrium come into alignment and fuse, resulting in the completion of the four-chambered heart. Altered development seen in the cardiogenetic process is involved in the pathogenesis of congenital heart defects. Therefore, understanding the molecular nature regulating the ,nodal point' during heart development is important in order to understand the etiology of congenital heart defects, as well as normal heart development. [source] Hemiazygos Venous Additional Pulmonary Flow for Successful Total Cavo-pulmonary ConnectionCONGENITAL HEART DISEASE, Issue 5 2007Koichi Sughimoto MD ABSTRACT Patients who underwent only Glenn procedure after being deemed unsuitable candidates for Fontan completion are not small in number, and may develop arterio-venous (AV) pulmonary malformations during the follow-up period. We present the case of a 17-year-old woman with severe systemic desaturation 13 years after Glenn procedure and repair of total anomalous pulmonary venous return. Among other anomalies, the patient disclosed hemiazygos continuation to a persistent left superior vena cava. This case supports the concept that returning flow from the abdominal vein plays an important role in the well-balanced growth of the pulmonary artery and in the inhibition of the pulmonary AV malformation. [source] NON-GYNAECOLOGICAL CYTOLOGY: THE CLINICIAN'S VIEWCYTOPATHOLOGY, Issue 2006I. Penman There is increased recognition of the importance of accurate staging of malignancies of the GI tract and lung, greater use of neoadjuvant therapies and more protocol-driven management. This is particularly important where regional lymph node involvement significantly impacts on curability. Multidetector CT and PET scanning have resulted in greater detection of potential abnormalities which, if positive for malignancy, would change management. There is also a greater recognition that many enlarged nodes may be inflammatory and that size criteria alone are unreliable in determining involvement. In other situations, especially pancreatic masses, not all represent carcinoma as focal chronic pancreatitis, autoimmune pancreatitis etc can catch out the unwary. A preoperative tissue diagnosis is essential and even if unresectable, oncologists are increasingly reluctant to initiate chemotherapy or enroll patients into trials without this. The approach to obtaining tissue is often hampered by the small size or relative inaccessibility of lesions by percutaneous approaches. As such novel techniques such as endoscopic ultrasound (EUS) guided FNA have been developed. A 120cm needle is passed through the instrument and, under real-time visualisation, through the gastrointestinal wall to sample adjacent lymph nodes or masses. Multiple studies have demonstrated the safety and performance of this technique. In oesophageal cancer, confirmation of node positivity by has a major negative influence on curative resection rates and will often lead to a decision to use neoadjuvant chemotherapy or a non-operative approach. Sampling of lymph nodes at the true coeliac axis upstages the patient to M1a status (stage IV) disease and makes the patient incurable. In NSCLC, subcarinal lymph nodes are frequently present but may be inflammatory. If positive these represent N2 (stage IIIA) disease and in most centres again makes the patient inoperable. Access to these lymph nodes would otherwise require mediastinosocopy whereas this can be done simply, safely and quickly by EUS. Overall the sensitivity for EUS , FNA of mediastinal or upper abdominal lymph nodes is 83,90% with an accuracy of 80,90%. In pancreatic cancer performance is less good but pooled analysis of published studies indicates a sensitivity of 85% and accuracy of 88%. In a recent spin-off from EUS, endobronchial ultrasound (EBUS) instruments have been developed and the ability to sample anterior mediastinal nodes has been demonstrated. It is likely that this EBUS , FNA technique will become increasingly utilised and may replace mediastinoscopy. The development of techniques such as EUS and EBUS to allow FNA sampling of lesions has increased the role of non-gynaecological cytology significantly in recent years. Cytology therefore remains important for a broad range of specialties and there is ongoing need for careful and close co-operation between cytologists and clinicians in these specialties. References:, 1. Williams DB, Sahai AV, Aabakken L, Penman ID, van Velse A, Webb J et al. Endoscopic ultrasound guided fine needle aspiration biopsy: a large single centre experience. Gut. 1999; 44: 720,6. 2. Silvestri GA, Hoffman BJ, Bhutani MS et al. Endoscopic ultrasound with fine-needle aspiration in the diagnosis and staging of lung cancer. Ann Thorac Surg 1996; 61: 1441,6. 3. Rintoul RC, Skwarski KM, Murchison JT, Wallace WA, Walker WS, Penman ID. Endobronchial and endoscopic ultrasound real-time fine-needle aspiration staging of the mediastinum ). Eur Resp J 2005; 25: 1,6. [source] Laser-Doppler Examination Shows High Flow in Some Common Telangiectasias of the Lower LimbDERMATOLOGIC SURGERY, Issue 4 2005Imre Bihari MD Background. The accepted pathophysiology of telangiectasias is reflux from superficial or deep veins. There are physical signs and scientific findings that do not fit this theory but support the possibility of arteriovenous (AV) shunt origin. Objective. If there is a higher flow in spider veins than in the surrounding skin, it means that AV shunts participate in the circulation of the telangiectasia. On the other hand, slow flow indicates reflux as the etiologic factor. Method. Telangiectasias and the surrounding skin of 22 legs of 19 patients were examined with laser-Doppler equipment. Results. The probe over the spider vein found a higher flow value (average 28.2 perfusion units [PU]) than in the surrounding skin (15.6 PU) in 13 limbs, but it was significantly higher only in 5 cases. In 9 limbs, the flow was slower. Conclusion. We interpret the higher flow values as a consequence of open AV shunts. This means that AV shunt pathophysiology was present in some of our cases. IMRE BIHARI, MD, PHD, ANIKÓ MURÁNYI, MD, AND PéTER BIHARI, MD, HAVE INDICATED NO SIGNIFICANT INTEREST WITH COMMERCIAL SUPPORTERS. [source] Characterization of molecular markers to assess cardiac cushions formation in XenopusDEVELOPMENTAL DYNAMICS, Issue 12 2009Young-Hoon Lee Abstract The valves and septa of the mature heart are derived from the cardiac cushions, which develop from discrete swellings in two regions of developing heart tube: the atrioventricular (AV) canal and the ventricular outflow tract (OFT). In higher vertebrates, three distinct lineages contribute to the heart valves and septa, the endocardium, the myocardium, and the cardiac neural crest that will populate the cardiac jelly of the OFT. Very little is known about cardiac cushions development in amphibians. Here, we describe the expression of eight genes during key stages of cardiac cushion development in Xenopus. Among these genes, the Wnt antagonist Frzb1 and the transcription factors Xl-Fli, Sox8, Sox9, and Sox10 are differentially expressed in the mesenchyme of the OFT and AV cushions. These genes can be used in combination with lineage-tracing experiments to determine the embryonic origin of the cardiac cushions mesenchyme in Xenopus. Developmental Dynamics 238:3257,3265, 2009. © 2009 Wiley-Liss, Inc. [source] Left-asymmetric expression of Galanin in the linear heart tube of the mouse embryo is independent of the nodal co-receptor gene crypticDEVELOPMENTAL DYNAMICS, Issue 12 2008Axel Schweickert Abstract Only very few left/right asymmetrically expressed genes are known in the mammalian embryo. In a screen for novel factors we identified the gene encoding the neuropeptide Galanin in mouse. At embryonic day (E) 8.5 asymmetric mRNA transcription was found in the left half of the linear heart tube. During heart looping and morphogenesis expression became restricted to the atrio-ventricular (AV) canal, followed by specific staining of the AV-node and AV-rings in the four-chambered heart. Expression was inverted in inv/inv and randomized in homozygous iv mutant embryos. Left-sided heart-specific transcription of mouse Gal thus should be controlled by the left-right pathway. The asymmetric pattern was retained in cryptic mutant embryos, in which the Nodal signaling cascade is disrupted. Surprisingly, Pitx2c was found to be expressed in 50% of cryptic mutant hearts as well, suggesting that some aspects of asymmetric gene expression in the heart are independent of cryptic. Developmental Dynamics 237:3557,3564, 2008. © 2008 Wiley-Liss, Inc. [source] Interaction of the G182C polymorphism in the APOA5 gene and fasting plasma glucose on plasma triglycerides in Type 2 diabetic subjectsDIABETIC MEDICINE, Issue 12 2005Y.-D. Jiang Abstract Aim Apolipoprotein AV (APOA5) is an important determinant of plasma triglyceride concentration. This study aimed to investigate the relationship of an amino acid substitution at position 182 (G182C) of the apolipoprotein AV (APOA5) gene with triglyceride concentration in a Taiwanese population. Methods This study enrolled two cohorts: non-diabetic subjects (112 males and 89 females) aged 50.3 ± 11.0 years (mean ± sd) and diabetic subjects (106 males and 96 females) aged 62.1 ± 10.3 years. The relationship between the G182C polymorphism (rs 2075291) and plasma triglycerides was examined. Demographic and metabolic parameters including age, sex, body mass index, fasting plasma glucose and total cholesterol were also obtained. Results The G182C polymorphism was a determinant of plasma triglycerides in both non-diabetic (P = 0.022) and diabetic (P = 0.003) groups, independent of age, gender, fasting plasma glucose, body mass index and total cholesterol. In the diabetic group, this genetic polymorphism interacts significantly (P = 0.032) with fasting plasma glucose concentration on plasma triglycerides after adjustment for age, sex, body mass index and total cholesterol. Conclusions In conclusion, the G182C polymorphism of the APOA5 gene affects plasma triglycerides in both non-diabetic and diabetic populations. The observed interaction of gene and glycaemic control further indicates a multifactorial nature of clinical phenotypes in subjects with Type 2 diabetes. Diabet. Med. (2005) [source] Discrepancy between Gradients Derived by Cardiac Catheterization and by Doppler Echocardiography in Aortic Stenosis: How Often Does Pressure Recovery Play a Role?ECHOCARDIOGRAPHY, Issue 9 2009Studies have shown very good correlation between Doppler-derived gradients and gradients obtained by cardiac catheterization (cath) in aortic stenosis (AS). However, the phenomenon of pressure recovery may lead to significant overestimation of aortic valve (AV) gradients by Doppler echocardiography (echo). We hypothesized that echo-derived gradients will be higher in mild,moderate AS because of pressure recovery. We studied 94 patients who had echo and cardiac caths in a span of 1 week. The mean age was 72 ± 13 years, 54% males, 79% had coronary artery disease, and the mean left ventricular ejection fraction was 45 ± 22%. The mean cardiac output and cardiac indices were 5.1 ± 1.4/2.7 ± 0.6 (l/mt), (l/m2), respectively. For those with mild AS, echo overestimated gradients in 9.5% of patients (4/42) by an average of 19 mmHg, thus misclassifying the degree of stenosis. In those with moderate AS, 14% (3/21) were misclassified as severe AS (gradient overestimation by an average of 13.6 mmHg). In those with severe AS, echo underestimated gradients in 13% (4/31) by an average of 22.7 mmHg. The aorta at the sinotubular junction was 2.8 cm in those patients with mild AS in whom gradients were overestimated by more than 20 mmHg compared to a sinotubular junction diameter of 3.12 cm in those with mild AS and no overestimation of gradients. The AV area/aortic root ratio was 0 .4 in those with mild AS and 0.2 in those with severe AS (P < 0.05). [source] A double-blind, randomized trial of intravenous versus intramuscular antivenom for Red-back spider envenomingEMERGENCY MEDICINE AUSTRALASIA, Issue 2 2005Rodney M Ellis Abstract Objective:, To compare the efficacy of intravenous versus intramuscular antivenom (AV) in the treatment of Red-back spider (RBS) envenoming. Methods:, Randomized, double-dummy, double-blind, multicentre trial of patients with red-back spider envenoming requiring AV treatment recruited from five hospital EDs in Western Australia. Results:, Thirty-five patients were recruited; two were excluded; 33 were available for initial analysis, but two who were unblinded after one ampoule of trial AV and given i.v. AV had limited data; 31 remained in the study and had more complete data. After AV, pain scores for both i.m. and i.v. groups improved rapidly. At 24 h, the i.v. group was better with a 55% absolute difference (76% vs. 21%; 95% CI 25,85% difference) in the proportion pain-free. There were no safety issues. Conclusions:, Red-back spider antivenom was initially effective by both i.m. and i.v. routes. The study generates the hypothesis that at 24 h, significantly more patients are pain-free with i.v. administration. Definitive recommendations on the optimal route of administration of RBS AV await the results of further studies. [source] Circulation in normal and inflamed dental pulpENDODONTIC TOPICS, Issue 1 2007ELLEN BERGGREEN In the pulp, arteries branch into a capillary network before they leave the pulp as venules through the apical foramina. The tissue has low compliance, as it is enclosed in dentin, and has a relatively high blood flow and blood volume. The interstitial fluid pressure (IFP) and colloid osmotic pressure are relatively high whereas the net driving blood pressure is low. The high pulsatile IFP is probably the major force for propelling lymph in the dental pulp. Vasodilation in neighboring tissue as well as arteriovenous (AV) shunts in the pulp itself can contribute to a fall in total and coronal pulpal blood flow, respectively. The pulp blood flow is under nervous, humoral, and local control. Inflammatory vascular responses, vasodilation, and increased vessel permeability induce an increase in IFP that can be followed by a temporarily impaired blood flow response. Lipopolysaccharides (LPS) from bacteria may cause endothelial activation in the pulp, leading to vasoconstriction and reduced vascular perfusion. Lymphatic vessels are identified with specific lymphatic markers in the pulp but so far, little is known about their function. Because of the special circulatory conditions in the pulp, there are several clinical implications that need to be considered in dental treatment. Received 13 February 2009; accepted 28 August 2009. [source] Cardiac function and antiepileptic drug treatment in the elderly: A comparison between lamotrigine and sustained-release carbamazepineEPILEPSIA, Issue 8 2009Erik Saetre Summary Purpose:, To investigate the comparative effects of carbamazepine (CBZ) and lamotrigine (LTG) on electrocardiography (ECG) parameters in elderly patients with newly diagnosed epilepsy. Methods:,, The study was conducted in the Norwegian subcohort (n = 108) of an international randomized double-blind 40-week trial, which compared the efficacy and tolerability of LTG and sustained-release CBZ in patients aged 65 and older with newly diagnosed epilepsy. Target maintenance doses were 400 mg/day for CBZ and 100 mg/day for LTG, with adjustments based on clinical response. Patients with significant unpaced atrioventricular (AV) conduction defect were excluded. Resting 12-lead ECG recordings were made under standardized conditions at pretreatment (baseline) and at the 40-week study visit (treatment visit). Changes in QRS interval (primary endpoint), heart rate (HR), PQ, and QTc (HR-corrected QT) intervals were assessed and compared between groups. Results:, Of the 108 patients randomized, 33 discontinued prematurely because of adverse events (n = 24, none of which was cardiac) or other reasons (n = 9), and 15 were nonevaluable due to incomplete ECG data. None of the assessed ECG parameters differed significantly between groups at baseline. No significant ECG changes were recorded between baseline and treatment visit for QRS duration and QTc intervals, whereas HR fell and PQ intervals increased slightly on both treatments. However, there were no differences between groups in changes from baseline to treatment visit. There were no significant relationships between individual ECG changes and serum drug concentrations, except for QTc intervals, which decreased slightly with increasing CBZ concentrations. The proportion of patients with ECG parameters outside the normal range at treatment visit was similar to that recorded at baseline. Discussion:, Clinically significant ECG changes are not common during treatment with CBZ or LTG in elderly patients with no preexisting significant AV conduction defects. [source] Effect of age and training on murmurs of atrioventricular valvular regurgitation in young ThoroughbredsEQUINE VETERINARY JOURNAL, Issue 3 2000L. E. Young Summary Cardiac auscultation was carried out on 111 Thoroughbred horses age 2,5 years to test the hypothesis that athletic training might influence the development of atrioventricular (AV) valve regurgitation in young Thoroughbreds. Murmurs of valvular regurgitation were identified and graded on a 1,6 scale. There were 2 sources of auscultation data: 1) 55 2-year-old horses that were examined by auscultation before training commenced and 9 months later when at race fitness; 2) 56 horses age 2,5 years that were examined on one occasion only (25 2-year-olds, 23 3-year-olds, five 4-year-olds and five 5-year olds). All horses in the second data set were in full training and racing regularly at the time of the examination. To conclude the study, 35 horses were selected randomly from both groups of horses and examined with colour-flow Doppler echocardiography. The aim of the final part of the study was to check specificity and sensitivity of auscultation for detection of AV valve murmurs and therefore validate the auscultation findings. Priorto training, the prevalence in 2-year-old racehorses of murmurs of mitral regurgitation and tricuspid regurgitation was 7.3% (4/55) and 12.7% (7/55), respectively. After training, the prevalence proportions increased to 21.8% (12/55) and 25.5% (14/55). After training, one horse developed a murmur characteristic of aortic regurgitation. The differences in murmur prevalence were statistically significant for mitral and tricuspid regurgitation (paired t test results: mitral regurgitation, P = 0.019; tricuspid regurgitation, P = 0.007), as were the differences in mean murmurgrade (P= 0.018 and P= 0.0006, respectively). There were no significant effects of age on the prevalence of valvular regurgitation in 56 horses examined at race fitness. Auscultation was a specific (specificity 100%) and reasonably sensitive method for detection of murmurs of mitral and tricuspid regurgitation (mitral regurgitation: positive predictive value 100%, negative predictive value 84%, tricuspid regurgitation: positive predictive value 100%, negative predictive value 65%). These data suggest that the prevalence and grade of murmurs of mitral and tricuspid valvular regurgitation increase in 2-year-old Thoroughbreds after 9 months of athletic training. Whereas the effects of age and growth on the prevalence of murmurs cannot be ruled out from these data, this study suggests that there is an influence of athletic training on the development of atrioventicular valvular regurgitation in flat-racing Thoroughbreds. [source] Electrical optimization of cardiac resynchronization in chronic heart failure is associated with improved clinical long-term outcomeEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 8 2010Christopher Adlbrecht Eur J Clin Invest 2010; 40 (8): 678,684 Abstract Background, Cardiac resynchronization therapy (CRT) is an established treatment option for symptomatic chronic heart failure (CHF) patients with pharmacological baseline therapy, but not all patients benefit from device therapy. One reason for this may be inadequate device settings. In real-world practice, echocardiographic evaluation of atrioventricular (AV) delay is not performed in a high proportion of patients, as the effect of electrical optimization of CRT is an issue open for investigation. Materials and methods, We performed a retrospective observational study analysing the effect of AV-interval evaluation with echocardiography on long-term [32 (23?43) months] clinical outcome in 205 CHF patients. A stepwise Cox regression model including a co-morbidity score, failed AV-interval evaluation, satisfactory device function after the first implantation attempt, failure to reach 100% of the recommended renin-angiotensin system inhibitor and beta-blocker dose at follow-up and CRT device implantation compared with CRT in combination with an implanted cardioverter defibrillator (ICD) was applied. Results, In the total study cohort, 124 (60·5%) patients had reached the primary combined endpoint death or cardiac hospitalization and 59 (28·8%) had died. Cox regression analysis revealed that failed AV-interval evaluation [HR = 1·72 (1·19,2·49), P = 0·004] non-optimized CHF pharmacotherapy dosages [HR = 2·12 (1·32,3·42), P = 0·002], the presence of a CRT/ICD combination device [HR = 1·87 (1·28,2·71), P = 0·001] and satisfactory device function after the first implantation attempt [HR = 0·44 (0·25,0·77), P = 0·004] were associated with the primary endpoint. Conclusion, Echocardiographic evaluation of the AV-interval in patients with CRT was independently associated with improved clinical outcome, impacting on daily clinical practice of HF patient care. [source] Extended X-ray Absorption Fine Structure Study of Copper(I) and Copper(II) Complexes in Atom Transfer Radical PolymerizationEUROPEAN JOURNAL OF INORGANIC CHEMISTRY, Issue 11 2003Tomislav Pintauer Abstract Extended X-ray Absorption Fine Structure (EXAFS) spectroscopy has been used to investigate structural features of CuIBr and CuIIBr2 complexes with dNbpy, PMDETA, Me6TREN, tNtpy, and Me4CYCLAM in various solvents {dNbpy = 4,4,-bis(5-nonyl)-2,2,-bipyridine, PMDETA = N,N,N,,N,,,N,, -pentamethyldiethylenetriamine, Me6TREN = tris[2-(dimethylamino)ethyl]amine, tNtpy = 4,4,,4,,-tris(5-nonyl)-2,2,:6,,2,,-terpyridine, Me4CYCLAM = 1,4,8,11-tetramethyl-1,4,8,11-tetraazacyclotetradecane}. The structures of the CuI and CuII complexes were found to depend on the solvent polarity and the number of nitrogen atoms in the ligand. Generally, in non-polar media and with monomers typically used in ATRP, CuI complexes preferred a tetracoordinate geometry, and were either ionic as observed in [CuI(dNbpy)2]+[CuIBr2], (CuI,NAV = 2.00 Å, CuI,BrAV = 2.25 Å) and [CuI(Me4CYCLAM)]+[CuIBr2], (CuI,NAV = 2.06 Å, CuI,BrAV = 2.23 Å), or neutral as in [CuI(PMDETA)Br] (CuI,NAV = 2.12 Å, CuI,BrAV = 2.33 Å), and [CuI(tNtpy)Br] (CuI,NAV = 2.03 Å, CuI,BrAV = 2.29 Å). The EXAFS analysis of CuIIBr2 complexes indicated a preference for a coordination number of five, such as in [CuII(dNbpy)2Br]+[Br], (CuII,NAV = 2.03 Å, CuII,BrAV = 2.43 Å), [CuII(PMDETA)Br2] (CuII,NAV = 2.03 Å, CuII,Br1,AV = 2.44 Å, CuII,Br2,AV = 2.64 Å) and [CuII(Me6TREN)Br]+[Br], (CuII,NAV = 2.09 Å, CuII -BrAV = 2.39 Å), with the exception of the neutral tetracoordinate [CuII(dNbpy)Br2] (CuII,NAV = 2.02 Å, CuII,BrAV = 2.36 Å), which has been observed in non-polar media. Additionally, polar media were found to favor bromide dissociation in [CuII(Me6TREN)Br]+[Br], and [CuII(PMDETA)Br2], as indicated by a decrease in the Br and Cu coordination numbers at the Cu- and Br- K -edges, respectively. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003) [source] Oxidative stability and acceptability of camelina oil blended with selected fish oilsEUROPEAN JOURNAL OF LIPID SCIENCE AND TECHNOLOGY, Issue 8 2010Deirdre Ní Eidhin Abstract The effects of blending camelina oil with a number of fish oils on oxidative stability and fishy odour were evaluated. Camelina oil was found to be more stable than tuna oil, ,omega-3' fish oil and salmon oil as indicated by predominantly lower ,-anisidine (AV), thiobarbituric acid reactive substances (TBARS) and conjugated triene levels (CT) during storage at 60,°C for 20,days (p,<,0.05). Peroxide values (PV) were similar for all oils until Day 13 when values for camelina oil were higher. Values for blends of the fish oils (50, 25, 15, 5%) with camelina oil were generally between those of their respective bulk oils indicating a dilution effect. Camelina oil had a similar odour score (p,<,0.05) to sunflower oil (9.2 and 9.6, respectively) indicating, as expected, an absence of fishy odours. In comparison, the fish oils had lower scores of 6.1 to 6.6 (p,<,0.05) indicating mild to moderate fishy odours. Odour scores were improved at the 25% fish oil levels (p,<,0.05) and were not different to camelina oil at the 15 or 5% levels (p,<,0.05). Practical applications: Camelina oil is a potentially important functional food ingredient providing beneficial n-3 PUFA. Oil extracted from Camelina sativa seeds contains greater than 50% polyunsaturated fatty acids of which 35-40% is ,-linolenic acid (C18:3,3, ALA), an essential omega-3 fatty acid 1. While EPA and DHA from fish oils are more potent nutritionally, they are less stable than ALA. This work evaluated innovative blends of fish oil with camelina oil for stability and acceptability. The results demonstrate that there is potential for use of blends of camelina oil with fish oils in food products, as the results show some benefits in terms of reduction of fishy odours. Such information could be valuable in relation to formulation of food products containing high levels of n-3 PUFA from both plant and fish sources. [source] In vivo voltammetric monitoring of norepinephrine release in the rat ventral bed nucleus of the stria terminalis and anteroventral thalamic nucleusEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 11 2009Jinwoo Park Abstract The role and contribution of the dense noradrenergic innervation in the ventral bed nucleus of the stria terminalis (vBNST) and anteroventral thalamic nucleus (AV) to biological function and animal behaviors is poorly understood due to the small size of these nuclei. The aim of this study was to compare norepinephrine release and uptake in the vBNST with that in the AV of anesthetized rats. Measurements were made in vivo with fast-scan cyclic voltammetry following electrical stimulation of noradrenergic projection pathways, either the dorsal noradrenergic bundle (DNB) or the ventral noradrenergic bundle (VNB). The substance detected was identified as norepinephrine based upon voltammetric, anatomical, neurochemical and pharmacological evidence. Fast-scan cyclic voltammetry enables the selective monitoring of local norepinephrine overflow in the vBNST evoked by the stimulation of either the DNB or the VNB while norepinephrine in the AV was only evoked by DNB stimulation. The ,2-adrenoceptor antagonist yohimbine and the norepinephrine uptake inhibitor desipramine increased norepinephrine overflow and slowed its disappearance in both regions. However, control of extracellular norepinephrine by both autoreceptors and uptake was greater in the AV. The greater control exerted by autoreceptors and uptake in the AV resulted in reduced extracellular concentration compared with the v,BNST when large numbers of stimulation pulses were employed. The differences in noradrenergic transmission observed in the terminal fields of the v,BNST and the AV may differentially regulate activity in these two regions that both contain high densities of norepinephrine terminals. [source] Small heat shock protein Hsp27 prevents heat-induced aggregation of F-actin by forming soluble complexes with denatured actinFEBS JOURNAL, Issue 22 2007Anastasia V. Pivovarova Previously, we have shown that the small heat shock protein with apparent molecular mass 27 kDa (Hsp27) does not affect the thermal unfolding of F-actin, but effectively prevents aggregation of thermally denatured F-actin [Pivovarova AV, Mikhailova VV, Chernik IS, Chebotareva NA, Levitsky DI & Gusev NB (2005) Biochem Biophys Res Commun331, 1548,1553], and supposed that Hsp27 prevents heat-induced aggregation of F-actin by forming soluble complexes with denatured actin. In the present work, we applied dynamic light scattering, analytical ultracentrifugation and size exclusion chromatography to examine the properties of complexes formed by denatured actin with a recombinant human Hsp27 mutant (Hsp27,3D) mimicking the naturally occurring phosphorylation of this protein at Ser15, Ser78, and Ser82. Our results show that formation of these complexes occurs upon heating and accompanies the F-actin thermal denaturation. All the methods show that the size of actin,Hsp27-3D complexes decreases with increasing Hsp27-3D concentration in the incubation mixture and that saturation occurs at approximately equimolar concentrations of Hsp27-3D and actin. Under these conditions, the complexes exhibit a hydrodynamic radius of ,,16 nm, a sedimentation coefficient of 17,20 S, and a molecular mass of about 2 MDa. It is supposed that Hsp27-3D binds to denatured actin monomers or short oligomers dissociated from actin filaments upon heating and protects them from aggregation by forming relatively small and highly soluble complexes. This mechanism might explain how small heat shock proteins prevent aggregation of denatured actin and by this means protect the cytoskeleton and the whole cell from damage caused by accumulation of large insoluble aggregates under heat shock conditions. [source] Dynamic versus static models in cost-effectiveness analyses of anti-viral drug therapy to mitigate an influenza pandemicHEALTH ECONOMICS, Issue 5 2010Anna K. Lugnér Abstract Conventional (static) models used in health economics implicitly assume that the probability of disease exposure is constant over time and unaffected by interventions. For transmissible infectious diseases this is not realistic and another class of models is required, so-called dynamic models. This study aims to examine the differences between one dynamic and one static model, estimating the effects of therapeutic treatment with antiviral (AV) drugs during an influenza pandemic in the Netherlands. Specifically, we focus on the sensitivity of the cost-effectiveness ratios to model choice, to the assumed drug coverage, and to the value of several epidemiological factors. Therapeutic use of AV-drugs is cost-effective compared with non-intervention, irrespective of which model approach is chosen. The findings further show that: (1) the cost-effectiveness ratio according to the static model is insensitive to the size of a pandemic, whereas the ratio according to the dynamic model increases with the size of a pandemic; (2) according to the dynamic model, the cost per infection and the life-years gained per treatment are not constant but depend on the proportion of cases that are treated; and (3) the age-specific clinical attack rates affect the sensitivity of cost-effectiveness ratio to model choice. Copyright © 2009 John Wiley & Sons, Ltd. [source] Molecular dynamics simulation of self-diffusion coefficient and its relation with temperature using simple Lennard-Jones potentialHEAT TRANSFER - ASIAN RESEARCH (FORMERLY HEAT TRANSFER-JAPANESE RESEARCH), Issue 2 2008Li Wei-Zhong Abstract The diffusion coefficient is indispensable to chemical engineering design and research. In practical engineering and research, there is still a great lack of available data. Therefore, methods need to be developed to solve this problem. In this paper, a molecular dynamics simulation method is used to predict the self-diffusion coefficient for a simple fluid by using the Green, Kubo relation (VACF) and the Einstein relation (MSD). The simulation results are in good agreement with experimental findings except for an error of about 10%. The algorithm average of the two methods (AV) reduces the error to 7%. The relationship of the diffusion coefficient with temperature has also been simulated. According to the simulation data, whose correlation is all above 0.99, the diffusion coefficient agrees well with temperature following the Arrenhius relationship. Activation energy for self-diffusion has been calculated and the result were 1258(VACF), 1272(MSD), and 1265(AV) J/mol separately. © 2008 Wiley Periodicals, Inc. Heat Trans Asian Res, 37(2): 86,93, 2008; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/htj.20191 [source] Mothers' Trait Verbal Aggressiveness as a Predictor of Maternal and Child Behavior During Playtime InteractionsHUMAN COMMUNICATION RESEARCH, Issue 3 2008Steven R. Wilson This article explores associations between mothers' trait verbal aggressiveness (VA) and maternal and child behavior during playtime interactions. Forty mothers completed a 10-minute play period with one of their children (range = 3,8 years) and then responded to D. A. Infante and C. J. Wigley's (1986) trait VA scale. Mothers' trait VA was associated positively (r = .48) with their rate of directing and inversely (r =,.44) with their child's rated cooperation. Qualitative analyses of a subset (n = 8) of interactions suggest that mothers high in trait VA used directives to control the choice, rate, and duration of activities, and used physical negative touch along with directives, more than low-VA mothers. Behaviors associated with trait VA occur even during brief mother,child interactions in which triggers for aggressive behavior largely are absent. Résumé Le trait d,agressivité verbale des mères comme variable explicative des comportements maternels et infantiles lors d'interactions de jeu Cet article explore les associations entre le trait d,agressivité verbale (AV) des mères et le comportement maternel et infantile lors d'interactions de jeu. 40 mères ont participéà une période de jeu de 10 minutes avec l,un de leurs enfants (tranche d'âge = 3-8 ans) puis ont répondu à l'échelle de trait d'AV d,Infante et Wigley (1986). Le trait d'AV des mères fut associé positivement (r= 0,48) à leur taux de contrôle et inversement (r= -0,44) au taux de coopération de leur enfant. Des analyses qualitatives d,un sous-ensemble (n= 8) d'interactions donnent à penser que les mères au trait d,AV élevé ont fait usage de directives pour contrôle le choix, le rythme et la durée des activités et qu'elles ont utilisé le toucher physique négatif en même temps que les directives, plus que ne l,ont fait les mères au trait d'AV faible. Les comportements associés au trait d'AV surviennent même lors de brèves interactions mère-enfant au cours desquelles les déclencheurs de comportements agressifs étaient largement absents. Abstract Das Müttermerkmal verbale Aggression als Prädiktor für Mutter-Kind-Verhalten in spielerischen Interaktionen Dieser Artikel untersucht den Zusammenhang zwischen dem Müttermerkmal verbale Aggression (VA) und dem Mutter-Kind-Verhalten in spielerischen Interaktionen. 40 Mütter spielten 10 Minuten lang mit einem ihrer Kinder (zwischen 3-8 Jahren) und beantworteten dann die VA-Eigenschaftsskala nach Infante & Wigley (1986). Das Müttermerkmal VA war positiv assoziiert (r= .48) mit der Häufigkeit des führenden Eingreifens und umgekehrt assoziiert (r= -.44) mit der vom Kind beurteilten Kooperation. Qualitative Analysen eines Teils (n= 8) der Interaktionen deuten darauf hin, dass Mütter mit hoher VA führendes Eingreifen nutzen, um die Wahl, Häufigkeit und Dauer von Aktivitäten zu kontrollieren. Sie nutzten außerdem häufiger physisch negative Berührungen zusammen mit dem führenden Eingreifen als Mütter mit niedriger VA. Mit dem Merkmal VA verbundene Verhaltensweisen finden sogar in kurzen Mutter-Kind-Interaktionen statt bei denen Auslöser für aggressives Verhalten weitestgehend fehlen. Resumen El Rasgo de la Agresividad Verbal de las Madres como Vaticinador del Comportamiento Materno y del Niño Durante las Interacciones en el Recreo Este artículo explora la asociación entre el rasgo de agresividad verbal de las madres (VA) y el comportamiento maternal y del niño durante las interacciones en el recreo. Cuarenta madres completaron un período de 10-minutos de juego con uno de sus hijos (oscilando = 3-8 años) y luego respondieron a la escala sobre el rasgo VA de Infante y Wigley (1986). El rasgo VA de las madres fue asociado positivamente (r= .48) con el grado de direccionamiento e inversamente (r= -.44) con el grado de cooperación de su niño. Los análisis cualitativos de un subset (n= 8) de interacciones sugieren que las madres con rasgos altos de VA usaron directivas para controlar la selección, el tipo, y la duración de las actividades, y usaron el contacto físico negativo junto con directivas, más que las madres con rasgos bajos de VA. Los comportamientos asociados con el rasgo VA durante las interacciones breves entre la madre y su niño que provocan el comportamiento agresivo se encuentran mayormente ausentes. ZhaiYao Yo yak [source] Electrophysiologic characteristics and radiofrequency ablation of focal atrial tachycardia arising from para-Hisian regionINTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 3 2007Y. Zhou Summary This study describes the electrophysiologic characteristics and radiofrequency ablation of focal atrial tachycardia (AT) arising from para-Hisian region in 14 (6.0%) patients of a consecutive series of 224 patients patients. Inverted or biphasic P wave in V1 and uncharacteristic P wave in inferior leads were observed during tachycardia, suggesting that there isn't a characteristic P-wave morphology for para-Hisian AT. During electrophysiological study, tachycardia could be induced with programmed atrial extrastimuli in 11 patients while a spontaneous onset and offset with ,warm-up and cool-down' phenomenon were seen in other three patients. Moreover, the tachycardias were sensitive to intravenous administration of adenosine triphosphate in all patients. On the basis of these findings, the mechanism is suggestive of triggered activity or micro-reentry, but automaticity cannot be conclusively excluded. Radiofrequency energy was delivered to the earliest site of atrial activation during AT. Ablating energy was carefully titrated, starting at 5 W and increasing gradually upto a maximum of 40 W, to achieve the ceasing of tachycardia. The long-term outcome was a 100% success rate in these 14 patients and there were no irreversible complications associated with ablation. Thus, the mapping and ablation of focal AT arising from para-Hisian region is safe and effective, delivery of radiofrequency energy in a titrated manner and continuous monitoring of atrioventricular (AV) conduction advocated to minimise the risk of damage to the anterograde AV conduction. [source] Second-degree atrioventricular block (Mobitz Type I) in an adolescent with anorexia nervosa: Intrinsic or acquired conduction abnormalityINTERNATIONAL JOURNAL OF EATING DISORDERS, Issue 6 2009Nuray Ö. Kanbur MD Abstract Anorexia nervosa (AN) can cause both functional and structural cardiac complications, including a variety of different conduction abnormalities. This is the first case report of symptomatic diurnal second-degree atrioventricular (AV) block (Mobitz Type I) in an adolescent with AN. We present a 12-year-old girl with AN, restrictor sub-type who reported cardiac symptoms during weight gain, at the time of the initial diagnosis of AV block. Second-degree AV block (Mobitz Type I) is discussed as a possible complication of the AN, as well as being an intrinsic conduction system disease. © 2009 by Wiley Periodicals, Inc. Int J Eat Disord 2009 [source] Early Hemodynamic Results of the Shelhigh SuperStentless Aortic BioprosthesesJOURNAL OF CARDIAC SURGERY, Issue 5 2007Paolo Cattaneo M.D. The aim of the study was to evaluate the early hemodynamic performance of the Shelhigh SuperStentless aortic valve (AV). Methods: Between July 2003 and June 2005, 35 patients (18 females; age 70.8 ± 11.7 years, range: 22-85) underwent AV replacement with the Shelhigh SuperStentless bioprostheses. Most recurrent etiology was senile degeneration in 25 (71%) patients and 24 (69%) were in New York Heart Association (NYHA) functional class III or IV. Concomitant coronary artery bypass grafting was performed in nine patients (25.7%) and mitral valve surgery in two patients (5.7%). Doppler echocardiography was performed before surgery, at six-month and one-year follow-up. Results: There were no hospital deaths and no valve-related perioperative complications. During one-year follow-up, no endocarditis or thromboembolic events were registered, no cases of structural dysfunction or valve thrombosis were noted. Mean and peak transvalvular gradients significantly decrease after AV replacement, with an evident reduction to approximately 50% of the preoperative values at six months. A 20% reduction was also observed for left ventricular mass (LVM) index at six months, with a further regression at one year. Correspondingly, significant increases in effective orifice area (EOA) and indexed EOA were determined after surgery (0.87 ± 0.14 versus 1.84 ± 0.29 cm2 and 0.54 ± 0.19 versus 1.05 ± 0.20 cm2/m2, respectively). Valve prosthesis-patient mismatch was moderate in five patients and severe in one case. Conclusions: Shelhigh SuperStentless AV provided good and encouraging hemodynamic results. Long-term follow-up is necessary to evaluate late hemodynamic performance and durability of this stentless bioprosthesis. [source] Repair of Partial Atrioventricular Septal Defect Through a Minimal Right Vertical Infra-Axillary ThoracotomyJOURNAL OF CARDIAC SURGERY, Issue 3 2002Xiubin Yang M.D. Methods: From November 1997 to January 2000, six patients with a mean age of 19.2 ± 7.7 years underwent minimal right vertical infraaxillary thoracotomy (VIAT) for PAVSD repair. Left atrioventricular (AV) valve regurgitation was tested on the beating heart before and after valvuloplasty. Commissuroplasty of the left AV valve and atrial septum repair were done in all patients. Results: There was no operative or late mortality, and no morbidity directly related to the thoracotomy approach. The average length of the incision was 8.3 ± 1.3 cm. The arrest times averaged 32.8 ± 8.3 minutes, and the cardiopulmonary bypass times averaged 66.0 ± 9.0 minutes. One patient had mild-to-moderate left AV valve regurgitation postoperatively. All patients were free of symptoms during follow-up. Conclusion: Minimal right VIAT is a safe, more cosmetic, and less invasive approach than median sternotomy for the repair of PAVSD. [source] Malignant Ventricular Arrhythmia in a Case of Adult Onset of Spinal Muscular Atrophy (Kugelberg,Welander Disease)JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 3 2009MARKUS ROOS M.D. We present a case of a 43-year-old male patient with adult onset of spinal muscular atrophy (SMA). The patient first came to our attention with atrioventricular (AV) block. A dual-chamber pacemaker (DDD-PM) was implanted. Four years later, the PM data log showed occurrence of frequent episodes of nonsustained ventricular tachycardia (NSVT). The episodes progressed in duration and frequency. An electrophysiological study revealed prolonged His-ventricular (HV) interval duration and induction of sustained ventricular tachycardia. The patient was successfully upgraded to a prophylactic dual-chamber cardioverter defibrillator. Our case is the first description of a patient with adult-onset SMA (Kugelberg,Welander disease [KWD]) and malignant ventricular arrhythmias. [source] Age- and Genotype-Specific Triggers for Life-Threatening Arrhythmia in the Genotyped Long QT SyndromeJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 8 2008TOMOKO SAKAGUCHI M.D. Introduction: Patients with long QT syndrome (LQTS) become symptomatic in adolescence, but some become at age of ,20 years. Since it remains unknown whether clinical features of symptomatic LQTS patients differ depending on the age of onset, we aimed to examine whether triggers for cardiac events are different depending on the age in genotyped and symptomatic LQTS patients. Methods and Results: We identified 145 symptomatic LQTS patients, divided them into three groups according to the age of first onset of symptoms (young <20, intermediate 20,39, and older ,40 years), and analyzed triggers of cardiac events (ventricular tachycardia, syncope, or cardiac arrest). The triggers were divided into three categories: (1) adrenergically mediated triggers: exercise, emotional stress, loud noise, and arousal; (2) vagally mediated triggers: rest/sleep; and (3) secondary triggers: drugs, hypokalemia, and atrioventricular (AV) block. In the young group, 78% of the cardiac events were initiated by adrenergically mediated triggers and 22% were vagally mediated, but none by secondary triggers. In contrast, the adrenergically mediated triggers were significantly lower in the intermediate group. The percentage of secondary triggers was significantly larger in the older group than in the other two groups (0% in young vs 23% in intermediate vs 72% in older; P < 0.0001). Concerning the subdivision of secondary triggers on the basis of genotype, hypokalemia was only observed in LQT1, drugs mainly in LQT2, and AV block only in LQT2. Conclusion: Arrhythmic triggers in LQTS differ depending on the age of the patients, stressing the importance of age-related therapy for genotyped LQTS patients. [source] Time and Temperature Profile of Catheter Cryoablation of Right Septal and Free Wall Accessory Pathways in ChildrenJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 4 2008JONATHAN R. KALTMAN M.D. Introduction: The overall acute success with cryoablation for accessory pathways (APs) has been reported to be lower than with radiofrequency ablation. Generally, prior cryomapping (limited to ,30°C) has been used to test for loss of AP conduction and absence of atrioventricular (AV) node impairment. However, the temperature at which loss of AP conduction occurs may be variable. The purpose of this study was to evaluate the time and temperature profile at which loss of AP conduction occurs. Methods and Results: A retrospective study evaluated 25 patients (mean age 13.3 ± 3.6 years) who underwent cryoablation for right-sided APs (22 manifest/3 concealed). Direct cryoablation (,80°C) without cryomapping was performed using a "time to success" strategy. If AP conduction was successfully interrupted within 25 seconds of the onset of cryoablation, the lesion was continued for 240 seconds; otherwise it was terminated and further mapping was performed. Cryoablation was successful in 24/25 (96%) patients. Temperature at loss of AP conduction was ,66.2 ±,16.7°C (range +32 to ,84°C) with conduction block at temperatures lower than ,30°C for all but 3 APs. Critical time to success (interval from cryoadherence to loss of AP conduction) was significantly shorter for permanently successful cryolesions, compared with transiently successful lesions (6.3 ± 4.1 vs. 11.2 ± 2.2 sec; P < 0.001). There were no major complications. Conclusions: Cryothermal energy required for successful ablation may be variable and restricting test applications to ,30°may limit its efficacy. A "time to success" strategy may improve outcome of cryoablation for right-sided APs in children without compromising safety. [source] Biventricular Versus Right Ventricular Pacing in Patients with AV Block (BLOCK HF): Clinical Study Design and RationaleJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 9 2007ANNE B. CURTIS M.D. Background: Right ventricular (RV) pacing restores ventricular systole in patients with atrioventricular (AV) block, yet recent studies have suggested that in patients with AV block and left ventricular (LV) dysfunction, RV pacing may exacerbate the progression to heart failure (HF). BLOCK HF is a prospective, multi-center, randomized, double-blind, controlled trial designed to determine whether patients with AV block, LV dysfunction (EF , 50%), and mild to moderate HF (NYHA I-III) who require pacing benefit from biventricular (BiV) pacing, compared with RV pacing alone. Objective: The primary objective of this trial is to determine whether the time to first event (all-cause mortality, heart failure-related urgent care, or a , 15% increase in left ventricular end systolic volume index [LVESVI]) for patients with BiV pacing is superior to that of patients with RV pacing. Methods: Patients with AV block and LV dysfunction who require permanent pacing and undergo successful implantation of a commercial Medtronic CRT device, with or without an ICD, will be randomized to BiV or RV pacing. Patients are followed at least every 6 months until study closure. Up to 1,636 patients may be enrolled in 150 centers worldwide. Conclusion: BLOCK HF is a large, randomized, clinical study in pacing-indicated patients with AV block, mild to moderate HF symptoms, and LV dysfunction to determine whether BiV pacing is superior to RV pacing in slowing the progression of HF. [source] | ||||||||||||||||||||||||||||||||||||||||||||||