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Terms modified by MJ Selected AbstractsOverexpression of CD49f in precursor B-cell acute lymphoblastic leukemia: Potential usefulness in minimal residual disease detectionCYTOMETRY, Issue 2 2009Joseph A. DiGiuseppe Abstract Background: The persistence of minimal residual disease (MRD) following therapy is an established prognostic factor in precursor B-cell acute lymphoblastic leukemia (pB-ALL). Detection of MRD in pB-ALL by flow cytometric immunophenotyping requires demonstration of abnormal antigen expression in leukemic B-cell precursors relative to that of normal B-cell precursors. The gene encoding CD49f (integrin ,-6) is one of several whose overexpression in pB-ALL at diagnosis has been associated with the subsequent detection of MRD. However, whether CD49f might be a useful reagent in the immunophenotypic detection of MRD in pB-ALL has not been evaluated. Methods: We evaluated CD49f expression by 4-color flow cytometry in normal B-cell precursors, and in a series of cases of pB-ALL, both at diagnosis and at intervals following the initiation of therapy. Results: In 10 control marrow samples, CD49f was undetectable or extremely dim in all but a minor subset of normal CD19+ B-lineage cells, whereas in 11 of 15 cases (73%) of pB-ALL, CD49f was moderate or bright at diagnosis, and persisted or became brighter after initiation of therapy. MRD detected using CD49f corresponded precisely with that obtained using a standard panel of antibodies, and permitted the detection of leukemic populations comprising as little as 0.02% of cells. Of the four pB-ALL cases in which CD49f was undetectable or dim at diagnosis, MRD was detected in two; in one of these, CD49f expression was substantially increased in the leukemic cells that persisted following initiation of therapy. Conclusions: CD49f is commonly overexpressed in p-B-ALL, and represents a potentially useful marker for the immunophenotypic detection of MRD. © 2008 Clinical Cytometry Society How to cite this article: DiGiuseppe JA, Fuller SG, Borowitz MJ. Overexpression of CD49f in precursor B-cell acute lymphoblastic leukemia: potential usefulness in minimal residual disease detection. Cytometry Part B 2008. [source] Protein methylation in full length Chlamydomonas flagellaCYTOSKELETON, Issue 8 2009Roger D. Sloboda Abstract Post-translational protein modification occurs extensively in eukaryotic flagella. Here we examine protein methylation, a protein modification that has only recently been reported to occur in flagella [Schneider MJ, Ulland M, Sloboda RD.2008. Mol Biol Cell 19(10):4319,4327.]. The cobalamin (vitamin B12) independent form of the enzyme methionine synthase (MetE), which catalyzes the final step in methionine production, is localized to flagella. Here we demonstrate, using immunogold scanning electron microscopy, that MetE is bound to the outer doublets of the flagellum. Methionine can be converted to S-adenosyl methionine, which then serves as the methyl donor for protein methylation reactions. Using antibodies that recognize symmetrically or asymmetrically methylated arginine residues, we identify three highly methylated proteins in intact flagella: two symmetrically methylated proteins of about 30 and 40 kDa, and one asymmetrically methylated protein of about 75 kDa. Several other relatively less methylated proteins could also be detected. Fractionation and immunoblot analysis shows that these proteins are components of the flagellar axoneme. Immunogold thin section electron microscopy indicates that the symmetrically methylated proteins are located in the central region of the axoneme, perhaps as components of the central pair complex and the radial spokes, while the asymmetrically methylated proteins are associated with the outer doublets. Cell Motil. Cytoskeleton 2009. © 2009 Wiley-Liss, Inc. [source] Neural correlates of movement generation in the ,at-risk mental state'ACTA PSYCHIATRICA SCANDINAVICA, Issue 4 2010M. R. Broome Broome MR, Matthiasson P, Fusar-Poli P, Woolley JB, Johns LC, Tabraham P, Bramon E, Valmaggia L, Williams SCR, Brammer MJ, Chitnis X, McGuire PK. Neural correlates of movement generation in the ,at-risk mental state'. Objective:, People with ,prodromal' symptoms have a very high risk of developing psychosis. We examined the neurocognitive basis of this vulnerability by using functional MRI to study subjects with an at-risk mental state (ARMS) while they performed a random movement generation task. Method:, Cross-sectional comparison of individuals with an ARMS (n = 17), patients with first episode schizophreniform psychosis (n = 10) and healthy volunteers (n = 15). Subjects were studied using functional MRI while they performed a random movement generation paradigm. Results:, During random movement generation, the ARMS group showed less activation in the left inferior parietal cortex than controls, but greater activation than in the first episode group. Conclusion:, The ARMS is associated with abnormalities of regional brain function that are qualitatively similar to those in patients who have recently presented with psychosis but less severe. [source] Sustained attention as a potential endophenotype for bipolar disorderACTA PSYCHIATRICA SCANDINAVICA, Issue 3 2010I. Ancín Ancín I, Santos JL, Teijeira C, Sánchez-Morla EM, Bescós MJ, Argudo I, Torrijos S, Vázquez-Álvarez B, De La Vega I, López-Ibor JJ, Barabash A, Cabranes-Díaz JA. Sustained attention as a potential endophenotype for bipolar disorder. Objective:, Nowadays, it is accepted that to identify the biological basis of psychiatric illnesses it would be useful to deconstruct them into the most basic manifestations, such as cognitive deficits. The aim of this study was to set attention deficit as a stable vulnerability marker of bipolar disorder. Method:, Sustained attention was evaluated by the Continuous Performance Test (DS-CPT) in 143 euthymic bipolar patients and 105 controls. To estimate the influence of clinical profile in attention, patients completed a semi-structured interview. Results:, Bipolar patients showed a deficit in attention during euthymic periods. This disturbance correlated with years of evolution, age of onset and age of first hospitalisation; and was not influenced by other clinical data. Conclusion:, Sustained attention may be considered as an endophenotype of the illness. [source] Prescription drug misuse: Is technology friend or foe?DRUG AND ALCOHOL REVIEW, Issue 1 2009SUZANNE NIELSEN Abstract Introduction and Aims. Prescription drug misuse and related harms have been increasing considerably over the past decade. At the same time, there has also been rapid growth in the use of online and Internet technologies. Thus, it is important that we understand the role online and Internet technologies play in prescription drug misuse. Design and Methods. Published work addressing the role of technology in prescription drug misuse is explored. Topics include: Internet supply, online monitoring of prescription drug use trends and electronic prescription monitoring. Results. Little is known about the prevalence of acquiring prescription drugs from online pharmacies. Prescription drugs are easily accessible through vendor websites, and ,rogue' no-prescription websites have proven difficult to control. There has so far been limited application of real-time monitoring to prevent overuse of prescription medications. Online monitoring of drug use trends may also prove to be a useful and timely source of information about new methods of ,off-label' prescription drug use. Discussion and Conclusions. Technology has the potential to play a more prominent role in facilitating drug acquisition, while also enhancing the monitoring and prevention of prescription drug misuse. As technology becomes more ubiquitous in everyday life, the continued investigation of its relationship with prescription drug misuse becomes even more important.[Nielsen S, Barratt MJ. Prescription drug misuse: Is technology friend or foe? Drug Alcohol Rev 2009;28:81,86] [source] Impact of chemical elicitor applications on greenhouse tomato plants and population growth of the green peach aphid, Myzus persicaeENTOMOLOGIA EXPERIMENTALIS ET APPLICATA, Issue 3 2006Anthony J. Boughton Abstract Recent advances in the understanding of plant signaling pathways have opened the way for using elicitor-induced plant resistance as a tactic for protecting plants against arthropod pests. Four common elicitors of induced responses in tomato, Lycopersicon esculentum Mill. (Solanaceae), were evaluated with regard to phytotoxicity, induction of plant defensive proteins, and effects on population growth and fecundity of a common pest, the green peach aphid, Myzus persicae (Sulzer) (Homoptera: Aphididae). Ethephon and methyl jasmonate (MJ) treatments caused varying degrees of phytotoxicity. Ethephon caused pronounced changes in plant growth form and severe, dose-dependent negative impacts on plant growth and flowering. Effects with MJ were milder, but still caused temporary inhibition of development, leading to smaller plants and delayed flowering. The commercial elicitors benzothiadiazole (BTH) and harpin did not cause detectable phytotoxicity. The highest doses of ethephon and MJ significantly increased leaf peroxidase (POD) levels but only MJ treatments significantly increased polyphenol oxidase (PPO) levels. BTH and harpin had no detectable effects on POD and PPO. Populations of green peach aphids grew significantly more slowly on plants treated with BTH or MJ than on control plants or plants treated with harpin or ethephon. Slowed aphid population growth on BTH-treated plants was due to significant reductions in aphid fecundity, although this was independent of changes in time to onset of reproduction or time to death. Aphid fecundity was also reduced on MJ-treated plants relative to controls, but this difference was not statistically significant, suggesting that other mechanisms are involved in slowing aphid population growth on MJ-treated plants. Growth of aphid populations on plants treated with a MJ,BTH mixture was reduced almost as much as with treatments of MJ alone, suggesting that antagonism between JA-dependant and SA-dependent plant signaling pathways is only mild with regard to induced defenses against aphids. [source] Iron status in Danish men 1984,94: a cohort comparison of changes in iron stores and the prevalence of iron deficiency and iron overloadEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 6 2002Nils Milman Abstract:,Background and objectives : From 1954 to 1987, flour in Denmark was fortified with 30 mg carbonyl iron per kg. This mandatory fortification was abolished in 1987. The aim of this study was to compare iron status in Danish men before and after abolition of iron fortification. Methods : Iron status (serum ferritin, haemoglobin), was assessed in population surveys in Copenhagen County during 1983,84 comprising 1324 Caucasian men (1024 non-blood-donors, 300 blood donors) and in 1993,94 comprising 1288 Caucasian men (1103 non-blood-donors, 185 donors), equally distributed in age cohorts of 40, 50, 60 and 70 yr. Results : In the 1984 survey median serum ferritin values in the four age cohorts in non-blood-donors were 136, 141, 133 and 111 µg/L, and in the 1994 survey 177, 173, 186 and 148 µg L ,1 , respectively. The difference was significant in all age groups ( P <0.001). There was no significant difference between the two surveys concerning the prevalence of small iron stores (ferritin 16,32 µg L ,1 ), depleted iron stores (ferritin <16 µg L ,1 ) or iron-deficiency anaemia (ferritin <13 µg L ,1 and Hb <5th percentile for iron-replete men). However, from 1984 to 1994, the prevalence of iron overload (ferritin >300 µg L ,1 ) increased from 11.3% to 18.9% ( P <0.0001). During the study period there was an increase in body mass index ( P <0.0001), alcohol consumption ( P <0.03) and use of non-steroid anti-inflammatory drugs (NSAID) ( P <0.0001), and a decrease in the use of vitamin,mineral supplements ( P <0.04) and in the prevalence of tobacco smoking ( P <0.0001). In contrast, median ferritin in blood donors showed a significant fall from 1984 to 1994 (103 vs. 74 µg L ,1 , P <0.02). Conclusion : Abolition of iron fortification reduced the iron content of the Danish diet by an average of 0.24 mg MJ ,1 , and the median dietary iron intake in men from 17 to 12 mg d ,1 . From 1984 to 1994, body iron stores and the prevalence of iron overload in Danish men increased significantly, despite the abolition of food iron fortification. The reason appears to be changes in dietary habits, with a lower consumption of dairy products and eggs, which inhibit iron absorption, and a higher consumption of alcohol, meat, and poultry, containing haem iron and enhancing iron absorption. The high prevalence of iron overload in men may constitute a health risk. [source] IMAGING STUDY: Prefrontal cortex morphometry in abstinent adolescent marijuana users: subtle gender effectsADDICTION BIOLOGY, Issue 4 2009Krista Lisdahl Medina ABSTRACT Adult human studies suggest frontal dysfunction associated with chronic marijuana (MJ) use, but due to continued neuromaturation, adult studies may not generalize to adolescents. This study characterized prefrontal cortex (PFC) morphometry in chronic MJ-using adolescents following 1 month of monitored abstinence. Data were collected from MJ users (n = 16) and controls (n = 16) aged 16,18. Extensive exclusionary criteria included co-morbid psychiatric and neurologic disorders. Substance use and anatomical measures were collected after 28 days of monitored abstinence. PFC volumes were ascertained from manual tracing by reliable raters on high-resolution magnetic resonance images. After controlling for lifetime alcohol use, gender and intracranial volume, MJ users did not differ from controls in PFC volume. However, marginal group-by-gender interactions were observed (P < 0.09): female MJ users demonstrated comparatively larger PFC volumes while male MJ users had smaller volumes compared with same-gender controls. Further, group status and total PFC volume interacted in predicting executive functioning (P < 0.05). Among MJ users, smaller PFC total volume was associated with better executive functioning while the opposite pattern was seen among the controls. These preliminary results indicate that gender may moderate the relationship between MJ use and PFC morphometry. Given the relationship between larger PFC total volumes and poorer executive functioning among MJ users, female MJ users may be at increased risk for neurocognitive consequences. Future research will measure PFC gray and white matter separately and follow boys and girls over adolescence to examine the influence of MJ use on neurodevelopment. [source] Enamel microhardness and bond strengths of self-etching primer adhesivesEUROPEAN JOURNAL OF ORAL SCIENCES, Issue 2 2010Olabisi A. Adebayo Adebayo OA, Burrow MF, Tyas MJ, Adams GG, Collins ML. Enamel microhardness and bond strengths of self-etching primer adhesives. Eur J Oral Sci 2010; 118: 191,196. © 2010 The Authors. Journal compilation © 2010 Eur J Oral Sci The aim of this study was to determine the relationship between enamel surface microhardness and microshear bond strength (,SBS). Buccal and lingual mid-coronal enamel sections were prepared from 22 permanent human molars and divided into two groups, each comprising the buccal and lingual enamel from 11 teeth, to analyze two self-etching primer adhesives (Clearfil SE Bond and Tokuyama Bond Force). One-half of each enamel surface was tested using the Vickers hardness test with 10 indentations at 1 N and a 15-s dwell time. A hybrid resin composite was bonded to the other half of the enamel surface with the adhesive system assigned to the group. After 24 h of water storage of specimens at 37ş°C, the ,SBS test was carried out on a universal testing machine at a crosshead speed of 1 mm min,1 until bond failure occurred. The mean ,SBS was regressed on the mean Vickers hardness number (VHN) using a weighted regression analysis in order to explore the relationship between enamel hardness and ,SBS. The weights used were the inverse of the variance of the ,SBS means. Neither separate correlation analyses for each adhesive nor combined regression analyses showed a significant correlation between the VHN and the ,SBS. These results suggest that the ,SBS of the self-etch adhesive systems are not influenced by enamel surface microhardness. [source] Using an airgun array in a land reservoir as the seismic source for seismotectonic studies in northern China: experiments and preliminary resultsGEOPHYSICAL PROSPECTING, Issue 4 2008Yong Chen ABSTRACT This paper reports the field setup and preliminary results of experiments utilizing an airgun array in a reservoir in north China for a seismotectonic study. Commonly used in offshore petroleum resource exploration, the airgun source was found to be more useful than a traditional explosive source for large-scale and long offset land seismic surveys. The airgun array, formed by four 1,500 in3 airguns (a total of 6,000 in3 in volume) was placed at a depth of 6,9 m into the reservoir to generate the pressure impulse. No direct evidence was found that the airgun source adversely affected the fish in the reservoir. The peak ground acceleration recorded on the top of the reservoir dam 100 m away was 17.8 gal in the horizontal direction; this is much less than the designed earthquake-resistance threshold of 125 gal for this dam. The energy for one shot of this airgun array is about 6.68 MJ, equivalent to firing a 1.7 kg explosive. The seismic waves generated by the airgun source were recorded by receivers of the regional seismic networks and a temporary wide-angle reflection and refraction profile formed by 100 short-period seismometers with the maximum source-receiver offset of 206 km. The seismic wave signature at these long-offset stations is equivalent to that generated by a traditional blast source in a borehole with a 1,000,2,000 kg explosive. Preliminary results showed clear seismic phases from refractions from the multi-layer crustal structures in the north China region. Forward modelling using numerical simulation confirms that the seismic arrivals are indeed from lower crustal interfaces. The airgun source is efficient, economical, environmentally friendly and suitable for being used in urbanized areas. It has many advantages over an explosive source for seismotectonic studies such as the high repeatability that is supreme for stacking to improve signal qualities. The disadvantage is that the source is limited to existing lakes or reservoirs, which may restrict experimental geometry. [source] Cluster headache: the challenge of clinical trials.HEADACHE, Issue 3 2003K Moore Curr Pain Headache. Rep 2002 Feb;6(1):52-56 The design and execution of clinical trials poses special problems for cluster headache. Although there is less inter-individual and intra-individual variability of attacks than seen with migraine, the brevity of attacks, spontaneous remissions unrelated to treatment, and the relative rarity of cluster headaches challenge investigators. The International Headache Society has developed guidelines that represent a compromise between scientific rigor and practicality. Only injectable sumatriptan for acute attacks and verapamil for prophylaxis have demonstrated a robust therapeutic effect in controlled clinical trials. Comment: Kenneth Moore raises important methodological considerations. It is possible to undertake crossover trials comparing different active treatments? He is correct in his assertion that few agents show robust efficacy. A major issue relates to the proportion of patients with episodic versus chronic cluster headache where efficacy of active treatments can vary. For example, oral zolmitriptan was effective against placebo only in those patients with episodic disease (Bahra A, Gawel MJ, Hardebo JE, Millson DS, Breen SA, Goadsby PJ. Oral zolmitriptan is effective in the acute treatment of cluster headache. Neurology. 2000;54:1832-1839). And a set of small studies on melatonin and cluster demonstrate the problems Dr. Moore describes. In one study (Leone M, D'Amico D, Moschiano F, Fraschini F, Busonne G. Metalonin versus placebo in the prophylaxis of cluster headache: a double-blind pilot study with parallel groups. Cephalalgia. 1996;16:494-496), the melatonin worked only in episodic, not chronic cluster patients. In the second study (Prinsheim T, Magnoux E, Dobson CF, Hamel E, Aube M. Melatonin as adjuctive therapy in the prophylaxis of cluster headache: a pilot study. Headache. 2002;42:787-792), melatonin did not work better than placebo in either episodic or chronic cluster patients. Furthermore, the paper abstracted above by Torelli and Manzoni suggests that episodic cluster may progress to chronic cluster as a result of extrinsic factors such as smoking. Finally, there are ethical issues in placebo-controlled cluster studies, given the severity of the pain and the availability of effective acute and chronic treatments. As noted above, Dr. Peter Goadsby points out the need to persevere with these studies to find nonvasoactive treatments for patients with cluster headache. DSM and SJT [source] Neuropsychological correlates of hippocampal and rhinal cortex volumes in patients with mesial temporal sclerosisHIPPOCAMPUS, Issue 8 2003Catherine E. O'Brien Abstract Considerable progress has been made toward understanding the function of the primate rhinal cortex, comprising the entorhinal (ErC) and perirhinal (PrC) cortices. However, translating animal models to human memory has been limited by the technological problems associated with characterizing neural structures in vivo. Functional correlates of hippocampal and rhinal cortex volume changes were examined in a sample of 61 temporal lobe epilepsy patients with mesial temporal sclerosis (MTS; 33 left, 28 right). Patients were administered the Wechsler Adult Intelligence Scale (revised or third edition), the Wechsler Memory Scale (revised or third edition), and a spatial maze task. Neuropsychological data, together with rhinal cortex and hippocampal volumes, collected in our earlier study (O'Brien CE, Bowden SC, Whelan G, Cook MJ, unpublished observations), were analyzed using multiple regression. The only significant predictor of verbal memory function was the difference score between the volume of left hippocampus and the left PrC. Spatial maze scores were predicted by the bilateral sum of ErC volume. The difference score between the left hippocampus and left PrC volumes was the most powerful predictor of verbal episodic memory. Right hippocampal volume was not a significant predictor of nonverbal episodic memory. Verbal and nonverbal semantic memory were not significantly predicted by any combination of rhinal cortex structures. This quantitative study suggests a lateralized or material-specific memory function for the left hippocampus and left PrC, in contrast to the bilateral role of the ErC. The left hippocampus and left PrC appear to act on verbal memory function through an opposing relationship. Finally, differentiation between hippocampal and subhippocampal components in terms of episodic and semantic memory, respectively, could not be supported by the current data. © 2003 Wiley-Liss, Inc. [source] Spatial patterns of suspended sediment yields in a humid tropical watershed in Costa RicaHYDROLOGICAL PROCESSES, Issue 12 2001Jagdish Krishnaswamy Abstract An Erratum has been published for this article in Hydrological Processes 16(5) 2002, 1130,1131. Humid tropical regions are often characterized by extreme variability of fluvial processes. The Rio Terraba drains the largest river basin, covering 4767 km2, in Costa Rica. Mean annual rainfall is 3139±419sd mm and mean annual discharge is 2168±492sd mm (1971,88). Loss of forest cover, high rainfall erosivity and geomorphologic instability all have led to considerable degradation of soil and water resources at local to basin scales. Parametric and non-parametric statistical methods were used to estimate sediment yields. In the Terraba basin, sediment yields per unit area increase from the headwaters to the basin mouth, and the trend is generally robust towards choice of methods (parametric and LOESS) used. This is in contrast to a general view that deposition typically exceeds sediment delivery with increase in basin size. The specific sediment yield increases from 112±11·4sd t km,2 year,1 (at 317·9 km2 on a major headwater tributary) to 404±141·7sd t km,2 year,1 (at 4766·7 km2) at the basin mouth (1971,92). The analyses of relationships between sediment yields and basin parameters for the Terraba sub-basins and for a total of 29 basins all over Costa Rica indicate a strong land use effect related to intensive agriculture besides hydro-climatology. The best explanation for the observed pattern in the Terraba basin is a combined spatial pattern of land use and rainfall erosivity. These were integrated in a soil erosion index that is related to the observed patterns of sediment yield. Estimated sediment delivery ratios increase with basin area. Intensive agriculture in lower-lying alluvial fans exposed to highly erosive rainfall contributes a large part of the sediment load. The higher elevation regions, although steep in slope, largely remain under forest, pasture, or tree-crops. High rainfall erosivity (>7400 MJ mm ha,1 h,1 year ,1) is associated with land uses that provide inadequate soil protection. It is also associated with steep, unstable slopes near the basin mouth. Improvements in land use and soil management in the lower-lying regions exposed to highly erosive rainfall are recommended, and are especially important to basins in which sediment delivery ratio increases downstream with increasing basin area. Copyright © 2001 John Wiley & Sons, Ltd. [source] SEM evaluation of root canal debridement with Sonicare CanalBrush irrigationINTERNATIONAL ENDODONTIC JOURNAL, Issue 5 2010M. I. Salman Salman MI, Baumann MA, Hellmich M, Roggendorf MJ, Termaat S. SEM evaluation of root canal debridement with Sonicare CanalBrush irrigation. International Endodontic Journal, 43, 363,369, 2010. Abstract Aim, To determine the efficacy of Sonicare CanalBrush irrigation for root canal cleaning. Methodology, Fifty human molar root canals were shaped with sequential NiTi rotary instruments up to size F3 (size 30, 0.09 taper; ProTaper system) and then enlarged apically with a Profile size 40, 0.04 taper. Five different irrigation protocols were tested (n = 10 canals per group) with 2 mL of distilled water (control, group I) or 2.5% NaOCl (control group II and test groups III, IV and V) between instrument size changes. Group III,IV received a final rinse with 17% EDTA for one min. This was extended by 30 s in group IV, whereas group V received this additional 30 s of 17% EDTA sonically dispersed with a Sonicare CanalBrush. For cleanliness evaluations, roots were split longitudinally, examined with scanning electron microscopy and scored according to Hülsmann et al. (1997) for debris and smear layer on the surface of the root canal wall. Walls were assessed at the coronal, middle and apical thirds. Data were analysed with the Kruskal,Wallis and Mann,Whitney tests. Results, Irrigation with 17% EDTA significantly reduced debris and smear layer scores (P < 0.05) compared to controls. The coronal and middle thirds had lower debris and smear layer scores than the apical third (P < 0.05). In all thirds, sonic agitation of the irrigant with a CanalBrush (group V) resulted in significantly cleaner canal walls compared to all other groups (P < 0.05). Conclusions, Irrigation by agitation with the Sonicare CanalBrush improved root canal debridement in the coronal, middle and particularly the apical thirds of the root canal. [source] Micro-CT evaluation of residual material in canals filled with Activ GP or GuttaFlow following removal with NiTi instrumentsINTERNATIONAL ENDODONTIC JOURNAL, Issue 3 2010M. J. Roggendorf Roggendorf MJ, Legner M, Ebert J, Fillery E, Frankenberger R, Friedman S. Micro-CT evaluation of residual material in canals filled with Activ GP or GuttaFlow following removal with NiTi instruments. International Endodontic Journal, 43, 200,209, 2010. Abstract Aim, To assess the efficacy of removing Activ GP or GuttaFlow from canals using NiTi instruments. Methodology, Root canals in 55 extracted pre-molars were prepared to apical size 40, 0.04 taper. The teeth were imaged with micro-CT, and 30 teeth selected that had consistent apical size and taper of the shaped canals. They were randomly assigned to root filling with either the glass-ionomer-based ActivGP system (n = 15) or the polyvinylsiloxane-based GuttaFlow system (n = 15). After 2 weeks, canals were retreated stepwise with size 40,50 EndoSequence 0.04 taper instruments. Micro-CT scans (8 ,m) were taken after use of each instrument to detect root filling residue in the coronal, middle and apical segment, and the retreatment time recorded. Residue, expressed as percentage of canal surface area, was compared between groups with t -tests, and within groups with repeated measures anova and Bonferroni-adjusted pairwise comparisons. Retreatment time was analysed with one-way anova. Results, The percentage of sealer residue-coated canal surface was consistently highest (P < 0.001) in the apical third of canals, and it did not differ significantly between the two root filling groups. Stepwise enlargement from size 40 to 50 significantly decreased the amount of sealer residue in both groups (P < 0.001). Retreatment time did not differ significantly between groups. Conclusions, Both root fillings with ActivGP and GuttaFlow were removed with nickel-titanium rotary instruments. Enlargement of canals up to two sizes beyond the pre-retreatment size was necessary to minimize the amount of sealer remaining. [source] Efficiency analysis of a combined PEFC and bioethanol-solar-reforming system for individual housesINTERNATIONAL JOURNAL OF ENERGY RESEARCH, Issue 7 2010Shin'ya Obara Abstract In this research, the development of a bioethanol reforming system for fuel cells (FBSR: fuel cell with bioethanol steam reforming) using sunlight as a heat source was investigated. The system was investigated using the experimental result of catalyst performance, and numerical analysis. If ethanol purity is high, the production method of the bioethanol used for the proposal system will not be limited. The overall efficiency of the production of electricity and heat power of this system was determined by examining its thermal output characteristic. The FBSR was introduced into standard individual houses in Sapporo, Japan, for analysis. The amount of hydrogen production, the production-of-electricity characteristic, and the thermal output characteristic were examined using meteorological data on representative days in March and August. Compared with the representative day in March (28.0,MJ,day,1), the solar radiation of the representative day in August (37.0,MJ,day,1) is large. However, the amount of solar radiation fluctuation of the representative day in August in this analysis is large compared with the representative day in March. It depends for the overall efficiency of the system on the amount of solar radiation fluctuation rather than the amount of solar radiation. As a result, the overall efficiency of the system, defined as the rate of power and heat output compared with the amount of solar heat collected, was calculated to be 47.4 and 41.9% on the representative days in March and August, respectively. Copyright © 2009 John Wiley & Sons, Ltd. [source] Operating schedule of a combined energy network system with fuel cellINTERNATIONAL JOURNAL OF ENERGY RESEARCH, Issue 13 2006S. ObaraArticle first published online: 16 MAY 200 Abstract The chromosome model showing system operation pattern is applied to GA (genetic algorithm), and the method of optimization operation planning of energy system is developed. The optimization method of this operation planning was applied to the compound system of methanol-steam-reforming-type fuel cell, geothermal heat pump and the electrolysis tank of water. The operation planning was performed for the energy system using the energy demand pattern of the individual residence of Sapporo city. From analysis results, the amount of outputs of a solar module and the relation of the operation cost of the system, which are changed by the weather were clarified. The representation day in February of the ratio of the operation cost in case of (0% of output rates) the rainy weather to the time of fine weather (100% of output rates) is 1.12. And the representation day in July is 1.71. Furthermore, the optimal capacity of accumulation of electricity and thermal storage was estimated, and they are 308 and 23 MJ, respectively. Copyright © 2006 John Wiley & Sons, Ltd. [source] Commentary on Vermeulen H, Ubbink DT, Schreuder SM and Lubbers MJ (2007) Inter- and intra-observer (dis)agreement among nurses and doctors to classify colour and exudation of open surgical wounds according to the Red,Yellow,Black scheme.JOURNAL OF CLINICAL NURSING, Issue 12 2008Journal of Clinical Nursing1, Kitagawa A (2007) A study of the efficiency, Konya C, Matsui Y, Okuwa M, Sanada H, Sugama J, convenience of an advanced portable wound measurement system (VISITRAKTM). [source] CYSTATIN ACCUMULATION IN TOMATO LEAVES AFTER METHYL JASMONATE TREATMENT OR MECHANICAL INJURYJOURNAL OF FOOD BIOCHEMISTRY, Issue 1 2002JU WEN WU The elicitation of cystatin accumulation in tomato leaves was studied with mature and seedling cv. Bonnie Best. Repetitive mechanical injury (MI) or methyl jasmonate (MJ) treatment of seedlings elicited plentiful cystatin accumulation in the leaves when plants were held at 30C under continuous lighting. Cystatin accumulation in leaves of MI seedlings decreased by 50% when incubated at a reduced light period of 12 h light/day. Cystatin accumulation in MJ treated plants was not influenced by reducing the light period from 24 h to 12 h/day. Cystatin accumulation after MJ treatment was optimal at 35C and negligible at 40C. At ambient field conditions (I8,33C), MJ treated seedlings still accumulated a significant amount of cystatin; however, very little cystatin accumulated in leaves of MI seedlings under these conditions of lower temperature and light exposure. The leaves of mature plants accumulated less cystatin after MJ or MI treatment than did those of seedlings. [source] REDUCTION IN MICROBIAL GROWTH AND IMPROVEMENT OF STORAGE QUALITY IN FRESH-CUT PINEAPPLE AFTER METHYL JASMONATE TREATMENTJOURNAL OF FOOD QUALITY, Issue 1 2005MAGALY MARTÍNEZ-FERRER ABSTRACT Maintaining the quality of a fresh-cut fruit or vegetable product is a major concern and a priority in the development and in the production of fresh-cut produce products of the industry. The industry has been searching for alternative methods to protect fresh-cut produce from decay and to prolong shelf life. The objective of this research is to enhance the quality and the shelf life of fresh-cut pineapple by exposure to methyl jasmonate (MJ). The exposure of the diced pineapple to a MJ emulsion at a concentration of 10,4 M for 5 min in a sealed container decreased microbiological growth by 3 logs after 12 days of storage at 7C, compared with the control pineapple. Methyl jasmonate as vapor or as dip did not affect the firmness or the color of the fruit. Methyl jasmonate may be a practical treatment to ensure the safety and the quality of fresh-cut pineapple and other fruits and vegetables. [source] Search for occult secondary osteoporosis: impact of identified possible risk factors on bone mineral densityJOURNAL OF INTERNAL MEDICINE, Issue 5 2002H. A. Deutschmann Abstract. Deutschmann HA, Weger M, Weger W, Kotanko P, Deutschmann MJ, Skrabal F (Krankenhaus der Barmherzigen Brüder, Marschallgasse, Teaching Hospital of the Karl-Franzens University Graz, Austria). Search for occult secondary osteoporosis: impact of identified possible risk factors on bone mineral density. J Intern Med 2002; 252: 389,397. Objectives. To determine whether the use of more elaborate diagnostic tests can identify possible risk factors for secondary osteoporosis and to evaluate the impact of these possible risk factors on the severity of bone disease in the study population. Design. Cross-sectional study. Setting and participants. ,We have investigated 377 subjects (285 females, 92 males) with osteoporosis (T-score less than ,2.5 in dual energy X-ray absorption) or nontraumatic lumbar vertebral fractures; these patients were referred to our hospital, a secondary care centre, for evaluation and treatment of osteoporosis. Results. Osteoporosis without attributable risk factor was diagnosed in 106 women (37%) and 30 men (33%). In 241 patients (179 women, 62 men) one or more possible risk factors for osteoporosis (in this paper also called subclinical disease) were revealed. The most common were lactose malabsorption, disturbed exocrine pancreatic function and renal tubular disturbances, including renal hypercalciuria, incomplete renal tubular acidosis and mild phosphate diabetes. The number of possible risk factors in the individual patient was significantly related to the severity of osteoporosis as assessed by Z-scores (Spearman correlation r = ,0.43, P < 0.001, n = 172 for females; r = ,0.28, P < 0.05, n = 65 for males). Conclusions. All the identified subclinical diseases would have remained undetected if the currently accepted guidelines for the investigation of patients with osteoporosis were applied. The statistically significant correlation between the number of identified possible risk factors and the severity of bone disease in the individual patient strongly suggests the pathogenetic significance of the identified subclinical diseases. It is yet to be shown, whether specific treatment of these subclinical diseases yields additional improvement of bone mass as compared with standard treatment of osteoporosis. [source] A high prevalence of hypovitaminosis D in Finnish medical in- and outpatientsJOURNAL OF INTERNAL MEDICINE, Issue 6 2001R. Kauppinen-Mäkelin Abstract.,Kauppinen-Mäkelin R, Tähtelä R, Löyttyniemi E, Kärkkäinen J, Välimäki MJ (Peijas Hospital, Vantaa; United Laboratories, Leiras Research, and Division of Endocrinology; Helsinki University Central Hospital, Helsinki, Finland). A high prevalence of hypovitaminosis D in Finnish medical in- and outpatients. J Intern Med 2001; 249: 559,563. Objective.,To study the prevalence of hypovitaminosis D [serum 25(OH)D , 37 nmol L,1)] in Finnish medical in- and outpatients in a cross-sectional study. Methods.,The subjects were 106 consecutive medical inpatients (57 females, 49 males with mean ages of 65 and 58 years) from the Peijas Hospital, Vantaa, Finland, and 99 ambulatory patients (48 females, 51 males with mean ages of 42 and 46 years) contacting a private outpatient centre in Helsinki, Finland. Serum 25(OH)D, vitamin D binding protein (DBP), free vitamin D index (FDI), intact PTH (iPTH), and albumin-corrected calcium were measured. Results.,Serum 25-hydroxyvitamin D [25(OH)D] was 37 nmol L,1 or less in 70% of female and in 61% of male inpatients and in 44% of female and in 37% of male outpatients. In the whole population, a statistically significant inverse association (P < 0.0001) was detected between iPTH and 25(OH)D levels; the iPTH concentration appeared to start increasing when 25(OH)D concentration was 50 nmol L,1 or less. The association remained the same (P < 0.0001) when FDI was used instead of 25(OH)D in the calculations. When the sexes were analysed separately, the statistically significant association was found only in females (P < 0.0001 for iPTH versus 25(OH)D; P < 0.0001 for iPTH versus FDI) but not in males. Conclusion.,Hypovitaminosis D is very common amongst Finnish in- and outpatients in both sexes, causing secondary hyperparathyroidism in females. More extensive studies are warranted to elucidate the vitamin D status of the Finnish population. [source] Consumption of raw brown onions variably modulate plasma lipid profile and lipoprotein oxidation in pigs fed a high-fat dietJOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE, Issue 1 2005Nicholas K Gabler Abstract This study was undertaken to determine the effects of two commercially available brown onion varieties, ,Cavalier' and ,Destiny', supplemented at two different levels, on blood lipid and oxidative status using the pig as a model. Twenty-five female cross-bred pigs were allocated to one of five dietary treatments that consisted of a high-fat control diet with no onion added, a low onion dose of 10 g onion MJ,1 DE and a high dose of 25 g onion MJ,1 DE for each variety of onion. Supplementation with ,Destiny' onion resulted in a 21% (p < 0.05) reduction in the averaged fasted and postprandial plasma triacylglyceride (TG) measurements taken over the six-week period in comparison with the control pigs. The average fasting and postprandial plasma cholesterol concentrations were significantly reduced by 5.5 and 12.4% in pigs that consumed the low and high dose of ,Destiny' onion, respectively (p < 0.010), while ,Cavalier' was only effective at lowering cholesterol levels by 10% at the lower dose of supplementation. Inhibition in the rate of serum lipoprotein oxidation, measured as lag time, was increased by 23% (p < 0.05) in plasma obtained from pigs that consumed ,Cavalier' compared with the control and ,Destiny' onion diets. These data indicate that onion consumption level may provide a dietary means of manipulating some of the risk indices associated with coronary heart disease, but the responses varied with type and dose of onion. Copyright © 2004 Society of Chemical Industry [source] Nutritional evaluation of peas for ducksJOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE, Issue 5 2004Charles M Nyachoti Abstract The nutritive value of four pea cultivars (AC Advantage, Carneval, CDC Mozart and Keoma) and soybean meal (SBM) was evaluated in a 102 h study with 48 male White Pekin ducks. All birds were tube-fed 25 g of dextrose at 24 and 30 h after feed withdrawal, then 25 g of each feedstuff was tube-fed to eight ducks at 48 and 54 h after feed withdrawal. Excreta were quantitatively collected during the next 54 h. Endogenous nitrogen, amino acids and energy per bird in the 54 h collection period were 1.06 ± 0.58 g, 0.047 ± 0.025 g and 0.098 ± 0.049 MJ respectively. There were differences (P < 0.05) in apparent amino acid digestibilities (AAAD) and true amino acid digestibilities (TAAD). On average, AAAD were 82.8, 82.0, 70.3, 82.4 and 77.7% and TAAD were 89.4, 89.2, 82.3, 89.5 and 85.3% for SBM, AC Advantage, Carneval, CDC Mozart and Keoma respectively. The nitrogen-corrected apparent and true metabolisable energy values did not differ among the pea diets and were 13.36 ± 0.071 and 14.59 ± 0.071 MJ kg,1 respectively. Respective values for SBM were 12.16 ± 0.16 and 13.39 ± 0.16 MJ kg,1 and both were lower (P < 0.05) than in peas. Copyright © 2004 Society of Chemical Industry [source] Chemical composition and ruminal degradability of lucerne (Medicago sativa) productsJOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE, Issue 15 2001Arif F Mustafa Abstract A study was conducted to determine the chemical composition and in situ nutrient ruminal degradability of three lucerne products. These were dehydrated pellets, sun-cured pellets and cubes. Results of the chemical analysis showed that sun-cured pellets had the highest (P,<,0.05) neutral and acid detergent fibre as well as total carbohydrate levels, followed by cubes and dehydrated pellets respectively. Crude protein (CP) content was highest (P,<,0.05) for dehydrated pellets (204.3,g,kg,1), intermediate for sun-cured pellets (160.0,g,kg,1) and lowest for cubes (153.2,g,kg,1). Intermediately degradable CP (buffer-insoluble CP minus neutral detergent-insoluble CP) was the main protein fraction in the three products and was higher (P,<,0.05) in cubes than in dehydrated and sun-cured pellets. Estimated net energy of lactation was highest (P,<,0.05) for dehydrated pellets (5.9,MJ,kg,1), intermediate for cubes (5.23,MJ,kg,1) and lowest (P,<,0.05) for sun-cured pellets (5.15,MJ,kg,1). Results of the in situ experiment indicated that dehydrated pellets had higher (P,<,0.05) ruminal protein degradability than sun-cured pellets and cubes. The estimated ruminal escape protein values for dehydrated pellets, sun-cured pellets and cubes were 361, 420 and 498,g,kg,1 CP respectively. It was concluded that differences in chemical composition and ruminal degradability among the three lucerne products were mainly due to differences in stage of maturity. It was also concluded that the dehydration process failed to increase the ruminal escape protein value of dehydrated pellets relative to sun-cured pellets and cubes. © 2001 Society of Chemical Industry [source] Management of anaphylaxis in primary care: Canadian expert consensus recommendationsALLERGY, Issue 9 2010S. Waserman To cite this article: Waserman S, Chad Z, Francoeur MJ, Small P, Stark D, Vander Leek TK, Kaplan A, Kastner M. Management of anaphylaxis in primary care: Canadian expert consensus recommendations. Allergy 2010; 65: 1082,1092. Abstract Background:, Anaphylaxis is often managed inadequately. We used findings from a systematic review of gaps in anaphylaxis management to develop evidence-based recommendations for gaps rated as clinically important by a panel of Canadian allergy experts. Methods:, The nominal group technique (NGT) consensus methodology was used to develop evidence-based recommendations for the management of anaphylaxis in primary care. Physician-specific gaps from our systematic review were prioritized by consensus meeting participants in two rounds, which involved the rating, discussion, and re-rating of gaps. Using current anaphylaxis guidelines, recommendations were then developed for each category of gaps that were identified by the panel as clinically important. Results:, Thirty unique physician gaps from the systematic review were categorized according to gaps of knowledge and anaphylaxis practice behaviors. The panel rated diagnosis of anaphylaxis, and when and how to use epinephrine auto-injectors as clinically important knowledge gaps; and rated infrequent or delayed epinephrine administration, low rate of auto-injector prescription, and infrequent or no referrals to allergy specialists after a reaction as important practice behavior gaps. Evidence from four guidelines was used to support the consensus recommendation statements for three resulting categories of gap themes: anaphylaxis management, epinephrine use, and follow-up care. Conclusion:, We used an NGT consensus methodology to develop an educational resource for primary care physicians and allergists to better understand how to manage patients with anaphylaxis. Next steps include testing our findings against observed data in primary care settings and to develop other strategies or tools to overcome gaps in anaphylaxis management. [source] Role of minor determinants of amoxicillin in the diagnosis of immediate allergic reactions to amoxicillinALLERGY, Issue 5 2010M. J. Torres To cite this article: Torres MJ, Ariza A, Fernández J, Moreno E, Laguna JJ, Montańez MI, Ruiz-Sanchez AJ, Blanca M. Role of minor determinants of amoxicillin in the diagnosis of immediate allergic reactions to amoxicillin. Allergy 2010; 65: 590,596. Abstract Background:, Skin testing of subjects with immediate hypersensitivity to amoxicillin is performed using major and minor determinants of benzylpenicillin plus amoxicillin. However, sensitivity is not optimal, and other determinants need to be considered. We assessed the sensitivity of stable, well-characterized minor determinants of amoxicillin in subjects with immediate allergic reactions to amoxicillin to improve skin test sensitivity. Methods:, Amoxicillin, amoxicilloic acid, and diketopiperazine were prepared and characterized by reverse-phase HPLC, tested in vivo by skin testing and in vitro by basophil activation test and RAST inhibition assay. Results:, Patients with immediate hypersensitivity to amoxicillin were selected: Group A (n = 32), skin test positive just to amoxicillin; Group B (n = 19), skin test positive to benzylpenicillin determinants; Group C (n = 10), skin test negative and amoxicillin drug provocation test positive. In Group A, 27 subjects (81.8%) were skin test positive to amoxicillin, ten (30.3%) to amoxicilloic acid, two (6.1%) to diketopiperacine, and six (18.2%) negative. In Group B, nine (50%) were positive to amoxicillin, eight (42.1%) to amoxicilloic acid, none to diketopiperacine, and nine (50%) negative. In Group C, skin tests were negative. BAT was positive to amoxicillin in 26 patients (50.9%), to amoxicilloic acid in 15 (29.1%), and diketopiperazine in four (7.8%). RAST inhibition studies showed > 50% inhibition in all sera, with the highest concentration of amoxicillin and amoxicilloic acid. Conclusions:, The combination of minor determinants of amoxicillin, amoxicilloic acid, and diketopiperazine seems to be of no greater value than the use of amoxicillin alone. Further efforts are needed to find new structures to improve sensitivity in the diagnosis of immediate hypersensitivity to betalactams. [source] Polymorphisms in IL13 pathway genes in asthma and chronic obstructive pulmonary diseaseALLERGY, Issue 4 2010B. Beghé To cite this article: Beghé B, Hall IP, Parker SG, Moffatt MF, Wardlaw A, Connolly MJ, Fabbri LM, Ruse C, Sayers I. Polymorphisms in IL13 pathway genes in asthma and chronic obstructive pulmonary disease. Allergy 2010; 65: 474,481. Abstract Background:, Asthma and chronic obstructive pulmonary disease (COPD) are chronic respiratory diseases involving an interaction between genetic and environmental factors. Interleukin-13 (IL13) has been suggested to have a role in both asthma and COPD. We investigated whether single nucleotide polymorphisms (SNPs) in the IL13 pathway may contribute to the susceptibility and severity of asthma and COPD in adults. Methods:, Twelve SNPs in IL13 pathway genes ,IL4, IL13, IL4RA, IL13RA1, IL13RA2 and STAT6, were genotyped in subjects with asthma (n = 299) and in subjects with COPD or healthy smokers (n = 992). Genetic association was evaluated using genotype and allele models for asthma severity, atopy phenotypes and COPD susceptibility. Linear regression was used to determine the effects of polymorphism on baseline lung function (FEV1, FEV1/FVC). Results:, In asthmatics, three IL13 SNPs , rs1881457(,1512), rs1800925(,1111) and rs20541(R130Q) , were associated with atopy risk. One SNP in IL4RA1 [rs1805010(I75V)] was associated with asthma severity, and several IL13 SNPs showed borderline significance. IL13 SNPs rs1881457(,1512) and rs1800925(,1111) were associated with better FEV1 and FEV1/FVC in asthmatics. IL13 SNPs rs2066960(intron 1), rs20541(R130Q) and rs1295685(exon 4) were associated with COPD risk and lower baseline lung function in the recessive model. In females, but not in males, rs2250747 of the IL13RA1 gene was associated with COPD and lower FEV1. Conclusion:, These data suggest that IL13 SNPs (promoter and coding region) and, to a lesser extent, IL4RA SNPs may contribute to atopy and asthma. We also provide tentative evidence that IL13 SNPs in the coding region may be of significance in COPD susceptibility. [source] Discovery of new nearby L and late-M dwarfs at low Galactic latitude from the DENIS data baseMONTHLY NOTICES OF THE ROYAL ASTRONOMICAL SOCIETY, Issue 3 2008N. Phan-Bao ABSTRACT We report on new nearby L and late-M dwarfs (dphot, 30 pc) discovered in our search for nearby ultracool dwarfs (I,J, 3.0, later than M8.0) at low Galactic latitude (|b| < 15°) over 4800 deg2 in the Deep Near Infrared Survey of the Southern Sky (DENIS) data base. We used late-M (, M8.0), L and T dwarfs with accurate trigonometric parallaxes to calibrate the MJ versus I,J colour,luminosity relation. The resulting photometric distances have standard errors of ,15 per cent, which we used to select candidates dphot, 30 pc. We measured proper motions from multi-epoch images found in the public archives ALADIN, DSS, 2MASS and DENIS, with at least three distinct epochs and time baselines of 10,21 yr. We then used a maximum reduced proper motion cut-off to select 28 candidates as ultracool dwarfs (M8.0,L8.0) and to reject one as a distant red star. No T dwarf candidates were found in this search, which required an object to be detected in all three DENIS bands. Our low-resolution optical spectra confirmed that 26 were indeed ultracool dwarfs, with spectral types from M8.0 to L5.5. Two contaminants and one rejected by the maximum reduced proper motion cut-off were all reddened F,K main sequence stars. 20 of these 26 ultracool dwarfs are new nearby ultracool dwarf members, three L dwarfs within 15 pc with one L3.5 at only ,10 pc. We determine a stellar density of dwarfs pc,3 mag,1 over 11.1 ,MJ, 13.1 based on this sample of M8,L3.5 ultracool dwarfs. Our ultracool dwarf density value is in good agreement with the measurement by Cruz et al. of the ultracool dwarf density at high Galactic latitude. [source] A Bayesian Kepler periodogram detects a second planet in HD 208487MONTHLY NOTICES OF THE ROYAL ASTRONOMICAL SOCIETY, Issue 4 2007P. C. Gregory ABSTRACT An automatic Bayesian Kepler periodogram has been developed for identifying and characterizing multiple planetary orbits in precision radial velocity data. The periodogram is powered by a parallel tempering Markov chain Monte Carlo (MCMC) algorithm which is capable of efficiently exploring a multiplanet model parameter space. The periodogram employs an alternative method for converting the time of an observation to true anomaly that enables it to handle much larger data sets without a significant increase in computation time. Improvements in the periodogram and further tests using data from HD 208487 have resulted in the detection of a second planet with a period of 90982,92 d, an eccentricity of 0.370.26,0.20, a semimajor axis of 1.870.13,0.14 au and an M sin i= 0.45+0.11,0.13MJ. The revised parameters of the first planet are period = 129.8 ± 0.4 d, eccentricity = 0.20 ± 0.09, semimajor axis = 0.51 ± 0.02 au and M sin i= 0.41 ± 0.05 MJ. Particular attention is paid to several methods for calculating the model marginal likelihood which is used to compare the probabilities of models with different numbers of planets. [source] | |||||||||||||||||||||||||||||||||||||||||||||||||