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Better Definition (good + definition)
Selected AbstractsAlternative therapy in pruritusDERMATOLOGIC THERAPY, Issue 2 2003Larry E. Millikan ABSTRACT: Because of its multitude of origins, the symptom complex of pruritus has a plethora of purported remedies and few therapeutic indications. Very few topical and systemic FDA approved medications have the indication of pruritus. Specific therapy still awaits a better definition of the exact physiologic events in chronic pruritus. Hence most medications actually focus on the central nervous system,the peripheral receptors,and the lack of specific physiologic targets has inhibited pharmacologic development. The resulting gap has opened the door to a variety of alternative therapies. [source] Defining paganism in the Carolingian worldEARLY MEDIEVAL EUROPE, Issue 4 2007James Palmer Generations of scholars have looked for evidence of ,paganism' in continental sources from the eighth and ninth centuries. This paper surveys some of the key problems in defining and conceptualizing the available literary evidence for such a project. Part one argues for a return to the sources to help escape the intellectual baggage created by discussions of ,pan-Germanic paganism', interpretatio Romana and, more recently, folk practices. From the perspective of the sources' producers, paganism needs to be understood as a category of difference employed to provide a better definition of Christianity itself. In part two this line of thought is pursued through a brief study of the ways in which classical learning framed not only Carolingian attitudes to paganism, but also related strategies of moralizing. [source] MICA and MICB microsatellite alleles in HLA extended haplotypesINTERNATIONAL JOURNAL OF IMMUNOGENETICS, Issue 5 2001E. Bolognesi Summary The present study is a contribution to the definition of the linkage disequilibrium relationship of MICA and MICB with adjacent loci and to the characterization of extended HLA haplotypes. These issues are of importance for the identification of disease associations and for a better definition of donor,recipient compatibility in bone-marrow grafts through the typing of haplospecific markers. The distribution of the five alleles of MICA and the 13 alleles of MICB microsatellites, located, respectively, in MICA transmembrane exon 5 and in MICB intron 1, was examined in 133 healthy Italian individuals previously typed for HLA class I, class II and complement loci and for the TNFa microsatellite. The MICB microsatellite was also analysed in 49 HTCLs for which MICA typing was already available. Very strong linkage disequilibria with HLA-B and TNFa were detected in the Italian population for both MICA and MICB microsatellite alleles, in spite of the high mutability rate of the larger MICB alleles. Some strong associations were also detected between MICB and DRB1. The strongest associations (P < 0.001, D, > 0.7) were those of MICA-A4 with HLA-B18, B27 and TNFa1, MICA-A5 with HLA-B35, B61 and B62, MICA-A5.1 with HLA-B7, B8, B13, B63 and MICB-CA24, MICA-A6 with HLA-B51, MICA-A9 with HLA-B39, B57 and TNFa2, MICB-CA14 with HLA-B14, B27 and TNFa1, MICB-CA15 with HLA-B52, TNFa4 and TNFa13, MICB-CA17 with HLA-B7 and TNFa11, MICB-CA18 with HLA-B13 and TNFa7, MICB-CA22 with HLA-B57, and MICB-CA24 with HLA-B8 and TNFa2. From pairwise associations in the random panel and results for the homozygous cell lines it was possible to deduce the MICA and MICB microsatellite alleles present in many of the well-known Caucasoid extended haplotypes. [source] Identification of Novel Regulators Associated With Early-Phase Osteoblast Differentiation,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 6 2004Diana S de Jong Abstract Key regulatory components of the BMP-induced osteoblast differentiation cascade remain to be established. Microarray and subsequent expression analyses in mice identified two transcription factors, Hey1 and Tcf7, with in vitro and in vivo expression characteristics very similar to Cbfa1. Transfection studies suggest that Tcf7 modulates BMP2-induced osteoblast differentiation. This study contributes to a better definition of the onset of BMP-induced osteoblast differentiation. Introduction: Elucidation of the genetic cascade guiding mesenchymal stem cells to become osteoblasts is of extreme importance for improving the treatment of bone-related diseases such as osteoporosis. The aim of this study was to identify regulators of the early phases of bone morphogenetic protein (BMP)2-induced osteoblast differentiation. Materials and Methods: Osteoblast differentiation of mouse C2C12 cells was induced by treatment with BMP2, and regulation of gene expression was studied during the subsequent 24 h using high-density microarrays. The regulated genes were grouped by means of model-based clustering, and protein functions were assigned. Real-time quantitative RT-PCR analysis was used to validate BMP2-induced gene expression patterns in C2C12 cells. Osteoblast specificity was studied by comparing these expression patterns with those in C3H10T1/2 and NIH3T3 cells under similar conditions. In situ hybridization of mRNA in embryos at embryonic day (E)14.5 and E16.5 of gestation and on newborn mouse tails were used to study in vivo expression patterns. Cells constitutively expressing the regulated gene Tcf7 were used to investigate its influence on BMP-induced osteoblast differentiation. Results and Conclusions: A total of 184 genes and expressed sequence tags (ESTs) were differentially expressed in the first 24 h after BMP2 treatment and grouped in subsets of immediate early, intermediate early, and late early response genes. Signal transduction regulatory factors mainly represented the subset of immediate early genes. Regulation of expression of these genes was direct, independent of de novo protein synthesis and independent of the cell type studied. The intermediate early and late early genes consisted primarily of genes related to processes that modulate morphology, basement membrane formation, and synthesis of extracellular calcified matrix. The late early genes require de novo protein synthesis and show osteoblast specificity. In vivo and in vitro experiments showed that the transcription factors Hey1 and Tcf7 exhibited expression characteristics and cell type specificity very similar to those of the osteoblast specific transcription factor Cbfa1, and constitutive expression of Tcf7 in C2C12 cells differentially regulated osteoblast differentiation marker genes. [source] Proton spectroscopic metabolite signal relaxation times in preterm infants: A prerequisite for quantitative spectroscopy in infant brainJOURNAL OF MAGNETIC RESONANCE IMAGING, Issue 6 2003Harald Kugel PhD Abstract Purpose To determine relaxation times of metabolite signals in proton magnetic resonance (MR) spectra of immature brain, which allow a correction of relaxation that is necessary for a quantitative evaluation of spectra acquired with long TE. Proton MR spectra acquired with long TE allow a better definition of metabolites as N-acetyl aspartate (NAA) and lactate especially in children. Materials and Methods Relaxation times were determined in the basal ganglia of 84 prematurely born infants at a postconceptional age of 37.8 ± 2.2 (mean ± SD) weeks. Metabolite resonances were investigated using the double-spin-echo volume selection method (PRESS) at 1.5 T. T1 was determined from intensity ratios of signals obtained with TRs of 1884 and 6000 msec, measured at 3 TEs (25 msec, 136 msec, 272 msec). T2 was determined from signal intensity ratios obtained with TEs of 136 msec and 272 msec, measured at 2 TR. Taking only long TEs reduced baseline distortions by macromolecules and lipids. For myo-inositol (MI), an apparent T2 for short TE was determined from the ratio of signals obtained with TE = 25 msec and 136 msec. Intensities were determined by fitting a Lorentzian to the resonance, and by integration. Results Relaxation times were as follows: trimethylamine-containing compounds (Cho): T1 = 1217 msec/T2 = 273 msec; total creatine (Cr) at 3.9 ppm: 1010 msec/111 msec; Cr at 3.0 ppm: 1388 msec/224 msec; NAA: 1171 msec/499 msec; Lac: 1820 msec/1022 msec; MI: 1336 msec/173 msec; apparent T2 at short TE: 68 msec. Conclusion T1 and T2 in the basal ganglia of premature infants do not differ much from previously published data from basal ganglia of older children and adults. T2 of Cho was lower than previous values. T2 of Cr at 3.9 ppm and Lac have been measured under different conditions before, and present values differ from these data. J. Magn. Reson. Imaging 2003;17:634,640. © 2003 Wiley-Liss, Inc. [source] Annotation: Deconstructing the attention deficit in fragile X syndrome: a developmental neuropsychological approachTHE JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY AND ALLIED DISCIPLINES, Issue 6 2004K.M. Cornish Background:, Fragile X syndrome is one of the world's leading hereditary causes of developmental delay in males. The past decade has witnessed an explosion of research that has begun to unravel the condition at its various levels: from the genetic and brain levels to the cognitive level, and then to the environmental and behavioural levels. Our aim in this review is to attempt to integrate some of the extensive body of knowledge to move the research a step closer to understanding how the dynamics of atypical development can influence the specific cognitive and behavioural end-states frequently observed in children and adolescents with fragile X syndrome. Methods:, We conducted a review of the current neuropsychological and neuropsychiatric approaches that have attempted to delineate the pattern of ,spared' and ,impaired' functions associated with the phenotype. Results:, The profile of findings suggests that fragile X syndrome should not be viewed merely as a catalogue of spared and impaired cognitive functions or modules. Instead, there appears to be a process of almost gradual modularisation whereby cognitive mechanisms become domain specific as a function of development itself (Karmiloff-Smith, 1992). The results of a decade of intense research point towards an early weakness in one or more components of executive control rather than single, static higher-level deficits (e.g., spatial cognition, speech processing). This weakness affects both the development of more complex functions and current performance. Conclusions:, The prevailing tendency to interpret developmental disorders in terms of fixed damage to distinct modular functions needs to be reconsidered. We offer this review as an example of an alternative approach, attempting to identify an initial deficit and its consequences for the course of development. Through better definition of the cognitive and behavioural phenotype, in combination with current progress in brain imaging techniques and molecular studies, the next decade should continue to hold exciting promise for fragile X syndrome and other neurodevelopmental disorders. [source] Patient Survival After Kidney Transplantation: Relationship to Pretransplant Cardiac Troponin T LevelsAMERICAN JOURNAL OF TRANSPLANTATION, Issue 6 2009L. T. J. Hickson Assessing cardiovascular (CV) risk pretransplant is imprecise. We sought to determine whether cardiac troponin T (cTnT) relates to patient survival posttransplant. The study includes 603 adults, recipients of kidney transplants. In addition to cTnT dobutamine stress echography and coronary angiography were done in 45% and 19% of the candidates respectively. During 28.4 ± 12.9 months 5.6% of patients died or had a major cardiac event. cTnT levels were elevated (>0.01 ng/ml) in 56.2% of patients. Elevated cTnT related to reduced event-free survival (hazard ratio (HR) = 1.81, CI 1.33,2.45, p < 0.0001) whether those events occurred during the first year or beyond. This relationship was statistically independent of all other variables tested, including older age, reduced left ventricular ejection fraction (EF) and delayed graft function. cTnT levels allowed better definition of risk in patients with other CV risk factors. Thus, event-free survival was excellent in older individuals, patients with diabetes, low EF and those with preexisting heart disease if their cTnT levels were normal. However, elevated cTnT together with another CV risk factor(s) identified patient with very poor survival posttransplant. Pretransplant cTnT levels are strong and independent predictors of posttransplant survival. These results suggest that cTnT is quite helpful in CV risk stratification of kidney transplant recipients. [source] Similar Outcomes with Different Rates of Delayed Graft Function May Reflect Center Practice, Not Center PerformanceAMERICAN JOURNAL OF TRANSPLANTATION, Issue 6 2009S. K. Akkina To better understand the implications for considering delayed graft function (DGF) as a performance measure, we compared outcomes associated with a 2- to 3-fold difference in the incidence of DGF at two transplant centers. We analyzed 5072 kidney transplantations between 1984 and 2006 at the University of Minnesota Medical Center (UMMC) and Hennepin County Medical Center (HCMC). In logistic regression the adjusted odds ratio for DGF at HCMC versus UMMC was 3.11 (95% Confidence Interval [CI]= 2.49,3.89) for deceased donors and 2.24 (CI = 1.45,3.47) for living donors. In Cox analysis of 4957 transplantations, slow graft function (SGF; creatinine ,3.0 mg/dL [230 ,mol/L] on day 5 without dialysis) was associated with graft failure at UMMC (Relative Risk [RR]= 1.43, CI = 1.25,1.64), but not HCMC (RR = 0.99, CI = 0.77,1.28). RR's of DGF were similar at both centers. Thus, the lower incidence of DGF at UMMC likely resulted in a higher incidence and higher risk of SGF compared to HCMC. Indeed, graft survival for recipients with DGF at HCMC was similar (p = 0.3741) to that of recipients with SGF at UMMC. We conclude that dialysis per se is likely not a cause of worse graft outcomes. A better definition is needed to measure early graft dysfunction and its effects across transplant programs. [source] CHARACTERIZING THE SEDIMENTARY HISTORY OF CAVE DEPOSITS, USING ARCHAEOMAGNETISM AND ROCK MAGNETISM, ATAPUERCA (NORTHERN SPAIN)ARCHAEOMETRY, Issue 5 2010J. M. PARÉS We use a combination of rock magnetism (anisotropy of magnetic susceptibility, AMS) and magnetic polarity to characterize cave deposits and as a proxy for sedimentary fabric. In three localities at the Atapuerca archaeological site (Galeria, Gran Dolina and Sala de los Cíclopes), magnetic foliation (Kmax/Kint) is always greater than lineation (Kint/Kmin), consistent with a primary, depositional, sedimentary fabric. Our results, although preliminary, reveal a higher degree of anisotropy in autochtonous deposits compared to allochthonous deposits, possibly indicative of a higher hydrodynamic regime in the former. At two localities the magnetic lineation (Kmax) defines a cluster, which is thought to be antipodal to the palaeocurrent direction. Hence we are able to retrieve palaeoflow directions in deposits that otherwise lack any other sedimentary structure. We conclude that AMS is a powerful tool for determining the hydrodynamic character of depositional environments in cave sediments at the Atapuerca archaeological site. A better understanding of the depositional environment and how sedimentation occurred allows reconstruction of the karst evolution and ultimately a better definition of human interaction with the environment. [source] Refined structure of Pyrococcus furiosus ornithine carbamoyltransferase at 1.87,AACTA CRYSTALLOGRAPHICA SECTION D, Issue 12 2003Jan Massant Using synchrotron radiation, X-ray data have been collected from Pyrococcus furiosus ornithine carbamoyltransferase (Pfu OTCase) to a maximal resolution of 1.87,Å, allowing the refinement of a previous structure at 2.7,Å [Villeret et al. (1998), Proc. Natl Acad. Sci. USA, 95, 2801,2806]. Thanks to the high resolution of this refined structure, two sulfate ions and 191 water molecules could be localized directly from the electron-density maps. The identification of these molecules allowed a more rigorous description of the active site and the identification of residues involved in binding carbamoyl phosphate. The improved quality of the model resulted in a better definition of several loops and the various interfaces. The dodecameric protein is composed of four catalytic trimers disposed in a tetrahedral manner. The extreme thermal stability of Pfu OTCase is mainly the result of the strengthening of the intersubunit interactions in a trimer and oligomerization of the trimers into a dodecamer. Interfaces between monomers in a catalytic trimer are characterized by an increase in ion-pair networks compared with mesophilic OTCases. However, the interfaces between catalytic trimers in the dodecameric oligomer are mainly hydrophobic and also involve aromatic,aromatic and cation,, interactions. [source] Haematopoietic stem cell transplantation for Shwachman,Diamond disease: a study from the European Group for blood and marrow transplantationBRITISH JOURNAL OF HAEMATOLOGY, Issue 2 2005Simone Cesaro Summary This report assessed the results of allogeneic stem cell transplantation (allo-SCT) in 26 patients with Shwachman,Diamond disease (SDS) and severe bone marrow abnormalities. The conditioning regimen was based on busulphan (54%), total body irradiation (23%), fludarabine (15%) or other chemotherapy combinations (8%). Standard prevention of graft versus host disease (GVHD) with ciclosporin ± methotrexate was adopted in 54% of the patients whilst in vivo or in vitro T-cell depletion was used in 17 and four patients respectively. Neutrophil and platelet engraftment were achieved in 21 (81%) and 17 (65%) of 26 patients after a median time of 18 days and 29 days respectively. The incidence of grade III and IV acute GVHD was 24% and of chronic GVHD 29%. Nine patients died after a median time of 70 d, post-SCT. After a median follow-up of 1·1 years, the transplant-related mortality was 35·5% (95% CI 17,54) whilst the overall survival was 64·5% (95% CI 45·7,83·2). Allo-SCT was found to be successful in more than half of SDS patients with severe bone marrow dysfunction. Further improvements would be anticipated by a better definition of the optimum time in the course of disease to transplant and by the adoption of less toxic conditioning regimens. [source] Parameters for Successful Implant Integration Revisited Part II: Algorithm for Immediate Loading Diagnostic FactorsCLINICAL IMPLANT DENTISTRY AND RELATED RESEARCH, Issue 2010FACD, Oded Bahat BDS ABSTRACT Immediate loading of dental implants has become a widely reported practice with success rates ranging from 70.8% to 100%. Although most studies have considered implant survival to be the only measure of success, a better definition includes the long-term stability of the hard and soft tissues around the implant(s) and other adjacent structures, as well as the long-term stability of all the restorative components. The parameters identified in 1981 by Albrektsson and colleagues as influencing the establishment and maintenance of osseointegration have been reconsidered in relation to immediate loading to improve the chances of achieving such success. Two of the six parameters (status of the bone/implant site and implant loading conditions) have preoperative diagnostic implications, whereas three (implant design, surgical technique, and implant finish) may compensate for less-than-ideal site and loading conditions. Factors affecting the outcome of immediate loading are reviewed to assist clinicians attempting to assess its risks and benefits. [source] Beyond six scents: defining a seventh Thymus vulgaris chemotype new to southern France by ethanol extractionFLAVOUR AND FRAGRANCE JOURNAL, Issue 3 2009Ken Keefover-Ring Abstract The concept of plant chemotype has long been useful to describe secondary chemical phenotypes; however, the idea has practical limitations, especially when applied to ecological questions. This work reports the discovery of a new 1,8-cineole chemotype of Thymus vulgaris from a well-studied area in southern France. Multivariate statistical analysis of ethanol-extracted plant terpenes was used to describe this new chemotype and three others found at the site, and the results are used to discuss the chemotype concept. While the total amount of essential oils among these chemotypes showed no difference, the concentration of the main terpene differed significantly, with the 1,8-cineole and cis -sabinene hydrate chemotypes having the lowest amounts of their respective main components, and the linalool chemotype having the highest. The , -terpinyl acetate chemotype had intermediate levels of its main terpene. A factor analysis revealed four factors which explained almost 89% of the total variation in plant essential oils. Each factor represented a separate chemotype, including a cis -sabinene hydrate, linalool, ,- terpinyl acetate and the new 1,8-cineole chemotype. Although the concept of plant chemotype is still valid, better definitions are important when evaluating the influences of a plant's secondary chemistry on other community members. Copyright © 2009 John Wiley & Sons, Ltd. [source] Bridging the Gap Between Genomics and EducationMIND, BRAIN, AND EDUCATION, Issue 4 2007Stephen A. Petrill ABSTRACT, Despite several decades of research suggesting the importance of both genetic and environmental factors, these findings are not well integrated into the larger educational literature. Following a discussion of quantitative and molecular genetic methods, this article reviews behavioral genetic findings related to cognitive and academic skills. This literature suggests that (a) the relative importance of genes and environments varies developmentally; (b) genetics, and to a lesser extend the environment, account for a substantial portion of the covariance within and across academic domains; and (c) some forms of disability are qualitatively different from the population, whereas others constitute the lower end of a continuum of ability. Following a discussion of the strengths and limitations of current behavioral genetic research and intervention research, we then discuss the ways in which understanding gene,environment interplay can be used to develop better definitions of learning impairment and better explain the substantial variability in response to intervention. [source] | |||||||||||||||||||