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First Investigation (first + investigation)
Selected AbstractsA finite element formulation based on the Cosserat point theoryPROCEEDINGS IN APPLIED MATHEMATICS & MECHANICS, Issue 1 2006Eiris F. I. Boerner The theory of Cosserat points is the basis of a 3D finite element formulation for large deformations in structural mechanics, that recently was presented by [1]. First investigations [2] have revealed, that this formulation is free of showing undesired locking or hourglassing-phenomena. It additionally shows excellent behaviour for any type of incompressible material, for large deformations and sensitive structures such as plates or shells. The formulation initially was restricted to a Neo-Hookean material. This work will present the extension to a general elastic Ogden material and the verification of the chosen model. (© 2006 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim) [source] Cross-sectional analysis of the association between age and corpus callosum size in chimpanzees (Pan troglodytes)DEVELOPMENTAL PSYCHOBIOLOGY, Issue 2 2010William D. Hopkins Abstract The CC is the major white matter tract connecting the cerebral hemispheres and provides for interhemispheric integration of sensory, motor and higher-order cognitive information. The midsagittal area of the CC has been frequently used as a marker of brain development in humans. We report the first investigation into the development of the corpus callosum and its regional subdivisions in chimpanzees (Pan troglodytes). Magnetic resonance images were collected from 104 chimpanzees (female n,=,63, male n,=,41) ranging in age from 6 years (pre-pubescent period) to 54 years (old age). Sustained linear growth was observed in the area of the CC subdivision of the genu; areas of the posterior midbody and anterior midbody displayed nonlinear growth during development. After adjusting for total brain size, we observed linear growth trajectories of the total CC and CC subdivisions of the genu, posterior midbody, isthmus and splenium, and nonlinear growth trajectories of the rostral body and anterior midbody. These developmental patterns are similar to the development of the CC in humans. As the growth curves of the CC mirrors growth seen in the percentage of white matter in humans, our results suggest chimpanzees show continued white matter development in regions related to cognitive development. © 2010 Wiley Periodicals, Inc. Dev Psychobiol 52:133,141, 2010 [source] Investigation of Adducin 2 (beta) DNA polymorphisms in genetic predisposition to diabetic nephropathy in Type 1 diabetesDIABETIC MEDICINE, Issue 8 2008D. Currie Abstract Aims Adducin 2 (beta) (ADD2) is a biological and positional candidate gene proposed to confer genetic risk for diabetic nephropathy. This study aimed to comprehensively investigate all common and putatively functional polymorphisms in the genomic region encompassing this gene. Methods Tag single nucleotide polymorphisms (n = 23) derived from phase II of the International HapMap Project and in silico functional variants (n = 2) were genotyped in 1467 White individuals from the British Isles (cases, n = 718; control subjects, n = 749) by a combination of Sequenom iPLEX and TaqMan technologies. Results ,2 analysis of genotype and allele frequencies in cases vs. control subjects revealed weak evidence for association of one variant at the 5% level of significance (rs10164951, P = 0.02). Adjusting for multiple testing in the present case,control collection negated this association. Conclusions We selected an appropriate subset of variants suitable for genetic investigations of the ADD2 gene and report the first investigation of polymorphisms in ADD2 with diabetic nephropathy. Our results suggest that common polymorphisms and putatively functional variants in the ADD2 gene do not strongly influence genetic susceptibility to diabetic nephropathy in this White population with Type 1 diabetes. [source] Fine-needle aspiration cytology of Sister Mary Joseph's (paraumbilical) nodulesDIAGNOSTIC CYTOPATHOLOGY, Issue 5 2008Uma Handa M.D. Abstract During a period of 5 years (2001,2005), six cases of Sister Mary Joseph's nodule (umbilical metastasis) were diagnosed by fine needle aspiration cytology (FNAC). In all the cases, FNAC of umbilical nodules was the first investigation and subsequently the patients were investigated for the primary tumor. The primary carcinoma was found in the stomach in three cases, ovary in two cases and one case was of non-Hodgkin's lymphoma. Based on our findings, we suggest FNAC as an initial diagnostic procedure in cases suspected of umbilical metastasis. It is not only simple, fast, accurate and inexpensive but can also save the patient from other invasive diagnostic procedures. Diagn. Cytopathol. 2008;36:348,350. © 2008 Wiley-Liss, Inc. [source] Structure and vertical stratification of plant galler,parasitoid food webs in two tropical forestsECOLOGICAL ENTOMOLOGY, Issue 3 2009MIGUEL R. PANIAGUA Abstract 1.,Networks of feeding interactions among insect herbivores and natural enemies such as parasitoids, describe the structure of these assemblages and may be critically linked to their dynamics and stability. The present paper describes the first quantitative study of parasitoids associated with gall-inducing insect assemblages in the tropics, and the first investigation of vertical stratification in quantitative food web structure. 2.,Galls and associated parasitoids were sampled in the understorey and canopy of Parque Natural Metropolitano in the Pacific forest, and in the understorey of San Lorenzo Protected Area in the Caribbean forest of Panama. Quantitative host,parasitoid food webs were constructed for each assemblage, including 34 gall maker species, 28 host plants, and 57 parasitoid species. 3.,Species richness was higher in the understorey for parasitoids, but higher in the canopy for gall makers. There was an almost complete turnover in gall maker and parasitoid assemblage composition between strata, and the few parasitoid species shared between strata were associated with the same host species. 4.,Most parasitoid species were host specific, and the few polyphagous parasitoid species were restricted to the understorey. 5.,These results suggest that, in contrast to better-studied leaf miner,parasitoid assemblages, the influence of apparent competition mediated by shared parasitoids as a structuring factor is likely to be minimal in the understorey and practically absent in the canopy, increasing the potential for coexistence of parasitoid species. 6.,High parasitoid beta diversity and high host specificity, particularly in the poorly studied canopy, indicate that tropical forests may be even more species rich in hymenopteran parasitoids than previously suspected. [source] Capillary electrophoretic investigation of the enantioselective metabolism of propafenone by human cytochrome P-450 SUPERSOMES: Evidence for atypical kinetics by CYP2D6 and CYP3A4ELECTROPHORESIS, Issue 8 2006Minoo Afshar Abstract An enantioselective CE method was used to identify the ability of CYP450 enzymes and their stereoselectivity in catalyzing the transformation of propafenone (PPF) to 5-hydroxy-propafenone (5OH-PPF) and N -despropyl-propafenone (NOR-PPF). Using in,vitro incubations with single CYP450 enzymes (SUPERSOMES), 5OH-PPF is shown to be selectively produced by CYP2D6 and N -dealkylation is demonstrated to be mediated by CYP2D6, CYP3A4, CYP1A2, and CYP1A1. For the elucidation of kinetic aspects of the metabolism with CYP2D6 and CYP3A4, incubations with individual PPF enantiomers and racemic PPF were investigated. With the exception of the dealkylation in presence of R -PPF only, which can be described by the Michaelis,Menten model, all CYP2D6-induced reactions were found to follow autoactivation kinetics. For CYP3A4, all NOR-PPF enantiomer formation rates as function of PPF enantiomer concentration were determined to follow substrate inhibition kinetics. The formation of NOR-PPF by the different enzymes is stereoselective and is reduced significantly when racemic PPF is incubated. Clearance values obtained for CYP3A4 dealkylation are stereoselective whereas those of CYP2D6 hydroxylation are not. This paper reports the first investigation of the PPF hydroxylation and dealkylation kinetics by the CYP2D6 enzyme and represents the first report in which enantioselective CE data provide the complete in,vitro kinetics of metabolic steps of a drug. [source] A 20-year follow-up study of endodontic variables and apical status in a Swedish populationINTERNATIONAL ENDODONTIC JOURNAL, Issue 12 2007M. Eckerbom Abstract Aim, To re-examine a population after 20 years and evaluate changes in prevalence of endodontic treatment and apical periodontitis, as well as the technical quality of root fillings. Methodology, One hundred and fifteen out of an original 200 patients living in the northern part of Sweden were re-examined with a full mouth radiographic survey after 20 years. Frequencies of root canal treated teeth, apical periodontitis and quality parameters of root fillings were registered. Results, The frequency of root canal treated teeth increased significantly (P < 0.05) from 13.9% at the first investigation to 17.7% after 20 years. There was also a statistically significant increase (P < 0.05) in teeth with apical periodontitis from 3.3% to 6.8%. Apical periodontitis both in connection with root canal treated teeth and teeth without endodontic treatment, had increased during the follow-up period. Even though the quality of the root fillings had improved, there was no corresponding improvement of the apical status in teeth with root fillings. Conclusions, There is still a great need for endodontic treatment in the Swedish population, and no improvement in apical health was found during this 20-year follow up. [source] Colorectal cancer screening: A comparison of 35 initiatives in 17 countries,,INTERNATIONAL JOURNAL OF CANCER, Issue 6 2008Victoria S. Benson Abstract Although in its infancy, organized screening for colorectal cancer (CRC) in the general population is increasing at regional and national levels. Documenting and describing these initiatives is critical to identifying, sharing and promoting best practice in the delivery of CRC screening. Subsequently, the International Colorectal Cancer Screening Network (ICRCSN) was established in 2003 to promote best practice in the delivery of organized screening programs. The initial aim was to identify and document organized screening initiatives that commenced before May 2004. Each identified initiative was sent 1 questionnaire per screening modality: fecal occult blood test, flexible sigmoidoscopy or total colonoscopy. Information was collected on screening methodology, testing details and initiative status. In total, 35 organized initiatives were identified in 17 countries, including 10 routine population-based screening programs, 9 pilots and 16 research projects. Fecal occult blood tests were the most frequently used screening modality, and total colonoscopy was seldom used as a primary screening test. The eligible age for screening ranged from 40 years old to no upper limit; most initiatives included participants aged 50 to 64. Recruitment was usually done by a mailed invitation or during a visit to a family physician. In conclusion, this is the first investigation describing the delivery of CRC screening protocols to various populations. The work of the ICRCSN is enabling valuable information to be shared and a common nomenclature to be established. © 2007 Wiley-Liss, Inc. [source] Pain-Sensitive Temperament and Postoperative PainJOURNAL FOR SPECIALISTS IN PEDIATRIC NURSING, Issue 3 2007Charmaine Kleiber PURPOSE.,To describe the relationship between pain-sensitive temperament and self-report of pain intensity following surgery. DESIGN AND METHODS.,Fifty-nine adolescents and young adults (average age 14 years) undergoing spinal fusion for adolescent idiopathic scoliosis completed the Sensitivity Temperament Inventory for Pain,Child version (STIP-C). The Pearson correlation between STIP-C scores and the highest pain intensity for each of the first three postoperative days was investigated. RESULTS.,There was a small but significant correlation between the Perceptual Sensitivity and Symptom Reporting subscales of the STIP-C and pain intensity measured on the third postoperative day. PRACTICE IMPLICATIONS.,Aspects of the pain-sensitive temperament may be important in understanding the variability in postoperative pain. This is the first investigation of the relationship between pain-sensitive temperament and surgical pain. More research is needed in this area. [source] Chitinolytic activities in Bacillus thuringiensis and their synergistic effects on larvicidal activityJOURNAL OF APPLIED MICROBIOLOGY, Issue 3 2002M. Liu Aims: To investigate the distribution of chitinase in Bacillus thuringiensis strains, and the enhancing effects of the chitinase-producing B. thuringiensis strains on insecticidal toxicity of active B. thuringiensis strain against Spodoptera exigua larvae. Methods and Results: The chitinolytic activities of B.thuringiensis strains representing the 70 serotypes were investigated by the whitish opaque halo and the colorimetric method. Thirty-eight strains produced different levels of chitinase at pH 7·0, and so did 17 strains at pH 10·0. The strain T04A001 exhibited the highest production, reaching a specific activity of 355 U ml,1 in liquid medium. SDS-PAGE and Western blotting showed that the chitinase produced by some B. thuringiensis strains had a molecular weight of about 61 kDa. The bioassay results indicated that the chitinase-producing B. thuringiensis strains could enhance the insecticidal activity of B. thuringiensis strain DL5789 against S. exigua larvae, with an enhancing ratio of 2·35-fold. Conclusion: This study demonstrated that chitinase was widely produced in B. thuringiensis strains and some of the strains could enhance the toxicity of active B. thuringiensis strain. Significance and Impact of the Study: This is the first investigation devoted exclusively to analyse the distribution of chitinase in B. thuringiensis. It infers that the chitinase produced by B. thuringiensis might play a role in the activity of the biopesticide. [source] The heritability of inducible defenses in tadpolesJOURNAL OF EVOLUTIONARY BIOLOGY, Issue 4 2005R. A. RELYEA Abstract The evolution of plastic traits requires phenotypic trade-offs and heritable traits, yet the latter requirement has received little attention, especially for predator-induced traits. Using a half-sib design, I examined the narrow-sense heritability of predator-induced behaviour, morphology, and life history in larval wood frogs (Rana sylvatica). Many of the traits had significant additive genetic variation in predator (caged Anax longipes) and no-predator environments. Whereas most traits had moderate to high heritability across environments, tail depth exhibited high heritability with predators but low heritability without predators. In addition, several traits had significant heritability for plasticity, suggesting a potential for selection to act on plasticity per se. Genetic correlations confirmed known phenotypic relationships across environments and identified novel relationships within each environment. This appears to be the first investigation of narrow-sense heritabilities for predator-induced traits and confirms that inducible traits previously shown to be under selection also have a genetic basis and should be capable of exhibiting evolutionary responses. [source] Chronic pancreatitis in Chinese children: Etiology, clinical presentation and imaging diagnosisJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 12 2009Wei Wang Abstract Background and Aims:, There is a paucity of literature regarding the clinical profile of chronic pancreatitis (CP) in children. The aims of this retrospective study were to determine the etiology and clinical presentation, and to present our experience in diagnosing CP in children in China. Methods:, Clinical data of children who were treated for CP at Changhai Hospital from January 1997 to August 2006 were reviewed. Results:, A total of 427 CP patients presented to our center. There were 42 (9.8%) children with CP, including 21 males and 21 females, with a mean age of 11.7 years at the first onset. The main etiological factor was idiopathic (73.8%). Of the patients, 78.5% had episodes of mild to moderate abdominal pain and 54.8% had multiple (, 4) episodes. The mean duration of symptoms prior to the diagnosis was 41.6 months and a definite diagnosis was not made until 2 years later in 57.1% of these patients. The positive rates of ultrasound (US), computed tomography (CT) and magnetic resonance cholangiopancreatography (MRCP) (or magnetic resonance imaging [MRI]) for detecting ductal changes and intraductal stones or pancreatic calcification were 51.4% and 45.4%, 71.4% and 87.5%, 80.0% and 61.5%, respectively. Conclusion:, The main etiological factor of Chinese children with CP is idiopathic. The main symptom in these patients is multiple episodes of mild to moderate abdominal pain, which often lead to a delay in the definite diagnosis. CT and MRCP (or MRI) should be used as the first investigation in the evaluation of these cases. [source] Morphology and ultrastructure of the malpighian tubules of the Chilean common tarantula (Araneae: Theraphosidae)JOURNAL OF MORPHOLOGY, Issue 1 2002S. Renee Hazelton Abstract Relatively little is known about the morphology and ultrastructure of the Malpighian tubules of spiders (Arachnida: Araneae). Our study represents the first investigation of the Malpighian tubules of a theraphosid spider and is the only study to examine the living Malpighian tubules using confocal laser scanning microscopy. In theraphosid spiders, the Malpighian tubules originate from the stercoral pocket in the posterior portion of the opisthosoma and extend forward toward the prosoma in a dendritic pattern. There are three distinct segments (initial, main, and terminal), all dark brown in appearance. Each segment has distinctive ultrastructural features. Both the terminal and the main segment appear to be composed of at least two cell types with finger-like cytoplasmic protrusions associated with one of these types. The terminal segment, which is most proximal to the stercoral pocket, is the largest in diameter. It is composed of large, cuboidal cells containing many mitochondria and lipid inclusions. The main segment is intermediate in diameter with many mitochondria and secretory vesicles present. The initial segment is relatively thin in comparison to the other segments and is intimately associated with the digestive gland. The cells of the initial segment contain very little cytoplasm, fewer mitochondria, secretory vesicles, and prominent inclusions. J. Morphol. 251:73,82, 2002. © 2002 Wiley-Liss, Inc. [source] Stabilization of Polymer Bilayers by Introducing Crosslinking at the Interface,MACROMOLECULAR RAPID COMMUNICATIONS, Issue 12 2006Narong An Abstract Summary: Bisphenol A solid epoxy serves as an effective reaction compatibilizer to the bisphenol A polycarbonate (PC)/PMMA bilayer systems. Addition of epoxy to the bottom PMMA layer can retard or even prevent the dewetting of PC films by introducing crosslinking between both components at the interface. This is the first investigation of polymer bilayers stabilized by chemical reactions. AFM topographic image of a representative dewetting hole. [source] Paleodemography of a medieval population in Japan: Analysis of human skeletal remains from the Yuigahama-minami siteAMERICAN JOURNAL OF PHYSICAL ANTHROPOLOGY, Issue 1 2006Tomohito Nagaoka Abstract The purpose of this study is to obtain demographic data regarding the medieval population buried at the Yuigahama-minami site in Kamakura, Japan, and to detect a secular trend in the life expectancy of Japanese population over the last several thousand years. The Yuigahama-minami skeletal sample consists of 260 individuals, including 98 subadults (under 20 years old) and 162 adults. A Yuigahama-minami abridged life-table analysis yielded a life expectancy at birth (e0) of 24.0 years for both sexes, a life expectancy at age 15 years (e15) of 15.8 years for males, and an e15 of 18.0 years for females. The reliability of the estimated e0 was confirmed by analysis of the juvenility index. Demographic profiles comparing the Yuigahama-minami series with other skeletal series indicated that both the survivorship curve and life expectancy of the Yuigahama-minami sample are similar to those of the Mesolithic-Neolithic Jomon population, but are far lower than those of the early modern Edo population. These comparisons strongly suggest that life expectancy changed little over the thousands of years between the Mesolithic-Neolithic Jomon and medieval periods, but then improved remarkably during the few hundred years between the medieval period and early modern Edo period. The short-lived tendency of the Yuigahama-minami sample does not contradict the archaeological hypothesis of unsanitary living conditions in medieval Kamakura. This is the first investigation to address the demographic features of a medieval population in Japan, and will help refine our understanding of long-term trends in the demographic profiles of inhabitants of Japan. Am J Phys Anthropol, 2006. © 2006 Wiley-Liss, Inc. [source] In Search of the Classics: A Study of the Impact of JPIM Papers from 1984 to 2003,THE JOURNAL OF PRODUCT INNOVATION MANAGEMENT, Issue 4 2010Wim Biemans The Journal of Product Innovation Management (JPIM) was launched in 1984 and over its first two decades of existence evolved into the leading journal in the field of innovation and the management of technology. During these 20 years JPIM contributed to the field by publishing 488 academic papers. This paper is a follow-up study to an earlier study that looked at how JPIM evolved in terms of knowledge stock and knowledge flows during the first two decades (published in JPIM, March 2007). That paper looked at what was published during the first 20 years, which sources were cited, and which journals cited JPIM papers. This study takes a closer look at the impact of JPIM on the field of innovation and the management of technology by identifying the most classic papers published in JPIM during its first two decades of existence. This study used multiple research methods to identify 64 candidate potential classics from the 488 papers published in the first 20 years of JPIM's existence, to analyze how they differ from the other 424 papers published in the journal, and to investigate authors' motivations for writing these papers. Finally, using survey responses from the Product Development and Management Association (PDMA) membership and other academics in innovation and new product development, the research then determines which 5 of the 64 candidate papers are considered to be the "most classic" papers published and the factors driving that determination. The findings show that classic papers are those presenting a "pioneering idea" in the field that creates buzz in both the academic and practitioner worlds. High numbers of citations are indeed the outcome of these endeavors, but being a classic requires more than having high numbers of citations. Authors of the true classics generally have worked hard to disseminate their research, usually to both academics and practitioners, perhaps also contributing to the network buzz created by their findings. While one of the five most classic papers represented the first investigation into a particular stream of research, the other four were culminations of a significant body of research, providing a distinct summary of known information on a topic at the time they were published and a clear road forward for future research on the topic. These bodies of knowledge have yet to be superseded by other culminating papers. [source] Photometric study of the OB star clusters NGC 1502 and NGC 2169 and mass estimation of their members at the University Observatory Jena,ASTRONOMISCHE NACHRICHTEN, Issue 5 2009M.M. Hohle Abstract In this work we present detailed photometric results of the trapezium like galactic nearby OB clusters NGC 1502 and NGC 2169 carried out at the University Observatory Jena. We determined absolute BVRI magnitudes of the mostly resolved components using Landolt standard stars. This multi colour photometry enables us to estimate spectral type and absorption as well as the masses of the components, which were not available for most of the cluster members in the literature so far, using models of stellar evolution. Furthermore, we investigated the optical spectrum of the components ADS 2984A and SZ Cam of the sextuple system in NGC 1502. Our spectra clearly confirm the multiplicity of these components, which is the first investigation of this kind at the University Observatory Jena (© 2009 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim) [source] Insights into the evolution of the nucleolus by an analysis of its protein domain repertoireBIOESSAYS, Issue 5 2004Eike Staub Recently, the first investigation of nucleoli using mass spectrometry led to the identification of 271 proteins. This represents a rich resource for a comprehensive investigation of nucleolus evolution. We applied a protocol for the identification of known and novel conserved protein domains of the nucleolus, resulting in the identification of 115 known and 91 novel domain profiles. The phyletic distribution of nucleolar protein domains in a collection of complete proteomes of selected organisms from all domains of life confirms the archaebacterial origin of the core machinery for ribosome maturation and assembly, but also reveals substantial eubacterial and eukaryotic contributions to nucleolus evolution. We predict that, in different phases of nucleolus evolution, protein domains with different biochemical functions were recruited to the nucleolus. We suggest a model for the late and continous evolution of the nucleolus in early eukaryotes and argue against an endosymbiotic origin of the nucleolus and the nucleus. Supplementary material for this article can be found on the BioEssays website at http://www.interscience.wiley.com/jpages/0265-9247/suppmat/index.html. BioEssays 26:567,581, 2004. © 2004 Wiley Periodicals, Inc. [source] Variations in the evaluation of colorectal cancer riskCOLORECTAL DISEASE, Issue 3 2005R. J. Hodder Abstract Objectives, To test the variability in estimating cancer risk and demonstrate the consequences that subjectivity has on patient care. Subjects and methods, Forty-three clinicians were each asked to assess 40 symptomatic colorectal referrals. Each clinician was provided with a comprehensive history on the 40 patients. The clinicians graded the referral according to a malignancy risk score, decided on the required first line investigation and the priority of that investigation. The main outcome measures used was accuracy in cancer detection and appropriateness of investigations selected. Results, There was a wide degree of variation among all clinicians grading both benign and malignant disease with the overall correct classification of 54% (P -value of <0.001). On average, the clinicians correctly diagnosed 71.3% of the cancer patients as compared to 44% of the benign patients. Of the cancer patients, 47% were correctly classified as an urgent referral whilst 52% of the benign patients were over classified and graded as an urgent referral. The mean number chosen by clinicians to have a flexible sigmoidoscopy as the appropriate first investigation was 13 (of 40 patients); this was despite the diagnosis being possible in all cases with a flexible sigmoidoscopy. The choice to use full colonic investigation was seen throughout all disciplines. Junior doctors demonstrated the highest tendency choosing full colonic investigation in 92.3%. Consultants and senior grades showed the least tendency to choose full colonic imaging although even here colonoscopy or barium enema represented 48.5%. Conclusion, Subjective assessment of cancer referrals is a significant problem that needs to be confronted. Improvements are needed to resolve the inherent problems of subjectivity and operator bias if uniform quality of patient care and best use of resources is to be achieved. [source] Materials Selection Process for Compound-Extruded Aluminium Matrix Composites,ADVANCED ENGINEERING MATERIALS, Issue 12 2005A. Weidenmann Compound extrusion is a near-net-shape process allowing for the rapid and flexible in-line production of unidirectionally-reinforced profiles. Regarding the use of this technology for the production of reinforced lightweight profiles for structural applications, no materials combination has yet been systematically assessed or examined since the first investigations on compound conductor rails starting in the 1970s. On this account, a materials selection process respecting the compound extrusion demands is mandatory. [source] Preface: phys. stat. sol. (b) 245/3PHYSICA STATUS SOLIDI (B) BASIC SOLID STATE PHYSICS, Issue 3 2008Christopher W. Smith This is the third Special Issue of physica status solidi (b) focusing on materials with a negative Poisson's ratio or other ,anomalous' physical properties. This issue contains selected papers from the First International Conference on Auxetics and Anomalous Systems held at the University of Exeter, UK, on 4,6 September 2006. Around 50 participants from all over the world as well as from a wide range of scientific and engineering disciplines contributed to what was a highly successful conference. This conference follows in the footsteps of two previous workshops held at the Mathematical Research and Conference Centre in B,dlewo near Pozna,, Poland, in 2004 and 2005 [1, 2]. The papers selected for this issue publish recent results obtained for ,anomalous systems' in experiment, theory and computer simulations. In the following we summarize very briefly their contents. Alderson and Coenen compare the performance of auxetic composites to similar systems with conventional positive Poisson's ratios. They find that there are indeed differences which appear to arise from the change of the overall Poisson's ratio of the composite, some beneficial like a rise in impact tolerance at low impact rates, and others deleterious such as the reduced tolerance at higher impact rates. This is one of the first investigations of possible applications for auxetic materials. The two papers by Gaspar and Koenders both examine the effects of disorder upon anomalous properties, especially negative Poisson's ratio. In the first one Gaspar demonstrates how a mean strain estimate fails to predict negative values of Poisson's ratio because of an inability to account for local fluctuations in elastic properties. For instance it is shown that the volume fraction of auxetic regions in an globally auxetic material (measured experimentally) are smaller than a mean strain homogenisation would require. Koenders and Gaspar explore the elastic properties, and especially Poisson's ratio, of a heterogeneous 2D network of bending beams. They predict auxetic behaviour arising from localised disorder in the packing, and therefore effective locally aggregated elastic properties of the beams. In the three articles by Gatt et al. and Grima et al. models based on simple geometry are used to explain the behaviour of seemingly disparate systems, i.e. 2D honeycombs systems and zeolite SiO2 networks. Two papers concerning honeycombs demonstrate relationships between elastic properties and structure and the bounds for auxetic behaviour. The paper concerning the zeolite Natrolite uses numerical force field based energy minimisation methods to simulate the response of this particular zeolite to applied forces and then simplifies the predicted properties even further by considering structural units as rigid 2D polyhedra linked by flexible hinges. In a similar vein, though using a different approach and concerning a very different form of matter, Heyes shows how the heterogeneity in an assembly of particles in a liquid can affect the elastic properties of a liquid and notably the infinite frequency Poisson's ratio. Heyes uses the Molecular Dynamics approach to simulate a Lennard,Jones fluid under various pressures, notably comparing behaviour under positive and negative pressures. In their first paper Jasiukiewicz and co-authors derive elastic constants of 2D crystals for all four classes of 2D crystalline solids: hexagonal (isotropic), quadratic, rectangular, and oblique systems. In their second paper they demonstrate conditions required for auxetic behaviour of 2D crystals. Auxetic solids are further divided into those with some negative Poisson's ratios (auxetic), all negative Poisson's ratios (completely auxetic) and no negative Poisson's ratios (non-auxetic). Lakes and Wojciechowski consider counterintuitive properties of matter, like negative compressibility, negative Poisson's ratio, negative thermal expansion, negative specific heat, and negative pressure. They present and interpret experimental observations of negative bulk modulus in pre-strained foams. They propose also a constrained microscopic model which exhibits negative compressibility. Finally, they solve a very simple thermodynamic model with negative thermal expansion. Martin et al. take a long stride toward a real world application of auxetic materials with a wide ranging study starting with numerical modelling of a wingbox section to experimental testing in a wind tunnel. They show that an auxetic core in a wing box section can allow a passive aero-elastic response which can be tailored by careful design of the core so that camber, and thus drag, is reduced with increasing airspeed but without sacrificing structural integrity. Miller et al. consider another anomalous physical property, negative thermal expansivity, and its application in the form of particulate composites for amelioration of stresses arising from thermal mismatch. They show via experiments that particles with a negative coefficient of thermal expansion may be used as a composite reinforcer to reduce overall thermal expansion and behave according to the standard volume fraction based models. Narojczyk and Wojciechowski examine the effects of disorder upon the bulk elastic properties of 3D fcc soft sphere systems in terms of particle size. Systems, such as colloids, can be thought of in such terms. The study shows that higher order moments of probability distribution do not influence the bulk elastic properties much, but that lower moments such as the standard deviation of particle size influence the elastic properties greatly. The "hardness" of the particle interaction potential is also important in this context. In general, it is shown that the effect of increasing polydispersity is to increase the Poisson's ratio, except the [110] [10] directions. Scarpa and Malischewsky in their paper on Rayleigh waves in auxetic materials show how the Rayleigh wave speed is affected by the Poisson's ratio. The behaviour is complex and depends upon the homogeneity within the material, for instance slowing with decreasing Poisson's ratio in isotropic solids, but showing the reverse trend and increased sensitivity to Poisson's ratio in laminate composites. Scarpa et al. explore the buckling behaviour of auxetic tubes via three types of model, a simple beam mechanics and Eulerian buckling model, a 3D linear elastic FE model and a bespoke non-linear continuum model. The more sophisticated models provide increasing insight into the buckling behaviour though the simple beam model predicts reasonably well in the pre-buckling linear region. Some unexpected and interesting behaviour is predicted by the continuum model as the Poisson's ratio approaches the isotropic limit of ,1, including increasing sensitivity to Poisson's ratio and rapid mode jumping between integer wave numbers. The paper by Shilko et al. presents an analysis of a particular kind of friction joint, a double lap joint, and explores the effects of altering the elastic properties of one component, in particular it's Poisson's ratio. The manuscript introduces the evolution of smart materials from monolithic materials, and the classification of composites exhibiting negative Poisson's ratios. The paper then presents the case of a double lap joint and performs a sensitivity type study, via a 2D FE model, of the effects of changing the elastic properties and degree of anisotropy of one section of the model on various parameters defining the limits of functionality of the joint. The main finding is that an enhanced shear modulus, via a negative Poisson's ratio, can endow such a friction joint with superior performance. Manufacturing of auxetic materials on a commercial scale has proved to be the largest obstacle to their fuller exploitation. The paper by Simkins et al. explores one route for post processing of auxetic polymers fibres produced by a conventional melt extrusion route. Simkins et al. showed that a post process thermal annealing treatment, with carefully optimised parameters, was able to even out otherwise inhomogenous auxetic properties, and moreover improve other elastic and fracture properties often sacrificed for auxetic behaviour. We gratefully acknowledge the support given by the sponsors of the conference, namely the EPSRC of the UK and Auxetic Technologies Ltd. (UK). We also thank the Scientific Committee, the Organising Committee, and all the participants of the conference. (© 2008 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim) [source] Progenitor cells in liver regeneration: molecular responses controlling their activation and expansion,APMIS, Issue 11-12 2005ERIC SANTONI-RUGIU Although normally quiescent, the adult mammalian liver possesses a great capacity to regenerate after different types of injuries in order to restore the lost liver mass and ensure maintenance of the multiple liver functions. Major players in the regeneration process are mature residual cells, including hepatocytes, cholangiocytes and stromal cells. However, if the regenerative capacity of mature cells is impaired by liver-damaging agents, hepatic progenitor cells are activated and expand into the liver parenchyma. Upon transit amplification, the progenitor cells may generate new hepatocytes and biliary cells to restore liver homeostasis. In recent years, hepatic progenitor cells have been the subject of increasing interest due to their therapeutic potential in numerous liver diseases as alternative or supportive/complementary tools to liver transplantation. While the first investigations on hepatic progenitor cells have focused on their origin and phenotypic characterization, recent attention has focused on the influence of the hepatic microenvironment on their activation and proliferation. This microenvironment comprises the extracellular matrix, epithelial and non-epithelial resident liver cells, and recruited inflammatory cells as well as the variety of growth-modulating molecules produced and/or harboured by these elements. The cellular and molecular responses to different regenerative stimuli seem to depend on the injury inflicted and consequently on the molecular microenvironment created in the liver by a certain insult. This review will focus on molecular responses controlling activation and expansion of the hepatic progenitor cell niche, emphasizing similarities and differences in the microenvironments orchestrating regeneration by recruitment of progenitor cell populations or by replication of mature cells. [source] Population pharmacokinetics of mycophenolic acid in children and young people undergoing blood or marrow and solid organ transplantationBRITISH JOURNAL OF CLINICAL PHARMACOLOGY, Issue 4 2010Lihua Zeng WHAT IS ALREADY KNOWN ABOUT THIS PROJECT? , Mycophenolate mofetil (MMF) is an immunosuppressant drug used for the treatment and prevention of graft vs. host disease in blood or marrow transplantation and acute graft rejection in solid organ transplantation. , Mycophenolic acid (MPA) pharmacokinetics have not been thoroughly studied in paediatric blood or marrow transplant recipients and guidance for optimal dosing of mycophenolic acid in children is lacking. , Mycophenolic acid exhibits considerable inter- and intra-patient pharmacokinetic variability in adults and paediatric transplant recipients. , The AUC of mycophenolic acid over a 12 h dose interval at steady-state is generally agreed to be the most reliable metric associated with the risk of acute rejection. , Population pharmacokinetic analysis can utilize concentration information from both intensive sampling and sparse sampling to provide pharmacokinetic parameter estimates, estimates of inter- individual and intra-individual variability in these parameters and allows patient characteristics explaining inter-individual variability to be quantified. WHAT THIS STUDY ADDS , This study is one of the first investigations in which a population pharmacokinetic modelling approach was applied to assess the pharmacokinetics of both intravenous and oral MMF in children and young people undergoing blood or marrow and solid organ transplantation. , Bodyweight and concomitant ciclosporin were found to influence MPA pharmacokinetics. , This study evaluated current dosing strategies and found that they may be suboptimal for children weighing less than 10 kg. AIMS To characterize the population pharmacokinetics of mycophenolic acid (MPA) and evaluate dose regimens using a simulation approach and accepted therapeutic drug monitoring targets in children and young people undergoing blood or marrow, kidney and liver transplantation. METHODS MPA concentration,time data were collected using an age specific sampling protocol over 12 h. Some patients provided randomly timed but accurately recorded blood samples. Total and unbound MPA were measured by HPLC. NONMEM was employed to analyze MPA pharmacokinetic data. Simulations (n= 1000) were conducted to assess the suitability of the MPA dose regimens to maintain total MPA AUC(0,12 h) within the range 30 and 60 mg l,1 h associated with optimal outcome. RESULTS A two-compartment pharmacokinetic model with first-order elimination best described MPA concentration,time data. Population mean estimates of MPA clearance, inter-compartmental clearance, volumes of distribution in the central and peripheral compartments, absorption rate constant and bioavailability were 6.42 l h,1, 3.74 l h,1, 7.24 l, 16.8 l, 0.39 h,1 and 0.48, respectively. Inclusion of bodyweight and concomitant ciclosporin reduced the inter-individual variability in CL from 54.3% to 31.6%. Children with a bodyweight of 10 kg receiving standard MPA dose regimens achieve an MPA AUC below the target range suggesting they may be at a greater risk of acute rejection. CONCLUSIONS The population pharmacokinetic model for MPA can be used to explore dosing guidelines for safe and effective immunotherapy in children and young people undergoing transplantation. [source] | ||||||||||||||||||||||