6,419 research outputs found
Growth, head growth, and neurocognitive outcome in children born very preterm: methodological aspects and selected results
No full textIn light of the growing number of surviving children born very preterm, there is an increasing focus on their long-term outcomes in terms of growth, metabolic status, and neurocognitive development. Therefore, it is of importance to follow such children from birth onwards with the aim of identifying the causes of atypical development, developing preventative measures, and improving outcomes. Since such long-term follow-up needs to be conducted with the least possible burden, clinical investigations such as anthropometry and neurocognitive tests, if conducted rigorously, will continue to have a predominant role. The aim of this review is to discuss the complexity of longitudinal anthropometry in children born very preterm and to provide an overview of the main studies that have examined associations between growth, in particular head growth, and neurocognitive outcomes at around school age
Halting a Runaway Train: Reforming Teacher Pensions for the 21st Century
No full textWhen it comes to public-sector pensions, writes lead author Michael B. Lafferty in this report, "A major public-policy (and public-finance) problem has been defined and measured, debated and deliberated, but not yet solved. Except where it has been." As recounted in "Halting a Runaway Train: Reforming Teacher Pensions for the 21st Century", these exceptions turn out to be revealing -- and encouraging
Michael Mark Papers
No full textMichael Mark (b. 1936) is an American music educator and author. He received his degrees in music from Catholic University (BM 1958 and DMA 1969), George Washington University (MA 1960), and the University of Michigan (MM 1962). During his career, Mark was employed by public school systems and universities in Maryland, Washington, D.C., and New York. As an author he has published numerous books and articles on music education, frequently on the history of that topic. This collection consists of educational materials, correspondence, writings, newspaper clippings, photographs, books, recordings, and scores related to his career as an educator and author
Insulin-like Growth Factor I (IGF-I), IGF Binding Protein-3 (IGFBP-3) und Alkaline Phosphatase (AP) with organic growth hormone deficiency (GHD), intrauterine growth retardation and idiopathic short stature (ISS)
No full textVollständiger Titel: Insulin-like Growth Factor I (IGF-I), IGF Binding Protein-3 (IGFBP-3) und Alkalische Phosphatase (AP) bei organischem Wachstumshormonmangel (GHD), intrauteriner Wachstumsretardierung und idiopathischem Kleinwuchs (ISS), vor und während der Therapie mit Wachstumshormon (GH)
In dieser Studie wurde untersucht, inwieweit bei bestehendem Kleinwuchs die Substitution mit hGH die Serumkonzentration von IGF-I, IGFBP-3 und AP beeinflusst, ob die Änderungen der einzelnen Parameter mit dem Größenwachstum korrelieren und welchen diagnostischen Stellenwert diese Parameter dabei einnehmen. Insgesamt wurden 70 Patienten (45 Jungen, 25 Mädchen) im Alter von 2 bis 17 Jahren auf drei Gruppen verteilt: Gruppe 1: Patienten mit Kleinwuchs bei organischem GHD, behandelt mit hGH = ~ 0,45 IE/kg/Woche (n=20); Gruppe 2: Patienten mit Kleinwuchs bei intrauteriner Wachstumsretardierung (IUGR), Silver-Russell- oder Noonan-Syndrom, therapiert mit hGH = ~ 0,80 IE/kg/Woche (n=20) und Gruppe 3: ISS-Patienten und Patienten mit nicht klassifizierbarem Kleinwuchs, behandelt mit hGH = ~ 0,57 IE/kg/Woche (n=30). Wachstumshormon wurde in jedem Fall täglich subcutan appliziert, der Beobachtungszeitraum betrug ein Jahr (70 Pat.) bzw. drei Jahre (60 Pat.). Mittleres Alter zu Therapiebeginn: 8,7 Jahre. Die höchste mittlere Zunahme der Serumspiegel bezüglich der untersuchten Parameter erfolgte im ersten Therapiejahr, insbesondere während den ersten drei Therapiemonaten: IGF-I stieg in Gruppe 1 sehr signifikant (p= 0,003), in den Gruppen 2 u. 3 jeweils hoch signifikant (p<0,001) an, die Zunahme von IGFBP-3 war in den drei Gruppen jeweils hoch signifikant (p<0,001), diejenige von AP in den Gruppen 1 und 2 jeweils sehr signifikant (p=0,003 bzw. p=0,007), in Gruppe 3 hoch signifikant (p<0,001). In dem entsprechenden Zeitraum nahm auch die Körpergröße in allen drei Gruppen hoch signifikant (p<0,001) zu. Aus der folgenden Tabelle sind in jeder Gruppe neben den Ausgangsdaten der Untersuchungsgrößen die ein- und dreijährigen Zunahmen, ausgedrückt als mittlerer Standard Deviation Score (SDS), ersichtlich (∆SDS: Differenz des Mittelwert-SDS nach einem Jahr bzw. nach drei Jahren Therapie und zu Therapiebeginn). Signifikante Unterschiede im Hinblick auf den Anstieg der Parameter im direkten Gruppenvergleich ergaben sich lediglich im ersten Jahr jeweils zwischen den Gruppen 1 und 3 in Bezug auf IGFBP-3 (p=0,03) und AP (p=0,02).
Je niedriger die Serumspiegel von IGF-I und IGFBP-3 zu Therapiebeginn waren, desto schneller und stärker vollzog sich deren Annäherung unter WH-Therapie an altersentsprechende Normwerte mit konsekutivem Aufholwachstum. Dieses Verhalten lässt sich nicht auf die alkalische Phosphatase übertragen. Die Ergebnisse dieser Studie belegen die Rolle von IGF-I, IGFBP-3 und AP im Patientenserum als unverzichtbare Indikatoren im Rahmen der Diagnostik und Therapie des Kleinwuchses.Full Title: Insulin-like Growth Factor I (IGF-I), IGF Binding Protein-3 (IGFBP-3) und Alkaline Phosphatase (AP) with organic growth hormone deficiency (GHD), intrauterine growth retardation and idiopathic short stature (ISS), before and during the therapy with growth hormone (GH)
In this study it was examined, to what extent with existing short stature the substitution with hGH affects the serum concentration of IGF-I, IGFBP-3 and AP, whether the changes of the individual parameters correlate with the size growth and which diagnostic value these parameters take thereby. Altogether 70 patients (45 boys, 25 girls) at the age of 2 to 17 years were distributed on three groups: group 1: patients with short stature with organic GHD, treated with hGH = ~ 0,45 IU/kg/week (n=20); group 2: patients with short stature with intrauterine growth retardation (IUGR), Silver-Russell- or Noonan-syndrome, treated with hGH = ~ 0,80 IU/kg/week (n=20) and group 3: patients with ISS and patients with non-classifi- able short stature, treated with hGH = ~ 0,57 IU/kg/week (n=30). Growth hormone was administered in each case daily subcutaneously, the period of observation amounted to one year (70 patients) and three years (60 patients), respectively. Mean age at start of therapy: 8,7 years. The highest mean increase of the serum levels with regard to the examined parameters occurred in the first year of therapy, in particular during the first three months of therapy: IGF-I rose very significantly (p=0,003) in group 1, in the groups 2 and 3 highly significant (p<0,001) in each case, the increase of IGFBP-3 in the three groups was highly significant (p<0,001) in each case, that of AP in the groups 1 and 2 very signi- ficantly (p=0,003 and p=0,007, respectively) in each case, in group 3 highly significant (p<0,001). In the corresponding period, the height also increased in all three groups highly significantly (p<0,001). From the following table, besides the original data of the investigation sizes, the one and three-year increases in each group, expressed as the mean standard deviation score (SDS), are evident (∆SDS: difference of the average value-SDS after one year and after three years of therapy, respectively and at start of therapy). Significant differences with regard to the rise of the parameters in the direct comparison of the groups only arose in the first year in each case between the groups 1 and 3 concerning IGFBP-3 (p=0,03) and AP (p=0,02).
At start of therapy, the lower the serum levels of IGF-I and IGFBP-3 were, the faster and more strongly carried out themselves their approximation to age- appropriate standard values under GH therapy with consecutive catch-up growth. This behavior can not be assigned onto the alkaline phosphatase. The results of this study cover the role of IGF-I, IGFBP-3 and AP in the patient serum as indispensable indicators within the diagnostics and therapy of short stature
Insulin-like Growth Factor I (IGF-I), IGFBP-3 and Alkaline Phosphatase (AP) in children with idiopathic Growth Hormone Deficiency (iGHD) and Neurosecretoric Dysfunction (NSD) before and during therapy with human Growth Hormone (GH)
No full textEs wurden 116 überwiegend präpubertäre Kinder über einen Zeitraum von einem bzw. vier Jahren untersucht, die an der Universitäts-Kinderklinik Tübingen wegen idiopathischem Wachstumshormonmangel (iGHD) oder wegen Neurosekretorischer Dysfunktion (NSD) mit ca. 0,6 IU rekombinantem Wachstumshormon pro kg Körpergewicht und Woche behandelt wurden. Die Diagnose iGHD wurde gestellt bei einer mittleren nächtlichen Spontansekretion von 10ng/ml GH. Es wurden folgende Parameter untersucht: Körpergröße/ -gewicht, Body-Mass-Index, Knochenalter, Insulin-like Growth Factor I (IGF-I), IGFBP-3 und Alkalische Phosphatase (AP). Die Körpergröße war bei beiden Diagnosen zu Therapiebeginn deutlich erniedrigt (iGHD: MW=-3,7+/-1,3SD; NSD: MW=-3,0+/-0,7SD). Die iGHD-Patienten zeigten zu Therapiebeginn signifikant niedrigere Werte für die Körpergröße, die IGF-I- und die IGFBP-3-Serumkonzentration (p10ng/ml). The following parameters were measured: height, weight, body-mass-index, bone age, insulin-like growth factor I (IGF-I), insulin-like growth factor binding protein 3 (IGFBP-3) and alkaline phosphatase (AP). In both groups height before GH-therapy was below the reference-data (mean[iGHD]=-3,7+/-1,3SD; mean[NSD]=-3,0+/-0,7SD). Furthermore the children with the diagnosis iGHD had significant lower hight, IGF-I- and IGFBP-3-serum-levels before therapy (p<0,001). In both groups (iGHD and NSD) a significant rise of hight, weight, IGF-I, IGFBP-3 and AP was found during the first year of therapy (p<0,001 except AP[NSD]: p=0,02). It could be seen that the iGHD-patients grew faster than the NSD-patients (1 year: p=0,04; 4 years: p=0,03). In the iGHD-group a significant correlation between the rapid catch-up growth during the first year on GH and small values of hight (p=0,007), IGF-I (p<0,001) and IGFBP-3 (p=0,002) before therapy onset were found
Important tools for use by pediatric endocrinologists in the assessment of short stature
No full textAssessment and management of children with growth failure has improved greatly over recent years. However, there remains a strong potential for further improvements by using novel digital techniques. A panel of experts discussed developments in digitalization of a number of important tools used by pediatric endocrinologists at the third 360 degrees European Meeting on Growth and Endocrine Disorders, funded by Merck KGaA, Germany, and this review is based on those discussions. It was reported that electronic monitoring and new algorithms have been devised that are providing more sensitive referral for short stature. In addition, computer programs have improved ways in which diagnoses are coded for use by various groups including healthcare providers and government health systems. Innovative cranial imaging techniques have been devised that are considered safer than using gadolinium contrast agents and are also more sensitive and accurate. Deep-learning neural networks are changing the way that bone age and bone health are assessed, which are more objective than standard methodologies. Models for prediction of growth response to growth hormone (GH) treatment are being improved by applying novel artificial intelligence methods that can identify non-linear and linear factors that relate to response, providing more accurate predictions. Determination and interpretation of insulin-like growth factor-1 (IGF-1) levels are becoming more standardized and consistent, for evaluation across different patient groups, and computer-learning models indicate that baseline IGF-1 standard deviation score is among the most important indicators of GH therapy response. While physicians involved in child growth and treatment of disorders resulting in growth failure need to be aware of, and keep abreast of, these latest developments, treatment decisions and management should continue to be based on clinical decisions. New digital technologies and advancements in the field should be aimed at improving clinical decisions, making greater standardization of assessment and facilitating patient-centered approaches.Developmen
Bernard Williams
No full textAn edited multi-author volume assessing the moral philosophy of the late British philosopher Bernard Williams. Contributors: Adrian Moore, John Skorupski, Alan Thomas, Robert B Louden, Michael Stocker, A. A. Long, Edward Crai
Postmodern Theory and the Choreography of Michael Clark
No full textThis study addresses two interrelated questions: Can postmodern ‘theory’ illuminate an understanding of Michael Clark’s work? and, a sub-question, In which ways, if at all, does Clark’s work demonstrate a postmodern sensibility? Chapter one, the introduction to this study, provides a ‘portrait’ of postmodernism, that is, it addresses the question What is postmodernism? Chapter two is a biography of Michael Clark. The seminal sections to this study, however, are chapters three and four. Here the author blends a discussion of a) subject matter, treatment and meanings in Clark’s choreography, b) journalistic criticisms of those features of his work, and c) postmodern theory. The outcome of these chapters is to demonstrate that Clark’s works do indeed require re-interpretation and re-evaluation, and to illustrate how these factors might be achieved
On the Michael addition of water to C = C bonds
No full text?-Hydroxy carbonyl compounds are an important class of compounds often found as a common structural motif in natural products. Although the molecules themselves look rather simple, their synthesis can be challenging. Water addition to conjugated C = C bonds opens up a straightforward route for the preparation of ?-hydroxy carbonyl compounds. Moreover, water addition to C = C bonds benefits a lot from its simplicity and excellent atom economy. However, the enantioselective addition of water to ?,?-unsaturated carbonyl (Michael) acceptors still represents a chemically very challenging reaction, due to the poor nucleophilicity of water and its small size, which make regio- and stereoinduction difficult. Equally, the often unfavorable equilibrium of water-addition reactions remains to be solved. In contrast, enzymes such as fumarase, malease, citraconase, aconitase, and enoyl-CoA hydratase have been successfully used on industrial scale, and their excellent (enantio-) selectivities are highly valued. Unfortunately, most hydratases are part of the primary metabolism where perfect substrate specificity is required. This very high substrate selectivity severely limits their practical applicability in organic synthesis. Thus, a straightforward approach with broad applicability still had not been described. The aim of the research presented in this thesis was to take up this challenge and dedicated to the search for a Michael hydratase with a more relaxed substrate specificity for the preparation of important ?-hydroxy carbonyl compounds. The stereospecificity of enzyme-catalysed reactions has been a fruitful source of information about the mechanisms of enzyme catalysis and vice versa; the application of stereospecifically labelled substrates allows for studying the course of the reaction. It offers a very promising opportunity to comprehensively understand the precise mechanistic and kinetic details of even the most complex enzymatic reactions. Thus Chapter 1 provides unifying ideas for stereochemistry of the enzymatic water addition to C = C bonds. This enhances our understanding of the chemistry of water addition to C = C bonds, and further allows us to find more hydratases from natural sources or obtained via protein engineering. In Chapter 2, a direct, enantioselective Michael addition of water in water to prepare important ?-hydroxy carbonyl compounds using whole cells of Rhodococcus strains is described. Good yields and excellent enantioselectivities were achieved with this method. This opens up an entirely new approach for the preparation of important ?-hydroxy carbonyl compounds. Deuterium labelling studies demonstrate that a Michael hydratase catalyzes the water addition exclusively with anti-stereochemistry, which belongs to the family members of hydratases: oleate hydratase, fumarase, malease, aconitase and type II dehydroquinase with a preference for the anti-addition; whereas, type I dehydroquinase, enoyl-CoA hydratase and artificial hydratase exclusive prefer for the syn-addition, as discussed in Chapter 1. The biocatalytic reaction system was carefully optimized for gram-scale synthesis, resulting in good conversions and excellent enantioselectivities. Under the optimized conditions, whole cells could be reused for 4 cycles without significant loss of activity while maintaining up to 90% ee. Since whole cells from Rhodococcus strains were used to catalyse the Michael addition of water in water to a series of ?,?-unsaturated carbonyl compounds, and when the work presented in Chapter 2 started, no genomic information of Rhodococcus strains was publically available, we sequenced and annotated the strain R. rhodochrous ATCC 17895. This is described in Chapter 3 together with features of the R. rhodochrous ATCC 17895. It is a Gram-positive aerobic bacterium with a rod-like morphology. The 6,869,887 bp long genome contains 6,609 protein-coding genes and 53 RNA genes. Our study suggests the Michael hydratase has not been described before. In the work presented in Chapter 2, we found that most ?-hydroxy ketones are not commercially available or commercially expensive as we mentioned in the first paragraph, which made the stereoselectivity determination of Michael addition products difficult. Indeed, many seemingly simple molecules have to be prepared via multi-step syntheses, in particular so if they are optically active. Therefore a straightforward approach to enantiomerically enriched (R)- and (S)-3-hydroxycyclopentanone was established by kinetic resolution in Chapter 4. This methodology allows us to prepare more ?-hydroxy carbonyl compounds structurally closely related to 3-hydroxycyclopentanone. The isolated chiral alcohols were used to determine the stereochemistry of the Michael addition of water in Chapter 2, saving us a lot of laboratory work. Moreover, unexpected stereoselective reduction of conjugated C = C bonds was discovered during studies on the enantioselective Michael addition of water. As mentioned in Chapter 2, the whole cells of R. rhodochrous ATCC 17895 reduced ?,?-unsaturated cyclic ketones into the corresponding ketones as initially undesired side reaction for the addition of water to C = C bonds. Therefore, ene-reductase activity was also investigated in Chapter 5. A series of substrates, including activated ketones, aldehydes, amines and nitro-compounds were screened for ene-reductase activity using whole cells of R. rhodochrous ATCC 17895. This showed that R. rhodochrous is a very promising catalyst for the reduction of C = C bonds and harbours ene-reductases. Indeed, looking for the annotated ene reductase from the genome of R. rhodochrous ATCC 17895 as described in Chapter 3, three candidates were observed and were classified as ene-reductases by amino acid sequence alignment with the known Old Yellow Enzymes (OYEs). Thus, the putative ene-reductase genes from R. rhodochrous ATCC 17895 were heterologously overexpressed in Escherichia coli and one of the encoded proteins was purified and characterized for their biocatalytic and biochemical properties. Based on these accomplishments it can be concluded that we have discovered a new Michael hydratase and three new ene reductases from Rhodococcus strains. Genome sequence and annotation of strain R. rhodochrous ATCC 17895 has been done, offering an excellent opportunity for the discovering novel enzymes, for instance, the Michael hydratase and S-selective ene reductase. The important chiral ?-hydroxy carbonyl compounds can be prepared by kinetic resolution of racemic alcohols using lipases or the direct enantioselective Michael addition of water using whole cells of Rhodococcus strains. The isolated products from kinetic resolution were readily used for the stereochemistry determination of Michael addition of water in water, completes the story of water addition to C = C bonds.BiotechnologyApplied Science
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