Somatostatin analogues in the treatment of gastroenteropancreatic neuroendocrine tumours, current aspects and new perspectives

Gastroenteropancreatic neuroendocrine tumours (GEP NETs) are rare tumours that present many clinical features

Plio-Pleistocene phylogeography of the Southeast Asian Blue Panchax killifish, Aplocheilus panchax

The complex climatic and geological history of Southeast Asia has shaped this region’s high biodiversity. In particular, sea level fluctuations associated with repeated glacial cycles during the Pleistocene both facilitated, and limited, connectivity between populations. In this study, we used data from two mitochondrial and three anonymous nuclear markers to determine whether a fresh/brackish water killifish, Aplocheilus panchax, Hamilton, 1822, could be used to further understand how climatic oscillations and associated sea level fluctuations have shaped the distribution of biota within this region, and whether such patterns show evidence of isolation within palaeodrainage basins. Our analyses revealed three major mitochondrial clades within A. panchax. The basal divergence of A. panchax mitochondrial lineages was approximately 3.5 Ma, whilst the subsequent divergence timings of these clades occurred early Pleistocene (~2.6 Ma), proceeding through the Pleistocene. Continuous phylogeographic analysis showed a clear west-east dispersal followed by rapid radiation across Southeast Asia. Individuals from Krabi, just north of the Isthmus of Kra, were more closely related to the Indian lineages, providing further evidence for a freshwater faunal disjunction at the Isthmus of Kra biogeographic barrier. Our results suggest that Sulawesi, across the Wallace Line, was colonised relatively recently (~30 ka). Nuclear DNA is less geographically structured, although Mantel tests indicated that nuclear genetic distances were correlated with geographic proximity. Overall, these results imply that recent gene flow, as opposed to historical isolation, has been the key factor determining patterns of nuclear genetic variation in A. panchax, however, some evidence of historical isolation is retained within the mitochondrial genome. Our study further validates the existence of a major biogeographic boundary at the Kra Isthmus, and also demonstrates the use of widely distributed fresh/brackishwater species in phylogeographic studies, and their ability to disperse across major marine barriers in relatively recent time periods

Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases

The production of peroxide and superoxide is an inevitable consequence of aerobic metabolism, and while these particular "reactive oxygen species" (ROSs) can exhibit a number of biological effects, they are not of themselves excessively reactive and thus they are not especially damaging at physiological concentrations. However, their reactions with poorly liganded iron species can lead to the catalytic production of the very reactive and dangerous hydroxyl radical, which is exceptionally damaging, and a major cause of chronic inflammation. We review the considerable and wide-ranging evidence for the involvement of this combination of (su)peroxide and poorly liganded iron in a large number of physiological and indeed pathological processes and inflammatory disorders, especially those involving the progressive degradation of cellular and organismal performance. These diseases share a great many similarities and thus might be considered to have a common cause (i.e. iron-catalysed free radical and especially hydroxyl radical generation). The studies reviewed include those focused on a series of cardiovascular, metabolic and neurological diseases, where iron can be found at the sites of plaques and lesions, as well as studies showing the significance of iron to aging and longevity. The effective chelation of iron by natural or synthetic ligands is thus of major physiological (and potentially therapeutic) importance. As systems properties, we need to recognise that physiological observables have multiple molecular causes, and studying them in isolation leads to inconsistent patterns of apparent causality when it is the simultaneous combination of multiple factors that is responsible. This explains, for instance, the decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference

Non-affirmative Theory of Education as a Foundation for Curriculum Studies, Didaktik and Educational Leadership

This chapter presents non-affirmative theory of education as the foundation for a new research program in education, allowing us to bridge educational leadership, curriculum studies and Didaktik. We demonstrate the strengths of this framework by analyzing literature from educational leadership and curriculum theory/didaktik. In contrast to both socialization-oriented explanations locating curriculum and leadership within existing society, and transformation-oriented models viewing education as revolutionary or super-ordinate to society, non-affirmative theory explains the relation between education and politics, economy and culture, respectively, as non-hierarchical. Here critical deliberation and discursive practices mediate between politics, culture, economy and education, driven by individual agency in historically developed cultural and societal institutions. While transformative and socialization models typically result in instrumental notions of leadership and teaching, non-affirmative education theory, previously developed within German and Nordic education, instead views leadership and teaching as relational and hermeneutic, drawing on ontological core concepts of modern education: recognition; summoning to self-activity and Bildsamkeit. Understanding educational leadership, school development and teaching then requires a comparative multi-level approach informed by discursive institutionalism and organization theory, in addition to theorizing leadership and teaching as cultural-historical and critical-hermeneutic activity. Globalisation and contemporary challenges to deliberative democracy also call for rethinking modern nation-state based theorizing of education in a cosmopolitan light. Non-affirmative education theory allows us to understand and promote recognition based democratic citizenship (political, economical and cultural) that respects cultural, ethical and epistemological variations in a globopolitan era. We hope an American-European-Asian comparative dialogue is enhanced by theorizing education with a non-affirmative approach

Das Volk als Autor? : der Ursprung einer kulturgeschichtlichen Fiktion im Werk Johann Gottfried Herders

Bis weit ins achtzehnte Jahrhundert hinein schöpft der Dichter seine Identität und Autorität aus einer Tradition, die im wesentlichen als diachrone "textual community" auftritt. Die Schrift ist das Medium, das die Kontinuität der Tradition sichert. [...] Wer außerhalb dieses Universums steht, wer zum Archiv der Schrift keinen Zugang hat, ist gedächtnislos, kann seine Individualität, kann seine Subjektivität nicht realisieren, ist allenfalls Objekt der Belehrung. Noch die aufklärerischen Konzepte der Volkserziehung – etwa bei Gottsched – speisen sich aus dieser Auffassung und beruhen auf dem Prinzip der In- bzw. Exklusion durch Teilhabe an der Schriftkultur. Dies scheint sich (in Deutschland) seit den sechziger und siebziger Jahren des achtzehnten Jahrhunderts grundlegend zu andern. [...] Als Phönix aus der Asche des poeta doctus steigt nun aber nicht nur das Originalgenie empor; zum Genialitätsparadigma gehört als komplementärer Pol wesentlich die Orientierung auf eine Sphäre, die im Horizont des Gelehrsamkeitsparadigmas außerhalb des Blickfelds geblieben war: jene des aliteralen Volks und der mündlichen Überlieferung. Das Volk gilt nicht mehr nur als Objekt der Erziehung, der Dichter nicht mehr einfach als sein Erzieher. Das Volk wird im Gegenteil zum Ursprungsort der Dichtung und damit das Mündliche zum Ursprungsort des Schriftlichen erhoben. Die Schriftkultur legitimiert sich fortan gar durch Bezug auf ein ihr gegenüber grundsätzlich anders strukturiertes semiotisches System. Diese Komplementarität berührt aber die Frage nach der Autorschaft bereits am kulturgeschichtlichen Ursprungsort ihres emphatischen Begriffes essentiell. Wer ist der Autor – das literale Originalgenie oder das aliterale Volk

The Pugh Controlled Convergence Method: Model-Based Evaluation and Implications for Design Theory

This paper evaluates the Pugh Controlled Convergence method and its relationship to recent developments in design theory. Computer executable models are proposed simulating a team of people involved in iterated cycles of evaluation, ideation, and investigation. The models suggest that: 1) convergence of the set of design concepts is facilitated by the selection of a strong datum concept; 2) iterated use of an evaluation matrix can facilitate convergence of expert opinion, especially if used to plan investigations conducted between matrix runs; and 3) ideation stimulated by the Pugh matrices can provide large benefits both by improving the set of alternatives and by facilitating convergence. As a basis of comparison, alternatives to Pugh's methods were assessed such as using a single summary criterion or using a Borda count. These models suggest that Pugh's method, under a substantial range of assumptions, results in better design outcomes than those from these alternative procedures