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VII
Kinds of VII Terms modified by VII Selected AbstractsCorpus callosum and posterior fossa development in monozygotic females: a morphometric MRI study of Turner syndromeDEVELOPMENTAL MEDICINE & CHILD NEUROLOGY, Issue 5 2003Susannah L Fryer BA Previous neuroimaging research in Turner syndrome (TS) has indicated parietal lobe anomalies, while anomalies in other brain loci have been less well-substantiated. This study focused on potential cerebellar abnormalities and possible disruptions of interhemispheric (parietal) callosal connections in individuals with TS. Twenty-seven female children and adolescents with TS (mean age 13 years, SD 4 years 2 months) and 27 age-matched female control individuals (mean age 13 years 2 months, SD 4 years 1 month) underwent MRI. Age range of all participants was 7 to 20 years. Morphometric analyses of midline brain structures were conducted using standardized, reliable methods. When compared with control participants, females with TS showed reduced areas of the genu of the corpus callosum, the pons, and vermis lobules VI,VII, and an increased area of the fourth ventricle. No group difference in intracranial area measurements was observed. The reduced area of the genu in TS may reflect compromised connectivity between inferior parietal regions. Further, cerebellar vermis hypoplasia associated with TS agrees with literature that suggests the posterior fossa as a region prone to structural alterations in the face of early developmental insult. [source] Light and scanning microscopic studies of integument differentiation in the grass snake Natrix natrix L. (Lepidosauria, Serpentes) during embryogenesisACTA ZOOLOGICA, Issue 1 2009Elwira Swad Abstract We analysed the differentiation of body cover in the grass snake (Natrix natrix L.) over the full length of the embryo's body at each developmental stage. Based on investigations using both light and scanning electron microscopes, we divided the embryonic development of the grass snake integument into four phases. The shape of the epidermal cells changes first on the caudal and ventral parts of the embryo, then gradually towards the rostral and dorsal areas. In stage V on the ventral side of the embryo the gastrosteges are formed from single primordia, but on the dorsal side the epidermis forms the scale primordia in stage VII. This indicates that scalation begins on the ventral body surface, and spreads dorsally. The appearance of melanocytes between the cells of the stratum germinativum in stage VII coincides with changes in embryo colouration. The first dermal melanocytes were detected in stage XI so in this stage the definitive skin pattern is formed. In the same stage the epidermis forms the first embryonic shedding complex and the periderm layer begins to detach in small, individual flakes. This process coincides with rapid growth of the embryos. [source] Age-dependent variations of cell response to oxidative stress: Proteomic approach to protein expression and phosphorylationELECTROPHORESIS, Issue 14 2005Yuri Miura Dr. Abstract We investigated the protein profiles of variously aged rat astrocytes in response to oxidative stress. After H2O2 -exposure of cells at 100,µM for 30,min, the relative intensity of ten protein spots changed on two-dimensional (2-D) gels compared with control gels after silver staining. Matrix-assisted laser desorption/ionization-time of flight-mass spectrometry (MALDI-TOF-MS) analysis after in-gel digestion revealed that six of these spots corresponded to three kinds of proteins, each of which was composed of a protein and its modified form with a different isoelectric point (pI). These three proteins were identified as peroxiredoxins (PRDXs) II and III, and calpactin I light chain (p11). H2O2 -exposure increased the intensity of the spot with lower pI and simultaneously decreased that of the spot with higher pI for both PRDXs II and III. In addition, the expression of annexin VII, S -adenosyl- L -homocysteine hydrolase, elongation factor II fragment (EF-II), and adenosine deaminase was increased by H2O2 -exposure in astrocytes from variously aged rats. Using the Pro-Q® Diamond staining, heat shock protein 60,kDa (Hsp 60) and ,-tubulin were observed to be phosphorylated upon H2O2 -exposure. While phosphorylation of ,-tubulin was correlated positively with age, the changes in abundance of ten protein spots as described above were independent of age. These results suggest that aging does not suppress the responses aimed at limiting injury and promoting repair brought about by severe oxidative stress, and might affect cell dynamics including the formation of microtubules. [source] Hydrogenase- and outer membrane c -type cytochrome-facilitated reduction of technetium(VII) by Shewanella oneidensis MR-1ENVIRONMENTAL MICROBIOLOGY, Issue 1 2008Matthew J. Marshall Summary Pertechnetate, 99Tc(VII)O4,, is a highly mobile radionuclide contaminant at US Department of Energy sites that can be enzymatically reduced by a range of anaerobic and facultatively anaerobic microorganisms, including Shewanella oneidensis MR-1, to poorly soluble Tc(IV)O2(s). In other microorganisms, Tc(VII)O4, reduction is generally considered to be catalysed by hydrogenase. Here, we provide evidence that although the NiFe hydrogenase of MR-1 was involved in the H2 -driven reduction of Tc(VII)O4,[presumably through a direct coupling of H2 oxidation and Tc(VII) reduction], the deletion of both hydrogenase genes did not completely eliminate the ability of MR-1 to reduce Tc(VII). With lactate as the electron donor, mutants lacking the outer membrane c -type cytochromes MtrC and OmcA or the proteins required for the maturation of c -type cytochromes were defective in reducing Tc(VII) to nanoparticulate TcO2·nH2O(s) relative to MR-1 or a NiFe hydrogenase mutant. In addition, reduced MtrC and OmcA were oxidized by Tc(VII)O4,, confirming the capacity for direct electron transfer from these OMCs to TcO4,. c -Type cytochrome-catalysed Tc(VII) reduction could be a potentially important mechanism in environments where organic electron donor concentrations are sufficient to allow this reaction to dominate. [source] rFVIIa, for acute rebleeding of a cerebral cavernous malformationEUROPEAN JOURNAL OF NEUROLOGY, Issue 1 2007K. Engelhardt Recurrent bleeding episodes of cavernomas especially in the brainstem can cause progressive neurological deficits. Therefore brainstem cavernomas are still a therapeutic dilemma and a treatment challenge for the neuro critical care community. We report a 39-year-old woman with spontaneous ataxia diplopia and vomiting, who has been treated for multiple intracerebral cavernomas during the last 10 years. A cerebral computed tomography (cCT) revealed a re-bleeding cavernoma in the left cerebral peduncle with consecutive obstructive hydrocephalus. As a result of the difficult anatomical location, no surgical approach was possible. As an off-label treatment, recombinant activated factor VII (rFVIIa) was administered to prevent possible further bleeding and especially further sequelae. The patient recovered well and no adverse events and especially no further bleeding of the cavernoma were observed. To our knowledge, this is the first report of the safe and successful use of rFVIIa to treat re-bleeding episodes in cavernomas. Further clinical studies are needed to specify the future potential of rFVIIa. [source] Phosphoglycerate kinase deficiency in two brothers with McArdle-like clinical symptomsEUROPEAN JOURNAL OF NEUROLOGY, Issue 1 2000J. Aasly Phosphoglycerate kinase (PGK) catalyses the transfer of the acylphosphate group of 1,3-diphosphoglycerate to ADP with formation of 3-phosphoglycerate and ATP in the terminal stage of the glycolytic pathway. Two young brothers are presented who both experienced muscle pain, cramps and stiffness shortly after beginning heavy exercise. After these episodes they noticed that the urine was dark brown, indicating rhabdomyolysis and myoglobinuria. The neurological examinations were without remarks. There was no lactate increase in the ischaemic forearm exercise test. Both had very low PGK levels in muscle, erythrocytes, leukocytes and fibroblasts. This is the first family with more than one affected case of PGK deficiency and exercise-induced stiffness, myalgia and rhabdomyolysis. The clinical manifestations may resemble myophosphorylase deficiency (McArdle's disease: glycogenosis Type V) and muscle phosphofructokinase deficiency (Tarui's disease: glycogenosis Type VII). PGK deficiency is inherited as an X-linked trait and may show other features such as mental retardation and/or haemolytic anaemia. [source] Heterogeneity of V2-derived interneurons in the adult mouse spinal cordEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 11 2007A. Al-Mosawie Abstract Spinal neurons and networks that generate rhythmic locomotor activity remain incompletely defined, prompting the use of molecular biological strategies to label populations of neurons in the postnatal mouse. During spinal cord development, expression of Lhx3 in the absence of Isl1 specifies a V2 interneuronal fate. In this study, postnatal V2-derived interneurons were identified by yellow fluorescent protein (YFP) expression in the double-transgenic offspring of Lhx3Cre/+ × thy1-loxP-stop-loxP-YFP mice. While some motoneurons were labelled, several populations of interneurons predominantly located in lamina VII could also be distinguished. Small interneurons were located throughout the spinal cord whereas larger interneurons were concentrated in the lumbar enlargement. Some V2-derived interneurons were propriospinal, with axons that bifurcated in the lateral funiculus. V2-derived interneurons gave rise to populations of both excitatory and inhibitory interneurons in approximately equal proportions, as demonstrated by in situ hybridization with VGLUT2 mRNA. Immunohistochemical studies revealed YFP+ boutons throughout the spinal cord. Both glutamatergic and glycinergic YFP+ boutons were observed in lamina IX where many apposed motoneuron somata. GABAergic YFP+ boutons were also observed in lamina IX, and they did not form P-boutons. At P0, more than half of the YFP+ interneurons expressed Chx10 and thus were derived from the V2a subclass. In adult mice, there was an increase in Fos expression in V2-derived interneurons following locomotion, indicating that these neurons are active during this behaviour. The heterogeneity of V2-derived interneurons in adult mice indicates that physiologically distinct subpopulations, including last-order interneurons, arise from these embryonically defined neurons. [source] Neurons with distinctive firing patterns, morphology and distribution in laminae V,VII of the neonatal rat lumbar spinal cordEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 3 2003Péter Szûcs Abstract It is generally accepted that neurons in the ventral spinal grey matter, a substantial proportion of which can be regarded as constituents of the spinal motor apparatus, receive and integrate synaptic inputs arising from various peripheral, spinal and supraspinal sources. Thus, a profound knowledge concerning the integrative properties of interneurons in the spinal ventral grey matter appears to be essential for a fair understanding of operational principles of spinal motor neural assemblies. Using the whole cell patch clamp configuration in a correlative physiological and morphological experimental approach, here we demonstrate that the intrinsic membrane properties of neurons vary widely in laminae V,VII of the ventral grey matter of the neonatal rat lumbar spinal cord. Based on their firing patterns in response to depolarizing current steps, we have classified the recorded neurons into four categories: ,phasic', ,repetitive', ,single' and ,slow'. Neurons with firing properties characteristic of the ,phasic', ,repetitive' and ,single' cells have previously been reported also in the superficial and deep spinal dorsal horn, but this is the first account in the literature in which ,slow' neurons have been recovered and described in the spinal cord. The physiological heterogeneity in conjunction with the morphological correlation and distribution of neurons argues that different components of motor neural assemblies in the spinal ventral grey matter possess different signal processing characteristics. [source] CuI -Catalyzed Azide,Alkyne Intramolecular i -to-(i+4) Side-Chain-to-Side-Chain Cyclization Promotes the Formation of Helix-Like Secondary StructuresEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 3 2010Mario Scrima Abstract A solid-phase assembly of model peptides derived from human parathyroid hormone-related protein (11,19) containing ,-azido- and ,-yl-,-amino acid residues in positions i and i+4 was cyclised in solution by an intramolecular CuI -catalyzed azide,alkyne 1,3-dipolar Huisgen cycloaddition. These series of heterodetic cyclo-nonapeptides varied in the size of the disubstituted 1,2,3-triazolyl-containing bridge, the location and the orientation of the 1,2,3-triazolyl moiety within the bridge. The 1,2,3-triazolyl moiety, presented at either 1,4- or 4,1-orientation, is flanked by side chains containing 1,4 CH2 groups that result in bridges comprised from 4,7 CH2 groups connecting residues 13 and 17. Comprehensive conformational analysis employing CD, NMR and molecular dynamics reveals the conformational propensities of these heterodetic cyclo-nonapeptides. Cyclo-nonapeptides containing either the 7 methylene bridge (VII and VIII) or the 4 methylene bridge (II) are unstructured in structure-promoting solvent. Cyclo-nonapeptide I in which the 1,4-disubstituted 1,2,3-triazolyl is flanked by 3 and 1 CH2 groups in proximity to the respective residues 13 and 17, is stabilized in a non-canonical structure. All the other heterodetic cyclo-nonapeptides (III,VI) in which the 1,2,3-triazolyl is flanked by a total of 5 or 6 CH2 groups nicely accommodate ,-helical structures and reproduce very closely the helical structure stabilized by the analogous cyclo-nonapeptide in which Lys13 and Asp17 are bridged by the isosteric lactam. These studies suggest that the bioorthogonal i -to-(i+4) side-chain-to-side-chain cyclization via the prototypic "click reaction" offers a new and powerful approach for generating stable helix mimetic structures. [source] Fucosyltransferase VII-positive, skin-homing T cells in the blood and skin lesions of atopic dermatitis patientsEXPERIMENTAL DERMATOLOGY, Issue 3 2008Yoshiko Mizukawa Abstract: Patients with atopic dermatitis (AD) have an abnormally increased frequency of cutaneous lymphocyte antigen (CLA)+ Th2 cells responsible for local inflammation; however, this is paradoxical, given the well-recognized defective capacity of Th2 cells to migrate to the skin sites of inflammation. These discrepant observations would stem from the ambiguity of CLA+ T cells, because CLA does not represent the epitope required for binding to E-selectin but the epitope generated by fucosyltransferase VII (Fuc-TVII) and because skin-homing T cells are composed of three distinct subpopulations; Fuc-TVII+ E-selectin ligand (ESL)+ CLA,, Fuc-TVII+ ESL+ CLA+ and Fuc-TVII, ESL, CLA+ cells. We therefore asked which subpopulations of skin-homing Th2 cells could be increased in the blood and skin lesions of AD. We analysed the frequencies of the three subpopulations in purified CD4+ peripheral blood T cells from AD patients and healthy controls by immunohistochemistry and flow cytometry. The Fuc-TVII+ CLA+ or CLA+ ESL+ CCR4+ cells were dramatically increased in frequency not only in the blood but also in the skin lesions of AD patients and this increase was related to the severity of the clinical symptoms. Our data indicate the clinical importance of identifying skin-homing T cells with the potent capacity to migrate into the skin by analysing their Fuc-TVII expression and E-selectin binding ability in patients with AD. [source] A unique binding epitope for salvinorin A, a non-nitrogenous kappa opioid receptor agonistFEBS JOURNAL, Issue 9 2006Brian E. Kane Salvinorin A is a potent kappa opioid receptor (KOP) agonist with unique structural and pharmacological properties. This non-nitrogenous ligand lacks nearly all the structural features commonly associated with opioid ligand binding and selectivity. This study explores the structural basis to salvinorin A binding and selectivity using a combination of chimeric and single-point mutant opioid receptors. The experiments were designed based on previous models of salvinorin A that locate the ligand within a pocket formed by transmembrane (TM) II, VI, and VII. More traditional sites of opioid recognition were also explored, including the highly conserved aspartate in TM III (D138) and the KOP selectivity site E297, to determine the role, if any, that these residues play in binding and selectivity. The results indicate that salvinorin A recognizes a cluster of residues in TM II and VII, including Q115, Y119, Y312, Y313, and Y320. Based on the position of these residues within the receptor, and prior study on salvinorin A, a model is proposed that aligns the ligand vertically, between TM II and VII. In this orientation, the ligand spans residues that are spaced one to two turns down the face of the helices within the receptor cavity. The ligand is also in close proximity to EL-2 which, based on chimeric data, is proposed to play an indirect role in salvinorin A binding and selectivity. [source] Transfection of the c- erbB2/neu gene upregulates the expression of sialyl Lewis X, ,1,3-fucosyltransferase VII, and metastatic potential in a human hepatocarcinoma cell lineFEBS JOURNAL, Issue 12 2001Fei Liu The pCMV4 plasmid containing the cancer-promoting gene, c- erbB2/neu, was cotransfected into the human hepatocarcinoma cell line 7721 with the pcDNA3 vector, which contains the ,neo' selectable marker. Several clones showing stable expression of c- erbB2/neu were established and characterized by determination of c- erbB2/neu mRNA and its encoded protein p185. Expression of Lewis antigens and ,1,3-fucosyltransferases and the biological behavior of 7721 cells after c- erbB2/neu transfection were studied using mock cells transfected with the vectors pCMV4 and pcDNA3 as controls. SLex expression on the surface of mock cells was high, whereas expression of SDLex, Lex and SLea was absent or negligible. This is compatible with the abundant expression of ,1,3-fucosyltransferase VII, very low expression of ,fucosyltransferase III/VI, and almost absent expression of ,1,3-fucosyltransferase IV in the mock cells. After transfection of c- erbB2/neu, expression of SLex and ,1,3-fucosyltransferase VII were simultaneously elevated, but that of ,fucosyltransferase III/VI was not altered. The expression of both SLex and ,1,3-fucosyltransferase VII correlated positively with the expression of c- erbB2/neu in different clones, being highest in clone 13, medium in clone 6, and lowest in clone 7. In addition, the adhesion of 7721 cells to human umbilical vein endothelial cells (HUVECs) or P-selectin, as well as cell migration and invasion, were increased in c- erbB2/neu -transfected cells. These increases also correlated positively with the expression intensities of c- erbB2/neu, SLex and ,1,3-fucosyltransferase VII in the different clones, whereas cell adhesion to fibronectin correlated negatively with these variables. mAbs to SLex (KM93) and SDLex (FH6) significantly and slightly, respectively, abolished cell adhesion to HUVECs or P-selectin and cell migration and invasion. mAbs to SDLex and SLea did not suppress cell adhesion to HUVECs nor inhibit cell migration and invasion. Transfection of ,1,3-fucosyltransferase VII cDNA into 7721 cells showed similar results to transfection of c- erbB2/neu, and the increased adhesion to HUVECs, cell migration, and invasion were also inhibited significantly by KM93 and slightly by FH6. These results indicate that expression of ,1,3-fucosyltransferase VII and its specific product, SLex, and their capacity for cell adhesion, migration and invasion are closely related. Therefore, the c- erbB2/neu gene is proposed to be a metastasis-promoting gene, and its effects are at least partially mediated by the increased expression of ,1,3-fucosyltransferase VII and SLex. [source] Effect of two oral doses of 17,-estradiol associated with dydrogesterone on thrombin generation in healthy menopausal women: a randomized double-blind placebo-controlled studyFUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 2 2010Alexandra Rousseau Abstract Oral hormone therapy is associated with an increased risk of venous thrombosis. Drug agencies recommend the use of the lowest efficient dose to treat menopausal symptoms for a better risk/ratio profile, although this profile has not been totally investigated yet. The aim of the study was to compare the effect of the standard dose of 17,-estradiol to a lower one on thrombin generation (TG). In a 2-month study, healthy menopausal women were randomized to receive daily 1mg or 2 mg of 17,-estradiol (E1, n = 24 and E2, n = 26; respectively) with 10 mg dydrogesterone or placebo (PL, n = 22). Plasma levels factors VII, X, VIII and II were assessed before and after treatment as well as Tissue factor triggered TG, which allows the investigation of the different phases of coagulation process. The peak of thrombin was higher in hormone therapy groups (E1: 42.39 ± 50.23 nm, E2: 31.08 ± 85.86 nm vs. 10.52 ± 40.63 nm in PL, P = 0.002 and P = 0.01). Time to reach the peak was also shortened (PL: 0.26 ± 0.69 min vs. E1: ,0.26 ± 0.80 min, E2: ,0.55 ± 0.79 min, P <10,3 for both comparisons) and mean rate index of the propagation phase of TG was significantly increased. Among the studied clotting factors, only the levels of FVII were significantly increased after treatment administration. The two doses of 17,-estradiol induced in a similar degree an acceleration of the initiation and propagation phase of tissue factor triggered thrombin generation and a significant increase of FVII coagulant activity. [source] Teaching and Learning Guide for: The Geopolitics of Climate ChangeGEOGRAPHY COMPASS (ELECTRONIC), Issue 5 2008Jon Barnett Author's Introduction Climate change is a security problem in as much as the kinds of environmental changes that may result pose risks to peace and development. However, responsibilities for the causes of climate change, vulnerability to its effects, and capacity to solve the problem, are not equally distributed between countries, classes and cultures. There is no uniformity in the geopolitics of climate change, and this impedes solutions. Author Recommends 1.,Adger, W. N., et al. (eds) (2006). Fairness in adaptation to climate change. Cambridge, MA: MIT Press. A comprehensive collection of articles on the justice dimensions of adaptation to climate change. Chapters discuss potential points at which climate change becomes ,dangerous', the issue of adaptation under the United Nations Framework Convention on Climate Change (UNFCCC), the unequal outcomes of adaptation within a society, the effects of violent conflict on adaptation, the costs of adaptation, and examples from Bangladesh, Tanzania, Botswana, and Hungary. 2.,Leichenko, R., and O'Brien, K. (2008). Environmental change and globalization: double exposures. New York: Oxford University Press. This book uses examples from around the world to show the way global economic and political processes interact with environmental changes to create unequal outcomes within and across societies. A very clear demonstration of the way vulnerability to environmental change is as much driven by social processes as environmental ones, and how solutions lie within the realm of decisions about ,development' and ,environment'. 3.,Nordås, R., and Gleditsch, N. (2007). Climate conflict: common sense or nonsense? Political Geography 26 (6), pp. 627,638. doi:10.1016/j.polgeo.2007.06.003 An up-to-date, systematic and balanced review of research on the links between climate change and violent conflict. See also the other papers in this special issue of Political Geography. 4.,Parry, M., et al. (eds) (2007). Climate change 2007: impacts adaptation and vulnerability. Contribution of Working Group II to the fourth assessment report of the intergovernmental panel on climate change. Cambridge, UK: Cambridge University Press. The definitive review of all the peer-reviewed research on the way climate change may impact on places and sectors across the world. Includes chapters on ecosystems, health, human settlements, primary industries, water resources, and the major regions of the world. All chapters are available online at http://www.ipcc.ch/ipccreports/ar4-wg2.htm 5.,Salehyan, I. (2008). From climate change to conflict? No consensus yet. Journal of Peace Research 45 (3), pp. 315,326. doi:10.1177/0022343308088812 A balanced review of research on the links between climate change and conflict, with attention to existing evidence. 6.,Schwartz, P., and Randall, D. (2003). An abrupt climate change scenario and its implications for United States national security. San Francisco, CA: Global Business Network. Gives insight into how the US security policy community is framing the problem of climate change. This needs to be read critically. Available at http://www.gbn.com/ArticleDisplayServlet.srv?aid=26231 7.,German Advisory Council on Global Change. (2007). World in transition: climate change as a security risk. Berlin, Germany: WBGU. A major report from the German Advisory Council on Global Change on the risks climate changes poses to peace and stability. Needs to be read with caution. Summary and background studies are available online at http://www.wbgu.de/wbgu_jg2007_engl.html 8.,Yamin, F., and Depedge, J. (2004). The International climate change regime: a guide to rules, institutions and procedures. Cambridge, UK: Cambridge University Press. A clear and very detailed explanation of the UNFCCC's objectives, actors, history, and challenges. A must read for anyone seeking to understand the UNFCCC process, written by two scholars with practical experience in negotiations. Online Materials 1.,Environmental Change and Security Program at the Woodrow Wilson International Center for Scholars http://www.wilsoncenter.org/ecsp The major website for information about environmental security. From here, you can download many reports and studies, including the Environmental Change and Security Project Report. 2.,Global Environmental Change and Human Security Project http://www.gechs.org This website is a clearing house for work and events on environmental change and human security. 3.,Intergovernmental Panel on Climate Change (IPCC) http://www.ipcc.ch/ From this website, you can download all the chapters of all the IPCC's reports, including its comprehensive and highly influential assessment reports, the most recent of which was published in 2007. The IPCC were awarded of the Nobel Peace Prize ,for their efforts to build up and disseminate greater knowledge about man-made (sic) climate change, and to lay the foundations for the measures that are needed to counteract such change'. 4.,Tyndall Centre for Climate Change Research http://www.tyndall.ac.uk The website of a major centre for research on climate change, and probably the world's leading centre for social science based analysis of climate change. From this site, you can download many publications about mitigation of and adaptation to climate change, and about various issues in the UNFCCC. 5.,United Nations Framework Convention on Climate Change http://unfccc.int/ The website contains every major document relation to the UNFCCC and its Kyoto Protocol, including the text of the agreements, national communications, country submissions, negotiated outcomes, and background documents about most key issues. Sample Syllabus: The Geopolitics of Climate Change topics for lecture and discussion Week I: Introduction Barnett, J. (2007). The geopolitics of climate change. Geography Compass 1 (6), pp. 1361,1375. United Nations Secretary General, Kofi Annan, address to the 12th Conference of Parties to the United Nations Framework Convention on Climate Change, Nairobi, 15 November 2006. Available online at http://www.unep.org/Documents.Multilingual/Default.asp?DocumentID=495&ArticleID=5424&l=en Week II: The History and Geography of Greenhouse Gas Emissions Topic: The drivers of climate change in space and time Reading Baer, P. (2006). Adaptation: who pays whom? In: Adger, N., et al. (eds) Fairness in adaptation to climate change. Cambridge, MA: MIT Press, pp. 131,154. Boyden, S., and Dovers, S. (1992). Natural-resource consumption and its environmental impacts in the Western World: impacts of increasing per capita consumption. Ambio 21 (1), pp. 63,69. Week III: The Environmental Consequences of climate change Topic: The risks climate change poses to environmental systems Reading Intergovernmental Panel on Climate Change. (2007). Climate change 2007: climate change impacts, adaptation and vulnerability: summary for policymakers. Geneva, Switzerland: IPCC Secretariat. Watch: Al Gore. The Inconvenient Truth. Weeks IV and V: The Social Consequences of Climate Change Topic: The risks climate change poses to social systems Reading Adger, W. N. (1999). Social vulnerability to climate change and extremes in coastal Vietnam. World Development 27, pp. 249,269. Comrie, A. (2007). Climate change and human health. Geography Compass 1 (3), pp. 325,339. Leary, N., et al. (2006). For whom the bell tolls: vulnerability in a changing climate. A Synthesis from the AIACC project, AIACC Working Paper No. 21, International START Secretariat, Florida. Stern, N. (2007). Economics of climate change: the Stern review. Cambridge, UK: Cambridge University Press (Chapters 3,5). Week VI: Mitigation of Climate Change: The UNFCCC Topic: The UNFCCC and the Kyoto Protocol Reading Najam, A., Huq, S., and Sokona, Y. (2003). Climate negotiations beyond Kyoto: developing countries concerns and interests. Climate Policy 3 (3), pp. 221,231. UNFCCC Secretariat. (2005). Caring for climate: a guide to the climate change convention and the Kyoto Protocol. Bonn, Germany: UN Framework Convention on Climate Change Secretariat. Weeks VII and VIII: Adaptation to Climate Change Topic: What can be done to allow societies to adapt to avoid climate impacts? Reading Adger, N., et al. (2007). Assessment of adaptation practices, options, constraints and capacity. In: Parry, M., et al. (eds) Climate change 2007: impacts, adaptation and vulnerability. Contribution of Working Group II to the fourth assessment report of the intergovernmental panel on climate change. Cambridge, UK: Cambridge University Press, pp. 717,744. Burton, I., et al. (2002). From impacts assessment to adaptation priorities: the shaping of adaptation policy. Climate Policy 2 (2,3), pp. 145,159. Eakin, H., and Lemos, M. C. (2006). Adaptation and the state: Latin America and the challenge of capacity-building under globalization. Global Environmental Change: Human and Policy Dimensions 16 (1), pp. 7,18. Ziervogel, G., Bharwani, S., and Downing, T. (2006). Adapting to climate variability: pumpkins, people and policy. Natural Resources Forum 30, pp. 294,305. Weeks IX and X: Climate Change and Migration Topic: Will climate change force migration? Readings Gaim, K. (1997). Environmental causes and impact of refugee movements: a critique of the current debate. Disasters 21 (1), pp. 20,38. McLeman, R., and Smit, B. (2006). Migration as adaptation to climate change. Climatic Change 76 (1), pp. 31,53. Myers, N. (2002). Environmental refugees: a growing phenomenon of the 21st century. Philosophical Transactions of the Royal Society 357 (1420), pp. 609,613. Perch-Nielsen, S., Bättig, M., and Imboden, D. (2008). Exploring the link between climate change and migration. Climatic Change (online first, forthcoming); doi:10.1007/s10584-008-9416-y Weeks XI and XII: Climate Change and Violent Conflict Topic: Will Climate change cause violent conflict? Readings Barnett, J., and Adger, N. (2007). Climate change, human security and violent conflict. Political Geography 26 (6), pp. 639,655. Centre for Strategic and International Studies. (2007). The age of consequences: the foreign policy and national security implications of global climate change. Washington, DC: CSIS. Nordås, R., and Gleditsch, N. (2007). Climate conflict: common sense or nonsense? Political Geography 26 (6), pp. 627,638. Schwartz, P., and Randall, D. (2003). An abrupt climate change scenario and its implications for United States national security. San Francisco, CA: Global Business Network. [online]. Retrieved on 8 April 2007 from http://www.gbn.com/ArticleDisplayServlet.srv?aid=26231 Focus Questions 1Who is most responsible for climate change? 2Who is most vulnerable to climate change? 3Does everyone have equal power in the UNFCCC process? 4Will climate change force people to migrate? Who? 5What is the relationship between adaptation to climate change and violent conflict? [source] Processing, modelling and predicting time-lapse effects of overpressured fluid-injection in a fractured reservoirGEOPHYSICAL JOURNAL INTERNATIONAL, Issue 2 2002Erika Angerer Summary Time-lapse seismology is important for monitoring subsurface pressure changes and fluid movements in producing hydrocarbon reservoirs. We analyse two 4-D, 3C onshore surveys from Vacuum Field, New Mexico, USA, where the reservoir of interest is a fractured dolomite. In Phase VI, a time-lapse survey was acquired before and after a pilot tertiary-recovery programme of overpressured CO2 injection, which altered the fluid composition and the pore-fluid pressure. Phase VII was a similar time-lapse survey in the same location but with a different lower-pressure injection regime. Applying a processing sequence to the Phase VI data preserving normal-incidence shear-wave anisotropy (time-delays and polarization) and maximizing repeatability, interval-time analysis of the reservoir interval shows a significant 10 per cent change in shear-wave velocity anisotropy and 3 per cent decrease in the P -wave interval velocities. A 1-D model incorporating both saturation and pressure changes is matched to the data. The saturation changes have little effect on the seismic velocities. There are two main causes of the time-lapse changes. Any change in pore-fluid pressures modifies crack aspect ratios. Additionally, when there are overpressures, as there are in Phase VI, there is a 90° change in maximum impedance directions, and the leading faster split shear wave, instead of being parallel to the crack face as it is for low pore-fluid pressures, becomes orthogonal to the crack face. The anisotropic poro-elasticity (APE) model of the evolution of microcracked rock, calculates the evolution of cracked rock to changing conditions. APE modelling shows that at high overburden pressures only nearly vertical cracks, to which normal incidence P waves are less sensitive than S waves, remain open as the pore-fluid pressure increases. APE modelling matches the observed time-lapse effects almost exactly demonstrating that shear-wave anisotropy is a highly sensitive diagnostic of pore-fluid pressure changes in fractured reservoirs. In this comparatively limited analysis, APE modelling of fluid-injection at known pressure correctly predicted the changes in seismic response, particularly the shear-wave splitting, induced by the high-pressure CO2 injection. In the Phase VII survey, APE modelling also successfully predicted the response to the lower-pressure injection using the same Phase VI model of the cracked reservoir. The underlying reason for this remarkable predictability of fluid-saturated reservoir rocks is the critical nature and high crack density of the fluid-saturated cracks and microcracks in the reservoir rock, which makes cracked reservoirs critical systems. [source] Pregnancy and rare bleeding disordersHAEMOPHILIA, Issue 5 2009R. KADIR Summary., Rare bleeding disorders include deficiency of fibrinogen, prothrombin, factor V, factor VII, factor X, factor XI and factor XIII together with combined deficiency disorders, factor V+VIII deficiency, and deficiency of the vitamin K-dependent factors (factor II, VII, IX and X). They account for 3,5% of all inherited coagulation disorders. Due to their rarity, information about pregnancy complications and management is limited and mostly derived from case reports. Deficiency of fibrinogen and FXIII are both found to be strongly associated with increased risk of recurrent miscarriage and placental abruption. Factor replacement is used to reduce these risks. However, the risk of miscarriage and ante-partum complications is less clear in women with other bleeding disorders. Haemostatic abnormalities in women with rare bleeding disorders seem to persist throughout pregnancy especially if the defect is severe. Therefore women affected with these disorders are at risk of post-partum haemorrhage. The fetus can also be affected and potentially at risk of bleeding complications. Specialised multidisciplinary management is essential to minimise the potential maternal and neonatal complications and ensure an optimal outcome. This paper presents literature review for pregnancy complications in each of the rare bleeding disorders. In addition general principles for management of pregnancy, labour and delivery are discussed. [source] The benefits of prophylactic treatment with APCC in patients with haemophilia and high-titre inhibitors: a retrospective case seriesHAEMOPHILIA, Issue 3 2009L. A. VALENTINO Summary., Prophylactic infusion of factor concentrates is a safe, effective intervention for preventing arthropathy in patients with haemophilia; on-demand treatment is insufficient to prevent the orthopaedic complications and subsequent haemophilic arthropathy that stem from recurrent joint haemorrhages. The usefulness of prophylaxis in haemophilia patients without inhibitors suggests that patients with haemophilia and inhibitors could derive similar benefits. In patients with haemophilia and high-titre (>5 BU mL,1) inhibitors, bleeding episodes are treated with bypassing agents such as activated prothrombin complex concentrates (APCCs) and recombinant activated factor VII (rFVIIa, NovoSeven®; Novo Nordisk A/S, Bagsvaerd, Denmark). It is possible to administer bypassing therapy regularly to prevent haemorrhages, with the goal of limiting arthropathy and serious life- and limb-threatening bleeding. The data evaluating the efficacy and safety of this approach in patients with inhibitors are limited, consisting of results from one prospective trial and retrospective case reports. This report describes our experience with the prophylactic use of the APCC Factor Eight Inhibitor Bypassing Activity, Anti-Inhibitor Coagulant Complex, Vapor Heated (FEIBAÔ; Baxter AG, Vienna, Austria). Data from patients at one treatment centre were retrospectively evaluated. Case records of six patients with haemophilia A or B and high-titre inhibitors were identified. When APCC was administered regularly, most patients exhibited a reduction in the numbers of haemorrhages, an improvement in orthopaedic status, and an improvement in quality of life. Prophylaxis with APCC can reduce haemorrhages and halt further joint deterioration in patients with haemophilia and inhibitors. [source] Efficacy of recombinant activated factor VII vs. activated prothrombin complex concentrate for patients suffering from haemophilia complicated with inhibitors: a Bayesian meta-regressionHAEMOPHILIA, Issue 2 2009M. J. TREUR Summary., The optimal on-demand treatment of joint bleeds in haemophilia patients with inhibitors is a source of debate, with studies reporting various efficacy levels for different drugs and dosage regimens. To analyse, in a unified Bayesian meta-regression model, the published efficacy of recombinant activated factor VII (rFVIIa) and/or activated prothrombin complex concentrate (aPCC) as on-demand treatments for joint bleeds in haemophilia patients with inhibitors. A systematic search was carried out to identify studies reporting on dosage and efficacy of rFVIIa and aPCC in the treatment of joint bleeds in the target patient population. Data were abstracted and included in the model and adjusted for potential sources of heterogeneity. Pooled efficacy levels for typical rFVIIa and aPCC regimens were estimated. Seventeen studies, collectively reporting on >2000 joint bleeds, were included. Medication type combined with dosage was the only significant explanatory parameter. The model predicts that a typical regimen of 90 ,g kg,1 rFVII repeated every 3 h if needed results in cumulative joint bleed resolution of 66%, 88% and 95% after 12, 24 and 36 h, respectively. In comparison, a typical regimen of 75 IU kg,1 aPCC repeated every 12 h if needed results in cumulative joint bleed resolution of 39%, 62% and 76%, respectively. These differences were statistically significant and were also robust in sensitivity analyses. This analysis suggests that a typical rFVIIa regimen will resolve joint bleeds more effectively than a typical aPCC regimen after 12, 24 and 36 h. [source] Differential response to bypassing agents complicates treatment in patients with haemophilia and inhibitorsHAEMOPHILIA, Issue 1 2009E. BERNTORP Summary., The bypassing agents factor eight inhibitor bypassing activity (FEIBA) anti-inhibitor coagulant complex and recombinant activated factor VII (rFVIIa) have been established as safe and effective therapies for treating bleeding episodes in haemophilia patients with inhibitors. However, the efficacy of each bypassing agent can vary, and neither agent is universally effective. The reasons for such variability have yet to be confirmed, but may involve patient-specific factors and the mechanisms of action (MOAs) and pharmacokinetic profiles of these two agents. This issue underscores the necessity of both products in the comprehensive care of patients with haemophilia and inhibitors. The objective of this review is to discuss the evidence of a differential haemostatic response to bypassing agents and the potential roles of MOA and patient-specific factors in contributing to the differences in response. [source] Haemostatic management of surgery for imperforate anus in a patient with 13q deletion syndrome with combined deficiency of factors VII and XHAEMOPHILIA, Issue 1 2009H. KUROSAWA No abstract is available for this article. [source] Applicability and safety of recombinant activated factor VII to control non-haemophilic haemorrhage: investigational experience in 265 childrenHAEMOPHILIA, Issue 4 2008M. HERBERTSON Summary., Experience of recombinant activated factor VII (rFVIIa, NovoSeven®; Novo Nordisk A/S, Bagsvaerd, Denmark) to control haemorrhage in non-haemophilic children is limited. The object of this study was to examine the applicability and safety of rFVIIa amongst a group of non-haemophilic paediatric subjects. Details of all non-haemophilic children ,16 years receiving rFVIIa whose data were recorded in the investigational, internet-based registry, haemostasis.com were analysed. A total of 265 children (mean age 7.7 years) were treated with rFVIIa; the median dose administered was 78.4 ,g kg,1 body weight (range 9.0,393.4) and the median total dose received 100.0 ,g kg,1 body weight (range 10.9,1341.2). Therapeutic areas included surgery (34.5%), coagulopathy (including thrombocytopenia; 29.0%), spontaneous bleeding (17.2%), trauma (8.4%) and intracranial haemorrhage (4.5%). Two patients experienced thromboembolic events following administration of rFVIIa. Thirty-nine patients died on account of haemorrhage or complications relating to their underlying condition; neither the thromboembolic events nor the deaths were related to rFVIIa administration. Bleeding stopped in 118/237 (49.8%), markedly decreased in 54/237 (22.8%), decreased in 51/237 (21.5%), remained unchanged in 13/237 (5.5%) and increased in 1/237 (0.4%) patients. These results suggest that rFVIIa is safe and widely applicable in children to control non-haemophilic haemorrhage. [source] Recombinant activated factor VII for haemophilia patients with inhibitors undergoing orthopaedic surgery: a review of the literatureHAEMOPHILIA, Issue 2 2008A. OBERGFELL Summary., Arthropathy is prevalent in patients with haemophilia and inhibitors and is a major source of pain and disability, significantly reducing quality of life. Recombinant activated factor VII (rFVIIa; NovoSeven®) is one of the treatments available for acute life-threatening bleeding episodes in haemophilia patients with inhibitors. It has also been used successfully in a range of orthopaedic surgical procedures in these patients. This is a review of published data on elective orthopaedic procedures in haemophilia patients with inhibitors under cover of rFVIIa from January 2002 to November 2006. Articles were retrieved from MEDLINE using specified search parameters. Twelve articles covering a total of 80 orthopaedic procedures were identified. In the vast majority of cases, rFVIIa provided safe and effective haemostatic cover during orthopaedic surgery with no bleeding complications. There was variation in the administered dose, although the majority of patients were treated with 90 ,g kg,1 bolus followed by either continuous infusion or bolus infusion. Of those cases reporting bleeding complications, most were considered to be related to an inadequate amount of rFVIIa. The cumulative experience presented here suggests that rFVIIa is safe and effective for providing adequate haemostatic cover for haemophilia patients with inhibitors undergoing orthopaedic surgery. The optimal dosing regimen and mode of administration has yet to be identified. Further controlled trials are needed to confirm these experiences. [source] A cost evaluation of treatment alternatives for mild-to-moderate bleeding episodes in patients with haemophilia and inhibitors in BrazilHAEMOPHILIA, Issue 5 2007M. C OZELO Summary., The first-line treatment for mild-to-moderate bleeding episodes in patients with haemophilia and inhibitors in Brazil is currently activated prothrombin complex concentrate (aPCC), with recombinant activated factor VII (rFVIIa) used as second-line therapy or as a last resort. The aim of this study was to determine the cost and effectiveness of these treatments from the perspective of the Brazilian National Health Service. A decision analysis model was constructed to assess total direct medical costs (including drug costs, costs of outpatient or inpatient care, ambulance transportation and cost of concomitant medications) of first-line treatment with aPCC or rFVIIa. Clinical outcome and resource utilization data were obtained both retrospectively and prospectively and validated by the consensus of an expert panel of Brazilian haematologists. A total of 103 bleeds in 25 patients were included in the analysis. rFVIIa resolved bleeds more quickly (4.4 h) than aPCC (62.6 h) and was more effective (100% vs. 56.7% respectively). Mean total direct medical costs (from initiation to cessation of bleed) were estimated to be US$13 500 (aPCC) and US$7590 (rFVIIa). Extensive sensitivity analyses confirmed the cost-effectiveness of rFVIIa. Compared with aPCC, rFVIIa was more effective and less expensive when used as first-line treatment for mild-to-moderate bleeding episodes in patients with haemophilia and inhibitors in Brazil. rFVIIa should be considered a first-line treatment for the management of these patients. [source] Pharmacokinetics of factors IX, recombinant human activated factor VII and factor XIIIHAEMOPHILIA, Issue 2006M.-C. POON Summary., There is now a volume of literature on the pharmacokinetics (PK) of coagulation factor concentrates, although the majority is on factor VIII (FVIII) and factor IX (FIX). PK of FIX and FVIII are different with FIX having a larger volume of distribution (Vdss), higher elimination clearance (CL), longer mean resident time (MRT) and longer terminal half-life (T1/2,,). Factor IX in vivo recovery (IVR) is also much shorter possibly due to reversible binding of FIX to the endothelium and possibly to platelets. There is considerable FIX PK variability between products (particularly between plasma-derived FIX and recombinant FIX), and between individuals. Important inter-individual factors leading to PK variability include age and body weight because plasma volume as a fraction of body weight decreases with increasing weight and hence age. Thus, IVR increases with body weight and hence age and is consequently lower in children than in adults. Absolute Vdss and CL increase linearly with body weight and age in children and adolescents, becoming stable in adults with more stable weight. Inter-individual variability also likely applies to other clotting factors, particularly to recombinant activated FVII (rFVIIa) but likely also to the less well studied factor XIII (FXIII). The former is known to have an extremely short T1/2,,, large Vdss, high CL, short MRT, whereas the latter has an extremely long T1/2,,, large Vdss, short CL and long MRT. Both are discussed in this article. Understanding of PK of specific clotting factors in individual patients is important in order to make decisions regarding appropriate dosage and dosage intervals to treat patients, and to allow by means of computer modelling the determination of dosage to achieve target trough level at various dosing intervals for patients undergoing prophylaxis. [source] Identifying and managing inhibitor patients requiring orthopaedic surgery , the multidisciplinary team approachHAEMOPHILIA, Issue 2005C. LUDLAM Summary., Until recently, surgery in haemophilia patients with inhibitors was strongly contraindicated and was therefore often not even contemplated. Inhibitor patients entering the surgical arena face unique challenges; the most frequently encountered problem during surgical intervention is bleeding, and thrombosis is occasionally observed. The activated prothrombin complex concentrate, FEIBATM, and recombinant activated factor VII (rFVIIa) are available as haemostatic cover during surgery. The use of rFVIIa enables inhibitor patients to undergo orthopaedic surgery with an expectation of success, and results are generally good. An organized team approach is critical to this success. However, further information is required to enable different procedures to be optimized in terms of both outcome and safety. [source] Health economics of treating haemophilia A with inhibitorsHAEMOPHILIA, Issue 2005C. KNIGHT Summary., Haemophilia is a rare, inherited blood disorder in which blood clotting is impaired such that patients suffer from excessive internal and external bleeding. At present there is no cure for haemophilia A and patients require expensive, life-long treatment involving clotting factor replacement therapy. Treatment costs are perceived to be higher for patients who have developed inhibitory antibodies to factor VIII, the standard therapy for haemophilia A. However, initial cost analyses suggest that clotting factor therapy with alternative haemostatic agents, such as recombinant activated factor VII or activated prothrombin complex concentrate, is no more expensive for the majority of haemophilia A patients with inhibitors than for those without inhibitors. With the availability of effective alternative haemostatic agents, orthopaedic surgery for haemophilia A patients with inhibitors is now a clinical option, and initial cost analyses suggest this may be a cost-effective treatment strategy for patients with inhibitors whose quality of life (QoL) is severely impaired by joint arthropathy. In an era of finite healthcare resourcing it is important to determine whether new treatments justify higher unit costs compared with standard therapies and whether such higher costs are justified from an individual perspective in terms of improved QoL, and from a societal perspective in terms of improved productivity and reduced overall healthcare costs. This paper examines current data on the health economics of treating haemophilia A patients with inhibitors, focusing on the overall costs of clotting factor replacement therapy and the cost consequences of joint replacement. [source] Management of oral bleedings with recombinant factor VIIa in children with haemophilia A and inhibitorHAEMOPHILIA, Issue 1 2005P. Laguna Summary., Dental extraction in patients with haemophilia A and high-titre inhibitor is always a high-risk procedure, which often presents a lot of problems associated with bleeding. Prothrombin complex concentrates or recombinant activated factor VII (rFVIIa) has been used to control bleeding. rFVIIa was administered to five boys with severe haemophilia A complicated with inhibitor, who underwent seven dental extractions. The age of the patients ranged between 8 and 13 years (median 10 years). The concentrate was administered in doses of 90,100 ,g kg,1 body weight. Duration in the therapy and intervals between rFVIIa doses depended on the severity of bleeding. rFVIIa was proven to be highly effective and no side-effects of the product were observed. [source] HIP/PAP accelerates liver regeneration and protects against acetaminophen injury in mice,HEPATOLOGY, Issue 3 2005Hanh-Tu Lieu Human hepatocarcinoma-intestine-pancreas/pancreatic-associated protein HIP/PAP is a secreted C-type lectin belonging to group VII, according to Drickamer's classification. HIP/PAP is overexpressed in liver carcinoma; however, its functional role remains unclear. In this study, we demonstrate that HIP/PAP is a paracrine hepatic growth factor promoting both proliferation and viability of liver cells in vivo. First, a low number of implanted hepatocytes deriving from HIP/PAP-transgenic mice (<1:1,000) was sufficient to stimulate overall recipient severe combined immunodeficiency liver regeneration after partial hepatectomy. After a single injection of HIP/PAP protein, the percentages of bromodeoxyuridine-positive nuclei and mitosis were statistically higher than after saline injection, indicating that HIP/PAP acts as a paracrine mitogenic growth factor for the liver. Comparison of the early events posthepatectomy in control and transgenic mice indicated that HIP/PAP accelerates the accumulation/degradation of nuclear phospho,signal transducer activator transcription factor 3 and tumor necrosis factor , level, thus reflecting that HIP/PAP accelerates liver regeneration. Second, we showed that 80% of the HIP/PAP-transgenic mice versus 25% of the control mice were protected against lethal acetaminophen-induced fulminate hepatitis. A single injection of recombinant HIP/PAP induced a similar cytoprotective effect, demonstrating the antiapoptotic effect of HIP/PAP. Comparison of Cu/Zn superoxide dismutase activity and glutathione reductase-like effects in control and transgenic liver mice indicated that HIP/PAP exerts an antioxidant activity and prevents reactive oxygen species-induced mitochondrial damage by acetaminophen overdose. In conclusion, the present data offer new insights into the biological functions of C-type lectins. In addition, HIP/PAP is a promising candidate for the prevention and treatment of liver failure. (HEPATOLOGY 2005;42:618,626.) [source] Henry VII and the Bristol expeditions to North America: the Condon documentsHISTORICAL RESEARCH, Issue 221 2010Evan T. Jones Little is known about the Bristol discovery voyages of the years 1496,1508 and, as my recent article in this journal has shown, even less is certain. The current article contributes to research in this field by publishing two ,new' documents, which were first discovered in the nineteen-seventies but, for the reasons explained here, have not been published until now. These documents are significant both because they reveal important new information about the voyages and because they serve to confirm some of the remarkable, but previously unsubstantiated, claims made about the expeditions by the late Dr. Alwyn Ruddock. [source] Politic history, New Monarchy and state formation: Henry VII in European perspectiveHISTORICAL RESEARCH, Issue 217 2009Steven Gunn Historians have repeatedly compared Henry VII with his continental contemporaries, Louis XI of France and Ferdinand of Aragon. Around 1600 the writers of politic history emphasized Henry's wisdom in drawing lessons in statecraft from his fellow monarchs. By 1900 analysts of the ,New Monarchy' placed more stress on the common circumstances that underlay the revival of monarchical power, but thereby raised awkward questions about similarities and differences in the development of national states. Latterly a model of European state formation has been constructed which sets Henry's kingship less comfortably alongside those of Louis and Ferdinand. This should lead us not to abandon, but to reshape the attempt to set Henry in his European context. [source] | |||||||||||||||||||||||||||||||||||||||||||