Mobilization of hematopoietic stem cells with the novel CXCR4 antagonist POL6326 (balixafortide) in healthy volunteers—Results of a dose escalation trial

Background: Certain disadvantages of the standard hematopoietic stem and progenitor cell (HSPC) mobilizing agent G-CSF fuel the quest for alternatives. We herein report results of a Phase I dose escalation trial comparing mobilization with a peptidic CXCR4 antagonist POL6326 (balixafortide) vs. G-CSF. Methods: Healthy male volunteer donors with a documented average mobilization response to G-CSF received, following ≥6 weeks wash-out, a 1–2 h infusion of 500–2500 µg/kg of balixafortide. Safety, tolerability, pharmacokinetics and pharmacodynamics were assessed. Results: Balixafortide was well tolerated and rated favorably over G-CSF by subjects. At all doses tested balixafortide mobilized HSPC. In the dose range between 1500 and 2500 µg/kg mobilization was similar, reaching 38.2 ± 2.8 CD34 + cells/µL (mean ± SEM). Balixafortide caused mixed leukocytosis in the mid-20 K/µL range. B-lymphocytosis was more pronounced, whereas neutrophilia and monocytosis were markedly less accentuated with balixafortide compared to G-CSF. At the 24 h time point, leukocytes had largely normalized. Conclusions: Balixafortide is safe, well tolerated, and induces efficient mobilization of HSPCs in healthy male volunteers. Based on experience with current apheresis technology, the observed mobilization at doses ≥1500 µg/kg of balixafortide is predicted to yield in a single apheresis a standard dose of 4× 10E6 CD34+ cells/kg from most individuals donating for an approximately weight-matched recipient. Exploration of alternative dosing regimens may provide even higher mobilization responses. Trial Registration European Medicines Agency (EudraCT-Nr. 2011-003316-23) and clinicaltrials.gov (NCT01841476

PLANETA ARTE: desenhando e compartilhando arte através de um ambiente virtual de aprendizagem

O presente artigo apresenta o Planeta Arte, no que se refere ao contexto envolvido, fundamentação teórica, questões técnicas, pedagógicas e de design. Trata-se de uma funcionalidade do ambiente virtual de aprendizagem PLANETA ROODA, disponívelem http://www.nuted.edu.ufrgs.br/planetarooda, o qual é destinado à Educação Infantil e Anos Iniciais

The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder

Exposure to second-hand smoke and direct healthcare costs in children – results from two German birth cohorts, GINIplus and LISAplus

Abstract Background Although the negative health consequences of the exposure to second hand tobacco smoke during childhood are already known, evidence on the economic consequences is still rare. The aim of this study was to estimate excess healthcare costs of exposure to tobacco smoke in German children. Methods The study is based on data from two birth cohort studies of 3,518 children aged 9-11 years with information on healthcare utilisation and tobacco smoke exposure: the GINIplus study (German Infant Study On The Influence Of Nutrition Intervention Plus Environmental And Genetic Influences On Allergy Development) and the LISAplus study (Influence of Life-Style Factors On The Development Of The Immune System And Allergies In East And West Germany Plus The Influence Of Traffic Emissions And Genetics). Direct medical costs were estimated using a bottom-up approach (base year 2007). We investigated the impact of tobacco smoke exposure in different environments on the main components of direct healthcare costs using descriptive analysis and a multivariate two-step regression analysis. Results Descriptive analysis showed that average annual medical costs (physician visits, physical therapy and hospital treatment) were considerably higher for children exposed to second-hand tobacco smoke at home (indoors or on patio/balcony) compared with those who were not exposed. Regression analysis confirmed these descriptive trends: the odds of positive costs and the amount of total costs are significantly elevated for children exposed to tobacco smoke at home after adjusting for confounding variables. Combining the two steps of the regression model shows smoking attributable total costs per child exposed at home of €87 [10–165] (patio/balcony) and €144 [6–305] (indoors) compared to those with no exposure. Children not exposed at home but in other places showed only a small, but not significant, difference in total costs compared to those with no exposure. Conclusions This study shows adverse economic consequences of second-hand smoke in children depending on proximity of exposure. Tobacco smoke exposure seems to affect healthcare utilisation in children who are not only exposed to smoke indoors but also if parents reported exclusively smoking on patio or balcony. Preventing children from exposure to second-hand tobacco smoke might thus be desirable not only from a health but also from an economic perspective.</p

Construindo novas funcionalidades para o Planeta ROODA : Planeta-Arte e Planeta-Pergunta

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Construindo novas funcionalidades para o Planeta ROODA : Planeta-Arte e Planeta-Pergunta

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Exposure to second-hand smoke and direct healthcare costs in children - results from two German birth cohorts, GINIplus and LISAplus.

ABSTRACT: BACKGROUND: Although the negative health consequences of the exposure to second hand tobacco smoke during childhood are already known, evidence on the economic consequences is still rare. The aim of this study was to estimate excess healthcare costs of exposure to tobacco smoke in German children. METHODS: The study is based on data from two birth cohort studies of 3,518 children aged 9-11 years with information on healthcare utilisation and tobacco smoke exposure: the GINIplus study (German Infant Study On The Influence Of Nutrition Intervention Plus Environmental And Genetic Influences On Allergy Development) and the LISAplus study (Influence of Life-Style Factors On The Development Of The Immune System And Allergies In East And West Germany Plus The Influence Of Traffic Emissions And Genetics). Direct medical costs were estimated using a bottom-up approach (base year 2007). We investigated the impact of tobacco smoke exposure in different environments on the main components of direct healthcare costs using descriptive analysis and a multivariate two-step regression analysis. RESULTS: Descriptive analysis showed that average annual medical costs (physician visits, physical therapy and hospital treatment) were considerably higher for children exposed to second-hand tobacco smoke at home (indoors or on patio/balcony) compared with those who were not exposed. Regression analysis confirmed these descriptive trends: the odds of positive costs and the amount of total costs are significantly elevated for children exposed to tobacco smoke at home after adjusting for confounding variables. Combining the two steps of the regression model shows smoking attributable total costs per child exposed at home of [euro sign]87 [10--165] (patio/balcony) and [euro sign]144 [6--305] (indoors) compared to those with no exposure. Children not exposed at home but in other places showed only a small, but not significant, difference in total costs compared to those with no exposure. CONCLUSIONS: This study shows adverse economic consequences of second-hand smoke in children depending on proximity of exposure. Tobacco smoke exposure seems to affect healthcare utilisation in children who are not only exposed to smoke indoors but also if parents reported exclusively smoking on patio or balcony. Preventing children from exposure to second-hand tobacco smoke might thus be desirable not only from a health but also from an economic perspective

Retours à Marcel Schwob

Par delà sa réputation de prodigieuse érudition et curiosité, Marcel Schwob (1867-1905) fut un créateur de formes d’une originalité inépuisable, dont l’influence secrète mais déterminante s’étend de Paul Valery à nos écrivains les plus contemporains, Jean Echenoz ou Antonio Tabucchi en passant par J.-L. Borges, P. Michon, P. Quignard ou encore Y. Gaillard. Ce volume, issu du colloque de Cerisy-la-Salle, organisé par Christian Berg, Alexandre Gefen et Monique Jutrin du 13 au 20 août 2005 pour marquer le centenaire de la mort de l’écrivain, a voulu rendre lisible les aspects complémentaires d’une œuvre polymorphe : contes et nouvelles, essais et critiques littéraires, chroniques journalistiques, essais philosophiques et pamphlets littéraires. À côté de l’inventeur du genre de la vie imaginaire, du roman à plusieurs voix, du verset poétique, de la fiction érudite, et, dans une large mesure, de la nouvelle symboliste, c’est le Schwob auteur de contes fantastiques aussi forts que ceux de Maupassant, l’exégète de Villon, le complice de Sarah Bernhardt, traducteur et préfacier d’Hamlet, l’ami d’Alfred Jarry et de Remy de Gourmont, que l’on découvrira enfin. La diversité d’approche des contributeurs, qui, comme le préconisait Schwob dans « Il libro della mia memoria », s’efforcent de construire « presque autant que l’auteur », en balayant largement les contextes culturels nourris de son influence, nous a paru justifier le pluriel du titre du volume : Retours à Marcel Schwob