Can the trabecular bone score (TBS) be considered as a major clinical risk factor (CRF) of osteoporotic fractures? A meta-like analysis

Abstract: To have an added value over BMD, a CRF of osteoporotic fracture must be predictable of the fracture, independent of BMD, reversible and quantifiable. Many major recognized CRF exist.Out of these factorsmany of themare indirect factor of bone quality. TBS predicts fracture independently of BMD as demonstrated from previous studies. The aim of the study is to verify if TBS can be considered as a major CRF of osteoporotic fracture. Existing validated datasets of Caucasian women were analyzed. These datasets stem from different studies performed by the authors of this report or provided to our group. However, the level of evidence of these studies will vary. Thus, the different datasets were weighted differently according to their design. This meta-like analysis involves more than 32000 women (≥50 years) with 2000 osteoporotic fractures from two prospective studies (OFELY&MANITOBA) and 7 crosssectional studies. Weighted relative risk (RR) for TBS was expressed for each decrease of one standard deviation as well as per tertile difference (TBS=1.300 and 1.200) and compared with those obtained for the major CRF included in FRAX®. Overall TBS RR obtained (adjusted for age) was 1.79 [95%CI-1.37-2.37]. For all women combined, RR for fracture for the lowest comparedwith themiddle TBS tertilewas 1.55[1.46- 1.68] and for the lowest compared with the highest TBS tertile was 2.8[2.70-3.00]. TBS is comparable to most of the major CRF (Fig 1) and thus could be used as one of them. Further studies have to be conducted to confirm these first findings.

Influence of learning on range expansion and adaptation to novel habitats.

Learning has been postulated to 'drive' evolution, but its influence on adaptive evolution in heterogeneous environments has not been formally examined. We used a spatially explicit individual-based model to study the effect of learning on the expansion and adaptation of a species to a novel habitat. Fitness was mediated by a behavioural trait (resource preference), which in turn was determined by both the genotype and learning. Our findings indicate that learning substantially increases the range of parameters under which the species expands and adapts to the novel habitat, particularly if the two habitats are separated by a sharp ecotone (rather than a gradient). However, for a broad range of parameters, learning reduces the degree of genetically-based local adaptation following the expansion and facilitates maintenance of genetic variation within local populations. Thus, in heterogeneous environments learning may facilitate evolutionary range expansions and maintenance of the potential of local populations to respond to subsequent environmental changes.

Liderança como factor de sucesso na gestão escolar O caso da Escola Secundária “Amor de Deus”

O presente trabalho de investigação destina-se a obtenção do grau de licenciatura em ciências de educação e praxis educativa, variante administração escolar na Universidade Jean Piaget de Cabo Verde, O trabalho de investigação intitula-se liderança como factor de sucesso na gestão escolar: O caso da escola secundária ―Amor de Deus‖ (cidade da praia), local de incidência de estudo. A metodologia utilizada permitiu-nos fazer consulta bibliográfica e sitografica sobre o tema. No que refere ao inquérito por questionário, uma amostra de 20 professores deram os seus contributos no universo de 43 docentes efectivo da escola, e a entrevista foi feita à directora da escola. Constatamos que a gestão das instituições do ensino secundário Amor de Deus que consideramos que uma escola nova está a atingir o nível alto de democratização uma vez que com os dirigentes aceitam as opiniões (quando relevante) dos diferentes elementos das organizações dando-lhes a autonomia e conferindo um vasto leque de competências aos seus diversos órgãos de gestão, nos planos administrativos, pedagógicos e disciplinar. O presente trabalho estudou o ciclo de gestão escolar das escolas secundárias a luz de do Decreto-Lei n° 20/2002 de 19 de Agosto, com vista a compreender os modelos de gestão escolar e a autonomia da escola como condição indispensável à prestação de um serviço educativo de qualidade. Muito são os problemas que se tem colocado às escolas secundárias de Cabo Verde nesse momento, como por exemplo os objectivos da escola, sua forma de actuação perante os dilemas gerado nessa sociedade em transformação e a sua forma de gestão. Neste sentido o tema em estudo é sem dúvida, polémico e de grande importância para as organizações educativas em geral, e em particular para a escola secundária em estudo.

Enabling mobile access to digital libraries in digital divide contexts

Digital libraries (DL) have had a tremendous impact on improving the accessibility of scientific and academic publications. In developing countries, they seem to be the great hope, due to the serious existing problems with the traditional publishing and distribution mechanisms and to the potential they have on enabling access to a great panoply of publications. Moreover, accessing digital libraries over mobile devices has the potential of reaching a broader community of users and on helping to bridge the digital divide, since there are very reduced computer and Internet penetration rates in these countries, along with a higher mobile phone usage. For developed countries, accessing digital libraries on the go might also bring important added value. This paper features an analysis of the major issues related to making digital libraries accessible over mobile devices. A specific study on the possibility of using mobile digital libraries in a developing country context is also presented along with a proposal for making DSpace based digital libraries accessible over mobile phones.

A liderança como Factor de Motivação para o Trabalho em Equipa

A liderança constitui, hoje, um tema muito debatido pela sua importância no seio das organizações. Este factor é considerado por todas as organizações que têm objectivos e metas a alcançar. Quando falamos no alcance dos objectivos e metas, torna-se necessário mencionar a equipa que vai trabalhar para este fim. Daí a importância de referirmos a “Liderança como Factor de Motivação para o Trabalho em Equipa”. Visando contribuir para análise desta temática e a obtenção do grau de licenciatura, escolhemos o contexto da instituição Centro de Emprego e Formação Profissional da Praia (CEFPP), para fazer o nosso estudo. Ela que é uma organização que promove a formação, orientação e inserção na vida profissional, e tal como outras organizações necessita do exercício da liderança para motivação de sua equipa, á obtenção de resultados satisfatórios. O objectivo principal do nosso estudo é saber se o estilo de liderança predominantemente adoptado no CEFP da Praia incentiva o trabalho em equipa. Para atingir esse objectivo, apoiamos teoricamente, em autores que têm trabalhado a temática em questão e empiricamente, no estudo de caso realizado no “Centro de Emprego e Formação Profissional da Praia”, situado em Chão de Areia, Cidade da Praia. De referir que a recolha de dados foi efectuada mediante a aplicação de um questionário aos colaboradores e realização de uma entrevista ao Director do Centro. Quanto ao tratamento dos dados recolhidos através do questionário, recorremos ao Método Estatístico e dos dados da entrevista o Método Descritivo. Dos dados obtidos concluímos que o estilo de liderança predominante é o estilo Democrático e este incentiva os colaboradores a trabalharem em equipa.

Indoleamine 2,3-dioxygenase-expressing mature human monocyte-derived dendritic cells expand potent autologous regulatory T cells.

A comprehensive understanding of the complex, autologous cellular interactions and regulatory mechanisms that occur during normal dendritic cell (DC)-stimulated immune responses is critical to optimizing DC-based immunotherapy. We have found that mature, immunogenic human monocyte-derived DCs (moDCs) up-regulate the immune-inhibitory enzyme, indoleamine 2,3-dioxygenase (IDO). Under stringent autologous culture conditions without exogenous cytokines, mature moDCs expand regulatory T cells (Tregs) by an IDO-dependent mechanism. The priming of resting T cells with autologous, IDO-expressing, mature moDCs results in up to 10-fold expansion of CD4(+)CD25(bright)Foxp3(+)CD127(neg) Tregs. Treg expansion requires moDC contact, CD80/CD86 ligation, and endogenous interleukin-2. Cytofluorographically sorted CD4(+) CD25(bright)Foxp3(+) Tregs inhibit as much as 80% to 90% of DC-stimulated autologous and allogeneic T-cell proliferation, in a dose-dependent manner at Treg:T-cell ratios of 1:1, 1:5, and as low as 1:25. CD4(+)CD25(bright)Foxp3(+) Tregs also suppress the generation of cytotoxic T lymphocytes specific for the Wilms tumor antigen 1, resulting in more than an 80% decrease in specific target cell lysis. Suppression by Tregs is both contact-dependent and transforming growth factor-beta-mediated. Although mature moDCs can generate Tregs by this IDO-dependent mechanism to limit otherwise unrestrained immune responses, inhibition of this counter-regulatory pathway should also prove useful in sustaining responses stimulated by DC-based immunotherapy.

The dexamethasone-induced inhibition of proliferation, migration, and invasion in glioma cell lines is antagonized by macrophage migration inhibitory factor (MIF) and can be enhanced by specific MIF inhibitors.

Glioblastomas (GBMs) are the most frequent and malignant brain tumors in adults. Glucocorticoids (GCs) are routinely used in the treatment of GBMs for their capacity to reduce the tumor-associated edema. Few in vitro studies have suggested that GCs inhibit the migration and invasion of GBM cells through the induction of MAPK phosphatase 1 (MKP-1). Macrophage migration inhibitory factor (MIF), an endogenous GC antagonist is up-regulated in GBMs. Recently, MIF has been involved in tumor growth and migration/invasion and specific MIF inhibitors have been developed on their capacity to block its enzymatic tautomerase activity site. In this study, we characterized several glioma cell lines for their MIF production. U373 MG cells were selected for their very low endogenous levels of MIF. We showed that dexamethasone inhibits the migration and invasion of U373 MG cells, through a glucocorticoid receptor (GR)- dependent inhibition of the ERK1/2 MAPK pathway. Oppositely, we found that exogenous MIF increases U373 MG migration and invasion through the stimulation of the ERK1/2 MAP kinase pathway and that this activation is CD74 independent. Finally, we used the Hs 683 glioma cells that are resistant to GCs and produce high levels of endogenous MIF, and showed that the specific MIF inhibitor ISO-1 could restore dexamethasone sensitivity in these cells. Collectively, our results indicate an intricate pathway between MIF expression and GC resistance. They suggest that MIF inhibitors could increase the response of GBMs to corticotherapy.

Site Development and Facility Expansion Regularly Assistance Program, November 1, 2006

The Iowa Department of Economic Development (IDED) helps businesses expand or locate all or part of their business in Iowa. It just makes sense for companies engaged in advanced manufacturing, biosciences and information solutions/financial services to look at Iowa and IDED helps to ensure theireconomic development timelines are met. Iowa is nationally recognized as an innovator in helping businesses by meeting their development needs in a timely and effective manner. IDED networks with Regulatory Assistance Coordinators in agencies across state government to reduce response time to businesses. This agency coordination helps to ensure that regulatory and compliance questions, or other needs associated with project site development and facility expansion are serviced quickly. We have listed information below about some of the more common regulatory requirements related to site development and expansion.

Achievement of at least very good partial response is a simple and robust prognostic factor in patients with multiple myeloma treated with high-dose therapy: long-term analysis of the IFM 99-02 and 99-04 Trials.

PURPOSE: The prognostic impact of complete response (CR) achievement in multiple myeloma (MM) has been shown mostly in the context of autologous stem-cell transplantation. Other levels of response have been defined because, even with high-dose therapy, CR is a relatively rare event. The purpose of this study was to analyze the prognostic impact of very good partial response (VGPR) in patients treated with high-dose therapy. PATIENTS AND METHODS: All patients were included in the Intergroupe Francophone du Myelome 99-02 and 99-04 trials and treated with vincristine, doxorubicin, and dexamethasone (VAD) induction therapy followed by double autologous stem-cell transplantation (ASCT). Best post-ASCT response assessment was available for 802 patients. RESULTS: With a median follow-up of 67 months, median event-free survival (EFS) and 5-year EFS were 42 months and 34%, respectively, for 405 patients who achieved at least VGPR after ASCT versus 32 months and 26% in 288 patients who achieved only partial remission (P = .005). Five-year overall survival (OS) was significantly superior in patients achieving at least VGPR (74% v 61% P = .0017). In multivariate analysis, achievement of less than VGPR was an independent factor predicting shorter EFS and OS. Response to VAD had no impact on EFS and OS. The impact of VGPR achievement on EFS and OS was significant in patients with International Staging System stages 2 to 3 and for patients with poor-risk cytogenetics t(4;14) or del(17p). CONCLUSION: In the context of ASCT, achievement of at least VGPR is a simple prognostic factor that has importance in intermediate and high-risk MM and can be informative in more patients than CR.

Transcriptional activation of the GLUT2 gene by the IPF-1/STF-1/IDX-1 homeobox factor.

The homeodomain protein PDX-1, referred as IPF-1/STF-1/IDX-1, is a transcriptional factor that plays a critical role in the control of several genes expressed in the pancreatic islet. PDX-1 gene expression has been previously shown to be reduced in cultured beta-cell lines chronically exposed to high glucose concentrations. As the glucose transporter type 2 (GLUT2) gene expression is selectively decreased in the beta-pancreatic cells of experimental models of diabetes, we postulated that the loss of GLUT2 gene expression in the pancreatic islets of diabetic animals may be due to the loss of PDX-1 transacting function on the GLUT2 gene. We, therefore, investigated the potential role of PDX-1 in the transcriptional control of GLUT2. We have identified a repeat of a TAAT motif (5'-TAATA-ATAACA-3') conserved in the sequence of the human and murine GLUT2 promoters. Recombinant PDX-1 binds to this GLUT2TAAT motif in electrophoretic mobility shift experiments. PDX-1 antiserum detects the formation of the complex of PDX-1 with the GLUT2TAAT motif in nuclear extracts from the pancreatic insulin-secreting cell line, beta TC3. The GLUT2TAAT motif was mutated in the murine GLUT2 promoter (-1308/+49 bp) linked to a luciferase reporter gene and transfected into beta TC3 cells. Compared with the transcriptional activity of the wild type promoter, that of the mutated promoter decreases by 41%. Multiple copies of the GLUT2TAAT motif were ligated 5' to a heterologous promoter and transfected into a PDX-1-expressing cell line (beta TC3) and into cell lines lacking the homeobox factor (InR1-G9 and JEG-3). The GLUT2TAAT motif mediates the activation of the heterologous promoter in the PDX-1-expressing cell line but not in InR1-G9 or JEG-3 cell lines. Furthermore, cotransfection in a PDX-1-deficient cell line with the expression vector encoding PDX-1 transactivates specifically the heterologous promoter containing the multimerized GLUT2TAAT motif. These data demonstrate that the murine GLUT2 promoter is controlled by the PDX-1 homeobox factor through the identified GLUT2TAAT motif.

L'apport de CoLaus en santé publique. [What CoLaus has brought to Public health].

Afin de mener à bien leur tâche, les acteurs de santé publique se doivent de disposer d'informations fiables et récentes concernant l'état de santé de la population. Grâce à l'étude CoLaus, il a été possible d'actualiser nos connaissances sur la prévalence et la prise en charge des principaux facteurs de risque cardiovasculaire au niveau de la population lausannoise. Les résultats montrent que la prise en charge des facteurs de risque cardiovasculaire peut être améliorée, et certaines strates de la population pourraient bénéficier d'actions de prévention ciblées. L'étude CoLaus a aussi permis de simuler l'effet de plusieurs politiques de prévention, ce qui permettra de sélectionner celles ayant le meilleur rapport coût/efficacité, une option importante dans l'état actuel de contention des dépenses de santé.[Abstract] In order to fulfil their duties, Public health authorities have to rely on valid and recent data on the health status of populations. The CoLaus study helped to update our knowledge regarding the prevalence and management of the main cardiovascular risk factors in the Lausanne population. The results indicate that cardiovascular risk factor management is suboptimal and can still be improved, namely that specific population subgroups could benefit from targeted prevention measures. The CoLaus study also allowed to simulate the effect of different preventive strategies, thus enabling to choose the most (cost)effective ones, an important issue taking into account the current health budget restrictions.

Maxillary advancement and transpalatal expansion using internal distraction in a patient with cleft lip and palate.

Correction of sagittal and transverse maxillary discrepancies in patients with cleft lip or palate remains a challenge for craniofacial surgeons. Distraction osteogenesis has revolutionized the conceptualization and approach to the craniofacial malformations and has become a reliable and irreplaceable part of the surgical armamentarium. We are reporting a case of sequential maxillary advancement and transpalatal expansion using internal distraction in a patient with unilateral cleft lip and palate presenting with severe maxillary sagittal and transverse deficiencies.

Thiamine-auxotrophic mutants of Pseudomonas fluorescens CHA0 are defective in cell-cell signaling and biocontrol factor expression.

In the biocontrol strain Pseudomonas fluorescens CHA0, the Gac/Rsm signal transduction pathway positively controls the synthesis of antifungal secondary metabolites and exoenzymes. In this way, the GacS/GacA two-component system determines the expression of three small regulatory RNAs (RsmX, RsmY, and RsmZ) in a process activated by the strain's own signal molecules, which are not related to N-acyl-homoserine lactones. Transposon Tn5 was used to isolate P. fluorescens CHA0 insertion mutants that expressed an rsmZ-gfp fusion at reduced levels. Five of these mutants were gacS negative, and in them the gacS mutation could be complemented for exoproduct and signal synthesis by the gacS wild-type allele. Furthermore, two thiamine-auxotrophic (thiC) mutants that exhibited decreased signal synthesis in the presence of 5 x 10(-8) M thiamine were found. Under these conditions, a thiC mutant grew normally but showed reduced expression of the three small RNAs, the exoprotease AprA, and the antibiotic 2,4-diacetylphloroglucinol. In a gnotobiotic system, a thiC mutant was impaired for biological control of Pythium ultimum on cress. Addition of excess exogenous thiamine restored all deficiencies of the mutant. Thus, thiamine appears to be an important factor in the expression of biological control by P. fluorescens.

Undocumented migrants in Switzerland: geographical origin versus legal status as risk factor for tuberculosis.

Undocumented migrants, meaning migrants without a legal residency permit, come to Geneva from countries with high tuberculosis (TB) incidence. We estimate here whether being undocumented is a determinant of TB, independently of origin. Cross-sectional study including undocumented migrants in a TB screening program in 2002; results were compared to 12,904 age and frequency matched participants in a general TB screening program conducted at various workplaces in Geneva, Switzerland from 1992 to 2002. A total of 206 undocumented migrants (36% male, 64% female, mean age 37.8 years (SD 11.8), 82.5% from Latin America) participated in the TB screening program. Compared to legal residents, undocumented migrants had an adjusted OR for TB-related fibrotic signs of 1.7 (95% CI 0.8;3.7). The OR of TB-related fibrotic signs for Latin American (vs. other) origin was 2.7 (95% CI 1.6;4.7) among legal residents and 5.5 (95% CI 2.8;10.8) among undocumented migrants. Chest X-ray screening identified a higher proportion of TB-related fibrotic signs among Latin Americans, independently of their residency status.

Reconstruction fronto-orbitaire complexe avec prothèse en PEEK et expansion cutanée : à propos d'un cas [Complex fronto-orbital reconstruction with a PEEK prosthesis and skin expansion: about a case].

INTRODUCTION: Reconstructions of the fronto-orbital area remain a challenge to the reconstructive surgeon, due to the functional and esthetic impact. OBSERVATION: The authors present a case of a complex fronto-orbital reconstruction with a PEEK (PolyEtherEtherKetone) implant, associated with a skin expansion. DISCUSSION: With a follow-up of over three years, the cosmetic result is excellent. The authors believe that this technique is reliable, fast with long-term good results.