Approche multidisciptinaire des coûts humains des lombalgies [Human cost of low back pain: a multi-disciplinary approach]

The valuation of human costs is a necessity, but this task poses many problems of method. A team made of a philosopher, a psychologist and a physician has been working with economist researchers in order to look into the meaning that the preferences announced at the time of the inquiries on human costs by QALY methods could assume. These methods are often used to obtain a valuation of the impact of a health attack on people's quality of life. The methods--in the frame of the argument assumed by the economic theory on well-being--hypothesize that people's choices depend mainly on cognitive work. The qualitative interviews show that the psychological construction process for the announced preferences largely overlap this frame. In this paper the authors hastily tackle the factors which have an effect on the preferences. They conclude that the QALY methods don't seem to be able to assess the quality of life nori to valuate the damage that the quality of life could include.

Single loci with major effects in fire ants : the effects of the complementary sex-determining locus and the green beard supergene on gene expression

Etant données la complexité et la redondance des réseaux de gènes influençant de nombreux phénotypes, l'étude des rares cas d'un locus unique ayant des effets importants sur de nombreux phénotypes peut fournir des informations cruciales sur l'évolution des traits complexes. Nous avons séquencé le génome de la fourmi de feu Solenopsis invicta pour étudier comment l'expression des gènes détermine les effets majeurs et étendus de deux loci uniques sur le phénotype. Le premier locus concerne la détermination du sexe par le modèle des allèles complémentaires. Ce locus est connu pour déterminer le sexe chez tous les hyménoptères mais n'a été caractérisé que chez les abeilles. Les hétérozygotes pour ce locus se développent en reines diploïdes (ou ouvrières stériles) alors que les homozygotes se développent en mâles diploïdes incapables de produire du sperme et les hémizygotes en mâles haploïdes fertiles. Nous avons comparé l'expression des gènes entre les reines et les deux types de mâles au stade pupe, ainsi que 1 et 11 jours après l'émergence. Nous avons trouvé un changement prononcé de l'expression des gènes chez les mâles diploïdes, passant de très proche de celle des reines au stade pupe à identique aux mâles haploïdes 11 jours après l'émergence. Cela signifie que les mâles diploïdes sont condamnés à être stériles parce que les effets après émergence du locus de détermination du sexe ne per¬mettent pas d'effacer les effets de la ploïdie sur l'expression des gènes pendant le stade pupe, quand la spermatogénèse prend place. Le second locus aux effets majeurs que nous avons étudié est le supergène dit "green beard", qui consiste en 616 gènes couvrant 55% d'un chromosome (13 Mb) et est caractérisé par une absence de recombinaison entre les deux variants du supergène : "Social B" et "Social b" (SB et Sb). Au travers de l'effet "green beard", par lequel les ouvrières avec le supergène Sb discriminent favorablement les reines qui partagent ce supergène de façon perceptible, le génotype des reines fondatrices au niveau de ce supergène détermine l'organisation de la colonie : soit elle contient une seule reine SB/SB, soit plusieurs reines SB/Sb. Nous avons montré que le chromosome Sb a évolué comme le chromosome Y, accumulant probablement des allèles favorables dans des colonies avec plusieurs reines mais défavorables dans des colonies avec une seule reine (cf. gènes sexuellement antagonistes), ainsi que des transposons et des séquences répéti¬tives. Nous avons également montré que le polymorphisme du supergène cause de grandes différences d'expression chez les ouvrières et particulièrement les reines mais pas chez les mâles. Pour comprendre comment le polymorphisme du supergène chez les reines peut affecter l'organisation de la colonie, nous avons comparé l'expression entre les génotypes SB/SB et SB/Sb chez des reines vierges (1 et 11 jours) et des reines matures. Nous avons montré que les reines SB/SB sur-régulent des gènes impliqués dans la reproduction, expli-quant pourquoi elle grandissent plus rapidement et peuvent fonder des colonies de façon indépendante, tandis que les reines SB/Sb (qui ne peuvent fonder une nouvelle colonie) sur-régulent des gènes de signalement chimique qui affectent l'organisation des colonies par l'effet "green beard". - Given the complexity and redundancy of the gene networks that underlie many pheno- types, the study of rare cases of a single locus having major effects on many phenotypes can give powerful insights into the evolution of complex traits. We sequenced the genome of Solenopsis invicta fire ants to study how gene expression mediates the widespread major effects of two single loci on phenotype. The first is the complementary sex-determining locus, which is known to exist in most Hymenoptera despite being characterized only for honeybees. Heterozygotes at this locus become diploid queens (or sterile workers), homozy¬gotes become aspermic diploid males, and hemizygotes become fertile haploid males. We compared gene expression between queens and both types of males in pupae and 1 and 11 days after eclosion. We found a pronounced shift in gene expression in diploid males, from being nearly identical to queens as pupae to identical to haploid males 11 days after eclosion. This means that diploid males are condemned to sterility because the overriding effects of the sex locus after eclosion cannot undo the ploidy effects on expression during the pupal stage, when spermatogenesis must be completed. The second locus with major ef¬fects that we studied was the so-called "green beard" supergene, which consists of 616 genes encompassing 55% of one chromosome (13 Mb), without recombination between the two variants "Social B" and "Social b" (SB and Sb) supergene. Through the green beard effect, i.e. workers with the Sb supergene discriminating in favor of queens who perceptibly share this supergene, the founding queen's genotype at the supergene determines colony organi¬zation: either headed by a single SB/SB queen or many SB/Sb queens. We show that the Sb chromosome evolved like a Y-chromosome, probably accumulating alleles beneficial in multi-queen colonies but disadvantageous in single-queen colonies (cf. sexually antagonistic genes), as well as transposons and repetitive sequences. We also show that the polymor¬phism of the supergene causes widespread expression differences in workers and especially queens but not in males. To understand how the polymorphism at the supergene in queen can transform colony organization, we compared the expression between SB/SB and SB/Sb virgin queens (1 and 11 days) and mother queens. We show that SB/SB queens up-regulate genes involved in reproduction, explaining why they mature faster and can found colonies independently, while SB/Sb queens (which cannot found colonies) up-regulate chemical signaling genes that can transform colonies through the green beard effect.

A comparison between joint coordinate system and attitude vector for multi-segment foot kinematics.

The joint angles of multi-segment foot models have been primarily described using two mathematical methods: the joint coordinate system and the attitude vector. This study aimed to determine whether the angles obtained through these two descriptors are comparable, and whether these descriptors have similar sensitivity to experimental errors. Six subjects walked eight times on an instrumented walkway while the joint angles among shank, hindfoot, medial forefoot, and lateral forefoot were measured. The angles obtained using both descriptors and their sensitivity to experimental errors were compared. There was no overall significant difference between the ranges of motion obtained using both descriptors. However, median differences of more than 6° were noticed for the medial-lateral forefoot joint. For all joints and rotation planes, both descriptors provided highly similar angle patterns (median correlation coefficient: R>0.90), except for the medial-lateral forefoot angle in the transverse plane (median R=0.77). The joint coordinate system was significantly more sensitive to anatomical landmarks misplacement errors. However, the absolute differences of sensitivity were small relative to the joints ranges of motion. In conclusion, the angles obtained using these two descriptors were not identical, but were similar for at least the shank-hindfoot and hindfoot-medial forefoot joints. Therefore, the angle comparison across descriptors is possible for these two joints. Comparison should be done more carefully for the medial-lateral forefoot joint. Moreover, despite different sensitivities to experimental errors, the effects of the experimental errors on the angles were small for both descriptors suggesting that both descriptors can be considered for multi-segment foot models.

The mechanisms of centriole biogenesis

Résumé : Le centrosome contient une paire de centrioles entourée par du matériel péricentriolaire (PCM) et cet ensemble constitue le centre organisateur des microtubules de la majorité des cellules animales. Tout comme l'ADN, 1'unique centrosome présent au début du cycle cellulaire est dupliqué une et une seule fois pour former deux centrosomes qui vont orchestrer la mise en place du fuseau mitotique. La duplication du centrosome doit être soumise à une régulation précise car la présence d'un seul ou de plus de deux centrosomes peut entraîner la formation d'un fuseau mitotique aberrant, la mauvaise ségrégation des chromosomes et l'aneuploïdie. Bien que la duplication des centrioles soit un phénomène clé pour la duplication du centrosome lui-même, les mécanismes impliqués dans la formation des centrioles sont peu connus et constituent une importante question de biologie cellulaire. Dans cette thèse, nous nous sommes concentrés sur l'analyse de HsSAS-6. Nous avons trouvé que cette protéine est nécessaire pour la formation d'un centriole et qu'elle est localisée spécifiquement à la base des nouveaux centrioles formés. Les niveaux de HsSAS-6 oscillent pendant le cycle cellulaire : la protéine est absente en G1, commence à s'accumuler au niveau du centriole et dans le cytoplasme dès le début de la phase S de synthèse et disparaît abruptement pendant l'anaphase, où probablement APC/CCdlh1 la dirige vers une dégradation par le protéasome 26S. Il est important de noter que la surexpression de HsSAS-6 entraîne la formation de multiples centrioles au lieu d'un seul, ce qui indique que les niveaux de HsSAS-6 déterminent le nombre de centrioles formés. En plus de HsSAS-6, nous avons aussi étudié la lignée mutante sas-2 de C. elegans qui quelques fois assemble un fuseau multi-polaire dans l'embryon à une cellule. Nous avons montré que ce phénotype est la conséquence de la présence de multiples centrioles dans les cellules du sperme. Enfin, nous avons aussi préparé une palette de vecteurs compatibles avec le système Gateway pour permettre la génération rapide de lignées cellulaires humaines exprimant des protéines de manière inductible. De plus, nous avons commencé à développer une méthode pour évaluer la duplication des centrioles par le biais d'une plateforme de criblage d'une librairie de siRNA humains. Dans l'ensemble, notre travail a pu apporter une nouvelle compréhension du processus de duplication des centrioles et a contribué au développement de nouveaux outils de recherche de ce processus. Summary : Centrosomes contain a pair of centrioles surrounded by pericentriolar material (PCM) and serve as the main microtubule organizing centers (MTOCs) of most animal cells. Just like the DNA, the single centrosome present early in the cell cycle duplicates once and only once to give rise to two centrosomes which will then direct assembly of a bipolar spindle. Centrosome duplication must be precisely regulated because the presence of either one or more than two centrosomes can lead to the assembly of an aberrant spindle, chromosome missegregation and aneuploidy. Although duplication of centrioles is key for that of the entire centrosome, the mechanisms underlying centriole formation are poorly understood and represent an important question in cell biology. In this thesis, we focused on the analysis of HsSAS-6. We found that this protein is required for centriole formation and that it is localized specifically at the base of newly forming centrioles. The levels of HsSAS-6 oscillate across the cell cycle. The protein is absent during G1, starts to accumulate at the centriole and in the cytoplasm at the onset of S phase and disappears abruptly during anaphase when it is targeted for 26S proteasome dependent degradation probably by the APC/CCdh1. Importantly, overexpression of HsSAS-6 leads to the formation of multiple centrioles instead of just one, indicating that levels of HsSAS-6 determine the number of centrioles at each cell cycle. Besides HsSAS-6 that is the main focus of this thesis, we have also investigated the C. elegans mutant strain sas-2, which sometimes assembles a multipolar spindle in the one cell stage embryo. We have shown that this phenotype derives from the presence of multiple centrioles in sperm cells. Moreover, we prepared a set of Gateway compatible vectors for fast generation of human cell lines with inducible protein expression. Finally, we started to develop an assay for centriole duplication that can be used in a high throughput setting for screening of human siRNA libraries. Taken together, our work brought novel insights into the process of centriole duplication and lead to the development of new tools for further investigation of this process.

Prognostic value of serial blood S100B determinations in stage IIB-III melanoma patients: a corollary study to EORTC trial 18952.

S100B is a prognostic factor for melanoma as elevated levels correlate with disease progression and poor outcome. We determined its prognostic value based on updated information using serial determinations in stage IIb/III melanoma patients. 211 Patients who participated in the EORTC 18952 trial, evaluating efficacy of adjuvant intermediate doses of interferon α2b (IFN) versus observation, entered a corollary study. Over a period of 36 months, 918 serum samples were collected. The Cox time-dependent model was used to assess prognostic value of the latest (most recent) S100B determination. At first measurement, 178 patients had S100B values <0.2 μg/l and 33 ≥ 0.2 μg/l. Within the first group, 61 patients had, later on, an increased value of S100B (≥ 0.2 μg/l). An initial increased value of S100B, or during follow-up, was associated with worse distant metastasis-free survival (DMFS); hazard ratio (HR) of S100B ≥ 0.2 versus S100B < 0.2 was 5.57 (95% confidence interval (CI) 3.81-8.16), P < 0.0001, after adjustment for stage, number of lymph nodes and sex. In stage IIb patients, the HR adjusted for sex was 2.14 (95% CI 0.71, 6.42), whereas in stage III, the HR adjusted for stage, number of lymph nodes and sex was 6.76 (95% CI 4.50-10.16). Similar results were observed regarding overall survival (OS). Serial determination of S100B in stage IIb-III melanoma is a strong independent prognostic marker, even stronger compared to stage and number of positive lymph nodes. The prognostic impact of S100B ≥ 0.2 μg/l is more pronounced in stage III disease compared with stage IIb.

What the Law Requires: Accessible Multi-family Housing in Iowa, 2003

Booklet produced by the Iowa Civil Rights Commission for individuals who own, design, build, or develop multi-family housing.

Testing for potential contextual bias effects during the verification stage of the ACE-V methodology when conducting fingerprint comparisons

This study was conducted to assess if fingerprint specialists could be influenced by extraneous contextual information during a verification process. Participants were separated into three groups: a control group (no contextual information was given), a low bias group (minimal contextual information was given in the form of a report prompting conclusions), and a high bias group (an internationally recognized fingerprint expert provided conclusions and case information to deceive this group into believing that it was his case and conclusions). A similar experiment was later conducted with laypersons. The results showed that fingerprint experts were influenced by contextual information during fingerprint comparisons, but not towards making errors. Instead, fingerprint experts under the biasing conditions provided significantly fewer definitive and erroneous conclusions than the control group. In contrast, the novice participants were more influenced by the bias conditions and did tend to make incorrect judgments, especially when prompted towards an incorrect response by the bias prompt.

Multi-scale label interaction to improve object detection and segmentation

The project aims at advancing the state of the art in the use of context information for classification of image and video data. The use of context in the classification of images has been showed of great importance to improve the performance of actual object recognition systems. In our project we proposed the concept of Multi-scale Feature Labels as a general and compact method to exploit the local and global context. The feature extraction from the discriminative probability or classification confidence label field is of great novelty. Moreover the use of a multi-scale representation of the feature labels lead to a compact and efficient description of the context. The goal of the project has been also to provide a general-purpose method and prove its suitability in different image/video analysis problem. The two-year project generated 5 journal publications (plus 2 under submission), 10 conference publications (plus 2 under submission) and one patent (plus 1 pending). Of these publications, a relevant number make use of the main result of this project to improve the results in detection and/or segmentation of objects.

Primera fase del proyecto de creación de una herramienta de ticketing web Ibermática multi-cliente y parametrizable

Primera fase del proyecto de creación de una herramienta de ticketing web Ibermática multi-cliente y parametrizable.

Multi-receptor binding profile of clozapine and olanzapine: a structural study based on the new beta (2) adrenergic receptor template

Schizophrenia is a devastating mental disorder that has a largeimpact on the quality of life for those who are afflicted and isvery costly for families and society.[1] Although the etiology ofschizophrenia is still unknown and no cure has yet beenfound, it is treatable, and pharmacological therapy often producessatisfactory results. Among the various antipsychoticdrugs in use, clozapine is widely recognized as one ofthemost clinically effective agents, even if it elicits significant sideeffects such as metabolic disorders and agranulocytosis. Clozapineand the closely related compound olanzapine are goodexamples ofdrug s with a complex multi-receptor profile ;[2]they have affinities toward serotonin, dopamine, a adrenergic,muscarinic, and histamine receptors, among others.

Estimation of inelastic seismic material properties of a surgical sea-bed from multi-component marine seismic data

To date, state-of-the-art seismic material parameter estimates from multi-component sea-bed seismic data are based on the assumption that the sea-bed consists of a fully elastic half-space. In reality, however, the shallow sea-bed generally consists of soft, unconsolidated sediments that are characterized by strong to very strong seismic attenuation. To explore the potential implications, we apply a state-of-the-art elastic decomposition algorithm to synthetic data for a range of canonical sea-bed models consisting of a viscoelastic half-space of varying attenuation. We find that in the presence of strong seismic attenuation, as quantified by Q-values of 10 or less, significant errors arise in the conventional elastic estimation of seismic properties. Tests on synthetic data indicate that these errors can be largely avoided by accounting for the inherent attenuation of the seafloor when estimating the seismic parameters. This can be achieved by replacing the real-valued expressions for the elastic moduli in the governing equations in the parameter estimation by their complex-valued viscoelastic equivalents. The practical application of our parameter procedure yields realistic estimates of the elastic seismic material properties of the shallow sea-bed, while the corresponding Q-estimates seem to be biased towards too low values, particularly for S-waves. Given that the estimation of inelastic material parameters is notoriously difficult, particularly in the immediate vicinity of the sea-bed, this is expected to be of interest and importance for civil and ocean engineering purposes.