On Boas-Type Problem

R.P. Boas has found necessary and sufficient conditions of belonging of function to Lipschitz class. From his findings it turned out, that the conditions on sine and cosine coefficients for belonging of function to Lip α(0 & α & 1) are the same, but for Lip 1 are different. Later his results were generalized by many authors in the viewpoint of generalization of condition on the majorant of modulus of continuity. The aim of this paper is to obtain Boas-type theorems for generalized Lipschitz classes. To define generalized Lipschitz classes we use the concept of modulus of smoothness of fractional order.

Una Aproximació a la construcció significativa del coneixement matemàtic a l'ESO

This study displays and analyzes the contents of the Mathematics subject in ESO’s second cycle from a constructivist perspective. This analysis has been carried out by contrasting two groups of participants (control group and experimental group). These groups were formed by a sample of 240 students between the ages of 14 and 16 from four different educational centres of the Osona area. Research – Action methodology has been employed, combining quantitative techniques (statistical study with the SPSS package) with qualitative analysis (transcriptions of interviews and discussion group). This study has been carried out after years of classroom observation, reflection and action. The theoretical framework employed is a cognitive one, based on Ausubel’s Significative Learning Theory. Quantitative analysis shows how the researcher’s design improves, on the one hand, the students’ academic motivation and, on the other hand, their comprehensive memory, enabling them to achieve a more significant learning of the subjects’ contents. Furthermore, our analysis shows that the proposed method is more comprehensive than those employed by teachers collaborating with control groups. The main aim of the qualitative analysis is that of identifying the elements which configure the programme and contribute to an improvement of the aspects mentioned above. The key elements here are: co-operation as the basis of group dynamics; the employment, in some cases, of easily handled materials; the type of interaction between teacher and students, where, through open discussion, students are lead by teaching staff towards the course objectives; induction, that is, deducing formulae by initially using examples which are close to the students’ knowledge and experience or taken from everyday life (what we could call “down-top” mathematics). We should add here that the qualitative analysis does not only corroborate the results obtained by quantitative techniques, but also displays an increase of motivation in teaching staff. Teachers did show a positive attitude and welcomed the use and development of these materials in the next academic year. Finally, we discuss possible directions for further research.

L'Avion, L'Avion

Combined media on photographic paper. 56" x 84" Yarema Family Foundation

New specific synonymy in Neotropical Simulium S. L. (Diptera: Simuliidae)

In an attempt to clarify the taxonomy of Neotropical Simuliidae prior to the production of keys to species, various nomenclatural problems are resolved. Information is given on the status of types, their depositories, the condition of type-material where relevant, and on already established synonyms. fifteen new synonyms are established and six lectotypes designated based on an examination of type-material and long series of reared specimens from many localities to take account of intraspecific variation.

Sistema de secreción de tipo III en Aeromonas mesòfilas

Aeromonas hydrophila és un bacil gram-negatiu, patogen oportunista d’animal i humans. La patogènesi d’A. Hydrophila és multifactorial. A fi d'identificar gens implicats en la virulència de la soca PPD134/91 d’A. hydrophila, vam realitzar experiments de substracció gènica, que van dur a la detecció de 22 fragments d’ADN que codificaven 19 potencials factors de virulencia, incloent un gen que codificava una proteïna de sistema de secreció de tipus III (T3SS). La importància creixent del T3SS en la patogènesi de diversos bacteris, ens va dur a identificar i analitzar l'agrupació gènica del T3SS de les soques AH-1 i AH-3 d’A. hydrophila. La inactivació dels gens de T3SS aopB i aopD d’A. hydrophila AH-1, i ascV d’A. hydrophila AH-3, comporta una disminució de la citotoxicitat, un increment de la fagocitosi, i una reducció de la virulència en diferents models animals. Aquests resultats demostren que el T3SS és necessari per a la patogenicitat. També vam clonar i seqüenciar una ADP-ribosiltransferasa (AexT) a la soca AH-3 d’A. hydrophila, i vam demostrar que aquesta toxina és translocada via el T3SS, sistema que al seu torn sembla ser induïble in vitro en condicions de depleció de calci. El mutant en el gen aexT de la soca AH-3 d’A. hydrophila va mostrar una lleugera reducció de la virulència, assajada amb diferents mètodes. Mitjançant l'ús de diferents sondes d’ADN, vam determinar la presència del T3SS en soques tant clíniques com ambientals de diferents espècies del gènere Aeromonas: A. hydrophila, A. veronii, i A. caviae, i la codistribució d'aquesta agrupació gènica i el gen aexT. Finalment, amb la finalitat d'estudiar la regulació transcripcional de l'agrupació gènica de T3SS i de l’efector AexT A. hydrophila AH-3, vam aïllar els promotors predits per l’operó aopN-aopD i el gen aexT, i els vam fusionar amb el gen reporter gfp (Green Fluorescence Protein). A més, vam demostrar que l'expressió d'ambdós promotors depèn de diferents components bacterians, com per exemple el sistema de dos components PhoP/PhoQ, el sistema de quorum sensing AhyI/AhyR, o el complex piruvat deshidrogenasa.

Role of cytokines in secondary lymphoid organ development

Summary Secondary lymphoid organs are sites of antigen presentation, clonal expansion of B and lymphocytes, and affinity maturation of B lymphocytes. In the intestine, these immune functions occur mainly in Peyer's patches (PP). PP develop through the interplay of two main cell types, haematopoietic cells and meserichyrnal cells. One particular haematopoietic cell type was identified as the inductive cell type in the formation of both PP and lymph nodes and was therefore designated as lymphoid tissue inducer cell. For a successful PP organogenesis, the crucial molecular components involved in the crosstalk of inducer cells and their mesenchymal target cells are adhesion molecules, lymphotoxin (LT) family members, and cytokines. In particular, the interleukin 7 receptor (IL-7R) expressed on inducer cells is absolutely required. To investigate the contribution of the ligand for the IL-7R. the cytokine IL-7, in the process of PP formation, we analyzed double transgenic (TG) mice. These mice resulted from an interbreeding of an IL-7TG mouse strain where the transgene is under the control of the MHC class II promoter with a second transgenic mouse strain, which overexpresses a transactivator for MHC class II genes. Double TG offsprings revealed higher levels of IL-7 mRNA occuring earlier in embryogenesis. Consequently, double TG mice showed a striking phenotype with a 3- to 5-fold increase in PP numbers compared to single IL-7TG or control littermates. Analysis of embryonic double TG intestines demonstrated that the process of PP development was already elevated during development as early as the embryonic day 16.5. Importantly, inducer cells were significantly increased in numbers in these embryonic intestines. Furthermore, the expression of LT? mRNA, which at this early time point is exclusively expressed by inducer cells, was also increased in double TG animals. These data clearly indicate a direct influence of IL-7 on the expansion of lymphoid tissue inducer cells and on the availability of LT? leading to a higher frequency of developing PP in fetal life. Interestingly, in addition to an enhanced frequency of PP development, in double TG mice, three additional phenotypic differences were observed. i) Lymphocyte infiltration in various non-lymphoid organs, such as stomach, salivary gland, and liver. Subsequent analysis demonstrated that B lymphocytes were predominant within these tertiary lymphoid structures. ii) Ectopic lymph node-like structures containing both B and T lymphocytes were found near the inguinal lymph node. iii) Double TG mice had a severe bone resorption syndrome most likely as a consequence of the pro-osteoclastic effect of IL-7. Taken together, these results show that IL-7 plays a key role in the homeostasis of inducer cells, in the generation of PP in the gut, in the formation of ectopic lymphoid tissue, and in bone resorption. Résumé Les organes lymphoïdes secondaires sont les lieux de présentation des antigènes aux lymphocytes, permettant l'expansion des lymphocytes B et T et la maturation d'affinité des lymphocytes B. Dans l'intestin, ces fonctions immunitaires se déroulent dans les plaques de Peyer (PP). Ces plaques se développent grâce à l'interaction des cellules hématopoïétiques avec des cellules mésenchymales. Un type particulier de cellules hématopoïétiques a été identifié comme cellule inductrice dans la formation des PP et des ganglions lymphatiques et de ce fait a été désigné cellule inductrice des tissus lymphoïdes. Durant l'organogénèse des PP, les composants moléculaires cruciaux impliqués dans l'interaction des cellules inductrices et des cellules mésenchymales sont les molécules d'adhésion, les membres de la famille des lymphotoxines (LT) et les cytokines. En particulier, le récepteur de l'interleukine 7 (IL-7R) exprimé par les cellules inductrices est absolument nécessaire. Pour étudier le rôle du ligand de l'IL-7R, l'interleukine IL-7, dans la formation des PP, nous avons croisé une lignée de souris transgénique (TG) surexprimant IL-7 sous contrôle du promoteur MHC class Il avec une lignée de souris transgénique surexprimant un transactivateur des genes MHC class II. Les souris doubles TG présentent une concentration élevée d'ARNm de l'IL-7 durant l'embryogénèse, ce qui résulte en une augmentation du nombre de PP de 3 à 5 fois en comparaison aux souris ayant seul le transgène IL-7 et aux souris contrôles. L'analyse des intestins des souris doubles TG démontre que le processus de développement des PP était élevé dès le jour 16.5 du développement embryonnaire. L'augmentation du nombre des cellules inductrices dans ces intestins embryonnaires est signilicative. De plus l'expression de l'ARNm LT?, qui à ce stade précoce est exclusivement exprimé dans les cellules inductrices, est également augmenté dans les doubles TG. Ces résultats indiquent clairement une influence directe d'IL-7 sur l'expansion des cellules inductrices des tissues lymphoïdes et sur la synthèse de LT? induisant une augmentation des PP se développant durant la vie foetale. En plus du développement accru des PP dans les souris doubles TG, trois différences phénotypiques ont été observées. i) L'infiltration lymphocytaire dans différents organes non-lymphoïdes, comme l'estomac, les glandes salivaires et le foie. Des analyses complémentaires ont demontré que les lymphocytes B étaient prédominants dans ces structures lymphoïdes tertiaires. ii) Des structures de ganglions lymphatiques ectopiques contenant des lymphocytes B et T ont été trouvées près des ganglions lymphatiques inguinaux. iii) Les souris doubles TG présentent un syndrome de résorption osseuse sévère probablement dû à l'effet pro-osteoclaste d'IL-7. Globalement, ces résultats montrent que IL-7 joue un rôle clé dans l'homéostasie des cellules inductrices dans la génèse de PP de l'intestin, dans la formation des tissus lymphoïdes ectopiques et dans la résorption osseuse.

Long-Term Trends of HIV Type 1 Drug Resistance Prevalence among Antiretroviral Treatment-Experienced Patients in Switzerland.

Background. Accurate quantification of the prevalence of human immunodeficiency virus type 1 (HIV-1) drug resistance in patients who are receiving antiretroviral therapy (ART) is difficult, and results from previous studies vary. We attempted to assess the prevalence and dynamics of resistance in a highly representative patient cohort from Switzerland. Methods. On the basis of genotypic resistance test results and clinical data, we grouped patients according to their risk of harboring resistant viruses. Estimates of resistance prevalence were calculated on the basis of either the proportion of individuals with a virologic failure or confirmed drug resistance (lower estimate) or the frequency-weighted average of risk group-specific probabilities for the presence of drug resistance mutations (upper estimate). Results. Lower and upper estimates of drug resistance prevalence in 8064 ART-exposed patients were 50% and 57% in 1999 and 37% and 45% in 2007, respectively. This decrease was driven by 2 mechanisms: loss to follow-up or death of high-risk patients exposed to mono- or dual-nucleoside reverse-transcriptase inhibitor therapy (lower estimates range from 72% to 75%) and continued enrollment of low-risk patients who were taking combination ART containing boosted protease inhibitors or nonnucleoside reverse-transcriptase inhibitors as first-line therapy (lower estimates range from 7% to 12%). A subset of 4184 participants (52%) had 1 study visit per year during 2002-2007. In this subset, lower and upper estimates increased from 45% to 49% and from 52% to 55%, respectively. Yearly increases in prevalence were becoming smaller in later years. Conclusions. Contrary to earlier predictions, in situations of free access to drugs, close monitoring, and rapid introduction of new potent therapies, the emergence of drug-resistant viruses can be minimized at the population level. Moreover, this study demonstrates the necessity of interpreting time trends in the context of evolving cohort populations.

L' Aprenentatge basat en problemes a través de casos clínics simulats. Una proposta metodològica de disseny i avaluació docent

RESUM Les exigències actuals de la professió de d’infermeria requereixen que la docència vagi orientada a interrelacionar els diferents rols a desenvolupar enla pràctica diària, per adquirir experiència en l’aprenentatge i així augmentar la qualitat de les cures d’infermeria. Per assolir aquest objectiu és important l’aprenentatge basat enproblemes. Aquest pretén en primer lloc que els estudiants aprenguin allò que permet desenvolupar-se enla vida professional de la manera més natural possible a partir d’una idea clara i profunda de l’evidència sobre la que s’ha d’actuar. Amb aquesta finalitat es vandissenyar casos clínics amb uns objectius que requerien la integració de coneixements, actituds i valors, en diferents fases a desenvolupar en un període de temps predeterminat. També ens vam proposar una estratègia docent que permetés a l’estudiant incorporar el coneixement científic que dóna suport a la pràctica assistencial per aproximar teoria i pràctica. Es pretén que els estudiants busquin una resposta basada en la millor evidència científica disponible, per prendre una decisió respecte a les cures del pacient. Els objectius de l’estudi són: Avaluar globalment l’aprenentatge basat en la simulació de casos Avaluar com els estudiants valoren la integració del model d’infermeria i del procés d’atenció en l’aprenentatge basat en la simulació de casos. Valorar les sensacions percebudes per l’estudiant durant la simulació del cas. Valorar l’actitud d el’estudiant en relació a la incorporació de l’evidència científica per una millora en la pràctica clínica. Avaluar el grau de dificultat manifestat per l’estudiant en relació al procés de documentació. Avaluar la idonietat de l’argumentació i la decisió de l’estudiant a la pregunta formulada en el cas clínic. Metodologia: L’assignatura d’Infermeria Medicoquirúrgica. Adult I del Departament d’Infermeria de la Universitat de Vic, va iniciar una experiència d’aprenentatge basat en la resolució de problemes, amb estudiants de 2on curs. Les professores responsables dels seminaris van realitzar una avaluació de l’experiència a través d’una enquesta. Aquesta es responia al cap d’un mes de la simulació al laboratori, quan es contrastaven els resultats obtinguts en aquesta entre professores i estudiants després de visualitzar la gravació feta durant el mateix. En el context del seminari de simulació de casos, es va introduir una pregunta/problema, a partir de la que els estudiants, en grup, havien de documentar-se amb el suport d’una guia. Per valorar l’actitud davant aquesta pregunta/problema es va dissenyar un qustionari tipus Likert. L’avaluació del grau de dificultat s’ha registrat a través d’unes escales de puntuació. Per a l’avaluació de la decisió presa, es van valorar les síntesis resum entregades en els treballs escrits pels diferents grups. Resultats: La realització de la simulació en el laboratori va ser avaluada per un alt percentatge d’estudiants (68,8%) amb puntuacions entre 6 i 8 mentre que un 26,6% la van situar en tre 9 i 10, només un 4,7 % la van puntuar amb 5. La integració del model d’infermeria va ser valorada pel 86% amb una puntuació entre 7 i 10. La valoració global de la simulació va ser qualificada pels estudiants amb una puntuació de 8 (34,4%) seguida d’un 28,1% amb una consideració de 7. Un 7,2% van puntuar entre 9 i 10. El 93,3% van assegurar que conèixer les fonts documentals els serviria per millorar l’assistència, el 86,7% esperen obtenir arguments sòlids respecte les seves desicions si la documentació consultada és de qualitat. Un 77,8% dels estudiants consideren estar més satisfets al saber incorporar la presa de decisions basada en evidències. Respecte el grau de dificultat en el procés de documentació la dificultat més gran la presenten en com buscar en les bases de dades de referències bibliogràfiques. Conclusions: L’aprenentatge dels estudiants a través de la simulació de casos és una estratègia vàlida que l’estudiant valora positivament al mateix temps que permet desenvolupar habilitats per a la pràctica professional. L’estratègia docent dissenyada per integrar les evidències en la presa de decisions es considera positiva, no obstant, després d’analitzar els resultats, s’han de modificar alguns aspectes per a la seva millora; tutoritzar per a millorar el procés de documentació i incidir més en la crítica i reflexió, de manera que les troballes de la investigació siguin canalitzades cap a la pràctica.

The identity type weak factorisation system

We show that the classifying category C(T)of a dependent type theory T with axioms for identity types admits a nontrivial weak factorisation system. After characterising this weak factorisation system explicitly, we relate it to the homotopy theory of groupoids.

NEUROPATHOPHYSIOLOGICAL MECHANISMS IN GLUTARIC ACIDURIA TYPE I: 3-HYDROXYGLUTARIC ACID LEADS TO AMMONIA INCREASE AND NON-APOPTOTIC CELL DEATH

A 3D in vitro model of rat organotypic brain cell cultures in aggregates was used to investigate neurotoxicity mechanisms in glutaric aciduria type I (GA-I). 1 mM glutarate (GA) or 3-hydroxyglutarate (3OHGA) were repeatedly added to the culture media at two different time points. In cultures treated with 3OHGA, we observed an increase in lactate in the medium, pointing to a possible inhibition of Krebs cycle and respiratory chain. We further observed that 3OHGA and to a lesser extend GA induced an increase in ammonia production with concomitant decrease of glutamine concentrations, which may suggest an inhibition of the astrocytic enzyme glutamine synthetase. These previously unreported findings may uncover a pathogenic mechanism in this disease which has deleterious effects on early stages of brain development. By immunohistochemistry we showed that 3OHGA increased non-apoptotic cell death. On the cellular level, 3OHGA and to a lesser extend GA led to cell swelling and loss of astrocytic fibers whereas a loss of oligodendrocytes was only observed for 3OHGA. We conclude that 3OHGAwas the most toxic metabolite in our model for GA-I. 3OHGA induced deleterious effects on glial cells, an increase of ammonia production, and resulted in accentuated cell death of non-apoptotic origin.

Flagellin promotes myeloid differentiation factor 88-dependent development of Th2-type response.

Activation of dendritic cells (DC) by microbial products via Toll-like receptors (TLR) is instrumental in the induction of immunity. In particular, TLR signaling plays a major role in the instruction of Th1 responses. The development of Th2 responses has been proposed to be independent of the adapter molecule myeloid differentiation factor 88 (MyD88) involved in signal transduction by TLRs. In this study we show that flagellin, the bacterial stimulus for TLR5, drives MyD88-dependent Th2-type immunity in mice. Flagellin promotes the secretion of IL-4 and IL-13 by Ag-specific CD4(+) T cells as well as IgG1 responses. The Th2-biased responses are associated with the maturation of DCs, which are shown to express TLR5. Flagellin-mediated DC activation requires MyD88 and induces NF-kappaB-dependent transcription and the production of low levels of proinflammatory cytokines. In addition, the flagellin-specific response is characterized by the lack of secretion of the Th1-promoting cytokine IL-12 p70. In conclusion, this study suggests that flagellin and, more generally, TLR ligands can control Th2 responses in a MyD88-dependent manner.

Autofluorescence Findings Of A Novel Maculopathy In Patient With Spinocerebellar Ataxia Type 1 And Of A Cone - Rod Type Retinal Dysfunction In Three Generation Family With Spinocerebellar Ataxia Type 7

Purpose: To report a novel maculopathy in a patient with SCA1. To describe autofluorescence findings in family with SCA7 and associated cone-rod retinal dysfunction.Methods: 4 affected patients from two families were assessed to investigate a progressive loss of visual acuity (VA). Examinations included fundus photography, autofluorescence (AF) fundus fluorescein angiogragraphy (FFA) and optical coherence tomography. Electroretinogram (full-field) was performed in 2 affected patients. All patients had color vision testing using Ishihara pseudoisochromatic plates. Molecular analysis was performed in family 2.Results: The patient with known diagnosis of SCA1 had a visual acuity of 20/200 bilaterally and dyschromatopsia. He had saccadic pursuit. Fundus examination showed mild retinal pigment epithelium (RPE) changes at the macula. OCT showed bilateral macular serous detachment, which was not obvious at the FFA and explained his VA. AF imaging showed a central hyperfluorescence. The 45 year old proband from family 2 had a visual acuity of 200/20 and dyschromatopsia. ERG testing showed cone type dysfunction of photoreceptors. Her daughter affected at a younger age had the same ERGs findings. Fundus examination showed mild RPE changes in proband, normal findings in her daughter. AF imaging of both patients showed a ring of high density AF around the fovea. The ring was also obvious on near infrared AF. Later onset of gait imbalance led to the diagnosis of SCA7Conclusions: Within the group of spinocerebellar ataxias, only the type 7 is associated with retinal dysfunction. We present the first report of maculopathy associated with SCA1 causing severe vision loss. The ring of high density AF in SCA7 confirmed an early retinal photoreceptor dysfunction in patient with normal fundus.

Garnet growth in the Nufenen Pass area (Swiss Alps)

Abstract : Textural division of a mineral in pyramids, with their apices located at the centre of the mineral and their bases corresponding to the mineral faces is called textural sector zoning. Textural sector zoning is observed in many metamorphic minerals like andalousite and garnet. Garnets found in the graphite rich black shales of the Mesozoic cover of the Gotthard Massif display textural sector zoning. The morphology of this sector zoning is not the same in different types of black shales observed in the Nufenen pass area. Garnets in foliated black shales display a well developed sector zoning while garnets found in cm-scale layered black shales display well developed sectors in the direction of the schistosity plane. This sector zoning is always associated with up to 30μm sized birefringent lamellae emanating radial from the sector boundaries. They alternate with isotrope lamellae. The garnet forming reaction was determined using singular value decomposition approach and results compared to thermodynamic calculations. It is of the form chl + mu + cc + cld = bt + fds + ank + gt + czo and is similar in both layered and foliated black shales. The calculated X(O) is close to 0.36 and does not significantly vary during the metamorphic history of the rock. This corresponds to X CO2, X CH4, and X H2O BSE imaging of garnets on oriented-cuts revealed that the orientation of the lamellae found within the sectors is controlled by crystallography. BSE imaging and electron microprobe analysis revealed that these lamellae are calcium rich compared to the isotropic lamellae. The addition of Ca to an almandine rich garnet causes a small distortion of the X site and potentially, ordering. Ordered and disordered garnet might have very similar free energies for this composition. Hence, two garnets with different composition can be precipitated with minor overstepping of the reaction. It is enough that continued nucleation of a new garnet layer slightly prefers the same structure to assure a fiber-like growth of both garnet compositions side by side. This hypothesis is in agreement with the thermodynamic properties of the garnet solid solution described in the literature and could explain the textures observed in garnets with these compositions. To understand the differences in sector zoning morphology, and crystal growth kinetics, crystal size distribution were determined in several samples using 2D spatial analysis of slab surfaces. The same nucleation rate law was chosen for all cases. Different growth rate law for non-layered black shales and layered black shales were used. Garnet in layered black shales grew according to a growth rate law of the form R=kt ½. The transport of nutrient is the limiting factor. Transport will occur preferentially on the schistosity planes. The shapes of the garnets in such rocks are therefore ovoid with the longest axis parallel to the schistosity planes. Sector zoning is less developed with sectors present only parallel to the schistosity planes. Garnet in non-layered blackshales grew according to a growth rate law of the form R=kt. The limiting factor is the attachment at the surface of the garnet. Garnets in these rocks will display a well developed sector zoning in all directions. The growth rate law is thus influenced by the texture of the rock. It favours or hinders the transport of nutrient to the mineral surface. Résumé : La zonation sectorielle texturale consiste en la division d'un cristal en pyramides dont les sommets sont localisés au centre du minéral. La base de ces pyramides correspond aux faces du minéral. Ce type de zonation est fréquemment observé dans les minéraux métamorphiques tels que l'andalousite ou le grenat. Les grenats présents dans les marnes riches en graphites de la couverture Mésozoïque du Massif du Gotthard présent une zonation sectorielle texturale. La morphologie de cette zonation n'est pas la même dans les marnes litées et dans les marnes foliées. Les grenats des marnes foliées montrent des secteurs bien développés dans 3 directions. Les grenats des marnes litées montrent des secteurs développés uniquement dans la direction des plans de schistosité. Cette zonation sectorielle est toujours associée à des lamelles biréfringentes de quelques microns de large qui partent de la limite des secteurs et qui sont perpendiculaires aux faces du grenat. Ces lamelles alternent avec des lamelles isotropes. La réaction de formation du grenat a été déterminée par calcul matriciel et thermodynamique. La réaction est de la forme chl + mu + cc + cld= bt + fds + ank + gt + czo. Elle est similaire dans les roches litées et dans les roches foliées. L'évaluation des conditions fluides montrent que le X(O) est proche de 0.36 et ne change pas de façon significative durant l'histoire métamorphique de la roche. Des images BSE sur des coupes orientées ont révélé que l'orientation de lamelles biréfringentes est contrôlée parla crystallographie. La comparaison des analyses à la microsonde électronique et des images BSE révèle également que les lamelles biréfringentes sont plus riches en calcium que les lamelles isotropes. L'addition de calcium va déformer légèrement le site X et ainsi créer un ordre sur ce site. L'énergie interne d'un grenat ordré et d'un grenat désordonné sont suffisamment proches pour qu'un léger dépassement de l'énergie de la réaction de formation permette la coexistence des 2 types de grenat dans le même minéral. La formation de lamelles est expliquée par le fait qu'un grenat préférera la même structure. Ces observations sont en accord avec la thermodynamique des solutions solides du grenat et permet d'expliquer les structures similaires observées dans des grenats provenant de lithologies différentes. Une étude de la distribution des tailles des grenats et une modélisation de la croissance a permis de mettre en évidence 2 mécanismes de croissance différents suivant la texture de la roche. Dans les 2 cas, la loi de nucléation est la même. Dans les roches litées, la loi de croissance est de forme R=kt½. Le transport des nutriments est le facteur limitant. Ce transport a lieu préférentiellement dans la direction des niveaux de schistosité. Les grenats ont une forme légèrement allongée car la croissance des secteurs est facilitée sur les niveaux de schistosité. La croissance des grenats dans les roches foliées suit une loi de croissance de la forme R=kt. Les seuls facteurs limitant la croissance sont les processus d'attachement à la surface du grenat. La loi de croissance de ces grenats est donc contrainte par la texture de la roche. Cela se marque par des différences dans la morphologie de la zonation sectorielle.

Neoadjuvant chemoradiotherapy with or without panitumumab in patients with wild-type KRAS, locally advanced rectal cancer (LARC): a randomized, multicenter, phase II trial SAKK 41/07.

BACKGROUND: We conducted a randomized, phase II, multicenter study to evaluate the anti-epidermal growth factor receptor (EGFR) mAb panitumumab (P) in combination with chemoradiotherapy (CRT) with standard-dose capecitabine as neoadjuvant treatment for wild-type KRAS locally advanced rectal cancer (LARC). PATIENTS AND METHODS: Patients with wild-type KRAS, T3-4 and/or N+ LARC were randomly assigned to receive CRT with or without P (6 mg/kg). The primary end-point was pathological near-complete or complete tumor response (pNC/CR), defined as grade 3 (pNCR) or 4 (pCR) histological regression by Dworak classification (DC). RESULTS: Forty of 68 patients were randomly assigned to P + CRT and 28 to CRT. pNC/CR was achieved in 21 patients (53%) treated with P + CRT [95% confidence interval (CI) 36%-69%] versus 9 patients (32%) treated with CRT alone (95% CI: 16%-52%). pCR was achieved in 4 (10%) and 5 (18%) patients, and pNCR in 17 (43%) and 4 (14%) patients. In immunohistochemical analysis, most DC 3 cells were not apoptotic. The most common grade ≥3 toxic effects in the P + CRT/CRT arm were diarrhea (10%/6%) and anastomotic leakage (15%/4%). CONCLUSIONS: The addition of panitumumab to neoadjuvant CRT in patients with KRAS wild-type LARC resulted in a high pNC/CR rate, mostly grade 3 DC. The results of both treatment arms exceeded prespecified thresholds. The addition of panitumumab increased toxicity.