Inhibition of mouse mammary tumor virus-induced T cell responses in vivo by antibodies to an open reading frame protein.

Minor lymphocyte stimulating (Mls) antigens specifically stimulate T cell responses that are restricted to particular T cell receptor (TCR) beta chain variable domains. The Mls phenotype is genetically controlled by an open reading frame (orf) located in the 3' long terminal repeat of mouse mammary tumor virus (MMTV); however, the mechanism of action of the orf gene product is unknown. Whereas predicted orf amino acid sequences show strong overall homology, the 20-30 COOH-terminal residues are strikingly polymorphic. This polymorphic region correlates with TCR V beta specificity. We have generated monoclonal antibodies to a synthetic peptide encompassing the 19 COOH-terminal amino acid residues of Mtv-7 orf, which encodes the Mls-1a determinant. We show here that these antibodies block Mls responses in vitro and can interfere specifically with thymic clonal deletion of Mls-1a reactive V beta 6+ T cells in neonatal mice. Furthermore, the antibodies can inhibit V beta 6+ T cell responses in vivo to an infectious MMTV that shares orf sequence homology and TCR specificity with Mtv-7. These results confirm the predicted extracellular localization of the orf COOH terminus and imply that the orf proteins of both endogenous and exogenous MMTV interact directly with TCR V beta.

Influence on screening performance of second reading strategies in two lowvolume programs

BACKGROUND: The European Guidelines specify a minimum of 5,000 screening cases to be read yearly by radiologists carrying out second reading in non-centralized programs. This professional requirement is difficult to reach and/or to implement in regional programs covering a sparse population with a high number of participating radiology units, so that alternative blind double reading strategies must be devised. OBJECTIVE: To evaluate the effect on breast cancer screening performances of two second reading strategies used in non-centralized, low-volume programs. METHODS: Reading performances in two Swiss regional breast cancer screening programs (cantons of Wallis and Vaud), covering female populations, aged 50-69, of about 31'000 and 72'000 inhabitants were computed and compared. Both programs had similar screening regimens and organizations, but differed with respect to second reading. One setting applied a selective strategy whereby only experienced radiologists performed second reading; the other elicited not to restrict second readers on the basis of their individual screening activity. Analysis included some 140,000 mammograms performed between 1999 and 2005. RESULTS: Overall, screening performances improved with increasing total volume of reading, albeit not in a linear fashion. Regardless of setting, radiologists attained a higher level of screening accuracy when performing second rather than first readings, and incident rather than prevalent screening cases. The effect of a selective, small group of second readers appeared to impact favorably on the false-positive rate and other indicators of screening quality. As the learning curve depends on the number of mammograms read, these distinct strategies may bear different outcome in the long run. Implications and practical issues for low-volume programs are discussed.

Implementació i avaluació d'un programa dirigit a l'alfabetització de les mares amb infants estragers en la seva llengua i en català

El projecte « Teixint Cultures » és un projecte de recerca-acció comunitari que intenta promoure des de l’àmbit de l’educació d’adults, l’aprenentatge de la llengua catalana a partir dels recursos lingüístics que les mares d’origen africà tenen en la seva llengua familiar. El programa es porta a terme des d’una biblioteca pública infantil, i atén a mares d’origen immigrat amb fills menors de tres anys no escolaritzats al seu càrrec. Tot el projecte està vehiculat a partir dels contes infantils. De fet, intenta recuperar els contes de tradició oral provinents del continent africà per posteriorment elaborar materials educatius bilingües (en català i en les seves llengües) que es puguin utilitzar com a llibres educatius de consulta, tant per les biblioteques públiques com pels centres educatius. Els resultats s'agrupen entres àmbits a) descripció de les característiques metodològiques i organitzatives que han fet possible el projecte; b) impacte del projecte en les participants (aprenentatge del català, actituds, satisfacció i autoestima, pràctiques al voltant de la narració i la lectura de contes a la llar); i c) impacte del projecte a la biblioteca i al context local de la població de Salt. El futur del projecte es relaciona amb el Pla d'Entorn lligat amb l'establiment de relacions de continuïtat família-escola, implicació de les entitats i associacions de persones estrangeres i el tractament educatiu de la llengua familiar de l'alumnat.

Plastic brain mechanisms for attaining auditory temporal order judgment proficiency.

Accurate perception of the order of occurrence of sensory information is critical for the building up of coherent representations of the external world from ongoing flows of sensory inputs. While some psychophysical evidence reports that performance on temporal perception can improve, the underlying neural mechanisms remain unresolved. Using electrical neuroimaging analyses of auditory evoked potentials (AEPs), we identified the brain dynamics and mechanism supporting improvements in auditory temporal order judgment (TOJ) during the course of the first vs. latter half of the experiment. Training-induced changes in brain activity were first evident 43-76 ms post stimulus onset and followed from topographic, rather than pure strength, AEP modulations. Improvements in auditory TOJ accuracy thus followed from changes in the configuration of the underlying brain networks during the initial stages of sensory processing. Source estimations revealed an increase in the lateralization of initially bilateral posterior sylvian region (PSR) responses at the beginning of the experiment to left-hemisphere dominance at its end. Further supporting the critical role of left and right PSR in auditory TOJ proficiency, as the experiment progressed, responses in the left and right PSR went from being correlated to un-correlated. These collective findings provide insights on the neurophysiologic mechanism and plasticity of temporal processing of sounds and are consistent with models based on spike timing dependent plasticity.

Fermat's treatise on quadrature: A new reading

The Treatise on Quadrature of Fermat (c. 1659), besides containing the first known proof of the computation of the area under a higher parabola, R x+m/n dx, or under a higher hyperbola, R x-m/n dx with the appropriate limits of integration in each case , has a second part which was not understood by Fermat s contemporaries. This second part of the Treatise is obscure and difficult to read and even the great Huygens described it as'published with many mistakes and it is so obscure (with proofs redolent of error) that I have been unable to make any sense of it'. Far from the confusion that Huygens attributes to it, in this paper we try to prove that Fermat, in writing the Treatise, had a very clear goal in mind and he managed to attain it by means of a simple and original method. Fermat reduced the quadrature of a great number of algebraic curves to the quadrature of known curves: the higher parabolas and hyperbolas of the first part of the paper. Others, he reduced to the quadrature of the circle. We shall see how the clever use of two procedures, quite novel at the time: the change of variables and a particular case of the formulaof integration by parts, provide Fermat with the necessary tools to square very easily curves as well-known as the folium of Descartes, the cissoid of Diocles or the witch of Agnesi.

Variation in performance across Swiss mammography screening programmes: the influence of reading strategy and experience.

[Abstract] Reading volume and mammography screening performance appear positively correlated. Performance was compared across organised Swiss screening programmes, which target relatively small populations. Except for accreditation of 2nd readers radiologists (restrictive vs non-restrictive strategy), Swiss programmes have similar screening regimen/procedures and duration, which maximises comparability. Variation in performance was explored in order to improve mammography practice and optimise screening performance. Indicators of quality and effectiveness were evaluated for about 200,000 screens performed over 4 screening rounds in the 3 longest-standing Swiss cantonal programmes (of Vaud, Geneva and Valais). Interval cancers were identified by linkage with cancer registries records. Most European standards of performance were met with a favourable cancer stage shift. Several performance indicators showed substantial variation across programmes. In subsequent rounds, compared with programmes (Vaud and Geneva) which accredited few 2nd readers to increase their individual reading volume, proportions of in situ lesions and of small cancers (? 1cm) were one third lower and halved, respectively, and the proportion of advanced lesions (stage II+) nearly 50% higher in the programme without a restrictive selection strategy. Discrepancy in second-year proportional incidence of interval cancers appears to be multicausal. Differences in performance could partly be explained by a selective strategy for 2nd readers and a prior experience in service screening, but not by the levels of opportunistic screening and programme attendance. This study provides clues for enhancing mammography screening performance in low-volume Swiss programmes.

Efectos de la presencia social de las lenguas escolares en el desarrollo lingüístico del alumnado extranjero. Un estudio empírico en Cataluña = The Social Presence of School Languages and Their Effects on the Development of Immigrant Students’ Linguistic Proficiency. An Empirical Study in Catalonia

El estudio de las variables relacionadas con la adquisición de las lenguas escolares en contextos bilingües y multilingües ha resurgido a raíz de la incorporación de alumnado extranjero al sistema educativo español. En este sentido, y gracias a su peculiar situación sociolingüística, Cataluña se ha convertido en un observatorio perfecto para estudiar el proceso de adquisición de lenguas del alumnado extranjero. En este artículo presentamos una parte de los datos obtenidos en la evaluación del conocimiento de catalán y del castellano de 668 alumnos extranjeros de sexto de Primaria escolarizados en 57 centros de Cataluña. Con ello pretendemos estudiar los efectos de la presencia y del uso social de las lenguas escolares en el conocimiento lingüístico de este alumnado. La hipótesis principal es que el desarrollo de buenos niveles de conocimiento escrito de las lenguas escolares por parte de los alumnos extranjeros depende, en buena medida, de las oportunidades que haya en el entorno social para que ellos puedan utilizar estas lenguas en los intercambios comunicativos informales con sus compañeros o con otros adultos. Las conclusiones del trabajo señalan las relaciones existentes entre el desarrollo de habilidades lingüísticas conversacionales y el de habilidades lingüísticas cognitivo-académicas (Cummins, 1979b), en el sentido de que tanto el conocimiento escrito de catalán como el de castellano que tiene el alumnado extranjero están condicionados por el nivel de desarrollo conversacional previo en ambas lenguas. Además, apuntan a que la transferencia de habilidades lingüísticas cognitivo-académicas no se produce directamente entre el catalán y el castellano, sino que depende fundamentalmente de la presencia social que tengan estas lenguas y de sus usos informales. Así, en la medida en que un buen número de estudiantes extranjeros no desarrolla suficiente competencia lingüística conversacional ni en catalán ni en castellano, el proceso de adquisición de las lenguas escolares se alarga más allá de los seis años