This paper examines the reproduction of both regular rhythms and irregular sequences by 5- and 7-year-old children, concentrating on the important role played by their organization around a pulse train. It is shown that: (a) the closer rhythms are to a regular beat the easier they are to reproduce and the greater are the improvements with age; (b) memory capacity is limited by the number of pulses around which the rhythm is organized rather than by the number of elements it contains; (c) all the children's productions contain two interval lengths that are in a ratio close to 1:2 and arranged in preferential sequences which we have called "stereotypes"; (d) arrhythmic sequences can only be reproduced if the intervals undergo a systematic distortion towards regularity. These results are interpreted in relation to a pulse-train hypothesis which states that on hearing a rhythm an "internal clock" or "time base" is evoked around which the rhythm is structured.

Objectives To study the percentage, suppressive function and plasticity of Treg in giant cell arteritis (GCA), and the effects of glucocorticoids and tocilizumab. Methods Blood samples were obtained from 40 controls and 43 GCA patients at baseline and after treatment with glucocorticoids + IV tocilizumab ( n = 20) or glucocorticoids ( n = 23). Treg percentage and phenotype were assessed by flow cytometry. Suppressive function of Treg was assessed by measuring their ability to inhibit effector T‐cell (Teff) proliferation and polarisation into Th1 and Th17 cells. Results Treg (CD4 + CD25 high FoxP3 + ) frequency in total CD4 + T cells was decreased in active GCA patients when compared to controls (2.5% vs. 4.7%, P < 0.001) and increased after treatment with tocilizumab but worsened after treatment with glucocorticoids alone. Treg lacking exon 2 of FoxP3 were increased in GCA patients when compared to controls (23% vs. 10% of total Treg, P = 0.0096) and normalised after treatment with tocilizumab + glucocorticoids but not glucocorticoids alone. In GCA patients, Treg were unable to control Teff proliferation and induced ˜50% increase in the amount of IL‐17 + Teff, which was improved after in vitro blockade of the IL‐6 pathway by tocilizumab. Conclusion This study reports quantitative and functional disruptions in the regulatory immune response of GCA patients and demonstrates that, unlike glucocorticoids, tocilizumab improves Treg immune response.

A musical rhythm can be described in terms of both its temporal and its dynamic structure. However, although 6-year-old children are able to perceive and reproduce simple temporalstructures, even 8-year-olds rarely reproduce intensity differences. Four experiments on the perception and reproduction of musical rhythms by 5-to Syear-old children demonstrate that even though dynamic structure is clearly dominated by its temporal support, intensity differences playa role in reinforcing the temporal structure. The inability of children to reproduce intensity differences appears to be due neither to an inability to control the intensity of their tap responses nor to the fact that they cannot perceive such changes in intensity. Rather, the results seem best interpreted in terms of the allocation of attentional resources. With simple stimulus material (Experiments 1-3), the children focused on temporal information, and only when the processing of temporal information was mastered did they have "enough attention left" to direct it to intensity differences (Experiment 2). With more complex orchestral music (Experiment 4), attention was primarily allocated to the dynamic structure.Psychologists concerned with the perception of music have tended to concentrate on either melodic or temporal aspects of the auditory sequence. The last few years, however, have seen the appearance of studies of the relation between the two, with two main explanations emerging. As for the first, Jones (1976, 1987) has proposed a model of perceptual interaction, in which perceived temporal structure affects pitch structure by guiding attention to the pitch events that coincide with stressed temporal events. Some empirical support for this model has been provided by Deutsch (1982) and Jones, Boltz, and Kidd (1982). The second explanation suggests, on the contrary, that temporal and pitch information could be perceived independently. Krurnhansl (1987a, 1987b) have presented some empirical evidence which indicates that the perceived dimensions are processed separately, with the listeners attending to one stimulus dimension at the expense of the other. Studies involving factorial analysis of discrimination tasks (Gabriels son, 1973;Monahan & Carterette, 1985) also describe two orthogonal factors (rhythm and pitch), with the former being more fundamental. The idea of independent processing has also been developed by Thomas and Weaver (1975), who proposed two information processing systems, one responsible for analyzing temporal information and anThe authors are grateful to G. Vallee, F. Leprince, and C. Basso for collecting part of the data. They wish to thank the anonymous reviewers for their helpful criticisms, M. C. Bolte for her help in controlling the stimuli and her comments on the paper, and W. Jay Dowling, L. 91other responsible for analyzing the characteristics of the sound, such as intensity or pitch.In this paper, we examine a similar question concerning the perception of musical rhythm. In the same way as the dependence or independence o...

Background Immunosuppressive cell-based therapy is a recent strategy for controlling Graft- versus -Host Disease (GvHD). Such cells ought to maintain their suppressive function in inflammatory conditions and in the presence of immunosuppressive agents currently used in allogeneic hematopoietic cell transplantation (allo-HCT). Moreover, these therapies should not diminish the benefits of allo-HCT, the Graft- versus -Leukemia (GvL) effect. We have previously reported on a novel subset of human monocyte-derived suppressor cells (HuMoSC) as a prospective approach for controlling GvHD.Objective The objective of this study was to explore the therapeutic relevance of the HuMoSC in clinical conditions. Methods Immune regulatory functions of HuMoSC were assessed in inflammatory conditions and in the presence of immunosuppressants. The therapeutic efficiency of the association of HuMoSC with immunosuppressants was evaluated in an experimental model of GvHD induced by human PBMC in NOD/SCID/IL2-Rγ c −/− (NSG) mice. Interestingly, the inhibitory functions of HuMoSC against T lymphocytes and their ability to polarize Treg are preserved, in vitro , in inflammatory environments and are not affected by immunosuppressive agents. In vivo , the association of HuMoSC-based treatment with an immunosuppressive drug showed a synergistic effect for controlling GvHD. Furthermore, HuMoSC control GvHD while preserving GvL effect in a xeno-GvHD conditioned mouse model with cell neoplasm (CAL-1). HuMoSC are generated according to good manufacturing practices (GMP) and we demonstrated that these cells tolerate long-term preservation with unaltered phenotype and function.Conclusion HuMoSC-based therapy represents a promising approach for controlling GvHD and could be quickly implemented in clinical practice.

Children of 5 to 6 years are generally thought not to have acquired a sense of stable key in music. This experiment shows that specialized tutoring allows them to acquire and use the specific functions of the tonic and dominant as points of stability and boundaries for grouping rhythmic sequences in a reproduction task. Untrained children of the same age do not use the cues provided by the tonal system, but lean rather upon verbal boundaries (in the sense of syntactic constituents). Three analyses of the results demonstrated that (a) verbal and melodic cues superimposed onto rhythmic models were used differently according to the musical competence of the child; (b) children do not always respect tempo or accentuation, but generally produce highly structured sequence; (c) the temporal sequences reproduced have a hierarchical organization on two levels: local organization, which can be considered related to episodic memory and global organization, which is related to semantic memory and so is dependent on the subject's musical knowledge.

Prosody is assumed to play a crucial role during the preverbal stage of infancy, as well as to be essential for the pragmatics of speech. Our experiments are aimed at analyzing the production and perception of illocutionary forms. Using a semantic neutralization procedure, the performance of children (5, 7, and 9 years old) and adults was compared in two experiments focusing on prosodic representations in production and perception tasks. The first experiment investigated subjects' control of prosody in the unfolding of utterances by studying the acoustic configurations of four illocutionary forms, two corresponding to the linguistic mode (assertion, interrogation) and two corresponding to the emotional mode (happiness, sadness). The second experiment examined subjects' identification of the same illocutionary forms as above, plus an additional form, irony, all produced by an expert speaker, using a word-by-word gating procedure. During speech production, control of the fundamental frequency of the voice emerged earlier in childhood (5-year-olds) than control of rhythmic parameters (7-year-olds) for the linguistic mode, whereas control of all parameters was achieved by the age of five for the emotional mode. Children were similar to adults with respect to the planning of intonation and they used it right from the beginning of the sentence, which was not the case for the planning of duration. During speech perception, only adults were able to anticipate illocutionary forms. Taken together, the results strengthen the idea that prosodic representations are acquired gradually during development, and they show that pitch contour is acquired before duration parameters.

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The surface structures of music and speech should coincide in musical prosody. Two processing systems have thus to be integrated, one devoted to the surface structure of speech, the other to that of music. This article is in two parts: a review of data on speech and music production and hearing, and two experimental studies on the synchronization between a rhythm and spoken sounds. In the first part, a comparison between some intensity and timing parameters that characterize the unfolding of spoken strings and of musical sequences is presented. Data from studies on performers (speakers, musicians) and listeners are compared with regard to spontaneous rates, location and duration of pauses, duration of sounds, and periodic occurrence of accents. In the second part, the ability to control the correspondence between taps and words is examined. Two experimental studies on 6-year-old children focus on the role of musical training. The reproductions of simple rhythms and simple sentences or onomatopoeias were analyzed as well as the coordination between a rhythmic sequence of taps and a spoken string. Young musicians succeeded better than nonmusicians of the same age in the synchronization between their verbal production and their motor accompaniment, mainly because they more markedly anticipated the musical string in which they integrated the spoken sounds subsequently. The results are discussed in relation to the acoustic, motor, and cognitive processes involved in the coordination of the two temporal strings.