955 resultados para Early Development


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The work in this thesis concerns the advanced development of polymeric membranes of two types; pervaporation and lateral-flow. The former produced from a solution casting method and the latter from a phase separation. All membranes were produced from casting lacquers. Early research centred on the development of viable membranes. This led to a supported polymer blend pervaporation membrane. Selective layer: plasticized 4:1 mass ratio sodium-alginate: poly(vinyl-alcohol) polymer blend. Using this membrane, pervaporation separation of ethanol/water mixtures was carefully monitored as a function of film thickness and time. Contrary to literature expectations, these films showed increased selectivity and decreased flux as film thickness was reduced. It is argued that morphology and structure of the polymer blend changes with thickness and that these changes define membrane efficiency. Mixed matrix membrane development was done using spherical, discreet, size-monodisperse mesoporous silica particles of 1.8 - 2μm diameter, with pore diameters of ~1.8 nm were incorporated into a poly(vinyl alcohol) [PVA] matrix. Inclusion of silica benefitted pervaporation performance for the dehydration of ethanol, improving flux and selectivity throughout in all but the highest silica content samples. Early lateral-flow membrane research produced a membrane from a basic lacquer composition required for phase inversion; polymer, solvent and non-solvent. Results showed that bringing lacquers to cloud point benefits both the pore structure and skin layers of the membranes. Advancement of this work showed that incorporation of ethanol as a mesosolvent into the lacquer effectively enhances membrane pore structure resulting in an improvement in lateral flow rates of the final membranes. This project details the formation mechanics of pervaporation and lateral-flow membranes and how these can be controlled. The principle methods of control can be applied to the formation of any other flat sheet polymer membranes, opening many avenues of future membrane research and industrial application.

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Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterised by the loss of midbrain dopaminergic neurons from the substantia nigra pars compacta(SNpc), which results in motor, cognitive and psychiatric symptoms. Evidence supports a role for the mitogen-activated protein kinase p38 in the demise of dopaminergic neurons, while mitogen-activated protein kinase phosphatase-1 (MKP-1), which negatively regulates p38 activity, has not yet been investigated in this context. Inflammation may also be associated with the neuropathology of PD due to evidence of increased levels of proinflammatory cytokines such as interleukin-1β (IL-1β) within the SNpc. Because of the specific loss of dopaminergic neurons in a discreet region of the brain, PD is considered a suitable candidate for cell replacement therapy but challenges remain to optimise dopaminergic cell survival and morphological development. The present thesis examined the role of MKP-1 in neurotoxic and inflammatory-induced changes in the development of midbrain dopaminergic neurons. We show that MKP-1 is expressed in dopaminergic neurons cultured from embryonic day (E) 14 rat ventral mesencephalon (VM). Inhibition of dopaminergic neurite growth induced by treatment of rat VM neurons with the dopaminergic neurotoxin 6- hydroxydopamine (6-OHDA) is mediated by p38, and is concomitant with a significant and selective decrease in MKP-1 expression in these neurons. Dopaminergic neurons transfected to overexpress MKP-1 displayed a more complex morphology and contributed to neuroprotection against the effects of 6-OHDA. Therefore, MKP-1 expression can promote the growth and elaboration of dopaminergic neuronal processes and can help protect them from the neurotoxic effects of 6-OHDA. Neural precursor cells (NPCs) have emerged as promising alternative candidates to fetal VM for cell replacement strategies in PD. Here we show that phosphorylated (and thus activated) p38 and MKP-1 are expressed at basal levels in untreated E14 rat VM NPCs (nestin, DCX, GFAP and DAT-positive cells) following proliferation as well as in their differentiated progeny (DCX, DAT, GFAP and βIII-tubulin) in vitro. Challenge with 6-OHDA or IL-1β changed the expression of endogenous phospho-p38 and MKP-1 in these cells in a time-dependent manner, and so the dynamic balance in expression may mediate the detrimental effects of neurotoxicity and inflammation in proliferating and differentiating NPCs. We demonstrate that there was an up-regulation in MKP-1 mRNA expression in adult rat midbrain tissue 4 days post lesion in two rat models of PD; the 6-OHDA medial forebrain bundle (MFB) model and the four-site 6-OHDA striatal lesion model. This was concomitant with a decrease in tyrosine hydroxylase (TH) mRNA expression at 4 and 10 days post-lesion in the MFB model and 10 and 28 days post-lesion in the striatal lesion model. There was no change in mRNA expression of the pro-apoptotic gene, bax and the anti-apoptotic gene, bcl-2 in the midbrain and striatum. These data suggest that the early and transient upregulation of MKP-1 mRNA in the midbrain at 4 days post-6-OHDA administration may be indicative of an attempt by dopaminergic neurons in the midbrain to protect against the neurotoxic effects of 6-OHDA at later time points. Collectively, these findings show that MKP-1 is expressed by developing and adult dopaminergic neurons in the midbrain, and can promote their morphological development. MKP-1 also exerts neuroprotective effects against dopaminergic neurotoxins in vitro, and its expression in dopaminergic neurons can be modulated by inflammatory and neurotoxic insults both in vitro and in vivo. Thus, these data contribute to the information needed to develop therapeutic strategies for protecting midbrain dopaminergic neurons in the context of PD.

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Background: Assessing child growth and development is complex. Delayed identification of growth or developmental problems until school entry has health, educational and social consequences for children and families. Health care professionals (HCPs), including Public Health Nurses work with parents to elicit and attend to their growth and development concerns. It is known that parents have concerns about their children’s growth and development which are not expressed in a timely manner. Measuring parental concern has not been fully effective to date and little is known about parents’ experiences of expressing concerns. Aim: To understand how parents make sense of child growth or development concerns. Method: The study was qualitative using Interpretative Phenomenological Analysis (IPA). A purposeful sample of 15 parents of pre-school children referred by their PHN to second tier services was used. Data were collected by semi-structured interviews. NVivo version 10 was used for data management purposes and IPA for analysis. Findings: Findings yielded two contextual themes which captured how parents described The Concern – ‘telling it as it is’ and their experiences of being Referred on. Four superordinate themes were found which encapsulated the Uncertainty – ‘a little bit not sure’ of parents as they made sense of the child’s growth and development problems. They were influenced by Parental Knowledge – ‘being and getting in the know’ which aided their sense-making before being prompted by Triggers to action. Parents then described Getting the child’s problem checked out as they went to express their concerns to HCPs. Conclusion and Implications: Parental expression of concerns about their child is a complex process that may not be readily understood by HCPs. A key implication of findings is to reappraise how parental concern is elicited and attended to in order to promote early referral and intervention of children who may have growth and development problems.

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Eczema prevalence rates among Irish infants are unreported, despite eczema being the most common inflammatory condition of infancy. Maternal and infant nutritional status including vitamin D and other fat-soluble vitamins as well as early infant feeding have been linked with eczema initiation and development. Therefore, early nutrition could be a potential modifiable risk factor. The objective of this thesis was to prospectively describe early infant feeding and complementary feeding practices, to evaluate infant vitamin D supplementation practice, to quantify cord serum 25-hydroxyvitamin D [25(OH)D] and propose reference intervals for vitamin D metabolites, to report eczema prevalence and explore the potential role of infant nutrition and eczema. These research needs were investigated through the Cork BASELINE (Babies After SCOPE: Evaluating the Longitudinal Impact with Neurological and Nutritional Endpoints) Birth Cohort Study (n 2137). This thesis was the first comprehensive report from the birth cohort, therefore it was important to describe the cohort sociodemographic profile. Although socio-demographic characteristics compared well with national data, there was an over-representation of educated mothers which may limit the generalizability of the results. From August 2008 through November 2011, comprehensive postnatal assessments were completed at day 2 and at 2, 6, 12 and 24 months. Breastfeeding rates were low, while complementary feeding practices were broadly compliant with national guidelines. The implementation of a national infant vitamin D supplementation policy had a major impact on supplementation practice. Low levels of serum 25(OH)D were universal among Irish neonates. Eczema is a complex and multifaceted disease, which is increasing globally. This was the first report of eczema prevalence data among Irish infants which compared with international reports. Given the high prevalence and considerable burden eczema has on the lives of sufferers, intensive research efforts to identify a cause and therapeutic strategies to prevent/reduce eczema was re-emphasized in this thesis.

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This thesis explores the evolution of kingship in early medieval Ireland (AD 400–1150) through a kingdom based and multi-scalar approach to royal landscapes. Through exploring the role of place and landscape in the construction of early medieval Irish kingship, this study will assess the relationship between the social, economic and ideological roles of the king in Irish society. Kingship in Ireland was vested in places, such that royal landscapes were the pre-eminent symbol of regality and authority. As such, an interdisciplinary study of kingship grounded in archaeological methodologies has a unique potential to contribute to our knowledge of the practice of kingship. Consequently, this research considers the material apparatus of different scales of kingships and explores the role of landscape in the construction of kingship and the evolution of kingdoms. It takes two major case studies; (i) Cashel, Munster and the Éoganachta federation; and (ii) the Uí Néill, Tara and the Síl nÁedo Sláine kingdom of Brega. Through interdisciplinary methodologies it charts the genesis and development of political federations, focusing specifically on the role that royal landscapes’ played in their evolution. Similarly, this thesis engages critically with the nature of assembly places and practices in Ireland, and focuses specifically on issues pertaining to the nature of assembly and the archaeological manifestation of such practices. It includes a list of 115 landscapes identified as assembly places, and through the analysis of this material, this thesis examines the ways in which different types of royal sites articulated together to create royal landscapes implicated in the exercise of kingship, and the construction and maintenance of authority. Moreover, through the analysis of assembly places within the context of the development of kingdoms, and structures of jurisdiction and administration, it also investigates the evolution of supra-regional scales of identity and community associated with the emergence of major political federations in early medieval Ireland.

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The application of biological effect monitoring for the detection of environmental chemical exposure in domestic animals is still in its infancy. This study investigated blood sample preparations in vitro for their use in biological effect monitoring. When peripheral blood mononuclear cells (PBMCs), isolated following the collection of multiple blood samples from sheep in the field, were cryopreserved and subsequently cultured for 24 hours a reduction in cell viability (<80%) was attributed to delays in the processing following collection. Alternative blood sample preparations using rat and sheep blood demonstrated that 3 to 5 hour incubations can be undertaken without significant alterations in the viability of the lymphocytes; however, a substantial reduction in viability was observed after 24 hours in frozen blood. Detectable levels of early and late apoptosis as well as increased levels of ROS were detectable in frozen sheep blood samples. The addition of ascorbic acid partly reversed this effect and reduced the loss in cell viability. The response of the rat and sheep blood sample preparations to genotoxic compounds ex vivo showed that EMS caused comparable dose-dependent genotoxic effects in all sample preparations (fresh and frozen) as detected by the Comet assay. In contrast, the effects of CdCl2 were dependent on the duration of exposure as well as the sample preparation. The analysis of leukocyte subsets in frozen sheep blood showed no alterations in the percentages of T and B lymphocytes but led to a major decrease in the percentage of granulocytes compared to those in the fresh samples. The percentages of IFN-γ and IL-4 but not IL-6 positive cells were comparable between fresh and frozen sheep blood after 4 hour stimulation with phorbol 12-myrisate 13-acetate and ionomycin (PMA+I). These results show that frozen blood gives comparable responses to fresh blood samples in the toxicological and immune assays used.

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Defects in commercial cheese result in a downgrading of the final cheese and a consequential economic loss to the cheese producer. Developments of defects in cheese are often not fully understood and therefore not controllable by the producer. This research investigated the underlying factors in the development of split and secondary fermentation defect and of pinking defects in commercial Irish cheeses. Split defect in Swiss-type cheese is a common defect associated with eye formation and manifests as slits and cracks visible in the cut cheese loaf (Reinbold, 1972; Daly et al., 2010). No consensus exists as to the definitive causes of the defect and possible factors which may contribute to the defect were reviewed. Models were derived to describe the relationship between moisture, pH, and salt levels and the distance from sample location to the closest external block surface during cheese ripening. Significant gradients within the cheese blocks were observed for all measured parameters in cheeses at 7 day post/after manufacture. No significant pH gradient was found within the blocks on exit from hot-room ripening and at three months post exit from the hot-room. Moisture content reached equilibrium within the blocks between exit from hot-room and 3 months after exit from hot-room while salt and salt-to-moisture levels had not reached equilibrium within the cheese blocks even at three months after exit from hot-room ripening. A characterisation of Swiss-type cheeses produced from a seasonal milk supply was undertaken. Cheeses were sampled on two days per month of the production year, at three different times during the manufacturing day, at internal and external regions of the cheese block and at four ripening time points (7 days post manufacture, post hot-room, 14 days post hot-room and 3 months in a cold room after exit from hot-room). Compositional, biochemical and microbial indices were determined, and the results were analysed as a splitplot with a factorial arrangement of treatments (season, time of day, area) on the main plot and ripening time on the sub-plot. Season (and interactions) had a significant effect on pH and salt-in-moisture levels (SM), mean viable counts of L. helveticus, propionic acid and non-starter lactic acid bacteria, levels of primary and secondary proteolysis and cheese firmness. Levels of proteolysis increased significantly during hot-room ripening but also during cold room storage, signifying continued development of cheese ripening during cold storage (> 8°C). Rheological parameters (e.g. springiness and cohesiveness) were significantly affected by interactions between ripening and location within cheese blocks. Time of day of manufacture significantly affected mean cheese calcium levels at 7 days post manufacture and mean levels of arginine and mean viable counts of NSLAB. Cheeses produced during the middle of the production day had the best grading scores and were more consistent compared to cheeses produced early or late during day of manufacture. Cheeses with low levels of S/M and low values of resilience were associated with poor grades at 7 days post manufacture. Chesses which had high elastic index values and low values of springiness in the external areas after exit from hot-room ripening also obtained good commercial grades. Development of a pink colour defect is an intermittent defect in ripened cheese which may or may not contain an added colourant, e.g., annatto. Factors associated with the defect were reviewed. Attempts at extraction and identification of the pink discolouration were unsuccessful. The pink colour partitioned with the water insoluble protein fraction. No significant difference was observed between ripened control and defect cheese for oxygen levels and redox potential or for the results of elemental analysis. A possible relationship between starter activity and defect development was established in cheeses with added coulourant, as lower levels of residual galactose and lactose were observed in defective cheese compared to control cheese free of the defect. Swiss-type cheese without added colourant had significantly higher levels of arginine and significantly lower lactate levels. Flow cell cytometry indicated that levels of bacterial cell viability and metabolic state differed between control and defect cheeses (without added colourant). Pyrosequencing analysis of cheese samples with and without the defect detected the previously unreported bacteria in cheese, Deinococcus thermus (a potential carotenoid producer). Defective Swiss-type cheeses had elevated levels of Deinococcus thermus compared to control cheeses, however the direct cause of pink was not linked to this bacterium alone. Overall, research was undertaken on underlying factors associated with the development of specific defects in commercial cheese, but also characterised the dynamic changes in key microbial and physicochemical parameters during cheese ripening and storage. This will enable the development of processing technologies to enable seasonal manipulation of manufacture protocols to minimise compositional and biochemical variability and to reduce and inhibit the occurrence of specific quality defects.

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A growing number of software development projects successfully exhibit a mix of agile and traditional software development methodologies. Many of these mixed methodologies are organization specific and tailored to a specific project. Our objective in this research-in-progress paper is to develop an artifact that can guide the development of such a mixed methodology. Using control theory, we design a process model that provides theoretical guidance to build a portfolio of controls that can support the development of a mixed methodology for software development. Controls, embedded in methods, provide a generalizable and adaptable framework for project managers to develop their mixed methodology specific to the demands of the project. A research methodology is proposed to test the model. Finally, future directions and contributions are discussed.

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Traditional higher education technology emphasizes knowledge transmission. In contrast, the Community platform presented in this paper follows a social approach that interleaves knowledge delivery with social and professional skills development, engaging with others, and personal growth. In this paper, we apply learning and complex adaptive systems theory to motivate and justify a continuous professional development model that improves higher education outcomes such as placement. The paper follows action design research (ADR) as the research method to propose and evaluate design principles.

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Although the management of breast cancer has improved over the past few decades, it remains an important challenge for the clinician. Cytotoxic chemotherapy and hormonotherapy, when given in the adjuvant setting, have a definitive though modest impact on the outcome of early-stage breast cancer. In metastatic disease, these therapies help to provide substantial palliation of symptoms but have a limited impact on survival. The discovery of vinorelbine and the taxanes, paclitaxel and docetaxel, certainly represented the most encouraging clinical development of the 1980s in breast cancer therapy. Several other new cytotoxic agents have been recognised for their potential in the treatment of this disorder. Many of them are only in a very early phase of their clinical development and it remains to be proven that they will have a major role in daily practice in the near future.

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BACKGROUND: Myosin VIIA (MyoVIIA) is an unconventional myosin necessary for vertebrate audition [1]-[5]. Human auditory transduction occurs in sensory hair cells with a staircase-like arrangement of apical protrusions called stereocilia. In these hair cells, MyoVIIA maintains stereocilia organization [6]. Severe mutations in the Drosophila MyoVIIA orthologue, crinkled (ck), are semi-lethal [7] and lead to deafness by disrupting antennal auditory organ (Johnston's Organ, JO) organization [8]. ck/MyoVIIA mutations result in apical detachment of auditory transduction units (scolopidia) from the cuticle that transmits antennal vibrations as mechanical stimuli to JO. PRINCIPAL FINDINGS: Using flies expressing GFP-tagged NompA, a protein required for auditory organ organization in Drosophila, we examined the role of ck/MyoVIIA in JO development and maintenance through confocal microscopy and extracellular electrophysiology. Here we show that ck/MyoVIIA is necessary early in the developing antenna for initial apical attachment of the scolopidia to the articulating joint. ck/MyoVIIA is also necessary to maintain scolopidial attachment throughout adulthood. Moreover, in the adult JO, ck/MyoVIIA genetically interacts with the non-muscle myosin II (through its regulatory light chain protein and the myosin binding subunit of myosin II phosphatase). Such genetic interactions have not previously been observed in scolopidia. These factors are therefore candidates for modulating MyoVIIA activity in vertebrates. CONCLUSIONS: Our findings indicate that MyoVIIA plays evolutionarily conserved roles in auditory organ development and maintenance in invertebrates and vertebrates, enhancing our understanding of auditory organ development and function, as well as providing significant clues for future research.

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The relation between social rejection and growth in antisocial behavior was investigated. In Study 1,259 boys and girls (34% African American) were followed from Grades 1 to 3 (ages 6-8 years) to Grades 5 to 7 (ages 10-12 years). Early peer rejection predicted growth in aggression. In Study 2,585 boys and girls (16% African American) were followed from kindergarten to Grade 3 (ages 5-8 years), and findings were replicated. Furthermore, early aggression moderated the effect of rejection, such that rejection exacerbated antisocial development only among children initially disposed toward aggression. In Study 3, social information-processing patterns measured in Study 1 were found to mediate partially the effect of early rejection on later aggression. In Study 4, processing patterns measured in Study 2 replicated the mediation effect. Findings are integrated into a recursive model of antisocial development.

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Barbara Hanning points out in her book Concise History of Western Music, that "Twentieth-century American music was in large measure an extension of European music" (Hanning 1998, 515). My dissertation/perforrnance project features cello works written by three contemporary composers who lived in America but were connected to the European heritage in different ways; each contributed significantly to the development of American classical concert life, music education, and even popular culture. Programs of my performances are intended to illustrate their unique compositional styles. The first recital consists of five cello compositions of Massachusetts-born Arthur Foote (1853 - 1937): Drei Stucke fur Pianoforte und Violoncello, Op. 1; Scherzo, Op.22; Romanza, Op.33; Aubade, Op.77; and Sonata for Violoncello and Piano, Op.78. Foote was influenced by the German-trained John Knowles Paine at Harvard University; he composed music famous for its extensive chromaticism in both harmony and melodic line, and for clearly-defined formal structure. The second recital explores the music of Swiss-American composer Ernest Bloch (1880-1959): a short Meditation Hebraique, a Suite No. I for Violoncello Solo and the famous rhapsody Schelomo. Born in Geneva, Switzerland, and settling in the United States in 1916, Bloch is a composer deeply influenced by the European late-Romantic tradition and is also well-known for employing "Hebraic" elements into his works. The final performance comprises two other of Bloch's cello works and one cello concerto by the Austrian-American composer, Erich Wolfgang Korngold (1897- 1957). Bloch's Voice in the Wilderness is a symphonic poem for orchestra and cello (accompanied by piano in this performance), consisting of six movements performed without pause. His Suite No.3 for Cello Solo is shorter and has a simpler style than the first Suite. Korngold was recognized as a child prodigy in his native Austria. After a Nazi-induced exile, he immigrated to America and became a film music composer in Hollywood. The Cello Concerto was used in the movie "Deception" (1 946), for which Korngold provided the film score. The impassioned harmonic language and lavish melodic lines inherited from the high-romanticism make this work one of comparative discordant beauty among other compositions of his time.

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The purpose of this study is to illustrate the development of piano variations as a genre during the Romantic era. In order to facilitate this examination of piano variations techniques, a brief look at the types of variation procedures used by composers of previous eras will assist in understanding developments that later occurred in the Romantic period. Throughout the Baroque era, composers preferred the fured-bass, fixed-melody, and harmonic forms of variation. The crowning achievement of Baroque keyboard music, Bach's Goldberg Variations (1725), contains examples of the "constantharmonic" method in its collection of 30 variations, each of which maintains both the bass and harmonic structure of the themes. While most composers of the classical period favored the "melodic-outline" form of variation, Haydn developed hybrid variation procedure that exhibits recurrence of material rather than repetition, alternating variation (ABABA), rondo variation (ABACA), and ternary variation (ABA). Haydn, Mozart and early Beethoven variations also exhibit simpler textures than do their Baroque predecessors. The nineteenth century produced numerous compositions that display variation techniques, some based on such older, classical models as melodic-outline variation and hybrid variation, others in the style of the character variation or fiee variation. At the beginning of the nineteenth century, Beethoven and Schubert used such classical variation techmques as melodic-outline variations and hybrid variations. Beethoven's late sonatas displayed such new means of expression as variation, fugue, and dramatic recitatives. The third movement of the Sonata in E major, Op. 109 (1820) has a theme and six variations of the melodic-outline type. Johannes Brahms was particularly fond of composing variations for piano. Among the best known examples of formal-outline variations are those found in the Variations and Fugue on a Theme of Handel, Op. 24 (1861). Character variations, in which styles are characterized by the retention and variability of particular elements, also flourished during the Romantic period. Cesar Franck's Variations Symphoniques (1885) are, perhaps, among the most important examples of free variations. This composition is a one-movement work consisting of three sections, Introduction, Variations, and Finale (all movements played "attaca"). This work combines two independent classical formal structures, the concerto and the variation.

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During the Romantic Era, the character piece flourished and became one of the most important genres. Even though character pieces existed as early as the eighteenth century, it was not until the nineteenth century that Romantic Era literary figures discovered that music was as powerful as any other artistic medium in expressing unspeakable emotions. The character piece allowed composers to express a definite mood, a programmatic idea, or a pictorial association. Character pieces often have titles that suggest briehess or casualness, such as a Beethoven Bagatelle, a Schubert Impromptu or Moment musicaux. Others have expressive programmatic titles, such as Schumann's Kreisleriana and Liszt's Apres une lecture de Dante. Ths dissertation was based on selected works from the nineteenth century and early-twentieth century in order to demonstrate the great variety of musical thought and stylistic development. I have examined composers from different countries and of different nationalities to establish what and how they contributed to the remarkable diversity in this genre. The selected works allowed for very personal programs. These concerts, in addition to being good combinations of pieces, are representative of the genre. The first program consisted of Chopin's Preludes, Op. 28; three pieces from Debussy7s Images Books I and 11; and Liszt7s Apres une lecture de Dante. The second program included seven of Beethoven's Bagatelles, Op. 33; Schumann's Kinderscenen, Op. 15; Poulenc's Mouvements perpetuels and Intermezzo in A-jlat Major; Faure7s Nocturne in B Major, Op. 33, No. 2 and Impromptu No. 2 in F Minor; three of Mompou's Canciones y Danzas; four of Villa-Lobos Prole do bebe Suite No. 1; and Albkniz's Navarra. The third and final program comprised four selections from Rachrnaninoff s Moment musicaux, Op. 16; five pieces from Grieg's Lyric Pieces; and Arensky7s Suite No. 1 for Two Pianos and Suite No. 2 for Two Pianos. I wanted to bring out nuances specific to the individual composers and show how their character pieces helped in shaping the Romantic Era. Even in the twenty-first century, an era of highly specialized musical tastes, the popularity and accessibility of character pieces stand out.