CIRQUE DE LA VOIX: VOCAL PERFORMANCES FOR THE 21st CENTURY AUDIENCE

This dissertation addresses the growing need to entice people to attend a classical solo vocal recital by incorporating thematic programming, multi-media presentations, collaborations and innovative marketing. It comprises four programs that use the above tactics, creating live performances of classical vocal music that appeal to the attention deficient 21st-century audience. Each program focuses on repertoire appropriate for the male alto voice and includes elements of spoken word, visual imagery and for movement through collaborations with actors, singers, dancers, designers and visual artists. Program one (March 1, 2004), La Voix Humaine: The Life of an Englishwoman in Music, Poetry, & Art, outlines the life of a fictitious Englishwoman through a self-composed narration, spoken by an actress, a Power Point presentation of visual art by 20th-century English artists and musical commentary provided by the collaboration of a vocalist and a pianist. Program two (October 15, 2004), La Voix Thfrmatique: Anima - Music that Moves, is a program of pieces ranging from the 14th- to the 20th-centuries of which half are choreographed by members of the University of Maryland Dance Department. Program three is a lecture recital entitled L 'Haute Voix: Identifying the High Male Voice and Appropriate Repertoire which is presented in collaboration with three singers, a pianist, a harpsichordist and a cellist. Program four, La Voix Dramatique: Opera Roles for the Countertenor Voice, comprises performances of George Frederic Handel's Giulio Cesare in Egitto (1724) in collaboration with the Maryland Opera Studio and the Clarice Smith Performing Arts Center (Leon Major, director; Kenneth Merrill, conductor). There are two performances each of the title role, Cesare (April 15 & 17, 2005), and his nemesis, Tolomeo (April 21 & 23,2005). All programs are documented in a digital audio format available on compact disc and are accompanied by program notes also available in digital format. Programs two and four are also documented in digital video format available on digital video disc.

Reclaiming the Vocal High Ground: Performing Baroque Repertoire in a Modern World

The early music revival of the late twentieth century revolutionized music with the birth of historically lnformed performance. With this revolution came a stereotype of the "early music singing voice" as small, bright, straight-toned, and unfortunately, often inferior techrucally to the mainstream opera singer. An assessment of the validity of this stereotype was made though readings of treatises and modern manuals of performance practice, and through listening to recordings. Sources on ornamentation, recitative, dance rhythm, and baroque gesture were examined, resulting in the finding that these issues are far more important to historical accuracy than are voice timbre and size. This dissertation is comprised of three historically informed performances intended to satisfy both the early music specialist and the mainstream voice teacher. Program One (May 15, 2004) is a performance of The "Peasant" Cantata, BWV 212, by J.S. Bach, with The Bach Sinfonia at the Washington Conservatory of Music. Program Two (January 29, 2005) is the role of Eurilla in a staged production of Antonio Vivaldi's serenata, Eurilla e Alcindo. The performance is a collaboration with the Baltimore-based ensemble, La Rocinante, and is conducted from the keyboard by Joseph Gascho. Program Three (March 14, 2005) is a solo recital entitled, Fairest Isle: Music of Baroque London. All three programs are documented in a digital audio format available on compact disc, with accompanying programs and notes also available in digital format.

Imaging Learned Song Representations in Populations of Sensorimotor Neurons Essential to Vocal Communication

Perceiving or producing complex vocalizations such as speech and birdsongs require the coordinated activity of neuronal populations, and these activity patterns can vary over space and time. How learned communication signals are represented by populations of sensorimotor neurons essential to vocal perception and production remains poorly understood. Using a combination of two-photon calcium imaging, intracellular electrophysiological recording and retrograde tracing methods in anesthetized adult male zebra finches (Taeniopygia guttata), I addressed how the bird's own song and its component syllables are represented by the spatiotemporal patterns of activity of two spatially intermingled populations of projection neurons (PNs) in HVC, a sensorimotor area required for song perception and production. These experiments revealed that neighboring PNs can respond at markedly different times to song playback and that different syllables activate spatially intermingled HVC PNs within a small region. Moreover, noise correlation analysis reveals enhanced functional connectivity between PNs that respond most strongly to the same syllable and also provides evidence of a spatial gradient of functional connectivity specific to PNs that project to song motor nucleus (i.e. HVC_RA cells). These findings support a model in which syllabic and temporal features of song are represented by spatially intermingled PNs functionally organized into cell- and syllable-type networks.

Molecular mapping of movement-associated areas in the avian brain: a motor theory for vocal learning origin.

Vocal learning is a critical behavioral substrate for spoken human language. It is a rare trait found in three distantly related groups of birds-songbirds, hummingbirds, and parrots. These avian groups have remarkably similar systems of cerebral vocal nuclei for the control of learned vocalizations that are not found in their more closely related vocal non-learning relatives. These findings led to the hypothesis that brain pathways for vocal learning in different groups evolved independently from a common ancestor but under pre-existing constraints. Here, we suggest one constraint, a pre-existing system for movement control. Using behavioral molecular mapping, we discovered that in songbirds, parrots, and hummingbirds, all cerebral vocal learning nuclei are adjacent to discrete brain areas active during limb and body movements. Similar to the relationships between vocal nuclei activation and singing, activation in the adjacent areas correlated with the amount of movement performed and was independent of auditory and visual input. These same movement-associated brain areas were also present in female songbirds that do not learn vocalizations and have atrophied cerebral vocal nuclei, and in ring doves that are vocal non-learners and do not have cerebral vocal nuclei. A compilation of previous neural tracing experiments in songbirds suggests that the movement-associated areas are connected in a network that is in parallel with the adjacent vocal learning system. This study is the first global mapping that we are aware for movement-associated areas of the avian cerebrum and it indicates that brain systems that control vocal learning in distantly related birds are directly adjacent to brain systems involved in movement control. Based upon these findings, we propose a motor theory for the origin of vocal learning, this being that the brain areas specialized for vocal learning in vocal learners evolved as a specialization of a pre-existing motor pathway that controls movement.

Durability of antiretroviral therapy and predictors of virologic failure among perinatally HIV-infected children in Tanzania: a four-year follow-up.

BACKGROUND: In Tanzania, HIV-1 RNA testing is rarely available and not standard of care. Determining virologic failure is challenging and resistance mutations accumulate, thereby compromising second-line therapy. We evaluated durability of antiretroviral therapy (ART) and predictors of virologic failure among a pediatric cohort at four-year follow-up. METHODS: This was a prospective cross-sectional study with retrospective chart review evaluating a perinatally HIV-infected Tanzanian cohort enrolled in 2008-09 with repeat HIV-1 RNA in 2012-13. Demographic, clinical, and laboratory data were extracted from charts, resistance mutations from 2008-9 were analyzed, and prospective HIV RNA was obtained. RESULTS: 161 (78%) participants of the original cohort consented to repeat HIV RNA. The average age was 12.2 years (55% adolescents ≥12 years). Average time on ART was 6.4 years with 41% receiving second-line (protease inhibitor based) therapy. Among those originally suppressed on a first-line (non-nucleoside reverse transcriptase based regimen) 76% remained suppressed. Of those originally failing first-line, 88% were switched to second-line and 72% have suppressed virus. Increased level of viremia and duration of ART trended with an increased number of thymidine analogue mutations (TAMs). Increased TAMs increased the odds of virologic failure (p = 0.18), as did adolescent age (p < 0.01). CONCLUSIONS: After viral load testing in 2008-09 many participants switched to second-line therapy. The majority achieved virologic suppression despite multiple resistance mutations. Though virologic testing would likely hasten the switch to second-line among those failing, methods to improve adherence is critical to maximize durability of ART and improve virologic outcomes among youth in resource-limited settings.

VIRTUOSIC ELEMENTS IN THE COLLABORATIVE PIANIST’S REPERTOIRE: SELECTED SOLO, VOCAL, AND CHAMBER WORKS OF RACHMANINOFF AND RAVEL

This dissertation project explores some of the technical and musical challenges that face pianists in a collaborative role—specifically, those challenges that may be considered virtuosic in nature. The material was chosen from the works of Rachmaninoff and Ravel because of the technically and musically demanding yet idiomatic piano writing. This virtuosic piano writing also extends into the collaborative repertoire. The pieces were also chosen to demonstrate these virtuosic elements in a wide variety of settings. Solo piano pieces were chosen to provide a point of departure, and the programmed works ranged from vocal to two-piano, to sonatas and a piano trio. The recitals were arranged to demonstrate as much contrast as possible, while being grouped by composer. The first recital was performed on April 24, 2009. This recital featured five songs of Rachmaninoff, as well as three solo piano preludes and his Suite No. 2 for two pianos. The second recital occurred on November 16, 2010. This recital featured the music of both Rachmaninoff and Ravel, as well as a short lecture introducing the solo work “Ondine” from Gaspard de la nuit by Ravel. Following the lecture were the Cinq mélodies populaires grecques and the program closed with the substantial Rachmaninoff Sonata for Cello and Piano. The final program was given on October 10, 2011. This recital featured the music of Ravel, and it included his Sonata for Violin and Piano, the Debussy Nocturnes transcribed for two pianos by Ravel, and the Piano Trio. The inclusion of a transcription of a work by another composer highlights Ravel’s particular style of writing for the piano. All of these recitals were performed at the Gildenhorn Recital Hall in the Clarice Smith Performing Arts Center at the University of Maryland. The recitals are recorded on compact discs, which can be found in the Digital Repository at the University of Maryland (DRUM).

Docetaxel Resistance in Prostate Cancer: Taking It Up a Notch.

Notch signaling is implicated in prostate cancer progression and docetaxel resistance. Cui and colleagues describe the additive efficacy and mechanisms of a γ-secretase inhibitor, PF-03084014, and docetaxel in preclinical models of prostate cancer, suggesting the need for further clinical development of Notch pathway modulators in men with metastatic prostate cancer.

ERM transactivation is up-regulated by the repression of DNA binding after the PKA phosphorylation of a consensus site at the edge of the ETS domain

The final step of the transduction pathway is the activation of gene transcription, which is driven by kinase cascades leading to changes in the activity of many transcription factors. Among these latter, PEA3/E1AF, ER81/ETV1, and ERM, members of the well conserved PEA3 group from the Ets family are involved in these processes. We show here that protein kinase A (PKA) increases the transcriptional activity of human ERM and human ETV1, through a Ser residue situated at the edge of the ETS DNA-binding domain. PKA phosphorylation does not directly affect the ERM transactivation domains but does affect DNA binding activity. Unphosphorylated wild-type ERM bound DNA avidly, whereas after PKA phosphorylation it did so very weakly. Interestingly, S367A mutation significantly reduced the ERM-mediated transcription in the presence of the kinase, and the DNA binding of this mutant, although similar to that of unphosphorylated wild-type protein, was insensitive to PKA treatment. Mutations, which may mimic a phosphorylated serine, converted ERM from an efficient DNA-binding protein to a poor DNA binding one, with inefficiency of PKA phosphorylation. The present data clearly demonstrate a close correlation between the capacity of PKA to increase the transactivation of ERM and the drastic down-regulation of the binding of the ETS domain to the targeted DNA. What we thus demonstrate here is a relatively rare transcription activation mechanism through a decrease in DNA binding, probably by the shift of a non-active form of an Ets protein to a PKA-phosphorylated active one, which should be in a conformation permitting a transactivation domain to be active.

The prognosis of incurable cachectic cancer patients on home parenteral nutrition: A multi-centre observational study with prospective follow-up of 414 patients

Background: The role of home parenteral nutrition (HPN) in incurable cachectic cancer patients unable to eat is extremely controversial. The aim of this study is to analyse which factors can influence the outcome. Patients and methods: We studied prospectively 414 incurable cachectic (sub)obstructed cancer patients receiving HPN and analysed the association between patient or clinical characteristics and surviving status. Results: Median weight loss, versus pre-disease and last 6-month period, was 24% and 16%, respectively. Median body mass index was 19.5, median KPS was 60, median life expectancy was 3 months. Mean/median survival was 4.7/3.0 months; 50.0% and 22.9% of patients survived 3 and 6 months, respectively. At the multivariable analysis, the variables significantly associated with 3- and 6-month survival were Glasgow Prognostic Score (GPS) and KPS, and GPS, KPS and tumour spread, respectively. By the aggregation of the significant variables, it was possible to dissect several classes of patients with different survival probabilities. Conclusions: The outcome of cachectic incurable cancer patients on HPN is not homogeneous. It is possible to identify groups of patients with a ≥6-month survival (possibly longer than that allowed in starvation). The indications for HPN can be modulated on these clinical/biochemical indices. © The Author 2013. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.

Analysis of the utility of QuantiFERON-TB gold in tube and measurement of IFNgamma release by peripheral mononuclear cells in response to different mycobacterium antigen in the work-up of patients with uveitis.

Evaluation Studies

FANTASIO: a versatile experimental set-up to investigate jet-cooled molecules

The design of a new apparatus, named FANTASIO, for studying jet-cooled molecules is described. It includes, around the same supersonic expansion cell, a high resolution Fourier transform spectrometer with single or multipass optics, a tunable diode laser spectrometer with optional cavity ring-down facilities, and a quadrupole mass spectrometer. Performance and operational procedures are illustrated.

Neurology and psychiatry: waking up to opportunities of sleep. State of the art and clinical/research priorities for the next decade.

In recent years, evidence has emerged for a bidirectional relationship between sleep and neurological and psychiatric disorders. First, sleep-wake disorders (SWDs) are very common and may be the first/main manifestation of underlying neurological and psychiatric disorders. Secondly, SWDs may represent an independent risk factor for neuropsychiatric morbidities. Thirdly, sleep-wake function (SWF) may influence the course and outcome of neurological and psychiatric disorders. This review summarizes the most important research and clinical findings in the fields of neuropsychiatric sleep and circadian research and medicine, and discusses the promise they bear for the next decade. The findings herein summarize discussions conducted in a workshop with 26 European experts in these fields, and formulate specific future priorities for clinical practice and translational research. More generally, the conclusion emerging from this workshop is the recognition of a tremendous opportunity offered by our knowledge of SWF and SWDs that has unfortunately not yet entered as an important key factor in clinical practice, particularly in Europe. Strengthening pre-graduate and postgraduate teaching, creating academic multidisciplinary sleep-wake centres and simplifying diagnostic approaches of SWDs coupled with targeted treatment strategies yield enormous clinical benefits for these diseases.