Unrecognized pretransplant and donor‐derived cryptococcal disease in organ transplant recipients.

BACKGROUND: Cryptococcosis occurring ≤30 days after transplantation is an unusual event, and its characteristics are not known. METHODS: Patients included 175 solid-organ transplant (SOT) recipients with cryptococcosis in a multicenter cohort. Very early-onset and late-onset cryptococcosis were defined as disease occurring ≤30 days or >30 days after transplantation, respectively. RESULTS: Very early-onset disease developed in 9 (5%) of the 175 patients at a mean of 5.7 days after transplantation. Overall, 55.6% (5 of 9) of the patients with very early-onset disease versus 25.9% (43 of 166) of the patients with late-onset disease were liver transplant recipients (P = .05). Very early cases were more likely to present with disease at unusual locations, including transplanted allograft and surgical fossa/site infections (55.6% vs 7.2%; P < .001). Two very early cases with onset on day 1 after transplantation (in a liver transplant recipient with Cryptococcus isolated from the lung and a heart transplant recipient with fungemia) likely were the result of undetected pretransplant disease. An additional 5 cases involving the allograft or surgical sites were likely the result of donor‐acquired infection. CONCLUSIONS: A subset of SOT recipients with cryptococcosis present very early after transplantation with disease that appears to occur preferentially in liver transplant recipients and involves unusual sites, such as the transplanted organ or the surgical site. These patients may have unrecognized pretransplant or donor-derived cryptococcosis.

Myosin VIIA, important for human auditory function, is necessary for Drosophila auditory organ development.

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.

Gene expression disruptions of organism versus organ in Drosophila species hybrids.

Hybrid dysfunctions, such as sterility, may result in part from disruptions in the regulation of gene expression. Studies of hybrids within the Drosophila simulans clade have reported genes expressed above or below the expression observed in their parent species, and such misexpression is associated with male sterility in multigenerational backcross hybrids. However, these studies often examined whole bodies rather than testes or had limited replication using less-sensitive but global techniques. Here, we use a new RNA isolation technique to re-examine hybrid gene expression disruptions in both testes and whole bodies from single Drosophila males by real-time quantitative RT-PCR. We find two early-spermatogenesis transcripts are underexpressed in hybrid whole-bodies but not in assays of testes alone, while two late-spermatogenesis transcripts seem to be underexpressed in both whole-bodies and testes alone. Although the number of transcripts surveyed is limited, these results provide some support for a previous hypothesis that the spermatogenesis pathway in these sterile hybrids may be disrupted sometime after the expression of the early meiotic arrest genes.

Instrument independent diffuse reflectance spectroscopy.

Diffuse reflectance spectroscopy with a fiber optic probe is a powerful tool for quantitative tissue characterization and disease diagnosis. Significant systematic errors can arise in the measured reflectance spectra and thus in the derived tissue physiological and morphological parameters due to real-time instrument fluctuations. We demonstrate a novel fiber optic probe with real-time, self-calibration capability that can be used for UV-visible diffuse reflectance spectroscopy in biological tissue in clinical settings. The probe is tested in a number of synthetic liquid phantoms over a wide range of tissue optical properties for significant variations in source intensity fluctuations caused by instrument warm up and day-to-day drift. While the accuracy for extraction of absorber concentrations is comparable to that achieved with the traditional calibration (with a reflectance standard), the accuracy for extraction of reduced scattering coefficients is significantly improved with the self-calibration probe compared to traditional calibration. This technology could be used to achieve instrument-independent diffuse reflectance spectroscopy in vivo and obviate the need for instrument warm up and post∕premeasurement calibration, thus saving up to an hour of precious clinical time.

ELGAR AND MART&: THE CELLO WORKS AND MUSICAL CHARACTERISTICS OF TWO REMARKABLE, SELF-TAUGHT, NATIONALISTIC COMPOSERS

The British Edward Elgar and Czech Bohuslav MartinB were two of the most prominent Nationalistic composers of their respective countries during the late nineteenth and early twentieth centuries. Their musical patriotism incorporates the unique paths of their lives as socially isolated and self-taught composers as expressed their outstanding Nationalistic compositions produced through the period of history encompassing the two World Wars.In the first chapter of this dissertation, a brief biography of Elgar is presented and the essential aspects of his formative years influencing him to become a self-taught musician are discussed. The second chapter demonstrates Elgar's musical characteristics through the study of a selection of his masterpieces. In the third chapter, a brief biography of Martinti is presented along with a history of his musical development, characterized by his social isolation during four different periods of his life-his residences in PoliCka, Prague, Paris, and then in the United States. The fourth chapter considers MartinB's musical characteristics as revealed through the study of a selection of his greatest works. In support of this doctoral project, I performed two recitals of cello works by Elgar and Martini3 at the University of Maryland, College Park. The first recital, accompanied by Susan Slingland and Hiroko Yamazaki, included three of Martini3's works, Sonata No. 2 for Cello and Piano (1941); Variations on a Theme of Rossini for Cello and Piano (1 942); and Sonata No. 3 for Cello and Piano (1952). The second recital, accompanied by Wonyoung Chang and Naoko Takao, presented Martini3's Sonata No. 1 for Cello and Piano (1939) and Elgar's Concerto for Cello and Orchestra Op. 85 in E minor (1 919).

The Oud Across Arabic Culture

This study is a compilation and compendium of information on the oud, the most important instrument in Arabic classical music. It has grown out of my own long-time involvement in studying and playing the oud, and in particular out of my interest in the lack of sources and knowledge available to the vast majority of oud players and researchers, as well as for the readers. My own path started from an intensive study of the oud, which included exposure to several treaties; some housed in museums around the globe, and some only available in the Arabic language. The study combines archival research (including Arabic poetry and pre-Islamic Era and medieval treaties), symbolism, new archaeological discoveries, field interviews, and analysis of existing scholarship, and draws on my professional performance experience for detailed stylistic analysis of the oud's performance practice and its historical development. The study consists of participant observation, personal performance, and interviews conducted in person, via telephone, and/or via e-mail, according to the choice of the performers. The performers have been selected from networks of musicians who perform regularly at lounges, concert halls, and private events. These performers have been chosen according to their musical knowledge, technical skill, experience, and activity in Arabic music and oud performance. Chapter one deals with the purpose of this study and the methods of investigation, as well as giving a brief overview of the history of the oud. In addition, there will be an introduction to the Arabic musical system (mâqâm), which is primarily based on the mechanics and sound production of the oud. Chapter two deals with the oud in Arabic sources: the first source is Arabic poetry in the pre-Islamic Era. The second source is Arabic poetry in the medieval era, in which I found a significant number of poets who allude to the oud, providing accurate descriptions of the player, singers, and the scenes within the contexts of oud performance. The third source is the Arab scholars' intensive treatises with meticulous accounts of the instrument's apparatii, including descriptions and measurements of the parts, strings, and tuning. While chapter three deals with the classification, the development of the oud, chapter four deals with topics such as: the symbolism of the oud and its relation to cosmology, astronomy, mathematics and anatomy. In most of the pertinent Arabic writings, philosophers mention a significant correlation between the oud and the other sciences. Chapter five deals with recreating the performance practice of the oud. A case study of the oud performers focuses on their style, technique, training, and personal experiences. Topics such as improvisation and ornamentation, the oud in the Arabic musical ensemble, the social uses and functions, and gender in musical performance practices will be included in detailed analysis. Other important topics will be analyzed such as traditional vs. modern technique, and the repertoire of the oud. Specifically, in regard to technique, the study outline the style of the music, the role of the oud in Arabic ensembles, the function of the oud in music composition, and the form of the ensembles in Arabic performance and practice.

Sikh Sabad Kirtan as a Musical Construction of Memory

The performance of devotional music in India has been an active, sonic conduit where spiritual identities are shaped and forged, and both history and mythology lived out and remembered daily. For the followers of Sikhism, congregational hymn singing has been the vehicle through which text, melody and ritual act as repositories of memory, elevating memory to a place where historical and social events can be reenacted and memorialized on levels of spiritual significance. This dissertation investigates the musical process of Shabad Kirtan, Sikh hymn singing, in a Sikh musical service as a powerful vehicle to forge a sense of identification between individual and the group. As an intimate part of Sikh life from birth to death, the repertoire of Shabad Kirtan draws from a rich mosaic of classical and folk genres as well as performance styles, acting as a musical and cognitive archive. Through a detailed analysis of the Asa Di Var service, Shabad Kirtan is explored as a phenomenological experience where time, place and occasion interact as a meaningful unit through which the congregation creates and recreates themselves, invoking deep memories and emotional experiences. Supported by explanatory tables, diagrams and musical transcriptions, the sonic movements of the service show how the Divine Word as Shabad is not only embodied through the Guru Granth Sahib, but also encountered through the human enactment of the service, aurally, viscerally and phenomenologically.

The role of B cells in solid organ transplantation.

The role of antibodies in chronic injury to organ transplants has been suggested for many years, but recently emphasized by new data. We have observed that when immunosuppressive potency decreases either by intentional weaning of maintenance agents or due to homeostatic repopulation after immune cell depletion, the threshold of B cell activation may be lowered. In human transplant recipients the result may be donor-specific antibody, C4d+ injury, and chronic rejection. This scenario has precise parallels in a rhesus monkey renal allograft model in which T cells are depleted with CD3 immunotoxin, or in a CD52-T cell transgenic mouse model using alemtuzumab to deplete T cells. Such animal models may be useful for the testing of therapeutic strategies to prevent DSA. We agree with others who suggest that weaning of immunosuppression may place transplant recipients at risk of chronic antibody-mediated rejection, and that strategies to prevent this scenario are needed if we are to improve long-term graft and patient outcomes in transplantation. We believe that animal models will play a crucial role in defining the pathophysiology of antibody-mediated rejection and in developing effective therapies to prevent graft injury. Two such animal models are described herein.

Primary vascularization of the graft determines the immunodominance of murine minor H antigens during organ transplantation.

Grafts can be rejected even when matched for MHC because of differences in the minor histocompatibility Ags (mH-Ags). H4- and H60-derived epitopes are known as immunodominant mH-Ags in H2(b)-compatible BALB.B to C57BL/6 transplantation settings. Although multiple explanations have been provided to explain immunodominance of Ags, the role of vascularization of the graft is yet to be determined. In this study, we used heart (vascularized) and skin (nonvascularized) transplantations to determine the role of primary vascularization of the graft. A higher IFN-γ response toward H60 peptide occurs in heart recipients. In contrast, a higher IFN-γ response was generated against H4 peptide in skin transplant recipients. Peptide-loaded tetramer staining revealed a distinct antigenic hierarchy between heart and skin transplantation: H60-specific CD8(+) T cells were the most abundant after heart transplantation, whereas H4-specific CD8(+) T cells were more abundant after skin graft. Neither the tissue-specific distribution of mH-Ags nor the draining lymph node-derived dendritic cells correlated with the observed immunodominance. Interestingly, non-primarily vascularized cardiac allografts mimicked skin grafts in the observed immunodominance, and H60 immunodominance was observed in primarily vascularized skin grafts. However, T cell depletion from the BALB.B donor prior to cardiac allograft induces H4 immunodominance in vascularized cardiac allograft. Collectively, our data suggest that immediate transmigration of donor T cells via primary vascularization is responsible for the immunodominance of H60 mH-Ag in organ and tissue transplantation.

Exploring Musical Diversity in the Collaborative Repertoire from 1880 through 1963

It is essential in musical performance not only to convey the unique language of the composers but also to approach each composition from the perspective of its style. During the 20th century, diverse musical idioms co-existed, sometimes mixing or fusing, yet retaining recognizable characteristics and thereby remaining distinctive. This dissertation explores myriad examples from Late Romanticism/Post- Romanticism, Naturalism, Neo-Classicism, Nationalism and Impressionism composed during this unusually rich period. In order to explore a broad range of collaborative repertoire and to deepen my knowledge of the styles and performance practices relating to these pieces, I studied and performed the repertoire with pianist Eunae Baik–Kim, clarinetist Jihoon Chang, and singers Joshua Brown and Young Joo Lee. The first program featured Post-Romantic, Neo-Classic and Impressionist two-piano works composed by Debussy, Rachmaninoff, and Stravinsky. Each of the three composers used their own distinctive harmonies, rhythms, melodic inventions, pedaling and figurations. In all of the works, both piano parts were densely interwoven, having equal importance. Lied and operatic aria was the focus of the second recital. Brahms’ Vier Ernste Gesänge Op. 121, Ravel’s Don Quichotte a Dulcineé and Italian, French and German operatic arias were the examples of Post-Romanticism and Nationalism. The representative composers were Verdi, Massenet, Korngold, Leoncavallo, Ravel and Wagner. Despite the fact that all of the repertoire was written in traditional musical forms, the composers’ unique voices mark each work as belonging to a particular genre. The third recital focused on Post-Romantic and Impressionistic music written for clarinet and piano: the Première Rhapsodie by Debussy, the Sonata by Poulenc and Brahms’ Sonata in F minor Op. 120, No. 1. These works, although profoundly different in style, share elements of simplicity, clarity and elegance as well as technical virtuosity, articulation and profound musical depth. The three recitals which comprise this dissertation project were performed at the University of Maryland Gildenhorn Recital Hall on February 27, 2010, October 25, 2010, and January 31, 2011. The recitals were recorded on compact disc and are archived within the Digital Repository at the University of Maryland (DRUM).

RECITAL REPERTOIRE FOR TROMBONE AND PERCUSSION

The solo trombone recital was once a rare musical event, but in recent years professional and amateur trombonists frequently present solo performances. The trombone has been around since the latter half of the 15th century and there is a wealth of ensemble repertoire, written for the instrument; however, there is no corresponding corpus of solo works. A small body of solo works does exist, from baroque sonatas and the alto trombone concertos of Leopold Mozart and Georg Wagenseil, to the romantic works by Ferdinand David and Nicolai Rimsky-Korsakov. This repertoire is small in number and a modern trombonist often has to resort to orchestral reductions and arrangements for modern performance in a solo recital setting. The trombone came into its own as a solo instrument in the 20th century and it is in this era where the bulk of a modern trombonist's repertoire resides. While there is now no shortage of music to choose from, presenting a diverse, yet musically cohesive recital remains a challenge though many interesting musical opportunities can arise to meet this challenge. While the piano is an extremely versatile instrument, pairing trombone with percussion opens up possibilities that are absent from the more traditional piano pairing. Percussion instruments can offer an almost unlimited variation of timbre and dynamics to complement the trombone. Dynamic range of the trombone must be considered as the instrument has the ability to play at the extremes of the dynamic range. Percussion instruments can match the trombone in these extremes. When presenting a recital of 20th and 21st century music, using timbre and dynamic range as selection criteria when planning the program are effective ways to bring a unique and intense musical experience to the audience. In this paper, the two considerations of dynamics and timbre will be explored and the need for a dissertation recital project will be explained.

DEGENERATE MUSIC?! MUSICAL CENSORSHIP IN THE THIRD REICH

In 1938, in Düsseldorf, the Nazis put on an exhibit entitled "Entartete Musik” (degenerate music), which included composers on the basis of their “racial origins” (i.e. Jews), or because of the “modernist style” of their music. Performance, publication, broadcast, or sale of music by composers deemed “degenerate” was forbidden by law throughout the Third Reich. Among these composers were some of the most prominent composers of the first half of the twentieth-century. They included Stravinsky, Schoenberg, Webern, Berg, Mahler, Ernst Krenek, George Gershwin, Kurt Weill, Erwin Schulhoff, and others. The music of nineteenth-century composers of Jewish origin, such as Mendelssohn and Meyerbeer, was also officially proscribed. In each of the three recitals for this project, significant works were performed by composers who were included in this exhibition, namely, Mendelssohn, Webern, Berg, Weill, and Hans Gal. In addition, as an example of self-censorship, a work of Karl Amadeus Hartmann was included. Hartmann chose “internal exile” by refusing to allow performance of his works in Germany during the Nazi regime. One notable exception to the above categories was a work by Beethoven that was presented as a bellwether of the relationship between music and politics. The range of styles and genres in these three recitals indicates the degree to which Nazi musical censorship cut a wide swath across Europe’s musical life with devastating consequences for its music and culture.

LIONEL TERTIS AND THE FLOWERING OF EARLY TWENTIETH CENTURY ENGLISH VIOLA REPERTOIRE

This performance project focused on English viola literature written in the first half of the twentieth century. During this time, numerous English composers were influenced by Lionel Tertis' unprecedented approach to the viola as a virtuosic and solo instrument. In addition to being an inspiration to composers of whom he was not in direct contact, Tertis' innovative vision for the viola led to numerous collaborations with prominent English composers of his generation. Ralph Vaughan Williams, Arnold Bax, York Bowen, Frank Bridge, Benjamin Britten, and Rebecca Clarke -his own protégé - composed some of the most important works for viola thus directly shaping the impression of the instrument as we know it today. Tertis' artistry as a performing violist was unmatched at the beginning of the twentieth century. He had a unique approach to the instrument which focused on concept of sound, tone color, concentrated listening, continuous vibrato, discreet portamento, and expressive interpretation. His convincing musical and technical ideas led him to write a treatise about how to achieve a beautiful tone. His passion for teaching and concern for the viola's posterity greatly enhanced the development of the viola. Tertis transcribed, edited, and premiered many works during his career. The music that Lionel Tertis influenced can be seen as a microcosm for a musical resurgence in England during the first half of the twentieth-century. The catalyst for this was artistic influences in the form of nationalism, folk music, romanticism, modernism, and impressionism, among others. Before this, England was widely referred to as ''the land without music" but in a very real sense, .Lionel Tertis was one of the pioneers who, through his artistry of the viola, led the way to the renaissance of music in England in the twentieth century.

BAROQUE MUSIC FOR TRUMPET: A STUDY OF SOLO AND CHAMBER REPERTOIRE

The trumpet experienced important changes in terms of its musical use during the middle and late Baroque period. Prior to the Baroque, and even in to the first half of the 17th century, the trumpet had historically been used for rather "non-musical" purposes, sometimes as an instrument for battle or as a tool to be used in the town square to announce the arrival of a dignitary. On the whole, the trumpet was most certainly not used as an instrument of melody -that was typically reserved for violins, flutes, and oboes. However, in the late 1600's, composers such as Allesandro Stradella and Henry Purcell began to treat the trumpet differently. They saw the melodic potential in the trumpet and began to feature the trumpet more as an instrument of melody, as opposed to relegating it to only outlining triads and emphasizing harmony. Of course, keyboard, string, and woodwind instruments had long established a significant catalogue of works by the late 17th century. Additionally, even after the trumpet had been established as an instrument of melody, prominent composers of the time still wrote significantly more solo music for these other instrument families than for the trumpet. Consequently, the overall Baroque repertoire for the solo trumpet pales in comparison to that of the other families of instruments. But, much of this Baroque literature not originally written for trumpet can be presented effectively in the form of a transcription, thereby adding greatly to the repertoire of the Baroque solo trumpet. The goal of these three dissertation recitals is twofold: 1) to perform literature that offers music from a variety of countries of origin that span the entire Baroque era and 2) to feature music that has remained relatively unknown in the trumpet world, yet is musically strong. I will also introduce viable "new" music to the trumpet repertoire through Baroque transcriptions originally written for other instruments or voice. The majority of the transcriptions I will be performing have originated from my own listening and study of Baroque music, and I have selected music that I felt would translate well for the trumpet.

MUSICAL EXOTICISM EXPLORED IN PIANO WORKS FROM THE EIGHTEENTH CENTURY THROUGH THE EARLY TWENTIETH CENTURY

Musical exoticism is the evocation of a culture different from that of the composer. It occurs anytime a composer tries to conjure up the music of a country not his own. Although there have been studies of exoticism in the piano works of an individual composer, namely Debussy, there has not been a comprehensive study of musical exoticism in the piano literature as a whole. Upon chronological examination of the piano repertoire, general trends exhibiting exoticism become evident. The first general trend is the emergence of the Turkish style (alia turca) in the eighteenth century. Turkish style soon transmuted to the Hungarian-Gypsy style (all 'ongarese or style hongrois). [In Beethoven's Op. 129, it is alia ingharese.] Composers often alternated between the two styles even in the same composition. By the late nineteenth century, style hongrois was firmly entrenched in the musical language of Austro-German composers, as seen in the works of Brahms. In the nineteenth century, composers turned to the Middle East, North Africa and Spain for inspiration. In particular are several compositions emulating Spanish dance music, culminating in the Spanish works of Debussy and Ravel. The gamelans from Indonesia and objects from the Far East of Japan and China, brought by advances in trade and transportation, captivated the imagination of composers at the turn of the twentieth century. Also in the early twentieth century, composers tried emulating dance and jazz music coming from the Americas, such as the cakewalk, minstrelsy, and the blues. One sees the ever widening sphere of exotic inspiration for western music composers: from the Turkish invasions to the traveling Gypsies of Hungary; to the captivating dance rhythms, soulful cante jondo sections, and guitar flourishes of Spain; expanding further to the far reaches of Asia and the jazzy rhythms of the Americas. This performance dissertation consists of three recitals presented at the University of Maryland, and is documented on compact disc recordings which are housed within the University of Maryland Library System. The recordings present the music of Balakirev, Beethoven, Brahms, Chopin, Debussy, Haydn, Hummel, Milhaud, Moszkowski, Mozart, Ravel, and Schubert.