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Journal articles on the topic 'Cumulative songs'
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Kupriyanova, Sophia Olegovna. "CUMULATIVE SONGS AND FAIRY-TALES AS THE LULLABY." Sovremennye issledovaniya sotsialnykh problem, no. 2 (May 24, 2015): 302. http://dx.doi.org/10.12731/2218-7405-2015-2-23.
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Till, Benedikt, Ulrich S. Tran, Martin Voracek, and Thomas Niederkrotenthaler. "Music and Suicidality." OMEGA - Journal of Death and Dying 72, no. 4 (March 9, 2015): 340–56. http://dx.doi.org/10.1177/0030222815575284.
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In recent years, the question whether personal suicidality is reflected in individual music preferences has been discussed. We assessed associations of preferred music genres and cumulative exposure to and rating of 50 preselected songs, including 25 suicide-related songs, with suicide risk factors in an online survey with 943 participants. Preferences for sad music were associated with high psychoticism, while fanship of music genres with predominantly joyful contents was linked to low psychoticism. There was a dose-response relationship of positive rating of suicide songs with high life satisfaction and low hopelessness. Music preferences partly reflect suicide risk factors, but enjoyment of suicide songs is negatively associated with risk factors of suicide, which may indicate a psychological defense mechanism against suicidal impulses.
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Andreiushkina, Tatiana N. "Poems-catalogues in the poetry of H.M.Enzensberger." Vestnik of Saint Petersburg University. Language and Literature 20, no. 3 (2023): 400–428. http://dx.doi.org/10.21638/spbu09.2023.301.
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The article analyses the types of cataloguing and various sub-genres of the catalog in the poetry of the German poet, playwright and prose writer H.M.Enzensberger (1929–2022). The poet’s collections of 1957–2013 were anilysed. The article traces such methods of cataloguing lyrical material as a name indicating cataloguing, a series of baroque metaphors in Enzensberger’s catalogue poems, an arbitrary enumeration as an example of the illogicality of phenomena/actions, anaphoric repetitions of personal pronouns as a way of organizing a lyrical catalogue, dialogue as a method of lyrical cataloguing, a cumulative effect in catalogue poems. It is shown how stylistic devices (repetition, gradation, cumulation, climax, anaphora, etc.) determine the structure of the text. Such sub-genres of the catalogue as inventory, emblem mystery, dialogue, poems about the seasons and days, laudatory song, testament, poetological catalogue are considered. Enzensberger relies on the German and European tradition in the use of genres, which goes back both to the culture of the ancient world and to folk art (incantations, songs, laments, dialogues), where the descriptive and enumerative nature of the text is manifested, which determines its structure. The lyrical catalogue is also akin to religious poems, in which nominalization prevailed, that goes back both to the culture of the ancient world and to folk art, where the descriptive and enumerative nature of the text is manifested, which determines its structure.
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Urbańska, Magdalena. "Pisanie performatywne (Głosy i performanse tekstów. Literatura – piosenki – ciało Pawła Tańskiego)." Przegląd Kulturoznawczy, no. 3 (49) (2021): 667–75. http://dx.doi.org/10.4467/20843860pk.21.046.14366.
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The review focuses on the analysis of PawełTański’s book Głosy i performanse tekstów. Literatura – piosenki – ciało [Voices and Performances of Texts: Literature – Songs – Body]. Contrary to the title, textual analysis overwhelmingly prevails over performance studies in Tański’s work which also abstains from research into this field. The author carries out a sketchy review of cultural texts – mainly poetry and songs. In my article I examine Tański’s study, with particular attention to his favourite motifs, i.e. self-referentiality, love for poetry and counter-culture. As the author often reduces scientific description to emotional interpretation and expresses personal preferences in an exaggeratedly emotional form, the reader receives a cumulative expression of love for literature in the form of a report from the inside. This is also evidenced by the number of literary references and extensive citations. In my review, I critically follow this affective delight, and recognise Tański’s analyses to not only be personally tinged but also to draw from performative writing.
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Oras, Janika. "Individual Rhythmic Variation in Oral Poetry: The Runosong Performances of Seto Singers." Open Linguistics 5, no. 1 (December 31, 2019): 570–82. http://dx.doi.org/10.1515/opli-2019-0031.
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AbstractThe article explores the individual differences of rhythmic variation in traditional sung oral poetry. The analysed group of ritual songs is part of the Seto singing culture – a subtradition of Finnic oral trochaic tetrameter. The rhythmic variation, created by different positioning of stressed syllables in the song line, reveals itself on two levels, in linguistic verse structure and in musical performance. In the singers’ performances the verse and musical structures complement each other, having a cumulative rhythmic effect. By designing the rhythm at both levels, the singers systematically take into consideration the linguistic features of the used words. A statistical analysis shows a remarkable divergence in the rhythmic variation of different lead singers. The results are more homogeneous at the level of linguistic verse structure and more diverse at the level of musical performance. Also, the rhythmic choices of the lead singer and his or her choir in the course of the performance may differ. We may speculate that this divergence in individual rhythmic strategies could have been caused by the singers’ type of creativity and skills, their different perceptions of genre features and intergeneric relations, and the musical influences between more closely related singers.
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Greenberg, Gillian. "Indications of the Faith of the Translator in the Peshitta to the 'Servant Songs' of Deutero-Isaiah." Aramaic Studies 2, no. 2 (2004): 175–92. http://dx.doi.org/10.1163/000000004781540399.
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Abstract The Peshitta of Deutero-Isaiah includes several passages relevant to the question of the faith of the translator: Jewish or Christian? There are inconsistencies: some differences between MT and P suggest a Christian or messianic nuance; one blunts an anti-Jewish phrase; in another an opportunity to introduce a Christian theme is resisted. The cumulative weight of examples suggests Christian input. The inconsistency could be explained by postulating a Jewish-Christian translator who attempted to play fair by his Vorlage, putting his own convictions and religious literature to the back of his mind, but occasionally failed.
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Phyland, Debra. "The Measurement and Effects of Vocal Load in Singing Performance. How Much Singing Can a Singer Sing if a Singer Can Sing Songs?" Perspectives of the ASHA Special Interest Groups 2, no. 3 (January 2017): 79–88. http://dx.doi.org/10.1044/persp2.sig3.79.
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Singing as both an art form and physical activity demands a level of health and skill fitness to meet performance demands. The determination of performance fitness relies on performers' self-evaluations of their vocal capacity for performance, based, amongst other factors, on the current vocal status and ability to manage the associated vocal load. Measurement of load and the impact on the vocal mechanism is complex and influenced by many intrinsic and extrinsic factors. Researchers have attempted to quantify vocal load effects by measuring physical impact stress on the vocal folds, self-reported perceived exertion, and/or clinical evaluation of physiologic, acoustic, or perceptual changes. Most studies have been conducted in laboratory rather than in performance contexts and studies on singers are substantially lacking. Heavy vocal load has been causally associated with the development of voice disorders, although the exact relationship and thresholds for acquiring laryngeal pathology require further elucidation, and little is also known about the development of voice disorders among singers. Further understanding of the short-term and cumulative effect on the vocal folds of performing as a singer and the nature and prevalence of voice problems among singers is crucial to the determination of appropriate prevention and therapeutic management.
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NAZAROV, Nazarii. "ALGEBRAIC SYMMETRY MODELS FOR BALTO-SLAVIC FOLKLORE TEXTS." Folia Philologica, no. 1 (2021): 34–54. http://dx.doi.org/10.17721/folia.philologica/2021/1/5.
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The present article suggests a tool for describing and analyzing the folklore texts' symmetry by introducing basicconcepts of abstract algebra: set theory, group theory, function, equation, and symmetry. The mathematical model showsthe internal homogeneity of folklore texts composition that is valid across the genre boundaries. The compositionallymeaningful entities of different language levels that constitute the core of a compositional pattern can be divided intotwo sets connected by a function of symmetrical reflection. Each element of the first set A is projected onto the elementof the second set B. The set A can be called input, the symmetrical set B – output. On the metrics and rhyme level, it isa constant reiteration of the same pattern reflected ad infinitum. On the level of syntactic order, this function connectssentences that constitute parallelistic structures. Thus, the composition and perception of folklore texts resemblea succession of linguistic equations: a singer introduces independent variables that should be given a specific dependentvariable, which can be chosen only from the thesaurus of elements accepted by a specific folklore tradition. The functionthat associates elements of the input set with the output set is the folklore poetics itself, so it can be defined in a seriesof elementary equations that show the connection between the number of compositionally significant elements and otherproperties of the texts, mainly the type of symmetry that is inherent to a particular text. Though all main types of symmetrycan be detected in the folklore texts, they can be reduced to a basic operation of reiterating a small number of elements belonging to one set, connected by an operation of symmetrical reflection constituting a group of symmetry. Compositionpatterns of seemingly different genres (riddles, ritual songs, cumulative fairytale, magical fairytale) have one fundamentalfeature in common that underlies them: when the enumeration of the input set A is over, the level of freedom for the choiceof the output set B is highly restricted, as each of the linguistic equations (L. Zadeh) should be solved: the hero, onceborn, should be either married or killed, the riddle should be answered traditionally, set of images of human life shouldbe confronted with the set of corresponding images of nature (in ritual songs), etc., thus giving the recipient pleasureof constant reiteration and decipherment of already known patterns. In this case, the new meaning of folklore texts canbe revealed. By introducing repetitive patterns of composition, they introduced elementary classification and logic tools.In this case, phenomena like I Quing turned out to be not an exception but rather a logical continuation of binary logicof folklore text composition, so overtly represented in the Balto-Slavic area but valid for a much broader realm of folkloretraditions.
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Sim, Woo Jang. "Playful Characteristics of a Six-Yard Straw Rope." Society Of Korean Oral Literature 72 (March 31, 2024): 193–242. http://dx.doi.org/10.22274/koralit.2024.72.006.
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The folktale Six-yard [seo-bal] Straw Rope is unique. Its formal characteristic of cumulative repetition is prominent, and the story is well-developed, making it seem sufficiently open to interpretation. However, discussing the meaning is not as easy as anticipated. This is because the coherence of characters and the causality of events, often emphasized when understanding works centered on content, is lacking, and the structure of the ending is dispersed. This study addresses these issues by focusing on the formal characteristics of the work; it seeks to reinterpret these formal features from a playful perspective.
The Six-yard Straw Rope follows a format similar to phrase-tail linking folk songs. The gradual exchange process from the six-yard straw rope to the maiden unfolds as a weaving play characterized by phrase-tail linking. The key in narrativizing lies in ‘creating a situation,’ which entails crafting a specific and appropriate situation where two objects can be exchanged. Ultimately, Six-yard Straw Rope is created by aptly weaving various situations where low- and high-value items can be exchanged into a narrative. This study names it the ‘Situation-Weaving Play.’ The lack of consistency in character portrayal and causality in event development and the dispersed structure of the resolution all stem from the playful nature of the work.
The playful characteristic of the Six-yard Straw Rope is deeply related to the situational thinking encouraged in oral culture. Utilizing common objects found in everyday spaces to create appropriate situations in folktales is the ultimate play that enhances situational thinking in oral culture. Folktales with a situational play abound beyond Six-yard Straw Rope, with Mole’s Wedding being a prime example. The charm of situational play, based on situational thinking, lies in the fact that humble objects like a six-yard straw rope can become a maiden or silk when well combined with situations, and even a humble mole can become the finest groom in the world under various situations.
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Bolaños Motta, José Ignacio, Laura Ximena Silva Ladino, and Elizabeth Casallas Forero. "La Canción de Contenido Acumulado (CCA*) como estrategia para el mejoramiento de los procesos atencionales en la Primera Infancia." Zona Próxima 35 (March 30, 2022): 49–66. http://dx.doi.org/10.14482/zp.35.155.4.
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El presente estudio tuvo por objetivo estimular los procesos atencionales de un grupo de estu-diantes pertenecientes a las Instituciones Educativas Antonio Nariño y Gimnasio Británico de la ciudad de Villavicencio (Colombia). A nivel metodológico, la investigación se desarrolló desde una perspectiva cualitativa en donde se analizaron Diarios de Campo y Entrevistas. Como resul-tado se diseñó la propuesta Canción de Contenido Acumulado (CCA), categoría que emerge de un amplio grupo de actividades desarrolladas dentro del marco de esta investigación, en la que la propuesta didáctica se generó desde el método desarrollado por Jacques-Dalcroze. A modo de con-clusión, el estudio establece que existe la posibilidad de potenciar los procesos atencionales de la primera infancia a través de la estrategia denominada CCA, la cual es susceptible de ser replicada en otros contextos del campo de la educación y la Pedagogía Infantil.
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Chen, J. R., L. Stepanek, and A. J. Doupe. "Differential contributions of basal ganglia and thalamus to song initiation, tempo, and structure." Journal of Neurophysiology 111, no. 2 (January 15, 2014): 248–57. http://dx.doi.org/10.1152/jn.00584.2012.
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Basal ganglia-thalamocortical circuits are multistage loops critical to motor behavior, but the contributions of individual components to overall circuit function remain unclear. We addressed these issues in a songbird basal ganglia-thalamocortical circuit (the anterior forebrain pathway, AFP) specialized for singing and critical for vocal plasticity. The major known afferent to the AFP is the premotor cortical nucleus, HVC. Surprisingly, previous studies found that lesions of HVC alter song but do not eliminate the ability of the AFP to drive song production. We therefore used this AFP-driven song to investigate the role of basal ganglia and thalamus in vocal structure, tempo, and initiation. We found that lesions of the striatopallidal component (Area X) slowed song and simplified its acoustic structure. Elimination of the thalamic component (DLM) further simplified the acoustic structure of song and regularized its rhythm but also dramatically reduced song production. The acoustic structure changes imply that sequential stages of the AFP each add complexity to song, but the effects of DLM lesions on song initiation suggest that thalamus is a locus of additional inputs important to initiation. Together, our results highlight the cumulative contribution of stages of a basal ganglia-thalamocortical circuit to motor output along with distinct involvement of thalamus in song initiation or “gating.”
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Douhard, Mathieu, Marco Festa-Bianchet, Sandra Hamel, Daniel H. Nussey, Steeve D. Côté, Josephine M. Pemberton, and Fanie Pelletier. "Maternal longevity and offspring sex in wild ungulates." Proceedings of the Royal Society B: Biological Sciences 286, no. 1896 (February 6, 2019): 20181968. http://dx.doi.org/10.1098/rspb.2018.1968.
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In species with sexual size dimorphism, the offspring of the larger sex usually have greater energy requirements and may lead to greater fitness costs for parents. The effects of offspring sex on maternal longevity, however, have only been tested in humans. Human studies produced mixed results and considerable debate mainly owing to the difficulty of distinguishing the effects of sexual dimorphism from sociocultural factors. To advance this debate, we examined how the relative number of sons influenced maternal longevity in four species of free-living ungulates (Soay sheep Ovis aries ; bighorn sheep, Ovis canadensis ; red deer, Cervus elaphus ; mountain goat, Oreamnos americanus ), with high male-biased sexual size dimorphism but without complicating sociocultural variables. We found no evidence for a higher cumulative cost of sons than of daughters on maternal longevity. For a given number of offspring, most females with many sons in all four populations lived longer than females with few sons. The higher cost of sons over daughters on maternal lifespan reported by some human studies may be the exception rather than the rule in long-lived iteroparous species.
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Derrickson, Kim C. "Yearly and Situational Changes in the Estimate of Repertoire Size in Northern Mockingbirds (Mimus polyglottos)." Auk 104, no. 2 (April 1, 1987): 198–207. http://dx.doi.org/10.1093/auk/104.2.198.
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Abstract The singing behavior of 4 male Northern Mockingbirds (Mimus polyglottos) was studied during 1980 and 1981. Over 10,000 song bouts (repetition of a particular song type) were analyzed spectrographically. Between 102 and 412 distinct song types were identified for each male in a given year. Many of these song types (25.8-57.4%) occurred only once in this sample of singing behavior. Repertoire size was estimated by fitting an exponential curve to a cumulative plot of distinct song types as a function of consecutive bouts sampled. The resulting asymptote was the estimate of repertoire size. Sequences of at least 50 consecutive bouts were used in estimating repertoire size. The technique of using consecutive bouts was required because of the high proportion of rare song types. Several estimates were made for each male and resulted in mean repertoire size estimates of 100-200 song types for the four males. Long sequences (125-150 bouts) of consecutive bouts are preferred to estimate repertoire size accurately. In addition, the social situation in which the singing behavior occurred can alter significantly the estimate of repertoire size. For example, estimates produced from singing during patrolling or countersinging were smaller than estimates generated from singing while associating with a female. The repertoire size estimate increased between 1980 and 1981 for 3 of 4 males. The one male not showing an increase spent much time patrolling and interacting with neighboring males before dying early in 1981. These results are consistent with the impression that repertoire size increases with age.
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Park, Song Ee, Moon Ki Jung, and In Gyu Hwang. "Abstract 4381: Predictive risk factors for cancer thrombosis in gastric cancer patients." Cancer Research 83, no. 7_Supplement (April 4, 2023): 4381. http://dx.doi.org/10.1158/1538-7445.am2023-4381.
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Abstract Background Gastric cancer is strongly associated cancer thromboembolism. We aimed to identify the Khorana risk score (KRS) and other risk factors for cancer thromboembolism in patients with gastric cancer after gastrectomy. Methods We reviewed 610 gastric patients, who had undergone D2 radical gastrectomy between January 2005 and December 2017. Kaplan-Meier survival analysis and Cox regression models were used to evaluate for independent predictor of cumulative incidence of cancer thromboembolism and survival. Results The median follow up was 67.0 months. There were 35 (5.7%) caner thromboembolism. The cumulative incidences of thromboembolism were 6.1%, 3.1%, 3.3%, and 20.7% in stages I, II, III, IV. 181 (29.7%) patients were relapsed cancer and 159 (26.1%) patients were died. A high KRS (cumulative incidence 5.8%) was not associated with cancer thromboembolism compared to an intermediate KRS (cumulative 5.7%) (HR=1.005, 95% CI = 0.540-2.061, P= 0.876). After gastrectomy, recurrent cancer (cumulative incidence 9.9%) was associated with cancer thromboembolism compared to no recurrence (cumulative incidence 4.0%) (HR 3.713, 95% CI 1.879-7.335, P < 0.001). Conclusions Recurrent gastric cancer patients after gastrectomy were significantly increased cancer thromboembolism risk compared to no recurrent cancer patients. Among patients with gastric cancer after gastrectomy, KRS did not stratify the patients at high risk of cancer thromboembolism. Citation Format: Song Ee Park, Moon Ki Jung, In Gyu Hwang. Predictive risk factors for cancer thrombosis in gastric cancer patients. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4381.
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Naumenko, Nataliia. "Narrative Polyphony of Sting’s Album “Ten Summoner’s Tales” (1993)." Pitannâ lìteraturoznavstva, no. 106 (December 30, 2022): 144–64. http://dx.doi.org/10.31861/pytlit2022.106.144.
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The article analyses the specifications of narrative structures and types of narrators in the song lyrics from the album “Ten Summoner’s Tales” (1993), based on “Canterbury Tales” by Geoffrey Chaucer and traditionally claimed the Magnum Opus of Sting. Apparently, Chaucerian style in all the twelve verses composing the album emerges not merely as the interpretation of original “Canterbury Tales” plots or impartment of the new features to the initial characters, but predominantly as exploitation of the lyrical and ironic intonations within an image of a narrator for a certain poem. Since a song is the synthetic generic structure marked with profound internal experience, Sting’s album reveals the diverse types of a speaker in every verse. Primarily, it is the ‘I-narrator’ embodied in poetic masks of a historian, a warrior, a saint, a gambler or a philosopher; some texts like “Fields of Gold” or “Shape of My Heart” represent the alternation of speaker types, which method of storytelling creates the special generic and narrative polyphony for a song. Subsequently, the narrative structure would determine the genre of a separate work: a detective story, a pastoral, a historical reflection, a cumulative tale, a confession, and somehow a Dante-styled epic poem. Overall, the various types of narrators in Sting’s lyrics composing “Ten Summoner’s Tales” (determined as ‘reflexive,’ ‘actor,’ ‘pointillist’ and ‘medium’ with all possible combinations) bring the elements of the author’s own vital and creative experience into the song where they gain the generalized meanings as symbols of human life, being surrounded with verbal images and amplified with musical accompaniment.
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Deshpande, Mugdha, Fakhriddin Pirlepesov, and Thierry Lints. "Rapid encoding of an internal model for imitative learning." Proceedings of the Royal Society B: Biological Sciences 281, no. 1781 (April 22, 2014): 20132630. http://dx.doi.org/10.1098/rspb.2013.2630.
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As in human infant speech development, vocal imitation in songbirds involves sensory acquisition and memorization of adult-produced vocal signals, followed by a protracted phase of vocal motor practice. The internal model of adult tutor song in the juvenile male brain, termed ‘the template’, is central to the vocal imitation process. However, even the most fundamental aspects of the template, such as when, where and how it is encoded in the brain, remain poorly understood. A major impediment to progress is that current studies of songbird vocal learning use protracted tutoring over days, weeks or months, complicating dissection of the template encoding process. Here, we take the key step of tightly constraining the timing of template acquisition. We show that, in the zebra finch, template encoding can be time locked to, on average, a 2 h period of juvenile life and based on just 75 s of cumulative tutor song exposure. Crucially, we find that vocal changes occurring on the day of training correlate with eventual imitative success. This paradigm will lead to insights on how the template is instantiated in the songbird brain, with general implications for deciphering how internal models are formed to guide learning of complex social behaviours.
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Poon, Cecilia Y. M., and Bob G. Knight. "Parental emotional support during emerging adulthood and Baby Boomers’ well-being in midlife." International Journal of Behavioral Development 37, no. 6 (September 5, 2013): 498–504. http://dx.doi.org/10.1177/0165025413498217.
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This study examined whether parental emotional support around emerging adulthood influenced well-being in midlife. We applied latent growth curve (LGC) models on 337 Baby Boomers who were in their late teens to early 20s when they entered the Longitudinal Study of Generations (LSOG) in 1971. There was a small but significant decline in self-rated health and positive emotions through 2005, but not depressive symptoms. Greater support from fathers in 1971 was associated with better self-rated health, less depression, and a slower decline in self-rated health across midlife. Greater support from mothers was associated with more positive emotions. These associations did not significantly differ among sons and daughters. Findings are discussed in the context of cumulative advantage/disadvantage and life-stage specific challenges to highlight the importance of parental emotional support during life transitions.
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Hartung, John. "Matrilineal inheritance: New theory and analysis." Behavioral and Brain Sciences 8, no. 4 (December 1985): 661–70. http://dx.doi.org/10.1017/s0140525x00045520.
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AbstractIn most cultures, extramarital sex is highly restricted for women. In most of those cultures, men transfer wealth to their own sons (patrilineal inheritance). In some cultures extramarital sex is not highly restricted for women, and in most of those cultures, men transfer wealth to their sisters' sons (matrilineal inheritance). Inheritance to sisters' sons ensures a man's biological relatedness to his heirs, and matrilineal inheritance has been posited as a male accommodation to cuckoldry—a paternity strategy—at least since the 15th century. However, longitudinal analysis of the cumulative effect of female extramarital sex indicates that matrilineal inheritance is most advantageous for women and would be more accurately considered a grandmaternity strategy. That is, if the probability that men's putative children are their biological children (ρ = probability of paternity) is less than 1, the probabilistic degree of relatedness between a female and her matrilineal heirs is higher than her corresponding relatedness to her patrilineal heirs. The same holds true for men only if ρ is very low (< 0.46). The upshot is that for moderate levels of female extramarital sex, matrilineal inheritance, relative to patrilineal inheritance, is highly advantageous for women and disadvantageous for men. Consideration of female variance in reproductive success beyond the first generation, and of a man's network of obligation to the inclusive fitness of his relatives, suggests that although the establishment of matrilineal inheritance may require extremely high levels of female extramarital sex, once established, it is likely to be maintained at levels of ρ that reasonably characterize many societies in the ethnographic record. New analysis of previously published data shows a strong association between matrilineal inheritance and moderate to low probability of paternity, and an even stronger relationship between patrilineal inheritance and high probability of paternity.
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Csörgő, Tibor, Péter Fehérvári, Zsolt Karcza, and Andrea Harnos. "Exploratory analyses ofmigration timing andmorphometrics of the Song Thrush (Turdus philomelos)." Ornis Hungarica 25, no. 1 (June 27, 2017): 120–46. http://dx.doi.org/10.1515/orhu-2017-0009.
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Abstract Ornithological studies often rely on long-term bird ringing data sets as sources of information. However, basic descriptive statistics of raw data are rarely provided. In order to fill this gap, here we present the third item of a series of exploratory analyses of migration timing and body size measurements of the most frequent Passerine species at a ringing station located in Central Hungary (1984-2016). First, we give a concise description of foreign ring recoveries of the Song Thrush in relation to Hungary. We then shift focus to data of 4137 ringed individuals and 1051 recaptures derived from the ringing station, where birds have been trapped, handled and ringed with standardized methodology since 1984. Timing is described through annual and daily capture and recapture frequencies and their descriptive statistics. We show annual mean arrival dates within the study period and present the cumulative distributions of first captures with stopover durations. We present the distributions of wing, third primary, tail length and body mass, and the annual means of these variables. Furthermore, we show the distributions of individual fat and muscle scores, and the distributions of body mass within each fat score category. We distinguish the spring and autumn migratory periods, breeding and wintering seasons, and age groups (i.e. juveniles and adults). Our aim is to provide a comprehensive overview of the analysed variables. However, we do not aim to interpret the obtained results, merely to draw attention to interesting patterns that may be worth exploring in detail. Data used here are available upon request for further analyses.
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Hofer, K. E. "Book Reviews : FROBABILISTIC MODELS OF CUMULATIVE DAMAGE J. L. Bogdanoff and F. Kozin J. Wiley and Sons, New York 1985, 341 pp." Shock and Vibration Digest 19, no. 10 (October 1, 1987): 20–21. http://dx.doi.org/10.1177/058310248701901004.
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van Schalkwyk, Garth J., and Peter J. Witbooi. "A model for bank reserves versus treasuries under Basel III." Applied Stochastic Models in Business and Industry 33, no. 2 (February 16, 2017): 237–47. http://dx.doi.org/10.1002/asmb.2238.
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Recently, the Basel Committee on Banking Supervision introduced strategies to protect banks from running out of liquidity. These measures included an increase of the minimum reserves that the bank ought to hold, in response to the global financial crisis. We propose a model to minimize risk for a bank by finding an appropriate mix of diversification, balanced against return on the portfolio. In particular, we consider jump diffusion models of bank reserves in order to address the risk due to deposit withdrawals. We formulate a stochastic optimal control problem related to the minimization of deposit risk and the reserve process, the net cash flows from depository activity, and cumulative cost of the bank's provisioning strategy. We analyze the main risk management issues arising from the optimization problem, with respect to the reserve requirement ratio, supported by simulations. Copyright © 2017 John Wiley & Sons, Ltd.
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Xie, Haiyan. "Interpreting Mythorealism: Disenchanted Shijing and Spiritual Crisis in Yan Lianke’s Ballad, Hymn, Ode." Modern Chinese Literature and Culture 34, no. 1 (June 2022): 32–65. http://dx.doi.org/10.3366/mclc.2022.0004.
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“Mythorealism” is a formal literary experiment developed by Yan Lianke, whose 2008 novel Ballad, Hymn, Ode ( Feng ya song) produces a cumulative effect of absurdity that has provoked controversy over the extent to which it offers an effective social critique. In response to the scholarship based on realist readings of the novel, this article analyzes it from a “mythorealistic” perspective. It argues that the mythorealist narrative does not necessarily cancel out Yan’s social commentary but instead transfers his critical impulse to a psychological exploration of marginal intellectuals in a desymbolized society. In particular, this article is concerned with thematic interpretation and the relation between literary form and meaning in Yan’s parody of the Shijing in Ballad, Hymn, Ode. By focusing on Yan’s symbolic representation of sex and disgust, this article investigates how such imagery and motifs speak from their own space to reveal Chinese intellectuals’ spiritual crisis in an academic world pervaded with an instrumentalist ethos.
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Ahmadi, Shukrullah, Margot Guth, Astrid Coste, Liacine Bouaoun, Aurélie Danjou, Marie Lefevre, Brigitte Dananché, et al. "Paternal Occupational Exposure to Heavy Metals and Welding Fumes and Testicular Germ Cell Tumours in Sons in France." Cancers 14, no. 19 (October 10, 2022): 4962. http://dx.doi.org/10.3390/cancers14194962.
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Testicular cancer is the most common cancer in young men. Its causes are largely unknown, although prenatal occupational and environmental exposures have been suggested. We investigated paternal occupational exposure to heavy metals and welding fumes and the risk of testicular germ cell tumors (TGCT) in their offspring. A total of 454 cases and 670 controls were included from a French nationwide case–control study. The INTEROCC job exposure matrix was used to assign occupational exposures (cadmium, chromium, iron, nickel, lead, and welding fumes) to the fathers’ jobs. Odds ratios (ORs) for TGCT were estimated using conditional logistic regression models for frequency-matched sets. Three complementary analytical approaches were used: (1) single-agent analysis, (2) analysis by groups, and (3) principal component analysis (PCA). The proportion of paternal exposure to different heavy metals and welding fumes ranged from 0.7% (cadmium) to 11.3% (lead). Based on PCA, three principal components explained 93.5% of the cumulative variance. No associations were found between heavy metals or welding fumes and TGCT. In this study, paternal occupational exposure to heavy metals or welding fumes was not associated with TGCT development in their sons.
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Islam, Tasnia. "Hajar Churashir Ma:." Crossings: A Journal of English Studies 10 (August 1, 2019): 62–70. http://dx.doi.org/10.59817/cjes.v10i.82.
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The surface story of Mahasweta Devi’s novel Hajar Churashir Ma (Mother of 1084) is a cumulative of glimpses of the incidents of how Kolkata responded to the massacre of Broti Chatterjee and his comrades who took part in the revolutionary communist Naxalite movement in the early 1970s. But underneath the guise of the crucial sociopolitical issues, this text is essentially about a female individual – a mother – who resists her conventional, marginalized, ignored, and silenced survival, and emerges from the periphery to the center and from silence to voice in order to redefine her life. The way she executes an inward revolution (metaphorically paralleled with her son’s armed revolution) to materialize her sense of being within the dominating patriarchy (mostly performed by her terrorizing marriage) and the way she breaks through the stereotypes and exploitations to create her own place – both domestic and social – produce a remarkable personal “herstory.” This paper, thus, attempts to explore the “herstorical” journey of Sujata towards psychological emancipation through the passage of self-realization and political consciousness. The paper also observes that the portrayal of Sujata’s journey is not limited to a single individual “herstory” because it symbolically represents the struggles of many other Sujatas who fight against gender stereotypes and attempt ideological liberation.
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Lindová, Jitka, Lenka Příplatová, and Jaroslav Flegr. "Higher Extraversion and Lower Conscientiousness in Humans Infected with Toxoplasma." European Journal of Personality 26, no. 3 (May 2012): 285–91. http://dx.doi.org/10.1002/per.838.
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Toxoplasmosis is associated with specific differences in the personality of infected subjects relative to non–infected subjects. These differences are usually considered to be a side effect of the manipulative activity of the parasite aimed to increase the probability of its transmission from the intermediate host to the definitive host by predation. The personality of infected subjects was studied mostly using the Cattell's questionnaire. However, this questionnaire is now considered outdated and has been mostly substituted with the Neuroticism–Extraversion–Openness Personality Inventory—Revised (NEO–PI–R) questionnaire in clinical practice. Here, we searched for the association between toxoplasmosis and the personality by screening a population of students with the NEO–PI–R questionnaire. We found that Toxoplasma–infected male and female students had significantly higher extraversion and lower conscientiousness. The conscientiousness negatively correlated with the length of infection in men, which suggested that the toxoplasmosis associated differences were more probably the result of slow cumulative changes induced by latent toxoplasmosis, rather than transient side effect of acute Toxoplasma infection. The existence of this correlation also supported (but of course not proved) the hypothesis that Toxoplasma infection influenced the personality, rather than the hypothesis that the personality influenced the probability of the infection. Copyright © 2011 John Wiley & Sons, Ltd.
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Parncutt, Richard. "Mother Schema, Obstetric Dilemma, and the Origin of Behavioral Modernity." Behavioral Sciences 9, no. 12 (December 6, 2019): 142. http://dx.doi.org/10.3390/bs9120142.
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What triggered the emergence of uniquely human behaviors (language, religion, music) some 100,000 years ago? A non-circular, speculative theory based on the mother-infant relationship is presented. Infant “cuteness” evokes the infant schema and motivates nurturing; the analogous mother schema (MS) is a multimodal representation of the carer from the fetal/infant perspective, motivating fearless trust. Prenatal MS organizes auditory, proprioceptive, and biochemical stimuli (voice, heartbeat, footsteps, digestion, body movements, biochemicals) that depend on maternal physical/emotional state. In human evolution, bipedalism and encephalization led to earlier births and more fragile infants. Cognitively more advanced infants survived by better communicating with and motivating (manipulating) mothers and carers. The ability to link arbitrary sound patterns to complex meanings improved (proto-language). Later in life, MS and associated emotions were triggered in ritual settings by repetitive sounds and movements (early song, chant, rhythm, dance), subdued light, dull auditory timbre, psychoactive substances, unusual tastes/smells and postures, and/or a feeling of enclosure. Operant conditioning can explain why such actions were repeated. Reflective consciousness emerged as infant-mother dyads playfully explored intentionality (theory of mind, agent detection) and carers predicted and prevented fatal infant accidents (mental time travel). The theory is consistent with cross-cultural commonalities in altered states (out-of-body, possessing, floating, fusing), spiritual beings (large, moving, powerful, emotional, wise, loving), and reports of strong musical experiences and divine encounters. Evidence is circumstantial and cumulative; falsification is problematic.
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Zaunbrecher, Michelle, and Kerri Reeks. "Cyclone evacuation in the Timor Sea—a case study." APPEA Journal 48, no. 1 (2008): 43. http://dx.doi.org/10.1071/aj07005.
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Nexus Energy (Nexus) is the operator of the ACP23 permit in the Territory of Ashmore Cartier in the Timor Sea. The permit contains the Crux gas and condensate field. During March 2007, Nexus was undertaking drilling operations at the Crux field using the semi-submersible drilling rig Songa Venus, operated by Songa Drilling. Nexus utilised the Truscott Airbase to land fixed wing aircraft from Darwin, and then flew helicopters from Truscott out to the rig. An incident occurred as a result of failing to completely down-man the Songa Venus in the face of approaching Tropical Cyclone George. The National Offshore Petroleum Safety Authority (NOPSA) issued an Improvement Notice to Songa as the Rig Safety Case owner. Nexus was responsible for providing aviation transport and logistics. The evacuation planning allowed for a 12 hour buffer. Nonetheless, rapid changes in weather resulted in this buffer time being inadequate. On the morning of the planned final evacuation flight, the Bureau of Meteorology (BOM) issued a forecast of cloud base below the aviation alternate minima for Truscott (1,079 ft above ground level and 4.4 km visibility). The weather forecast of the cloud base minima being predicted to be below the aviation alternate minima invokes an aviation regulatory rule. This aviation regulatory rule requires that a suitable onshore alternate landing site is available before the helicopter is allowed to take off. The designated alternate landing point at Troughton Island was predicted to be similarly affected by weather and not suitable as an alternate landing point. The selected alternate landing site cannot then also require an alternate. Therefore, the helicopter was not able to take off and the flight to the rig was consequently aborted leaving 17 people onboard the rig. Nexus has since dedicated significant effort and resources to rectifying the situation that occurred. Nexus plans to develop the Crux field and therefore must find a reliable solution for future cyclone evacuations. Nexus undertook an extensive review of regional alternate landing sites relevant to Truscott airbase and Crux. The most viable and reliable options for the Crux field were assessed as Cape Leveque and Kupang, West Timor. Along with other technical solutions, Nexus has funded the upgrade of the existing Truscott BOM weather station facilities to an Automatic Weather Information System (AWIS), which will be operational for the 2007/08 cyclone season. The AWIS includes: a ceilometer that measures cloud base minima, a vis-meter that measures cloud cover, and an air pressure sensing pparatus (QNH). This information is measured and transmitted in real time to aviator operators. The documented height above the runway designated as the alternate minima is determined by the height of the surrounding terrain. The philosophy behind the lowering of the alternate level, when AWIS information is available, is based upon the flight crew being able to accurately set a known current QNH reading onto an altimeter sub scale, thus increasing altimeter integrity. The improved weather measurement information has allowed for a 100 ft reduction in approach and alternate minima for the airbase. This is of potentially significant benefit given that the incident described in this paper was directly related to the inability of the helicopter to take off from Truscott due to restrictions on alternate minima. In addition, the installation of the AWIS will allow for more accurate weather forecasting for Truscott and the region. A key outcome of the assessment undertaken was to improve the definition of the tasks that need to be undertaken for cyclone emergency planning, and clearly assign these tasks to positions in the emergency response team. The revised emergency response team is comprised of three key roles: cyclone evacuation coordinator; transport coordinator; and aviation technical advisor. The cumulative effect of multiple operators working in the region needs to be assessed on an ongoing basis. Substantial improvements can be made to cyclone evacuation infrastructure and resources via an industry-wide approach.
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Liu, Wei Ping, Yan Feng Xu, Yan Xie, Xiaopei Wang, Yuqin Song, and Jun Zhu. "Incidence, Clinical Characteristics and Outcome of Cardiac Toxicity in Elderly Patients with Diffuse Large B-Cell Lymphoma." Blood 132, Supplement 1 (November 29, 2018): 5416. http://dx.doi.org/10.1182/blood-2018-99-117955.
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Abstract Backgroud: Cardiac toxicity is a life-threatening complication in elderly patients with lymphoma, which lead to a delay or premature termination of chemotherapy. Methods: A total of 462 consecutive patients with diffuse large B-cell lymphoma over 60 years old between 2007 and 2017 were reviewed. Of these, 87 patients were excluded from the study. Finally, 375 lymphoma patients were included. Data about general information, clinical feature, laboratory examination, pathological results, therapeutic methods and cardiac toxicity were collected by case retrieval system. Cardiac toxicity was graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE). Results: The incidence of cardiac disorders was 5.3% (20/375). The median number of chemotherapy cycles before cardiac toxicity was 1 (range, 1-4). Ventricular arrhythmia was the most frequent cardiac disorder (n=6), followed by palpitations (n=4), left ventricular systolic dysfunction (n=3), heart failure (n=3), atrial fibrillation (n=2), myocardial infarction (n=1) and paroxysmal atrial tachycardia (n=1). At the end of treatment, grades 3 to 5 cardiac events were observed in 8 patients. In a multivariate Cox regression analysis, ECOG performance status ≥2 and history of cardiovascular disease were identified as risk factors for IP. The cumulative incidence of cardiac disorders were 2.3% (6/266) for patients without risk factors, 11.6% (11/95) for patients with 1 risk factors, and 21.4% (3/14), respectively. Conclusion: Cardiac toxicity is not rare in elderly patients with lymphoma, and a comprehensive management strategy is needed. Disclosures Song: Peking University Cancer Hospital (Beijing Cancer Hospital): Employment. Zhu:Beijing Cancer Hospital: Employment.
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Kuzmina, Aitalina A. "Archaic and Late Layers of Poetics of the Yakut Heroic Epic Olonkho (based on the Material of the Vilyui Expedition of 1938)." Nauchnyi dialog, no. 7 (July 30, 2020): 254–65. http://dx.doi.org/10.24224/2227-1295-2020-7-254-265.
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The article is devoted to the study of the historical poetics of the Olonkho Vilyui Yakuts. The relevance of the study is due to the need for an in-depth study of the archaic and late layers of the Yakut heroic epic based on the materials of the Vilyui expedition of 1938, with the help of which it is possible to reveal the specifics of the olonkho of the Vilyui region. The author of the article concludes that the materials of this expedition accurately reflect the peculiarities of the local tradition under consideration. The archaic stratum of olonkho is revealed, which is characterized by a ritual parenthetic song before or after the performance of the epic, the preservation of the mythologeme of the creation of the world, the image of the sacred birch Aar Kuduk Khatyng, a less developed description in the epic beginning. It has been established that the formation of the late layer of olonkho poetics is associated with a number of reasons, including the following: the cumulative nature of the characters’ actions under the influence of a fairy tale; demythologization; replacement of the heroic with everyday life; reflection of the negative consequences of the development of society; the appearance of borrowed words, the names of Russian cities, Christian concepts, images of Russian girls, the fire-breathing Serpent Gorynych, Baba Yaga as a result of close ties with Russians, their culture and worldview; the emergence of a war motive between the aiyy and abaasy tribes as a reflection of the Great Patriotic War; the image of the achievements of technical progress (in particular, the steamer); displacement of images; using the image of a shaman; the introduction of an intermediate layer of images of semi-ayy and semi-baasy.
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Saraiva, A., A. Maduro, B. Mendes, A. Carones Esteves, M. Luis, J. A. P. Da Silva, and L. Inês. "AB0589 CANCER PREVALENCE IN SYSTEMIC LUPUS ERYTHEMATOSUS: A PORTUGUESE COHORT STUDY WITH 15 YEARS OF FOLLOW-UP." Annals of the Rheumatic Diseases 82, Suppl 1 (May 30, 2023): 1495.1–1495. http://dx.doi.org/10.1136/annrheumdis-2023-eular.4627.
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BackgroundAn increased risk of malignancy was reported in patients with Systemic Lupus Erythematosus (SLE) [1-3].ObjectivesTo estimate the prevalence of cancer in a Portuguese cohort of patients with SLE over long term follow-up.MethodsPatients followed up between 01/01/2006 and 31/10/2021 at the Centro Universitário de Coimbra Lupus Clinic were included. All patients fulfilling SLE classification criteria (EULAR/ACR 2019 or SLICC 2012 or ACR 1999) and assessed at least in two visits were included. Cancer cases were only considered if the diagnosis was established after SLE diagnosis. Patient and SLE clinical and treatment data were collect from the cohort electronic database. Disease activity was assessed with the SLE Disease Activity Score (SLE-DAS) and organ damage with the SLICC/ACR Damage Index (SDI). Associations with malignancy were tested using theChi-square test,Fisher exact test,Student’s t-test,orMann-Whitney U test, as appropriate. Statistical significance with Bonferroni adjustment accounting for multiple comparisons was considered for p<0.005ResultsIn total, 438 patients were included (mean age: 49.6±15.8 years-old; female: 85.4%; mean disease duration: 14.2±9.8 years). At the last study visit, 68.8% were in remission, and mean SLE-DAS was 1.9±2.5. The total cumulative prevalence for cancer was 7.1% (n=31), with 4 patients presenting metastatic disease at the time of cancer diagnosis. The most common malignancies were non-melanoma skin cancer (1.1%), colorectal (1.1%), hematologic (1.1%), lung (0.7%), and breast cancer (0.7%). Cancer patients were older (64.5±14.9 vs. 48.5 years, p<0.001) and had higher any-cause mortality (35.5% vs. 5.9%, p<0.001). There were no significant differences regarding disease activity at last visit, disease duration, organ damage or cumulative immunosuppressive therapy usage (38.7% vs 54%, p=0.099). Death as a direct result of malignancy occurred in 8 (72.7%) patients, accounting for 22.9% of death in our cohort.ConclusionThis is the first study reporting cancer prevalence in a Portuguese SLE cohort. Our results are similar to those reported by Sultan et all (5.4%) (2), but substantially lower than those reported in a Finish cohort (22%) (3).References[1]Song L, Wang Y, Zhang J, et al. The risks of cancer development in systemic lupus erythematosus (SLE) patients: a systematic review and meta-analysis. Arthritis Res Ther 2018;20:270. doi: 10.1186/s13075-018-1760-3.[2]Sultan SM, Ioannou Y, Isenberg DA. Is there an association of malignancy with systemic lupus erythematosus? An analysis of 276 patients under long-term review. Rheumatology (Oxford) 2000;39:1147-52.[3]Tallbacka KR, Pettersson T, Pukkala E. Increased incidence of cancer in systemic lupus erythematosus: a Finnish cohort study with more than 25 years of follow-up. Scand J Rheumatol 2018;47:461-4.Acknowledgements:NIL.Disclosure of InterestsNone Declared.
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Ding, Fang. "The Making of Classics: Li Bai and Du Fu’s Poems in Anthologies of Tang Poetry between the Tang and the Ming Dynasties." Journal of Chinese Humanities 8, no. 2 (September 14, 2022): 163–88. http://dx.doi.org/10.1163/23521341-12340131.
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Abstract The canonization of Li Bai and Du Fu’s poetry occurred over a period that spanned centuries and dynasties. The treatment of Li Bai and Du Fu’s works differed through the ages. Among anthologies from the Tang and the Five Dynasties that remain to our disposition today, only three contain poems by Li Bai, and only one includes some by Du Fu. Tang compilers had a poor opinion of the two poets. Their criticism contrasts substantially with the praise that was offered by Han Yu and other poets. During the Song and Yuan dynasties, scholars held Li Bai and Du Fu in high regard, yet their poems were often omitted by compilers. The main reason for this exclusion was that both poets’ complete works had long been considered unworthy and set aside. Compilers respected the skills of the two poets, but they did not truly appreciate their work. During the Ming dynasty, anthologies would comment on the two poets as important figures of literary history. Compilers praised their art as being of the highest quality. By then, both poets were highly respected, and their poems had officially already been made into classics. In the process of becoming classics, works of art can be seen as enduring, and as cumulating value through different periods of time. Times keep on changing, yet the significance of Li Bai and Du Fu’s poetry became all the more obvious as centuries passed.
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Завьялова, Мария Вячеславовна. "The Ant’s Pilgrimage from India to Occitania." ТРАДИЦИОННАЯ КУЛЬТУРА, no. 1 (May 10, 2022): 51–68. http://dx.doi.org/10.26158/tk.2022.23.1.005.
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В статье анализируется каталанский фольклорный текст кумулятивного типа о путешествии муравья в Иерусалим, нашедший отражение в современной фантастической трилогии французского писателя Бернара Вербера о муравьях. Рассматриваются истоки этого сюжета, одна часть которого повторяет цепь персонажей еврейской пасхальной песни «Хад Гадья» (отголоски которой многочисленны в Европе), а другая восходит к индийской «Панчатантре» (сюжет попал в Европу благодаря басне Лафонтена). Отдельно рассматривается также роль муравья в мифологиях народов мира, где он, несмотря на свою малость, является носителем сверхъестественных качеств и обладает способностью легко переходить границу между мирами живых и мертвых, актуализируя таким образом особую тему «муравьиного пути». На основании анализа полученных данных, а также исторических фактов, имеющих отношение к месту записи фольклорного текста о муравье, делается вывод о том, что сюжет о путешествии муравья в Иерусалим неслучайно появился именно на территории Окситании и имеет отношение к историко-культурным реалиям местности, восходящим к эпохе Крестовых походов. This article analyzes a Catalan folklore text of the cumulative type about the journey of an ant to Jerusalem, which is reflected in a fantastic trilogy about ants by the modern French writer Bernard Werber. It examines the origins of this plot. One part of it repeats the chain of characters from the Jewish Passover song “Had Gadya”; echoes of this plot are numerous in European culture. The other part derives from the Indian Panchatantra; this plot came to Europe thanks to La Fontaine’s fables. The author also considers the role of the ant in world mythology; here, despite its size, the ant may possess supernatural qualities and have the ability to cross between the worlds of the living and of the dead, thus actualizing the special theme of the “ant’s journey.” Based on the foregoing analysis as well as research about the place where the folklore text was recorded, the author concludes that the plot about the ant’s journey to Jerusalem did not appear on the territory of Occitania by accident and that it relates to the historical and cultural realities of the area, dating back to the era of the Crusades.
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Abramovskikh, E. V., S. M. Pasashkova, and M. A. Smolenskaya. "G. IVANOV`S POEM «I DO NOT ASK FOR LOVE, I DO NOT SING ABOUT SPRING ...» IN THE CONTEXT OF HISTORICAL POETICS: INTERPRETATION EXPERIENCE." Izvestiya of the Samara Science Centre of the Russian Academy of Sciences. Social, Humanitarian, Medicobiological Sciences 24, no. 84 (2022): 107–14. http://dx.doi.org/10.37313/2413-9645-2022-24-84-107-114.
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The article was written as part of participation of students of the Faculty of Philology of the Samara State Social and Pedagogical University in the II regional methodological theoretical seminar «Theoretical studies»: «Historical poetics», which took place in November 2020 [1]. The interpretation of the poem by Georgy Ivanov is given from the standpoint of works on historical poetics and mythopoetics by A.N. Veselovsky, O.M. Freidenberg, E.M. Meletinsky, S.N. Broitman, Yu.M. Lotman. The authors consider that the thinking of the lyric subject of the poem by Georgy Ivanov is distinguished by neosyncretism, which is implemented in the motives of death and rebirth associated with the natural cycle. The understanding of the fusion of wedding and funeral rites, the antinomy of the real world and the other world, which establish a close connection between them, speaks of «neosyncretism» in the poem. The cumulation which leads to the fact that all sensations received through various channels of perception are collected into one common sense-knowledge is shown in the arrangement of artistic images. This is where the desire to find a common in everything, essential similarity, arising from the experience of unity (syncretism) of the entire surrounding world and all its manifestations that affect a person, who should also be its inseparable part, comes from. The article shows that such unity is also manifested in the subjective sphere: the lyrical «I» and the lyrical «you» are not separated from each other and are not opposed. Their unity is manifested in the metaphysical plane: they are united by the «snowy paradise». It is a paradise because love makes the lyric subject happy, but this paradise is «snowy» because lovers cannot be together. The paper examines in detail the key images of the text in connection with folk culture; the specificity of the genre of the song is noted from the point of view of historical poetics.
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Manabe, A., K. Kadoba, R. Hiwa, M. Shoji, M. Shirakashi, H. Tsuji, K. Kitagori, et al. "AB0782 RISK FACTORS FOR SERIOUS INFECTION IN PATIENTS WITH MICROSCOPIC POLYANGIITIS: RESULTS FROM THE REVEAL COHORT." Annals of the Rheumatic Diseases 82, Suppl 1 (May 30, 2023): 1601.1–1601. http://dx.doi.org/10.1136/annrheumdis-2023-eular.1057.
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BackgroundMany studies have reported risk factors for infection in ANCA-associated vasculitis, but the consistency of these risk factors varies between studies[1-5]. In addition, few reports have focused specifically on patients with microscopic polyangiitis (MPA) or have focused on the impact of glucocorticoids (GC) reduction on the risk of infection.ObjectivesIn this study, we aimed to examine risk factors of serious infections (SI) in patients with MPA in the REVEAL cohort, a Japanese multicenter cohort. As one of the risk factors, we also focused on the pace of GC reduction.Methods181 MPA patients hospitalized for induction therapy and followed for at least three months were recruited from the REVEAL cohort. We evaluated the demographic, clinical, and laboratory findings, and treatments. To assess the pace of GC reduction, GC doses at 3, 12, and 24 months were extracted, and the ratio of each to the initial dose was calculated. Univariate analysis and COX regression analysis were performed to identify risk factors for SI, defined as infections requiring hospitalization in these patients. Gray test was performed for the comparison of the cumulative incidence of SI between groups.ResultsThere were 115 patients without SI and 66 patients with SI. Univariate analysis showed that age, smoking index, CRP, and GC dose ratio (3 months/initial dose) were associated with SI. In the COX regression analysis (shown in Table 1), age, CRP, and GC dose ratio (3 months/initial dose) were identified as significant risk factors (p values are <0.005, <0.005, and 0.04, respectively). In addition, the group with GC dose ratio (3 months/initial dose) ≥ 0.4 had significantly higher cumulative incidence of SI than the other group (p=0.032) (shown in Figure 1).ConclusionAge, CRP, and GC dose ratio (3 months/initial dose) were identified as risk factors for SI in MPA patients.References[1]Lai QY, Ma TT, Li ZY, et al. Predictors for mortality in patients with antineutrophil cytoplasmic autoantibody-associated vasculitis: a study of 398 Chinese patients. J Rheumatol. 2014;41:1849–55.[2]Little MA, Nightingale P, Verburgh CA, et al. Early mortality in systemic vasculitis: relative contribution of adverse events and active vasculitis. Ann Rheum Dis. 2010;69:1036–43.[3]Mohammad AJ, Segelmark M, Smith R, et al. Severe Infection in Antineutrophil Cytoplasmic Antibody-associated Vasculitis. J Rheumatol. 2017;44:1468–75.[4]Yoo J, Jung SM, Song JJ, et al. Birmingham vasculitis activity and chest manifestation at diagnosis can predict hospitalised infection in ANCA-associated vasculitis. Clin Rheumatol. 2018;37:2133–41.[5]Yang L, Xie H, Liu Z, et al. Risk factors for infectious complications of ANCA-associated vasculitis: a cohort study. BMC Nephrol. 2018;19:138.Table 1Odds ratio [95% CI]p valueAge (years)1.08 [1.04-1.12]<0.005Sex (Female)0.57 [0.30-1.07]0.08Smoking index1.00 [1.00-1.00]0.26CRP1.08 [1.03-1.13]<0.005GC dose ratio (3 months/initial dose)6.53 [1.08-39.52]0.04Figure 1AcknowledgementsNone.Disclosure of InterestsAtsushi Manabe: None declared, Keiichiro Kadoba: None declared, Ryosuke Hiwa: None declared, Mikihito Shoji: None declared, Mirei Shirakashi: None declared, Hideaki Tsuji: None declared, Koji Kitagori: None declared, Syuji Akizuki Grant/research support from: Asahi Kasei, Ran Nakashima Speakers bureau: Astellas, Boehringer Ingelheim, Asahi Kasei, Japan Blood Products Organization, Nihon Pharmaceutical, Grant/research support from: Boehringer Ingelheim, Medical & Biological Laboratories Co., Ltd., Hajime Yoshifuji: None declared, Wataru Yamamoto: None declared, Ayana Okazaki: None declared, Shogo Matsuda Speakers bureau: Abbvie, Takuya Kotani Speakers bureau: Abbvie, Bristol Myers Squibb, Chugai, Eisai, Eli Lilly, Pfizer, Takaho Gon: None declared, Ryu Watanabe Speakers bureau: Asahi Kasei, Eli Lilly, Chugai, GSK, Sanofi, Grant/research support from: AbbVie, Motomu Hashimoto Speakers bureau: Eli Lilly, Chugai, Tanabe-Mitsubishi, Bristol Myers Squibb, Eisai, Grant/research support from: AbbVie, Asahi Kasei, Astellas, Bristol Myers Squibb, Eisai, Daiichi Sankyo, Eli Lilly, Novartis, Akio Morinobu Speakers bureau: Chugai, Eli Lilly, Eisai, Bristol Myers Squibb, Tanabe-Mitsubishi, Astellas, Grant/research support from: Asahi Kasei, Chugai, Tanabe-Mitsubishi, Taisho, Eisai.
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Huang, Huaizhi, Ronan E. Couch, Holly LaDuca, Siddhartha Yadav, Eric C. Polley, Nicholas J. Boddicker, Jie Na, et al. "Abstract A003: Risks of ductal carcinoma in situ of the breast associated with pathogenic variants in cancer predisposition genes." Cancer Prevention Research 15, no. 12_Supplement_1 (December 1, 2022): A003. http://dx.doi.org/10.1158/1940-6215.dcis22-a003.
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Abstract Introduction: The relationship between germline pathogenic variants (PVs) in cancer predisposition genes and ductal carcinoma in situ (DCIS) is not well established. The objective of this study is to determine the risks of DCIS and contralateral breast cancer among women with DCIS associated with germline PVs in cancer predisposition genes. Methods: Associations between pathogenic variants in 11 cancer predisposition genes (ATM, BARD1, BRCA1, BRCA2, BRIP1, CDH1, CHEK2, MSH6, PALB2, RAD51C, and RAD51D) and DCIS were determined in case control analyses of a population-based cohort of 3876 women with DCIS and age-matched unaffected women, and in a clinical cohort of 9887 DCIS cases undergoing clinical genetic testing at Ambry Genetics and unaffected reference controls. The incidence of contralateral breast cancer risk in BRCA1, BRCA2, and PALB2 PV carriers with DCIS was also evaluated in a time-to-event analysis. Results: The mean age at diagnosis of DCIS was 50 years in the clinical testing cohort and 59 years in the population-based cohort. The frequency of PVs in 11 predisposition genes among DCIS cases was 6.9% in the clinical testing cohort and 4.9% in the population-based cohort. PVs in ATM, BRCA1, BRCA2, CHEK2, MSH6, PALB2, and RAD51D were associated with significantly increased risks (Odds Ratio (OR) >2) of DCIS in the clinical testing cohort whereas only PVs in BRCA1, CHEK2, PALB2, and ATM were associated with significantly increased risks of DCIS in the population-based cohort. The cumulative incidence of contralateral breast cancer among BRCA1, BRCA2, and PALB2 PV carriers with DCIS was 11% in 5-years and 20% in 15-years. Conclusions: This study provides new insights into PVs that predispose to DCIS. In addition, it establishes an increased risk of contralateral breast cancer risk among women with DCIS who are carriers of PVs in BRCA1, BRCA2, or PALB2. These findings will guide surveillance and risk reducing strategies in germline PV carriers with DCIS. Citation Format: Huaizhi Huang, Ronan E. Couch, Holly LaDuca, Siddhartha Yadav, Eric C. Polley, Nicholas J. Boddicker, Jie Na, Rohan D. Gnanaolivu, David E. Goldgar, Tina Pesaran, Steven N. Hart, Jill S. Dolinsky, Julie R. Palmer, Lauren Teras, Alpa V. Patel, Kathryn J. Ruddy, Janet E. Olson, Celine M. Vachon, Peter Kraft, Song Yao, Amy Trentham-Dietz, Katherine L. Nathanson, Jeffrey N. Weitzel, Susan M. Domchek, Fergus J. Couch, Chunling Hu. Risks of ductal carcinoma in situ of the breast associated with pathogenic variants in cancer predisposition genes [abstract]. In: Proceedings of the AACR Special Conference on Rethinking DCIS: An Opportunity for Prevention?; 2022 Sep 8-11; Philadelphia, PA. Philadelphia (PA): AACR; Can Prev Res 2022;15(12 Suppl_1): Abstract nr A003.
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Plascak, Jesse J., Kellie Archer, Adana A. Llanos, Stephen J. Mooney, Cathleen Y. Xing, Andrew G. Rundle, Helmut Zarbl, et al. "Abstract 6128: Association between neighborhood disinvestment and all-cause survival moderated by epigenetic age among women with breast cancer." Cancer Research 84, no. 6_Supplement (March 22, 2024): 6128. http://dx.doi.org/10.1158/1538-7445.am2024-6128.
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Abstract Background: DNA methylation is hypothesized to mediate relationships between chronic social disadvantage and cancer outcomes. We investigated whether epigenetic age acceleration mediates the association between modifiable neighborhood disinvestment and survival within a cohort of women with breast cancer. Methods: Individual-level data were from the Women’s Circle of Health Follow-up Study, a breast cancer cohort comprising women self-identifying as African American or Black, diagnosed 2013-2019 in New Jersey residents. Demographic, socioeconomic, health behavior, and dietary characteristics were self-reported. Peripheral blood samples from 312 participants collected 18-24 months after diagnosis were profiled for DNA methylation using Illumina’s MethylationEPIC array. After pre-processing, pace of biological aging was estimated using DunedinPACE. Neighborhood disinvestment was assessed using a previously validated virtual audit of 6 disinvestment indicators - garbage, graffiti, dumpsters, poor building conditions, poor yard conditions, abandoned buildings - in 14,671 Google Streetview streetscapes. Accelerated failure time models of all-cause mortality as functions of neighborhood disinvestment and pace of biologic aging were fit to estimate survival time ratios (TR), adjusted for stage at diagnosis and neighborhood socioeconomic composition using causal mediation analyses. End of follow-up was August 13, 2023. Results: There were 46 all-cause deaths through follow-up (median=6.9 years), and 5-year overall survival probability was 0.90 (95% CI: 0.86, 0.93). Minimum, median, and maximum pace of biologic aging was 0.87, 1.26, and 1.72 indicating accelerated aging (> 1.0) among most participants. There was no evidence for mediation of the neighborhood disinvestment - survival effect by pace of biologic aging (indirect effect p-value=0.33). There was evidence of an interaction between pace of biologic aging and neighborhood disinvestment in the adjusted model: survival time decreased 37% (95% CI: 4% - 59%, p=0.03) per 1 standard deviation (SD) increase in neighborhood disinvestment at pace of biologic aging values 1 SD below the average (< 1.13). There was no evidence of such association at pace of biologic aging values 1 SD above the average (p=0.86). Conclusion: Greater neighborhood disinvestment may be associated with shorter survival following a breast cancer diagnosis among those with slower than average epigenetic age acceleration, due to the cumulative nature of neighborhood disinvestment as a chronic indicator of social disadvantage. Citation Format: Jesse J. Plascak, Kellie Archer, Adana A. Llanos, Stephen J. Mooney, Cathleen Y. Xing, Andrew G. Rundle, Helmut Zarbl, B Qin, Nur Zeinomar, Mario Schootman, Song Yao, Christine Ambrosone, Karen Pawlish, Kitaw Demissie, Elisa V. Bandera, Chi-Chen Hong. Association between neighborhood disinvestment and all-cause survival moderated by epigenetic age among women with breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6128.
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Wang, Junxiao, Yushuai Yu, Jie Zhang, and Chuangui Song. "Abstract PO2-04-07: Efficacy and Safety of First-line Therapy in Patients with HER-2 positive Advanced Breast Cancer:A network Meta-analysis of Randomized Controlled Trials." Cancer Research 84, no. 9_Supplement (May 2, 2024): PO2–04–07—PO2–04–07. http://dx.doi.org/10.1158/1538-7445.sabcs23-po2-04-07.
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Abstract Background: The numerous but conflicting first-line treatment regimens for Her-2 positive advanced breast cancer necessitate a comprehensive evaluation to inform clinical decision-making. In this study, we conducted a Bayesian network meta-analysis (NMA) to compare the efficacy and safety of different interventions. Methods: We systematically searched for relevant randomized controlled trials (RCTs) in Pubmed, Embase, Cochrane Library and online abstracts published by ASCO, SABCS. NMA was performed using R software, STATA and Review Manager 5.4 to calculate and analyze the primary endpoint progression free survival (PFS), as well as the secondary endpoints of overall survival (OS), objective response rate (ORR) and adverse events (AE) higher than grade 3. Results: Out of the 8,603 manuscripts retrieved, we included 30 RCTs involving 12,045 patients in our analysis. Regarding PFS, the combination of trastuzumab with TKI was more favorable than dual-target therapy (hazard ratio=0.54, 95% [CI]: 0.40–0.72), and combination chemotherapy was superior to monotherapy (HR=0.66, 0.53-0.83). It is important to note that the addition of anthracycline did not result in improved PFS (HR=1.27, 0.87-1.86). For the HR+HER2+ population, dual-target plus endocrine therapy was more effective than single-target plus endocrine therapy (HR=0.65, 0.53-0.80). Monotherapy combined with dual-target therapy significantly improved OS and ORR compared to monotherapy with single-target therapy (HR=0.69, 0.56-0.84; OR=1.89, 1.34-2.65). A comprehensive analysis of both PFS and AE higher than grade 3 indicated that monotherapy plus dual-target therapy struck a balanced approach between effectiveness and toxicity compared to other regimens. Conclusions: Monotherapy plus dual-target therapy remains the optimal choice among all first-line treatment options for advanced breast cancer. The combination of trastuzumab with TKI demonstrated a significant improvement in PFS, but further data are warranted to confirm the survival benefit. Figure 1. Network diagrams of PFS, OS, ORR and adverse events higher than grade 3 in eligible experimental arms. Figure 2. Forest plot of PFS, OS, ORR and adverse events higher than grade 3 in eligible experimental arms. (A): PFS of HER2+ for experimental arms. (B): PFS of HR+ and HER2+ for experimental arms. (C): OS of HER2+ for experimental arms. (D): ORR of HER2+ for experimental arms. (E): Adverse events higher than grade 3 of HER2+ for experimental arms. Figure 3. Each endpoint ranking for experimental arms. (SUCRA, surface under the cumulative ranking) (A): PFS ranking for experimental arms. (B): OS ranking for experimental arms. (C): ORR ranking for experimental arms. (D): Adverse events higher than grade 3 ranking for experimental arms. (E): Experimental arms ordered by their overall probability as the best treatment in terms of both efficacy and safety Citation Format: Junxiao Wang, Yushuai Yu, Jie Zhang, Chuangui Song. Efficacy and Safety of First-line Therapy in Patients with HER-2 positive Advanced Breast Cancer:A network Meta-analysis of Randomized Controlled Trials [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-04-07.
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Van Vollenhoven, R., A. Rubbert-Roth, S. Hall, R. Xavier, A. Shmagel, Y. Song, S. Anyanwu, and V. Strand. "POS0693 IMPACT OF UPADACITINIB VERSUS ABATACEPT ON INDIVIDUAL DISEASE OUTCOMES IN PATIENTS WITH RHEUMATOID ARTHRITIS AND INADEQUATE RESPONSES TO BIOLOGIC DMARDS." Annals of the Rheumatic Diseases 81, Suppl 1 (May 23, 2022): 626.1–626. http://dx.doi.org/10.1136/annrheumdis-2022-eular.2536.
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BackgroundThe phase 3 SELECT-CHOICE trial of patients with rheumatoid arthritis (RA) and prior inadequate response to biologic DMARD(s) (bDMARD-IR) demonstrated superiority of the JAK inhibitor upadacitinib (UPA) vs abatacept (ABA) in the mean change from baseline (BL) in DAS28(CRP) and in the proportion achieving DAS28(CRP) <2.6 at week (wk) 12, with higher incidence of serious adverse events reported in the UPA treatment group.ObjectivesTo evaluate the impact of UPA vs ABA on individual components of composite measures of disease activity in SELECT-CHOICE.MethodsIn SELECT-CHOICE, a double-blind phase 3 trial, bDMARD-IR patients were randomly assigned to UPA 15 mg once daily or ABA, each with background conventional synthetic DMARDs, for 24 wks. For this post hoc analysis, the proportions of patients achieving improvement from BL through wk 24 in ACR core variables (including SJC, TJC, Patient Global Assessment [PtGA], Physician Global Assessment [PhGA], pain, HAQ-DI, and hsCRP) and Boolean remission criteria were evaluated. Differences in the cumulative distributions of CDAI, DAS28(hsCRP), SDAI, and ACR-n (the lowest of percent change in TJC, percent change in SJC, or median of the other 5 ACR components) were determined using the Kolmogorov-Smirnov test and are reported as observed. For all other variables, non-responder imputation was applied for missing data. Nominal P values are provided throughout.ResultsA total of 616 bDMARD-IR patients with moderate to severe RA were randomized in SELECT-CHOICE (UPA 15 mg, n=303; ABA, n=309). BL demographic and disease characteristics were generally comparable between treatment groups, with a mean disease duration of approximately 12 years and mean CDAI of 39.6. At wk 12, more patients receiving UPA vs ABA achieved ≥50% improvements from BL in TJC68, PtGA, and hsCRP, with comparable proportions observed between UPA and ABA for the remaining ACR components (Figure 1). At wk 24, similar proportions of patients receiving UPA and ABA achieved ≥50% improvements in all but the hsCRP component. Overall, 15% and 26% of patients on UPA compared with 6% and 15% on ABA demonstrated ≥50% improvements across all ACR components at wks 12 and 24, respectively. At wks 12 and 24, Boolean remission was achieved by 6% and 14% of patients on UPA vs 2% and 10% of patients on ABA, respectively; the proportion of patients in both treatment groups achieving the individual Boolean components were also reported (Table 1). While comparable at BL, cumulative distributions of CDAI, SDAI, DAS28(hsCRP), and ACR-n were improved on UPA vs ABA at wk 12 (all nominal P <0.05); differences persisted for most measures at wk 24.Table 1.Proportions of Patients Achieving Boolean Remission and Its Components at Week 12 and 24 (NRI)Week 12Week 24n (%)UPA 15 mgABAUPA 15 mgABA(N=303)(N=309)(N=303)(N=309)Boolean Remission19 (6)***5 (2)42 (14)*30 (10) PtGA ≤1054 (18)***29 (9)80 (26)*66 (21) TJC ≤189 (29)***64 (21)134 (44)*115 (37) SJC ≤1127 (42)**106 (34)169 (56)*152 (49) hsCRP ≤1 mg/dL257 (85)***209 (68)244 (81)***199 (64)Nominal ***P <.001, **P <.01, *P <.05 for UPA vs ABA. ABA, abatacept; PtGA, Patient’s Global Assessment of disease severity; UPA, upadacitinib.ConclusionIn this post hoc analysis of bDMARD-IR RA patients, improvements in components of disease measures were reported for both UPA and ABA through 24 weeks, with numeric differences noted for several components. Nominally higher attainment of Boolean remission and its components were observed for UPA over ABA.References[1]Rubbert-Roth A, et al. N Engl J Med 2020; 383:1511-21.AcknowledgementsAbbVie and the authors thank the patients, study sites, and investigators who participated in these clinical trials. AbbVie funded these studies and participated in the study design, research, analysis, data collection, interpretation of data, reviewing, and approval of the publication. All authors had access to relevant data and participated in the drafting, review, and approval of this publication. No honoraria or payments were made for authorship. Medical writing support was provided by Matthew Eckwahl, PhD, of AbbVie.Disclosure of InterestsRonald van Vollenhoven Speakers bureau: AbbVie, Galapagos, GSK, Janssen, Pfizer, R-Pharma, UCB, Consultant of: AbbVie, AstraZeneca, Biogen, BMS, Galapagos, Janssen, Miltenyi, Pfizer, UCB, Grant/research support from: Research: BMS, GSK, UCB; Educational programs: MSD, Pfizer, Roche, Andrea Rubbert-Roth Speakers bureau: AbbVie, Pfizer, Sanofi, UCB, BMS, Lilly, Gilead, Roche, Consultant of: AbbVie, Gilead, Lilly, BMS, Sanofi, R-Pharm, Stephen Hall Consultant of: AbbVie, BMS, Lilly, Janssen, Pfizer, UCB, Novartis, Grant/research support from: AbbVie, BMS, Lilly, Janssen, Pfizer, UCB, Novartis, Ricardo Xavier Consultant of: AbbVie, Amgen, BMS, Lilly, Janssen, Novartis, Pfizer, UCB, Anna Shmagel Shareholder of: AbbVie, Employee of: AbbVie, Yanna Song Shareholder of: AbbVie, Employee of: AbbVie, Samuel Anyanwu Shareholder of: AbbVie, Employee of: AbbVie, Vibeke Strand Consultant of: AbbVie, Amgen, Arena, AstraZeneca, Bayer, BMS, Boehringer Ingelheim, Chemocentryx, BMS, Celltrion, Lilly, Genentech/Roche, Gilead, GlaxoSmithKline, Ichnos, Inmedix, Janssen, Kiniksa, Lilly, Merck, Myriad Genetics, Novartis, Pfizer, Regeneron Pharmaceuticals, Rheos, R-Pharma, Samsung, Sandoz, Sanofi, Scipher, Setpoint, Sorrento, Spherix, UCB
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Fleischmann, R., I. H. Song, J. Enejosa, E. Mysler, L. Bessette, P. Durez, A. Ostor, J. Swierkot, Y. Song, and M. C. Genovese. "THU0201 LONG-TERM SAFETY AND EFFECTIVENESS OF UPADACITINIB OR ADALIMUMAB IN PATIENTS WITH RHEUMATOID ARTHRITIS: RESULTS AT 72 WEEKS FROM THE SELECT-COMPARE STUDY." Annals of the Rheumatic Diseases 79, Suppl 1 (June 2020): 323. http://dx.doi.org/10.1136/annrheumdis-2020-eular.1418.
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Background:In the SELECT-COMPARE study in rheumatoid arthritis (RA) patients with inadequate response to methotrexate (MTX), upadacitinib (UPA), a Janus Kinase (JAK) 1-selective inhibitor, showed significant improvements in treatment of signs and symptoms when compared to placebo (PBO) and adalimumab (ADA) up to 48 weeks.1Objectives:To report safety and efficacy of UPA vs ADA up to 72 weeks in patients with RA from the ongoing long-term extension (LTE) of SELECT-COMPARE.Methods:Patients were randomized to once daily (QD) UPA 15 mg, PBO, or ADA 40 mg every other week, with all patients continuing background MTX. The study was double-blind for 48 weeks. Between Weeks 14-26, patients were rescued (from PBO to UPA, UPA to ADA, or ADA to UPA) if there was <20% improvement in tender/swollen joint count at Weeks 14/18/22 or if Clinical Disease Activity Index (CDAI) was >10 at Week 26; all PBO patients who were not rescued were switched to UPA at Week 26. Patients continued UPA or ADA in a blinded manner until the last patient completed the Week 48 visit; patients received open-label treatment thereafter. Study visits occurred at Week 60, 72, and every 12 weeks thereafter. Treatment-emergent adverse events (TEAEs) per 100 patient years (PY) were summarized up to December 26, 2018. Efficacy was analyzed by randomized group.Results:In total, 651, 651 and 327 patients were randomized at baseline to receive UPA, PBO, and ADA, respectively. Subsequently, 252 patients were switched from UPA to ADA, 159 were switched from ADA to UPA, and all PBO patients were switched to UPA. 1403 patients entered the LTE at Week 48 (UPA: 1091 [565 switched from PBO; 66 rescued from ADA; 460 on continued UPA]; ADA: 312 [110 rescued from UPA; 202 on continued ADA]). The cumulative exposures were 1396.7 and 515.1 PYs for UPA and ADA, respectively. UPA + MTX was generally well-tolerated as assessed by the frequency of AEs, including serious AEs, AEs leading to discontinuation of study drug, and AEs of special interest ([AESIs] including serious and opportunistic infections, malignancy, adjudicated major adverse cardiac events or venous thromboembolism; Figure 1). The event rates of AESIs were generally comparable between UPA + MTX and ADA + MTX, except for herpes zoster, lymphopenia, hepatic disorder, and CPK elevation, which were numerically higher with UPA + MTX. At both Weeks 60 and 72, significantly greater proportions of patient receiving UPA + MTX achieved ACR20/50/70 (P ≤.01/.001/.001), low disease activity (P ≤.001) and remission (P ≤.001) compared to those receiving ADA + MTX; Figure 2). Similarly, improvements in pain and function were significantly greater in the UPA vs ADA group through Week 72 (P ≤.01).Conclusion:The safety profile for UPA + MTX was consistent with that reported previously and with the integrated Phase 3 safety analysis.1,2UPA + MTX maintained significantly higher levels of clinical response, including remission compared to ADA + MTX through Week 72.References:[1]Fleischmann R, et al.Annals of the Rheumatic Diseases.2019;78:744-745.[2]Cohen SB, et al. Thu0167.Annals of the Rheumatic Diseases. 2019;78:357.Disclosure of Interests: :Roy Fleischmann Grant/research support from: AbbVie, Akros, Amgen, AstraZeneca, Bristol-Myers Squibb, Boehringer, IngelhCentrexion, Eli Lilly, EMD Serono, Genentech, Gilead, Janssen, Merck, Nektar, Novartis, Pfizer, Regeneron Pharmaceuticals, Inc., Roche, Samsung, Sandoz, Sanofi Genzyme, Selecta, Taiho, UCB, Consultant of: AbbVie, ACEA, Amgen, Bristol-Myers Squibb, Eli Lilly, Gilead, GlaxoSmithKline, Novartis, Pfizer, Sanofi Genzyme, UCB, In-Ho Song Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., Jeffrey Enejosa Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., Eduardo Mysler Grant/research support from: AbbVie, Amgen, Bristol Myers Squibb, Roche, Eli Lilly, Novartis, Janssen, Sanofi, and Pfizer., Speakers bureau: AbbVie, Amgen, Bristol Myers Squibb, Roche, Eli Lilly, Novartis, Janssen, Sanofi, and Pfizer, Louis Bessette Grant/research support from: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Merck, Novartis, Pfizer, Roche, Sanofi, UCB Pharma, Consultant of: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Merck, Novartis, Pfizer, Roche, Sanofi, UCB Pharma, Speakers bureau: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Merck, Novartis, Pfizer, Sanofi, Patrick Durez Speakers bureau: AbbVie, Bristol-Myers Squibb, Celltrion, Eli Lilly, Pfizer, Sanofi, Andrew Ostor Consultant of: MSD, Pfizer, Lilly, Abbvie, Novartis, Roche, Gilead and BMS, Speakers bureau: MSD, Pfizer, Lilly, Abbvie, Novartis, Roche, Gilead and BMS, Jerzy Swierkot Grant/research support from: AbbVie, Sandoz, Pfizer, Roche, BMS, UCB, MSD, Accord, Janssen, Consultant of: AbbVie, Sandoz, Pfizer, Roche, BMS, UCB, MSD, Accord, Janssen, Speakers bureau: AbbVie, Sandoz, Pfizer, Roche, BMS, UCB, MSD, Accord, Janssen, Yanna Song Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., Mark C. Genovese Grant/research support from: Abbvie, Eli Lilly and Company, EMD Merck Serono, Galapagos, Genentech/Roche, Gilead Sciences, Inc., GSK, Novartis, Pfizer Inc., RPharm, Sanofi Genzyme, Consultant of: Abbvie, Eli Lilly and Company, EMD Merck Serono, Genentech/Roche, Gilead Sciences, Inc., GSK, Novartis, RPharm, Sanofi Genzyme
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Toye, Fran, Kate Seers, and Karen Barker. "A meta-ethnography of health-care professionals’ experience of treating adults with chronic non-malignant pain to improve the experience and quality of health care." Health Services and Delivery Research 6, no. 17 (April 2018): 1–106. http://dx.doi.org/10.3310/hsdr06170.
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BackgroundPeople with chronic pain do not always feel that they are being listened to or valued by health-care professionals (HCPs). We aimed to understand and improve this experience by finding out what HCPs feel about providing health care to people with chronic non-malignant pain. We did this by bringing together the published qualitative research.Objectives(1) To undertake a qualitative evidence synthesis (QES) to increase our understanding of what it is like for HCPs to provide health care to people with chronic non-malignant pain; (2) to make our findings easily available and accessible through a short film; and (3) to contribute to the development of methods for QESs.DesignWe used the methods of meta-ethnography, which involve identifying concepts and progressively abstracting these concepts into a line of argument.Data sourcesWe searched five electronic bibliographic databases (MEDLINE, EMBASE, Cumulative Index to Nursing and Allied Health Literature, PsycINFO and Allied and Complementary Medicine Database) from inception to November 2016. We included studies that explored HCPs’ experiences of providing health care to people with chronic non-malignant pain. We utilised the Grading of Recommendations Assessment, Development and Evaluation Confidence in the Evidence from Reviews of Qualitative research (GRADE-CERQual) framework to rate our confidence in the findings.ResultsWe screened 954 abstracts and 184 full texts and included 77 studies reporting the experiences of > 1551 HCPs. We identified six themes: (1) a sceptical cultural lens and the siren song of diagnosis; (2) navigating juxtaposed models of medicine; (3) navigating the patient–clinician borderland; (4) the challenge of dual advocacy; (5) personal costs; and (6) the craft of pain management. We produced a short film, ‘Struggling to support people to live a valued life with chronic pain’, which presents these themes (seeReport Supplementary Material 1; URL:www.journalslibrary.nihr.ac.uk/programmes/hsdr/1419807/#/documentation; accessed 24 July 2017). We rated our confidence in the review findings using the GRADE-CERQual domains. We developed a conceptual model to explain the complexity of providing health care to people with chronic non-malignant pain. The innovation of this model is to propose a series of tensions that are integral to the experience: a dualistic biomedical model compared with an embodied psychosocial model; professional distance compared with proximity; professional expertise compared with patient empowerment; the need to make concessions to maintain therapeutic relationships compared with the need for evidence-based utility; and patient advocacy compared with health-care system advocacy.LimitationsThere are no agreed methods for determining confidence in QESs.ConclusionsWe highlight areas that help us to understand why the experience of health care can be difficult for patients and HCPs. Importantly, HCPs can find it challenging if they are unable to find a diagnosis and at times this can make them feel sceptical. The findings suggest that HCPs find it difficult to balance their dual role of maintaining a good relationship with the patient and representing the health-care system. The ability to support patients to live a valued life with pain is described as a craft learnt through experience. Finally, like their patients, HCPs can experience a sense of loss because they cannot solve the problem of pain.Future workFuture work to explore the usefulness of the conceptual model and film in clinical education would add value to this study. There is limited primary research that explores HCPs’ experiences with chronic non-malignant pain in diverse ethnic groups, in gender-specific contexts and in older people living in the community.FundingThe National Institute for Health Research Health Services and Delivery Research programme.
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Chen, Cheng, Qian Dong, Qin Na, Nan Song, John Easton, Heather L. Mulder, Emily Walker, et al. "Abstract 4363: Monocyte-specific epigenetic age acceleration and cardiomyopathy risk among survivors of childhood cancer." Cancer Research 83, no. 7_Supplement (April 4, 2023): 4363. http://dx.doi.org/10.1158/1538-7445.am2023-4363.
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Abstract Our assessment of epigenetic age acceleration (EAA), calculated with DNA methylation (DNAm) data generated from bulk DNA derived from peripheral blood mononuclear cells (PBMC), supports accelerated aging in childhood cancer survivors (CCS). It is challenging to disentangle variation of DNAm at cell-type specific levels from the effects of age-dependent cell type composition, and bulk measurements may obfuscate the links between EAA and age-related outcomes (e.g., cardiomyopathy). Methylation profiling was generated using Infinium EPIC BeadChips on PBMC-derived DNA from CCS in the St. Jude Lifetime Cohort. Tensor composition analysis was employed to deconvolute bulk DNAm and infer DNAm at each leukocyte subtype level, i.e., a single n (individuals) by m (DNAm sites) matrix of observed DNAm data was deconvoluted into multiple n by m matrices of DNAm data. Epigenetic age (EA, using Levine’s clock) and EAA (residuals from the fit of a simple linear regression of EA on chronological age at blood draw) were calculated for bulk PBMCs and each cell subtype (CD4T, CD8T, B, natural killer, and monocyte). Cardiomyopathy (CMP) was assessed by echocardiography, and severity graded (2 = moderate, 3 = severe/disabling, 4 = life-threatening and 5 = fatal) using a modified version of the National Cancer Institute Common Terminology Criteria for Adverse Events. Cumulative doses of anthracyclines and mean heart radiation doses (heart-RT) calculated through radiation dosimetry were abstracted from medical records. Associations between EAA and CMP were evaluated by multivariable Cox regression. Cell-type specific EA was highly correlated with bulk EA with Pearson r2 between 0.63 (CD8T) and 0.79 (CD4T), but the linear regression lines of cell-type specific EA against bulk EA differed in both intercept and slope, suggesting heterogeneity across leukocyte subtypes. Cell-type specific EAA was moderately correlated with bulk EAA with Pearson r2 between 0.23 (monocyte) and 0.29 (CD8T). Among 2,044 CCS (median age = 33.7 years), 104 (5.1%) developed CMP (≥grade 3). Among bulk EAA and five cell-type specific EAAs, monocyte EAA was the only one significantly associated with CMP (hazard ratio per standard deviation increase in EAA = 1.25, 95% CI = 1.04-1.50, P = 0.018). Cell sorting of PBMC followed by DNAm is currently underway for further validation. We showed an in-depth view of the variability of EAA across leukocyte subtypes, and more importantly, demonstrated that monocyte EAA was associated with CMP risk. Our novel finding is plausible and consistent with the literature implicating monocyte-derived cardiac macrophages in cardiac remodeling, which can be induced by cardiotoxic cancer treatment exposures in CCS. Therapeutic strategies that prevent deleterious effects of monocytes contributing to adverse cardiac remodeling, while sparing their essential immune functions, may prevent or ameliorate CMP among CCS. Citation Format: Cheng Chen, Qian Dong, Qin Na, Nan Song, John Easton, Heather L. Mulder, Emily Walker, Geoffrey Neale, Emily R. Finch, Qian Li, Yutaka Yasui, Daniel A. Mulrooney, Melissa M. Hudson, Kirsten K. Ness, Jinghui Zhang, Xiang Chen, Hui Wang, Leslie L. Robison, Zhaoming Wang. Monocyte-specific epigenetic age acceleration and cardiomyopathy risk among survivors of childhood cancer. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4363.
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Plonski, Noel-Marie, Cheng Chen, Qian Dong, Na Qin, Nan Song, John Easton, Heather Mulder, et al. "Abstract 3503: Racial disparity and roles of social determinants of health in epigenetic age acceleration among survivors of childhood cancer." Cancer Research 83, no. 7_Supplement (April 4, 2023): 3503. http://dx.doi.org/10.1158/1538-7445.am2023-3503.
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Abstract Our published studies demonstrated that epigenetic age acceleration (EAA) is significantly higher in childhood cancer survivors than non-cancer controls. Additionally, EAA is associated with germline genetics, cancer treatments, unfavorable health behaviors, and chronic health conditions. However, our previous studies were limited to non-Hispanic whites (NHW). We aimed to investigate and compare the EAA between non-Hispanic blacks (NHB) and NHW, and evaluate the contribution of social determinants of health (SDOH) to potential racial disparity in EAA. Methylation profiling was generated using Infinium EPIC BeadChips on blood derived DNA from 460 NHB and 2,052 NHW from the St. Jude Lifetime Cohort. EAA was estimated as the residual from the fit of a simple linear regression of epigenetic age (EA, using Levine’s clock) on chronological age (CA, i.e., age at DNA sampling). Cumulative doses of chemotherapy and region-specific radiation exposures were abstracted from medical records. Educational attainment was categorized into 3 levels (< high school, high school, ≥ college). Personal income was categorized into 3 levels (none, < $40,000 and ≥ $40,000). For socioeconomic area deprivation index (ADI), we considered >75th percentile, 40th to 75th percentile, and <40th percentile as high, moderate, and low deprivation, respectively. Multivariable linear regression evaluated associations of EAA with race and SDOH adjusting for sex and cancer treatments. Mediation analysis treated SDOH as mediators, EAA as an outcome, and race as an exposure. The Pearson r between EA and CA was 0.85 and 0.58, and the age slope of EA (i.e., annual change rate of EA) was 1.21 and 0.91, for NHW and NHB, respectively. EAA was much higher in NHB (mean, 5.31; sd, 7.21) than NHW (mean, -1.19; sd, 12.48) with significance in a multivariable regression model adjusting for sex and cancer treatment (NHB vs. NHW: β = 1.90, P = 9.24×10-5). EAA was also associated with educational attainment (high school vs. <high school: β = -2.84, P = 3.22×10-5; college vs. <high school: β = -3.75, P = 2.03×10-7) and ADI (moderate vs. low: β= 1.07, P = 0.026; high vs. low: β = 1.58, P = 2.26×10-3), but not personal income. Notably, after adjusting for SDOH, the association between EAA and race was moderately attenuated (β = 1.50, P = 8.37×10-3). Both educational attainment (15.5%) and ADI (21.4%) mediated the association between race and EAA. We found racial disparity in EAA, with both personal and geographic SDOH as mediators of the association between race and EAA. These data indicate that changes in the social support system at both a personal and community level are needed to reduce socioeconomic disadvantage (e.g., lower education and poor living conditions) and hence the biological aging trajectory. In addition, moderate correlation between EA and CA among NHB suggests that further refined measurement of EA for NHB survivors is needed. Citation Format: Noel-Marie Plonski, Cheng Chen, Qian Dong, Na Qin, Nan Song, John Easton, Heather Mulder, Emily Walker, Geoffrey Neale, Jinghui Zhang, Kevin Krull, Kirsten K. Ness, Melissa M. Hudson, Leslie L. Robison, I-Chan Huang, Zhaoming Wang. Racial disparity and roles of social determinants of health in epigenetic age acceleration among survivors of childhood cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3503.
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Ailioaie, L., and C. Ailioaie. "FRI0638-HPR IMPACT OF PARENTAL MIGRATION IN THE CONTEXT OF THE MULTIFACTORIAL ETIOLOGY OF CHRONIC ARTHRITIS IN CHILDHOOD." Annals of the Rheumatic Diseases 79, Suppl 1 (June 2020): 923–24. http://dx.doi.org/10.1136/annrheumdis-2020-eular.6118.
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Background:Migration of Romanians to work abroad began after 1990 with the aim to provide a better income and life for their family. Current studies show that the migration of one parent or both, even when it is temporary, produces negative long-term effects on the health and psychosocial evolution of the children affected. Children and adolescents exposed to chronic stress due to migration, misunderstandings between the parents, alcoholism, violence, divorce of the parents etc., present an increased risk of illness. More and more data from the literature suggest that prolonged stress and depression induces inadequate cortisol along with norepinephrine secretion, increased synthesis of proinflammatory cytokines, which are the basis for autoimmune pathologies, such as chronic arthritis.Objectives:Given the extended phenomenon of migration from Romania and the increase in the cases with autoimmune pathology in children and adolescents, we aimed to evaluate the association between the disorders related to the permanent stress induced by the parental migration abroad and the risk of developing arthritis during childhood.Methods:The study included 201 children and adolescents aged 13.4 ± 3.7 years, who were in evidence of an outpatient health unit, from 2016-2019. These cases were included in a chronic disease registry with the diagnosis of Juvenile Idiopathic Arthritis (JIA), established by a pediatric rheumatologist.For the initial evaluation, we used a questionnaire that included the socio-demographic data. In comparison, we studied 40 healthy children (control group). The family drawing test was used for patients between 5 and 16 years of age to identify possible conflicts with certain family members, to assess the emotional and psychological maturity of the child or adolescent, and to find out if are there any problems at home.Results:At the end of the study, only 181 (90%) of the eligible patients completed the questionnaire and the family drawing test. Demographic data showed that patients from rural areas predominated (71.8%), compared to 28.2% from urban areas.In terms of sex, 52.5% were male, compared to 47.5% female. Family history (mother, father, sister, brother, grandfather, aunt, uncle) of autoimmune disease was encountered in 28.1% of patients, as follows: spondylarthritis in 9.4% cases, rheumatoid arthritis in 8.8% cases, JIA in 3.9% cases and other autoimmune diseases (Systemic Lupus Erythematosus, Scleroderma, Diabetes, Asthma) in 6% cases. Patients from low-income families were in 82.3% of cases. 72.5% of the cases had a prolonged state of stress by migrant parents for working abroad [38.7% only one parent (30% mother) and both parents in 17.7% of cases], divorce in the family in 11.6% of cases, unmarried mother in 2.8% of cases, and a close relative recently deceased in 1.7% of patients.Subcategories of JIA included: polyarticular JIA negative Rheumatoid Factor (RF) in 39.77% of cases, enthesitis-related arthritis in 27.07% of cases, polyarticular JIA positive RF in 14.36% of cases, oligoarticular JIA in 14.9% of cases, systemic JIA in 3.31% of cases and psoriatic JIA in 0.59% of patients.Conclusion:Both the data from the questionnaires, but especially the family drawing tests, suggest that the prolonged state of stress with anxiety, sadness, pain and depression, in combination with starvation, lack of parental love and the genetic predisposition, have contributed to the emergence of chronic arthritis, pathology that is growing more and more in recent years in Romania.References:[1] Dube SR, Fairweather D, Pearson WS, Felitti VJ, Anda RF, Croft JB. Cumulative childhood stress and autoimmune disease in adults. Psychosom Med. 2009; 71:243–250.[2] Song H, Fang F, Tomasson G, et al. Association of stress-related disorders with subsequent autoimmune disease. JAMA, 2018; 319:2388–2400.[3] Vallerand IA, Patten SB, Barnabe C. Depression and the risk of rheumatoid arthritis. Curr Opin Rheumatol. 2019; 31(3):279-284.Disclosure of Interests:None declared
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Aldoss, Ibrahim, Tracey Stiller, Joo Y. Song, Monzr M. al Malki, Haris Ali, Amandeep Salhotra, Samer K. Khaled, et al. "Philadelphia (Ph) Chromosome (BCR-ABL1 fusion) As a Recurrent Genetic Abnormality Among Therapy-Related Acute Leukemia." Blood 128, no. 22 (December 2, 2016): 3974. http://dx.doi.org/10.1182/blood.v128.22.3974.3974.
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Abstract Philadelphia (Ph) chromosome [t(9;22)] was reported as a rare recurrent balanced translocation among therapy-related acute leukemia (N=10, 2%) [Gene Chromosomes Cancer. 2002]. Here, we conducted a retrospective analysis of therapy-related acute leukemia with Ph chromosome (Ph+ t-AL) to better understand this entity. We included cases diagnosed at our institution between 2000 and 2016, excluding patients with CML in blastic phase. We defined Ph+ t-AL as acute lymphoblastic leukemia (ALL) or acute myeloid leukemia (AML) harboring Ph chromosome that developed after prior exposure to cytotoxic therapy (chemotherapy, radiation or both). Of the 330 patients with Ph+ AL, 28 cases (8.4%) met our definition of Ph+ t-AL, including 25 (89%) B-cell ALL, 1 case of T-cell ALL, and 2 cases of AML. The median age at diagnosis was 56 years (range: 29-79), and 64% (N=18) of them were female. Breast cancer was the most common prior malignancy [N=8, 29%], followed by lymphoma [N=6, 21%] and sarcoma [N=4, 14%]. Prior cytotoxic therapy consisted of chemotherapy (32%), radiotherapy (29%) and chemoradiation (39%). Among 20 patients who had prior chemotherapy, 70% had received alkylating agents (i.e., cyclophosphamide, temozolomide), 70% had received topoisomerase II inhibitors (i.e., etoposide, anthracycline), 40% had received antimetabolites, (i.e., methotrexate) and 50% both alkylators and topoisomeraseII inhibitor. The median interval between prior malignancy and Ph+ t-AL diagnosis was 6.8 years (range: 2.5-19.6) and was not different according to prior cytotoxic therapy modality [chemotherapy/radiotherapy vs. either chemotherapy or radiotherapy alone (P = 0.66)]. The median white blood cells count at presentation was 20 x103/µL (range: 1.4-230). Myelodysplastic syndrome preceded one case of AML. Among 22 patients with available standard cytogenetics, 7 (32%) had Ph chromosome as the sole abnormality, while 15 (68%) had an additional cytogenetic abnormality (ACA). Complex (≥ 3 abnormalities) or monosomal karyotypes were observed respectively in 12 and 9 cases. Chromosome 7 abnormality was observed in 6 (27%) cases, including 5 of them with monosomy 7. In 18 patients (ALL = 17; AML = 1) with available molecular study for BCR/ABL1, all were positive for p190 fusion transcript, including 3 patients who carried both p210 and p190 (ALL =2; AML =1). The median time from prior diagnosis to AL onset was not different according to cytogenetics (isolated Ph chromosome vs. complex/monosomy karyotype) (P> 0.99). However, prior exposure to topoisomeraseII inhibitor was more common among patients with isolated Ph chromosome compared to patients with complex/monosomy karyotype (86% vs. 33%, P= 0.02). Tyrosine-kinase inhibitor (TKI) was administered as part of initial induction regimen to all patients except 4 (N= 24, 86%), who received TKI only upon leukemia relapse/progression. Of the 28 patients, 25 (89%) achieved complete remission (CR) with induction, and 17 (61%) patients subsequently underwent alloHCT; of them, 13 (76%) were in CR1. The 2-year overall survival and event-free survival were respectively 48% and 36% for all patients, and 63% and 41% for those who underwent alloHCT, respectively. The 2-year cumulative incidence rates of relapse and non-relapse mortality for transplanted patients were 19% and 25%, respectively. In conclusion, Ph+ chromosome is a recurrent therapy-related chromosomal aberration presenting most often as a B-cell ALL phenotype, and only rarely as T-cell ALL or AML. Ph+ t-AL is associated with high incidence of ACA, including complex and monosomal karyotype as well as chromosome 7 abnormalities, similar to therapy-related myeloid neoplasms. Similar to de novo Ph+ ALL, a high response rate to TKI-based regimen was observed among Ph+ t-AL. Given its therapeutic implication, presence of Ph chromosome should be excluded in all cases of t-AL. Disclosures Song: Seattle Genetics: Consultancy. Ali:Incyte Corporation: Research Funding. Salhotra:Alexion: Consultancy. Snyder:Ariad: Consultancy; Novartis: Consultancy. Stein:Amgen: Consultancy, Research Funding, Speakers Bureau; Seattle Genetics: Research Funding; Stemline Therapeutics: Consultancy, Research Funding; Argios: Research Funding; Celgene: Research Funding. Forman:Mustang Therpapeutics: Other: Construct licensed by City of Hope.
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Gubler, Lorenz, Tym de Wild, Tamas Nemeth, and Thomas Nauser. "Radical Attack and Damage Mitigation in Hydrocarbon-Based Ionomers." ECS Meeting Abstracts MA2023-02, no. 39 (December 22, 2023): 1917. http://dx.doi.org/10.1149/ma2023-02391917mtgabs.
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In an operating polymer electrolyte fuel cell (PEFC) radical intermediates are formed as a result of the interaction of H2 and O2 on the surface of the Pt-based electrocatalyst. Of the various radical intermediates, •OH is of particular concern owing to its high oxidative strength, E°(•OH,H+/H2O) = 2.72 V) [1]. In PFSA ionomers, •OH reacts relatively slowly with the polymer and has a lifetime on the order of microseconds. This leaves sufficient time for additives, such as Ce(III), to scavenge the radicals and thus mitigate radical induced damage of the ionomer. In hydrocarbon-based ionomers containing aromatic units, •OH reacts within nanoseconds with polymer constituents [2]. Radical scavenging can therefore not be effective. In the development of alternative antioxidant strategies for hydrocarbon-based ionomers, it is crucial to elucidate polymer degradation mechanisms triggered by radical attack. In addition to studying the initial reactions of primary radicals, i.e. •OH, it is equally important to characterize the nature of the formed polymer intermediates, their lifetime, stability and reactivity. Sufficiently long-lived intermediates can be repaired by suitable additives, thereby restoring the original ionomer [3]. In the fuel cell, the thus protected membranes show a much lower rate of degradation in an accelerated stress test (AST) at open circuit voltage (OCV) [4]. In this contribution, we provide an overview of methods to study reaction of radicals with small-molecule model compounds and ionomer constituents [5, 6]. The interaction of ionizing radiation (MeV electrons or photons) with water leads to the formation of radicals, such as •OH, at known rates. Water radiolysis can therefore be used to study the kinetics of radical attack and follow-up reactions as a function of pH, electron density of the aromatic ring, and presence of additives. Examples relevant to the acidic conditions in the proton exchange membrane (see Figure, Panel a) as well as the alkaline conditions in an anion exchange membrane (AEM) will be given. Moreover, the use of suitable antioxidants to mitigate degradation through the repair of intermediates will be discussed. Fuel cell tests with hydrocarbon-based membranes containing polymer-bound antioxidants will be shown (see Figure, Panel b) and prospects for long-term stability of non-fluorinated ionomers assessed. Figure caption: a) Analysis of the effect of Ce(III) ions on the extent of degradation of 1 mM of 4-cumenesulfonate (4CS) and 4-(tert-butyl)phenylsulfonate (BPS) at pH 0 (1 M H2SO4) in 1 mM H2O2 upon exposure to a radiolytic dose provided by a 60Co-source of 800 Gy (corresponding to a cumulative amount of •OH of 0.22 mM). ‘Excess degradation’ indicates the difference to the extent of degradation in the absence of Ce(III) and H2O2. Data for BPS from [5]. b) Ohmic resistance of single cells (average of several experiments) with partially fluorinated membrane containing a tethered crown ether with and without Ce(III) metal center during an accelerated stress test. Ion exchange capacity at the end of test was measured to represent remaining membrane state of health. Conditions: open circuit voltage (OCV), H2/O2, 80 °C, 2.5 bara, and 100% R.H. [4]. References: H. A. Schwarz, R. W. Dodson, J. Phys. Chem., 88, 3643 (1984). L. Gubler, W.H. Koppenol, in: The Chemistry of Membranes Used in Fuel Cells: Degradation and Stabilization, S. Schlick (Ed.), 107-138, John Wiley & Sons (2018). T. De Wild, T. Nemeth, T.M. Nolte, T.J. Schmidt, T. Nauser, L. Gubler, J. Electrochem. Soc., 168, 054514 (2021). T. de Wild, T. Nemeth, P. Becker, D. Günther, T. Nauser, T.J. Schmidt, L. Gubler, J. Power Sources 560, 232525 (2023). T. Nemeth, T. de Wild, L. Gubler, T. Nauser, Phys. Chem. Chem. Phys. 24, 2, 895 (2022). T. Nemeth, T. de Wild, L. Gubler, T. Nauser, J. Electrochem. Soc. 169, 054529 (2022). Figure 1
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Lee, S. S., T. H. Kim, W. Park, Y. W. Song, C. H. Suh, S. Kim, and D. Yoo. "POS0911 SIMILAR CLINICAL RESPONSES ACHIEVED WITH LOWER VERSUS STANDARD DOSES OF INFLIXIMAB BIOSIMILAR CT-P13 IN PATIENTS WITH ANKYLOSING SPONDYLITIS: REAL-WORLD RESULTS FROM THE RAAS STUDY." Annals of the Rheumatic Diseases 80, Suppl 1 (May 19, 2021): 716.1–716. http://dx.doi.org/10.1136/annrheumdis-2021-eular.1055.
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Background:CT-P13, an infliximab biosimilar, is effective for treating ankylosing spondylitis (AS) at a dose of 5 mg/kg infused once every 6–8 weeks. Evidence suggests that patients with AS may benefit from a lower dose, and individualised dose/interval adjustments should be based on treatment response.Objectives:To analyse real-world treatment patterns (doses and infusion intervals) and outcomes for CT-P13-treated patients with AS over 5 years.Methods:The RAAS study collected medical record data for adults with AS treated with CT-P13 at five referral hospitals in the Republic of Korea (2012–2017). Patients were infliximab naïve at CT-P13 initiation (‘naïve’) or had switched to CT-P13 from reference infliximab (‘switched’). Patients were analysed by baseline dose (BD) (<4 mg/kg; ≥4–<5 mg/kg; ≥5 mg/kg), defined as the third (naïve) or first (switched) infusion dose. Baseline infusion intervals were the average of the three infusion intervals after BD. Over time, patients with both constant dose and infusion interval were compared with those with changes in dose and/or infusion interval. Data were analysed by Kruskal–Wallis test, chi-squared test and one-way analysis of variance, and drug survival by log-rank test.Results:Overall, 337 patients (219 naïve; 118 switched) were identified. Of those with BD data, 71, 117 and 82 patients had BDs of <4 mg/kg, ≥4–<5 mg/kg and ≥5 mg/kg, respectively. Most patients were male (74.8%). Patients with higher BDs tended to have higher Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) scores; switched patients had lower scores than naïve patients. Of 186 evaluable patients (118 naïve; 68 switched), 85 (46 naïve; 39 switched) did not have dose and/or interval changes (‘combined constant’ group). More naïve (n=72; 61.0%) versus switched (n=29; 42.6%) patients had dose and/or interval changes (‘combined changed’ group). Considering dose and interval separately, 18/235 evaluable patients (152 naïve; 83 switched) had dose changes (12 increased; 6 decreased) and 110/224 evaluable patients (140 naïve; 84 switched) had interval changes (79 increased; 31 decreased). Cumulative annual doses were similar between naïve and switched patients; switched patients had longer infusion intervals than naïve patients (Figure 1). There were no significant differences in drug survival between BD groups overall or for naïve and switched patients. BASDAI scores over time showed that disease activity was well controlled (Table 1). Patients in the combined changed versus combined constant group had greater improvements in BASDAI score.Table 1.BASDAI scoresGroupStatisticW0W54W102W156W210Combined constantTotal (N=85)n7273574231Mean (SD)5.50 (3.12)2.50 (1.71)2.35 (1.66)2.42 (1.66)2.36 (1.68)Median6.322.602.402.552.60Naïve (n=46)n3939261812Mean (SD)7.86 (1.45)2.49 (1.82)2.41 (1.75)2.34 (1.70)1.94 (1.58)Median7.802.201.751.901.44Switched (n=39)n3334312419Mean (SD)2.71 (2.07)2.50 (1.60)2.31 (1.60)2.48 (1.67)2.63 (1.73)Median2.582.752.502.802.70Combined changedTotal (N=101)n8785765335Mean (SD)5.68 (2.89)1.81 (1.45)1.58 (1.27)1.49 (1.34)1.40 (1.24)Median6.701.321.191.201.00Naïve (n=72)n6360543418Mean (SD)7.18 (1.37)2.01 (1.44)1.65 (1.22)1.54 (1.26)1.52 (0.97)Median7.301.831.351.311.35Switched (n=29)n2425221917Mean (SD)1.74 (1.94)1.33 (1.36)1.42 (1.41)1.39 (1.50)1.28 (1.50)Median0.920.800.850.700.58SD, standard deviation; W, WeekConclusion:These real-world data demonstrate that adjusting dose and infusion interval can improve clinical outcomes for CT-P13-treated patients with AS. Drug survival and BASDAI results show that patients with lower baseline BASDAI receiving low CT-P13 doses can achieve the same outcomes as those dosed with ≥5 mg/kg. Findings support the lack of impact of switching from reference infliximab to CT-P13 on efficacy, underlining conclusions previously drawn for efficacy and safety.1References:[1]Kim T-H, et al. Clin Drug Investig 2020;40:541–53.Acknowledgements:Funding: This study was supported by Celltrion Healthcare Co., Ltd. (Incheon, Republic of Korea). Medical writing support was provided by Beatrice Tyrrell, DPhil (Aspire Scientific, Bollington, UK), and funded by Celltrion Healthcare Co., Ltd. (Incheon, Republic of Korea).Disclosure of Interests:Shin-Seok Lee: None declared, Tae-Hwan Kim: None declared, Won Park Consultant of: Celltrion, Inc., Yeong Wook Song: None declared, Chang-Hee Suh Speakers bureau: AbbVie Inc., Astellas Pharma Inc., Samsung Bioepis Co., Ltd, Consultant of: Celltrion Healthcare Co., Ltd., Eli Lilly and Company, GlaxoSmithKline plc, Janssen Pharmaceuticals, Yungjin Pharmaceutical, Co., Ltd, SooKyoung Kim Shareholder of: Celltrion Healthcare Co., Ltd., Employee of: Celltrion Healthcare Co., Ltd., DaeHyun Yoo Speakers bureau: Celltrion, Consultant of: Celltrion, Grant/research support from: Celltrion
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Smolen, J. S., P. Emery, W. Rigby, Y. Tanaka, J. Ignacio Vargas, N. Damjanov, M. Jain, et al. "THU0213 UPADACITINIB AS MONOTHERAPY IN PATIENTS WITH RHEUMATOID ARTHRITIS AND PRIOR INADEQUATE RESPONSE TO METHOTREXATE: RESULTS AT 84 WEEKS FROM THE SELECT-MONOTHERAPY STUDY." Annals of the Rheumatic Diseases 79, Suppl 1 (June 2020): 331.2–332. http://dx.doi.org/10.1136/annrheumdis-2020-eular.961.
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Background:In the SELECT-MONOTHERAPY trial, upadacitinib (UPA), an oral JAK inhibitor, demonstrated significantly greater efficacy compared to continuing methotrexate (MTX) when used as monotherapy over 14 weeks (wks) in patients (pts) with rheumatoid arthritis (RA) and prior inadequate response to MTX.1Objectives:To describe the long-term safety and efficacy of UPA monotherapy in an ongoing long-term extension (LTE) of the SELECT-MONOTHERAPY trial.Methods:Pts on stable MTX were randomized to either continue MTX (cMTX, given as blinded study drug) or switch to once-daily (QD) UPA 15 (UPA15) or 30 (UPA30) mg monotherapy for 14 wks. From Wk14, pts could enter a blinded LTE and continue to receive UPA15 or UPA30; pts randomized to cMTX were switched to UPA15 or UPA30 per pre-specified assignment at baseline. Treatment-emergent adverse events (TEAEs) per 100 pt yrs (PYs) of exposure are summarized up to a cut-off data of 5 February 2019, when all pts had reached Wk84. Efficacy outcomes through Wk84 are reported as observed and using non-responder imputation.Results:Of 648 pts randomized, 598 (92%) completed 14 wks and entered the LTE on blinded UPA. By the cut-off date, 20% in total had discontinued due to the following: AE (6%), consent withdrawal (4%), lost to follow-up (2%), lack of efficacy (1%), or other reasons (7%). Cumulative exposures were 421.5 and 425.9 PYs for UPA15 and UPA30, respectively. The most frequently reported TEAEs were urinary tract infection, creatine phosphokinase (CPK) increase, upper respiratory tract infection, nasopharyngitis, worsening of RA, bronchitis, herpes zoster (HZ), and alanine aminotransferase increase; the most common serious AE was pneumonia. Events of HZ, hepatic disorder, and CPK elevations were higher among pts receiving UPA30, while rates of serious infection and malignancy appeared comparable between doses (Figure). Most HZ events involved 1-2 dermatomes, with a single disseminated cutaneous event (UPA30) and none with CNS involvement. Five patients experienced MACE, and there were 5 VTE events (UPA15: 4; UPA30: 1). All MACE and VTE events occurred in pts with underlying risk factors. Pts continuing to receive UPA15 and UPA30 achieved stringent endpoints at Week 84 (Table). Pts who switched from cMTX to UPA15 or UPA30 demonstrated comparable efficacy responses to those initially randomized to UPA.Conclusion:The adverse event profile associated with long-term exposure to UPA15 or 30 as monotherapy was consistent with an integrated analysis of UPA safety across the entire phase 3 program, with no new safety signals identified. Further, UPA15 or 30 monotherapy resulted in continued and sustained improvements in RA signs and symptoms through 84 wks.References:[1]Smolen, et al.Lancet2019;393(10188):2303-11.Table.Proportion of Patients at Week 84Parameter (%)cMTX→UPA 15 mgn=108cMTX→UPA 30 mgn=108UPA 15 mgn=217UPA 30 mgn=215AONRIAONRIAONRIAONRIACR20/50/7086/71/4967/56/3990/68/5066/51/3888/71/5465/53/4196/78/6674/62/52DAS28(CRP) ≤3.2/<2.680/5664/4479/6362/4976/6057/4685/7767/61CDAI ≤10/≤2.878/3862/3085/2965/2274/3455/2585/4967/39Boolean Remission2722231826204133AO, as observed; NRI, non-responder imputation.Disclosure of Interests: :Josef S. Smolen Grant/research support from: AbbVie, Eli Lilly, Janssen, Merck Sharp & Dohme, Pfizer, Roche – grant/research support, Consultant of: AbbVie, Amgen Inc., AstraZeneca, Astro, Celgene Corporation, Celtrion, Eli Lilly, Glaxo, ILTOO, Janssen, Medimmune, Merck Sharp & Dohme, Novartis, Pfizer, Roche, Samsung, Sanofi, UCB – consultant, Speakers bureau: AbbVie, Amgen Inc., AstraZeneca, Astro, Celgene Corporation, Celtrion, Eli Lilly, Glaxo, ILTOO, Janssen, Medimmune, Merck Sharp & Dohme, Novartis, Pfizer, Roche, Samsung, Sanofi, UCB – speaker, Paul Emery Grant/research support from: AbbVie, Bristol-Myers Squibb, Merck Sharp & Dohme, Pfizer, Roche (all paid to employer), Consultant of: AbbVie (consultant, clinical trials, advisor), Bristol-Myers Squibb (consultant, clinical trials, advisor), Lilly (clinical trials, advisor), Merck Sharp & Dohme (consultant, clinical trials, advisor), Novartis (consultant, clinical trials, advisor), Pfizer (consultant, clinical trials, advisor), Roche (consultant, clinical trials, advisor), Samsung (clinical trials, advisor), Sandoz (clinical trials, advisor), UCB (consultant, clinical trials, advisor), William Rigby Grant/research support from: Bristol-Myers Squibb, Consultant of: AbbVie, Bristol-Myers Squibb, Genentech, Pfizer, Yoshiya Tanaka Grant/research support from: Asahi-kasei, Astellas, Mitsubishi-Tanabe, Chugai, Takeda, Sanofi, Bristol-Myers, UCB, Daiichi-Sankyo, Eisai, Pfizer, and Ono, Consultant of: Abbvie, Astellas, Bristol-Myers Squibb, Eli Lilly, Pfizer, Speakers bureau: Daiichi-Sankyo, Astellas, Chugai, Eli Lilly, Pfizer, AbbVie, YL Biologics, Bristol-Myers, Takeda, Mitsubishi-Tanabe, Novartis, Eisai, Janssen, Sanofi, UCB, and Teijin, Juan Ignacio Vargas Consultant of: AbbVie, Nemanja Damjanov Grant/research support from: from AbbVie, Pfizer, and Roche, Consultant of: AbbVie, Gedeon Richter, Merck, Novartis, Pfizer, and Roche, Speakers bureau: AbbVie, Gedeon Richter, Merck, Novartis, Pfizer, and Roche, Manish Jain Grant/research support from: AbbVie, Novartis, Celgene, Medac, and Takeda, Speakers bureau: AbbVie, Novartis, Celgene, Medac, and Takeda, Yanna Song Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., Nasser Khan Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., Jose Jeffrey Enejosa Shareholder of: AbbVie, Employee of: AbbVie, Stanley B. Cohen Grant/research support from: Amgen, Abbvie, Boehringer Ingelheim, Pfizer and Sandoz, Consultant of: Amgen, Abbvie, Boehringer Ingelheim, Pfizer and Sandoz
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Van Vollenhoven, R., T. Takeuchi, M. Rischmueller, R. Blanco, R. Xavier, M. Howard, A. Friedman, Y. Song, and V. Strand. "THU0217 UPADACITINIB MONOTHERAPY IN METHOTREXATE-NAÏVE PATIENTS WITH RHEUMATOID ARTHRITIS: RESULTS AT 72 WEEKS FROM SELECT-EARLY." Annals of the Rheumatic Diseases 79, Suppl 1 (June 2020): 334–35. http://dx.doi.org/10.1136/annrheumdis-2020-eular.1857.
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Background:Upadacitinib (UPA), an oral JAK inhibitor, demonstrated significant improvements in signs, symptoms, and structural inhibition as monotherapy vs methotrexate (MTX) in a randomized, controlled trial (RCT) of MTX-naive RA patients (pts) through 48 weeks (wks).1Objectives:To present the safety and effectiveness of UPA through 72 wks in an ongoing long-term extension (LTE) of the SELECT-EARLY RCT.Methods:SELECT-EARLY included 2 study periods: (1) a 48-wk double-blind, active comparator-controlled, with pts randomized to UPA monotherapy 15 or 30 mg once daily or MTX (titrated to 20 mg/wk by Wk8); (2) an LTE, up to 4 years. Pts received open-label treatment once the last pt reached Wk48. Rescue therapy was added (MTX, for UPA groups; UPA, for MTX group) to pts not achieving CDAI remission (≤2.8) at Wk26. Non-responder imputation (NRI) was used for missing data as well as for pts receiving rescue therapy. Treatment-emergent adverse events (TEAEs) are summarized per 100 pt yrs (PY) through the cut-off date of 21 Feb 2019, when all pts had reached Wk72. Data are censored at the time of MTX or UPA addition among rescued patients.Results:Of 945 pts randomized and treated, 781 (83%) completed Period 1. Of these, 775 entered the LTE, including 57 rescued pts (MTX, 33; UPA 15 mg, 17; UPA 30 mg, 7). A total of 52 (7%) pts discontinued during the LTE through the cut-off date (primary reasons: AEs [n=16, 2.1%]; consent withdrawal [n=12, 1.5%]; lost to follow-up [n=10, 1.3%]). Cumulative exposures to monotherapy with MTX, UPA 15 mg, and UPA 30 mg were 350.6, 389.5, and 383.9 PYs, respectively. Both UPA 15 mg and 30 mg as monotherapy was associated with continued statistically significant improvements in disease activity measures vs MTX monotherapy through 72 wks (Table). The safety profiles of the UPA 15 and 30 mg groups were comparable for total TEAEs and numerically higher than MTX. Serious TEAEs and TEAEs leading to discontinuation of study drug were comparable across all groups (Figure). Most AEs of special interest were comparable across MTX and UPA groups, with the exception of higher rates of herpes zoster, opportunistic infections, and elevated creatine phosphokinase among the UPA groups. Two pts receiving MTX monotherapy experienced a venous thromboembolic event, with one event reported on UPA 30 mg and none on UPA 15 mg. There were 12 deaths (including 3 non-treatment-emergent) due to varied causes.Table.Proportion of Patients at Week 72 (NRI)Parameter (%)MTXMonotherapyUPA 15 mg QDMonotherapyUPA 30 mg QDMonotherapyACR20/50/7050/39/2671***/62***/47***72***/67***/54***DAS28(CRP) ≤3.2/<2.638/2863***/52***69***/61***CDAI ≤10/≤2.842/1960***/35***69***/44***Boolean Remission1329***33******,P<0.001 for differences between MTX and UPA 15 and UPA 30 mg groups.MTX, methotrexate; UPA, upadacitinib; QD, once daily; ACR, American College of Rheumatology; DAS28(CRP), 28-joint disease activity index based on C-reactive protein; CDAI, clinical disease activity index.Figure.Treatment-emergent Adverse Events Through ≥72 Weeks (E/100 PYs, 95% CI).Conclusion:Long-term UPA monotherapy was associated with continued improvements in RA signs and symptoms vs MTX monotherapy through 72 wks, and only a small proportion of pts required MTX addition at Wk26. Through 72 wks of treatment, the safety profile of UPA monotherapy remained consistent with data reported through 48 wks.1References:[1]van Vollenhoven R,et al.Ann Rheum Dis2019;78(S):376.Disclosure of Interests: :Ronald van Vollenhoven Grant/research support from: AbbVie, Arthrogen, Bristol-Myers Squibb, GlaxoSmithKline, Lilly, Pfizer, and UCB, Consultant of: AbbVie, AstraZeneca, Biotest, Bristol-Myers Squibb, Celgene, GSK, Janssen, Lilly, Medac, Merck, Novartis, Pfizer, Roche, and UCB, Tsutomu Takeuchi Grant/research support from: Eisai Co., Ltd, Astellas Pharma Inc., AbbVie GK, Asahi Kasei Pharma Corporation, Nippon Kayaku Co., Ltd, Takeda Pharmaceutical Company Ltd, UCB Pharma, Shionogi & Co., Ltd., Mitsubishi-Tanabe Pharma Corp., Daiichi Sankyo Co., Ltd., Chugai Pharmaceutical Co. Ltd., Consultant of: Chugai Pharmaceutical Co Ltd, Astellas Pharma Inc., Eli Lilly Japan KK, Speakers bureau: AbbVie GK, Eisai Co., Ltd, Mitsubishi-Tanabe Pharma Corporation, Chugai Pharmaceutical Co Ltd, Bristol-Myers Squibb Company, AYUMI Pharmaceutical Corp., Eisai Co., Ltd, Daiichi Sankyo Co., Ltd., Gilead Sciences, Inc., Novartis Pharma K.K., Pfizer Japan Inc., Sanofi K.K., Dainippon Sumitomo Co., Ltd., Maureen Rischmueller Consultant of: Abbvie, Bristol-Meyer-Squibb, Celgene, Glaxo Smith Kline, Hospira, Janssen Cilag, MSD, Novartis, Pfizer, Roche, Sanofi, UCB, Ricardo Blanco Grant/research support from: Abbvie, MSD and Roche, Consultant of: Abbvie, Pfizer, Roche, Bristol-Myers, Janssen and MSD, Speakers bureau: Abbvie, Pfizer, Roche, Bristol-Myers, Janssen, Lilly and MSD, Ricardo Xavier Consultant of: AbbVie, Pfizer, Novartis, Janssen, Eli Lilly, Roche, Mark Howard Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., Alan Friedman Shareholder of: AbbVie Inc, Employee of: AbbVie Inc, Yanna Song Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., Vibeke Strand Consultant of: AbbVie, Amgen, Biogen, Celltrion, Consortium of Rheumatology Researchers of North America, Crescendo Bioscience, Eli Lilly, Genentech/Roche, GlaxoSmithKline, Hospira, Janssen, Merck, Novartis, Pfizer, Regeneron Pharmaceuticals, Inc., Sanofi, UCB
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Weisel, Katja, Agne Paner, Monika Engelhardt, Fiona Taylor, Kim Cocks, Ashlee Espensen, Mihaela Popa-McKiver, Clara Chen, and Michele Cavo. "Quality-of-Life Outcomes in Patients with Relapsed/Refractory Multiple Myeloma Treated with Elotuzumab Plus Pomalidomide and Dexamethasone: Results from the Phase 2 Randomized Eloquent-3 Study." Blood 132, Supplement 1 (November 29, 2018): 2288. http://dx.doi.org/10.1182/blood-2018-99-112080.
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Abstract Introduction: Novel therapies for relapsed/refractory multiple myeloma (RRMM) have demonstrated durable responses that prolong survival, thus assessing health-related quality of life (HRQoL) is becoming increasingly important in patient (pt) care. Long-term RRMM treatment may lead to a higher cumulative symptom burden and negatively affect HRQoL. Indeed, the effect of treatment on HRQoL is reduced in pts with RRMM on later vs initial lines of therapy (LoTs) (Nielsen et al, Eur J Hematol 2017). Consequently, there is a need for treatments that demonstrate durable efficacy while preserving HRQoL. Pomalidomide plus dexamethasone (Pd) has been shown to be an effective treatment for RRMM that does not negatively affect HRQoL in later LoTs (Song et al, Haematologica 2015). In the randomized phase 2 ELOQUENT-3 study (NCT02654132), addition of the SLAMF7-targeted monoclonal antibody elotuzumab (elo) to Pd (EPd) showed a 46% reduction in the risk of progression/death vs Pd, and acceptable safety in pts with refractory or relapsed and refractory MM for whom therapy with lenalidomide and a proteasome inhibitor had failed (Dimopoulos et al, EHA 2018 [LB2606]). We present pt-reported outcome (PRO) data to assess the impact of EPd on HRQoL in pts from ELOQUENT-3. Methods: The M.D. Anderson Symptom Inventory MM module (MDASI-MM) and the 3-level version of the EuroQoL 5 Dimensions Questionnaire (EQ-5D-3L), which included the global health visual analog scale (VAS) measure, were administered at baseline (BL) and at the start of every 28-day treatment cycle until discontinuation and at survival follow-up. All randomized pts with BL and ≥1 post-BL assessment were included in the PRO analysis. Changes from BL scores were evaluated descriptively: high scores indicate better health for EQ-5D-3L, but more severe symptoms for MDASI-MM. Time to first deterioration was evaluated, with a deterioration event defined as the absolute value of the change from BL ≥ the responder definition threshold (MDASI-MM symptom item assessing pain, fatigue, and bone aches: 2; EQ-5D-3L VAS: 7). Results: This analysis included 117 randomized pts (EPd, n=60; Pd, n=57) who had received a median of 3 prior LoTs. PRO completion rates at BL were 79% for MDASI-MM (EPd, 85%; Pd, 72%) and 84% for EQ-5D-3L (EPd, 88%; Pd, 79%). Although completion rates between treatment groups were similar throughout the study, analysis of QoL was not feasible after Cycles 13 for EPd and 10 for Pd as the number of pts with questionnaires dropped below 20%. Mean BL QoL scores were similar for EPd vs Pd (EQ-5D-3L utility, 0.676 vs 0.682; EQ-5D-3L VAS global health status, 61.9 vs 62.9). A clinically meaningful deterioration from BL in EQ-5D-3L VAS health status (mean change -9.0) was observed with Pd at Cycle 2. In contrast, there were no clinically relevant deteriorations in EQ-5D-3L VAS health status with EPd, and a sustained improvement from BL was observed between Cycles 9 and 12 (mean change 8.2, 11.7, 9.7, and 10.4, respectively; Figure). MDASI-MM symptom scores for pain and bone aches showed no clinically relevant change from BL levels in both groups, but fatigue worsened (mean change 2.5) in the Pd group at Cycle 9. Pts who discontinued treatment early tended to have lower HRQoL in both treatment arms. There were no differences in time to first deterioration for EPd vs Pd for MDASI-MM symptoms pain, fatigue, or bone aches, or EQ-5D-3L and VAS domains. Although the risk of deterioration in the severity of MDASI-MM core symptoms (symptoms common across cancer types and treatments) was reduced by 17% (hazard ratio 0.83; 95% CI 0.49-1.42) for those receiving EPd vs Pd, this was not statistically significant (p=0.618); the median time to deterioration was 3.8 mo with EPd and 1.2 mo with Pd. Conclusions: In ELOQUENT-3, pt-reported health status was maintained in pts who remained on EPd per EQ-5D-3L VAS, with no worsening of pain, fatigue, or bone aches per MDASI-MM. There were minimal differences in QoL between pts who received EPd and Pd, suggesting that the addition of elo to Pd does not impair HRQoL, although HRQoL may have been overestimated due to the small sample and treatment discontinuation. These pt-reported findings complement strong clinical data that demonstrated clinically relevant improvements in efficacy and a favorable safety profile for EPd, further supporting the use of this regimen in RRMM. Study support: BMS. Writing support: Simon Wigfield, Caudex, funded by BMS. Figure. Figure. Disclosures Weisel: Amgen, BMS, Celgene, Janssen, and Takeda: Honoraria; Amgen, BMS, Celgene, Janssen, Juno, Sanofi, and Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees; Amgen, Celgene, Janssen, and Sanofi: Research Funding. Paner:Takeda: Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria. Taylor:Adelphi Values: Employment; Bristol-Myers Squibb: Consultancy. Cocks:Adelphi Values: Employment; Amgen: Consultancy; Bristol-Myers Squibb: Consultancy; Celgene: Consultancy; Endomag Ltd.: Consultancy. Espensen:Adelphi Values: Employment; Bristol-Myers Squibb: Consultancy, Other: I am an employee of Adelphi Values, a consulting firm that has received payment from BMS for statistical data analysis in BMS trials. Popa-McKiver:Bristol-Myers Squibb: Employment. Chen:Bristol-Myers Squibb: Employment. Cavo:Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees; GlaxoSmithKline: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Adaptive Biotechnologies: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees.
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Pliushchenko, M. Yu. "“Jazz Slide” by M. Tovpeko – A. Strilets: Aspects of the original source interpretation." Problems of Interaction Between Arts, Pedagogy and the Theory and Practice of Education 53, no. 53 (November 20, 2019): 124–44. http://dx.doi.org/10.34064/khnum1-53.08.
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Background. This article is devoted to the actual issues of musical interpretation in connection with one of the most common genres of modern art – genre of transcription in its various aspects. These questions are considered in aspect of genre specificity of transcription as the work with dual authorship that determines a special methodology of such musical samples study, the need of the comparative analysis of the original and transcription versions, the study of principles of composition and artistic interpretation, the manifestations of the performing characteristics in it. This field of creativity encourages researchers to study the principles of artistic thinking, inter-style communication, and virtual creative dialogue between the authors of the original and the version at all levels of musical content and form using the samples of transcriptions. The example of such approach is the given research, which studies the mechanisms of musical interpretation creation in the genres transcription and arrangement in aspect of the contemporary composing and performing practices. The object of the study is the creativity by a bright representative of the Kharkiv school of the playing on folk instruments, Andrii Strilets, the subject of consideration in this article are his orchestra transcriptions-arrangements. The purpose of the research is to determine the principles of interpretation and inter-style dialogue in the genre of transcription on the example of the musical piece “Jazz-slide” by M. Tovpeco for two accordions in the arrangement by A. Strilets. For the first time in musicology this composition becomes an object for the theoretical analysis in aspect of the artistic interpretation and inter-style dialogue in genre of transcription-arrangement. This determines the relevance and scientific novelty of the study. For the first time also, the research is focused on the multifaceted creative activity of the talented Kharkiv musician A. Strilets, which combines the various directions – composition, conducting, bayan performance and pedagogy. Results of the study. The list of the works by A. Strilets includes dozens of positions, in particular, the orchestral opuses – about 40, the vocal pieces – more than 40, there are also the dance music, vocal-choreographic compositions and others. Composer prepared for publication the author’s collection “Concert works for bayan”, which will be a musical presentation of his work. Pedagogical work of the musician is successfully combined with the performing activity. A. Strilets is a talented accordion / bayan performer (the winner of all-Ukrainian and international competitions, among them, the prestigious international competition “Vogtland Music Days” in Klingenthal, Germany; participant of tours as a bayan player-performer in Belgium, Germany, Poland, Ukraine) and conductor. He worked as a conductor at the Kharkiv City Theater of Folk Music “Oberegi”; he made a significant contribution to the creation of the “Slobozhanskii Big Academic Song and Dance Ensemble” (2011), which he conducts nowadays, and also acts as an author and arranger of a significant part of the musical repertoire of this ensemble. Being the head of the folk instruments orchestra, musician directs his actions, first of all, to improve the performing level of the musicians, to expand the concert repertoire and the genre diversity of the performed compositions, to change and complete the instrumental compositions. The study also highlights several signs of the pedagogy of A. Strilets. As a teacher, he encourages in his class the independent thinking of the performer and the searching of a reasonable interpretation, provides the information about stylistic features of works for fully disclosing of its content, he takes into account the analysis of their dramaturgy and form, carefully relates to the reproduction of author’s remarks, aims from the musicians the task of the most accurate composer’s intention disclosure. These pedagogical principles project onto the compositional features of A. Strilets’ works, which are clearly demonstrated in sphere of his arranger’s work. The study specifies a number of basic composer principles and methods used by A. Strilets in the transcription-arrangement of “Jazz Slide”. 1. First of all, the arranger updates the timbre-texture complex of the original, redistributing certain content and form-building components in the musical “space” and “time”, giving them new configurations, which leads to strengthening or, in opposite, leveling (down to rotation) of their original dramatic functions – general and minor, solo and accompanying, monological and dialogical, ensemble and orchestral, melodic, harmonic, rhythmic and others. 2. The sound-texture aspect demonstrates both smallest and systemic changes of musical and expressive complex of the original – from the separate elements to their cumulative action, which contributes to the genre-style qualities transformation of the work, strengthening the through development in it, up to the presence of signs of symphonization. 3. Hence, the genre concept of the work is updated, and it leads to the emergence of a new genre quality – “concert-ness” – and to the consolidation of the concert status of the work (which becomes similar to a concert for two accordions / bayans with an orchestra). The quality of “concert” is also achieved due to the growing role of soloists, in particular, the strengthening of solo replicas in the orchestra (separation of elements of the original melodic themes and distribution them to orchestral groups), which leads to the polyphonization of the musical facture, emphasizing (new coloring) some features of the melodic lines of the soloists and like other. 4. At the level of harmony, on the one hand, the emphasis of its original content, on the other hand, the search of its melodic potential is observed. 5. The rhythmic parameter of sound-facture complex contributes to the enhancement of genre-style semantics of the original source, taking into account its jazz “filling”. 6. Comparative analysis of the original and version reveals signs of a method of composer interpretation that involves a creative component in arranging, supplementing, and rethinking the content of the original. Conclusion. In course of studying it was found that the arranger, at the preserving of the structure of the original piece – a contrast-composite form, updates the procession-dynamic and dramatic sides of it, primarily due to the action of the timbre-texture complex as the key interpretative factor in creating of the orchestral version of the original. The prospect of the research. The considered issues require, of course, the further research – both from the point of view of the artistic significance of genres, arrangement and transcription, in particular, for orchestras and ensembles of folk instruments, and in the aspect of the action of mechanisms of artistic interpretation and the features of the transcription process, which naturally combines composer and performing arts. The work of the talented Kharkiv musician Andrii Strilets who is one of the most prominent representatives of the Kharkiv school of folk instruments, deserves a separate study.