Predictive biomarkers of sensitivity to androgen receptor signaling (ARS) and taxane-based chemotherapy in circulating tumor cells (CTCs) of patients (pts) with metastatic castration resistant prostate cancer (mCRPC).

2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 147-147 ◽  
Author(s):  
Howard I. Scher ◽  
Jessica Louw ◽  
Adam Jendrisak ◽  
Richard Martin Bambury ◽  
Daniel Costin Danila ◽  
...  
Keyword(s):  
De Novo ◽  
Digital Pathology ◽  
Predictive Biomarkers ◽  
The Other ◽  
Castration Resistant Prostate Cancer ◽  
Optimal Sequence ◽  
Individual Agent ◽  
Line Of Therapy ◽  
The Individual ◽  
Blood Biopsy

147 Background: The optimal sequence to administer approved life prolonging ARS inhibitors: Abiraterone (A) and Enzalutamide (E),and taxanes: Docetaxel (D) and Cabazitaxel (C), to maximize individual pt benefit is an unmet medical need. Sensitivity to an individual agent is dependent on the intrinsic biology of the tumor and the treatment to which it has been exposed. For each agent, response rates are lower in pts who have received prior treatment with any of the other drugs, but for the individual, sensitivity to one does not necessarily predict sensitivity to the other. We sought to develop response and resistance signatures to A & E or D & C from a baseline blood sample. Methods: 91 pt blood samples collected from 79 pts for CTC analysis with the Epic Sciences platform prior to treatment (27 pre-A, 28 pre-E, 28 pre-D, 8 pre-C). Epic analysis identified traditional CTCs (CK+, CD45-, intact nuclei, morph distinct), CK- CTCs (CK-, CD45-, intact nuclei, morph distinct), small CTCs (CK+, CD45-, intact nuclei, small cell size), and CTC clusters. IF staining for AR N, AR C exp were performed, digital pathology algorithms analyzed CTC morphology. A classifier was developed to associate clinical phenotypes with outcome to a specific agent. Results: A and E signatures included: AR N/C exp. and presence of CK+, AR+, Nucleoli+ CTCs. D and C signatures by: presence of CK+, small, AR-, Nucleoli+ CTCs. Multivariate algorithms for A and E and D & C were statistically associated with de novo resistance. Line of therapy was not a univariate predictor of response. Conclusions: Characterization of CTCs identified predictive biomarkers of sensitivity to ARS Tx and taxane chemotherapy in mCRPC pts. The proposed A&E signature differs from C and D, providing the opportunity to better guide treatment selection and improve patient outcomes using a real-time, non-invasive blood biopsy. Prospective trials to validate results are planned. [Table: see text]

Sequencing of cabazitaxel and abiraterone acetate following docetaxel in metastatic castration-resistant prostate cancer (mCRPC).

2013 ◽  
Vol 31 (6_suppl) ◽  
pp. 79-79 ◽  
Author(s):  
Ian D. Schnadig ◽  
Menaka Bhor ◽  
Nicholas J. Vogelzang ◽  
Daniel Hennessy ◽  
Leonardo V. Nicacio ◽  
...  
Keyword(s):  
Treatment Options ◽  
Predictive Biomarkers ◽  
Abiraterone Acetate ◽  
Patient Specific ◽  
Castration Resistant Prostate Cancer ◽  
Community Based ◽  
Optimal Sequence ◽  
New Agents ◽  
Large Community ◽  
Castration Resistant

79 Background: Following docetaxel (D), treatment options for mCRPC include cabazitaxel (CBZ), abiraterone acetate (AA), and enzalutamide. With the introduction of new agents, optimal sequencing is undefined. We evaluated the prevalence of sequencing of AA and CBZ following D in a large community-based cohort to develop a hypothesis for the most optimal sequence. Methods: A retrospective analysis of treatment patterns using the MSH iKnowMed EHR was conducted. Post-D mCRPC patients receiving CBZ and/or AA at full EHR sites with ≥2 visits were included; clinical trial patients excluded. CBZ utilization between Jun’10 and May’12 and sequencing of CBZ or/and AA from Apr’11 and May’12 (when both drugs were available) were examined. OS, time to treatment failure (TTF), and demographics analyses are ongoing. Results: 667 evaluable patients were identified. Overall CBZ (n=359 pts/2 y) utilization declined between Jun’10-May’11 (n=232) and Jun’11-May’12 (n=127). From Apr’11 to May’12: overall AA (n=465 pts/y) utilization increased between Mar-May’11 (n=73) to Jun-Aug’11 (n=164) and subsequently decreased (n=57) from Mar-May’12. Between Apr’11-May’12, 130 patients received both CBZ and AA. More men (P<0.001) received D→CBZ→AA (n=88, 67.7%) compared with D→AA→CBZ (n=42, 32.3%). Median age of patients receiving both CBZ and AA was 67 (44-89) y and their median baseline PSA (111 evaluable) was 84.3 (0.4-7672.2) ng/mL. Conclusions: AA was administered more frequently than CBZ in post-D mCRPC patients. However, the sequence of D→CBZ→AA was more prevalent than D→AA→CBZ in this large community-based cohort. Until predictive biomarkers and outcomes with respective sequences are identified, delivery of all active agents according to patient-specific clinical factors should probably be considered. [Table: see text]

Efficacy of sequential therapy comprising of docetaxel, abiraterone, enzalutamide, and cabazitaxel in patients with castration-resistant prostate cancer.

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 239-239
Author(s):  
Akiyuki Yamamoto ◽  
Masashi Kato ◽  
Toyonori Tsuzuki ◽  
Momokazu Gotoh ◽  
Yushi Naito ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
De Novo ◽  
Progression Free Survival ◽  
Sequential Therapy ◽  
The Other ◽  
Castration Resistant Prostate Cancer ◽  
Free Survival ◽  
Castration Resistant ◽  
Number Of Patients ◽  
Significant Difference

239 Background: The sequence of use of life-prolonging therapy (docetaxel, abiraterone, enzalutamide, and cabazitaxel) is unclear in patients with castration-resistant prostate cancer (CRPC). Methods: We retrospectively identified a total of 316 patients diagnosed with CRPC from September 2003 to April 2019 at Nagoya University and its affiliated hospitals. All patients were treated with >2 life-prolonging therapies. We divided these patients into four groups based on the sequence of drug administration. The group of patients who were treated using the sequence of abiraterone to enzalutamide or enzalutamide to abiraterone was termed as AA. The group treated using the sequence of abiraterone or enzalutamide to docetaxel was termed as AD. The group treated using the sequence of docetaxel to abiraterone or enzalutamide was termed as DA. Lastly, the group treated using the sequence of docetaxel to cabazitaxel was termed as DC. We investigated the overall survival (OS) from the time of diagnosis of CRPC. In addition, we estimated combined progression-free survival (combined PFS) defined as the sum of the PFS of each agent. Results: The number of patients in AA, AD, DA, and DC was 106, 69, 130, and 11, respectively. Regarding AA, AD, DA, and DC, the median ages were 72, 70, 68, and 64 years, respectively. The proportion of patients who had de novo distant metastasis was 66%, 65%, 58%, and 73% in AA, AD, DA, and DC, respectively. Further, the median OS was 68.7, 54.5, 68.6, and 22.0 months for AA, AD, DA, and DC, respectively. Notably, no significant differences related to OS were observed between AA and AD ( p = 0.06), AA and DA ( p = 0.24), as well as AD and DA ( p = 0.46). The median combined PFS was 8.6, 10.1, 13.9, and 5.6 months for AA, AD, DA, and DC, respectively. In terms of combined PFS, a significant difference was observed between AA and DA ( p < 0.001) as well as AD and DA ( p = 0.003). OS and combined PFS were significantly poor in DC compared with those in the other groups. Conclusions: No significant differences related to OS were observed regarding the sequence of use of docetaxel, abiraterone, and enzalutamide. Notably, combined PFS was comparatively better in DA than in any other group.

Writing in Aphasia Rehabilitation: Cursive vs Manuscript

1976 ◽  
Vol 41 (4) ◽  
pp. 523-529 ◽  
Author(s):  
Daniel R. Boone ◽  
Harold M. Friedman
Keyword(s):  
Correct Response ◽  
The Other ◽  
Read Aloud ◽  
Writing Style ◽  
Reading And Writing ◽  
Manual Responses ◽  
Significant Difference ◽  
Written Form ◽  
The Individual ◽  
Read Number

Reading and writing performance was observed in 30 adult aphasic patients to determine whether there was a significant difference when stimuli and manual responses were varied in the written form: cursive versus manuscript. Patients were asked to read aloud 10 words written cursively and 10 words written in manuscript form. They were then asked to write on dictation 10 word responses using cursive writing and 10 words using manuscript writing. Number of words correctly read, number of words correctly written, and number of letters correctly written in the proper sequence were tallied for both cursive and manuscript writing tasks for each patient. Results indicated no significant difference in correct response between cursive and manuscript writing style for these aphasic patients as a group; however, it was noted that individual patients varied widely in their success using one writing form over the other. It appeared that since neither writing form showed better facilitation of performance, the writing style used should be determined according to the individual patient’s own preference and best performance.

Margaret Mahy: An Adlerian Reading

2008 ◽  
Vol 1 (2) ◽  
pp. 187-199
Author(s):  
KATHRYN WALLS
Keyword(s):  
Young Female ◽  
The Other ◽  
Individual Psychology ◽  
The Novel ◽  
Alfred Adler ◽  
Female Protagonists ◽  
Magical Power ◽  
Margaret Mahy ◽  
The Individual

According to the ‘Individual Psychology’ of Alfred Adler (1870–1937), Freud's contemporary and rival, everyone seeks superiority. But only those who can adapt their aspirations to meet the needs of others find fulfilment. Children who are rejected or pampered are so desperate for superiority that they fail to develop social feeling, and endanger themselves and society. This article argues that Mahy's realistic novels invite Adlerian interpretation. It examines the character of Hero, the elective mute who is the narrator-protagonist of The Other Side of Silence (1995) , in terms of her experience of rejection. The novel as a whole, it is suggested, stresses the destructiveness of the neurotically driven quest for superiority. Turning to Mahy's supernatural romances, the article considers novels that might seem to resist the Adlerian template. Focusing, in particular, on the young female protagonists of The Haunting (1982) and The Changeover (1984), it points to the ways in which their magical power is utilised for the sake of others. It concludes with the suggestion that the triumph of Mahy's protagonists lies not so much in their generally celebrated ‘empowerment’, as in their transcendence of the goal of superiority for its own sake.

Gewalt und Kommunikation

2011 ◽  
Vol 2011 (1) ◽  
pp. 5-28
Author(s):  
Jens Bonnemann
Keyword(s):  
Twentieth Century ◽  
Moral Philosophy ◽  
The Other ◽  
Practical Philosophy ◽  
Valuable Contribution ◽  
Human Species ◽  
Normal Case ◽  
Jean Paul ◽  
Philosophy Of Dialogue ◽  
The Individual

In ethics, when discussing problems of justice and a just social existence one question arises obviously: What is the normal case of the relation between I and you we start from? In moral philosophy, each position includes basic socio-anthropological convictions in that we understand the other, for example, primarily as competitor in the fight for essential resources or as a partner in communication. Thus, it is not the human being as isolated individual, or as specimen of the human species or socialised member of a historical society what needs to be understood. Instead, the individual in its relation to the other or others has been studied in phenomenology and the philosophy of dialogue of the twentieth century. In the following essay I focus on Martin Buber’s and Jean-Paul Sartre’s theories of intersubjectivity which I use in order to explore the meaning of recognition and disrespect for an individual. They offer a valuable contribution to questions of practical philosophy and the socio-philosophical diagnosis of our time.

Whither the people in the ASEAN Community?

2020 ◽  
Vol 10 (3) ◽  
pp. 43-57
Author(s):  
See Seng Tan
Keyword(s):  
Southeast Asia ◽  
Political Ideology ◽  
Management Development ◽  
The Other ◽  
Asean Member ◽  
Derechos Humanos ◽  
The People ◽  
Droits Humains ◽  
The One ◽  
The Individual

Abstract: The longstanding effort to develop a people-based regionalism in Southeast Asia has been shaped by an inherent tension between the liberal inclination to privilege the individual and the community under formation, on the one hand, and the realist insistence on the primacy of the state, on the other. This article explores the conditions and constraints affecting ASEAN’s progress in remaking Southeast Asia into a people-focused and caring community in three areas: disaster management, development, and democratization (understood here as human rights). Arguably, the persistent gap in Southeast Asia between aspiration and expectation is determined less by political ideology than by the pragmatic responses of ASEAN member states to the forces of nationalism and protectionism, as well as their respective sense of local and regional responsibility.Resumen: El esfuerzo histórico para desarrollar un regionalismo basado en las personas del sudeste de Asia ha estado marcado por una tensión fundamental entre la inclinación liberal de privilegiar el individuo y la comunidad y la insistencia realista sobre la primacía del estado. Este artículo explora las condiciones y limitaciones que afectan el progreso de la ASEAN en la reestructuración de Asia sudoriental en una comunidad centrada en el cuidado de las personas en: gestión de desastres, desarrollo y democratización (i.e., derechos humanos). La brecha persistente en el sudeste asiático entre la aspiración y la expectativa está determinada por las respuestas pragmáticas de los miembros de la ASEAN sometidos a las fuerzas del nacionalismo y proteccionismo, así como su respectivo sentido de responsabilidad local y regional.Résumé: L’effort historique pour développer un régionalisme fondé sur les peuples en Asie du Sud-Est a été marqué par une tension fondamentale entre l’inclination libérale qui privilégie, d’une part, l’individu et la communauté et, d’autre part, l’insistance réaliste sur la primauté de l’État. Cet article explore les conditions et les contraintes qui nuisent aux progrès de l’ANASE dans le cadre d’une refonte de l’Asie du Sud-Est en une communauté centrée et attentive aux peuples dans trois domaines : la gestion des désastres, le développement et la démocratisation (en référence aux droits humains). Le fossé persistant en Asie du Sud-Est entre les aspirations et les attentes est vraisemblablement moins déterminé par l’idéologie politique que par les réponses pragmatiques des États membres de l’ANASE soumis aux forces du nationalisme et du protectionnisme ainsi que par leur sens respectif de la responsabilité locale et régionale.

Ummah’s Rights or Human Rights? Universalism, Individualism, and Islamic Ethics in the Twenty-first Century

2010 ◽  
Vol 27 (3) ◽  
pp. 1-23 ◽  
Author(s):  
Marie-Luisa Frick
Keyword(s):  
Human Rights ◽  
First Century ◽  
The Other ◽  
Moral Code ◽  
Bill Of Rights ◽  
Islamic Ethics ◽  
Specific Content ◽  
Societal Needs ◽  
The One ◽  
The Individual

Against the background of the trend of Islamizing human rights on the one hand, as well as increasing skepticism about the compatibility of Islam and human rights on the other, I intend to analyze the potential of Islamic ethics to meet the requirements for vitalizing the idea of human rights. I will argue that the compatibility of Islam and human rights cannot be determined merely on the basis of comparing the specific content of the Islamic moral code(s) with the rights stipulated in the International Bill of Rights, but by scanning (different conceptions of) Islamic ethics for the two indispensable formal prerequisites of any human rights conception: the principle of universalism (i.e., normative equality) and individualism (i.e., the individual enjoyment of rights). In contrast to many contemporary (political) attempts to reconcile Islam and human rights due to urgent (global) societal needs, this contribution is solely committed to philosophical reasoning. Its guiding questions are “What are the conditions for deriving both universalism and individualism from Islamic ethics?” and “What axiological axioms have to be faded out or reorganized hierarchically in return?”

Assessment of Pain During Laser-based Procedures in the Treatment of Glaucoma

2019 ◽  
Vol 70 (6) ◽  
pp. 2105-2107
Author(s):  
Gheorghita Popa ◽  
Olimpiu L. Karancsi ◽  
Maria Alexandra Preda ◽  
Marius Cristian Suta ◽  
Lavinia Stelea ◽  
...  
Keyword(s):  
Minimally Invasive ◽  
Pain Score ◽  
The Other ◽  
Study Group ◽  
Moderate Pain ◽  
Pain Level ◽  
Analog Scale ◽  
Intense Pain ◽  
The Individual ◽  
Individual Information

Our study aimed to determine pain levels and the state of welfare connected to laser-based procedures in the treatment of patients diagnosed with uncontrolled glaucoma. The study group included 100 eyes of 100 patients diagnosed with glucoma, 50 of them being treated with micropulse transscleral laser cyclophotocoagulation, and the other 50 eyes being treated with continuous transscleral laser cyclophotocoagulation. We used visual analog scale to gather information from each patient. After analysing the individual information the following results were obtained: the pain level for the micropulse transscleral laser cyclophotocoagulation was 60.23 mm, signifying moderate pain; and the pain score for the continuous transscleral laser cyclophotocoagulation was 76.34 mm, corresponding to moderate-intense pain. Pain level generated by minimally invasive laser procedures is discussed.

Laughter on the Fringes

2019 ◽  
Author(s):  
Anna Peterson
Keyword(s):  
The Other ◽  
Literary Canon ◽  
Autobiographical Writing ◽  
Treasure Trove ◽  
Old Comedy ◽  
Other Hand ◽  
Aggressive Humor ◽  
The One ◽  
The Individual ◽  
The Impact

This book examines the impact that Athenian Old Comedy had on Greek writers of the Imperial era. It is generally acknowledged that Imperial-era Greeks responded to Athenian Old Comedy in one of two ways: either as a treasure trove of Atticisms, or as a genre defined by and repudiated for its aggressive humor. Worthy of further consideration, however, is how both approaches, and particularly the latter one that relegated Old Comedy to the fringes of the literary canon, led authors to engage with the ironic and self-reflexive humor of Aristophanes, Eupolis, and Cratinus. Authors ranging from serious moralizers (Plutarch and Aelius Aristides) to comic writers in their own right (Lucian, Alciphron), to other figures not often associated with Old Comedy (Libanius) adopted aspects of the genre to negotiate power struggles, facilitate literary and sophistic rivalries, and provide a model for autobiographical writing. To varying degrees, these writers wove recognizable features of the genre (e.g., the parabasis, its agonistic language, the stage biographies of the individual poets) into their writings. The image of Old Comedy that emerges from this time is that of a genre in transition. It was, on the one hand, with the exception of Aristophanes’s extant plays, on the verge of being almost completely lost; on the other hand, its reputation and several of its most characteristic elements were being renegotiated and reinvented.

Intra-individual variation in adults and children: measuring and conceptualizing individual dialect–standard repertoires

2021 ◽  
Vol 7 (s2) ◽  
Author(s):  
Irmtraud Kaiser ◽  
Andrea Ender
Keyword(s):  
Language Acquisition ◽  
Individual Variation ◽  
The Other ◽  
Standard Language ◽  
Methodological Choices ◽  
Standard Spectrum ◽  
Speech Data ◽  
Adults And Children ◽  
The One ◽  
The Individual

Abstract This paper explores intra-individual variation as a manifestation of language-internal multilingualism in the Central-Bavarian Austrian context. Based on speech data from children and adults in different contexts, we discuss different methods of measuring and analyzing inter-situational variation along the dialect and standard language spectrum. By contrasting measures of dialectality, on the one hand, and proportions of turns in dialect, standard language or intermediate/mixed forms on the other, we gain complementary insights not only into the individual dialect-standard repertoires but also into the consequences of different methodological choices. The results indicate that intra-individual variation is ubiquitous in adults and children and that individual repertoires need to be taken into account from the beginning of the language acquisition process. We suggest that while intra-individual variation can be attested through the use of various methods, the revealed level of granularity and the conclusions that can be drawn as to the individual repertoires on the dialect-standard spectrum largely depend on the measures used and their inherent assumptions and intrinsically necessary categorizations.

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