6,684 research outputs found
Development of a Ki-67-based clinical trial assay for neoadjuvant endocrine therapy response monitoring in breast cancer
No full textPURPOSE: The recent publication of the ACOSOG Z1031 trial results demonstrated that Ki-67 proliferation marker-based neoadjuvant endocrine therapy response monitoring could be used for tailoring the use of adjuvant chemotherapy in ER+HER2-negative breast cancer patients. In this paper, we describe the development of the Ki-67 clinical trial assay used for this study. METHODS: Ki-67 assay assessment focused on reproducing a 2.7% Ki-67 cut-point (CP) required for calculating the Preoperative Endocrine Prognostic Index and a 10% CP for poor endocrine therapy response identification within the first month of neoadjuvant endocrine treatment. Image analysis was assessed to increase the efficiency of the scoring process. Clinical outcome concordance for two independent Ki-67 scores was the primary performance metric. RESULTS: Discordant scores led to a triage approach where cases with complex histological features that software algorithms could not resolve were flagged for visual point counting (17%). The final Ki-67 scoring approach was run on T1/2 N0 cases from the P024 and POL trials (N = 58). The percent positive agreement for the 2.7% CP was 87.5% (95% CI 61.7-98.5%); percent negative agreement 88.9% (95% CI: 65.3-98.6%). Minor discordance did not affect the ability to predict similar relapse-free outcomes (Log-Rank P = 0.044 and P = 0.055). The data for the 10% early triage CP in the POL trial were similar (N = 66), the percentage positive agreement was 100%, and percent negative agreement 93.55% (95% CI: 78.58-99.21%). The independent survival predictions were concordant (Log-rank P = 0.0001 and P = 0.01). CONCLUSIONS: We have developed an efficient and reproducible Ki-67 scoring system that was approved by the Clinical Trials Evaluation Program for NCI-supported neoadjuvant endocrine therapy trials. Using the methodology described here, investigators are able to identify a subgroup of patients with ER+HER2-negative breast cancer that can be safely managed without the need of adjuvant chemotherapy
Ki-67 is a PP1-interacting protein that organises the mitotic chromosome periphery
No full textCopyright @ 2014 Booth et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.When the nucleolus disassembles during open mitosis, many nucleolar proteins and RNAs associate with chromosomes, establishing a perichromosomal compartment coating the chromosome periphery. At present nothing is known about the function of this poorly characterised compartment. In this study, we report that the nucleolar protein Ki-67 is required for the assembly of the perichromosomal compartment in human cells. Ki-67 is a cell-cycle regulated protein phosphatase 1-binding protein that is involved in phospho-regulation of the nucleolar protein B23/nucleophosmin. Following siRNA depletion of Ki-67, NIFK, B23, nucleolin, and four novel chromosome periphery proteins all fail to associate with the periphery of human chromosomes. Correlative light and electron microscopy (CLEM) images suggest a near-complete loss of the entire perichromosomal compartment. Mitotic chromosome condensation and intrinsic structure appear normal in the absence of the perichromosomal compartment but significant differences in nucleolar reassembly and nuclear organisation are observed in post-mitotic cells
Emerging concepts about prenatal genesis, aberrant metabolism and treatment paradigms in polycystic ovary syndrome
No full textThe interactive nature of the 8th Annual Meeting of the Androgen Excess and PCOS Society Annual Meeting in Munich, Germany (AEPCOS 2010) and subsequent exchanges between speakers led to emerging concepts in PCOS regarding its genesis, metabolic dysfunction, and clinical treatment of inflammation, metabolic dysfunction, anovulation and hirsutism. Transition of care in congenital adrenal hyperplasia from pediatric to adult providers emerged as a potential model for care transition involving PCOS adolescents.Selma F. Witchel, Sergio E. Recabarren, Frank González, Evanthia Diamanti-Kandarakis, Kai I. Cheang, Antoni J. Duleba, Richard S. Legro, Roy Homburg, Renato Pasquali, Rogerio A. Lobo, Christos C. Zouboulis, Fahrettin Kelestimur, Franca Fruzzetti, Walter Futterweit, Robert J. Norman, David H. Abbot
Physical dance performance: An investigation into the development of a performance technique based on the integration of certain Korean dance technique and contemporary Western styles of dance and physical theatre
No full textThis thesis was submitted for the degree of Doctor of Philosophy and awarded by Brunel University, 04/10/2001.This development of a performer practice that integrates elements of traditional Korean dance technique and Western forms of physical theatre and contemporary dance is based on an approach to internal understanding and external execution. Central to the work is the concept of body energy, or Ki. This ancient Eastern term is translated into a contemporary practice that enables a performer to engage mental and physical training. Breath and the use of breath in performing are the principal means of achieving this level of engagement
Les marqueurs de prolifération en oncologie vétérinaire : applications à l'étude pronostique du mastocytome cutané canin
No full textLe mastocytome cutané représente un type tumoral dominant de la cancérologie du chien mais demeure l'une des tumeurs canines au comportement clinique les plus imprévisibles. L'auteur évalue dans une étude rétrospective portant sur 120 chiens porteurs de mastocytome cutané, la valeur pronostique de la détection immunohistochimique des marqueurs de prolifération PCNA et Ki-67. Il montre que la détermination de l'expression de l'antigène Ki-67 permet de prédire avec une grande fiabilité l'évolution clinique post-chirurgicale de ce type tumoral
Tatari, tautoko, tauawhi - Hei awhina tamariki ki te panui pukapuka: Some preliminary findings
No full textThe Tatari, Tautoko, Tauawhi reading tutoring procedures have been adapted from the procedures known as Pause, Prompt, Praise, first developed in Mangere in 1977. The first author offered the procedures as a koha at a Special Education Service hui at Poho o Rawiri in 1991. The second author took up the koha and obtained the support of kaumatua and kuia at Hairini marae Tauranga Moana, and the support of senior Maori staff of the Special Education Service National Office to produce a Maori language video and training booklet. This began an important bicultural journey through the processes of producing instructional materials and trailing and evaluating them in ways that are biculturally appropriate. This paper reports on that journey and presents some preliminary data on the implementation of Tatari, Tautoko, Tauawhi by seven tuakana - teina pairs in a bi-lingual classroom
Genomic Instability and TP53 Genomic Alterations Associate With Poor Antiproliferative Response and Intrinsic Resistance to Aromatase Inhibitor Treatment.
No full textPURPOSE: Although aromatase inhibitor (AI) treatment is effective in estrogen receptor-positive postmenopausal breast cancer, resistance is common and incompletely explained. Genomic instability, as measured by somatic copy number alterations (SCNAs), is important in breast cancer development and prognosis. SCNAs to specific genes may drive intrinsic resistance, or high genomic instability may drive tumor heterogeneity, which allows differential response across tumors and surviving cells to evolve resistance to treatment rapidly. We therefore evaluated the relationship between SCNAs and intrinsic resistance to treatment as measured by a poor antiproliferative response. PATIENTS AND METHODS: SCNAs were determined by single nucleotide polymorphism array in baseline and surgery core-cuts from 73 postmenopausal patients randomly assigned to receive 2 weeks of preoperative AI or no AI in the Perioperative Endocrine Therapy-Individualizing Care (POETIC) trial. Fifty-six samples from the AI group included 28 poor responders (PrRs, less than 60% reduction in protein encoded by the MKI67 gene [Ki-67]) and 28 good responders (GdRs, greater than 75% reduction in Ki-67). Exome sequencing was available for 72 pairs of samples. RESULTS: Genomic instability correlated with Ki-67 expression at both baseline (P < .001) and surgery (P < .001) and was higher in PrRs (P = .048). The SCNA with the largest difference between GdRs and PrRs was loss of heterozygosity observed at 17p (false discovery rate, 0.08), which includes TP53. Nine of 28 PrRs had loss of wild-type TP53 as a result of mutations and loss of heterozygosity compared with three of 28 GdRs. In PrRs, somatic alterations of TP53 were associated with higher genomic instability, higher baseline Ki-67, and greater resistance to AI treatment compared with wild-type TP53. CONCLUSION: We observed that primary tumors with high genomic instability have an intrinsic resistance to AI treatment and do not require additional evolution to develop resistance to estrogen deprivation therapy
Ki-Bot
No full textCopyright is held by the owner/author(s).This paper explores the development of a robotic toy that will be helping students in kinematic physics. Physics has always been a hard class and it is very difficult for students to understand the concepts behind each topic in physics. Ki-bot will help students not only solve kinematic word problems, but also understand the concept of kinematic word problems by testing their answers to word problems on the bot. Ki-bot will essentially bring kinematic word problems to life to help the student understand kinematic physics. The paper will explore the advantages and disadvantages of using interactive toys for learning and will also discuss the other products in the market that help students in kinematic physics. I will also discuss the design decisions, coding decisions, and some of the testing I did in the process of building and developing Ki-Bot. Ki-bot has been successful in showing the proof of concept that this will work in helping students test their answer to word problems and understand them. Additionally, I will discuss the future work that could be done to improve Ki-bot
Overall survival curves for high and low HE staining based on tumour molecular subtype.
No full text<p>Univariate Cox regression used to determine HR; logrank p-values reported. Molecular subtypes were defined by IHC expression of ER, HER2 and Ki-67 as suggested by Cheang <i>et al.</i> (2009) and Hugh <i>et al.</i> (2009). HE: HSP90B1 staining in malignant epithelial tissue. HR: Hazard ratio.</p
Generiert von Kreativer KI: Erforschung Menschlicher Reaktionen auf Informationen über KI als Quelle Kreativer Inhalte
No full textArtificial intelligence (AI) can now be used to produce a wide range of creative content, such as images, stories, music or poems. Reactions to this technological advancement could have an impact on the future development and use of this technology. This thesis examines how the information that creative content has been generated by an AI influences the experience and evaluation of creative works. The focus here is on the reception of stories and images. Possible effects on different forms of experience and judgment are examined using different stimuli materials. In addition, the mechanisms underlying these effects are tested using empirical methods. Furthermore, the potential influence of various individual differences on reactions to AI artist or author information is examined.
Manuscript 1 presents the results of two experiments (N1 = 325, N2 = 489) that indicate a negative influence of AI author information on transportation into a story. Furthermore, it was shown that genre of the story can influence this effect. The negative effects of AI author information are only evident for contemporary fiction stories, but not for the science fiction genre. The eeriness experienced while reading and the willingness to share the story are not influenced by AI artist information as originally hypothesized. Openness, affinity for technology and attitude towards AI do not influence the effect of author information on transportation. Manuscript 2 examines in two experiments (N1 = 176, N2 = 381) whether a lower appreciation of supposedly AI-generated images can be attributed to the reduced agency and experience ascribed to AI compared to humans. Both experiments show a significant indirect effect of AI artist information on the appreciation of AI-generated images, although no total effect can be observed. In addition, a positive deviation from pre-set expectations is considered as a potential mediator of a positive effect of AI artist information on appreciation. However, no mediating effect becomes apparent. Manuscript 3 addresses a possible algorithmic bias in AI-generated images. Results of a content analysis of 324 AI-generated images of people working in STEM professions show that women and POC are
strongly underrepresented. Results of an experiment (N = 495) indicate that these biases are not reflected in responses to AI artist information. Rather, the information that images are AI-generated increases the perceived objectivity of some of the images. Furthermore, AI artist information causes moral outrage when the AI-generated images show older people.
In sum, the information that creative content has been generated by an AI, and not created by a human, can impact responses to these works. However, these effects can be influenced by the genre or the specific content. The reactions to AI artist or author information do not always have to reflect actual tendencies but depend on perceptions of AI.Künstliche Intelligenz (KI) kann inzwischen zur Erstellung vieler kreativer Inhalte, wie Bildern, Geschichten, Musik oder Gedichten genutzt werden. Reaktionen auf diesen technologischen Fortschritt könnten sich auf die künftige Weiterentwicklung und Nutzung dieser Technologie auswirken. Die vorliegende Arbeit untersucht wie die Information, dass kreative Inhalte durch eine KI generiert wurden, das Erleben und die Beurteilung kreativer Werke beeinflusst. Hierbei steht die Rezeption von Geschichten und Bildern im Fokus. Es werden mögliche Effekte auf unterschiedliche Formen des Erlebens und des Beurteilens anhand von unterschiedlichem Stimulusmaterial untersucht. Darüber hinaus werden diesen Effekten zugrunde liegende Wirkmechanismen mit empirischen Methoden geprüft. Außerdem wird der potentielle Einfluss verschiedener individueller Unterschiede auf die Reaktionen auf KI-Künstler- oder Autoreninformationen überprüft.
Manuskript 1 stellt die Ergebnisse zweier Experimente (N1 = 325, N2 = 489) vor, die auf einen negativen Einfluss von KI-Autoreninformationen auf die Transportation in eine gelesene Geschichte hindeuten. Des Weiteren zeigt sich, dass das Genre der Geschichte diesen Effekt beeinflussen kann. Die negativen Effekte der KI-Autoreninformationen zeigen sich nur für Contemporary Fiction Geschichten, nicht aber für Geschichten aus dem Genre Science-Fiction. Die erlebte Eeriness während des Lesens und die Bereitschaft die Geschichte zu teilen werden nicht wie erwartet von KI-Künstlerinformationen beeinflusst. Offenheit, Technikaffinität, sowie die Einstellung gegenüber KI haben keinen Einfluss auf die Wirkung der Autoreninformation auf die erlebte Transportation. Manuskript 2 (N1 = 176, N2 = 381) untersucht, ob eine geringere Wertschätzung vermeintlich KI-generierter Bilder auf die geringere Agency und Experience zurückgeführt werden kann, die KI im Vergleich zu Menschen zugeschrieben wird. In beiden Experimenten zeigt sich ein signifikanter indirekter Effekt der KI-Künstlerinformation auf die Wertschätzung KI-generierter Bilder, obwohl kein totaler Effekt beobachtet werden kann. Darüber hinaus wird eine positive Abweichung von den Erwartungen vor der Rezeption als möglicher positiver Wirkmechanismus von KI-Künstlerinformation auf die Wertschätzung untersucht. Allerdings zeigt sich hier kein mediierender Effekt. Manuskript 3 thematisiert eine mögliche algorithmische Darstellungsverzerrung in KI-generierten Bildern. Ergebnisse einer Inhaltsanalyse von 324 KI-generierten Bildern von Personen, die in MINT-Berufen arbeiten zeigt, dass Frauen und POC stark unterrepräsentiert sind. Ergebnisse eines Experiments (N = 495) deuten darauf hin, dass diese Verzerrungen nicht in den Reaktionen auf KI-Künstlerinformationen abgebildet sind. Vielmehr erhöht die Information, dass Bilder KI-generiert sind für einige der Bilder die wahrgenommene Objektivität dieser. Darüber hinaus rufen KI-Künstlerinformationen Empörung hervor, wenn die KI-generierten Bilder ältere Menschen zeigen.
Zusammenfassend lässt sich festhalten, dass die Information kreative Inhalte seien durch eine KI generiert und nicht durch einen Menschen geschaffen, zu veränderten Reaktionen auf diese Werke führen kann. Diese Effekte können allerdings durch das Genre bzw. den spezifischen Inhalten beeinflusst werden. Hierbei müssen die Reaktionen auf KI-Künstler- oder Autoreninformation nicht immer tatsächliche Tendenzen widerspiegeln, sondern sind stärker von der Wahrnehmung von KI abhängig
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