Peter Miller Research Articles

Abstract P5-14-03: Clonal hematopoiesis of indeterminate potential after (neo)adjuvant chemotherapy versus endocrine therapy for early breast cancer: the CIRCE-eBC prospective cohort study

Abstract Clonal hematopoiesis of indeterminate potential after (neo)adjuvant chemotherapy versus endocrine therapy for early breast cancer: the CIRCE-eBC prospective cohort study Background: Clonal hematopoiesis of indeterminate potential (CHIP) is an age-related condition associated with higher risk of hematologic malignancies, cardiovascular disease, and all-cause mortality. Patients (pts) with early breast cancer (eBC) receiving chemotherapy (CT) have increased risk of treatment-related myeloid neoplasms (tMN); the benefit of CT in eBC pts is often limited. Little is known about the prevalence and dynamics of CHIP in eBC pts. Methods: We prospectively identified two cohorts of pts with eBC: cohort A – pts receiving (neo)adjuvant CT with or without adjuvant endocrine therapy (ET); cohort B – pts receiving ET only. Blood was collected prior to initiation of treatment (T1) and after either (neo)adjuvant CT or 6-18 months of adjuvant ET (T2). We performed targeted sequencing of cryopreserved peripheral blood mononuclear cell (PBMC)-derived genomic DNA and defined CHIP as the presence of ≥1 pathogenic somatic mutation at variant allele fraction (VAF) ≥0.02. In additional analyses we used VAF≥0.005. Results: We enrolled 118 and 116 pts in cohorts A and B, respectively. Pts in cohort A were younger (median age 51 vs 57, p< 0.001), less frequently Caucasian (83.9 vs 96.6%; p=0.005) and former/current smokers (28.0 vs 43.1%, p=0.038). All pts in cohort B had hormone receptor-positive (HR+) eBC; in cohort A 50% of pts had HR+/HER2-, 16% had HR+/HER2+, 8.5% had HR-/HER2+ and 25.4% had HR-/HER2- eBC (p< 0.001). Pts in cohort A had higher stage (stage II-III 68.7 vs 27.6%; p< 0.001) and grade (grade 3 65.3 vs 15.5%; p< 0.001) tumors. Genetic testing was more frequently performed in pts receiving CT (88.1 vs 68.1%, p< 0.001), though the rate of germline pathogenic variants was similar (13.5 vs 17.7%, p=0.079). In cohort A, 38% received anthracyclines, 7% platinum and 57% anthracycline/platinum-sparing CT. Median time between T1 and T2 was 189.5 (150,406) and 280 (147, 425) days in cohort A and B (p< 0.001). The prevalence of CHIP, defined by mutations at VAF ≥ 0.02, was similar at T1 in cohort A (14.4%) vs B (18.1%) (p=0.556). Number of pts with new CHIP variants at T2 was also similar (A 3.4% vs B 6.0%) (p=0.373). After adjusting for age and stage, odds ratio (OR) of developing new CHIP variants in cohort B vs A was 1.28 (95% CI 0.32 – 5.68, p=0.733). Age correlated with baseline prevalence of CHIP (p< 0.001). Most frequent new CHIP variants at T2 in cohort A were DNMT3A (3), PPM1D (1), NF1 (1). To investigate whether pts receiving CT were more likely to have emergence of small hematopoietic clones, we assessed pathogenic variants present at VAF ≥0.005. These were detected at T1 in 55 (46.6%) and 61 (52.6%) pts in cohort A and B, respectively. Few pts without pathogenic variants at T1 developed them at T2 (3 pts in cohort A and 4 in cohort B). 21 pts (27 variants) in cohort A and 11 pts (12 variants) in cohort B had new variants at T2. Pts with new variants vs not (32 vs 202 pts) had similar characteristics, excepting age (median 60.5 vs 54.0, p=0.011). After correcting for age and stage, OR of developing new pathogenic variants given ET vs CT was 0.25 (95% CI 0.10-0.62, p=0.003). Most frequent newly detected variants were in DNMT3A (14), PPM1D (5), TET2 (4) and TP53 (2) in cohort A; DNMT3A (3), TET2 (3) and ZNF318 (2) in cohort B. Conclusions: In the CIRCE-eBC study, CT administration did not lead to emergence of CHIP over a 6-9 month period vs ET alone. This finding is reassuring in the setting of long life-expectancy for eBC pts and the association of CHIP with significant morbidity and mortality. However, consistent with known risk of development of MN, CT was associated with emergence of low frequency pathogenic variants in PPM1D and TP53, which have been associated with elevated risk of tMN. The evolution and prognostic role of these small clones is unclear and warrants additional investigation. Citation Format: Stefania Morganti, Qingchun Jin, Katheryn Santos, Christopher Gibson, Ashka Patel, Alex Wilson, Margaret Merrill, Julie Vincuilla, Samantha Stokes, Marla Lipsyc-Sharf, Tonia Parker, Tari King, Elizabeth A. Mittendorf, Giuseppe Curigliano, Melissa E. Hughes, Nabihah Tayob, Nancy U. Lin, Peter Miller, Sara Tolaney, Judy Garber, Heather A. Parsons. Clonal hematopoiesis of indeterminate potential after (neo)adjuvant chemotherapy versus endocrine therapy for early breast cancer: the CIRCE-eBC prospective cohort study [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P5-14-03.

Accounting as a social practice: US railroad regulation, value of service accounting, and regional economic development

Employing a methodological model proposed by Anthony G. Hopwood and refined by Peter Miller, which emphasizes the role of accounting as a social practice, this study examines how the US Interstate Commerce Commission (ICC) accepted the application of the value of service accounting in rate-setting to facilitate the redistribution of income and wealth to the undeveloped economies of the South and West regions of the US.

Abstract 153: Quantifying tumor heterogeneity and mapping complex immune cell interactions with high-throughput, 7-color multispectral slide scans

Abstract Introduction As the need for multiple biomarker assessment in immune-oncology has become more clear, multiplex fluorescent immunohistochemistry (fIHC) techniques have become integral to immune oncology research. Applying multispectral approaches to fIHC improves the quantitative performance by ensuring removal of autofluorescence signals and ensuring signal specificity by removing bleed-through between spectrally-adjacent dyes. We have recently demonstrated a novel high-throughput multispectral scanning approach that allows acquisition of a 7-color multispectral slide scan in 5 - 10 minutes. Here, we demonstrate the spatial measurements that have now been made possible by this high-throughput, translational workflow. These measurements span the scales related to tumor biology from the distance between nearest cell neighbors to the extent of the invasive margin. Methods Formalin-fixed paraffin-embedded samples of primary tumors were immunostained using Opal™ reagents. Tissue sections from primary tumors (lung, melanoma, colorectal, lymphoma)were stained against 5 markers of key interest in the field of immune oncology (CD8, FoxP3, PD-1, PD-L1, CD68) along with a tumor marker (Cytokeratin, Sox10&S100, PAX5 or PAX8) and DAPI counterstain, resulting in 7 colors on each slide. Conventional and multispectral digital scans were acquired on a Vectra Polaris® automated imaging system and analyzed with inForm® and R software using the phenoptr and phenoptrReports packages. Results Multispectral scans showed a wide variety of immunological states among samples and within samples. We observed differences in the overall composition and density of immune cells in the tumor microenvironment, and further distinctions when looking at the local proximities of cell types and cells expressing either PD-1 or PD-L1, based on marker combinations that could not be observed with a conventional 3- or 4-color slide scan. We developed spatial analyses to visualize and quantify this observed heterogeneity, both across the entire tissue and along the invasive margin. These tools revealed hot spots of immune activity and were further used to compare and categorize the properties of different tumors. Furthermore, when compared with results from analogous scans analyzed without spectral unmixing, the unmixed imagery showed a marked improvement in the dynamic range of detected positive cells. Conclusion These tools for spatial analyses of whole-section 7-color multispectral slide scans provide translational researchers the opportunity to discover and validate biomarkers that capture immuno-biological interactions at microscopic and macroscopic scales, to better understand drug method-of-action and why some patients respond and some don’t. Citation Format: Carla Coltharp, Kent Johnson, Wenliang Zhang, Chichung Wang, Kristin Roman, Daniel Eversole, Clifford Hoyt, Peter Miller. Quantifying tumor heterogeneity and mapping complex immune cell interactions with high-throughput, 7-color multispectral slide scans [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 153.

Un panorama del efecto Foucault en contabilidad y gestión pública temáticas, autores y retos de investigación desde la gubernamentalidad

En este documento se presenta un panorama del efecto Foucault en contabilidad y gestión pública, con el fin de evidenciar temáticas, autores y vacíos de investigación desde los estudios en gubernamentalidad. La unidad de análisis fueron setenta textos seleccionados en una revisión sistemática de artículos publicados entre 2012 y 2016, en cinco de las principales revistas internacionales relacionadas con las disciplinas analizadas. Para la recolección de los datos y la codificación de la información se utilizó una matriz de Excel y el software de investigación cualitativa Atlas.ti, versión 7.5.16. La comprensión de la información se complementó con un método de análisis de frecuencia y un análisis de red. Dentro de los resultados se destacan cuatro ejes temáticos: la gestión calculada, el gobierno a distancia, la modernización del gobierno y la contabilidad de la ciudad. Además, los cinco autores que más han publicado en el tema: Dean Neu, Cameron Graham, Eric Pezet, Ingrid Jeacle y Peter Miller, así como las redes de cooperación entre países, dentro de los cuales se evidencia a Reino Unido y Canadá. También se identifica que el principal reto de investigación está en entender la contabilidad de las ciudades de las llamadas economías emergentes. Así, este artículo hace contribuciones importantes para la contaduría y la administración, en especial, se establecen herramientas teóricas para que los investigadores estudien la contabilidad y su incidencia en la gestión de las ciudades, desde la perspectiva de la gubernamentalidad, en aras de avanzar en este tópico que requiere de discusión en Latinoamérica para repensar las incidencias del cálculo contable y la gestión del ciudadano.

These Aren't the Paraproteins You Have Been Looking for: A Case of Light Chain Deposition Disease

SESSION TITLE: Pulmonary Manifestations of Systemic Disease SESSION TYPE: Affiliate Case Report Slide PRESENTED ON: Tuesday, October 31, 2017 at 08:45 AM - 10:00 AM INTRODUCTION: Light chain deposition disease (LCDD) is a rare paraproteinemia with primarily renal involvement characterized most commonly by kappa light chain deposits in the kidney. While case reports exist, lung involvement continues to be a rare finding. CASE PRESENTATION: 73 year old male with a past medical history of osteoporosis presented with a two month history of back pain and generalized weakness. Initial presentation was notable for pancytopenia as well as acute kidney injury. Serum protein electrophoresis showed an M-spike in the beta region as well as elevated IgA monoclonal protein with light chain specificity. A bone marrow biopsy was performed and showed extensive serous atrophy and markedly hypocellular marrow. Extensive work-up for multiple myeloma remained non-diagnostic. The patient developed respiratory failure requiring intubation. CTA of chest demonstrated diffuse ground glass opacification throughout all lung fields. There was concern for infection, but all cultures including bronchoalveolar lavage were negative. The patient had worsening respiratory and renal function despite aggressive care. Ultimately, family decided to pursue comfort directed care in accordance with patient’s previously stated wishes regarding prolonged mechanical ventilation and dialysis. Renal specimens obtained at autopsy revealed congo red negative fractured intratubular eosinophilic casts with kappa staining on immunofluorescence consistent with light chain deposition disease. Lung pathology revealed diffuse bronchiolitis obliterans with organizing pneumonia as well as congo red negative amorphous eosinophilic material within alveoli consistent with LCDD. DISCUSSION: Light chain deposition disease remains an important differential in plasma cell dyscrasias, particularly AL amyloidosis. Lung involvement of LCDD is an especially rare finding of an already rare disease. While organizing pneumonia is described with hematologic malignancy, it has not been described with LCDD which typically is characterized by nodules and/or cysts. CONCLUSIONS: This case demonstrates an unusual presentation of a rare manifestation of light chain deposition disease. Recognition of secondary bronchiolitis obliterans as a potential manifestation may help avoid critical delays in treatment. Reference #1: Sayed, RH, et al. “Natural history and outcome of light chain deposition disease.” Blood (2015);126:2805-2810 Reference #2: Sheard, S, et al. “Pulmonary light-chain deposition disease: CT and pathology findings in nine patients.” Clinical Radiology (2015); 70;515-522 DISCLOSURE: The following authors have nothing to disclose: Aaron Lampkin, Peter Miller, Tim Gallagher No Product/Research Disclosure Information

Abstract 3832: Optimization strategy for fluorescent multiplex immunohistochemistry tissue staining

Abstract Introduction: Recent insights into the tumor microenvironment have fueled the need for additional information beyond the one or two phenotypes provided by traditional immunohistochemistry (IHC). As a response, manual and automated fluorescent multiplex immunohistochemistry (fIHC) techniques have been recently developed and accepted by the immuno-oncology space. Fluorescent multiplex immunohistochemistry (fIHC) assays are designed to simultaneously measure multiple biomarkers in tissue sections with visual context that is lost in other methods, such as flow cytometry. Here we describe a novel optimization strategy to achieve quantitative, robust, and specific multiplex fIHC staining results with both manual and automated multiple-color Opal procedures. Methods: Formalin-fixed paraffin-embedded samples of primary tumors were immunostained using Opal™ reagents both manually and on a fully automated Leica BOND RX™ stainer. The impact of different reagent concentrations and quantities were analyzed in respect to signal specificity and robustness, stripping efficiency, signal co-localization, signal to noise, and color separation. Images were acquired on a Vectra 3.0® automated imaging system, and analyzed with inForm® software. Results: The goals of this study were two-fold: -to understand the impact of Opal reagent concentrations/quantities on fluorescent signal intensities acquired from cells within the context of tissue. -to develop an Opal reagent optimization method that yields more consistent, quantitative results from separated and co-localized fluorescent signals. We’ve applied this novel fIHC experimental approach and optimization strategy to Opal monoplex and multiplex assays and explored staining robustness, contextual specificity, staining order independence, and co-localized signal separation. Using the novel optimization strategy, we have achieved optimal staining patterns with improved confidence in the quantitative characteristics of the assay. Tissue sections stained after optimization have exhibited staining order independence and closely align with traditional IHC patterns. Conclusion: This novel optimization strategy, developed for Opal fIHC assays, is more quantitative, improves staining results, and minimizes interference between co-localized biomarkers. Citation Format: Yi zheng, Carla Coltharp, Ryan Dilworth, Linying Liu, Darryn Unfricht, Cliff Hoyt, Milind Rajopadhye, Peter Miller. Optimization strategy for fluorescent multiplex immunohistochemistry tissue staining [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3832. doi:10.1158/1538-7445.AM2017-3832

Abstract 4246: Multispectral open-air fluorescence-guided imaging and detection of tumors using a hands-free translational platform with liquid crystal tunable filters (LCTF)

Abstract Intraoperative identification and resection of tumors currently relies on the ability of the surgeon to visually detect or palpate the tumors and residual malignant tissue. As such, minuscule tumor nodules can go undetected or be inadequately removed, with such cases often resulting in the need for secondary treatment or additional surgical intervention. The Solaris™ platform is an open-air fluorescent imaging instrument designed for large animal fluorescence-guided surgery, with the advantage of real-time acquisition of fluorescence images/video under surgical light conditions. Solaris supports four fixed fluorescent channels ranging from visible to near infrared (NIR), and a multispectral channel where a liquid crystal tunable filter (LCTF) is used to acquire spectral data by sweeping across the green-to-red portion of the visible spectrum. This range of imaging channels allows for single-wavelength and multispectral imaging of widely used reagents (e.g. indocyanine green [ICG] and Fluorescein isothiocyanate [FITC]) and unique NIR fluorescent dyes used for detecting and labeling tumors. While fluorescent imaging using NIR imaging agents (680, 750, 800 nm) offered effective tumor detection, identification of tumors implanted in nude mice or rats using visible (400-650 nm) reagents such as FITC presented challenges considering the presence of auto-fluorescence originating from tissue and food (alfalfa). For these reagents, Solaris acquired multispectral images using the LCTF under ambient light conditions, and an automated spectral unmixing algorithm was applied to the multispectral data, after background correction and ambient light removal, to separate tissue and food auto-fluorescence from the reagent fluorescent signal. The algorithm used vertex component analysis to automatically extract the primary pure spectra present in the multispectral images and unmix the reagent fluorescent signal by non-negative least squares fitting. To test the spectral unmixing capabilities of Solaris, in vivo experiments were performed using small amounts of locally injected FITC in mice and rats. In the absence of unmixing, it was not possible to accurately detect sites of FITC signal, but with unmixing the labeled regions were well defined. Additional studies in tumor-bearing mice and rats substantiated the ability to spectrally unmix FITC agent signal in deep tumor masses imaged under ambient light, enhancing the ability to surgically resect them. To further validate this concept, bioluminescent tumor cell lines were implanted in mice. After image-guided tumor resection, both the residual tumor bed and the resected tumors were imaged to confirm complete removal. These data demonstrate that intraoperative image-guided resection of fluorescent-labeled tumors can be achieved using LCTF-based open-air multispectral imaging on the Solaris. Citation Format: Ali Behrooz, Kristine Vasquez, Peter Waterman, Jeff Meganck, Jeffrey Peterson, Peter Miller, Joshua Kempner, Wael Yared. Multispectral open-air fluorescence-guided imaging and detection of tumors using a hands-free translational platform with liquid crystal tunable filters (LCTF). [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4246.

Book review: Peiresc’s Orient: Antiquarianism as Cultural History in the Seventeenth Century, written by Peter Miller

Book review: Peiresc’s Orient: Antiquarianism as Cultural History in the Seventeenth Century, written by Peter Miller

Christopher Chapman, David Cooper, and Peter Miller ed. 2009. Accounting, Organizations and Institutions:

Christopher Chapman, David Cooper, and Peter Miller ed. 2009. Accounting, Organizations and Institutions:

Governing culture: Legislators, interpreters and accountants

Cultural policy has become dominated by questions of how to account for the intangible value of government investments. This is as a result of longstanding developments within government’s approaches to policy making, most notably those influenced by practices of audit and accounting. This paper will outline these developments with reference to Peter Miller’s concept of calculative practices, and will argue two central points: first, that there are practical solutions to the problem of measuring the value of culture that connect central government discourses with the discourses of the cultural sector; and second, the paper will demonstrate how academic work has been central to this area of policy making. As a result of the centrality of accounting academics in cultural policy, for example in providing advice on the appropriate measurement tools and techniques, questions are raised about the role academia might take vis-a-vis public policy. Accounting professionals and academics not only provide technical expertise that informs state calculative practices, but also play a surveillance role through the audit and evaluation of government programmes, and act as interpreters in defining terms of performance measurement, success and failure. The paper therefore concludes by reflecting on recent work by Phillip Schlesinger to preserve academic integrity whilst allowing accounting scholars and academics influence and partnership in policy.

Valuation and Calculation at the Margins

Not Available.

Examining Torture: Empirical Studies of State Repression. Edited by Tracy Lightcap and James Pfiffner. New York: Palgrave Macmillan, 2014. 218 pp. $105 cloth.

Examining Torture: Empirical Studies of State Repression. Edited by Tracy Lightcap and James Pfiffner. New York: Palgrave Macmillan, 2014. 218 pp. $105 cloth.Torture is a difficult subject to research. Perpetrators almost always attempt to hide their acts, making any kind of systematic data collection challenging. If one is able to gather data, research on such a subject is often received with ambivalence. Raising the question of whether torture works can run the risk of seeming to justify the violence, as can inquiries into the reasons states and their representatives engage in torture. Still, it is of great importance to glean what is possible about why torture occurs and how it might be prevented. Makes a significant contribution to that aim.Many of the studies refute common assumptions. Rejecting the claim that an American majority supports torture, Peter Miller and his colleagues show that this has rarely been the case. Support for torture did increase, however, among Republicans during the Obama Administration, which the authors argue indicates the effect of elite messages on public opinion. Jeremy Mayer and his colleagues find that terrorism does not increase support for torture, contrary to what many researchers assume, but that the degree of political freedom in a country is inversely related to such support. A study of anti-torture advocacy by Courtenay Conrad and Jacqueline DeMeritt fails to show any positive effect of naming and shaming for government practices, and in fact shows that such efforts are associated with increased government repression in other areas. The authors seem to regret this finding, and express the hope that naming and shaming is effective in ways not captured by their study. These studies call readers' attention to the ways in which common assumptions, such as about the factors that influence support for torture and the measures that prevent it, are not always supported by evidence.Other chapters provide further empirical and theoretical support to conclusions that are more prevalent or intuitive. Henry Carey points to a country's reliance on international alliances and corresponding willingness to uphold international agreements as key to whether a government engages in torture. Tracy Lightcap shows that governments are more likely to torture when there is an asymmetrical war that threatens the stronger regime's position or projects. James Pfiffner makes a strong argument in two chapters that torture has undermined both the moral authority and strategic interests of the United States, and that it is ineffective at producing good intelligence.The authors address distinct but interrelated questions, and synthesizing their findings or at least considering them in light of each other would be illuminating. For example, drawing on a previous study he conducted on torture reform in the United States, France, Israel, and Argentina, Carey concludes that a government's willingness to engage in reform depends on perceived national security threats. In another chapter, however, Miller and colleagues find that the actual level of threat does not predict the use of torture by a government. What might explain this discrepancy? Should the reader conclude that the level of real or perceived threat from acts of terrorism is not sufficient to induce a government to begin using torture, but that a government that already uses torture will be unwilling to change its practices as long as the threat prevails? …

Abstract LB-208: Open air fluorescence imaging of tumors using a new, hands-free translational imaging system

Abstract Intraoperative tumor resection currently relies on the ability of a surgeon to visually detect and/or palpate the tumor and tumor margins. Small tumor nodules can be missed or tumor margins may be inadequately removed, resulting in the need for secondary treatment. Intraoperative fluorescence imaging can help improve the initial resection and, therefore, both improve outcomes and reduce cost. Unconjugated fluorescent dyes have been previously used for this type of study to identify tumors in first-in-human studies. However, dyes conjugated to a targeting moiety have better specificity for the tumor itself and provide better guidance for the surgeon to locate the tumor and remove margins. The new Solaris imaging system is an open air fluorescence imaging instrument designed specifically for intraoperative imaging in small to large animals. The system supports 4 different fluorescence channels to image common dyes (e.g. indocyanine green [ICG] and Fluorescein isothiocyanate [FITC]) and more unique near-infrared (NIR) fluorescent dyes. All of these can be imaged in ambient light to achieve sensitivities of 10 nM for single, long exposures and 10-100 nM for videos. The imaging head is attached to an adjustable arm so that it be can be positioned 75 cm above the object plane, far enough to be considered outside of the sterile field. The imaging head also has two cameras for simultaneous fluorescence and bright field (color) imaging; these images can be overlaid in the software. Single, long exposure images acquired from 2 different wavelengths can be overlaid to enable multiplexing and improve tumor identification; previously published studies have shown this to be useful for sentinel lymph node detection. For FITC, a custom liquid crystal tunable filter (LCTF) is included in the system in tandem with spectral unmixing software to separate tissue autofluorescence from fluorescence emitted by the dye. Although this system is designed for larger animals, proof of concept intraoperative tumor resection has been performed in rodents. Subcutaneous tumors have been resected while imaging mice injected with either the targeted agent IntegriSense™ 680 or the activatable agent ProSense® 750. To investigate a more challenging model, tumor cell lines have also been implanted intrasplenically in rats. After injection with either the targeted agent BombesinRSense™ 680 or the activatable agent MMPSense® 750, deep tissue tumors can be identified intraoperatively and removed. Both the residual tumor bed (in vivo) and the resected tumors (ex vivo) can be imaged to confirm complete resection. In addition, although there are depth limitations due to the absorption and scattering of light in tissue, images acquired using a rat osteoarthritis model also provides insight into the ability to detect targeted fluorescence agents non-invasively. These results suggest that intraoperative resection of tumors detected with both targeted and activatable fluorescent agents is feasible using the new Solaris imaging system. Citation Format: Jeffrey A. Meganck, Kristine Vasquez, Jeffrey Peterson, Chris Condron, Ali Behrooz, Josh Kempner, Alexandra de Lille, Yiyong Tan, Pete Harvey, Hongyan Gu, Paul Kennedy, Mathew Roxo, Ilias Faqir, Yan Zhang, Leo Mirkin, Peter Miller, Wael Yared. Open air fluorescence imaging of tumors using a new, hands-free translational imaging system. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr LB-208. doi:10.1158/1538-7445.AM2015-LB-208

Destabilizing Haemon: Radically Reading Gender and Authority in Sophocles’ Antigone

Destabilizing Haemon: Radically Reading Gender and Authority in Sophocles’ Antigone1 Peter Miller (bio) As Mark Griffith (1999, 51) has remarked, “Gender lies at the root of the problems of Antigone,” but much of that attention to gender has focused on analyzing Antigone (e.g., Griffith 2001, Žižek 2004), or the relationship of marriage and consummation in Haemon’s violent suicide (Seaford 1987, 120–1; Griffith 1999, 339; Ormand 1999, 79–98). While Haemon’s suicide has been understood as a sexual act, scholars have overlooked the inherent ambiguities in this performative action. By connecting Haemon’s suicide to Antigone’s broader interest in alternative constructions of gender, I read here his multifarious and performative death as an indicator of gender’s fluidity and instability; Haemon problematizes the construction of subjectivity, since it is intrinsically linked to gendered identity. Although the play ends conservatively (Griffith 1999, 56–7), readers and audiences are not obliged to accept this conclusion. Rather, Haemon’s actions in the play destabilize, at least, the binary and categorical construction of gender and sexuality and the hierarchical and repressive understanding of subjectivity, which remains, even at the tragedy’s conclusion, institutionalized. Through an interpretation that emphasizes the multiplicity of performativities and identities that cohere in Haemon, and the reception of his radical identity in the course of the tragedy, an alternative emerges that stresses ambiguity and anti-authoritarianism, instead of descriptivism and tyranny.2 Although there is a rich history of criticism that locates a confrontation between oikos and polis in Antigone (e.g., Hegel 1977; cf. Sourvinou-Inwood 1989, 137), or a confirmation of or challenge to kinship models (e.g., Butler 2000, Lacan 2000), my focus is on social identity and the relationship of gender, subjectivity, and authority. By defining Haemon’s suicide as a fundamentally ambiguous performative action, I underscore its malleability in the plot of the tragedy, and the ability of audiences both internal (e.g., the Theban dêmos) and external (e.g., the Athenian dêmos, and audiences and readers today) to find, in Haemon’s death, a potential escape from the strictures of authority. I begin with an analysis of the agôn between Creon and Haemon (631–780), in which Creon’s [End Page 163] challenge to Haemon’s social and gendered identity begins. Having interpreted this interaction in light of Creon’s increasingly totalitarian control over the polis, I move to the Messenger’s speech, Creon’s actions prior to entering the cave (1192–1218), and finally, the interaction between Haemon and Creon in the cave with the suicide itself (1226–43). By situating the confrontation in the cave as a continuation of the prior agôn, I stress how Creon’s tyranny has undermined the ability of Haemon to claim a social and gendered identity outside the bounds of his regime. In the conclusion, however, I reread the suicide scene, taking into account the political unrest in Thebes, as well as Judith Butler’s critique of Althusser, and the potential radicalism of the subject who refuses ideologically contingent subjectivity (especially Butler 1993, 121–40). The suicide scene is the culmination of the interaction between Haemon and Creon in Antigone; this interaction, however, begins prior to the Haemon’s appearance on the tragic stage. Just before Haemon’s entrance, Creon foresees a possible dispute with his son in what, as we shall see, is significant language: (631–4) We’ll soon know, better than the seers. My child, having heard the final decree concerning your future bride, Surely you aren’t coming here now, raving mad with your father? Or, in everything I do, am I dear to you?3 After Creon’s initial explanation of what makes an ideal child (639–80: constructed, perhaps tellingly, through masculine clichés), Haemon enacts an ultimately futile defense of Antigone. First, he reports the opinions of the Theban population, gathered by eavesdropping from the shadows (, 692). While such reports likely represent unrest within the city, the gendered quality of gossip may be relevant (McClure 1999, 56–62), especially given Creon’s imminent turn to gender-based insults.4 Such insults may hinge on (700) as a dangerous corruption of...

Unsettled Scores: Meter and Play in Two Music Poems by Browning

Previous articleNext article No AccessArticlesUnsettled Scores: Meter and Play in Two Music Poems by BrowningHerbert F. TuckerHerbert F. Tucker Search for more articles by this author PDFPDF PLUSFull Text Add to favoritesDownload CitationTrack CitationsPermissionsReprints Share onFacebookTwitterLinkedInRedditEmail SectionsMoreDetailsFiguresReferencesCited by Critical Inquiry Volume 41, Number 1Autumn 2014 Article DOIhttps://doi.org/10.1086/678156 Views: 117Total views on this site Citations: 3Citations are reported from Crossref © 2014 by The University of Chicago. 0093-1896/14/4101-0011$10.00. All rights reserved.PDF download Crossref reports the following articles citing this article:Peter Miller Prosody, Media, and the Poetry of Edgar Allan Poe, PMLA/Publications of the Modern Language Association of America 135, no.22 (Oct 2020): 315–328.https://doi.org/10.1632/pmla.2020.135.2.315Jahan Ramazani The Local Poem in a Global Age, Critical Inquiry 43, no.33 (Mar 2017): 670–696.https://doi.org/10.1086/691005Anna Peak THE CONDITION OF MUSIC IN VICTORIAN SCHOLARSHIP, Victorian Literature and Culture 44, no.22 (May 2016): 423–437.https://doi.org/10.1017/S1060150315000716

Research Spotlights

The analysis of generalized eigenvalue problems is central to understanding a number of complex phenomena, including the stability of nonlinear waves. One generally seeks a characterization of a linearized spectrum in relation to the complex plane (e.g., eigenvalues strictly in the right half plane) from which one can deduce the stability of the system and the presence of features such as bifurcations of Hamiltonian--Hopf type. Two fundamentally different but useful tools for analyzing spectral stability include the Krein signature and the Evans function. The Krein signature is helpful in investigating the stability of purely imaginary eigenvalues (i.e., whether eigenvalues will move toward the right half plane under perturbations), while the Evans function can be used to detect eigenvalue locations. The paper “Graphical Krein Signature Theory and Evans--Krein Functions,” by Richard Kollár and Peter Miller, highlights a graphical interpretation of the Krein signature and more specifically stresses the utility of this graphical interpretation. On the computational side, the graphic interpretation is used to adapt the notion of an Evans function to an Evans--Krein function. The new generalization allows one to calculate the Krein signature in a way that is easy to incorporate into existing simulation capabilities that are already capable of evaluating an Evans function. This is in contrast to the traditional Evans function which cannot generally be used to directly deduce the Krein signature. In addition to this computational utility, the graphical interpretation of the Krein signature has nice theoretical properties as demonstrated by a set of proofs associated with index theorems for linearized Hamiltonians and includes relations to the well-known Vakhitov--Kolokolov criterion.

The Ethical Implications of Organism-Environment Interdependency

Modern ethical perspectives toward the environment often emphasize the connection of humans to a broader biotic community. The full intimacy of this connectedness, however, is only now being revealed as scientific findings in developmental biology and genetics provide new insights into the importance of environmental interaction for the development of organisms. These insights are reshaping our understanding of how organism-environment interaction contributes to both consistency and variation in organism development, and leading to a new perspective whereby an “organism” is not solely viewed as the adaptive product of evolutionary selection to an external environment over generations, but as continuously being constructed through systems of interactions that link an organism’s characteristics developmentally to the physical and social influences it experiences during life. This newfound emphasis on “interaction” leads to an interdependency whereby any change to an “environment” impacts the interacting “organism(s),” and an alteration to the “organism” eventually affects its “environment.” The causal reciprocity embedded within this organism-environment interdependency holds implications for our moral obligations to environments, given their compulsory role in shaping all organisms including ourselves. * Biological Sciences Department, Center for Coastal Marine Sciences, California Polytechnic State University, San Luis Obispo, CA 93407; e–mail: slema@calpoly.edu. Lema’s research focuses on understanding the physiological and genetic mechanisms underlying the phenotypic responses of organisms to changing environments, the effects of chemical pollutants on hormone signaling, and the incorporation of phenotypic plasticity into new approaches for animal conservation. The author thanks Kenneth Wilson, Kristin Hardy, and two anonymous referees, Peter Miller and Holmes Rolston, III, for their helpful comments and suggestions on this manuscript. 1 See, for example, Don E. Marietta, Jr., “The Interrelationship of Ecological Science and Environ -mental Ethics,”

Art for integration: political rationalities and technologies of governmentalisation in the city of Malmö

Cities increasingly use artistic and cultural activities to promote active citizenship and social cohesion. We suggest that city-sponsored cultural and artistic practices in Sweden are finding a new discursive context in migration. In this article, we look at two artistic and cultural institutions in Malmö, Sweden: Arena 305 and Drömmarnas hus. We develop a typology of governmentalisation based on the work of Nicholas Rose and Peter Miller, which allows us to describe the governing activity of Arena 305 and Drömmarnas hus. What becomes visible is the discrepancy between the moral form of the political rationalities and the technologies of government: even though institutions may harbour ideals and principles of inclusion, they are perfectly capable of sustaining activities that brighten the very boundaries they set out to challenge.

Abstract 2679: Clinical validation of high throughput AQUA and multispectral imaging for breast cancer.

Abstract Introduction: The high discordance currently identified in the scoring of breast cancer biomarkers ER, PR, Ki67 and Her2, which directly impact patient management, drives a growing clinical need for the development of diagnostic tests which will offer enhanced reproducibility while maintaining accuracy in a high throughput environment. We currently offer AQUA® technology in our clinical lab for breast cancer. A significant limitation to using this technology within a diagnostic laboratory is low throughput and manual annotation of patient invasive tumor. To address this, we evaluated the Vectra2™ automated multispectral slide analysis system to address these issues in a clinical environment with a focus on quality and pathologist involvement. Materials and Methods: All results were generated using clinical samples. The Vectra system was used to acquire breast biomarker expression in invasive tumor regions scored by AQUA technology. The multi-step process of image acquisition was assessed in conjunction with the reproducibility of region selection for scoring as determined by invasive cancer tissue classifier algorithms developed through the use of Inform and Nuance applications. We also developed a review application to allow remote access to images prior to reporting of patient results. Results: Normalization of system intensity compensation produced intensity values approaching unity. Algorithms defining invasive tissue score were found to be highly correlative (R2=0.949) to the current clinical platform with pathologist annotation. Together, these features resulted in acquisition of conserved regions of invasive tumor in a highly reproducible fashion, such that for the same sample on multiple days and instruments, R2=0.9571 (∼12%CV). Scores were consistent amongst varying parameters, including repeated scanning (∼9 %CV, n=13 runs) and differing field sampling parameters while decreasing time to 15 min per slide for processing with parallel analysis. Our development of the Vectra Review software enables visualization of regions selected for biomarker scoring that can be reviewed by clinical staff remotely, while not impacting overall workflow. Conclusion: We show that the Vectra 2 platform is as accurate as our currently clinically validated platform for AQUA scoring of ER, PR, Her2, and Ki67. Introduction of advanced tissue finding algorithms concisely recognize relevant tissue regions unique to each biomarker without manual annotation, greatly improving the clinical workflow. This deployment of digitalized pathology results in a reduction of time to generate scores which marks a significant advance for our clinical lab. Overall, we demonstrate the AQUA paired Vectra2 system as a highly robust, reproducible and high throughput advance to our currently available diagnostic breast cancer platform, while addressing the need to easily allow for clinical lab and pathologist review. Citation Format: Cristen K. Hays, Danielle Murphy, Bana Mouwakeh, Peter Miller, Clifford Hoyt, Jason Christiansen. Clinical validation of high throughput AQUA and multispectral imaging for breast cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2679. doi:10.1158/1538-7445.AM2013-2679

Nikolas Rose

Nikolas Rose