An Aggregation of Aggregation Methods in Computational Pathology

Image analysis and machine learning algorithms operating on multi-gigapixel whole-slide images (WSIs) often process a large number of tiles (sub-images) and require aggregating predictions from the tiles in order to predict WSI-level labels. In this paper, we present a review of existing literature on various types of aggregation methods with a view to help guide future research in the area of computational pathology (CPath). We propose a general CPath workflow with three pathways that consider multiple levels and types of data and the nature of computation to analyse WSIs for predictive modelling. We categorize aggregation methods according to the context and representation of the data, features of computational modules and CPath use cases. We compare and contrast different methods based on the principle of multiple instance learning, perhaps the most commonly used aggregation method, covering a wide range of CPath literature. To provide a fair comparison, we consider a specific WSI-level prediction task and compare various aggregation methods for that task. Finally, we conclude with a list of objectives and desirable attributes of aggregation methods in general, pros and cons of the various approaches, some recommendations and possible future directions.Comment: 32 pages, 4 figure

Civilization Past & Present (11th Edition)

The authors of the Eleventh Edition of Civilization Past and Present specialists in Islamic, African, Asian, Ancient, Russian, and East European history weave the diverse trends of world history into a clear and accessible analysis for today\u27s students. Civilization Past and Present, well known in the marketplace as a highly readable survey text, delivers a strong narrative of world history and a level of detail that is manageable for students and solid for instructors. Using images and documents that enhance the text\u27s content, the narrative traces connections across cultures and introduces intriguing avenues of historical interpretation. The text examines all aspects of world history social, political, economic, religious, cultural, and geographic.https://scholarcommons.scu.edu/faculty_books/1303/thumbnail.jp

A structural study of dithizone coordination chemistry

Dithizone, since its discovery in 1878, has become essential in colorimetric assays for numerous transition metal ions. However, despite it being a vital reagent its coordination chemistry is not fully understood. Here we give insight into the binary complexes of dithizone, which contain two different metal ions, and the secondary complexes with Cu(II) which can either involve reduction of the metal ion or double deprotonation of dithizone giving the self-assembled [(H-DPTC)8Cu8] and [(DPTC)4Cu4] species respectively

Civilizations Past & Present, Combined Volume (12th Edition)

Civilizations Past and Present , written by specialists in Islamic, African, Asian, Ancient, and East European history— offers a clear and accessible analysis of diverse trends shaping world history. Civilizations Past and Present, now in its Twelfth Edition, is a survey text well known in the marketplace for its readability, offering a strong narrative exploration of world history that examines details at levels appropriate for both students and instructors. The book’s narrative–enriched by photographs, maps, primary source documents, timelines, and other pedagogical aids–places great emphasis on the connections between the world’s many cultures and regions. The book uses intriguing avenues of historical interpretation and examines all of the major areas of historical study: social, political, economic, religious, cultural, and geographic.https://scholarcommons.scu.edu/faculty_books/1302/thumbnail.jp

India and women's poetry of the 1830s: femininity and the picturesque in the poetry of Emma Roberts and Letitia Elizabeth Landon

This analysis of women’s writing on colonial India studies their work against the accounts of the picturesque and its function in colonial writing on India established by Sara Suleri and Nigel Leask. Roberts and Landon both work within this tradition, but ultimately find it inadequate to contain their explorations of domestic as well as colonial femininity. At this point, they supplement the poetic with other forms: prose versions, epigraphs or endnotes. These have the effect of drawing attention to and disrupting the ‘screen effect’ of the picturesque and explore those ‘more shattering aspects of [India’s] difference’ (Suleri), which it was normally the woman writer’s function to alleviate

A novel systemically administered toll-like receptor 7 agonist potentiates the effect of ionizing radiation in murine solid tumor models

Although topical TLR7 therapies such as imiquimod have proved successful in the treatment of dermatological malignancy, systemic delivery may be required for optimal immunotherapy of nondermatological tumors. We report that intravenous delivery of the novel small molecule TLR7 agonist, DSR-6434, leads to the induction of type 1 interferon and activation of T and B lymphocytes, NK and NKT cells. Our data demonstrate that systemic administration of DSR-6434 enhances the efficacy of ionizing radiation (IR) and leads to improved survival in mice bearing either CT26 or KHT tumors. Of the CT26 tumor-bearing mice that received combined therapy, 55% experienced complete tumor resolution. Our data reveal that these long-term surviving mice have a significantly greater frequency of tumor antigen specific CD8(+) T cells when compared to age-matched tumor-naïve cells. To evaluate therapeutic effects on spontaneous metastases, we showed that combination of DSR-6434 with local IR of the primary tumor significantly reduced metastatic burden in the lung, when compared to time-matched cohorts treated with IR alone. The data demonstrate that systemic administration of the novel TLR7 agonist DSR-6434 in combination with IR primes an antitumor CD8(+) T-cell response leading to improved survival in syngeneic models of colorectal carcinoma and fibrosarcoma. Importantly, efficacy extends to sites outside of the field of irradiation, reducing metastatic load. Clinical evaluation of systemic TLR7 therapy in combination with IR for the treatment of solid malignancy is warranted. WHAT'S NEW? Recent evidence suggests that damage from ionizing radiation (IR) can render tumor cells immunogenic. Unfortunately, established tumors often suppress this anti-tumor immune response. Combination therapy with IR and immune-modulators such as Toll-like-receptor (TLR) family agonists may overcome this problem. In this proof-of-concept study, the authors examined one such small-molecule drug, called DSR-6434. They found that systemic administration of DSR-6434 can enhance the effectiveness of radiotherapy in mice, and that this occurs via the generation of tumor-specific immune responses. Easily delivered drugs that activate TLR-family molecules may thus offer a promising therapeutic approach

Intravenous administration of the selective toll-like receptor 7 agonist DSR-29133 leads to anti-tumor efficacy in murine solid tumor models which can be potentiated by combination with fractionated radiotherapy.

Strategies to augment anti-cancer immune responses have recently demonstrated therapeutic utility. To date clinical success has been achieved through targeting co-inhibitory checkpoints such as CTLA-4, PD-1, and PD-L1. However, approaches that target co-activatory pathways are also being actively being developed. Here we report that the novel TLR7-selective agonist DSR-29133 is well tolerated in mice and leads to acute immune activation. Administration of DSR-29133 leads to the induction of IFNα/γ, IP-10, TNFα, IL-1Ra and IL-12p70, and to a reduction in tumor burden in syngeneic models of renal cancer (Renca), metastatic osteosarcoma (LM8) and colorectal cancer (CT26). Moreover, we show that the efficacy of DSR-29133 was significantly improved when administered in combination with low-dose fractionated radiotherapy (RT). Effective combination therapy required weekly administration of DSR-29133 commencing on day 1 of a fractionated RT treatment cycle, whereas no enhancement of radiation response was observed when DSR-29133 was administered at the end of the fractionated RT cycle. Combined therapy resulted in curative responses in a high proportion of mice bearing established CT26 tumors which was dependent on the activity of CD8(+) T-cells but independent of CD4(+) T-cells and NK/NKT cells. Moreover, long-term surviving mice originally treated with DSR-29133 and RT were protected by a tumor-specific memory immune response which could prevent tumor growth upon rechallenge. These results demonstrate that DSR-29133 is a potent selective TLR7 agonist that when administered intravenously can induce anti-tumor immune responses that can be further enhanced through combination with low-dose fractionated RT