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Using pre-treatment gene expression, protein/phosphoprotein, and clinical data from the I-SPY2 neoadjuvant platform trial (NCT01042379), we create alternative breast cancer subtypes incorporating tumor biology beyond clinical hormone receptor (HR) and human epidermal growth factor receptor-2 (HER2) status to better predict drug responses. We assess the predictive performance of mechanism-of-action biomarkers from ∼990 patients treated with 10 regimens targeting diverse biology. We explore >11 subtyping schemas and identify treatment-subtype pairs maximizing the pathologic complete response (pCR) rate over the population. The best performing schemas incorporate Immune, DNA repair, and HER2/Luminal phenotypes. Subsequent treatment allocation increases the overall pCR rate to 63% from 51% using HR/HER2-based treatment selection. pCR gains from reclassification and improved patient selection are highest in HR+ subsets (>15%). As new treatments are introduced, the subtyping schema determines the minimum response needed to show efficacy. This data platform provides an unprecedented resource and supports the usage of response-based subtypes to guide future treatment prioritization.

In this article, I present discussions of conditions for reviving public morale and, in the process, public morality, which would ultimately be a political goal, using examples from the Victorian era in Britain and what Americans refer to as the Progressive Era at the beginning of the twentieth century in the United States. I begin with an older book by Gertrude Himmelfarb that emphasises the revitalisation of public morality in Victorian Britain. A book by Robert D. Putnam and Shaylyn Romney Garrett makes similar claims for the effects of the Progressive Era in the US, and for how a similar approach could be useful in the present era. Both books emphasise cultural critique and discount the effects of causality going in the opposite direction, starting with economic revival, and I discuss this dilemma in this article. Keywords: censorship without morality, poor law, public morale, public morality, social solidarity, working-class life, Gertrude Himmelfarb, The De-Moralization of Society: From Victorian Virtues to Modern Values. London: Institute of Economic Affairs, 1995, 320 pp. Robert D. Putnam and Shaylyn Romney Garrett, The Upswing: How [...]

EsopredictTM is a prognostic assay that risk-stratifies Barrett's esophagus patients to predict future progression to high-grade dysplasia (HGD) or esophageal adenocarcinoma (EAC). Established based on foundational studies at Johns Hopkins University, a risk algorithm was developed and clinically validated in two independent studies (n = 320). EsopredictTM is currently offered as a clinical test under the Clinical Laboratory Improvement Amendments (CLIA) guidelines. Here we present the analytical validation by repeated testing of FFPE tissues (n = 26 patients), cell lines, and contrived DNA controls to determine assay performance regarding analytical sensitivity (as defined by the limit of detection (LOD)), analytical specificity (as defined by the limit of blank (LOB)), accuracy as determined from the average positive and negative agreement, repeatability, and reproducibility. The LOD for the assay at 1.5% DNA methylation was significantly higher than the LOB, as determined by an unmethylated DNA control (0% methylated DNA). Inter- and intra-assay average positive agreement (APA) were 88% and 94%, respectively, while average negative agreement (ANA) values were 90% and 94%, respectively. Average inter- and intra-assay precision were <9% and <5% coefficient of variation (CV), respectively. These results confirm that EsopredictTM is a highly reproducible, sensitive, and specific risk categorization assay for the prediction of progression to HGD or EAC within 5 years. [ABSTRACT FROM AUTHOR]

Objectives: Designing cancer screening trials for multi-cancer early detection (MCED) tests presents a significant methodology challenge, as natural histories of cell-free DNA-shedding cancers are not yet known. A microsimulation model was developed to project the performance and utility of an MCED test in cancer screening trials. Methods: Individual natural history of preclinical progression through cancer stages for 23 cancer classes was simulated by a stage-transition model under a broad range of cancer latency parameters. Cancer incidences and stage distributions at clinical presentation in simulated trials were set to match the data from Surveillance, Epidemiology, and End Results program. One or multiple rounds of annual screening using a targeted methylation-based MCED test (Galleri Ⓡ) was conducted to detect preclinical cancers. Mortality benefit of early detection was simulated by a stage-shift model. Results: In simulated trials, accounting for healthy volunteer effect and varying test sensitivity, positive predictive value in the prevalence screening round reached 48% to 61% in 6 natural history scenarios. After 3 rounds of annual screening, the cumulative proportions of stage I/II cancers increased by approximately 9% to 14%, the incidence of stage IV cancers was reduced by 37% to 46%, the reduction of stages III and IV cancer incidences was 9% to 24%, and the reduction of mortality reached 13% to 16%. Greater reductions of late-stage cancers and cancer mortality were achieved by five rounds of MCED screening. Conclusions: Simulation results guide trial design and suggest that adding this MCED test to routine screening in the United States may shift cancer detection to earlier stages, and potentially save lives. [ABSTRACT FROM AUTHOR]

BackgroundThe intestinal mucosa displays robust virus replication and pronounced CD4+ T-cell loss during acute human immunodeficiency virus type 1 (HIV-1) infection. The ability of HIV-specific CD8+ T-cells to modulate disease course has prompted intensive study, yet the significance of virus-specific CD8+ T-cells in mucosal sites remains unclear.Methods and findingsWe evaluated five distinct effector functions of HIVgag-specific CD8+ T-cells in rectal mucosa and blood, individually and in combination, in relationship to clinical status and antiretroviral therapy (ART). In subjects not on ART, the percentage of rectal Gag-specific CD8+ T-cells capable of 3, 4 or 5 simultaneous effector functions was significantly related to blood CD4 count and inversely related to plasma viral load (PVL) (p

"Ages of American Capitalism: A History of the United States" by Jonathan Levy is a comprehensive exploration of American economic history, with a focus on labor economics and legal history. The book examines the relevance of institutional economics and the writings of John R. Commons in understanding changes in labor conditions and labor relations. Levy traces the development of American capitalism from the industrial revolution to the present day, highlighting the increasing control over workers and the emphasis on short-term profits. The book also discusses the failed populist movement and its goals of providing an alternative to the economic developments of the time. Overall, Levy's work provides a well-balanced commentary on management practices and their impact on the American economy. [Extracted from the article]

Liah Greenfeld, Mind, Modernity, Madness; The Impact of Culture On Human Experience Cambridge, MA: Harvard University Press, 2013, 688 pp, $49.95. ISBN: 978-0674072763 Liah Greenfeld, University Professor and Professor of [...]

Hans Joas and Wolfgang Knobl, War in Social Thought: Hobbes to the Present Princeton, NJ: Princeton University Press, 2013. 338 pp. $35.00. ISBN: 978-0691150840 One of the more realistic goals [...]

To authenticate to the full-text of this article, please visit this link: http://dx.doi.org/10.1111/j.1468-2451.2009.00693.x Byline: Jerome Braun (1) Abstract: In this article a framework is developed for comparing a number of present-day societies in terms of their ability to produce social order and moral character. America is compared with Europe, and then, in less detail, to Latin America and the Islamic world. Reference is also made to Alain Touraine's What is democracy? to show a present-day French perspective on democracy. The place of the middle class in America and in Europe in providing compromise solutions for their societies is noted, together with the possible relationship between social and political democracy, and how they may converge and diverge. Cultural elements involved in the production of social order are taken into account. Reference is made to the different checks and balances in different societies between the central and local government and local communities, as well as between elites and the masses. This reflects the cultural factors as well as the degree of bureaucratisation of these societies. Finally, there is a summary of various principles of honour governing differing structures of political power derived from the Baron de Montesquieu's The spirit of the laws. Author Affiliation: (1)Princeton University