Tufts University

About: Tufts University is a education organization based out in Medford, Massachusetts, United States. It is known for research contribution in the topics: Population & Medicine. The organization has 32800 authors who have published 66881 publications receiving 3451152 citations. The organization is also known as: Tufts College & Universitatis Tuftensis.

New Criteria for Response to Treatment in Immunoglobulin Light Chain Amyloidosis Based on Free Light Chain Measurement and Cardiac Biomarkers: Impact on Survival Outcomes

Abstract: PURPOSE: To identify the criteria for hematologic and cardiac response to treatment in immunoglobulin light chain (AL) amyloidosis based on survival analysis of a large patient population. PATIENTS AND METHODS: We gathered for analysis 816 patients with AL amyloidosis from seven referral centers in the European Union and the United States. A different cohort of 374 patients prospectively evaluated at the Pavia Amyloidosis Research and Treatment Center was used for validation. Data was available for all patients before and 3 and/or 6 months after initiation of first-line therapy. The prognostic relevance of different criteria for hematologic and cardiac response was assessed. RESULTS: There was a strong correlation between the extent of reduction of amyloidogenic free light chains (FLCs) and improvement in survival. This allowed the identification of four levels of response: amyloid complete response (normal FLC ratio and negative serum and urine immunofixation), very good partial response (difference between involved and uninvolved FLCs [dFLC] 50%), and no response. Cardiac involvement is the major determinant of survival, and changes in cardiac function after therapy can be reliably assessed using the cardiac biomarker N-terminal natriuretic peptide type B (NT-proBNP). Changes in FLC and NT-proBNP predicted survival as early as 3 months after treatment initiation. CONCLUSION: This study identifies and validates new criteria for response to first-line treatment in AL amyloidosis, based on their association with survival in large patient populations, and offers surrogate end points for clinical trials.

Time and the Observer: the Where and When of Consciousness in the Brain

Abstract: We compare the way two models of consciousness treat subjective timing. According to the standard “Cartesian Theater” model, there is a place in the brain where “it all comes together,” and the discriminations in all modalities are somehow put into registration and “presented” for subjective judgment. The timing of the events in this theater determines subjective order. According to the alternative “Multiple Drafts” model, discriminations are distributed in both space and time in the brain. These events do have temporal properties, but those properties do not determine subjective order because there is no single, definitive “stream of consciousness,” only a parallel stream of conflicting and continuously revised contents. Four puzzling phenomena that resist explanation by the Cartesian model are analyzed: (1) a gradual apparent motion phenomenon involving abrupt color change (Kolers & von Grunau 1976), (2) an illusion of an evenly spaced series of “hops” produced by two or more widely spaced series of taps delivered to the skin (Geldard & Sherrick's “cutaneous rabbit” [1972]), (3) backwards referral in time, and (4) subjective delay of consciousness of intention (both reported in this journal by LIbet 1985a; 1987; 1989a). The unexamined assumptions that have always made the Cartesian Theater so attractive are exposed and dismantled. The Multiple Drafts model provides a better account of the puzzling phenomena, avoiding the scientific and metaphysical extravagances of the Cartesian Theater: The temporal order of subjective events is a product of the brain's interpretational processes, not a direct reflection of events making up those processes.