568 research outputs found
Apparatus for Distilling Alcohol from Biological Fluids and a Calculator for Harger Titrations
For the determination of alcohol in body fluids the Harger (1935) titration is extensively used with distillates obtained in various ways; e.g., by steam distillation, desiccation, distillation from picric acid, picrate-tartrate or tungstic acid. Gibson (1939) has combined it with the simple distillation from picric acid solution (Nicloux, et al. 1934) to produce an essentially satisfactory and rapid determination. Clinical simplicity with research accuracy has been achieved by the use of a specially designed distillation apparatus with the method (Johnston and Gibson, 1940). After using this method for a long period the authors have been able to revise it for still more convenience in use, and to design a calculator for obtaining the alcohol concentration in a body fluid directly from the burette readings of Harger titrations. This paper presents the revised design of the apparatus, with some modifications in use, and the calculator
Sticky central limit theorems on open books
Given a probability distribution on an open book (a metric space obtained by
gluing a disjoint union of copies of a half-space along their boundary
hyperplanes), we define a precise concept of when the Fr\'{e}chet mean
(barycenter) is sticky. This nonclassical phenomenon is quantified by a law of
large numbers (LLN) stating that the empirical mean eventually almost surely
lies on the (codimension and hence measure ) spine that is the glued
hyperplane, and a central limit theorem (CLT) stating that the limiting
distribution is Gaussian and supported on the spine. We also state versions of
the LLN and CLT for the cases where the mean is nonsticky (i.e., not lying on
the spine) and partly sticky (i.e., is, on the spine but not sticky).Comment: Published in at http://dx.doi.org/10.1214/12-AAP899 the Annals of
Applied Probability (http://www.imstat.org/aap/) by the Institute of
Mathematical Statistics (http://www.imstat.org
Joint and individual analysis of breast cancer histologic images and genomic covariates
A key challenge in modern data analysis is understanding connections between
complex and differing modalities of data. For example, two of the main
approaches to the study of breast cancer are histopathology (analyzing visual
characteristics of tumors) and genetics. While histopathology is the gold
standard for diagnostics and there have been many recent breakthroughs in
genetics, there is little overlap between these two fields. We aim to bridge
this gap by developing methods based on Angle-based Joint and Individual
Variation Explained (AJIVE) to directly explore similarities and differences
between these two modalities. Our approach exploits Convolutional Neural
Networks (CNNs) as a powerful, automatic method for image feature extraction to
address some of the challenges presented by statistical analysis of
histopathology image data. CNNs raise issues of interpretability that we
address by developing novel methods to explore visual modes of variation
captured by statistical algorithms (e.g. PCA or AJIVE) applied to CNN features.
Our results provide many interpretable connections and contrasts between
histopathology and genetics
On Hirschman and log-Sobolev inequalities in mu-deformed Segal-Bargmann analysis
We consider a deformation of Segal-Bargmann space and its transform. We study
L^p properties of this transform and obtain entropy-entropy inequalities
(Hirschman) and entropy-energy inequalities (log-Sobolev) that generalize the
corresponding known results in the undeformed theory.Comment: 42 pages, 3 figure
Smoke gets in your eyes:what is sociological about cigarettes?
Contemporary public health approaches increasingly draw attention to the unequal social distribution of cigarette smoking. In contrast, critical accounts emphasize the importance of smokers’ situated agency, the relevance of embodiment and how public health measures against smoking potentially play upon and exacerbate social divisions and inequality. Nevertheless, if the social context of cigarettes is worthy of such attention, and sociology lays a distinct claim to understanding the social, we need to articulate a distinct, positive and systematic claim for smoking as an object of sociological enquiry. This article attempts to address this by situating smoking across three main dimensions of sociological thinking: history and social change; individual agency and experience; and social structures and power. It locates the emergence and development of cigarettes in everyday life within the project of modernity of the nineteenth and twentieth centuries. It goes on to assess the habituated, temporal and experiential aspects of individual smoking practices in everyday lifeworlds. Finally, it argues that smoking, while distributed in important ways by social class, also works relationally to render and inscribe it
Outcomes of off-label drug uses in hospitals: a multicentric prospective study
Purpose: The study aims to assess the clinical evidence, outcome and cost of off-label use of medicines in the hospital setting. Methods: A multicentric prospective cohort study of patients treated with off-label medicines was carried out in five tertiary hospitals from May 2011 to May 2012. Information on clinical characteristics of patients, drugs, outcomes and costs was collected. Patients were followed up to 6 months, and information was assessed by reviewing clinical records and interviewing physicians. Results: A total of 226 patients were included. The median (interquartile range (IQR)) age of patients was 46 (3362) years; 59 % were women. Patients had received a median of three previous treatments, and a lack of response (or suboptimal) was the main reason for off-label use (72.1 %). A total of 232 off-label medicines were administered for 102 different indications. The most frequent medicines were rituximab (49; 21.1 %), botulinum toxin (25; 10.7 %) and omalizumab (14; 6.0 %). In 117 (51.8 %) cases, the level of clinical evidence for their use was low. A partial clinical response was observed in 82 patients (36.3 %), complete response in 71 (31.4 %) and stabilization in 11 (4.9 %). A total of 58 (26.5 %) patients had adverse effects, which in 11 (4.9 %) were severe. The median (IQR) cost per patient was 2,943.07 (541.95,872.54). Conclusions: There was a high variability of off-label medicines and indications. Although the clinical evidence of off-label medicines was often low, clinical response was observed in many patients with previous multiple treatment failure, but at the expense of some adverse effects and a high cost. Registers of patients would be helpful for clinical decisions, although clinical trials are needed
SWISS MADE: Standardized WithIn Class Sum of Squares to Evaluate Methodologies and Dataset Elements
Contemporary high dimensional biological assays, such as mRNA expression microarrays, regularly involve multiple data processing steps, such as experimental processing, computational processing, sample selection, or feature selection (i.e. gene selection), prior to deriving any biological conclusions. These steps can dramatically change the interpretation of an experiment. Evaluation of processing steps has received limited attention in the literature. It is not straightforward to evaluate different processing methods and investigators are often unsure of the best method. We present a simple statistical tool, Standardized WithIn class Sum of Squares (SWISS), that allows investigators to compare alternate data processing methods, such as different experimental methods, normalizations, or technologies, on a dataset in terms of how well they cluster a priori biological classes. SWISS uses Euclidean distance to determine which method does a better job of clustering the data elements based on a priori classifications. We apply SWISS to three different gene expression applications. The first application uses four different datasets to compare different experimental methods, normalizations, and gene sets. The second application, using data from the MicroArray Quality Control (MAQC) project, compares different microarray platforms. The third application compares different technologies: a single Agilent two-color microarray versus one lane of RNA-Seq. These applications give an indication of the variety of problems that SWISS can be helpful in solving. The SWISS analysis of one-color versus two-color microarrays provides investigators who use two-color arrays the opportunity to review their results in light of a single-channel analysis, with all of the associated benefits offered by this design. Analysis of the MACQ data shows differential intersite reproducibility by array platform. SWISS also shows that one lane of RNA-Seq clusters data by biological phenotypes as well as a single Agilent two-color microarray
Germline Analysis from Tumor–Germline Sequencing Dyads to Identify Clinically Actionable Secondary Findings
To evaluate germline variants in hereditary cancer susceptibility genes among unselected cancer patients undergoing tumor-germline sequencing
B Cells and T Follicular Helper Cells Mediate Response to Checkpoint Inhibitors in High Mutation Burden Mouse Models of Breast Cancer
This study identifies mechanisms mediating responses to immune checkpoint inhibitors using mouse models of triple-negative breast cancer. By creating new mammary tumor models, we find that tumor mutation burden and specific immune cells are associated with response. Further, we developed a rich resource of single-cell RNA-seq and bulk mRNA-seq data of immunotherapy-treated and non-treated tumors from sensitive and resistant murine models. Using this, we uncover that immune checkpoint therapy induces T follicular helper cell activation of B cells to facilitate the anti-tumor response in these models. We also show that B cell activation of T cells and the generation of antibody are key to immunotherapy response and propose a new biomarker for immune checkpoint therapy. In total, this work presents resources of new preclinical models of breast cancer with large mRNA-seq and single-cell RNA-seq datasets annotated for sensitivity to therapy and uncovers new components of response to immune checkpoint inhibitors
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