THE DESIGN AND ANALYSIS OF EXPERIMENTS. By Oscar Kempthorne. New York, John Wiley and Sons, Inc., 1952. 631 pp. $8.50. This book by a teacher of statistics (as well as a consultant for \"experimenters\") is a comprehensive study of the philosophical background for the statistical design of experiment. It is necessary to have some facility with algebraic notation and manipulation to be able to use the volume intelligently. The problems are presented from the theoretical point of view, without such practical examples as would be helpful for those not acquainted with mathematics. The mathematical justification for the techniques is given. As a somewhat advanced treatment of the design and analysis of experiments, this volume will be interesting and helpful for many who approach statistics theoretically as well as practically. With emphasis on the \"why,\" and with description given broadly, the author relates the subject matter to the general theory of statistics and to the general problem of experimental inference. MARGARET J. ROBERTSON

The Design and Analysis of Experiments

Hereditary haemochromatosis (HH), which affects some 1 in 400 and has an estimated carrier frequency of 1 in 10 individuals of Northern European descent, results in multi-organ dysfunction caused by increased iron deposition, and is treatable if detected early. Using linkage-disequilibrium and full haplotype analysis, we have identified a 250-kilobase region more than 3 megabases telomeric of the major histocompatibility complex (MHC) that is identical-by-descent in 85% of patient chromosomes. Within this region, we have identified a gene related to the MHC class I family, termed HLA-H, containing two missense alterations. One of these is predicted to inactivate this class of proteins and was found homozygous in 83% of 178 patients. A role of this gene in haemochromatosis is supported by the frequency and nature of the major mutation and prior studies implicating MHC class I-like proteins in iron metabolism.

A novel MHC class I–like gene is mutated in patients with hereditary haemochromatosis

A novel MHC class-I-like gene is mutated in patients with hereditary haemochromatosis

Open Innovation: The New Imperative for Creating and Profiting from Technology

Models that depict innovation as a smooth, well-behaved linear process badly misspecify the nature and direction of the causal factors at work. Innovation is complex, uncertain, somewhat disorderly, and subject to changes of many sorts. Innovation is also difficult to measure and demands close coordination of adequate technical knowledge and excellent market judgment in order to satisfy economic, technological, and other types of constraints—all simultaneously. The process of innovation must be viewed as a series of changes in a complete system not only of hardware, but also of market environment, production facilities and knowledge, and the social contexts of the innovation organization.

An Overview of Innovation

Iron overload in β2-microglobulin-deficient mice

Characteristics of Brazilian innovative firms: An empirical analysis based on PINTEC—industrial research on technological innovation

Solar energy technologies and open innovation: A study based on bibliometric and social network analysis

Hereditary haemochromatosis (HH) is an autosomal recessive disease linked to certain MHC class-I specificities. The disease is characterized by increased iron absorption and, in some patients, abnormally low numbers of CD8+ T cells in the periphery. We were interested in whether CD4- and CD8-associated p56lck kinase activities were altered in patients with HH. In a study of 18 patients with HH (with and without low numbers of CD8+ cells), the level of autophosphorylation of the CD8-associated p56lck as well as its phosphotransferase activity, as determined by phosphorylation of an exogenous substrate, was significantly reduced by two- to three-fold relative to a control population of 23 healthy blood donors (P < 6 x 10(-7). CD8-p56lck activity was decreased in 16 out of 18 patients (ranging from 1.5- to 10-fold decrease). By contrast, the level of CD4-p56lck activity did not show an overall decrease relative to controls. In addition to an occasional decrease in the amount of CD8-associated lck, HH patient-derived T cells showed a consistent decrease in the relative CD8-p56lck specific activity. Immunofluorescence staining showed further that the difference could not be accounted by a discrepancy in the expression of CD8 alpha alpha or CD8 alpha beta complexes or MHC class I molecules. Decreased CD8-p56lck activity was seen both in patients undergoing intensive phlebotomy treatment and in patients in maintenance therapy (i.e. patients who had reached normal levels of iron stores), indicating that this abnormality does not appear to be corrected by iron depletion. To our knowledge, this is the first demonstration of an abnormality in a src-like receptor associated kinase in a human disease state linked to MHC class-I antigens.

Decreased CD8-p56lck activity in peripheral blood T-lymphocytes from patients with hereditary haemochromatosis.

An analysis of the emerging patent landscape of gene therapies under development, focusing on non-viral vectors.

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Geciane Silveira Porto

Papers

Iron overload in β2-microglobulin-deficient mice

Characteristics of Brazilian innovative firms: An empirical analysis based on PINTEC—industrial research on technological innovation

Solar energy technologies and open innovation: A study based on bibliometric and social network analysis

Decreased CD8-p56lck activity in peripheral blood T-lymphocytes from patients with hereditary haemochromatosis.

Emerging patent landscape for non-viral vectors used for gene therapy.