Probabilistic classification of acute myocardial infarction from multiple cardiac markers

Logistic regression and Gaussian mixture model (GMM) classifiers have been trained to estimate the probability of acute myocardial infarction (AMI) in patients based upon the concentrations of a panel of cardiac markers. The panel consists of two new markers, fatty acid binding protein (FABP) and glycogen phosphorylase BB (GPBB), in addition to the traditional cardiac troponin I (cTnI), creatine kinase MB (CKMB) and myoglobin. The effect of using principal component analysis (PCA) and Fisher discriminant analysis (FDA) to preprocess the marker concentrations was also investigated. The need for classifiers to give an accurate estimate of the probability of AMI is argued and three categories of performance measure are described, namely discriminatory ability, sharpness, and reliability. Numerical performance measures for each category are given and applied. The optimum classifier, based solely upon the samples take on admission, was the logistic regression classifier using FDA preprocessing. This gave an accuracy of 0.85 (95% confidence interval: 0.78-0.91) and a normalised Brier score of 0.89. When samples at both admission and a further time, 1-6 h later, were included, the performance increased significantly, showing that logistic regression classifiers can indeed use the information from the five cardiac markers to accurately and reliably estimate the probability AMI. © Springer-Verlag London Limited 2008.

A new polycythaemia vera-associated SOCS3 SH2 mutant (SOCS3(F136L)) cannot regulate erythropoietin responses

Recently several different JAK2 exon12 mutations have been identified in V617F negative polycythaemia vera (PV) or idiopathic erythrocytosis (IE) patients. The patients present with erythrocytosis, ligand-independent cell growth and low serum erythropoietin (EPO) levels. Within this group, a deletion of amino acids 542-543 (N542-E543del) of JAK2 is most prevalent. We have previously shown that in the presence of JAK2(V617F), suppressor of cytokine signalling 3 (SOCS3) is unable to negatively regulate EPO signalling and proliferation of V617F-expressing cells. Here we report a PV patient heterozygous for the somatic JAK2(N542-E543del) mutation and a previously unreported germline mutation within the SH2 domain of SOCS3 (F136L). Interestingly, the SOCS3(F136L) mutation was detected in a Japanese myeloproliferative disorder patient cohort at double the frequency of healthy controls. Cells expressing SOCS3(F136L) had markedly elevated EPO-induced proliferation and extended EPO-induced JAK2 phosphorylation. Additionally, compared to wild-type SOCS3, mutant SOCS3 had an extended half-life in the presence of JAK2 and JAK2(N542-E543del). Our findings suggest that this loss-of-function SOCS3 mutation may have contributed to disease onset by causing deregulated JAK2 signalling in the presence of a constitutively active JAK2(N542-E543del) mutant.

The Philosophy and Practice of Interpretivist Research in Entrepreneurship Quality, Validation, and Trust

Knowledge production in entrepreneurship requires inclusivity as well as diversity and pluralism in research perspectives and approaches. In this article, the authors address concerns about interpretivist research regarding validity, reliability, objectivity, generalizability, and communicability of results that militate against its more widespread acceptance. Following the nonfoundationalist argument that all observation is theory-laden, context specific, and that there are no external criteria against which to assess research design and execution and the data produced, the authors propose that quality must be internalized within the underlying research philosophy rather than something to be tested upon completion. This requires a shift from the notion of validity as an outcome to validation as a process. To elucidate this, they provide a guiding framework and present a case illustration that will assist an interpretivist entrepreneurship researcher to establish and demonstrate the quality of their work.

Post-release GPS tracking of hand-reared Irish hare Lepus timidus hibernicus leverets, Slemish, Co. Antrim, Northern Ireland.

Animal rescue centres release large numbers of captive-bred, rehabilitated or translocated animals into the wild annually but little is known about their post-release survival and behaviour. We developed a novel and innovative coupling of traditional radio-tags with new GPS loggers to track hand-reared Irish hare Lepus timidus hibernicus leverets after release into the wild. Cyanoacrylate SuperGlue® proved a poor fixative with two out of three leverets managing to detach their tags within 24 hours. Nevertheless, a total of 2,505 GPS locations were recorded every 60 seconds for one leveret over three nights (approx. 835 per night). The leveret dispersed