Bounded Stopping Times for a Class of Sequential Bayes Tests

Consider the problem of sequentially testing a null hypothesis vs an alternative hypothesis when the risk function is a linear combination of probability of error in the terminal decision and expected sample size (i.e., constant cost per observation.) Assume that the parameter space is the union of null and alternative, the parameter space is convex, the intersection of null and alternative is empty, and the common boundary of the closures of null and alternative is nonempty and compact. Assume further that observations are drawn from a p-dimensional exponential family with an open p-dimensional parameter space. Sufficient conditions for Bayes tests to have bounded stopping times are given

Properties of Bayes Sequential Tests

Consider the problem of sequentially testing composite, contiguous hypotheses where the risk function is a linear combination of the probability of error in the terminal decision and the expected sample size. Assume that the common boundary of the closures of the null and the alternative hypothesis is compact. Observations are independent and identically distributed. We study properties of Bayes tests. One property is the exponential boundedness of the stopping time. Another property is continuity of the risk functions. The continuity property is used to establish complete class theorems as opposed to the essentially complete class theorems in Brown, Cohen and Strawderman

Enalapril and low protein reverse chronic puromycin aminonucleoside nephropathy

Enalapril and low protein reverse chronic puromycin aminonucleoside nephropathy. The effects of dietary protein and converting enzyme inhibition (CEI) on chronic puromycin aminonucleoside nephropathy (PAN) were studied. PAN was induced with seven SQ injections of puromycin aminonucleoside 20 mg/kg over 10 weeks in male Sprague-Dawley rats. The rats were divided into a 22.5% protein diet group (Gr 1), a 6% protein diet group (Gr 2), and an enalapril-treated group on 22.5% protein diet (Gr 3). Group 4 animals served as age-matched controls. Both diets were isocaloric and had the same phosphorus content. Rats from groups 1, 2, and 4 were sacrificed at 12, 18 and 24 weeks. Five rats of group 3 were sacrificed at 12 weeks, and the others were divided in subgroups 3A (diet changed to 6% protein) and 3B (no changes); half of each subgroup was sacrificed at 18 and 24 weeks, respectively. Group 2 had significantly less proteinuria than group 1 at all times. Group 3 had the same proteinuria as group 1 until 12 weeks and then began to decrease. In group 3A proteinuria decreased to group 2 levels, while in group 3B the decrease was slower but still prominent. Early lesions of focal and segmental glomerular sclerosis/hyalinosis (FSH) were present in groups 1, 2, 3 at 12 weeks (16 ± 1.2%, 15 ± 1.3%, 7 ± 1.3%, respectively, versus 1.3 ± 0.4% in controls), but by 18 weeks a reversal in FSH was seen in groups 2 and 3A/B (3 ± 1.6%, 2 ± 0.4%, and 3 ± 0.9%, respectively, vs. 14 ± 1.5% in group 1). This reversal persisted at 24 weeks (5 ± 2.5%, 3 ± 0.8%, 4 ± 0.8% vs. 18 ± 2.6%). At 24 weeks mean glomerular diameter was significantly less in group 2 compared to group 1, 100.7 ± 2.0 µ versus 112.2 ± 2.7 µ, P = 0.009. In summary, both low protein diet and CEI for 24 weeks reversed both proteinuria and early FSH lesions in chronic PAN after cessation of PA injections

Experimental model of lead nephropathy. I. Continuous high-dose lead administration

Experimental model of lead nephropathy. I. Continuous high-dose lead administration. This study followed the progression of lead nephropathy in male Sprague-Dawley rats (E) administered lead acetate (0.5%) continuously in drinking water for periods ranging from 1 to 12 months. Control animals (C) were pair-fed. Observations included renal pathology by light and electron microscopy, wet and dry kidney weights, and glomerular filtration rate (GFR) to assess renal function. Urinary excretion of lead, the enzymes N-acetyl-beta-D-glucosaminidase (NAG) and glutathione-S-transferase (GST), and brush border antigens (BB50, CG9, and HF5) were utilized to explore possible markers of kidney injury. GFR was increased significantly after three months of lead exposure, but was decreased significantly after 12 months. Kidney wet weights were significantly greater in E than C from three months on. Kidney dry weight/wet weight ratio was constant up to three months, but decreased in E at 12 months. Glomerular diameters were normal at all time periods; the nephromegaly was related primarily to hypertrophy of proximal tubules. Lead inclusion bodies were found in nuclei of proximal convoluted tubules and pars recta at all times. Tubular atrophy and interstitial fibrosis first appeared at six months, and increased in severity thereafter. Brush borders of proximal tubules were disrupted at one and three months, but recovered thereafter. Focal and segmental glomerulosclerosis was observed in 2 of 10 rats at 12 months. Arteries and arterioles remained normal at all time periods. Urinary NAG was elevated in E above C after three months of lead exposure. However, urinary NAG in C also increased with age, obscuring changes in the 12 month E rats. GST was elevated after three months of lead administration in E, not without an attendant age-related increase in C rats. In three-month E rats, urinary brush border antigens were increased above C, but were decreased at six and 12 months, correlating with the morphologic changes in brush border. We conclude that a high dose of lead in rats may initially stimulate both renal cortical hypertrophy and an increase in GFR. Later, the adverse effects of lead on the tubulointerstitium predominate, and GFR falls. The urinary marker, NAG, was abnormal in the early stages of the disease, but age-related changes obscured its utility at later stages; urinary GST appeared to be a more consistent marker of injury

Exploration and exploitation in the presence of network externalities

This paper examines the conditions under which exploration of a new, incompatible technologyis conducive to firm growth in the presence of network externalities. In particular, this studyis motivated bythe divergent evolutions of the PC and the workstation markets in response to a new technology: reduced instruction set computing (RISC). In the PC market, Intel has developed new microprocessors bymaintaining compatibilitywith the established architecture, whereas it was radicallyr eplaced byRISC in the workstation market. History indicates that unlike the PC market, the workstation market consisted of a large number of power users, who are less sensitive to compatibilitythan ordinaryusers. Our numerical analysis indicates that the exploration of a new, incompatible technologyis more likelyto increase the chance of firm growth when there are a substantial number of power users or when a new technologyis introduced before an established technologytakes off. (; ; ;

Roles of the TRAF6 and Pellino E3 ligases in MyD88 and RANKL signaling

It is widely accepted that the essential role of TRAF6 in vivo is to generate the Lys63-linked ubiquitin (K63-Ub) chains needed to activate the "master" protein kinase TAK1. Here, we report that TRAF6 E3 ligase activity contributes to but is not essential for the IL-1-dependent formation of K63-Ub chains, TAK1 activation, or IL-8 production in human cells, because Pellino1 and Pellino2 generate the K63-Ub chains required for signaling in cells expressing E3 ligase-inactive TRAF6 mutants. The IL-1-induced formation of K63-Ub chains and ubiquitylation of IRAK1, IRAK4, and MyD88 was abolished in TRAF6/Pellino1/Pellino2 triple-knockout (KO) cells, but not in TRAF6 KO or Pellino1/2 double-KO cells. The reexpression of E3 ligase-inactive TRAF6 mutants partially restored IL-1 signaling in TRAF6 KO cells, but not in TRAF6/Pellino1/Pellino2 triple-KO cells. Pellino1-generated K63-Ub chains activated the TAK1 complex in vitro with similar efficiently to TRAF6-generated K63-Ub chains. The early phase of TLR signaling and the TLR-dependent secretion of IL-10 (controlled by IRAKs 1 and 2) was only reduced modestly in primary macrophages from knockin mice expressing the E3 ligase-inactive TRAF6[L74H] mutant, but the late-phase production of IL-6, IL-12, and TNFα (controlled only by the pseudokinase IRAK2) was abolished. RANKL-induced signaling in macrophages and the differentiation of bone marrow to osteoclasts was similar in TRAF6[L74H] and wild-type cells, explaining why the bone structure and teeth of the TRAF6[L74H] mice was normal, unlike TRAF6 KO mice. We identify two essential roles of TRAF6 that are independent of its E3 ligase activity

Faint High Latitude Carbon Stars Discovered by the Sloan Digital Sky Survey: Methods and Initial Results

We report the discovery of 39 Faint High Latitude Carbon Stars (FHLCs) from Sloan Digital Sky Survey commissioning data. The objects, each selected photometrically and verified spectroscopically, range over 16.6 < r* < 20.0, and show a diversity of temperatures as judged by both colors and NaD line strengths. At the completion of the Sloan Survey, there will be many hundred homogeneously selected and observed FHLCs in this sample. We present proper motion measures for each object, indicating that the sample is a mixture of extremely distant (>100 kpc) halo giant stars, useful for constraining halo dynamics, plus members of the recently-recognized exotic class of very nearby dwarf carbon (dC) stars. Motions, and thus dC classification, are inferred for 40-50 percent of the sample, depending on the level of statistical significance invoked. The new list of dC stars presented here, although selected from only a small fraction of the final SDSS, doubles the number of such objects found by all previous methods. (Abstract abridged).Comment: Accepted for publication in The Astronomical Journal, Vol. 124, Sep. 2002, 40 pages, 7 figures, AASTeX v5.

Randomised trial of glutamine and selenium supplemented parenteral nutrition for critically ill patients

Background: Mortality rates in the Intensive Care Unit and subsequent hospital mortality rates in the UK remain high. Infections in Intensive Care are associated with a 2–3 times increased risk of death. It is thought that under conditions of severe metabolic stress glutamine becomes "conditionally essential". Selenium is an essential trace element that has antioxidant and anti-inflammatory properties. Approximately 23% of patients in Intensive Care require parenteral nutrition and glutamine and selenium are either absent or present in low amounts. Both glutamine and selenium have the potential to influence the immune system through independent biochemical pathways. Systematic reviews suggest that supplementing parenteral nutrition in critical illness with glutamine or selenium may reduce infections and mortality. Pilot data has shown that more than 50% of participants developed infections, typically resistant organisms. We are powered to show definitively whether supplementation of PN with either glutamine or selenium is effective at reducing new infections in critically ill patients. Methods/design: 2 × 2 factorial, pragmatic, multicentre, double-blind, randomised controlled trial. The trial has an enrolment target of 500 patients. Inclusion criteria include: expected to be in critical care for at least 48 hours, aged 16 years or over, patients who require parenteral nutrition and are expected to have at least half their daily nutritional requirements given by that route. Allocation is to one of four iso-caloric, iso-nitrogenous groups: glutamine, selenium, both glutamine & selenium or no additional glutamine or selenium. Trial supplementation is given for up to seven days on the Intensive Care Unit and subsequent wards if practicable. The primary outcomes are episodes of infection in the 14 days after starting trial nutrition and mortality. Secondary outcomes include antibiotic usage, length of hospital stay, quality of life and cost-effectiveness. Discussion: To date more than 285 patients have been recruited to the trial from 10 sites in Scotland. Recruitment is due to finish in August 2008 with a further six months follow up. We expect to report the results of the trial in summer 2009. Trial registration: This trial is registered with the International Standard Randomised Controlled Trial Number system. ISRCTN87144826Not peer reviewedPublisher PD

Ernst Freund as Precursor of the Rational Study of Corporate Law

Gindis, David, Ernst Freund as Precursor of the Rational Study of Corporate Law (October 27, 2017). Journal of Institutional Economics, Forthcoming. Available at SSRN: https://ssrn.com/abstract=2905547, doi: https://dx.doi.org/10.2139/ssrn.2905547The rise of large business corporations in the late 19th century compelled many American observers to admit that the nature of the corporation had yet to be understood. Published in this context, Ernst Freund's little-known The Legal Nature of Corporations (1897) was an original attempt to come to terms with a new legal and economic reality. But it can also be described, to paraphrase Oliver Wendell Holmes, as the earliest example of the rational study of corporate law. The paper shows that Freund had the intuitions of an institutional economist, and engaged in what today would be called comparative institutional analysis. Remarkably, his argument that the corporate form secures property against insider defection and against outsiders anticipated recent work on entity shielding and capital lock-in, and can be read as an early contribution to what today would be called the theory of the firm.Peer reviewe

Standard‐space atlas of the viscoelastic properties of the human brain

Standard anatomical atlases are common in neuroimaging because they facilitate data analyses and comparisons across subjects and studies. The purpose of this study was to develop a standardized human brain atlas based on the physical mechanical properties (i.e., tissue viscoelasticity) of brain tissue using magnetic resonance elastography (MRE). MRE is a phase contrast-based MRI method that quantifies tissue viscoelasticity noninvasively and in vivo thus providing a macroscopic representation of the microstructural constituents of soft biological tissue. The development of standardized brain MRE atlases are therefore beneficial for comparing neural tissue integrity across populations. Data from a large number of healthy, young adults from multiple studies collected using common MRE acquisition and analysis protocols were assembled (N = 134; 78F/ 56 M; 18–35 years). Nonlinear image registration methods were applied to normalize viscoelastic property maps (shear stiffness, μ, and damping ratio, ξ) to the MNI152 standard structural template within the spatial coordinates of the ICBM-152. We find that average MRE brain templates contain emerging and symmetrized anatomical detail. Leveraging the substantial amount of data assembled, we illustrate that subcortical gray matter structures, white matter tracts, and regions of the cerebral cortex exhibit differing mechanical characteristics. Moreover, we report sex differences in viscoelasticity for specific neuroanatomical structures, which has implications for understanding patterns of individual differences in health and disease. These atlases provide reference values for clinical investigations as well as novel biophysical signatures of neuroanatomy. The templates are made openly available (github.com/mechneurolab/mre134) to foster collaboration across research institutions and to support robust cross-center comparisons