Showing papers by "University of Washington published in 1995"

Bayesian Model Selection in Social Research

Abstract: It is argued that P-values and the tests based upon them give unsatisfactory results, especially in large samples. It is shown that, in regression, when there are many candidate independent variables, standard variable selection procedures can give very misleading results. Also, by selecting a single model, they ignore model uncertainty and so underestimate the uncertainty about quantities of interest. The Bayesian approach to hypothesis testing, model selection, and accounting for model uncertainty is presented. Implementing this is straightforward through the use of the simple and accurate BIC approximation, and it can be done using the output from standard software. Specific results are presented for most of the types of model commonly used in sociology. It is shown that this approach overcomes the difficulties with P-values and standard model selection procedures based on them. It also allows easy comparison of nonnested models, and permits the quantification of the evidence for a null hypothesis of interest, such as a convergence theory or a hypothesis about societal norms.

Implicit Social Cognition: Attitudes, Self-Esteem, and Stereotypes.

Abstract: Social behavior is ordinarily treated as being under conscious (if not always thoughtful) control. However, considerable evidence now supports the view that social behavior often operates in an implicit or unconscious fashion. The identifying feature of implicit cognition is that past experience influences judgment in a fashion not introspectively known by the actor. The present conclusion--that attitudes, self-esteem, and stereotypes have important implicit modes of operation--extends both the construct validity and predictive usefulness of these major theoretical constructs of social psychology. Methodologically, this review calls for increased use of indirect measures--which are imperative in studies of implicit cognition. The theorized ordinariness of implicit stereotyping is consistent with recent findings of discrimination by people who explicitly disavow prejudice. The finding that implicit cognitive effects are often reduced by focusing judges' attention on their judgment task provides a basis for evaluating applications (such as affirmative action) aimed at reducing such unintended discrimination.

Market Orientation and the Learning Organization

Abstract: Effective organizations are configurations of management practices that facilitate the development of the knowledge that becomes the basis for competitive advantage. A market orientation, complemen...

A quantitative assessment of plasma homocysteine as a risk factor for vascular disease. Probable benefits of increasing folic acid intakes

Abstract: Objective. —To determine the risk of elevated total homocysteine (tHcy) levels for arteriosclerotic vascular disease, estimate the reduction of tHcy by folic acid, and calculate the potential reduction of coronary artery disease (CAD) mortality by increasing folic acid intake. Data Sources. —MEDLINE search for meta-analysis of 27 studies relating homocysteine to arteriosclerotic vascular disease and 11 studies of folic acid effects on tHcy levels. Study Selection and Data Extraction. —Studies dealing with CAD, cerebrovascular disease, and peripheral arterial vascular disease were selected. Three prospective and six population-based case-control studies were considered of high quality. Five cross-sectional and 13 other case-control studies were also included. Causality of tHcy's role in the pathogenesis of vascular disease was inferred because of consistency across studies by different investigators using different methods in different populations. Data Synthesis. —Elevations in tHcy were considered an independent graded risk factor for arteriosclerotic vascular diseases. The odds ratio (OR) for CAD of a 5-μmol/L tHcy increment is 1.6(95% confidence interval [Cl], 1.4 to 1.7) for men and 1.8 (95% Cl, 1.3 to 1.9) for women. A total of 10% of the population's CAD risk appears attributable to tHcy. The OR for cerebrovascular disease (5-μmol/L tHcy increment) is 1.5 (95% Cl, 1.3 to 1.9). Peripheral arterial disease also showed a strong association. Increased folic acid intake (approximately 200 μg/d) reduces tHcy levels by approximately 4 μmol/L. Assuming that lower tHcy levels decrease CAD mortality, we calculated the effect of (1) increased dietary folate, (2) supplementation by tablets, and (3) grain fortification. Under different assumptions, 13 500 to 50 000 CAD deaths annually could be avoided; fortification of food had the largest impact. Conclusions. —A 5-μmol/L tHcy increment elevates CAD risk by as much as cholesterol increases of 0.5 mmol/L (20 mg/dL). Higher folic acid intake by reducing tHcy levels promises to prevent arteriosclerotic vascular disease. Clinical trials are urgently needed. Concerns about masking cobalamin deficiency by folic acid could be lessened by adding 1 mg of cobalamin to folic acid supplements. ( JAMA . 1995;274:1049-1057)

Instrumental stakeholder theory: a synthesis of ethics and economics

Abstract: This article is intended to enhance the position of stakeholder theory as an integrating theme for the business and society field. It offers an instrumental theory of stakeholder management based on a synthesis of the stakeholder concept, economic theory, behavioral science, and ethics. The core theory—that a subset of ethical principles (trust, trustworthiness, and cooperativeness) can result in significant competitive advantage—is supplemented by nine research propositions along with some research and policy implications.

Candidate gene for the chromosome 1 familial Alzheimer's disease locus

Abstract: A candidate gene for the chromosome 1 Alzheimer's disease (AD) locus was identified (STM2). The predicted amino acid sequence for STM2 is homologous to that of the recently cloned chromosome 14 AD gene (S182). A point mutation in STM2, resulting in the substitution of an isoleucine for an asparagine (N141l), was identified in affected people from Volga German AD kindreds. This N141l mutation occurs at an amino acid residue that is conserved in human S182 and in the mouse S182 homolog. The presence of missense mutations in AD subjects in two highly similar genes strongly supports the hypothesis that mutations in both are pathogenic.

Chemical mass transfer in magmatic processes IV. A revised and internally consistent thermodynamic model for the interpolation and extrapolation of liquid-solid equilibria in magmatic systems at elevated temperatures and pressures

Abstract: A revised regular solution-type thermodynamic model for twelve-component silicate liquids in the system SiO2-TiO2-Al2O3-Fe2O3-Cr2O3-FeO-MgO-CaO-Na2O-K2O-P2O5-H2O is calibrated. The model is referenced to previously published standard state thermodynamic properties and is derived from a set of internally consistent thermodynamic models for solid solutions of the igneous rock forming minerals, including: (Mg,Fe2+,Ca)-olivines, (Na,Mg,Fe2+,Ca)M2 (Mg,Fe2+, Ti, Fe3+, Al)M1 (Fe3+, Al,Si)2TETO6-pyroxenes, (Na,Ca,K)-feldspars, (Mg,Fe2+) (Fe3+, Al, Cr)2O4-(Mg,Fe2+)2 TiO4 spinels and (Fe2+, Mg, Mn2+)TiO3-Fe2O3 rhombohedral oxides. The calibration utilizes over 2,500 experimentally determined compositions of silicate liquids coexisting at known temperatures, pressures and oxygen fugacities with apatite ±feldspar ±leucite ±olivine ±pyroxene ±quartz ±rhombohedral oxides ±spinel ±whitlockite ±water. The model is applicable to natural magmatic compositions (both hydrous and anhydrous), ranging from potash ankaratrites to rhyolites, over the temperature (T) range 900°–1700°C and pressures (P) up to 4 GPa. The model is implemented as a software package (MELTS) which may be used to simulate igneous processes such as (1) equilibrium or fractional crystallization, (2) isothermal, isenthalpic or isochoric assimilation, and (3) degassing of volatiles. Phase equilibria are predicted using the MELTS package by specifying bulk composition of the system and either (1) T and P, (2) enthalpy (H) and P, (3) entropy (S) and P, or (4) T and volume (V). Phase relations in systems open to oxygen are determined by directly specifying the fo2 or the T-P-fo2 (or equivalently H-P-fo2, S-P-fo2, T-V-fo2) evolution path. Calculations are performed by constrained minimization of the appropriate thermodynamic potential. Compositions and proportions of solids and liquids in the equilibrium assemblage are computed.

Multiple-scattering calculations of x-ray-absorption spectra

Abstract: A high-order multiple-scattering (MS) approach to the calculation of polarized x-ray-absorption spectra, which includes both x-ray-absorption fine structure and x-ray-absorption near-edge structure, is presented. Efficient calculations in arbitrary systems are carried out by using a curved-wave MS path formalism that ignores negligible paths, and has an energy-dependent self-energy and MS Debye-Waller factors. Embedded-atom background absorption calculations on an absolute energy scale are included. The theory is illustrated for metallic Cu, Cd, and Pt. For these cases the MS expansion is found to converge to within typical experimental accuracy, both to experiment and to full MS theories (e.g., band structure), by using only a few dozen important paths, which are primarily single-scattering, focusing, linear, and triangular.

Safeware: System Safety and Computers

Abstract: I The Nature Of Risk. Risk In Modern Society. Changing Attitudes Toward Risk. Is Increased Concern Justified?. Unique Risk Factors in Industrialized Society. Computers And Risk. The Role of Computers in Accidents. Software Myths. Why Software Engineering is hard. The Reality We Face. Causes Of Accidents. The Concept of Causality. Flaws in the Safety Culture. Ineffective Organizational Structure. Ineffective Technical Activities. Human Error And Risk. Do Humans Cause Most Accidents?. The Need for Humans in Automated Systems. Human Error as Human-Task Mismatch. Conclusions. The Role Of Humans In Automated Systems. Mental Models. The Human as Monitor. The Human as Backup. The Human as Partner. Conclusions. II Introduction To System Safety. Foundations Of System Safety. Safety Engineering Pre-World War II. Systems Theory. Systems Engineering. Systems Analysis. Fundamentals Of System Safety. Historical Development. Basic Concepts. Software System Safety. Cost and Effectiveness of System Safety. Other Approaches To Safety. Industrial Safety. Reliability Engineering. Application-Specific Approaches to Safety. III Definitions And Models. Terminology. Failure and Error. Accident and Incident. Hazard. Risk. Safety. Safety and Security. Accident And Human Error Models. Accident Models. Human Task and Error Models. Summary. IV Elements Of A Safeware Program. Managing Safety. The Role of General Management. Place in the Organizational Structure. Documentation. The System And Software Safety Process. The General Tasks. Conceptual Development. Design. Full-Scale Development. Production and Deployment. Operation. "Examples. Hazard Analysis. The Hazard Analysis Process. Types of System Models. General Types of Analysis. Limitations and Criticisms of Hazard Analysis. Hazard Analysis Models And Techniques. Checklists. Hazard Indices. Fault Tree Analysis. Management Oversight and Risk Tree (MORT) Analysis. Event Tree Analysis. Cause-Consequence analysis (CCA). Hazards and Operability Analysis (HAZOP). Interface Analyses. Failure Modes and Effects Analysis (FMEA). Failure Modes, Effects, and Criticality Analysis (FMECA). Fault Hazard Analysis (FHA). State Machine Hazard Analysis (SMHA). Task and Human Error Analysis Techniques. Evaluations of Hazard Analysis Techniques. Software Hazard And Requirements Analysis. Process Considerations. Requirements Specification Components. Completeness in Requirements Specifications. Completeness Criteria for Requirements Analysis. Constraint Analysis. Designing For Safety. The Design Process. Design Techniques. Design Modification and Maintenance. Design Of The Human-Machine Interface. General Process Considerations. Matching Tasks to Human Characteristics. Reducing Safety-Critical Human Errors. Providing Appropriate Information and Feedback. Training and Maintaining Skills. Guidelines for Safe HMI Design. Verification Of Safety. Dynamic Analysis. Static Analysis. Independent Verification and Validation. Summary.

Cyclic nucleotide phosphodiesterases: functional implications of multiple isoforms

Abstract: In the last few years there has been a veritable explosion of knowledge about cyclic nucleotide phosphodiesterases. In particular, the accumulating data showing that there are a large number of different phosphodiesterase isozymes have triggered an equally large increase in interest about these enzymes. At least seven different gene families of cyclic nucleotide phosphodiesterase are currently known to exist in mammalian tissues. Most families contain several distinct genes, and many of these genes are expressed in different tissues as functionally unique alternative splice variants. This article reviews many of the more important aspects about the structure, cellular localization, and regulation of each family of phosphodiesterases. Particular emphasis is placed on new information obtained in the last few years about how differential expression and regulation of individual phosphodiesterase isozymes relate to their function(s) in the body. A substantial discussion of the currently accepted nomenclature is also included. Finally, a brief discussion is included about how the differences among distinct phosphodiesterase isozymes are beginning to be used as the basis for developing therapeutic agents.

Understanding the Intentions of Others: Re-Enactment of Intended Acts by 18-Month-Old Children.

Abstract: Investigated was whether children would re-enact what an adult actually did or what the adult intended to do. In Experiment 1 children were shown an adult who tried, but failed, to perform certain target acts. Completed target acts were thus not observed. Children in comparison groups either saw the full target act or appropriate controls. Results showed that children could infer the adult's intended act by watching the failed attempts. Experiment 2 tested children's understanding of an inanimate object that traced the same movements as the person had followed. Children showed a completely different reaction to the mechanical device than to the person: They did not produce the target acts in this case. Eighteen-month-olds situate people within a psychological framework that differentiates between the surface behavior of people and a deeper level involving goals and intentions. They have already adopted a fundamental aspect of folk psychology-persons (but not inanimate objects) are understood within a framework involving goals and intentions.

Simultaneous multithreading: maximizing on-chip parallelism

Abstract: This paper examines simultaneous multithreading, a technique permitting several independent threads to issue instructions to a superscalar's multiple functional units in a single cycle. We present several models of simultaneous multithreading and compare them with alternative organizations: a wide superscalar, a fine-grain multithreaded processor, and single-chip, multiple-issue multiprocessing architectures. Our results show that both (single-threaded) superscalar and fine-grain multithreaded architectures are limited their ability to utilize the resources of a wide-issue processor. Simultaneous multithreading has the potential to achieve 4 times the throughput of a superscalar, and double that of fine-grain multithreading. We evaluate several cache configurations made possible by this type of organization and evaluate tradeoffs between them. We also show that simultaneous multithreading is an attractive alternative to single-chip multiprocessors; simultaneous multithreaded processors with a variety of organizations outperform corresponding conventional multiprocessors with similar execution resources.While simultaneous multithreading has excellent potential to increase processor utilization, it can add substantial complexity to the design. We examine many of these complexities and evaluate alternative organizations in the design space.

Collaborative management to achieve treatment guidelines : impact on depression in primary care

Abstract: Objective. —To compare the effectiveness of a multifaceted intervention in patients with depression in primary care with the effectiveness of "usual care" by the primary care physician. Design. —A randomized controlled trial among primary care patients with major depression or minor depression. Patients. —Over a 12-month period a total of 217 primary care patients who were recognized as depressed by their primary care physicians and were willing to take antidepressant medication were randomized, with 91 patients meeting criteria for major depression and 126 for minor depression. Interventions. —Intervention patients received increased intensity and frequency of visits over the first 4 to 6 weeks of treatment (visits 1 and 3 with a primary care physician, visits 2 and 4 with a psychiatrist) and continued surveillance of adherence to medication regimens during the continuation and maintenance phases of treatment. Patient education in these visits was supplemented by videotaped and written materials. Main Outcome Measures. —Primary outcome measures included short-term (30-day) and long-term (90-day) use of antidepressant medication at guideline dosage levels, satisfaction with overall care for depression and antidepressant medication, and reduction in depressive symptoms. Results. —In patients with major depression, the intervention group had greater adherence than the usual care controls to adequate dosage of antidepressant medication for 90 days or more (75.5% vs 50.0%;P Conclusion. —A multifaceted intervention consisting of collaborative management by the primary care physician and a consulting psychiatrist, intensive patient education, and surveillance of continued refills of antidepressant medication improved adherence to antidepressant regimens in patients with major and with minor depression. It improved satisfaction with care and resulted in more favorable depressive outcomes in patients with major, but not minor, depression. (JAMA. 1995;273:1026-1031)

Multiresolution analysis of arbitrary meshes

Abstract: In computer graphics and geometric modeling, shapes are often represented by triangular meshes. With the advent of laser scanning systems, meshes of extreme complexity are rapidly becoming commonplace. Such meshes are notoriously expensive to store, transmit, render, and are awkward to edit. Multiresolution analysis offers a simple, unified, and theoretically sound approach to dealing with these problems. Lounsbery et al. have recently developed a technique for creating multiresolution representations for a restricted class of meshes with subdivision connectivity. Unfortunately, meshes encountered in practice typically do not meet this requirement. In this paper we present a method for overcoming the subdivision connectivity restriction, meaning that completely arbitrary meshes can now be converted to multiresolution form. The method is based on the approximation of an arbitrary initial mesh M by a mesh MJ that has subdivision connectivity and is guaranteed to be within a specified tolerance. The key ingredient of our algorithm is the construction of a parametrization of M over a simple domain. We expect this parametrization to be of use in other contexts, such as texture mapping or the approximation of complex meshes by NURBS patches. CR

Association between Bacterial Vaginosis and Preterm Delivery of a Low-Birth-Weight Infant

Abstract: Background Bacterial vaginosis is believed to be a risk factor for preterm delivery. We undertook a study of the association between bacterial vaginosis and the preterm delivery of infants with low birth weight after accounting for other known risk factors. Methods In this cohort study, we enrolled 10,397 pregnant women from seven medical centers who had no known medical risk factors for preterm delivery. At 23 to 26 weeks' gestation, bacterial vaginosis was determined to be present or absent on the basis of the vaginal pH and the results of Gram's staining. The principal outcome variable was the delivery at less than 37 weeks' gestation of an infant with a birth weight below 2500 g. Results Bacterial vaginosis was detected in 16 percent of the 10,397 women. The women with bacterial vaginosis were more likely to be unmarried, to be black, to have low incomes, and to have previously delivered low-birth-weight infants. In a multivariate analysis, the presence of bacterial vaginosis was related to preterm de...

Method to Correlate Tandem Mass Spectra of Modified Peptides to Amino Acid Sequences in the Protein Database

Abstract: A method to correlate uninterpreted tandem mass spectra of modified peptides, produced under low-energy (10-50 eV) collision conditions, with amino acid sequences in a protein database has been developed. The fragmentation patterns observed in the tandem mass spectra of peptides containing covalent modifications is used to directly search and fit linear amino acid sequences in the database. Specific information relevant to sites of modification is not contained in the character-based sequence information of the databases. The search method considers each putative modification site as both modified and unmodified in one pass through the database and simultaneously considers up to three different sites of modification. The search method will identify the correct sequence if the tandem mass spectrum did not represent a modified peptide. This approach is demonstrated with peptides containing modifications such as S-carboxymethylated cysteine, oxidized methionine, phosphoserine, phosphothreonine, or phosphotyrosine. In addition, a scanning approach is used in which neutral loss scans are used to initiate the acquisition of product ion MS/MS spectra of doubly charged phosphorylated peptides during a single chromatographic run for data analysis with the database-searching algorithm. The approach described in this paper provides a convenient method to match the nascent tandem mass spectra of modified peptides to sequences in a protein database and thereby identify previously unknown sites of modification.

Galaxy Harassment and the Evolution of Clusters of Galaxies

Abstract: Disturbed spiral galaxies with high rates of star formation pervaded clusters of galaxies just a few billion years ago, but nearby clusters exclude spirals in favor of ellipticals. ``Galaxy harassment" (frequent high speed galaxy encounters) drives the morphological transformation of galaxies in clusters, provides fuel for quasars in subluminous hosts and leaves detectable debris arcs. Simulated images of harassed galaxies are strikingly similar to the distorted spirals in clusters at $z \sim 0.4$ observed by the Hubble Space Telescope.

Graft copolymers that exhibit temperature-induced phase transitions over a wide range of pH

Abstract: There are many potential applications of 'intelligent' aqueous polymer systems in medicine, biotechnology, industry and in environmental problems. Many of these polymer systems undergo reversible phase transitions--for example, abrupt changes in volume--in response to external stimuli such as temperature, pH or the nature of the solvent. Most of the polymers studied previously are responsive to only one kind of stimulus. But for some applications, independent responsiveness to several factors, such as temperature and pH, may be required. Here we describe a polymer that undergoes marked solubility changes in water in response to temperature and/or pH changes. The polymer is prepared by grafting temperature-sensitive side chains onto a pH-sensitive backbone. We also find that block copolymers, in which the temperature- and pH-sensitive units alternate along the chain, show similar behaviour.

Correlation between climate events in the North Atlantic and China during the last glaciation

Abstract: EPISODES of massive iceberg release (Heinrich events)1-3 into the North Atlantic Ocean during the last glaciation were associated with recurring episodes of unusually cold North Atlantic surface water (Bond cycles)4 and cold air temperatures over Greenland (Dansgaard-Oeschger events)5,6. Four of the youngest of these cold events have also been reported in climate records from sites outside the North Atlantic region7, but until now the entire suite has been identified only in North Atlantic marine sediments, Greenland ice-core records and, tentatively, in French lake sediments8. Here we examine grain-size data from Chinese loess and intercalated accretionary palaeosols of last-glacial age for evidence of similar climate signals remote from the North Atlantic region. We see grain-size maxima with ages that match those of the last six Heinrich events, which we interpret as an indication of the changing strength of the East Asian winter monsoon, which largely controls the transport and deposition of central Asian aeolian dust. Thus it seems that these Heinrich events have left their signature in the Chinese loess record. This is consistent with simulations of the glacial climate9, which imply that the climates of the North Atlantic and China were linked by the effect of westerly winds.

Bayesian Graphical Models for Discrete Data

Abstract: Pendant plus d'un demi-siecle, les graphes ont ete utilises pour representer des modeles statistiques en analyse de donnees. En particulier, les graphes decrivant l'independance conditionnelle sont apparus comme une classe importante de ces modeles. Des applications en analyse d'image, analyse de pedigree, ou encore en systeme expert sont a l'origine de leur developpement, et plusieurs livres de synthese ont deja ete publies a ce sujet. Le developpement d'un cadre Bayesien de ces modeles est en revanche moins connu, et les applications en systemes experts ont motive la recherche dans ce domaine. La possibilite de construire des modeles capables de se remettre a jour au fur et a mesure que de nouvelles donnees sont disponibles est a l'origine d'un interet intense de la part de la communaute travaillant en intelligence artificielle. Cependent, leur application a une classe plus vaste d'analyse de donnees a ete largement negligee. L'objet de cet article est de montrer comment les modeles Bayesiens de graphes permettent d'unifier et de simplifier des problemes standards, tels que les modeles log-lineaires Bayesiens (avec des donnees completes ou non), l'estimation d'une population fermee ou le double echantillonnage. Dans la mesure ou le choix d'un modele conventionel unique echoue dans ce type de situation, nous construisons des distributions a posteriori des quantites d'interet en moyennant sur les modeles possibles. Plus particulierement, nous introduisons la composition de chaines de Markov-Monte Carlo, une methode de Monte-Carlo permettant de moyenner sur les modeles retenus.

The Forward Discount Anomaly and the Risk Premium: A Survey of Recent Evidence

Abstract: Forward exchange rate unbiasedness is rejected in tests from the current floating exchange rate era. This paper surveys advances in this area since the publication of Hodrick's (1987) survey. It documents that the change in the future exchange rate is generally negatively related to the forward discount. Properties of the expected forward forecast error are reviewed. Issues such as the relation of uncovered interest parity to real interest parity, and the implications of uncovered interest parity for cointegration of various quantities are discussed. The modeling and testing for risk premiums is surveyed. Included in this area are tests of the consumption CAPM, tests of the latent variable model, and portfolio-balance models of risk premiums. General equilibrium models of the risk premium are examined and their empirical implications explored. The survey does not cover the important areas of learning and peso problems, tests of rational expectations based on survey data, or the models of irrational expectations and speculative bubbles.

How Wide is the Border

Abstract: Failures of the law of one price explain much of the variation in real C.P.I. exchange rates. We use C.P.I. data for U.S. cities and Canadian cities for 14 categories of consumer prices to examine the nature of the deviations from the law of one price. The distance between cities explains a significant amount of the variation in the prices of similar goods in different cities. But, the variation of the price is much higher for two cities located in different countries than for two equidistant cities in the same country. By our most conservative measure, crossing the border adds as much to the volatility of prices as adding 2500 miles between cities.

Predictors of 30-Day Mortality in the Era of Reperfusion for Acute Myocardial Infarction Results From an International Trial of 41 021 Patients

Abstract: Background Despite remarkable advances in the treatment of acute myocardial infarction, substantial early patient mortality remains. Appropriate choices among alternative therapies and the use of clinical resources depend on an estimate of the patient's risk. Individual patients reflect a combination of clinical features that influence prognosis, and these factors must be appropriately weighted to produce an accurate assessment of risk. Prior studies to define prognosis either were performed before widespread use of thrombolysis or were limited in sample size or spectrum of data. Using the large population of the GUSTO-I trial, we performed a comprehensive analysis of relations between baseline clinical data and 30-day mortality and developed a multivariable statistical model for risk assessment in candidates for thrombolytic therapy. Methods and Results For the 41 021 patients enrolled in GUSTO-I, a randomized trial of four thrombolytic strategies, relations between clinical descriptors routinely collected at initial presentation, and death within 30 days (which occurred in 7% of the population) were examined with both univariable and multivariable analyses. Variables studied included demographics, history and risk factors, presenting characteristics, and treatment assignment. Risk modeling was performed with logistic multiple regression and validated with bootstrapping techniques. Multivariable analysis identified age as the most significant factor influencing 30-day mortality, with rates of 1.1% in the youngest decile ( 75 (adjusted chi(2)=717, P<.0001). Other factors most significantly associated with increased mortality were lower systolic blood pressure (chi(2)=550, P<.0001), higher Killip class (chi(2)=350, P<.0001), elevated heart rate (chi(2)=275, P<.0001), and anterior infarction (chi(2)=143, P<.0001). Together, these five characteristics contained 90% of the prognostic information in the baseline clinical data. Other significant though less important factors included previous myocardial infarction, height, time to treatment, diabetes, weight, smoking status, type of thrombolytic, previous bypass surgery, hypertension, and prior cerebrovascular disease. Combining prognostic variables through logistic regression, we produced a validated model that stratified patient risk and accurately estimated the likelihood of death. Conclusions The clinical determinants of mortality in patients treated with thrombolytic therapy within 6 hours of symptom onset are multifactorial and the relations complex. Although a few variables contain most of the prognostic information, many others contribute additional independent prognostic information. Through consideration of multiple characteristics, including age, medical history, physiological significance of the infarction, and medical treatment, the prognosis of an individual patient can be accurately estimated.

Misoprostol Reduces Serious Gastrointestinal Complications in Patients with Rheumatoid Arthritis Receiving Nonsteroidal Anti-Inflammatory Drugs: A Randomized, Double-Blind, Placebo-Controlled Trial

Abstract: . Objective : To investigate whether concurrent administration of misoprostol reduces the occurrence of serious upper gastrointestinal complications, such as perforation, gastric outlet obstruction, or bleeding, in patients with rheumatoid arthritis who are receiving nonsteroidal anti-inflammatory drugs (NSAIDs). . Design : 6-month randomized, double-blind, placebo-controlled trial. . Setting : 664 clinical practices of family medicine, internal medicine, or rheumatology in the United States and Canada. . Patients : 8843 men and women (mean age, 68 years) receiving continuous therapy with any of 10 specified NSAIDs for control of symptoms of rheumatoid arthritis. Patients were enrolled between July 1991 and August 1993. . Intervention : Patients were randomly assigned to receive 200 μg of misoprostol or placebo four times a day. . Measurements : Development of serious upper gastrointestinal complications detected by clinical symptoms or findings (not by scheduled endoscopy). . Results : Serious upper gastrointestinal complications were reduced by 40% (odds ratio, 0.598 [95% Cl, 0.364 to 0.982 ; P = 0.0491) among patients receiving misoprostol (25 of 4404 patients) compared with those receiving placebo (42 of 4439 patients). During the first month, more patients receiving misoprostol (20%) than placebo (15%) withdrew from the study, primarily because of diarrhea and related problems (P I 0.001). Risk factors for serious upper gastrointestinal complications were increasing age, history of peptic ulcer or bleeding, and cardiovascular disease. Patients with all four risk factors would have a 9% risk for a major complication in 6 months. . Conclusions : In older patients with rheumatoid arthritis, misoprostol reduced serious NSAID-induced upper gastrointestinal complications by 40% compared with placebo.

Extensibility safety and performance in the SPIN operating system

Abstract: This paper describes the motivation, architecture and performance of SPIN, an extensible operating system. SPIN provides an extension infrastructure, together with a core set of extensible services, that allow applications to safely change the operating system's interface and implementation. Extensions allow an application to specialize the underlying operating system in order to achieve a particular level of performance and functionality. SPIN uses language and link-time mechanisms to inexpensively export fine-grained interfaces to operating system services. Extensions are written in a type safe language, and are dynamically linked into the operating system kernel. This approach offers extensions rapid access to system services, while protecting the operating system code executing within the kernel address space. SPIN and its extensions are written in Modula-3 and run on DEC Alpha workstations.

Cell biology of atherosclerosis

Abstract: The process of atherosclerosis is a life-threatening disease that affects critical organs including the heart and brain. It results from the influence of noxious agents associated with hyperlipidemia, hypertension, diabetes, cigarette smoking, homocysteinemia, and other agents that may, in altering the homeostatic condition of the artery wall, injure the endothelium and smooth muscle. The result is a protective, inflammatory, fibroproliferative response that becomes excessive and in its excess results in the disease process we call atherosclerosis.

The Intima: Soil for Atherosclerosis and Restenosis

Abstract: Thirty years ago, John French wrote a seminal review describing the unique properties of the arterial intima.1 His major point was that the smooth muscle cells of the intima have a unique morphology (Fig 1⇓). French also pointed out that intimal formation appeared during normal development and aging as well as in the response of arteries to almost any imaginable injury, including atherosclerosis. Figure 1. Top left, Histology of intima vs media. Coronary artery is from an adult patient with idiopathic dilated cardiomyopathy. In the absence of atherosclerosis, there remains diffuse intimal hyperplasia. The intima is several cell layers thick and composed of smooth muscle cells and is separated from the distinct media by the internal elastic lamina (arrows) (hematoxylin and eosin, original magnification ×200). Top right, Advanced atherosclerosis of the left circumflex coronary artery. This lesion was treated by percutaneous balloon angioplasty 23 days before the patient’s death. Note the complex nature of the lesion with a distinct fibrous cap (FC), intimal hyperplasia (IHP), intramural hemorrhage (H), and a necrotic core (NC) composed of inflammatory cells and accumulated lipid (hematoxylin and eosin, original magnification ×100). Bottom left, Myxomatous tissue. Directional coronary atherectomy specimen from a restenotic lesion shows stellate-shaped smooth muscle cells. Smooth muscle cells with this appearance are often regarded as evidence of proliferation. Note the homogeneity of these cells and the absence of inflammatory and endothelial cells in this region (hematoxylin and eosin, original magnification ×200). Bottom right, Directional coronary atherectomy specimen from a primary lesion. Again, note the presence of stellate-shaped smooth muscle cells but a denser connective tissue matrix (hematoxylin and eosin, original magnification ×200). This article attempts to update French’s review. We will discuss the developmental origins of the intima and suggest that the arterial intima is a distinct tissue with a long and …