Showing papers by "University of Washington published in 1993"

The pathogenesis of atherosclerosis: a perspective for the 1990s

Abstract: Atherosclerosis, the principal cause of heart attack, stroke and gangrene of the extremities, is responsible for 50% of all mortality in the USA, Europe and Japan. The lesions result from an excessive, inflammatory-fibroproliferative response to various forms of insult to the endothelium and smooth muscle of the artery wall. A large number of growth factors, cytokines and vasoregulatory molecules participate in this process. Our ability to control the expression of genes encoding these molecules and to target specific cell types provides opportunities to develop new diagnostic and therapeutic agents to induce the regression of the lesions and, possibly, to prevent their formation.

Cognitive-Behavioral Treatment of Borderline Personality Disorder

Abstract: Part I: Theory and Concepts Borderline Personality Disorder: Concepts, Controversies, and Definitions Dialectical and Biosocial Underpinnings of Treatment Behavioral Patterns: Dialectical Dilemmas in the Treatment of Borderline Patients Part II: Treatment Overview and Goals Overview of Treatment: Targets, Strategies, and Assumptions in a Nutshell Behavioral Targets in Treatment: Behaviors to Increase and Decrease Structuring Treatment around Target Behaviors: Who Treats What and When Part III: Basic Treatment Strategies Dialectical Treatment Strategies Core Strategies: Validation Core Strategies: Problem Solving Change Procedures: Contingency Procedures of Managing Contingencies and Observing Limits Change Procedures: Skills Training, Exposure, Cognitive Modification Stylistic Strategies: Balancing Communication Case Management Strategies: Interacting with the Community Part IV: Strategies for Specific Tasks Structural Strategies Special Treatment Strategies Appendix: Suggesting Reading References Index

Approximate inference in generalized linear mixed models

Abstract: Statistical approaches to overdispersion, correlated errors, shrinkage estimation, and smoothing of regression relationships may be encompassed within the framework of the generalized linear mixed model (GLMM). Given an unobserved vector of random effects, observations are assumed to be conditionally independent with means that depend on the linear predictor through a specified link function and conditional variances that are specified by a variance function, known prior weights and a scale factor. The random effects are assumed to be normally distributed with mean zero and dispersion matrix depending on unknown variance components. For problems involving time series, spatial aggregation and smoothing, the dispersion may be specified in terms of a rank deficient inverse covariance matrix. Approximation of the marginal quasi-likelihood using Laplace's method leads eventually to estimating equations based on penalized quasilikelihood or PQL for the mean parameters and pseudo-likelihood for the variances. Im...

Measuring health-related quality of life.

Abstract: Clinicians and policymakers are recognizing the importance of measuring health-related quality of life (HRQL) to inform patient management and policy decisions. Self- or interviewer-administered qu...

Development and psychometric evaluation of the Resilience Scale

Abstract: This study describes the development and initial psychometric evaluation of the 25-item Resilience Scale (RS) in a sample of 810 community-dwelling older adults. Principal components factor analysis of the RS was conducted followed by oblimin rotation indicating that the factor structure represented two factors (Personal Competence and Acceptance of Self and Life). Positive correlations with adaptational outcomes (physical health, morale, and life satisfaction) and a negative correlation with depression supported concurrent validity of the RS. The results of this study support the internal consistency reliability and concurrent validity of the RS as an instrument to measure resilience.

Skills Training Manual for Treating Borderline Personality Disorder

Abstract: Rationale for Psychosocial Skills Training with Borderline Patients. Practical Issues in Psychosocial Skills Training. Session Format and Starting Skills Training. Application of Structural Strategies and Skills Training Procedures to Psychosocial Skills Training. Application of Other Strategies and Procedures to Psychosocial Skills Training. Session-by-Session Outlines for Psychosocial Skills Training. Core Mindfulness Skills. Interpersonal Effectiveness Skills. Emotion Regulation Skills. Distress Tolerance Skills. Handouts and Homework Sheets. References. Index.

Spectral Analysis for Physical Applications

Abstract: Note: Includes bibliographical references and indexes Reference Record created on 2004-09-07, modified on 2016-08-08

Comparison of oxygen isotope records from the GISP2 and GRIP Greenland ice cores

Abstract: RECENT results1,2 from the Greenland Ice-core Project (GRIP) Summit ice core suggest that the climate in Greenland has been remarkably stable during the Holocene, but was extremely unstable for the time period represented by the rest of the core, spanning the last two glaciations and the intervening Eemian inter-glacial. Here we present the complete oxygen isotope record for the Greenland Ice Sheet Project 2 (GISP2) core, drilled 28 km west of the GRIP core. We observe large, rapid climate fluctuations throughout the last glacial period, which closely match those reported for the GRIP core. However, in the bottom 10% of the cores, spanning the Eemian interglacial and the previous glacia-tion, there are significant differences between the two records. It is possible that ice flow may have altered the chronological sequences of the stratigraphy for the bottom part of one or both of the cores. Considerable further work will be necessary to evaluate the likelihood of this, and the extent to which it will still be possible to extract meaningful climate information from the lowest sections of the cores.

Flexural rigidity of microtubules and actin filaments measured from thermal fluctuations in shape.

Abstract: Microtubules are long, proteinaceous filaments that perform structural functions in eukaryotic cells by defining cellular shape and serving as tracks for intracellular motor proteins. We report the first accurate measurements of the flexural rigidity of microtubules. By analyzing the thermally driven fluctuations in their shape, we estimated the mean flexural rigidity of taxol-stabilized microtubules to be 2.2 x 10(-23) Nm2 (with 6.4% uncertainty) for seven unlabeled microtubules and 2.1 x 10(-23) Nm2 (with 4.7% uncertainty) for eight rhodamine-labeled microtubules. These values are similar to earlier, less precise estimates of microtubule bending stiffness obtained by modeling flagellar motion. A similar analysis on seven rhodamine-phalloidin-labeled actin filaments gave a flexural rigidity of 7.3 x 10(-26) Nm2 (with 6% uncertainty), consistent with previously reported results. The flexural rigidity of these microtubules corresponds to a persistence length of 5,200 microns showing that a microtubule is rigid over cellular dimensions. By contrast, the persistence length of an actin filament is only approximately 17.7 microns, perhaps explaining why actin filaments within cells are usually cross-linked into bundles. The greater flexural rigidity of a microtubule compared to an actin filament mainly derives from the former's larger cross-section. If tubulin were homogeneous and isotropic, then the microtubule's Young's modulus would be approximately 1.2 GPa, similar to Plexiglas and rigid plastics. Microtubules are expected to be almost inextensible: the compliance of cells is due primarily to filament bending or sliding between filaments rather than the stretching of the filaments themselves.

Pruning algorithms-a survey

Abstract: A rule of thumb for obtaining good generalization in systems trained by examples is that one should use the smallest system that will fit the data. Unfortunately, it usually is not obvious what size is best; a system that is too small will not be able to learn the data while one that is just big enough may learn very slowly and be very sensitive to initial conditions and learning parameters. This paper is a survey of neural network pruning algorithms. The approach taken by the methods described here is to train a network that is larger than necessary and then remove the parts that are not needed. >

The Seasonal Cycle of Low Stratiform Clouds

Abstract: The seasonal cycle of low stratiform clouds is studied using data from surface-based cloud climatologies. The impact of low clouds on the radiation budget is illustrated by comparison of data from the Earth Radiation Budget Experiment with the cloud climatologies. Ten regions of active stratocumulus convection are identified. These regions fall into four categories: subtropical marine, midlatitude marine, Arctic stratus, and Chinese stratus. With the exception of the Chinese region, all the regions with high amounts of stratus clouds are over the oceans. In all regions except the Arctic, the season of maximum stratus corresponds to the season of greatest lower-troposphere static stability. Interannual variations in stratus cloud amount also are related to changes in static stability. A linear analysis indicates that a 6 percent increase in stratus fractional area coverage is associated with each 1 C increase in static stability. Over midlatitude oceans, sky-obscuring fog is a large component of the summertime stratus amount. The amount of fog appears to be related to warm advection across sharp gradients of SST.

Quantification of the relationship between insulin sensitivity and beta-cell function in human subjects. Evidence for a hyperbolic function.

Abstract: To determine the relationship between insulin sensitivity and β-cell function, we quantified the insulin sensitivity index using the minimal model in 93 relatively young, apparently healthy human subjects of varying degrees of obesity (55 male, 38 female; 18–44 yr of age; body mass index 19.5–52.2 kg/m 2 ) and with fasting glucose levels I was compared with measures of body adiposity and β-cell function. Although lean individuals showed a wide range of S I , body mass index and S I were related in a curvilinear manner ( P I and the β-cell measures was more clearly curvilinear and reciprocal for fasting insulin ( P glucose ; P n = 56; P max ; n = 43; P I and the β-cell measures could not be distinguished from a hyperbola, i.e., S I × β-cell function = constant. This hyperbolic relationship described the data significantly better than a linear function ( P I , a proportionate reciprocal difference occurs in insulin levels and responses in subjects with similar carbohydrate tolerance. We conclude that in human subjects with normal glucose tolerance and varying degrees of obesity, β-cell function varies quantitatively with differences in insulin sensitivity. Because the function governing this relationship is a hyperbola, when insulin sensitivity is high, large changes in insulin sensitivity produce relatively small changes in insulin levels and responses, whereas when insulin sensitivity is low, small changes in insulin sensitivity produce relatively large changes in insulin levels and responses. Percentile plots based on knowledge of this interaction are presented for evaluating β-cell function in populations and over time.

An investigation of the Therac-25 accidents

Abstract: Between June 1985 and January 1987, the Therac-25 medical electron accelerator was involved in six massive radiation overdoses. As a result, several people died and others were seriously injured. A detailed investigation of the factors involved in the software-related overdoses and attempts by users, manufacturers, and government agencies to deal with the accidents is presented. The authors demonstrate the complex nature of accidents and the need to investigate all aspects of system development and operation in order to prevent future accidents. The authors also present some lessons learned in terms of system engineering, software engineering, and government regulation of safety-critical systems containing software components. >

The Science of Prevention: A Conceptual Framework and Some Directions for a National Research Program

Abstract: A conceptual framework for studying the prevention of human dysfunction is offered. On the basis of recent advances in research on the development of psychological disorders and methods of preventive intervention, generalizations about the relation of risk and protective factors to disorder are put forward, along with a set of principles for what may be identified as the science of prevention. Emerging themes from the study of human development, in general, need to be incorporated in the models for explaining and preventing serious problems of human adaptation. The article concludes with a set of recommendations for a national prevention research agenda.

Prader-Willi Syndrome: Consensus Diagnostic Criteria

Abstract: The diagnosis of Prader-Willi syndrome (PWS) is based on clinical findings that change with age. Hypotonia is prominent in infancy. Obesity, mild mental retardation or learning disability, and behavior problems, especially in association with food and eating, result in a debilitating physical and developmental disability in adolescence and adulthood. No consistent biological marker is yet available for PWS in spite of recent research activity in cytogenetics and molecular genetics. Diagnostic criteria for PWS were developed by consensus of seven clinicians experienced with the syndrome in consultation with national and international experts. Two scoring systems are provided: one for children aged 0 to 36 months and another one for children aged 3 years to adults. These criteria will aid in recognition of the syndrome in hypotonic infants and in obese, mildly retarded, behaviorally disturbed adolescents and adults. They will also ensure uniform diagnosis for future clinical and laboratory research in PWS.

Ankle-arm index as a marker of atherosclerosis in the Cardiovascular Health Study. Cardiovascular Heart Study (CHS) Collaborative Research Group.

Abstract: BACKGROUNDPeripheral arterial disease measured noninvasively by the ankle-arm index (AAI) is common in older adults, largely asymptomatic, and associated with clinically manifest cardiovascular disease (CVD). The criteria for an abnormal AAI have varied in previous studies. To determine whether there is an inverse dose-response relation between the AAI and clinical CVD, subclinical disease, and risk factors, we examined the relation of the AAI to cardiovascular risk factors, other noninvasive measures of subclinical atherosclerosis using carotid ultrasound, echocardiography and electrocardiography, and clinical CVD.METHODS AND RESULTSThe AAI was measured in 5084 participants > or = 65 years old at the baseline examination of the Cardiovascular Health Study. All subjects had detailed assessment of prevalent CVD, measures of cardiovascular risk factors, and noninvasive measures of disease. Participants were stratified by baseline clinical CVD status and AAI ( or = 0.8 to or = 0.9 to < 1.0, ...

A fiber-optic chemical sensor based on surface plasmon resonance

Abstract: A fiber-optic chemical sensor is presented which utilizes surface plasmon resonance excitation The sensing element of the fiber has been fabricated by removing a section of the fiber cladding and symmetrically depositing a thin layer of highly reflecting metal onto the fiber core A white-light source is used to introduce a range of wavelengths into the fiber optic Changes in the sensed parameters (eg, bulk refractive index, film thinkness and film refractive index) are determined by measuring the transmitted spectral-intensity distribution Experimental results of the sensitivity and the dynamic range in the measurement of the refractive indices of aqueous solutions are in agreement with the theoretical model of the sensor

The Risk and Predictability of International Equity Returns

Abstract: We investigate predictability in national equity market returns, and its relation to global economic risks. We show how to consistently estimate the fraction of the predictable variation that is captured by an assetpricing modelfor the expected returns. We use a model in which conditional betas of the national equity markets depend on local information variables, while global risk premia depend on global variables. We examine singleand multiple-beta models, using monthly data for 1970 to 1989. The models capture much of thepredictability for many countries. Most of this is related to time variation in the global risk premia. We investigate the sources of risk and predictability of international equity market returns. We examine several global economic risk factors, including a world market portfolio, exchange rate fluctuations, mea

Abrupt increase in Greenland snow accumulation at the end of the Younger Dryas event

Abstract: THE warming at the end of the last glaciation was characterized by a series of abrupt returns to glacial climate, the best-known of which is the Younger Dryas event1. Despite much study of the causes of this event and the mechanisms by which it ended, many questions remain unresolved1. Oxygen isotope data from Greenland ice cores2–4 suggest that the Younger Dryas ended abruptly, over a period of about 50 years; dust concentrations2,4 in these cores show an even more rapid transition (≲20 years). This extremely short timescale places severe constraints on the mechanisms underlying the transition. But dust concentrations can reflect subtle changes in atmospheric circulation, which need not be associated with a large change in climate. Here we present results from a new Greenland ice core (GISP2) showing that snow accumulation doubled rapidly from the Younger Dryas event to the subsequent Preboreal interval, possibly in one to three years. We also find that the accumulation-rate change from the Oldest Dryas to the Bo11ing/Allerod warm period was large and abrupt. The extreme rapidity of these changes in a variable that directly represents regional climate implies that the events at the end of the last glaciation may have been responses to some kind of threshold or trigger in the North Atlantic climate system.

Mitochondrial ribosomal RNA mutation associated with both antibiotic-induced and non-syndromic deafness.

Abstract: Maternally transmitted non-syndromic deafness was described recently both in pedigrees with susceptibility to aminoglycoside ototoxicity and in a large Arab-Israeli pedigree. Because of the known action of aminoglycosides on bacterial ribosomes, we analysed the sequence of the mitochondrial rRNA genes of three unrelated patients with familial aminoglycoside-induced deafness. We also sequenced the complete mitochondrial genome of the Arab-Israeli pedigree. All four families shared a nucleotide 1555 A to G substitution in the 12S rRNA gene, a site implicated in aminoglycoside activity. Our study offers the first description of a mitochondrial rRNA mutation leading to disease, the first cases of non-syndromic deafness caused by a mitochondrial DNA mutation and the first molecular genetic study of antibiotic-induced ototoxicity.

The reality of repressed memories.

Abstract: Repression is one of the most haunting concepts in psychology. Something shocking happens, and the mind pushes it into some inaccessible corner of the unconscious. Later, the memory may emerge into consciousness. Repression is one of the foundation stones on which the structure of psychoanalysis rests. Recently there has been a rise in reported memories of childhood sexual abuse that were allegedly repressed for many years. With recent changes in legislation, people with recently unearthed memories are suing alleged perpetrators for events that happened 20, 30, even 40 or more years earlier. These new developments give rise to a number of questions: (a) How common is it for memories of child abuse to be repressed? (b) How are jurors and judges likely to react to these repressed memory claims? (c) When the memories surface, what are they like? and (d) How authentic are the memories?

Systemic gene expression after intravenous DNA delivery into adult mice

Abstract: Direct gene transfer into adult animals resulting in generalized or tissue-specific expression would facilitate rapid analysis of transgene effects and allow precise in vivo manipulation of biologic processes at the molecular level. A single intravenous injection of expression plasmid:cationic liposome complexes into adult mice efficiently transfected virtually all tissues. In addition to vascular endothelial cells, most of the extravascular parenchymal cells present in many tissues including the lung, spleen, lymph nodes, and bone marrow expressed the transgene without any apparent treatment-related toxicity. The transgene was still expressed in large numbers of cells in multiple tissues for at least 9 weeks after a single injection. Expression could be targeted to specific tissues and cell types, depending on the promoter element used.

A direct measurement of the terrestrial mass accretion rate of cosmic dust.

Abstract: The mass of extraterrestrial material accreted by the Earth as submillimeter particles has not previously been measured with a single direct and precise technique that samples the particle sizes representing most of that mass. The flux of meteoroids in the mass range 10(-9) to 10(-4) grams has now been determined from an examination of hypervelocity impact craters on the space-facing end of the Long Duration Exposure Facility satellite. The meteoroid mass distribution peaks near 1.5 x 10(-5) grams (200 micrometers in diameter), and the small particle mass accretion rate is (40 +/- 20) x 106 kilograms per year, higher than previous estimates but in good agreement with total terrestrial mass accretion rates found by geochemical methods. This mass input is comparable with or greater than the average contribution from extraterrestrial bodies in the 1-centimeter to 10-kilometer size range.

Lipid lowering and plaque regression. New insights into prevention of plaque disruption and clinical events in coronary disease.

Abstract: The consensus of evidence from angiographic trials demonstrates both coronary artery and clinical benefits from lowering of lipids by a variety of regimens. The findings of reduced arterial disease progression and increased regression have been convincing but, at best, modest in their magnitude. For example, among those treated intensively in FATS, the mean improvement in proximal stenosis severity per patient was < 1% stenosis, and only 12% of all lesions showed convincing regression. In view of these modest arterial benefits, the associated reductions in cardiovascular events have been surprisingly great. For example, coronary events were reduced 75% in FATS; this was entirely a result of a 93% reduction in the likelihood that a mildly or moderately diseased arterial segment would experience substantial progression to a severe lesion at the time of a clinical event. We believe that the magnitude of the clinical benefit is best explained in terms of this observation, according to the following lines of reasoning. Clinical events most commonly spring from lesions that are initially of mild or moderate severity and then abruptly undergo a disruptive transformation to a severe culprit lesion. The process of plaque fissuring, leading to plaque disruption and thrombosis, triggers most clinical coronary events. Fissuring is predicted by a large accumulation of core lipid in the plaque and by a high density of lipid-laden macrophages in its thinned fibrous cap. Lesions with these characteristics constitute only 10-20% of the overall lesion population but account for 80-90% of the acute clinical events. In the experimental setting, normalization of an atherogenic lipid profile substantially decreases the number of lipid-laden intimal macrophages (foam cells) and depletes cholesterol from the core lipid pool. In the clinical setting, intensive lipid lowering virtually halts the progression of mild and moderate lesions to clinical events. Thus, the reduction in clinical events observed in these trials appears to be best explained by the relation of the lipid and foam cell content of the plaque to its likelihood of fissuring and by the effects of lipid-lowering therapy on these "high-risk" features of plaque morphology. The composite of data presented here supports the hypothesis that lipid-lowering therapy selectively depletes (regresses) that relatively small but dangerous subgroup of fatty lesions containing a large lipid core and dense clusters of intimal macrophages. By doing so, these lesions are effectively stabilized and clinical event rate is accordingly decreased.

Management of urinary tract infections in adults.

Abstract: Urinary tract infections account for more than 7 million visits to physicians' offices and necessitate or complicate well over 1 million hospital admissions in the United States annually1,2. It is helpful to categorize adult patients with urinary infection into five groups: young women with acute uncomplicated cystitis, young women with recurrent cystitis, young women with acute uncomplicated pyelonephritis, all adults with complicated urinary infection, and all adults with asymptomatic bacteriuria. This review will highlight recent advances in the treatment of patients in each of these categories, emphasizing cost-effective strategies that may be particularly important in the coming era . . .

CD40 ligand gene defects responsible for X-linked hyper-IgM syndrome

Abstract: The ligand for CD40 (CD40L) is a membrane glycoprotein on activated T cells that induces B cell proliferation and immunoglobulin secretion. Abnormalities in the CD40L gene were associated with an X-linked immunodeficiency in humans [hyper-IgM (immunoglobulin M) syndrome]. This disease is characterized by elevated concentrations of serum IgM and decreased amounts of all other isotypes. CD40L complementary DNAs from three of four patients with this syndrome contained distinct point mutations. Recombinant expression of two of the mutant CD40L complementary DNAs resulted in proteins incapable of binding to CD40 and unable to induce proliferation or IgE secretion from normal B cells. Activated T cells from the four affected patients failed to express wild-type CD40L, although their B cells responded normally to wild-type CD40L. Thus, these CD40L defects lead to a T cell abnormality that results in the failure of patient B cells to undergo immunoglobulin class switching.