Showing papers by "Johns Hopkins University published in 1986"

Longitudinal data analysis using generalized linear models

Abstract: SUMMARY This paper proposes an extension of generalized linear models to the analysis of longitudinal data. We introduce a class of estimating equations that give consistent estimates of the regression parameters and of their variance under mild assumptions about the time dependence. The estimating equations are derived without specifying the joint distribution of a subject's observations yet they reduce to the score equations for multivariate Gaussian outcomes. Asymptotic theory is presented for the general class of estimators. Specific cases in which we assume independence, m-dependence and exchangeable correlation structures from each subject are discussed. Efficiency of the proposed estimators in two simple situations is considered. The approach is closely related to quasi-likelih ood. Some key ironh: Estimating equation; Generalized linear model; Longitudinal data; Quasi-likelihood; Repeated measures.

Parallel Organization of Functionally Segregated Circuits Linking Basal Ganglia and Cortex

Abstract: Information about the basal ganglia has accumulated at a prodigious pace over the past decade, necessitating major revisions in our concepts of the structural and functional organization of these nuclei. From earlier data it had appeared that the basal ganglia served primarily to integrate diverse inputs from the entire cerebral cortex and to "funnel" these influences, via the ventrolateral thalamus, to the motor cortex (Allen & Tsukahara 1974, Evarts & Thach 1969, Kemp & Powell 1971). In particular, the basal

Development of criteria for the classification and reporting of osteoarthritis: Classification of osteoarthritis of the knee

Abstract: For the purposes of classification, it should be specified whether osteoarthritis (OA) of the knee is of unknown origin (idiopathic, primary) or is related to a known medical condition or event (secondary). Clinical criteria for the classification of idiopathic OA of the knee were developed through a multicenter study group. Comparison diagnoses included rheumatoid arthritis and other painful conditions of the knee, exclusive of referred or para-articular pain. Variables from the medical history, physical examination, laboratory tests, and radiographs were used to develop sets of criteria that serve different investigative purposes. In contrast to prior criteria, these proposed criteria utilize classification trees, or algorithms.

Actin and Actin-Binding Proteins. A Critical Evaluation of Mechanisms and Functions

Abstract: PERSPECTIVES AND SUMMARY 988 INTRODUCTION 988 THE ACTIN MOLECULE 989 MECHANISM OF POL YMERIZA TION , , 994 MECHANICAL PROPERTIES , 1004 ACTIN MONOMER BINDING PROTEINS 1006 CAPPING PROTEINS , 1011 LOW-MOLECULAR-WEIGHT SEVERING PROTEINS 1018 PROTEINS THAT BIND TO THE SIDES OF ACTIN FILAMENTS 1019 MEMBRANE ATTACHMENT PROTEINS 1026 FUTURE RESEARCH 1029

Liberalism and world politics

Abstract: Building on a growing literature in international political science, I reexamine the traditional liberal claim that governments founded on a respect for individual liberty exercise “restraint” and “peaceful intentions” in their foreign policy. I look at three distinct theoretical traditions of liberalism, attributable to three theorists: Schumpeter, a democratic capitalist whose explanation of liberal pacifism we often invoke; Machiavelli, a classical republican whose glory is an imperialism we often practice; and Kant, a liberal republican whose theory of internationalism best accounts for what we are. Despite the contradictions of liberal pacifism and liberal imperialism, I find, with Kant and other democratic republicans, that liberalism does leave a coherent legacy on foreign affairs. Liberal states are different. They are indeed peaceful. They are also prone to make war. Liberal states have created a separate peace, as Kant argued they would, and have also discovered liberal reasons for aggression, as he feared they might. I conclude by arguing that the differences among liberal pacifism, liberal imperialism, and Kant's internationalism are not arbitrary. They are rooted in differing conceptions of the citizen and the state.

Positron emission tomography reveals elevated D2 dopamine receptors in drug-naive schizophrenics

Abstract: In postmortem studies of patients with schizophrenia, D2 dopamine receptors in the basal ganglia have been observed to be more numerous than in patients with no history of neurological or psychiatric disease. Because most patients with schizophrenia are treated with neuroleptic drugs that block D2 dopamine receptors in the caudate nucleus, it has been suggested that this increase in the number of receptors is a result of adaptation to these drugs rather than a biochemical abnormality intrinsic to schizophrenia. With positron emission tomography (PET), the D2 dopamine receptor density in the caudate nucleus of living human beings was measured in normal volunteers and in two groups of patients with schizophrenia--one group that had never been treated with neuroleptics and another group that had been treated with these drugs. D2 dopamine receptor densities in the caudate nucleus were higher in both groups of patients than in the normal volunteers. Thus, schizophrenia itself is associated with an increase in brain D2 dopamine receptor density.

Classification system for human T-lymphotropic virus type III/lymphadenopathy-associated virus infections

Abstract: This article presents a classification system for patients with the spectrum of clinical and laboratory findings attributable to human T-lymphotropic virus type III/lymphadenopathy-associated virus (HTLV-III/LAV). This classification system is primarily for public health purposes, including disease reporting and surveillance, epidemiologic studies, prevention and control activities, and public health policy and planning. The system classifies the manifestations of HTLV-III/LAV infection into 4 groups: I) patients with transient signs and symptoms that appear at the time of, or shortly after, initial infection with HTLV-III/LAV as identified by laboratory studies; II) patients with no signs or symptoms of HTLV-III/LAV infection, who in turn can be subclassified on the basis of whether hematologic and/or immunologic studies have been done and whether results are abnormal; III) patients with persistent generalized lymphadenopathy at 2 or more extra-inguinal sites persisting for more than 3 months in the absence of a condition other than HTLV-III/LAV infection to explain these findings; and IV) patients with clinical symptoms and signs of HTLV-III/LAV infection other than or in addition to lymphadenopathy. Patients in Group IV are further categorized into 5 subgroups: A) constitutional disease, B) neurologic disease, C) secondary infectious disease, D) secondary cancers, and E) other conditions resulting from HTLV-III/LAV infection. This classificatory system will require periodic revision as new information about HTLV-III/LAV infection is accumulated. Patients whose clinical presentations fulfill the surveillance definition of acquired immunedeficiency syndrome (AIDS) should be classified in Group IV.

Best-Evidence Synthesis: An Alternative to Meta-Analytic and Traditional Reviews

Abstract: This paper proposes an alternative to both meta-analytic and traditional reviews. The method, “best-evidence synthesis,” combines the quantification of effect sizes and systematic study selection procedures of quantitative syntheses with the attention to individual studies and methodological and substantive issues typical of the best narrative reviews. Best-evidence syntheses focus on the “best evidence” in a field, the studies highest in internal and external validity, using well-specified and defended a priori inclusion criteria, and use effect size data as an adjunct to a full discussion of the literature being reviewed.

Silent ischemia as a marker for early unfavorable outcomes in patients with unstable angina.

Abstract: We examined the prevalence and prognostic importance of silent myocardial ischemia detected by continuous electrocardiographic monitoring in 70 patients with unstable angina. All the patients received intensive medical treatment with nitrates, beta-blockers, and calcium-channel blockers. Continuous electrocardiographic recordings were made during the first two days in the coronary care unit to quantify the frequency and duration of asymptomatic ischemic episodes, defined as a transient ST-segment shift of 1 mm or more. Thirty-seven patients (Group 1) had at least one episode of silent ischemia, and the other 33 patients had no silent ischemia (Group 2). Over the subsequent month, myocardial infarction occurred in 6 patients in Group 1 and in only 1 in Group 2 (P less than 0.01); bypass surgery or angioplasty was required for recurrent symptomatic angina in 10 patients in Group 1 and only 3 in Group 2 (P = 0.02). Survival-curve analysis demonstrated that silent ischemia was associated with these outcomes (P less than 0.002), and multivariate analysis showed that silent ischemia was the best predictor of these outcomes among the 15 variables tested (P less than 0.002). Patients in Group 1 with 60 minutes or more of silent ischemia per 24 hours had a worse prognosis than those with under 60 minutes per 24 hours (P = 0.04). Silent ischemia occurred in more than 50 percent of our patients with unstable angina, despite intensive medical therapy, and it identified a subset who were at high risk for early unfavorable outcomes.

Parents' Reactions to Teacher Practices of Parent Involvement

Abstract: The Elementary School Journal Volume 86, Number S O 1986 by The University of Chicago. All rights reserved. 0013-5984/86/8603-0002$01.00 Teachers have strong opinions about parent involvement. Some believe that they can be effective only if they obtain parental assistance on learning activities at home. Others believe that their professional status is in jeopardy if parents are involved in activities that are typically the teachers' responsibilities. The different philosophies and beliefs of teachers reflect the two main, opposing theories of school and family relations. One perspective emphasizes the inherent incompatibility, competition, and conflict between families and schools and supports the separation of the two institutions (Parsons, 1959; Waller, 1932; Weber, 1947). It assumes that school bureaucracies and family organizations are directed, respectively, by educators and parents, who can best fulfill their different goals, roles, and responsibilities independently. Thus, these distinct goals are achieved most efficiently and effectively when teachers maintain their professional, general standards and judgments about the children in their classrooms and when parents maintain their personal, particularistic standards and judgments about their children at home.

Molecular heterogeneity of the bullous pemphigoid antigens as detected by immunoblotting.

Abstract: Sera from 28 patients with bullous pemphigoid (BP), four patients with cicatricial pemphigoid (CP), and 24 controls (normal volunteers and patients with pemphigus, systemic lupus erythematosus, or other skin diseases) were tested against extracts of human epidermis by immunoblotting techniques. The extraction buffer included 1% SDS, 5% beta-mercaptoethanol, and six protease inhibitors with various specificities. BP sera from individual patients showed different patterns of reactivity with the same epidermal extract, and each pattern consisted of one or more bands. A total of five bands of 240 kD, 200 kD, 180 kD, 97 kD, and 77 kD reacted with BP sera; the 240-kD band reacted with one CP sera, and none of these bands was detected by the control sera. The 240-kD and 180-kD bands reacted very strongly with some sera and were most frequently observed (43% and 29%, respectively). The 200-kD, 97-kD, and 77-kD bands were less frequently observed (25%, 7%, and 7%, respectively), but when present, their reactions were usually strong. Eleven percent of the BP sera did not react with any bands. Contrary to previous reports, this study shows that BP autoantibodies react with several protein bands, as detected by immunoblotting. We have recently shown by immunoelectron microscopy that BP autoantibodies bind to the basal cell hemidesmosomes. It remains to be determined which of these protein bands represent specific hemidesmosomal proteins and which antibody-antigen interactions are relevant to the pathogenesis of this disease.

Serum beta-carotene, vitamins A and E, selenium, and the risk of lung cancer.

Abstract: We studied the relation of serum vitamin A (retinol), beta-carotene, vitamin E, and selenium to the risk of lung cancer, using serum that had been collected during a large blood-collection study performed in Washington County, Maryland, in 1974. Levels of the nutrients in serum samples from 99 persons who were subsequently found to have lung cancer (in 1975 to 1983) were compared with levels in 196 controls who were matched for age, sex, race, month of blood donation, and smoking history. A strong inverse association between serum beta-carotene and the risk of squamous-cell carcinoma of the lung was observed (relative odds, 4.30; 95 percent confidence limits, 1.38 and 13.41). Mean (+/- SD) levels of vitamin E were lower among the cases than the controls (10.5 +/- 3.2 vs. 11.9 +/- 4.90 mg per liter), when all histologic types of cancer were considered together. In addition, a linear trend in risk was found (P = 0.04), so that persons with serum levels of vitamin E in the lowest quintile had a 2.5 times higher risk of lung cancer than persons with levels in the highest quintile. These data support an association between low levels of serum vitamin E and the risk of any type of lung cancer and between low levels of serum beta-carotene and the risk of squamous-cell carcinoma of the lung.

The Pure Theory of Country Risk

Abstract: This paper attempts to survey, and to put into perspective, recent lterature that has analyzed the nature of credit relations between developed and developing countries.This analysis has made use of recent advances in the economics of information and strategic interaction. Traditional concepts of solvency and liquidity are of little help in understanding problems of soverign debt. Creditors do not have the means to seize the assets of a borrower in default. Hence the borrower who is expected eventually to repay his debts should be able to borrow to meet any current debt-service obligations. A problem that is essential to a theory of international lending is that of enforcement. The difficulty is one of ensuring that the two sides of a loan contract adhere to it, in particular that the borrower repays the lender and the lenders can commit themselves to penalize the borrower if he does not.

Concepts and applications of backup coverage

Abstract: Backup coverage, the second coverage of a demand node, is suggested as a decision criterion in modelling the location of emergency services on a network. The efficient handling of stochastic demand by vehicles which can respond to only one call at a time may require backup coverage in areas of high demand as a means to maintain a more uniform level of service. This new criterion is applied in the context of the classic covering models, the Location Set Covering Problem and the Maximal Covering Location Problem. First coverage as defined in these models is traded off against backup coverage in the present work. Other efforts which incorporate additional levels of coverage are reviewed. We also show how to extend these models to third as well as subsequent coverage. Based on an example problem we show that significant levels of backup coverage may possibly be provided within a system without substantial loss of first coverage.

Autologous Bone Marrow Transplantation in Patients with Acute Nonlymphocytic Leukemia, Using ex Vivo Marrow Treatment with 4-Hydroperoxycyclophosphamide

Abstract: We studied 25 patients with acute nonlymphocytic leukemia in second remission (20 patients) or third remission (5 patients) in whom autologous bone marrow transplantation was performed with use of marrow incubated ex vivo with the alkylating agent 4-hydroperoxycyclophosphamide. Patients received intensive cytoreductive therapy with busulfan and cyclophosphamide or cyclophosphamide and total body irradiation, followed by an infusion of marrow that had been collected in remission, treated with 4-hydroperoxycyclophosphamide, and cryopreserved. Four patients died from bacterial or fungal sepsis within the first month after transplantation, and one patient with persistent marrow hypoplasia died from gram-negative sepsis 155 days after infusion with autologous marrow. In the remaining patients, peripheral-blood levels of neutrophils in excess of 0.5 X 10(9) per liter and platelet counts over 50 X 10(9) per liter were attained at median intervals of 29 and 57 days after transplantation, respectively. Nine patients had leukemic relapses at 73 to 316 days (median, 182 days) after infusion of autologous marrow, for an actuarial relapse rate of 46 percent. Eleven patients (eight in second remission and three in third) remained in remission at a median of more than 400 days (range, greater than 230 to greater than 1653 days) after transplantation. The observed disease-free survival after transplantation with autologous marrow treated with 4-hydroperoxycyclophosphamide compares favorably with the results of syngeneic or allogeneic transplantation in similar groups of patients.

Association of BK Viruria with Hemorrhagic Cystitis in Recipients of Bone Marrow Transplants

Abstract: Fifty-three recipients of bone marrow transplants were monitored prospectively for urinary excretion of human polyomaviruses by enzyme-linked immunosorbent assays of urinary supematants and DNA hybridization assays of urinary cells. Excretion of BK virus was demonstrated in 47 percent of the transplant recipients and was the result of the reactivation of latent virus. Hemorrhagic cystitis of long duration (≥7 days) was associated with BK viruria. The disease occurred four times more frequently in patients who excreted BK virus than in those who did not, and the virus was identified in 55 percent of the urine specimens during episodes of cystitis as compared with 8 to 11 percent of the specimens during cystitisfree periods. BK viruria often preceded or coincided with the onset of the disease. Among 19 patients with BK viruria lasting seven days or longer, hemorrhagic cystitis occurred in 15. Occurrence of the disease was related to the source of marrow. The disease occurred in 50 percent of 38 rec...

Feedback control of nonlinear systems by extended linearization

Abstract: For single-input, multiple-output, nonlinear systems, we consider a design method based on the family of linearizations of the system, parameterized by constant operating points. Nonlinear state feedback control laws and observer/state feedback control laws are designed such that the eigenvalues of the family of linearized closed-loop systems are placed at specified values that are locally invariant with respect to the closed-loop operating point. The method is illustrated by application to the problem of automatically balancing an inverted pendulum.

Autoradiographic localization of sigma receptor binding sites in guinea pig and rat central nervous system with (+)3H-3-(3-hydroxyphenyl)-N-(1- propyl)piperidine

Abstract: (+)3H-3-PPP [(+)3H-3-(3-Hydroxyphenyl)-N-(1-propyl)-piperidine] binds with high affinity to brain membranes with a pharmacological profile consistent with that of sigma receptors. The distribution of (+)3H-3- PPP binding sites in brain and spinal cord of both guinea pig and rat has been determined by in vitro autoradiography with binding densities quantitated by computer-assisted densitometry. (+)3H-3-PPP binding to slide-mounted brain sections is saturable and displays high affinity and a pharmacological specificity very similar to sites labeled in homogenates. (+)3H-3-PPP binding sites are heterogeneously distributed. Highest concentrations of binding sites occur in spinal cord, particularly the ventral horn and dorsal root ganglia; the pons- medulla, associated with the cranial nerve and pontine nuclei and throughout the brain stem reticular formation; the cerebellum, over the Purkinje cell layer; the midbrain, particularly the central gray and red nucleus; and hippocampus, over the pyramidal cell layer. Lowest levels are seen in the basal ganglia and parts of the thalamus, while all other areas, including hypothalamus and cerebral cortex, exhibit moderate grain densities. Quinolinic acid-induced lesions of the hippocampus indicate that (+)3H-3-PPP labels hippocampal pyramidal cells and granule cells in the dentate gyrus. Intrastriatal injection of ibotenic acid dramatically reduces (+)3H-3-PPP binding in this area, while injection of 6-hydroxydopamine produces a relatively slight decrease. The distribution of (+)3H-3-PPP binding sites does not correlate with the receptor distribution of any recognized neurotransmitter or neuropeptide, including dopamine. However, there is a notable similarity between the distribution of (+)3H-3-PPP sites and high-affinity binding sites for psychotomimetic opioids, such as the benzomorphan (+)SKF 10,047.

Reduction in experimental infarct size by recombinant human superoxide dismutase: insights into the pathophysiology of reperfusion injury.

Abstract: To determine the importance of reperfusion injury and the ability of the free-radical scavenger recombinant human superoxide dismutase (h-SOD) to prevent it, open-chest dogs underwent 90 min of proximal circumflex coronary artery occlusion, and only at the moment of reperfusion received either h-SOD (400,000 IU bolus into the left atrium followed by a 300,000 IU iv infusion over 1 hr) or saline. After 48 hr the surviving animals were killed and measurements were made of the risk region (by postmortem angiography) and infarct size (by gross pathology). All measurements were made by investigators blinded to treatment given, and the code was broken only at the end of the study. Hemodynamic variables and collateral flow during ischemia were similar in the two groups. Infarct size in control animals (n = 8) averaged 22.4 +/- 3.1% of the left ventricle and 52.2 +/- 7.1% of the risk region, compared with 13.3 +/- 0.8% of the left ventricle and 33.6 +/- 2.1% of the risk region in h-SOD-treated dogs (n = 8) (p less than .05). Infarcts in treated animals were not only smaller, but also exhibited a distinctive "patchiness," suggesting protection along vascular distributions. Furthermore, analysis of the relationship between infarct size and collateral flow measured during ischemia in the two groups indicated that protection by h-SOD was greatest in animals with the lowest collateral flows. This study supports the concept that reperfusion of ischemic myocardium results in a separate component of cell damage, presumably linked to the generation of oxygen free radicals on reflow. Since the h-SOD preventable reperfusion component of injury was most pronounced in hearts with the most severe ischemia, scavenging of oxygen radicals at the time of reflow may offer a novel and particularly promising therapeutic approach for the protection of ischemic myocardium.