Showing papers by "University of Pennsylvania published in 1991"
TL;DR: The updated information on tolerance of normal tissues of concern in the protocols of this contract, based on available data, is presented, with a special emphasis on partial volume effects.
Abstract: The importance of knowledge on tolerance of normal tissue organs to irradiation by radiation oncologists cannot be overemphasized. Unfortunately, current knowledge is less than adequate. With the increasing use of 3-D treatment planning and dose delivery, this issue, particularly volumetric information, will become even more critical. As a part of the NCI contract N01 CM-47316, a task force, chaired by the primary author, was formed and an extensive literature search was carried out to address this issue. In this issue. In this manuscript we present the updated information on tolerance of normal tissues of concern in the protocols of this contract, based on available data, with a special emphasis on partial volume effects. Due to a lack of precise and comprehensive data base, opinions and experience of the clinicians from four universities involved in the contract have also been contributory. Obviously, this is not and cannot be a comprehensive work, which is beyond the scope of this contract.
4,133 citations
University of Texas Health Science Center at Houston1, Virginia Commonwealth University2, Stony Brook University3, University of California, Los Angeles4, University of Pittsburgh5, University of Pennsylvania6, New York University7, University of Colorado Denver8, University of Illinois at Chicago9, Harvard University10, National Institutes of Health11, Cleveland Clinic12
TL;DR: Mortality was most closely associated with right ventricular hemodynamic function and can be characterized by means of an equation using three variables: mean pulmonary artery pressure, mean right atrial pressure, and cardiac index.
Abstract: Objective To characterize mortality in persons diagnosed with primary pulmonary hypertension and to investigate factors associated with survival. Design Registry with prospective follow-up. Setting Thirty-two clinical centers in the United States participating in the Patient Registry for the Characterization of Primary Pulmonary Hypertension supported by the National Heart, Lung, and Blood Institute. Patients Patients (194) diagnosed at clinical centers between 1 July 1981 and 31 December 1985 and followed through 8 August 1988. Measurements At diagnosis, measurements of hemodynamic variables, pulmonary function, and gas exchange variables were taken in addition to information on demographic variables, medical history, and life-style. Patients were followed for survival at 6-month intervals. Main results The estimated median survival of these patients was 2.8 years (95% Cl, 1.9 to 3.7 years). Estimated single-year survival rates were as follows: at 1 year, 68% (Cl, 61% to 75%); at 3 years, 48% (Cl, 41% to 55%); and at 5 years, 34% (Cl, 24% to 44%). Variables associated with poor survival included a New York Heart Association (NYHA) functional class of III or IV, presence of Raynaud phenomenon, elevated mean right atrial pressure, elevated mean pulmonary artery pressure, decreased cardiac index, and decreased diffusing capacity for carbon monoxide (DLCO). Drug therapy at entry or discharge was not associated with survival duration. Conclusions Mortality was most closely associated with right ventricular hemodynamic function and can be characterized by means of an equation using three variables: mean pulmonary artery pressure, mean right atrial pressure, and cardiac index. Such an equation, once validated prospectively, could be used as an adjunct in planning treatment strategies and allocating medical resources.
3,301 citations
Posted Content•
TL;DR: The Penn World Table as discussed by the authors is a set of national accounts economic time series covering many countries and its expenditure entries are denominated in common set of prices in a common currency so that real quantity comparisons can be made, both between countries and over time.
Abstract: The Penn World Table displays a set of national accounts economic time series covering many countries. Its expenditure entries are denominated in a common set of prices in a common currency so that real quantity comparisons can be made, both between countries and over time. It also provides information about relative prices within and between countries, as well as demographic data and capital stock estimates. This updated, revised, and expanded Mark 5 version of the table includes more countries, years, and variables of interest to economic researchers. The Table is available on personal computer diskettes and through BITNET.
3,160 citations
TL;DR: The presence of publication bias in a cohort of clinical research studies is confirmed and it is suggested that conclusions based only on a review of published data should be interpreted cautiously, especially for observational studies.
2,800 citations
TL;DR: The Penn World Table as discussed by the authors is a set of national accounts economic time series covering many countries and its expenditure entries are denominated in common set of prices in a common currency so that real quantity comparisons can be made, both between countries and over time.
Abstract: The Penn World Table displays a set of national accounts economic time series covering many countries. Its expenditure entries are denominated in a common set of prices in a common currency so that real quantity comparisons can be made, both between countries and over time. It also provides information about relative prices within and between countries, as well as demographic data and capital stock estimates. This updated, revised, and expanded Mark 5 version of the table includes more countries, years, and variables of interest to economic researchers. The Table is available on personal computer diskettes and through BITNET.
2,790 citations
TL;DR: It is concluded that enlargement of the CAG repeat in the androgen receptor gene is probably the cause of X-LINKED spinal and bulbar muscular atrophy.
Abstract: X-linked spinal and bulbar muscular atrophy (Kennedy's disease) is an adult-onset form of motorneuron disease which may be associated with signs of androgen insensitivity. We have now investigated whether the androgen receptor gene on the proximal long arm of the X chromosome is a candidate gene for this disease. In patient samples we found androgen receptor gene mutations with increased size of a polymorphic tandem CAG repeat in the coding region. These amplified repeats were absolutely associated with the disease, being present in 35 unrelated patients and none of 75 controls. They segregated with the disease in 15 families, with no recombination in 61 meioses (the maximum log likelihood ratio (lod score) is 13.2 at a recombination rate of 0). The association is unlikely to be due to linkage disequilibrium, because 11 different disease alleles were observed. We conclude that enlargement of the CAG repeat in the androgen receptor gene is probably the cause of this disorder.
2,704 citations
TL;DR: A resource-based approach to strategic management focuses on costly-to-copy attributes of the firm as sources of economic rents and, therefore, as the fundamental drivers of performance and competitive advantage as discussed by the authors.
2,674 citations
TL;DR: During insulin stimulation, the IRS-1 protein undergoes tyrosine phosphorylation and binds phosphatidylinositol 3-kinase, suggesting that IRS–1 acts as a multisite Mocking' protein to bind signal-transducing molecules containing Src-homology 2 and SRC-Homology-3 domains, which may link the insulin receptor kinase and enzymes regulating cellular growth and metabolism.
Abstract: Since the discovery of insulin nearly 70 years ago, there has been no problem more fundamental to diabetes research than understanding how insulin works at the cellular level. Insulin binds to the alpha subunit of the insulin receptor which activates the tyrosine kinase in the beta subunit, but the molecular events linking the receptor kinase to insulin-sensitive enzymes and transport processes are unknown. Our discovery that insulin stimulates tyrosine phosphorylation of a protein of relative molecular mass between 165,000 and 185,000, collectively called pp185, showed that the insulin receptor kinase has specific cellular substrates. The pp185 is a minor cytoplasmic phosphoprotein found in most cells and tissues; its phosphorylation is decreased in cells expressing mutant receptors defective in signalling. We have now cloned IRS-1, which encodes a component of the pp185 band. IRS-1 contains over ten potential tyrosine phosphorylation sites, six of which are in Tyr-Met-X-Met motifs. During insulin stimulation, the IRS-1 protein undergoes tyrosine phosphorylation and binds phosphatidylinositol 3-kinase, suggesting that IRS-1 acts as a multisite 'docking' protein to bind signal-transducing molecules containing Src-homology 2 and Src-homology-3 domains. Thus IRS-1 may link the insulin receptor kinase and enzymes regulating cellular growth and metabolism.
1,574 citations
TL;DR: The major subunits of a class of PHFs are A68 proteins and the excessive or inappropriate phosphorylation of normal tau may change its apparent Mr, thus transforming tau into A68.
Abstract: Putative Alzheimer disease (AD)-specific proteins (A68) were purified to homogeneity and shown to be major subunits of one form of paired helical filaments (PHFs). The amino acid sequence and immunological data indicate that the backbone of A68 is indistinguishable from that of the protein tau (tau), but A68 could be distinguished from normal human tau by the degree to which A68 was phosphorylated and by the specific residues in A68 that served as phosphate acceptors. The larger apparent relative molecular mass (Mr) of A68, compared to normal human tau, was attributed to abnormal phosphorylation of A68 because enzymatic dephosphorylation of A68 reduced its Mr to close to that of normal tau. Moreover, the LysSerProVal motif in normal human tau appeared to be an abnormal phosphorylation site in A68 because the Ser in this motif was a phosphate acceptor site in A68, but not in normal human tau. Thus, the major subunits of a class of PHFs are A68 proteins and the excessive or inappropriate phosphorylation of normal tau may change its apparent Mr, thus transforming tau into A68.
1,444 citations
TL;DR: In this paper, the authors estimate the extent to which technological innovations in various industries have been based on recent academic research, and the time lags between the investment in academic research projects and the industrial utilization of their findings.
1,276 citations
TL;DR: In this paper, the authors developed the perspective that joint ventures are created as real options to expand in response to future technological and market developments, and the exercise of the option is accompanied by an acquisition of the venture.
Abstract: This article develops the perspective that joint ventures are created as real options to expand in response to future technological and market developments. The exercise of the option is accompanied by an acquisition of the venture. It is hypothesized that the timing of the acquisition should be triggered by a product market signal indicating an increase in the venture's valuation. Based on a sample of 92 manufacturing joint ventures, this hypothesis is tested by estimating the effect of product market signals on the hazard of acquisition. The results indicate that unexpected growth in the product market increases the likelihood of acquisition; unexpected shortfalls in product shipments have no effect on the likelihood of dissolution. This asymmetry in the results strongly supports the interpretation of joint ventures as options to expand.
TL;DR: Data seem to implicate malignant cytology as a serious adverse finding, especially with respect to the risk for regional/distant and abdominal failure, in patients with negative surgical-pathological risk factors.
TL;DR: Findings lend support to the hypothesized importance of the temporal-hippocampal region in understanding the pathophysiology of schizophrenia and the selectivity and relative severity compared with other behavioral functions.
Abstract: • Unmedicated schizophrenic patients (according to DSM-III-R criteria) (n = 36) and age-matched normal controls (n = 36), balanced for parental socioeconomic status, were administered a battery of standardized neuropsychological tests. Patients showed generalized impairment relative to controls and a selective deficit in memory and learning compared with other functions. Selective impairment was not found on tests related to frontal system function (abstraction, verbal fluency, and motor). The observed pattern is consistent with greater involvement of the temporal-hippocampal system, against the background of diffuse dysfunction. Although impairment in memory and learning has been reported, the selectivity and relative severity compared with other behavioral functions have not been recognized. The specificity of this profile merits further examination. These findings lend support to the hypothesized importance of the temporal-hippocampal region in understanding the pathophysiology of schizophrenia.
TL;DR: It is demonstrated that when T‐lymphoblasts are introduced into the circulation they rapidly appear in the CNS tissue, and lymphocytes which have entered, exit within 1 to 2 days.
Abstract: The entry of T-lymphocytes into the parenchyma of the central nervous system is a critical early feature in the pathogenesis of many experimental and spontaneously occurring immune-mediated illnesses. The physiological mechanisms controlling this entry have not been elucidated. This study reports that T-cell entry into the rat CNS appears to be primarily dependent upon the activation state of the lymphocytes; T-lymphoblasts enter the CNS (and all other tissues examined) in an apparently random manner while T cells not in blast phase are excluded. Antigen specificity, MHC compatibility, T-cell phenotype, and T-cell receptor gene usage do not appear related to the ability of cells to enter. This study demonstrates that when T-lymphoblasts are introduced into the circulation they rapidly appear in the CNS tissue. Their concentration in the CNS reaches a peak between 9 and 12 hr, and lymphocytes which have entered, exit within 1 to 2 days. Cells capable of reacting with a CNS antigen remain in the tissue or cyclically reenter to initiate inflammation if they are able to recognize their antigen in the correct MHC context. This observation also appears to pertain to the entry of activated T cells into many other tissues, although their concentrations in these non-CNS sites was not quantitated.
TL;DR: In this article, a first-order phase transition from a low-temperature simple-cubic structure with a four-molecule basis to a face-centered-cUBIC structure at 249 K was shown.
Abstract: Synchrotron-x-ray powder-diffraction and differential-scanning-calorimetry measurements on solid ${\mathrm{C}}_{60}$ reveal a first-order phase transition from a low-temperature simple-cubic structure with a four-molecule basis to a face-centered-cubic structure at 249 K. The free-energy change at the transition is approximately 6.7 J/g. Model fits to the diffraction intensities are consistent with complete orientational disorder at room temperature, and with the development of orientational order rather than molecular displacements or distortions at low temperature.
TL;DR: Polyvalent pneumococcal vaccine is efficacious in preventing invasive pneumitiscal infections in immunocompetent patients with indications for its administration and should be used more widely.
Abstract: Background Although the protective efficacy of pneumococcal polysaccharide vaccine has been demonstrated in randomized trials in young African gold miners, there has been controversy about its efficacy in older Americans at risk for serious pneumococcal infections. To assess the vaccine's protective efficacy against invasive pneumococcal infections, we conducted a hospital-based case-control study of the efficacy of pneumococcal vaccine in adults with a condition recognized to be an indication for receiving the vaccine. Methods From 1984 to 1990, adults in whom Streptococcus pneumoniae was isolated from any normally sterile site were identified by prospective surveillance in the microbiology laboratories of 11 large hospitals; those with an indication for pneumococcal vaccine were enrolled as case patients. For each case patient, one control was matched according to age, underlying illness, and site of hospitalization. We contacted all providers of medical care to ascertain each subject's history of immunization with pneumococcal vaccine. Isolates of S. pneumoniae were serotyped by an investigator unaware of the subject's vaccination history. Results Thirteen percent of the 1,054 case patients and 20 percent of the 1,054 matched controls had received pneumococcal vaccine (P less than 0.001). When vaccine was given in either its 14-valent or its 23-valent form, its aggregate protective efficacy (calculated as a percentage: 1 minus the odds ratio of having been vaccinated times 100) against infections caused by the serotypes represented in the vaccine was 56 percent (95 percent confidence interval, 42 percent to 67 percent; P less than 0.00001) for all 983 patients infected with a serotype represented in the vaccine, 61 percent for a subgroup of 808 immunocompetent patients (95 percent confidence interval, 47 percent to 72 percent; P less than 0.00001), and 21 percent for a subgroup of 175 immunocompromised patients (95 percent confidence interval, -55 percent to 60 percent; P = 0.48). The vaccine was not efficacious against infections caused by serotypes not represented in the vaccine (protective efficacy, -73 percent; 95 percent confidence interval, -263 percent to 18 percent; P = 0.15). Conclusions Polyvalent pneumococcal vaccine is efficacious in preventing invasive pneumococcal infections in immunocompetent patients with indications for its administration. This vaccine should be used more widely.
TL;DR: In this article, the authors examined whether the consumption of stockholders differs from the consumption consumption of non-stockholders and whether these differences help explain the empirical failures of the consumption-based CAPM.
TL;DR: This article found that subjects often rated harmful omissions as less immoral, or less bad as decisions, than harmful commissions, and such ratings were associated with judgments that omissions do not cause outcomes.
TL;DR: In this paper, a refined concept of organizational environments as complex and fluid is proposed, and implications for future research in organization theory are discussed. But the authors focus on the internal dynamics of multinational enterprises and do not consider the external factors that influence the structures and processes of these enterprises.
Abstract: Multinational enterprises (MNEs) serve as catalysts for reconceptualizing organization-environment relations because they operate simultaneously in multiple nations. We argue that subsidiaries of MNEs face dual pressures: They are pulled to achieve isomorphism with the local institutional environment, and they also face an imperative for consistency within the organization. We develop hypotheses regarding the factors that influence the structures and processes of MNEs. Based on an examination of the pressures imposed on MNEs. We offer a refined concept of organizational environments as complex and fluid, and we suggest implications for future research in organization theory.
TL;DR: It is proposed that dystrophin deficiency alters the threshold for work-induced injury and provides a quantitative framework for studying the pathogenesis of dystrophy and extend the application of the mdx mouse as an animal model.
Abstract: ALTHOUGH murine X-linked muscular dystrophy (mdx) and Duchenne muscular dystrophy (DMD) are genetically homologous and both characterized by a complete absence of dystrophin1,2, the limb muscles of adult mdx mice suffer neither the detectable weakness nor the progressive degeneration that are features of DMD3–8. Here we show that the mdx mouse diaphragm exhibits a pattern of degeneration, fibrosis and severe functional deficit comparable to that of DMD limb muscle, although adult mice show no overt respiratory impairment. Progressive functional changes include reductions in strength (to 13.5% of control by two years of age), elasticity, twitch speed and fibre length. The collagen density rises to at least seven times that of control diaphragm and ten times that of mdx hind-limb muscle. By 1.5 years of age, similar but less severe histological changes emerge in the accessory muscles of respiration. On the basis of these findings, we propose that dystrophin deficiency alters the threshold for work-induced injury. Our data provide a quantitative framework for studying the pathogenesis of dystrophy and extend the application of the mdx mouse as an animal model.
TL;DR: A study of 750 patients with complaints of abnormal smell or taste perception from the University of Pennsylvania Smell and Taste Center, Philadelphia suggests that chemosensory dysfunction influences quality of life.
Abstract: Smell and taste disorders are common in the general population, yet little is known about their nature or cause. This article describes a study of 750 patients with complaints of abnormal smell or taste perception from the University of Pennsylvania Smell and Taste Center, Philadelphia. Major findings suggest that: chemosensory dysfunction influences quality of life; complaints of taste loss usually reflect loss of smell function; upper respiratory infection, head trauma, and chronic nasal and paranasal sinus disease are the most common causes of the diminution of the sense of smell, with head trauma having the greatest loss; depression frequently accompanies chemosensory distortion; low body weight accompanies burning mouth syndrome; estrogens protect against loss of the sense of smell in postmenopausal women; zinc therapy may provide no benefit to patients with chemosensory dysfunction; and thyroid hormone function is associated with oral sensory distortion. The findings are discussed in relation to management of patients with chemosensory disturbances.
TL;DR: In this article, a new variational structure is proposed that yields a prescription for the effective energy potential of nonlinear composites in terms of the corresponding energy potentials for linear composites with the same microstructural distributions.
Abstract: A new variational structure is proposed that yields a prescription for the effective energy potentials of nonlinear composites in terms of the corresponding energy potentials for linear composites with the same microstructural distributions. The prescription can be used to obtain bounds and estimates for the effective mechanical properties of nonlinear composites from any bounds and estimates that may be available for the effective properties of linear composites. The main advantages of the procedure are the simplicity of its implementation, the generality of its applications and the strength of its results. The general prescription is applied to three special nonlinear composites : a porous material, a two-phase incompressible composite and a rigidly reinforced material. The results are compared with previously available results for the special case of power-law constitutive behavior.
TL;DR: A number of factors that have been identified as risk factors for falls are also associated with hip fracture, including lower-limb dysfunction, neurologic conditions, barbiturate use, and visual impairment.
Abstract: Background. Although even in the elderly most falls are not associated with fractures, over 90 percent of hip fractures are the result of a fall. Few studies have assessed whether the risk factors for falls are also important risk factors for hip fracture. Methods. To examine the importance of risk factors for falls in the epidemiology of hip fracture, we performed a case–control study of 174 women (median age, 80 years) admitted with a first hip fracture to 1 of 30 hospitals in New York and Philadelphia. Controls, matched to the case patients according to age and hospital, were selected from general surgical and orthopedic surgical hospital services. Information was obtained by direct interview. Results. As measured by the odds ratio, increased risks for hip fracture were associated with lower-limb dysfunction (odds ratio = 1.7; 95 percent confidence interval, 1.1 to 2.8), visual impairment (odds ratio = 5.1; 95 percent confidence interval, 1.9 to 13.9), previous stroke (odds ratio = 2.0; 95 per...
TL;DR: It is demonstrated that MyoD, in conjunction with E12/E47-like proteins, is functioning as a regulatory nodal point for activation of several other downstream muscle regulators.
Centers for Disease Control and Prevention1, Johns Hopkins University2, University of Rochester3, Georgetown University4, University of Minnesota5, University of Pennsylvania6, Harvard University7, University of California, Los Angeles8, National Institutes of Health9, University of Pittsburgh10, Northwestern University11, University of California, San Diego12, World Health Organization13, University College London14, Columbia University15, Max Planck Society16
TL;DR: These definitions have been developed in conjunction with the International Classification of Diseases-10 (ICD-10, unpublished draft of the World Health Organization) and the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV, unpublishedDraft of the American Psychiatric Association) and are not identical.
Abstract: Infection with human immunodeficiency virus-type 1 (HIV-1) has been associated with avariety of neurologic disorders thought to be caused, directly or indirectly, by HIV-1.1-6 Although these disorders have been described clinically, there is no consensus terminology or criteria for diagnosis. To develop consensus nomenclature and case definitions for HIV-1-associated neurologic conditions for research purposes, the American Academy of Neurology AIDS Task Force convened a working group of neurologists, neuropsychologists, psychiatrists, and sociologists that included representatives of the American Neurological Association, the World Federation of Neurology, the International Neuropsychological Society, the National Academy of Neuropsychology, the American Psychological Association, the American Psychiatric Association, the World Health Organization, and the Centers for Disease Control (CDC). These definitions have been developed in conjunction with the International Classification of Diseases-10 (ICD-10, unpublished draft of the World Health Organization) and the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV, unpublished draft of the American Psychiatric Association). Although consistent with the ICD-10, the definitions are not identical. HIV-2 may cause similar disorders, but the neurologic manifestations of HIV-2 are unknown and are not addressed in this article.
TL;DR: Analysis of amplified DNA sequences present in a tumorigenic mouse cell line provided evidence that a gene, mdm2, that is amplified more than 50‐fold in the 3T3DM cell line, induces tumorigenicity when experimentally overexpressed in NIH3T3 cells and in Rat2 cells.
Abstract: We have carried out an analysis of amplified DNA sequences present in a tumorigenic mouse cell line, designated 3T3DM, to determine if the presence of cellular transforming activity is correlated with the elevated expression of any of the amplified genes These studies utilized a selection protocol that allowed for DNA sequence amplification after the introduction of each gene into non-transformed recipient cells Cell lines obtained from this selection protocol were assayed for tumorigenicity in nude mice The results provided evidence that a gene, mdm2, that is amplified more than 50-fold in the 3T3DM cell line, induces tumorigenicity when experimentally overexpressed in NIH3T3 cells and in Rat2 cells Analysis of the predicted amino acid composition of the mdm2 product(s) revealed features similar to those that have been shown to be functionally significant in certain DNA binding proteins/transcriptional activators These include two potential metal binding motifs and a negatively charged domain rich in acidic amino acid residues Overall, the data support the conclusion that mdm2 represents an evolutionarily conserved gene with tumorigenic potential and a predicted role in mechanisms of cellular growth control
TL;DR: A proof-theoretic characterization of logical languages that form suitable bases for Prolog-like programming languages is provided and it is shown that first-order and higher-order Horn clauses with classical provability are examples of such a language.
TL;DR: In this paper, the authors explore the macroeconomic implications of including household production in an otherwise standard real business cycle model and find that introducing home production significantly improves the quantitative performance of the standard model along several dimensions.
Abstract: This paper explores some macroeconomic implications of including household production in an otherwise standard real business cycle model. We calibrate the model on the basis of macroeconomic evidence and long-run considerations, simulate it, and examine its statistical properties. We find that introducing home production significantly improves the quantitative performance of the standard model along several dimensions. It also implies a very different interpretation of the nature of aggregate fluctuations.
TL;DR: In this article, the authors show that in some circumstances, even with significant piracy, not protecting can be the best policy, both raising firm profits and lowering selling prices, since consumers have an incentive to economize on post-purchase learning and customization costs.
Abstract: Software piracy by users is generally believed to harm both software firms through lower profits and buying customers through higher prices. Thus, it is thought that perfect and costless technological protection would benefit both firms and consumers. The model developed here suggests that in some circumstances, even with significant piracy, not protecting can be the best policy, both raising firm profits and lowering selling prices. Key to the analysis is joining the presence of a positive network externality with the fact that piracy increases the total number of program users. The network externality exists because consumers have an incentive to economize on post-purchase learning and customization costs.