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Showing papers by "University of Pittsburgh published in 1998"


Journal ArticleDOI
TL;DR: In this article, a rigorous distribution theory for kernel-based matching is presented, and the method of matching is extended to more general conditions than the ones assumed in the statistical literature on the topic.
Abstract: This paper develops the method of matching as an econometric evaluation estimator. A rigorous distribution theory for kernel-based matching is presented. The method of matching is extended to more general conditions than the ones assumed in the statistical literature on the topic. We focus on the method of propensity score matching and show that it is not necessarily better, in the sense of reducing the variance of the resulting estimator, to use the propensity score method even if propensity score is known. We extend the statistical literature on the propensity score by considering the case when it is estimated both parametrically and nonparametrically. We examine the benefits of separability and exclusion restrictions in improving the efficiency of the estimator. Our methods also apply to the econometric selection bias estimator. Matching is a widely-used method of evaluation. It is based on the intuitively attractive idea of contrasting the outcomes of programme participants (denoted Y1) with the outcomes of "comparable" nonparticipants (denoted Y0). Differences in the outcomes between the two groups are attributed to the programme. Let 1 and 11 denote the set of indices for nonparticipants and participants, respectively. The following framework describes conventional matching methods as well as the smoothed versions of these methods analysed in this paper. To estimate a treatment effect for each treated person iecI, outcome Yli is compared to an average of the outcomes Yoj for matched persons je10 in the untreated sample. Matches are constructed on the basis of observed characteristics X in Rd. Typically, when the observed characteristics of an untreated person are closer to those of the treated person ieI1, using a specific distance measure, the untreated person gets a higher weight in constructing the match. The estimated gain for each person i in the treated sample is

3,861 citations


Journal ArticleDOI
01 May 1998-Science
TL;DR: Results confirm that this region shows activity during erroneous responses, but activity was also observed in the same region during correct responses under conditions of increased response competition, which suggests that the ACC detects conditions under which errors are likely to occur rather than errors themselves.
Abstract: An unresolved question in neuroscience and psychology is how the brain monitors performance to regulate behavior. It has been proposed that the anterior cingulate cortex (ACC), on the medial surface of the frontal lobe, contributes to performance monitoring by detecting errors. In this study, event-related functional magnetic resonance imaging was used to examine ACC function. Results confirm that this region shows activity during erroneous responses. However, activity was also observed in the same region during correct responses under conditions of increased response competition. This suggests that the ACC detects conditions under which errors are likely to occur rather than errors themselves.

3,236 citations


Book
01 Jan 1998
TL;DR: Workplace flexibility is the topic of Richard Sennett's new book, "The Corrosion of Character: The Personal Consequences of Work in the New Capitalism,” his latest analysis of class, work, and social relations as mentioned in this paper.
Abstract: Workplace flexibility is the topic of Richard Sennett's new book, “The Corrosion of Character: The Personal Consequences of Work in the New Capitalism,” his latest analysis of class, work, and social relations. Sennett seeks to remind us that stability—currently so maligned by business writers and consultants--has distinct benefits for individuals and society. More important, he raises a warning flag about the costs of flexibility and the toll it can take on our energy, our relationships, and our very characters.

3,106 citations


Journal ArticleDOI
TL;DR: This paper provided a crude initial estimate of the value of ecosystem services to the economy using data from previous published studies and a few original calculations, and estimated the current economic value of 17 ecosystem services for 16 biomes.

2,592 citations


Journal ArticleDOI
TL;DR: Physiological roles and relationships between the pathways of arginine synthesis and catabolism in vivo are complex and difficult to analyse, owing to compartmentalized expression of various enzymes at both organ and subcellular levels.
Abstract: Arginine is one of the most versatile amino acids in animal cells, serving as a precursor for the synthesis not only of proteins but also of nitric oxide, urea, polyamines, proline, glutamate, creatine and agmatine. Of the enzymes that catalyse rate-controlling steps in arginine synthesis and catabolism, argininosuccinate synthase, the two arginase isoenzymes, the three nitric oxide synthase isoenzymes and arginine decarboxylase have been recognized in recent years as key factors in regulating newly identified aspects of arginine metabolism. In particular, changes in the activities of argininosuccinate synthase, the arginases, the inducible isoenzyme of nitric oxide synthase and also cationic amino acid transporters play major roles in determining the metabolic fates of arginine in health and disease, and recent studies have identified complex patterns of interaction among these enzymes. There is growing interest in the potential roles of the arginase isoenzymes as regulators of the synthesis of nitric oxide, polyamines, proline and glutamate. Physiological roles and relationships between the pathways of arginine synthesis and catabolism in v i v o are complex and difficult to analyse, owing to compartmentalized expression of various enzymes at both organ (e.g. liver, small intestine and kidney) and subcellular (cytosol and mitochondria) levels, as well as to changes in expression during development and in response to diet, hormones and cytokines. The ongoing development of new cell lines and animal models using cDNA clones and genes for key arginine metabolic enzymes will provide new approaches more clearly elucidating the physiological roles of these enzymes. Correspondence may be addressed to either Dr. G. Wu (e-mail g-wu@tamu.edu) or Dr. S. M. Morris, Jr. (e-mail sid@hoffman.mgen.pitt.edu) at the addresses given.

2,553 citations


Journal ArticleDOI
TL;DR: Evidence for predictive validity is provided by a laboratory study in which VFI motivations predicted the persuasive appeal of messages better when message and motivation were matched than mismatched, and by field studies in which the extent to which volunteers' experiences matched their motivations predicted satisfaction.
Abstract: The authors applied functionalist theory to the question of the motivations underlying volunteerism, hypothesized 6 functions potentially served by volunteerism, and designed an instrument to assess these functions (Volunteer Functions Inventory; VFI). Exploratory and confirmatory factor analyses on diverse samples yielded factor solutions consistent with functionalist theorizing; each VFI motivation, loaded on a single factor, possessed substantial internal consistency and temporal stability and correlated only modestly with other VFI motivations (Studies 1, 2, and 3). Evidence for predictive validity is provided by a laboratory study in which VFI motivations predicted the persuasive appeal of messages better when message and motivation were matched than mismatched (Study 4), and by field studies in which the extent to which volunteers' experiences matched their motivations predicted satisfaction (Study 5) and future intentions (Study 6). Theoretical and practical implications are discussed.

2,343 citations


Journal ArticleDOI
TL;DR: Four error-checking algorithms are implemented in a new computer program, PedCheck, which will assist researchers in identifying all Mendelian inconsistencies in pedigree data and will provide them with useful and detailed diagnostic information to help resolve the errors.
Abstract: Summary Prior to performance of linkage analysis, elimination of all Mendelian inconsistencies in the pedigree data is essential. Often, identification of erroneous genotypes by visual inspection can be very difficult and time consuming. In fact, sometimes the errors are not recognized until the stage of running linkage-analysis software. The effort then required to find the erroneous genotypes and to cross-reference pedigree and marker data that may have been recoded and renumbered can be not only tedious but also quite daunting, in the case of very large pedigrees. We have implemented four error-checking algorithms in a new computer program, PedCheck, which will assist researchers in identifying all Mendelian inconsistencies in pedigree data and will provide them with useful and detailed diagnostic information to help resolve the errors. Our program, which uses many of the algorithms implemented in VITESSE, handles large data sets quickly and efficiently, accepts a variety of input formats, and offers various error-checking algorithms that match the subtlety of the pedigree error. These algorithms range from simple parent-offspring–compatibility checks to a single-locus likelihood-based statistic that identifies and ranks the individuals most likely to be in error. We use various real data sets to illustrate the power and effectiveness of our program.

2,158 citations


Journal ArticleDOI
TL;DR: Preoperative chemotherapy is as effective as postoperative chemotherapy, permits more lumpectomies, is appropriate for the treatment of certain patients with stages I and II disease, and can be used to study breast cancer biology.
Abstract: PURPOSETo determine, in women with primary operable breast cancer, if preoperative doxorubicin (Adriamycin) and cyclophosphamide (Cytoxan; AC) therapy yields a better outcome than postoperative AC therapy, if a relationship exists between outcome and tumor response to preoperative chemotherapy, and if such therapy results in the performance of more lumpectomies.PATIENTS AND METHODSWomen (1,523) enrolled onto National Surgical Adjuvant Breast and Bowel Project (NSABP) B-18 were randomly assigned to preoperative or postoperative AC therapy. Clinical tumor response to preoperative therapy was graded as complete (cCR), partial (cPR), or no response (cNR). Tumors with a cCR were further categorized as either pathologic complete response (pCR) or invasive cells (pINV). Disease-free survival (DFS), distant disease-free survival (DDFS), and survival were estimated through 5 years and compared between treatment groups. In the preoperative arm, proportional-hazards models were used to investigate the relationship b...

2,057 citations


Journal ArticleDOI
TL;DR: The prevalence of community violence by people discharged from acute psychiatric facilities varies considerably according to diagnosis and, particularly, co-occurring substance abuse diagnosis or symptoms.
Abstract: Background The public perception that mental disorder is strongly associated with violence drives both legal policy (eg, civil commitment) and social practice (eg, stigma) toward people with mental disorders. This study describes and characterizes the prevalence of community violence in a sample of people discharged from acute psychiatric facilities at 3 sites. At one site, a comparison group of other residents in the same neighborhoods was also assessed. Methods We enrolled 1136 male and female patients with mental disorders between the ages of 18 and 40 years in a study that monitored violence to others every 10 weeks during their first year after discharge from the hospital. Patient self-reports were augmented by reports from collateral informants and by police and hospital records. The comparison group consisted of 519 people living in the neighborhoods in which the patients resided after hospital discharge. They were interviewed once about violence in the past 10 weeks. Results There was no significant difference between the prevalence of violence by patients without symptoms of substance abuse and the prevalence of violence by others living in the same neighborhoods who were also without symptoms of substance abuse. Substance abuse symptoms significantly raised the rate of violence in both the patient and the comparison groups, and a higher portion of patients than of others in their neighborhoods reported symptoms of substance abuse. Violence in both patient and comparison groups was most frequently targeted at family members and friends, and most often took place at home. Conclusions "Discharged mental patients" do not form a homogeneous group in relation to violence in the community. The prevalence of community violence by people discharged from acute psychiatric facilities varies considerably according to diagnosis and, particularly, co-occurring substance abuse diagnosis or symptoms.

1,372 citations


Journal ArticleDOI
TL;DR: Introduction.
Abstract: Introduction. Aspects of Interpretation. Technical Considerations. Statistical Analysis. Special Methods for Joint Responses. Some Examples. Strategical Aspects. More Specialized Topics. Appendices.

1,296 citations


Journal ArticleDOI
TL;DR: Preoperative chemotherapy with a combination of cisplatin and fluorouracil did not improve overall survival among patients with epidermoid cancer or adenocarcinoma of the esophagus.
Abstract: Background We performed a multi-institutional randomized trial comparing preoperative chemotherapy followed by surgery with surgery alone for patients with local and operable esophageal cancer. Methods Preoperative chemotherapy for patients randomly assigned to the chemotherapy group included three cycles of cisplatin and fluorouracil. Surgery was performed two to four weeks after the completion of the third cycle; patients also received two additional cycles of chemotherapy after the operation. Patients randomly assigned to the immediate-surgery group underwent the same surgical procedure. The main end point was overall survival. Results Of the 440 eligible patients with adequate data, 213 were assigned to receive preoperative chemotherapy and 227 to undergo immediate surgery. After a median possible study time of 55.4 months, there were no significant differences between the two groups in median survival: 14.9 months for the patients who received preoperative chemotherapy and 16.1 months for those who u...

Journal ArticleDOI
TL;DR: There is a growing body of European literature that can be characterized as "governance without government, " stressing as it does the importance of networks, partnerships, and markets (especially international markets) as discussed by the authors.
Abstract: The concept of governance has come to be used more commonly in the discussion of public administration, but the meaning of the term is not always clear. There is a growing body of European literature that can be characterized as "governance without government, " stressing as it does the importance of networks, partnerships, and markets (especially international markets). This body of literature can be related to the new public management; yet it has a number of distinctive elements. This article discusses the strengths and weaknesses of this literature and its applicability to public administration in the United States. The traditional conceptualization of the public sector has come under increasing strain during the past several decades. The idea that national governments are the major actors in public policy and that they are able to influence the economy and society through their actions now appears to be in doubt. Some of the strain on national governments has been the result of the increased importance of the international environment and of an arguably diminished capacity of those governments to insulate their economies and societies from the global pressures. Those pressures on national governments come about through international capital markets (Strange 1996; but see Hirst and Thompson 1996; Peters 1998) as well as through supranational organizations such as the European Union (Scharpf 1997). Another strain on the traditional conception of governing arises from changes in the relationship between government and the private sector. At the extreme it is argued that "governance without government" is becoming the dominant pattern of management for advanced industrial democracies (Rhodes 1997). Other characterizations include "hollow" states and governments 223/Journal of Public Administration Research and Theory J-PART 8(1998):2:223-243 This content downloaded from 157.55.39.163 on Wed, 23 Nov 2016 04:26:57 UTC All use subject to http://about.jstor.org/terms Rethinking Public Administration (Peters 1993; Rhodes 1994) and "negotiated" states and economies (Nielsen and Pedersen 1990). In all these depictions of changing patterns of government, it is argued that societal actors have become influential over policy and administration and have done so in ways that were unimaginable in earlier times. Government is seen as weakened and as incapable of "steering" as it had in the past. The traditional concept of government as a controlling and regulating organization for society is argued to be outmoded (Bekke, Kickert, and Kooiman 1995). The discussion of governance without government has been largely European and has concentrated primarily in the United Kingdom and the Netherlands. The European roots of this debate appear to be in part a function of the preeminent role of government in the welfare state in Europe and of the strength and established position of interest groups in these societies (Kooiman 1993; Schmitter and Lembruch 1979). In essence government has much more power to lose, more areas of policy involvement, and a network structure already in place that can replace or supplement the power of government. In the United Kingdom the emergence of this pattern of governing is a direct challenge to the Whitehall model of strong, centralized government. Although the governance debate has been largely European, it is beginning to diffuse to the United States. There is some objective evidence that the same changes-such as contracting, public-private partnerships, and a variety of other interactions with the private sector-move government away from its role as the central source of the "authoritative allocation of values" for the society. Also, in the United States there is the beginning of a body of literature that relates these changes in the relationship with society to broader questions of managing the State (O'Toole 1997; Thomas 1997). The objectives and concrete design of administrative reform mirror the historical, political, and societal roles of public administration as well as its internal culture. Such reforms are path-dependent, probably to a much greater extent than we generally realize. Path-dependency refers to the range of policy choice available for administrative reformers; reform strategies are embedded in systems of norms and administrative practices and therefore reform strategies are shaped more by what already exists than by the desired model of public administration. In this article we will examine the emerging governance debate in Europe and the United States and will describe both the dimensions of the debate over the capacity of the state to continue to govern as it has in the past and the development of 224/J-PART, April 1998 This content downloaded from 157.55.39.163 on Wed, 23 Nov 2016 04:26:57 UTC All use subject to http://about.jstor.org/terms Rethinking Public Administration alternative mechanisms for exerting control over society. We will also address the question of whether this is purely an academic debate, the product of developing a theoretical language suitable for the analysis, or whether a real change is occurring in the nature of government. WHAT IS THE GOVERNANCE DEBATE? The conception of governance as it has developed over the past several years in the European debate has several constituent elements. As we indicated above, however, taken together these elements would amount to a prescription for steering society through less direct means and weakening the power of the State to control policy. These changes would, in turn, have implications for the meaning of democracy in the contemporary political system. We will not evaluate these arguments here; rather we will save that for the discussion of how the governance arguments fit within the context of both European and American public administration. The Importance of Networks Perhaps the dominant feature of the governance model is the argument that networks have come to dominate public policy. The assertion is that these amorphous collections of actors-not formal policy-making institutions in government-control policy. State agencies may place some imprimatur on the policy, so the argument goes, but the real action occurs within the private sector. Further, in the more extreme versions of the argument, if governments attempt to impose control over policy, these networks have sufficient resiliency and capacity for self-organization1 (Kooiman 1993; Marsh and Rhodes 1992; de Bruijn and ten Heuvelhof 1997) to evade the control of govermment. It long has been argued that the private sector has real influence over public policy through structures with varying degrees of formality, but this conception carries the argument to that of dominance. This dominance is possible partly because the State has become delegitimated. The loss of legitimacy is in part because state actors are excessively clumsy, bureaucratic, and path dependent and in part because of the control of information and implementation structures by private actors. It appears that whatever the State does it does poorly, while the private sector (for profit and not for profit) is more effective. 225/J-PART, April 1998 'Especially within the Dutch and Germnan literature the term autopoesis is used to describe this self-organizing nature of

Journal ArticleDOI
TL;DR: In this article, the authors proposed to use the idea of super levels first pioneered by Anderson to improve the performance of the non-LTE radiative transfer code of Hillier stars with stellar winds.
Abstract: Extensive modifications to the non-LTE radiative transfer code of Hillier have been made in order to improve the spectroscopic analysis of stars with stellar winds. The main improvement to the code is the inclusion of blanketing due to thousands of overlapping lines. To implement this effect, we have used the idea of super levels first pioneered by Anderson. In our approach, levels with similar excitation energies and levels are grouped together. Within this group, we assume that the departure coefficients are identical. Only the population (or equivalently, the departure coefficient) of the super level need be solved in order to fully specify the populations of the levels within a super level. Our approach is a natural extension of the single-level LTE assumption, and thus LTE is recovered exactly at depth. In addition to the line blanketing modifications, the code has been improved significantly in other regards. In particular, the new code incorporates the effect of level dissolution, the influence of resonances in the photoionization cross sections, and the effect of Auger ionization. Electron scattering with a thermal redistribution can be considered, although it is normally treated coherently in the comoving frame (which still leads to redistribution in the observer's frame). Several example calculations are described to demonstrate the importance of line blanketing on spectroscopic analysis. We find that the inclusion of blanketing modifies the strengths of some optical CNO lines in Wolf-Rayet (W-R) stars by factors of 2-5. In particular, the strengths of the WC classification lines C III λ5696 and C IV λ5805 are both increased because of iron blanketing. This should help alleviate problems found with nonblanketed models, which were incapable of matching the strengths of these lines. We also find that, in the UV (1100-1800 A), the influence of Fe is readily seen in both emission and absorption. The emission is sensitive to the iron abundance and should allow, for the first time, Fe abundances to be deduced in W-R stars. The improvements made to our code should greatly facilitate the spectroscopic analysis of stars with stellar winds. We will be able to determine the importance and influence of line blanketing, as well as of several other effects that have been included in the new code. It will also allow us to better determine W-R star parameters, such as luminosity, elemental abundances, wind velocity, and mass-loss rate. With future application to related objects, such as novae and supernovae, our new code should also improve our understanding of these objects with extended outflowing atmospheres.

Journal ArticleDOI
25 Feb 1998-JAMA
TL;DR: Objective measures of subclinical disease and disease severity were independent and joint predictors of 5-year mortality in older adults, along with male sex, relative poverty, physical activity, smoking, indicators of frailty, and disability.
Abstract: Context—Multiple factors contribute to mortality in older adults, but the extent to which subclinical disease and other factors contribute independently to mortality risk is not knownObjective—To determine the disease, functional, and personal characteristics that jointly predict mortality in community-dwelling men and women aged 65 years or olderDesign—Prospective population-based cohort study with 5 years of follow-up and a validation cohort of African Americans with 425-year follow-upSetting—Four US communitiesParticipants—A total of 5201 and 685 men and women aged 65 years or older in the original and African American cohorts, respectivelyMain Outcome Measures—Five-year mortalityResults—In the main cohort, 646 deaths (12%) occurred within 5 years Using Cox proportional hazards models, 20 characteristics (of 78 assessed) were each significantly (P<05) and independently associated with mortality: increasing age, male sex, income less than $50000 per year, low weight, lack of moderate or vigorous exercise, smoking for more than 50 pack-years, high brachial (>169 mm Hg) and low tibial (≤127 mm Hg) systolic blood pressure, diuretic use by those without hypertension or congestive heart failure, elevated fasting glucose level (>72 mmol/L [130 mg/dL]), low albumin level (≤37 g/L), elevated creatinine level (≥106 µmol/L [12 mg/dL]), low forced vital capacity (≤206 mL), aortic stenosis (moderate or severe) and abnormal left ventricular ejection fraction (by echocardiography), major electrocardiographic abnormality, stenosis of internal carotid artery (by ultrasound), congestive heart failure, difficulty in any instrumental activity of daily living, and low cognitive function by Digit Symbol Substitution test score Neither high-density lipoprotein cholesterol nor low-density lipoprotein cholesterol was associated with mortality After adjustment for other factors, the association between age and mortality diminished, but the reduction in mortality with female sex persisted Finally, the risk of mortality was validated in the second cohort; quintiles of risk ranged from 2% to 39% and 0% to 26% for the 2 cohortsConclusions—Objective measures of subclinical disease and disease severity were independent and joint predictors of 5-year mortality in older adults, along with male sex, relative poverty, physical activity, smoking, indicators of frailty, and disability Except for history of congestive heart failure, objective, quantitative measures of disease were better predictors of mortality than was clinical history of disease

Journal ArticleDOI
23 Dec 1998-Cell
TL;DR: Investigation of the potential of double-stranded RNA to interfere with the function of genes in Drosophila demonstrated that dsRNA interference can be used to analyze many aspects of gene function.

Journal ArticleDOI
TL;DR: This book aims to provide a history of DNA methylation in the immune system and some of the mechanisms leading to disease, as well as some examples of successful and unsuccessful attempts to correct these problems.
Abstract: 116 nature genetics volume 20 october 1998 Berkeley, California 94720, USA. 2Department of Pathology, University of Washington, Seattle, Washington 98195, USA. 3Department of Radiation Biology, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA. Correspondence should be addressed to J.C. (e-mail: jcampisi@lbl.gov). 1. Martin, G.M. Birth Defects 14, 5−39 (1978). 2. Goto, M. Mech. Ageing Dev. 98, 239–254 (1997). 3. Martin, G.M., Sprague, C.A. & Epstein, C.J. Lab. Invest. 23, 86–92 (1970). 4. Salk, D., Bryant, E., Hoehn, H., Johnston, P. & Martin, G.M. Adv. Exp. Bio. Med. 190, 305–311 (1985). 5. Fukuchi, K., Martin, G.M. & Monnat, R.J. Proc. Natl Acad. Sci. USA 86, 5893–5897 (1989). 6. Cheng, R.Z., Murano, S., Kurz, B. & Shmookler-Reis, R.J. Mutat. Res. 237, 259–269 (1990). 7. Yu, C.E. et al. Science 272, 258–262 (1996). 8. German, J. Medicine 72, 393–406 (1993). 9. Main, I.S. Nucleic Acids Res. 25, 3187–3195 (1997). 10. Mushegian, A.R., Bassett, D.E. Jr, Boguski, M.S., Bork, P., & Koonin, E.V. Proc. Natl Acad. Sci. USA 94, 5831–5836 (1997). 11. Gray, M.D. et al. Nature Genet. 17, 100–103 (1997). 12. Linn, S.M., Lloyd, R.S. & Roberts, R.T. Nucleases (Cold Spring Harbor Laboratory Press, New York, 1993). 13. Yamagata, K. et al. Proc. Natl Acad. Sci. USA 95, 8733–8738 (1998). 14. Ogburn, C.E. et al. Hum. Genet. 101, 121–125 (1997). 15. Yan, H., Chen, C.-Y., Kobayashi, R. & Newport, J. Nature Genet. 19, 375–378 (1998).

Journal ArticleDOI
TL;DR: Quantitation of EGFR and TGF-a protein levels in primary head and neck squamous cell carcinomas may be useful in identifying subgroups of patients at high risk of tumor recurrence and in guiding therapy.
Abstract: Background: The most accurate predictor of disease recurrence in patients treated for head and neck squamous cell carcinoma is, at present, the extent of regional lymph node metastasis. Since elevated levels of epidermal growth factor receptor (EGFR) and of its ligand, transforming growth factor-a (TGF-a), have been detected in primary tumors of patients with head and neck squamous cell carcinoma, we determined whether tumor levels of these proteins were of prognostic importance. Methods: Monoclonal antibodies specific for EGFR and TGF-a were used for immunohistochemical detection of each protein in tissue sections of primary tumors from 91 patients who were treated by surgical resection. Levels of immunoreactive EGFR and TGF-a were quantified by use of a computerized image analysis system and were normalized to appropriate standards. The logrank test and proportional hazards regression analysis were used to calculate the probability that EGFR and TGF-a levels were associated with disease-free survival (i.e., no recurrence of cancer) and cause-specific survival (i.e., patients do not die of their disease). All P values were two-sided. Results: When tumor levels of EGFR or TGF-a were analyzed as continuous variables, disease-free survival and cause-specific survival were reduced among patients with higher levels of EGFR (both P = .0001) or TGF-a (both P = .0001). In a multivariate analysis, tumor site, tumor level of EGFR, and tumor level of TGF-a were statistically significant predictors of disease-free survival; in a similar analysis, regional lymph node stage and tumor levels of EGFR and of TGF-a were significant predictors of cause-specific survival. Conclusion: Quantitation of EGFR and TGF-a protein levels in primary head and neck squamous cell carcinomas may be useful in identifying subgroups of patients at high risk of tumor recurrence and in guiding therapy. [J Natl Cancer Inst 1998; 90:824‐32]

Journal ArticleDOI
TL;DR: Although phototherapy successfully reduces serum bilirubin levels, patients are again at risk for kernicterus around the time of puberty, when phototherapy becomes less effective, and liver transplantation is the only definitive treatment.
Abstract: Crigler–Najjar syndrome type I is a recessively inherited disorder characterized by severe unconjugated hyperbilirubinemia beginning at birth. The syndrome results from an absence of hepatic uridine diphosphoglucuronate (UDP) glucuronosyltransferase activity, which is essential for the conjugation and excretion of bilirubin. Because of the accumulation of unconjugated bilirubin in plasma, patients are at risk for kernicterus.1 Although phototherapy successfully reduces serum bilirubin levels, patients are again at risk for kernicterus around the time of puberty, when phototherapy becomes less effective.2 The necessary daily duration of phototherapy often approaches 14 to 16 hours. At present, liver transplantation is the only definitive treatment. . . .

Journal ArticleDOI
TL;DR: A comparison of likelihood ratios for the nonword repetition task and for a traditional language test revealed that non word repetition distinguished between children independently identified as LI and LN with a high degree of accuracy, by contrast with theTraditional language test.
Abstract: A brief, processing-dependent, nonword repetition task, designed to minimize biases associated with traditional language tests, was investigated In Study 1, no overlap in nonword repetition perfor

Journal ArticleDOI
TL;DR: It is found that 755 of 4,288 ORFs have been introduced into the E. coli genome in at least 234 lateral transfer events since this species diverged from the Salmonella lineage 100 million years ago.
Abstract: The availability of the complete sequence of Escherichia coli strain MG1655 provides the first opportunity to assess the overall impact of horizontal genetic transfer on the evolution of bacterial genomes. We found that 755 of 4,288 ORFs (547.8 kb) have been introduced into the E. coli genome in at least 234 lateral transfer events since this species diverged from the Salmonella lineage 100 million years (Myr) ago. The average age of introduced genes was 14.4 Myr, yielding a rate of transfer 16 kb/Myr/lineage since divergence. Although most of the acquired genes subsequently were deleted, the sequences that have persisted (≈18% of the current chromosome) have conferred properties permitting E. coli to explore otherwise unreachable ecological niches.

Journal ArticleDOI
TL;DR: The proof of principle of CT-based attenuation correction of 3D positron emission tomography (PET) data is demonstrated by using scans of bone and soft tissue equivalent phantoms and scans of humans to conclude that using CT information is a feasible way to obtain attenuation Correction factors for 3D PET.
Abstract: In this work we demonstrate the proof of principle of CT-based attenuation correction of 3D positron emission tomography (PET) data by using scans of bone and soft tissue equivalent phantoms and scans of humans. This method of attenuation correction is intended for use in a single scanner that combines volume-imaging (3D) PET with x-ray computed tomography (CT) for the purpose of providing accurately registered anatomical localization of structures seen in the PET image. The goal of this work is to determine if we can perform attenuation correction of the PET emission data using accurately aligned CT attenuation information. We discuss possible methods of calculating the PET attenuation map at 511 keV based on CT transmission information acquired from 40 keV through 140 keV. Data were acquired on separate CT and PET scanners and were aligned using standard image registration procedures. Results are presented on three of the attenuation calculation methods: segmentation, scaling, and our proposed hybrid segmentation/scaling method. The results are compared with those using the standard 3D PET attenuation correction method as a gold standard. We demonstrate the efficacy of our proposed hybrid method for converting the CT attenuation map from an effective CT photon energy of 70 keV to the PET photon energy of 511 keV. We conclude that using CT information is a feasible way to obtain attenuation correction factors for 3D PET.

Journal ArticleDOI
TL;DR: A general overview of ideas, techniques, results and open problems of this candidate theory of quantum gravity is provided, and a guide to the relevant literature is provided.
Abstract: The problem of describing the quantum behavior of gravity, and thus understanding quantum spacetime, is still open. Loop quantum gravity is a well-developed approach to this problem. It is a mathematically well-defined background-independent quantization of general relativity, with its conventional matter couplings. Today research in loop quantum gravity forms a vast area, ranging from mathematical foundations to physical applications. Among the most significant results obtained so far are: (i) The computation of the spectra of geometrical quantities such as area and volume, which yield tentative quantitative predictions for Planck-scale physics. (ii) A physical picture of the microstructure of quantum spacetime, characterized by Planck-scale discreteness. Discreteness emerges as a standard quantum effect from the discrete spectra, and provides a mathematical realization of Wheeler’s “spacetime foam” intuition. (iii) Control of spacetime singularities, such as those in the interior of black holes and the cosmological one. This, in particular, has opened up the possibility of a theoretical investigation into the very early universe and the spacetime regions beyond the Big Bang. (iv) A derivation of the Bekenstein-Hawking black-hole entropy. (v) Low-energy calculations, yielding n-point functions well defined in a background-independent context. The theory is at the roots of, or strictly related to, a number of formalisms that have been developed for describing background-independent quantum field theory, such as spin foams, group field theory, causal spin networks, and others. I give here a general overview of ideas, techniques, results and open problems of this candidate theory of quantum gravity, and a guide to the relevant literature.

Journal ArticleDOI
TL;DR: A gas-filled microbubble with anti-ICAM-1 antibody on its shell specifically binds to activated ECs overexpressing ICam-1.
Abstract: Background—Preclinical atherosclerosis is associated with increased endothelial cell (EC) expression of leukocyte adhesion molecules (LAMs), which mediate monocyte adhesion during atherogenesis. Identification of cell-surface LAMs may uniquely allow assessment of endothelial function, but there are no in vivo methods for detecting LAMs. We tested a new microbubble designed to bind to and allow specific ultrasound detection of intercellular adhesion molecule-1 (ICAM-1). Methods and Results—A perfluorobutane gas–filled lipid-derived microsphere with monoclonal antibody to ICAM-1 covalently bound to the bubble shell was synthesized. Bubbles with either nonspecific IgG or no protein on the shell were synthesized as controls. Coverslips of cultured human coronary artery ECs were placed in a parallel-plate perfusion chamber and exposed to 1 of the 3 microbubble species, followed by perfusion with culture medium. Experiments were performed with either normal or interleukin-1β–activated ECs overexpressing ICAM-1,...

Journal ArticleDOI
01 Feb 1998-Geoderma
TL;DR: The strontium (Sr) isotope method can be a powerful tool in studies of chemical weathering and soil genesis, cation provenance and mobility, and the chronostratigraphic correlation of marine sediments.

Journal ArticleDOI
TL;DR: The large proportion of bimodal tactile and visual neurons with congruent response properties in area VIP indicates that there are important functional differences between area VIP and other dorsal stream areas involved in the analysis of motion.
Abstract: Duhamel, Jean-Rene, Carol L. Colby, and Michael E. Goldberg. Ventral intraparietal area of the macaque: congruent visual and somatic response properties. J. Neurophysiol. 79: 126–136, 1998. In a pr...

Journal ArticleDOI
TL;DR: Significant nonrandom association between two markers located 22 cM apart (FY-null and AT3) is detected, most likely due to admixture linkage disequilibrium created in the interbreeding of the two parental populations, emphasize the importance of admixed populations as a useful resource for mapping traits with different prevalence in two parental population.
Abstract: We analyzed the European genetic contribution to 10 populations of African descent in the United States (Maywood, Illinois; Detroit; New York; Philadelphia; Pittsburgh; Baltimore; Charleston, South Carolina; New Orleans; and Houston) and in Jamaica, using nine autosomal DNA markers. These markers either are population-specific or show frequency differences >45% between the parental populations and are thus especially informative for admixture. European genetic ancestry ranged from 6.8% (Jamaica) to 22.5% (New Orleans). The unique utility of these markers is reflected in the low variance associated with these admixture estimates (SEM 1.3%-2.7%). We also estimated the male and female European contribution to African Americans, on the basis of informative mtDNA (haplogroups H and L) and Y Alu polymorphic markers. Results indicate a sex-biased gene flow from Europeans, the male contribution being substantially greater than the female contribution. mtDNA haplogroups analysis shows no evidence of a significant maternal Amerindian contribution to any of the 10 populations. We detected significant nonrandom association between two markers located 22 cM apart (FY-null and AT3), most likely due to admixture linkage disequilibrium created in the interbreeding of the two parental populations. The strength of this association and the substantial genetic distance between FY and AT3 emphasize the importance of admixed populations as a useful resource for mapping traits with different prevalence in two parental populations.


Journal ArticleDOI
04 Nov 1998-JAMA
TL;DR: In the calendar period when potent antiretroviral therapy was introduced, the time to development of AIDS and time to death were extended, and rate of CD4 cell count decline was arrested.
Abstract: Context.—Time to development of acquired immunodeficiency syndrome (AIDS) and time to death have been extended with the increased use of combination therapy and protease inhibitors. Cohort studies following up persons with human immunodeficiency virus (HIV) infection in periods characterized by different therapies offer the opportunity to estimate therapy effectiveness at the population level.Objective.—To assess the effectiveness of self-reported, long-term potent antiretroviral therapy in a cohort of 536 men whose duration of HIV infection was known (seroconverters).Design.—Cohort study. The cohort was compared for time to development of AIDS and time to death in 1984 to 1990, 1990 to 1993, 1993 to July 1995, and July 1995 to July 1997 when the major treatments were no therapy, monotherapy, combined therapy, and potent antiretroviral therapy, respectively. Survival analysis methods with time zero set as the date of seroconversion and incorporating staggered entries into each period were used. Mean CD4 cell change, stratified by infection duration, was determined for each period using a random effects model.Setting.—The Multicenter AIDS Cohort Study (MACS) in 4 urban areas (Baltimore, Md; Chicago, Ill; Los Angeles, Calif; and Pittsburgh, Pa).Participants.—A total of 5622 men who were 18 years or older were enrolled into MACS. Of the 5622, there were 2191 HIV-positive individuals at enrollment. Of the 3431 men who were HIV-negative, 536 were observed to seroconvert and were followed up for up to 13 years. The group of 536 who seroconverted constituted the study population.Main Outcome Measures.—Time from seroconversion to development of AIDS and to death and change in CD4 cell count.Results.—A total of 231 seroconverters developed AIDS, and 200 men died. Using 1990 to 1993 as the reference period, the relative hazard of AIDS was 1.04 (95% confidence interval [CI], 0.73-1.48) during 1993 to July 1995 and 0.35 (95% CI, 0.20-0.61) during July 1995 to July 1997. Relative hazards of death were 0.87 (95% CI, 0.58-1.31) and 0.62 (95% CI, 0.38-1.01) for the same periods. The relative time (the factor by which times are contracted or expanded) to development of AIDS was 0.97 (95% CI, 0.86-1.09) for 1993 to July 1995 and 1.63 (95% CI, 1.40-1.89) for July 1995 to July 1997. Relative survival time for 1993 to July 1995 was 1.01 (95% CI, 0.91-1.12) and for July 1995 to July 1997 was 1.21 (95% CI, 1.07-1.36) relative to 1990 to 1993. The rate of CD4 cell count decline in July 1995 to July 1997 was significantly lower (P<.05) compared with the previous 2 periods.Conclusions.—In the calendar period when potent antiretroviral therapy was introduced, the time to development of AIDS and time to death were extended, and rate of CD4 cell count decline was arrested.

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TL;DR: Data suggest that caspase-3 activity contributes to delayed neuronal death after transient ischemia and ventricular infusion of Z-DEVD-FMK, a casp enzyme-3 inhibitor, decreased caspasesase- 3 activity in the hippocampus and significantly reduced cell death and DNA fragmentation in the CA1 sector up to 7 d after ischemIA.
Abstract: Delayed neuronal death after transient cerebral ischemia may be mediated, in part, by the induction of apoptosis-regulatory gene products. Caspase-3 is a newly characterized mammalian cysteine protease that promotes cell death during brain development, in neuronal cultures, and in other cell types under many different conditions. To determine whether caspase-3 serves to regulate neuronal death after cerebral ischemia, we have (1) cloned a cDNA encoding the rat brain caspase-3; (2) examined caspase-3 mRNA and protein expression in the brain using in situ hybridization, Northern and Western blot analyses, and double-labeled immunohistochemistry; (3) determined caspase-3-like activity in brain cell extracts; and (4) studied the effect of caspase-3 inhibition on cell survival and DNA fragmentation in the hippocampus in a rat model of transient global ischemia. At 8-72 hr after ischemia, caspase-3 mRNA and protein were induced in the hippocampus and caudate-putamen (CPu), accompanied by increased caspase-3-like protease activity. In the hippocampus, caspase-3 mRNA and protein were predominantly increased in degenerating CA1 pyramidal neurons. Proteolytic activation of the caspase-3 precursor was detected in hippocampus and CPu but not in cortex at 4-72 hr after ischemia. Double-label experiments detected DNA fragmentation in the majority of CA1 neurons and selective CPu neurons that overexpressed caspase-3. Furthermore, ventricular infusion of Z-DEVD-FMK, a caspase-3 inhibitor, decreased caspase-3 activity in the hippocampus and significantly reduced cell death and DNA fragmentation in the CA1 sector up to 7 d after ischemia. These data strongly suggest that caspase-3 activity contributes to delayed neuronal death after transient ischemia.

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TL;DR: The document emphasizes the importance of rhinitis management for comorbid conditions (asthma, sinusitis, otitis media) and when consultation with an allergist-immunologist should be considered.
Abstract: This document contains complete guidelines for diagnosis and management of rhinitis developed by the Joint Task Force on Practice Parameters in Allergy, Asthma and Immunology, representing the American Academy of Allergy, Asthma and Immunology, the American College of Allergy, Asthma and Immunology and the Joint Council on Allergy, Asthma and Immunology. The guidelines are comprehensive and begin with statements on clinical characteristics and diagnosis of different forms of rhinitis (allergic, non-allergic, occupational rhinitis, hormonal rhinitis [pregnancy and hypothyroidism], drug-induced rhinitis, rhinitis from food ingestion), and other conditions that may be confused with rhinitis. Recommendations on patient evaluation discuss appropriate use of history, physical examination, and diagnostic testing, as well as unproven or inappropriate techniques that should not be used. Parameters on management include use of environmental control measures, pharmacologic therapy including recently introduced therapies and allergen immunotherapy. Because of the risks to patients and society from sedation and performance impairment caused by first generation antihistamines, second generation antihistamines that reduce or eliminate these side effects should usually be considered before first generation antihistamines for the treatment of allergic rhi-nitis. The document emphasizes the importance of rhinitis management for co-morbid conditions (asthma, sinusitis, otitis media). Guidelines are also presented on special considerations in patients subsets (children, the elderly, pregnancy, athletes and patients with rhinitis medicamentosa); and when consultation with an allergist-immunologist should be considered.