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Showing papers by "University of Pittsburgh published in 1997"


Journal ArticleDOI
TL;DR: In this paper, a theory of stakeholder identification and saliency based on stakeholders possessing one or more of three relationship attributes (power, legitimacy, and urgency) is proposed, and a typology of stakeholders, propositions concerning their saliency to managers of the firm, and research and management implications.
Abstract: Stakeholder theory has been a popular heuristic for describing the management environment for years, but it has not attained full theoretical status. Our aim in this article is to contribute to a theory of stakeholder identification and salience based on stakeholders possessing one or more of three relationship attributes: power, legitimacy, and urgency. By combining these attributes, we generate a typology of stakeholders, propositions concerning their salience to managers of the firm, and research and management implications.

10,630 citations


Journal ArticleDOI
TL;DR: Results suggest the K-SADS-PL generates reliable and valid child psychiatric diagnoses.
Abstract: Objective To describe the psychometric properties of the Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime version (K-SADS-PL) interview, which surveys additional disorders not assessed in prior K-SADS, contains improved probes and anchor points, includes diagnosis-specific impairment ratings, generates DSM-III-R and DSM-IV diagnoses, and divides symptoms surveyed into a screening interview and five diagnostic supplements. Method Subjects were 55 psychiatric outpatients and 11 normal controls (aged 7 through 17 years). Both parents and children were used as informants. Concurrent validity of the screen criteria and the K-SADS-PL diagnoses was assessed against standard self-report scales. Interrater ( n = 15) and test-retest ( n = 20) reliability data were also collected (mean retest interval: 18 days; range: 2 to 38 days). Results Rating scale data support the concurrent validity of screens and K-SADS-PL diagnoses. Interrater agreement in scoring screens and diagnoses was high (range: 93% to 100%). Test-retest reliability κ coefficients were in the excellent range for present and/or lifetime diagnoses of major depression, any bipolar, generalized anxiety, conduct, and oppositional defiant disorder (.77 to 1.00) and in the good range for present diagnoses of posttraumatic stress disorder and attention-deficit hyperactivity disorder (.63 to .67). Conclusion Results suggest the K-SADS-PL generates reliable and valid child psychiatric diagnoses. J. Am. Acad. Child Adolesc. Psychiatry , 1997, 36(7): 980–988.

8,742 citations


Journal ArticleDOI
TL;DR: This paper decompose the conventional measure of evaluation bias into several components and find that bias due to selection on unobservables, commonly called selection bias in econometrics, is empirically less important than other components, although it is still a sizeable fraction of the estimated programme impact.
Abstract: This paper considers whether it is possible to devise a nonexperimental procedure for evaluating a prototypical job training programme. Using rich nonexperimental data, we examine the performance of a two-stage evaluation methodology that (a) estimates the probability that a person participates in a programme and (b) uses the estimated probability in extensions of the classical method of matching. We decompose the conventional measure of programme evaluation bias into several components and find that bias due to selection on unobservables, commonly called selection bias in econometrics, is empirically less important than other components, although it is still a sizeable fraction of the estimated programme impact. Matching methods applied to comparison groups located in the same labour markets as participants and administered the same questionnaire eliminate much of the bias as conventionally measured, but the remaining bias is a considerable fraction of experimentally-determined programme impact estimates. We test and reject the identifying assumptions that justify the classical method of matching. We present a nonparametric conditional difference-in-differences extension of the method of matching that is consistent with the classical index-sufficient sample selection model and is not rejected by our tests of identifying assumptions. This estimator is effective in eliminating bias, especially when it is due to temporally-invariant omitted variables.

5,069 citations


Journal ArticleDOI
TL;DR: A prediction rule that stratifies patients into five classes with respect to the risk of death within 30 days accurately identifies the patients with community-acquired pneumonia who are at low risk for death and other adverse outcomes and may help physicians make more rational decisions about hospitalization for patients with pneumonia.
Abstract: Background There is considerable variability in rates of hospitalization of patients with community-acquired pneumonia, in part because of physicians' uncertainty in assessing the severity of illness at presentation. Methods From our analysis of data on 14,199 adult inpatients with community-acquired pneumonia, we derived a prediction rule that stratifies patients into five classes with respect to the risk of death within 30 days. The rule was validated with 1991 data on 38,039 inpatients and with data on 2287 inpatients and outpatients in the Pneumonia Patient Outcomes Research Team (PORT) cohort study. The prediction rule assigns points based on age and the presence of coexisting disease, abnormal physical findings (such as a respiratory rate of > or = 30 or a temperature of > or = 40 degrees C), and abnormal laboratory findings (such as a pH or = 30 mg per deciliter [11 mmol per liter] or a sodium concentration Results There were no significant differences in mortality in each of the five risk classes among the three cohorts. Mortality ranged from 0.1 to 0.4 percent for class I patients (P=0.22), from 0.6 to 0.7 percent for class II (P=0.67), and from 0.9 to 2.8 percent for class III (P=0.12). Among the 1575 patients in the three lowest risk classes in the Pneumonia PORT cohort, there were only seven deaths, of which only four were pneumonia-related. The risk class was significantly associated with the risk of subsequent hospitalization among those treated as outpatients and with the use of intensive care and the number of days in the hospital among inpatients. Conclusions The prediction rule we describe accurately identifies the patients with community-acquired pneumonia who are at low risk for death and other adverse outcomes. This prediction rule may help physicians make more rational decisions about hospitalization for patients with pneumonia.

3,996 citations


Journal ArticleDOI
TL;DR: This study compared the prognostic value of plasma viral load with that of clinical, serologic, and cellular markers in a large cohort of HIV-infected men and incorporated the two most predictive markers-plasma viral load and CD4+ lymphocyte count-into a regression tree that is useful for assessing the prognosis of individual patients.
Abstract: Background: The rate of disease progression among persons infected with human immunodeficiency virus type 1 (HIV-1) varies widely, and the relative prognostic value of markers of disease activity h...

2,137 citations


Journal ArticleDOI
TL;DR: In most HIV-infected patients with prior antiretroviral therapy, the combination of indinavir, zidovudine, and lamivudine reduces levels of HIV RNA to less than 500 copies per milliliter for as long as one year.
Abstract: Background The new protease inhibitors are potent inhibitors of the human immunodeficiency virus (HIV), and in combination with other antiretroviral drugs they may be able to cause profound and sustained suppression of HIV replication. Methods In this double-blind study, 97 HIV-infected patients who had received zidovudine treatment for at least 6 months and had 50 to 400 CD4 cells per cubic millimeter and at least 20,000 copies of HIV RNA per milliliter were randomly assigned to one of three treatments for up to 52 weeks: 800 mg of indinavir every eight hours; 200 mg of zidovudine every eight hours combined with 150 mg of lamivudine twice daily; or all three drugs. The patients were followed to monitor the occurrence of adverse events and changes in viral load and CD4 cell counts. Results The decrease in HIV RNA over the first 24 weeks was greater in the three-drug group than in the other groups (P<0.001 for each comparison). RNA levels decreased to less than 500 copies per milliliter at week 24 in 28 of...

1,867 citations


Journal ArticleDOI
23 Oct 1997-Nature
TL;DR: The preparation of a material that changes colour in response to a chemical signal by means of a change in diffraction (rather than absorption) properties is reported, anticipating that this strategy can be used to prepare ‘intelligent’ materials responsive to a wide range of analytes, including viruses.
Abstract: Chemical sensors respond to the presence of a specific analyte in a variety of ways. One of the most convenient is a change in optical properties, and in particular a visually perceptible colour change. Here we report the preparation of a material that changes colour in response to a chemical signal by means of a change in diffraction (rather than absorption) properties. Our material is a crystalline colloidal array of polymer spheres (roughly 100 nm diameter) polymerized within a hydrogel that swells and shrinks reversibly in the presence of certain analytes (here metal ions and glucose). The crystalline colloidal array diffracts light at (visible) wavelengths determined by the lattice spacing, which gives rise to an intense colour. The hydrogel contains either a molecular-recognition group that binds the analyte selectively (crown ethers for metal ions), or a molecular-recognition agent that reacts with the analyte selectively. These recognition events cause the gel to swell owing to an increased osmotic pressure, which increases the mean separation between the colloidal spheres and so shifts the Bragg peak of the diffracted light to longer wavelengths. We anticipate that this strategy can be used to prepare 'intelligent' materials responsive to a wide range of analytes, including viruses.

1,861 citations


Journal ArticleDOI
10 Apr 1997-Nature
TL;DR: Functional magnetic resonance imaging is used to examine brain activation in human subjects during performance of a working memory task and to show that prefrontal cortex along with parietal cortex appears to play a role in active maintenance.
Abstract: Working memory is responsible for the short-term storage and online manipulation of information necessary for higher cognitive functions, such as language, planning and problem-solving. Traditionally, working memory has been divided into two types of processes: executive control (governing the encoding manipulation and retrieval of information in working memory) and active maintenance (keeping information available 'online'). It has also been proposed that these two types of processes may be subserved by distinct cortical structures, with the prefrontal cortex housing the executive control processes, and more posterior regions housing the content-specific buffers (for example verbal versus visuospatial) responsible for active maintenance. However, studies in non-human primates suggest that dorsolateral regions of the prefrontal cortex may also be involved in active maintenance. We have used functional magnetic resonance imaging to examine brain activation in human subjects during performance of a working memory task. We used the temporal resolution of this technique to examine the dynamics of regional activation, and to show that prefrontal cortex along with parietal cortex appears to play a role in active maintenance.

1,824 citations


Journal ArticleDOI
TL;DR: Women with lupus in the 35- to 44-year age group were over 50 times more likely to have a myocardial infarction than were women of similar age in the Framingham Offspring Study.
Abstract: The authors ascertained cardiovascular events (myocardial infarction and angina pectoris) in 498 women with systemic lupus erythematosus seen at the University of Pittsburgh Medical Center from 1980 to 1993 (3,522 person-years). Subjects were stratified by age, and cardiovascular event incidence rates were determined. The authors compared these rates with cardiovascular event rates were determined. The authors compared these rates with cardiovascular event rates occurring over the same time period in 2,208 women of similar age participating in the Framingham Offspring Study (17,519 person-years). Age-specific rate ratios were computed to determine whether the cardiovascular events in the lupus cohort were greater than expected. The risk factors associated with cardiovascular events in women with lupus were determined. There were 33 first events (11 myocardial infarction, 10 angina pectoris, and 12 both angina pectoris and myocardial infarction) after the diagnosis of lupus: two thirds were under the age of 55 years at the time of event. Women with lupus in the 35- to 44-year age group were over 50 times more likely to have a myocardial infarction than were women of similar age in the Framingham Offspring Study (rate ratio = 52.43, 95% confidence interval 21.6-98.5). Older age at lupus diagnosis, longer lupus disease duration, longer duration of corticosteroid use, hypercholesterolemia, and postmenopausal status were more common in the women with lupus who had a cardiovascular event than in those who did not have an event. Premature cardiovascular disease is much more common in young premenopausal women with lupus than in a population sample. With the increased life expectancy of lupus patients due to improved therapy, cardiovascular disease has emerged as a significant threat to the health of these women. The impact of this problem has been underrecognized, with little focus placed on aggressive management of hypercholesterolemia and other possible risk factors.

1,689 citations


Journal ArticleDOI
TL;DR: Preoperative therapy reduced the size of most breast tumors and decreased the incidence of positive nodes in women with primary breast cancer and should be considered for the initial management of breast tumors judged too large for lumpectomy.
Abstract: PURPOSETo determine whether preoperative doxorubicin and cyclophosphamide (AC) permits more lumpectomies to be performed and decreases the incidence of positive nodes in women with primary breast cancer.PATIENTS AND METHODSWomen (n = 1,523) were randomized to National Surgical Adjuvant Breast and Bowel Project (NSABP) B-18; 759 eligible patients received postoperative AC and 747, preoperative AC. The clinical size of breast and axillary tumors was determined before each of four cycles of AC and before surgery. Tumor response to preoperative therapy was clinically complete (cCR), partial (cPR), stable (cSD), or progressive disease (cPD). Tissue from patients with a cCR was evaluated for a pathologic complete response (pCR).RESULTSBreast tumor size was reduced in 80% of patients after preoperative therapy; 36% had a cCR. Tumor size and clinical nodal status were independent predictors of cCR. Twenty-six percent of women with a cCR had a pCR. Clinical nodal response occurred in 89% of node-positive patients:...

1,677 citations


Journal ArticleDOI
TL;DR: This work defines risk and a risk factor (protective factor) and their potency, set out the conceptual basis of the methods by which risk factors are identified and potency demonstrated, and proposes criteria for establishing the status of a risk factors as a fixed or variable marker or a causal risk factor.
Abstract: Terms such as risk, risk factors, and especially the term cause are inconsistently and imprecisely used, fostering scientific miscommunication and misleading research and policy. Clarifying such terms is the essential first step. We define risk and a risk factor (protective factor) and their potency, set out the conceptual basis of the methods by which risk factors are identified and potency demonstrated, and propose criteria for establishing the status of a risk factor as a fixed or variable marker or a causal risk factor. All definitions are based on the state of scientific knowledge (empirical documentation), rather than on hypotheses, speculations, or beliefs. We discuss common approaches and pitfalls and give a psychiatric research example. Imprecise reports can impede the search for understanding the cause and course of any disease and also may be a basis of inadequate clinical or policy decision-making. The issues in risk research are much too important to tolerate less than precise terminology or the less than rigorous research reporting that results from imprecise and inconsistent terminology.

Journal ArticleDOI
TL;DR: A randomized, controlled trial compared the effects of moderate hypothermia and normothermia in 82 patients with severe closed head injuries and found thatHypothermia may limit some of the deleterious metabolic responses of traumatic brain injury.
Abstract: Early reports of therapeutic hypothermia for severe traumatic brain injury can be traced back to the first half of the 20th century. It is only within the last two decades that clinical studies have demonstrated that therapeutic moderate hypothermia for brief durations can improve patient outcomes following brain injury. The historical background, recent clinical experience, and mechanisms of action of moderate hypothermia are reviewed.

Journal ArticleDOI
TL;DR: A panel of recognized experts in liver transplantation pathology, hepatology, and surgery agreed on a common nomenclature and a set of histopathological criteria for the grading of acute liver allograft rejection, and a preferred method of reporting.

Journal ArticleDOI
TL;DR: The National Weight Control Registry identified a large sample of individuals who were highly successful at maintaining weight loss and indicated that weight loss led to improvements in their level of energy, physical mobility, general mood, self-confidence, and physical health.

Journal ArticleDOI
TL;DR: A six-item dispositional self-report index called the Children's Hope Scale is introduced and validated for use with children ages 8-16 and suggests that the scale evidence internal consistency, and is relatively stable over retesting.
Abstract: Assuming that children are goal-oriented, it is suggested that their thoughts are related to two components--agency and pathways. Agency thoughts reflect the perception that children can initiate and sustain action toward a desired goal; pathways thoughts reflect the children's perceived capability to produce routes to those goals. Hope reflects the combination of agentic and pathways thinking toward goals. A six-item dispositional self-report index called the Children's Hope Scale is introduced and validated for use with children ages 8-16. Results suggest that the scale evidence internal consistency, and is relatively stable over retesting. Additionally, the scale exhibits convergent, discriminant, and incremental validity. Limitations and uses of the scale are discussed.

Journal Article
TL;DR: This work has shown clear trends in the use of physical activity questionnaires in the general population and in the older adults, and these trends are likely to continue into the next decade.
Abstract: Introduction; Section I. Physical Activity Questionnaires Used in the General Population; Section II. Physical Activity Questionnaires for Older Adults; Section III. Physical Activity Questionnaires Used in Major Population-Based Surveys

Journal ArticleDOI
TL;DR: Although inhibitory processes have typically been associated with more ventral or orbital frontal regions, the current study revealed activation that was distributed across both dorsolateral and orbitofrontal cortices, consistent with animal and human lesion studies.
Abstract: This study examines important developmental differences in patterns of activation in the prefrontal cortex during performance of a Go-No-Go paradigm using functional magnetic resonance imaging (fMRI). Eighteen subjects (9 children and 9 adults) were scanned using gradient echo, echo planar imaging during performance of a response inhibition task. The results suggest four general findings. First, the location of activation in the prefrontal cortex was not different between children and adults, which is similar to our earlier pediatric fMRI results of prefrontal activation during a working memory task (Casey et al., 1995). Second, the volume of activation was significantly greater for children relative to adults. These differences in volume of activation were observed predominantly in the dorsal and lateral prefrontal cortices. Third, although inhibitory processes have typically been associated with more ventral or orbital frontal regions, the current study revealed activation that was distributed across both dorsolateral and orbitofrontal cortices. Finally, consistent with animal and human lesion studies, activity in orbital frontal and anterior cingulate cortices correlated with behavioral performance (i.e., number of false alarms). These results further demonstrate the utility of this methodology in studying pediatric populations.

Journal ArticleDOI
01 Oct 1997-Diabetes
TL;DR: As a component of central adiposity, subcutaneous abdominal fat has as strong an association with insulin resistance as visceral fat, and altered muscle composition, suggestive of increased fat content, is an important independent marker of insulin resistance in obesity.
Abstract: Whether visceral adipose tissue has a uniquely powerful association with insulin resistance or whether subcutaneous abdominal fat shares this link has generated controversy in the area of body composition and insulin sensitivity. An additional issue is the potential role of fat deposition within skeletal muscle and the relationship with insulin resistance. To address these matters, the current study was undertaken to measure body composition, aerobic fitness, and insulin sensitivity within a cohort of sedentary healthy men ( n = 26) and women ( n = 28). The subjects, who ranged from lean to obese (BMI 19.6-41.0 kg/m2), underwent dual energy X-ray absorptiometry (DEXA) to measure fat-free mass (FFM) and fat mass (FM), computed tomography to measure cross-sectional abdominal subcutaneous and visceral adipose tissue, and computed tomography (CT) of mid-thigh to measure muscle cross-sectional area, muscle attenuation, and subcutaneous fat. Insulin sensitivity was measured using the glucose clamp technique (40 mU · m∼2 · min−1), in conjunction with [3-3H]glucose isotope dilution. Maximal aerobic power (Vo2max) was determined using an incremental cycling test. Insulin-stimulated glucose disposal ( R d) ranged from 3.03 to 16.83 mg · min−1· kg−1 FFM. R d was negatively correlated with FM ( r = -0.58), visceral fat ( r = -0.52), subcutaneous abdominal fat ( r = -0.61), and thigh fat ( r = -0.38) and positively correlated with muscle attenuation ( r = 0.48) and Vo2max ( r = 0.26, P < 0.05). In addition to manifesting the strongest simple correlation with insulin sensitivity, in stepwise multiple regression, subcutaneous abdominal fat retained significance after adjusting for visceral fat, while the converse was not found. Muscle attenuation contributed independent significance to multiple regression models of body composition and insulin sensitivity, and in analysis of obese subjects, muscle attenuation was the strongest single correlate of insulin resistance. In summary, as a component of central adiposity, subcutaneous abdominal fat has as strong an association with insulin resistance as visceral fat, and altered muscle composition, suggestive of increased fat content, is an important independent marker of insulin resistance in obesity.

Journal ArticleDOI
TL;DR: It is shown that during fetal development and childhood, mRNAs for insulin and other islet cell autoantigens are expressed at low levels in the human thymus, and this finding provides a plausible explanation for the dominant protective effect of class III VNTRs, and suggests that diabetes susceptibility and resistance associated with IDDM2 may derive from the VN TR influence on INS transcription in the thymos.
Abstract: Type 1, or insulin-dependent diabetes mellitus (IDDM) is an autoimmune disease associated with loss of tolerance to several pancreatic islet cell molecules, including insulin, glutamic acid decarboxylase (GAD), ICA69 and the tyrosine phosphatase IA-2 (refs 1-3). Among several predisposing loci, IDDM2 maps to the insulin gene (INS) VNTR (variable number of tandem repeats) minisatellite on chromosome 11p15 (refs 4-9). Allelic variation at this VNTR locus correlates with steady-state levels of INS mRNA in pancreas and transfected rodent cell lines, but it is difficult to reconcile the association of lower INS mRNA levels in the pancreas with class III VNTRs that are dominantly protective from IDDM. We show that during fetal development and childhood, mRNAs for insulin and other islet cell autoantigens (GAD, ICA69, IA-2) are expressed at low levels in the human thymus. Critically, we also detect proinsulin and insulin protein. VNTR alleles correlate with differential INS mRNA expression in the thymus where, in contrast to the pancreas, protective class III VNTRs are associated with higher steady-state levels of INS mRNA expression. This finding provides a plausible explanation for the dominant protective effect of class III VNTRs, and suggests that diabetes susceptibility and resistance associated with IDDM2 may derive from the VNTR influence on INS transcription in the thymus. Higher levels of (pro)insulin in the thymus may promote negative selection (deletion) of insulin-specific T-lymphocytes which play a critical role in the pathogenesis of type-1 diabetes.

Journal ArticleDOI
TL;DR: The aim of this study was to assess the frequency of pancreatic cancer and other tumors in patients with hereditary form of pancreatitis and to determine the natural history of hereditary pancreatitis.
Abstract: BACKGROUND Hereditary pancreatitis is an autosomal-dominant disease, with a variable expression and an estimated penetrance of 80%. The gene for this disease has recently been mapped to chromosome 7q35, and the defect is believed to be caused by a mutation in the cationic trypsinogen gene. Acute attacks of abdominal pain begin early in life and the disease often progresses to chronic pancreatitis. Although the risk of pancreatic cancer is thought to be increased in more common types of chronic pancreatitis, the frequency of pancreatic cancer in the inherited type of pancreatitis is uncertain. PURPOSE The aim of this study was to assess the frequency of pancreatic cancer and other tumors in patients with hereditary form of pancreatitis. METHODS To determine the natural history of hereditary pancreatitis, we invited all members of the American Pancreatic Association and the International Association of Pancreatology to participate in a longitudinal study of this rare form of pancreatitis. The initial criteria for patient eligibility were as follows: early age (< or = 30 years) at onset of symptoms, positive family history, and absence of other causes. From April 1995 through February 1996, 37 physicians from 10 countries contributed medical records of 246 (125 males and 121 females) patients thought to have hereditary pancreatitis as the most likely diagnosis. This group included 218 patients where the diagnosis appeared to be highly probable and 28 additional patients where the diagnosis of hereditary pancreatitis was less certain: 25 patients who had relatively late onset of disease and a positive family history and three patients with onset of disease before age 30 years but with an uncertain family history. We reviewed all causes of death and compared the observed to the expected frequency of cancer in this historical cohort of patients with hereditary pancreatitis. The strength of the association between pancreatitis and pancreatic cancer was estimated by the standardized incidence ratio (SIR), which is the ratio of observed pancreatic cancer cases in the cohort to the expected pancreatic cancers in the background population, adjusted for age, sex, and country. RESULTS The mean age (+/- standard deviation [SD]) at onset of symptoms of pancreatitis was 13.9 +/- 12.2 years. Compared with an expected number of 0.150, eight pancreatic adenocarcinomas developed (mean age +/- SD at diagnosis of pancreatic cancer: 56.9 +/- 11.2 years) during 8531 person-years of follow-up, yielding an SIR of 53 (95% confidence interval [CI] = 23-105). The frequency of other tumors was not increased: SIR = 0.7 (95% CI = 0.3-1.6). Eight of 20 reported deaths in the cohort were from pancreatic cancer. Thirty members of the cohort have already been tested for the defective hereditary pancreatitis gene: all 30 carry a mutated copy of the trypsinogen gene. The transmission pattern of hereditary pancreatitis was known for 168 of 238 patients without pancreatic cancer and six of eight with pancreatic cancer. Ninety-nine of the 238 patients without pancreatic cancer and six of the patients with pancreatic cancer inherited the disease through the paternal side of the family. The estimated cumulative risk of pancreatic cancer to age 70 years in patients with hereditary pancreatitis approaches 40%. For patients with a paternal inheritance pattern, the cumulative risk of pancreatic cancer is approximately 75%. CONCLUSIONS Patients with hereditary pancreatitis have a high risk of pancreatic cancer several decades after the initial onset of pancreatitis. A paternal inheritance pattern increases the probability of developing pancreatic cancer.

Journal ArticleDOI
TL;DR: The role played in acute inflammation by IL-1, TNF-alpha, IL-6,IL-11, Il-8 and other chemokines, G-CSF, and GM- CSF is described and features of the cell-surface receptors that mediate the inflammatory effects of the described cytokines are summarized.
Abstract: Inflammation is mediated by a variety of soluble factors, including a group of secreted polypeptides known as cytokines. Inflammatory cytokines can be divided into two groups: those involved in acute inflammation and those responsible for chronic inflammation. This review describes the role played in acute inflammation by IL-1, TNF-alpha, IL-6, IL-11, IL-8 and other chemokines, G-CSF, and GM-CSF. It also describes the involvement of cytokines in chronic inflammation. This latter group can be subdivided into cytokines mediating humoral responses such as IL-4, IL-5, IL-6, IL-7, and IL-13, and those mediating cellular responses such as IL-1, IL-2, IL-3, IL-4, IL-7, IL-9, IL-10, IL-12, interferons, transforming growth factor-beta, and tumor necrosis factor alpha and beta. Some cytokines, such as IL-1, significantly contribute to both acute and chronic inflammation. This review also summarizes features of the cell-surface receptors that mediate the inflammatory effects of the described cytokines.

Journal ArticleDOI
TL;DR: It is reported that NO prevents hepatocyte apoptosis initiated by the removal of growth factors or exposure to TNFα or anti-Fas antibody and by direct inhibition of caspase-3-like activity through proteinS-nitrosylation.

Journal ArticleDOI
TL;DR: It is shown that CRP was associated with incident events in the elderly, especially in those with subclinical disease at baseline, and in women but not men, the mean CRP level was higher for case subjects than for control subjects.
Abstract: Markers of inflammation, such as C-reactive protein (CRP), are related to risk of cardiovascular disease (CVD) events in those with angina, but little is known about individuals without prevalent clinical CVD. We performed a prospective, nested case-control study in the Cardiovascular Health Study (CHS; 5201 healthy elderly men and women). Case subjects (n = 146 men and women with incident CVD events including angina, myocardial infarction, and death) and control subjects (n = 146) were matched on the basis of sex and the presence or absence of significant subclinical CVD at baseline (average follow-up, 2.4 years). In women but not men, the mean CRP level was higher for case subjects than for control subjects (P < or = .05). In general, CRP was higher in those with subclinical disease. Most of the association of CRP with female case subjects versus control subjects was in the subgroup with subclinical disease; 3.33 versus 1.90 mg/L, P < .05, adjusted for age and time of follow-up. Case-control differences were greatest when the time between baseline and the CVD event was shortest. The strongest associations were with myocardial infarction, and there was an overall odds ratio for incident myocardial infarction for men and women with subclinical disease (upper quartile versus lower three quartiles) of 2.67 (confidence interval [CI] = 1.04 to 6.81), with the relationship being stronger in women (4.50 [CI = 0.97 to 20.8]) than in men (1.75 [CI = 0.51 to 5.98]). We performed a similar study in the Rural Health Promotion Project, in which mean values of CRP were higher for female case subjects than for female control subjects, but no differences were apparent for men. Comparing the upper quintile with the lower four, the odds ratio for CVD case subjects was 2.7 (CI = 1.10 to 6.60). In conclusion, CRP was associated with incident events in the elderly, especially in those with subclinical disease at baseline.

Journal ArticleDOI
TL;DR: It is proposed here that organizations will innovate in the presence of knowledge barriers when the burden of organizational learning is effectively lower, either because much of the required know-how already exists within the organization, or because such knowledge can be acquired more easily or more economically.
Abstract: The burden of organizational learning surrounding software process innovations SPIs-and complex organizational technologies in general-creates a "knowledge barrier" that inhibits diffusion. Attewell Attewell, P. 1992. Technology diffusion and organizational learning the case of business computing. Organ. Sci.31 1-19. has suggested that many organizations will defer adoption until knowledge barriers have been sufficiently lowered; however, this leaves open the question of which organizations should be more likely to innovate, even in face of high knowledge barriers. It is proposed here that organizations will innovate in the presence of knowledge barriers when the burden of organizational learning is effectively lower, either because much of the required know-how already exists within the organization, or because such knowledge can be acquired more easily or more economically. Specifically, it is hypothesized that organizations will have a greater propensity to initiate and sustain the assimilation of SPIs when they have a greater scale of activities over which learning costs can be spread learning-related scale, more extensive existing knowledge related to the focal innovation related knowledge, and a greater diversity of technical knowledge and activities diversity. An empirical study using data on the assimilation of object-oriented programming languages OOPLs by 608 information technology organizations strongly confirmed the importance of the three hypothesized factors in explaining the assimilation of OOPLs.

Journal ArticleDOI
TL;DR: In this article, the authors examined and illustrated how classroom-based factors can shape students' engagement with mathematical tasks that were set up to encourage high-level mathematical thinking and reasoning, and found that when students engagement is successfully maintained at a high level, a large number of support factors are present.
Abstract: In order to develop students' capacities to "do mathematics," classrooms must become environments in which students are able to engage actively in rich, worthwhile mathematical activity. This paper focuses on examining and illustrating how classroom-based factors can shape students' engagement with mathematical tasks that were set up to encourage high-level mathematical thinking and reasoning. The findings suggest that when students' engagement is successfully maintained at a high level, a large number of support factors are present. A decline in the level of students' engagement happens in different ways and for a variety of reasons. Four qualitative portraits provide concrete illustrations of the ways in which students' engagement in high-level cognitive processes was found to continue or decline during classroom work on tasks.

Journal ArticleDOI
TL;DR: In conclusion, the mouse overexpressing TNF-alpha recapitulated the phenotype of congestive heart failure and provides a novel model to elucidate the role of this cytokine in the development of congestives heart failure.
Abstract: The failing human heart expresses tumor necrosis factor-α (TNF-α). However, its pathophysiological significance is not clear. We previously reported that robust overexpression of TNF-α in the murine heart causes lethal myocarditis. In this study, we modified the transgene to reduce the production of TNF-α by preserving the destabilizing sequence in TNF-α cDNA. Expression was driven by the murine α-myosin heavy chain promoter. Use of this modified construct allowed us to establish a murine transgenic line (TG). TG offspring were examined at 6, 12, and 24 weeks. All showed a significantly higher heart weight–to–body weight ratio. Northern blot analysis confirmed the expression of transgene in the heart, and enzyme-linked immunosorbent assay demonstrated the presence of TNF-α protein. The TG heart demonstrated a mild, diffuse, lymphohistiocytic interstitial inflammatory infiltrate. Cardiomyocyte necrosis and apoptosis were present but not abundant. Magnetic resonance imaging showed that the TG heart...

Journal ArticleDOI
TL;DR: The Department of Veterans Affairs has successfully implemented a system for the prospective collection and comparative reporting of risk-adjusted postoperative mortality rates after major noncardiac operations and risk adjustment had an appreciable impact on the rank ordering of the hospitals and provided a means for monitoring and potentially improving the quality of surgical care.
Abstract: Background: The National Veterans Affairs Surgical Risk Study was designed to collect reliable, valid data on patient risk and outcomes for major surgery in the Veterans Health Administration and to report comparative risk-adjusted postoperative mortality rates for surgical services in Veterans Health Administration. Study Design: This cohort study was conducted in 44 Veterans Affairs Medical Centers. Included were 87,078 major noncardiac operations performed under general, spinal, or epidural anesthesia between October 1, 1991, and December 31, 1993. The main outcomes measure was all-cause mortality within 30 days after the index procedure. Multivariable logistic regression risk-adjustment models for all operations and for eight surgical subspecialties were developed. Risk-adjusted surgical mortality rates were expressed as observed-to-expected ratios and were compared with unadjusted 30-day postoperative mortality rates. Results: Patient risk factors predictive of postoperative mortality included serum albumin level, American Society of Anesthesia class, emergency operation, and 31 additional preoperative variables. Considerable variability in unadjusted mortality rates for all operations was observed across the 44 hospitals (1.2-5.4%). After risk adjustment, observed-to-expected ratios ranged from 0.49 to 1.53. Rank order correlation of the hospitals by unadjusted and risk-adjusted mortality rates for all operations was 0.64. Ninety-three percent of the hospitals changed rank after risk adjustment, 50% by more than 5 and 25% by more than 10. Conclusions: The Department of Veterans Affairs has successfully implemented a system for the prospective collection and comparative reporting of risk-adjusted postoperative mortality rates after major noncardiac operations. Risk adjustment had an appreciable impact on the rank ordering of the hospitals and provided a means for monitoring and potentially improving the quality of surgical care.

Journal ArticleDOI
TL;DR: This work presents a meta-anatomy of the adrenal gland and its role in the development and management of disease and urges further investigation into the role of “cell reprograming” and “reconcretization” in the course of disease progression.

Journal ArticleDOI
TL;DR: The data suggest a role of the right prefrontal cortex in suppressing responses to salient, but otherwise irrelevant events while the basal ganglia appear to be involved in executing these behavioral responses.
Abstract: Objective To examine the relation between specific frontostriatal structures (prefrontal cortex and basal ganglia) and response inhibition deficits observed in attention-deficit/hyperactivity disorder (ADHD). Method Children with ADHD and age-matched normal controls were scanned using magnetic resonance imaging (MRI) and tested on three response inhibition tasks. Behavioral performance was correlated with MRI-based anatomical measures of frontostriatal circuitry (prefrontal cortex and basal ganglia) implicated in ADHD. Results First, significant differences in performance by children with ADHD and normal volunteers were observed on all three response inhibition tasks. Second, performance on these tasks correlated only with those anatomical measures of frontostriatal circuitry observed to be abnormal in children with ADHD (e.g., the region of the prefrontal cortex, caudate, and globus pallidus, but not the putamen) in the authors' previous study. Third, significant correlations between task performance and anatomical measures of the prefrontal cortex and caudate nuclei were predominantly in the right hemisphere, supporting a role of right frontostriatal circuitry in response inhibition and ADHD. Conclusion The data suggest a role of the right prefrontal cortex in suppressing responses to salient, but otherwise irrelevant events while the basal ganglia appear to be involved in executing these behavioral responses.

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TL;DR: After considering other recognized risk factors including co‐infections, pregnant women infected with T. vaginalis at mid‐gestation were statistically significantly more likely to have a low birth weight infant, to deliver preterm, and to have an preterm low birth Weight infant.
Abstract: Background:Several studies have suggested that pregnant women infected withTrichomonas vaginalismay be at increased risk of an adverse outcome.Goal:To evaluate prospectively the association betweenT. vaginalisand risk of adverse pregnancy outcome in a large cohort of ethnically diverse women.Study D