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Showing papers by "Virginia Commonwealth University published in 2001"


Journal ArticleDOI
TL;DR: The data suggest that the COMT Val allele, because it increases prefrontal dopamine catabolism, impairs prefrontal cognition and physiology, and by this mechanism slightly increases risk for schizophrenia.
Abstract: Abnormalities of prefrontal cortical function are prominent features of schizophrenia and have been associated with genetic risk, suggesting that susceptibility genes for schizophrenia may impact on the molecular mechanisms of prefrontal function. A potential susceptibility mechanism involves regulation of prefrontal dopamine, which modulates the response of prefrontal neurons during working memory. We examined the relationship of a common functional polymorphism (Val(108/158) Met) in the catechol-O-methyltransferase (COMT) gene, which accounts for a 4-fold variation in enzyme activity and dopamine catabolism, with both prefrontally mediated cognition and prefrontal cortical physiology. In 175 patients with schizophrenia, 219 unaffected siblings, and 55 controls, COMT genotype was related in allele dosage fashion to performance on the Wisconsin Card Sorting Test of executive cognition and explained 4% of variance (P = 0.001) in frequency of perseverative errors. Consistent with other evidence that dopamine enhances prefrontal neuronal function, the load of the low-activity Met allele predicted enhanced cognitive performance. We then examined the effect of COMT genotype on prefrontal physiology during a working memory task in three separate subgroups (n = 11-16) assayed with functional MRI. Met allele load consistently predicted a more efficient physiological response in prefrontal cortex. Finally, in a family-based association analysis of 104 trios, we found a significant increase in transmission of the Val allele to the schizophrenic offspring. These data suggest that the COMT Val allele, because it increases prefrontal dopamine catabolism, impairs prefrontal cognition and physiology, and by this mechanism slightly increases risk for schizophrenia.

2,402 citations


Journal ArticleDOI
TL;DR: Data indicate that peripheral insulin resistance, increased fatty acid beta oxidation, and hepatic oxidative stress are present in both fatty liver and NASH, but NASH alone is associated with mitochondrial structural defects.

1,938 citations


Journal ArticleDOI
12 Apr 2001-Nature
TL;DR: It is shown that following temporary food restriction, CB1 receptor knockout mice eat less than their wild-type littermates, and the CB1 antagonist SR141716A reduces food intake in wild- type but not knockout mice, which indicates that endocannabinoids in the hypothalamus may tonically activate CB1 receptors to maintain food intake and form part of the neural circuitry regulated by leptin.
Abstract: Leptin is the primary signal through which the hypothalamus senses nutritional state and modulates food intake and energy balance1. Leptin reduces food intake by upregulating anorexigenic (appetite-reducing) neuropeptides, such as α-melanocyte-stimulating hormone2,3, and downregulating orexigenic (appetite-stimulating) factors, primarily neuropeptide Y4. Genetic defects in anorexigenic signalling, such as mutations in the melanocortin-4 (ref. 5) or leptin receptors6, cause obesity. However, alternative orexigenic pathways maintain food intake in mice deficient in neuropeptide Y7. CB1 cannabinoid receptors8 and the endocannabinoids anandamide and 2-arachidonoyl glycerol are present in the hypothalamus9, and marijuana10 and anandamide11,12 stimulate food intake. Here we show that following temporary food restriction, CB1 receptor knockout mice eat less than their wild-type littermates, and the CB1 antagonist SR141716A reduces food intake in wild-type but not knockout mice. Furthermore, defective leptin signalling is associated with elevated hypothalamic, but not cerebellar, levels of endocannabinoids in obese db/db and ob/ob mice and Zucker rats. Acute leptin treatment of normal rats and ob/ob mice reduces anandamide and 2-arachidonoyl glycerol in the hypothalamus. These findings indicate that endocannabinoids in the hypothalamus may tonically activate CB1 receptors to maintain food intake and form part of the neural circuitry regulated by leptin.

1,540 citations


Journal ArticleDOI
TL;DR: Treatment with hypothermia, with the body temperature reaching 33 degrees C within eight hours after injury, is not effective in improving outcomes in patients with severe brain injury.
Abstract: Background Induction of hypothermia in patients with brain injury was shown to improve outcomes in small clinical studies, but the results were not definitive. To study this issue, we conducted a multicenter trial comparing the effects of hypothermia with those of normothermia in patients with acute brain injury. Methods The study subjects were 392 patients 16 to 65 years of age with coma after sustaining closed head injuries who were randomly assigned to be treated with hypothermia (body temperature, 33°C), which was initiated within 6 hours after injury and maintained for 48 hours by means of surface cooling, or normothermia. All patients otherwise received standard treatment. The primary outcome measure was functional status six months after the injury. Results The mean age of the patients and the type and severity of injury in the two treatment groups were similar. The mean (±SD) time from injury to randomization was 4.3±1.1 hours in the hypothermia group and 4.1±1.2 hours in the normothermia group, a...

1,305 citations


Journal ArticleDOI
TL;DR: This paper assessed transactional and charismatic CEO leadership as predictors of financial performance using data from 48 Fortune 500 firms and found that the relationship between transactional leadership and financial performance was positively correlated.
Abstract: Using data from 48 Fortune 500 firms, the authors assessed transactional and charismatic CEO leadership as predictors of financial performance. The authors also hypothesized that the relationship b...

1,159 citations


Journal ArticleDOI
TL;DR: Criteria to delineate categories of mastocytosis together with an updated consensus classification system are proposed and proposed, based on typical clinical and histological skin lesions and absence of definitive signs (criteria) of systemic involvement.

996 citations


BookDOI
27 Sep 2001
TL;DR: In this paper, the authors present a detailed overview of the history of the field of flow simulation for MEMS and discuss the current state-of-the-art in this field.
Abstract: Part I: Background and Fundamentals Introduction, Mohamed Gad-el-Hak, University of Notre Dame Scaling of Micromechanical Devices, William Trimmer, Standard MEMS, Inc., and Robert H. Stroud, Aerospace Corporation Mechanical Properties of MEMS Materials, William N. Sharpe, Jr., Johns Hopkins University Flow Physics, Mohamed Gad-el-Hak, University of Notre Dame Integrated Simulation for MEMS: Coupling Flow-Structure-Thermal-Electrical Domains, Robert M. Kirby and George Em Karniadakis, Brown University, and Oleg Mikulchenko and Kartikeya Mayaram, Oregon State University Liquid Flows in Microchannels, Kendra V. Sharp and Ronald J. Adrian, University of Illinois at Urbana-Champaign, Juan G. Santiago and Joshua I. Molho, Stanford University Burnett Simulations of Flows in Microdevices, Ramesh K. Agarwal and Keon-Young Yun, Wichita State University Molecular-Based Microfluidic Simulation Models, Ali Beskok, Texas A&M University Lubrication in MEMS, Kenneth S. Breuer, Brown University Physics of Thin Liquid Films, Alexander Oron, Technion, Israel Bubble/Drop Transport in Microchannels, Hsueh-Chia Chang, University of Notre Dame Fundamentals of Control Theory, Bill Goodwine, University of Notre Dame Model-Based Flow Control for Distributed Architectures, Thomas R. Bewley, University of California, San Diego Soft Computing in Control, Mihir Sen and Bill Goodwine, University of Notre Dame Part II: Design and Fabrication Materials for Microelectromechanical Systems Christian A. Zorman and Mehran Mehregany, Case Western Reserve University MEMS Fabrication, Marc J. Madou, Nanogen, Inc. LIGA and Other Replication Techniques, Marc J. Madou, Nanogen, Inc. X-Ray-Based Fabrication, Todd Christenson, Sandia National Laboratories Electrochemical Fabrication (EFAB), Adam L. Cohen, MEMGen Corporation Fabrication and Characterization of Single-Crystal Silicon Carbide MEMS, Robert S. Okojie, NASA Glenn Research Center Deep Reactive Ion Etching for Bulk Micromachining of Silicon Carbide, Glenn M. Beheim, NASA Glenn Research Center Microfabricated Chemical Sensors for Aerospace Applications, Gary W. Hunter, NASA Glenn Research Center, Chung-Chiun Liu, Case Western Reserve University, and Darby B. Makel, Makel Engineering, Inc. Packaging of Harsh-Environment MEMS Devices, Liang-Yu Chen and Jih-Fen Lei, NASA Glenn Research Center Part III: Applications of MEMS Inertial Sensors, Paul L. Bergstrom, Michigan Technological University, and Gary G. Li, OMM, Inc. Micromachined Pressure Sensors, Jae-Sung Park, Chester Wilson, and Yogesh B. Gianchandani, University of Wisconsin-Madison Sensors and Actuators for Turbulent Flows. Lennart Loefdahl, Chalmers University of Technology, and Mohamed Gad-el-Hak, University of Notre Dame Surface-Micromachined Mechanisms, Andrew D. Oliver and David W. Plummer, Sandia National Laboratories Microrobotics Thorbjoern Ebefors and Goeran Stemme, Royal Institute of Technology, Sweden Microscale Vacuum Pumps, E. Phillip Muntz, University of Southern California, and Stephen E. Vargo, SiWave, Inc. Microdroplet Generators. Fan-Gang Tseng, National Tsing Hua University, Taiwan Micro Heat Pipes and Micro Heat Spreaders, G. P. "Bud" Peterson, Rensselaer Polytechnic Institute Microchannel Heat Sinks, Yitshak Zohar, Hong Kong University of Science and Technology Flow Control, Mohamed Gad-el-Hak, University of Notre Dame) Part IV: The Future Reactive Control for Skin-Friction Reduction, Haecheon Choi, Seoul National University Towards MEMS Autonomous Control of Free-Shear Flows, Ahmed Naguib, Michigan State University Fabrication Technologies for Nanoelectromechanical Systems, Gary H. Bernstein, Holly V. Goodson, and Gregory L. Snider, University of Notre Dame Index

951 citations


Journal ArticleDOI
TL;DR: Results are consistent with obesity's being an important contributing factor to the earlier onset of puberty in girls, and a multivariate analysis confirms that obesity (as measured by BMI) is significantly associated with early puberty in white girls and is associated withEarly puberty in black girls as well, but to a lesser extent.
Abstract: Objective. A recent study conducted by the Pediatric Research in Office Settings network provided evidence that girls in the United States, especially black girls, are starting puberty at a younger age than earlier studies had found, but the reasons for this are not known. Because nutritional status is known to affect timing of puberty and there is a clear trend for increasing obesity in US children during the past 25 years, it was hypothesized that the earlier onset of puberty could be attributable to the increasing prevalence of obesity in young girls. Therefore, the objective of this study was to reexamine the Pediatric Research in Office Settings puberty data by comparing the age-normalized body mass index (BMI-ZS; a crude estimate of fatness) of girls who had breast or pubic hair development versus those who were still prepubertal, looking at the effects of age and race. Results. For white girls, the BMI-ZS were markedly higher in pubertal versus prepubertal 6- to 9-year-olds; for black girls, a smaller difference was seen, which was significant only for 9-year-olds. Higher BMI-ZS also were found in girls who had pubic hair but no breast development versus girls who had neither pubic hair nor breast development. A multivariate analysis confirms that obesity (as measured by BMI) is significantly associated with early puberty in white girls and is associated with early puberty in black girls as well, but to a lesser extent. Conclusions. The results are consistent with obesity9s being an important contributing factor to the earlier onset of puberty in girls. Factors other than obesity, however, perhaps genetic and/or environmental ones, are needed to explain the higher prevalence of early puberty in black versus white girls.

698 citations



Journal ArticleDOI
TL;DR: The concept and feasibility of MAX-T and the capability of the treatment machine to deliver such a treatment were investigated by performing measurements for uniform and IMRT fields using a mechanical sinusoidal oscillator to simulate target motion.
Abstract: Intrafraction motion caused by breathing requires increased treatment margins for chest and abdominal radiotherapy and may lead to `motion artefacts' in dose distributions during intensity modulated radiotherapy (IMRT). Technologies such as gated radiotherapy may significantly increase the treatment time, while breath-hold techniques may be poorly tolerated by pulmonarily compromised patients. A solution that allows reduced margins and dose distribution artefacts, without compromising delivery time, is to synchronously follow the target motion by adapting the x-ray beam using a dynamic multileaf collimator (MLC), i.e. motion adaptive x-ray therapy, or MAX-T for short. Though the target is moving with time, in the MAX-T beam view the target is static. The MAX-T method superimposes the target motion due to respiration onto the beam originally planned for delivery. Thus during beam delivery the beam is dynamically changing position with respect to the isocentre using a dynamic MLC, the leaf positions of which are dependent upon the target position. Synchronization of the MLC motion and target motion occurs using respiration gated radiotherapy equipment. The concept and feasibility of MAX-T and the capability of the treatment machine to deliver such a treatment were investigated by performing measurements for uniform and IMRT fields using a mechanical sinusoidal oscillator to simulate target motion. Target dose measurements obtained using MAX-T for a moving target were found to be equivalent to those delivered to a static target by a static beam.

561 citations


Journal ArticleDOI
TL;DR: In this paper, the authors developed and evaluated a moral distress scale from 1994 to 1997, which consists of 32 items in a 7-point Likert format; a higher score reflects a higher level of normal distress.
Abstract: Development and evaluation of a moral distress scale Aim of the study: This methodological research developed and evaluated the moral distress scale from 1994 to 1997. Background/Rationale: Although nurses confront moral questions in their practice daily, few instruments are available to measure moral concepts. The methodological design used a convenience sample consisted of 214 nurses from several Unites States hospitals. The framework guiding the development of the moral distress scale (MDS) included Jameton’s conceptualization of moral distress, House and Rizzo’s role conflict theory, and Rokeach’s value theory. Items for the MDS were developed from research on the moral problems that nurses confront in hospital practice. The MDS consists of 32 items in a 7-point Likert format; a higher score reflects a higher level of normal distress. Results: Mean scores on each item ranged from 3·9 to 5·5, indicating moderately high levels of moral distress. The item with the highest mean score (M=5·47) was working where the number of staff is so low that care is inadequate. Factor analysis yielded three factors: individual responsibility, not in the patient’s best interest, and deception. No demographic or professional variables were related to moral distress. Fifteen percent of the nurses had resigned a position in the past because of moral distress. Conclusions: The results support the reliability and validity of the MDS.

Journal ArticleDOI
26 Sep 2001-JAMA
TL;DR: To assess the current validity of 17 clinical practice guidelines published by the US Agency for Healthcare Research and Quality (AHRQ) that are still in circulation, and to estimate how quickly guidelines become obsolete, criteria for defining when a guideline needs updating are developed.
Abstract: ContextPractice guidelines need to be up-to-date to be useful to clinicians. No published methods are available for assessing whether existing practice guidelines are still valid, nor does any empirical information exist regarding how often such assessments need to be made.ObjectivesTo assess the current validity of 17 clinical practice guidelines published by the US Agency for Healthcare Research and Quality (AHRQ) that are still in circulation, and to use this information to estimate how quickly guidelines become obsolete.Design, Setting, and ParticipantsWe developed criteria for defining when a guideline needs updating, mailed surveys to members of the original AHRQ guideline panels (n = 170; response rate, 71%), and searched the literature for evidence through March 2000 (n = 6994 titles yielding 173 articles plus 159 new guidelines on the same topics).Main Outcome MeasuresIdentification of new evidence calling for a major, minor, or no update of the 17 guidelines; survival analysis of the rate at which guidelines became outdated.ResultsFor 7 guidelines, new evidence and expert judgment indicated that a major update is required; 6 were found to be in need of a minor update; 3 were judged as still valid; and for 1 guideline, we could reach no conclusion. Survival analysis indicated that about half the guidelines were outdated in 5.8 years (95% confidence interval [CI], 5.0-6.6 years). The point at which no more than 90% of the guidelines were still valid was 3.6 years (95% CI, 2.6-4.6 years).ConclusionsMore than three quarters of the AHRQ guidelines need updating. As a general rule, guidelines should be reassessed for validity every 3 years.

Journal ArticleDOI
TL;DR: The results suggest that the greater prevalence of major depression in women versus men is due neither to differences in the rates of reported stressful life events nor to differential sensitivity to their pathogenic effect.
Abstract: OBJECTIVE: Women are at greater risk for major depression than men. The authors sought to determine whether the gender difference in prevalence for major depression was due to more frequent exposure to stressful life events and/or greater sensitivity to their depressogenic effects. METHOD: Male-male, female-female, and male-female twin pairs from a popu-lation-based registry were personally interviewed. Each interview assessed the occurrence, to the nearest month, of 18 personal and social network classes of stressful life events and episode onsets of major depression. Standard logistic regression analyses were conducted for the same-sex pairs, and each female twin in the opposite-sex pairs was compared with her male co-twin by using conditional logistic regression. RESULTS: Women consistently reported higher rates of housing problems, loss of confidant, crises and problems getting along with individuals in their proximal network, and illness of individuals within their distal network. In both the same-se...

Journal Article
TL;DR: Measurements of radiation-induced mitogen-activated protein kinase activity indicate that this sensing/amplification mechanism is necessary for activation of some cytoplasmic signaling pathways by low doses of radiation.
Abstract: Transient generation of reactive oxygen or nitrogen (ROS/RNS), detected with dihydrodichlorofluoroscein by fluorescence microscopy, occurs within minutes of exposing cells to ionizing radiation. In the 1-10 Gy dose range, the amount of ROS/RNS produced/cell is constant, but the percentage of producing cells increases with dose (20 to 80%). Reversible depolarization of the mitochondrial membrane potential () and decrease in fluorescence of a mitochondria-entrapped dye, calcein, are observed coincidentally. Radiation-induced ROS/RNS, depolarization, and calcein fluorescence decrease are inhibited by the mitochondrial permeability transition inhibitor, cyclosporin A, but not the structural analogue, cyclosporin H. Radiation-stimulated ROS/RNS is also inhibited by overexpressing the Ca(2+)-binding protein, calbindin 28K, or treating cells with an intracellular Ca(2+) chelator. Radiation-induced ROS/RNS is observed in several cell types with the exception of rho(o) cells deficient in mitochondrial electron transport. rho(o) cells show neither radiation-induced ROS/RNS production nor depolarization. We propose that radiation damage in a few mitochondria is transmitted via a reversible, Ca(2+)-dependent mitochondrial permeability transition to adjacent mitochondria with resulting enhanced ROS/RNS generation. Measurements of radiation-induced mitogen-activated protein kinase activity indicate that this sensing/amplification mechanism is necessary for activation of some cytoplasmic signaling pathways by low doses of radiation.

Journal ArticleDOI
TL;DR: The association between stressful life events and the onset of major depression decreases as the number of previous depressive episodes increases, and genetic risk factors for depression produce a "prekindling" effect rather than increase the speed of kindling.
Abstract: OBJECTIVE: The association between stressful life events and the onset of major depression decreases as the number of previous depressive episodes increases. How do genetic risk factors for major depression impact on this “kindling” phenomenon? In particular, do those at high genetic risk exhibit an increase in the speed of kindling, or are they “prekindled”? METHOD: Using discrete-time survival analysis, the authors examined the interaction between genetic risk, number of previous depressive episodes, and life event exposure in the prediction of episodes of major depression in female-female twin pairs from a population-based registry. The twins were interviewed four times over a 9-year period, producing 92,521 person-months of exposure. RESULTS: The decline in the association between stressful life events and risk for major depression as the number of previous depressive episodes increased was strongest in those at low genetic risk and was weak to absent in those at high genetic risk. In the absence of p...

Journal ArticleDOI
TL;DR: In this article, the ability to control the fiber diameter of poly(glycolic acid) as a function of solution concentration and fiber orientation was demonstrated, as well as a correlation between the fiber orientation, elastic modulu, and strain to failure of PGA in uniaxial model.
Abstract: Poly(glycolic acid) (PGA) has long been a popular polymer in the tissue engineering field. PGA possesses many favorable properties such as biocompatibility, bioabsorbability, and tensile strength. The traditional fiber formation techniques of melt extrusion and cold-drawing are generally limited to fibers of 10–12 μm in diameter. Electrostatic spinning, or electrospinning, is an attractive approach for the production of much smaller diameter fibers which are of interest as tissue engineering scaffolds. We demonstrate the ability to control the fiber diameter of PGA as a function of solution concentration and fiber orientation, as well as show a correlation between the fiber orientation, elastic modulu, and strain to failure of PGA in a uniaxial model.

Journal ArticleDOI
TL;DR: Hredity contributes to development of IBS, but social learning (what an individual learns from those in his or her environment) has an equal or greater influence.

Journal ArticleDOI
TL;DR: This article reviewed the history of such tests and presented the results of a meta-analysis on criterion-related and construct validity, concluding that situational judgment tests typically evidence relationships with cognitive ability, particularly in terms of recent investigations into tacit knowledge.
Abstract: Although situational judgment tests have a long history in the psychological assessment literature and continue to be frequently used in employment contexts, there has been virtually no summarization of this literature. The purpose of this article is to review the history of such tests and present the results of a meta-analysis on criterion-related and construct validity. On the basis of 102 coefficients and 10,640 people, situational judgment tests showed useful levels of validity (rho = .34) that were generalizable. A review of 79 correlations between situational judgment tests and general cognitive ability involving 16,984 people indicated that situational judgment tests typically evidence relationships with cognitive ability (rho = .46). On the basis of the literature review and meta-analytic findings, implications for the continued use of situational judgment tests are discussed, particularly in terms of recent investigations into tacit knowledge.

Journal ArticleDOI
TL;DR: The Transgression Narrative Test of Forgivingness (TNTF) as mentioned in this paper is a five-item scenario-based scale, which measures the disposition to forgive interpersonal transgressions over time and across situations.
Abstract: Forgivingness is the disposition to forgive interpersonal transgressions over time and across situations. There is currently no acceptable measure of forgivingness for use in testing theoretical propositions. The authors describe a five-item scenario-based scale, the Transgression Narrative Test of Forgivingness (TNTF). In five studies examining 518 university students from three disparate universities, the authors assess the item and full-scale functioning of the TNTF and its concurrent and 8- week predictive validity relative to trait anger, rumination, neuroticism, agreeableness, and hostility. Test-retest reliability and stability of item locations were both good. Norms are presented by gender, ethnicity, and religious activity. The TNTF is a brief measure of forgivingness that is not theory dependent and is therefore useful in basic and intervention research from a variety of theoretical perspectives.

Journal ArticleDOI
TL;DR: It is shown that rats with biliary cirrhosis have low blood pressure, which is elevated by the CB1 receptor antagonist SR141716A, and this results implicate anandamide and vascular CB1 receptors in the vasodilated state in advanced Cirrhosis and indicate a novel approach for its management.
Abstract: Advanced cirrhosis is associated with generalized vasodilation of unknown origin, which contributes to mortality. Cirrhotic patients are endotoxemic, and activation of vascular cannabinoid CB1 receptors has been implicated in endotoxin-induced hypotension. Here we show that rats with biliary cirrhosis have low blood pressure, which is elevated by the CB1 receptor antagonist SR141716A. The low blood pressure of rats with CCl4-induced cirrhosis was similarly reversed by SR141716A, which also reduced the elevated mesenteric blood flow and portal pressure. Monocytes from cirrhotic but not control patients or rats elicited SR141716A-sensitive hypotension in normal recipient rats and showed significantly elevated levels of anandamide. Compared with non-cirrhotic controls, in cirrhotic human livers there was a three-fold increase in CB1 receptors on isolated vascular endothelial cells. These results implicate anandamide and vascular CB1 receptors in the vasodilated state in advanced cirrhosis and indicate a novel approach for its management.

Journal ArticleDOI
TL;DR: It is clearly demonstrates that HDAC1 is overexpressed in GC and probably plays a significant role in gastric carcinogenesis.
Abstract: Although histone deacetylases (HDACs) appear to play a crucial role in carcinogenesis, the expression status of HDACs in primary human cancer tissues has not yet been reported. In this study, we investigated the expression level of HDAC1 in 25 paired primary human gastric cancer (GC) tissues and corresponding normal tissues through semi-quantitative RT-PCR and immunoblot analysis. The HDAC1 expression pattern was also topologically examined through immunohistochemistry. Overexpression of HDAC1 mRNA was detected in 68% of GC tissues (17 of 25), and the relative density of HDAC1 mRNA in GC tissue was increased 1.8-fold versus the normal counterpart (P < 0.01). Elevated expression of HDAC1 protein was also detected in 61% of GC samples (11 of 18), which also showed an increased mRNA level of HDAC. Immunohistochemically, overexpression of HDAC1 was predominantly localized in the nuclei of most neoplastic cells, including embolic tumor cells, whereas normal glandular epithelial cells revealed only weak HDAC1 expression that was focal in distribution. Thus, the present study clearly demonstrates that HDAC1 is overexpressed in GC and probably plays a significant role in gastric carcinogenesis.

Journal ArticleDOI
TL;DR: This paper examined the relationship between organizational ethical culture in two large international CPA firms, auditors' personal values and the ethical orientation that those values dictate, and judgments in ethical dilemmas typical of those that accountants face.
Abstract: This paper examines the relationship between organizational ethical culture in two large international CPA firms, auditors' personal values and the ethical orientation that those values dictate, and judgments in ethical dilemmas typical of those that accountants face. Using an experimental task consisting of multiple judgments designed to vary in "moral intensity" (Jones, 1991), and unique as well as tried-and-true approaches to variable measurements, this study examined the judgments of more than three hundred participants in our study. ANCOVA and path analysis results indicate that: (1) Ethical judgments in situations of high moral intensity are affected by personal values and by environmental variables, such as the professional code of conduct (direct and indirect effects) and previous ethics instruction (direct effect only). (2) Corporate ethical culture, and a relatively strong firm rules-orientation, affect auditors' idealism but not relativism, and therefore indirectly affect ethical judgments. Jones' (1991) moral intensity argument is supported: differences in the characteristics of specific judgment tasks apparently result in different decision processes.

Journal ArticleDOI
TL;DR: Two highly homologous genes, located in a head-to-head configuration on chromosome 2p21, are involved as causes of sitosterolemia, and studies indicate that both sterolin-1 and sterol-2 are indispensable for the regulation of sterol absorption and excretion.
Abstract: Sitosterolemia is a rare autosomal recessive disorder characterized by (a) intestinal hyperabsorption of all sterols, including cholesterol and plant and shellfish sterols, and (b) impaired ability to excrete sterols into bile. Patients with this disease have expanded body pools of cholesterol and very elevated plasma plant-sterol species and frequently develop tendon and tuberous xanthomas, accelerated atherosclerosis, and premature coronary artery disease. In previous studies, we have mapped the STSL locus to human chromosome 2p21. Recently, we reported that a novel member of the ABC-transporter family, named "sterolin-1" and encoded by ABCG5, is mutated in 9 unrelated families with sitosterolemia; in the remaining 25 families, no mutations in sterolin-1 could be identified. We identified another ABC transporter, located <400 bp upstream of sterolin-1, in the opposite orientation. Mutational analyses revealed that this highly homologous protein, termed "sterolin-2" and encoded by ABCG8, is mutated in the remaining pedigrees. Thus, two highly homologous genes, located in a head-to-head configuration on chromosome 2p21, are involved as causes of sitosterolemia. These studies indicate that both sterolin-1 and sterolin-2 are indispensable for the regulation of sterol absorption and excretion. Identification of sterolin-1 and sterolin-2 as critical players in the regulation of dietary-sterol absorption and excretion identifies a new pathway of sterol transport.

Journal ArticleDOI
TL;DR: The use of interphase fluorescence in situ hybridization (FISH) and pulsed-field gel electrophoresis (PFGE) is reported to identify a genomic polymorphism in families with WBS, consisting of an inversion of the WBS region, suggesting the presence of a newly identified genomic variant within the population that may be associated with the disease.
Abstract: Williams-Beuren syndrome (WBS) is most often caused by hemizygous deletion of a 1.5-Mb interval encompassing at least 17 genes at 7q11.23 (refs. 1,2). As with many other haploinsufficiency diseases, the mechanism underlying the WBS deletion is thought to be unequal meiotic recombination, probably mediated by the highly homologous DNA that flanks the commonly deleted region3. Here, we report the use of interphase fluorescence in situ hybridization (FISH) and pulsed-field gel electrophoresis (PFGE) to identify a genomic polymorphism in families with WBS, consisting of an inversion of the WBS region. We have observed that the inversion is hemizygous in 3 of 11 (27%) atypical affected individuals who show a subset of the WBS phenotypic spectrum but do not carry the typical WBS microdeletion. Two of these individuals also have a parent who carries the inversion. In addition, in 4 of 12 (33%) families with a proband carrying the WBS deletion, we observed the inversion exclusively in the parent transmitting the disease-related chromosome. These results suggest the presence of a newly identified genomic variant within the population that may be associated with the disease. It may result in predisposition to primarily WBS-causing microdeletions, but may also cause translocations and inversions.

Journal ArticleDOI
TL;DR: A method has been developed to provide the data necessary to make decisions as to the CTV to PTV margins to apply to a gated treatment plan and account for any difference in phase between the internal tumor motion and external marker motion.
Abstract: Respiration-gated radiotherapy for tumor sites affected by respiratory motion will potentially improve radiotherapy outcomes by allowing reduced treatment margins leading to decreased complication rates and/or increased tumorcontrol. Furthermore, for intensity-modulated radiotherapy(IMRT), respiratory gating will minimize the hot and cold spot artifacts in dose distributions that may occur as a result of interplay between respiratory motion and leaf motion. Most implementations of respiration gating rely on the real time knowledge of the relative position of the internal anatomy being treated with respect to that of an external marker. A method to determine the amplitude of motion and account for any difference in phase between the internal tumor motion and external marker motion has been developed. Treating patients using gating requires several clinical decisions, such as whether to gate during inhale or exhale, whether to use phase or amplitude tracking of the respiratory signal, and by how much the intrafraction tumor motion can be decreased at the cost of increased delivery time. These parameters may change from patient to patient. A method has been developed to provide the data necessary to make decisions as to the CTV to PTV margins to apply to a gated treatment plan.

Journal ArticleDOI
TL;DR: In this paper, 39 participants were classified as either happy (19 male, 20 female) or unhappy (n = 20) with a relationship and salivary cortisol was measured.
Abstract: In all, 39 participants (19 male, 20 female) were classified as either happy (n = 19) or unhappy (n = 20) with a relationship. Baseline salivary cortisol was measured. Participants imagined (for a 5-min duration) scenes typical of their relationship, and salivary cortisol was measured again. Participants in unhappy relationships had higher cortisol reactivity (indicating higher stress) following the imagery. Cortisol reactivity was predicted by relationship variables (high love and liking for the partner, high happiness with the relationship) and personality variables (high forgivingness, low trait anger). Personality had an indirect effect through the relationship variables. Physical health was predicted by personality variables. Mental health was predicted by both personality and relationship variables. Implications of these results for counseling health psychology are discussed.

Journal ArticleDOI
TL;DR: There is an environmentally mediated effect of life events on depression/anxiety, and genetic factors play a significant role in individual differences in susceptibility to these environmentally mediated risks.
Abstract: Background There is huge individual variation in people's response to negative life events. Aims To test the hypothesis that genetic factors moderate susceptibility to the environmentally mediated risks associated with negative life events. Method The Virginia Twin Study of Adolescent Behavioral Development (VTSABD) was used to study the effects of independent life events (assessed from maternal interview) on depression/anxiety (assessed from child interview) in 184 same-gender female twin pairs, aged 14-17 years, measured on two occasions. Results There was no genetic effect on the independent negative life events studied. A significant gene—environment interaction was found using structural equation modelling. There was no effect of independent life events on adolescents' depression in the absence of parental emotional disorder, but a significant effect in its presence. Conclusions There is an environmentally mediated effect of life events on depression/anxiety. Genetic factors play a significant role in individual differences in susceptibility to these environmentally mediated risks.

Journal ArticleDOI
TL;DR: In this article, the authors summarize current practice concerning situational judgment tests in personnel selection and discuss the legal aspect of situational judgment measures, as well as meta-analytic evidence concerning the construct validity of such tests.
Abstract: In this article, we seek to summarize current practice concerning situational judgment tests in personnel selection. We begin by describing the manner in which situational judgment tests are developed and examining the diverse ways in which situational items are presented and scored. We then offer speculation concerning constructs assessed by situational judgment tests as well as discuss the legal aspect of situational judgment measures. We also review meta-analytic evidence concerning the construct validity of situational judgment tests and offer several new meta-analytic findings. Situational judgment tests are shown to be typically correlated moderately with general mental ability. Their primary personality correlates are emotional stability, conscientiousness, and agreeableness. Situational test scores also tend to increase with increasing years of job experience. The article concludes with a list of areas that need addressed in future research.

Journal ArticleDOI
TL;DR: This article reviewed the literature and examined the effect of increased opportunities to respond to academic requests (OTR) on academic and behavioral outcomes of students with emotional and behavioral disorders (EBD).
Abstract: The purpose of this article is to review the literature and examine the effect of increased opportunities to respond to academic requests (OTR) on academic and behavioral outcomes of students with emotional and behavioral disorders (EBD). The studies reviewed suggest that increased rates of OTR result in higher task engagement and academic achievement and in lower rates of inappropriate classroom behaviors. However, descriptive research in classrooms for students with EBD suggests that teachers rarely provide adequate OTR. Implications of these findings and future research needs are discussed.

Journal ArticleDOI
TL;DR: The surgical method of colon management after resection for penetrating trauma does not affect the incidence of abdominal complications, irrespective of associated risk factors, and primary anastomosis should be considered in all such patients.
Abstract: BackgroundThe management of colon injuries that require resection is an unresolved issue because the existing practices are derived mainly from class III evidence. Because of the inability of any single trauma center to accumulate enough cases for meaningful statistical analysis, a multicenter prosp