Showing papers by "University of Illinois at Chicago published in 2000"
TL;DR: Algorithm sensitivities and specificities for autism and PD DNOS relative to nonspectrum disorders were excellent, with moderate differentiation of autism from PDDNOS.
Abstract: The Autism Diagnostic Observation Schedule-Generic (ADOS-G) is a semistructured, standardized assessment of social interaction, communication, play, and imaginative use of materials for individuals suspected of having autism spectrum disorders. The observational schedule consists of four 30-minute modules, each designed to be administered to different individuals according to their level of expressive language. Psychometric data are presented for 223 children and adults with Autistic Disorder (autism), Pervasive Developmental Disorder Not Otherwise Specified (PDDNOS) or nonspectrum diagnoses. Within each module, diagnostic groups were equivalent on expressive language level. Results indicate substantial interrater and test-retest reliability for individual items, excellent interrater reliability within domains and excellent internal consistency. Comparisons of means indicated consistent differentiation of autism and PDDNOS from nonspectrum individuals, with some, but less consistent, differentiation of autism from PDDNOS. A priori operationalization of DSM-IV/ICD-10 criteria, factor analyses, and ROC curves were used to generate diagnostic algorithms with thresholds set for autism and broader autism spectrum/PDD. Algorithm sensitivities and specificities for autism and PDDNOS relative to nonspectrum disorders were excellent, with moderate differentiation of autism from PDDNOS.
7,012 citations
TL;DR: In this study, celecoxib, at dosages greater than those indicated clinically, was associated with a lower incidence of symptomatic ulcers and ulcer complications combined, as well as other clinically important toxic effects, compared with NSAIDs at standard dosages.
Abstract: ContextConventional nonsteroidal anti-inflammatory drugs (NSAIDs) are associated
with a spectrum of toxic effects, notably gastrointestinal (GI) effects, because
of inhibition of cyclooxygenase (COX)-1. Whether COX-2–specific inhibitors
are associated with fewer clinical GI toxic effects is unknown.ObjectiveTo determine whether celecoxib, a COX-2–specific inhibitor, is
associated with a lower incidence of significant upper GI toxic effects and
other adverse effects compared with conventional NSAIDs.DesignThe Celecoxib Long-term Arthritis Safety Study (CLASS), a double-blind,
randomized controlled trial conducted from September 1998 to March 2000.SettingThree hundred eighty-six clinical sites in the United States and Canada.ParticipantsA total of 8059 patients (≥18 years old) with osteoarthritis (OA)
or rheumatoid arthritis (RA) were enrolled in the study, and 7968 received
at least 1 dose of study drug. A total of 4573 patients (57%) received treatment
for 6 months.InterventionsPatients were randomly assigned to receive celecoxib, 400 mg twice per
day (2 and 4 times the maximum RA and OA dosages, respectively; n = 3987);
ibuprofen, 800 mg 3 times per day (n = 1985); or diclofenac, 75 mg twice per
day (n = 1996). Aspirin use for cardiovascular prophylaxis (≤325 mg/d)
was permitted.Main Outcome MeasuresIncidence of prospectively defined symptomatic upper GI ulcers and ulcer
complications (bleeding, perforation, and obstruction) and other adverse effects
during the 6-month treatment period.ResultsFor all patients, the annualized incidence rates of upper GI ulcer complications
alone and combined with symptomatic ulcers for celecoxib vs NSAIDs were 0.76%
vs 1.45% (P = .09) and 2.08% vs 3.54% (P = .02), respectively. For patients not taking aspirin, the annualized
incidence rates of upper GI ulcer complications alone and combined with symptomatic
ulcers for celecoxib vs NSAIDs were 0.44% vs 1.27% (P
= .04) and 1.40% vs 2.91% (P = .02). For patients
taking aspirin, the annualized incidence rates of upper GI ulcer complications
alone and combined with symptomatic ulcers for celecoxib vs NSAIDs were 2.01%
vs 2.12% (P = .92) and 4.70% vs 6.00% (P = .49). Fewer celecoxib-treated patients than NSAID-treated patients
experienced chronic GI blood loss, GI intolerance, hepatotoxicity, or renal
toxicity. No difference was noted in the incidence of cardiovascular events
between celecoxib and NSAIDs, irrespective of aspirin use.ConclusionsIn this study, celecoxib, at dosages greater than those indicated clinically,
was associated with a lower incidence of symptomatic ulcers and ulcer complications
combined, as well as other clinically important toxic effects, compared with
NSAIDs at standard dosages. The decrease in upper GI toxicity was strongest
among patients not taking aspirin concomitantly.
3,213 citations
Posted Content•
TL;DR: In a survey of 1478 R&D labs in the U.S. manufacturing sector in 1994, the authors found that firms typically protect the profits due to invention with a range of mechanisms, including patents, secrecy, lead time advantages and the use of complementary marketing and manufacturing capabilities.
Abstract: Based on a survey questionnaire administered to 1478 R&D labs in the U.S. manufacturing sector in 1994, we find that firms typically protect the profits due to invention with a range of mechanisms, including patents, secrecy, lead time advantages and the use of complementary marketing and manufacturing capabilities. Of these mechanisms, however, patents tend to be the least emphasized by firms in the majority of manufacturing industries, and secrecy and lead time tend to be emphasized most heavily. A comparison of our results with the earlier survey findings of Levin et al. [1987] suggest that patents may be relied upon somewhat more heavily by larger firms now than in the early 1980s. For the protection of product innovations, secrecy now appears to be much more heavily employed across most industries than previously. Our results on the motives to patent indicate that firms patent for reasons that often extend beyond directly profiting from a patented innovation through either its commercialization or licensing. In addition to the prevention of copying, the most prominent motives for patenting include the prevention of rivals from patenting related inventions (i.e., patent blocking'), the use of patents in negotiations and the prevention of suits. We find that firms commonly patent for different reasons in discrete' product industries, such as chemicals, versus complex' product industries, such as telecommunications equipment or semiconductors. In the former, firms appear to use their patents commonly to block the development of substitutes by rivals, and in the latter, firms are much more likely to use patents to force rivals into negotiations.
1,679 citations
TL;DR: The evidence strongly suggests that the numerous mechanisms of quinone toxicity can be correlated with the known pathology of the parent compound(s), including benzene, polycyclic aromatic hydrocarbons, estrogens, and catecholamines.
Abstract: Quinones represent a class of toxicological intermediates which can create a variety of hazardous effects in vivo, including acute cytotoxicity, immunotoxicity, and carcinogenesis. The mechanisms by which quinones cause these effects can be quite complex. Quinones are Michael acceptors, and cellular damage can occur through alkylation of crucial cellular proteins and/or DNA. Alternatively, quinones are highly redox active molecules which can redox cycle with their semiquinone radicals, leading to formation of reactive oxygen species (ROS), including superoxide, hydrogen peroxide, and ultimately the hydroxyl radical. Production of ROS can cause severe oxidative stress within cells through the formation of oxidized cellular macromolecules, including lipids, proteins, and DNA. Formation of oxidatively damaged bases such as 8-oxodeoxyguanosine has been associated with aging and carcinogenesis. Furthermore, ROS can activate a number of signaling pathways, including protein kinase C and RAS. This review explore...
1,499 citations
TL;DR: The selective down-regulation of RELN and GAD(67) in prefrontal cortex of patients with schizophrenia and bipolar disorder who have psychosis is consistent with the hypothesis that these parameters are vulnerability factors in psychosis; this plus the loss of the correlation between these 2 parameters that exists in nonpsychotic subjects support the hypotheses that these changes may be liability factors underlying psychosis.
Abstract: Background Reelin (RELN) is a glycoprotein secreted preferentially by cortical γ-aminobutyric acid-ergic (GABAergic) interneurons (layers I and II) that binds to integrin receptors located on dendritic spines of pyramidal neurons or on GABAergic interneurons of layers III through V expressing the disabled-1 gene product (DAB1), a cytosolic adaptor protein that mediates RELN action. To replicate earlier findings that RELN and glutamic acid decarboxylase (GAD) 67 , but not DAB1 expression, are down-regulated in schizophrenic brains, and to verify whether other psychiatric disorders express similar deficits, we analyzed, blind, an entirely new cohort of 60 postmortem brains, including equal numbers of patients matched for schizophrenia, unipolar depression, and bipolar disorder with nonpsychiatric subjects. Methods Reelin, GAD 65 , GAD 67 , DAB1, and neuron-specific–enolase messenger RNAs (mRNAs) and respective proteins were measured with quantitative reverse transcriptase–polymerase chain reaction (RT-PCR) or Western blot analyses. Reelin-positive neurons were identified by immunohistochemistry using a monoclonal antibody. Results Prefrontal cortex and cerebellar expression of RELN mRNA, GAD 67 protein and mRNA, and prefrontal cortex RELN-positive cells was significantly decreased by 30% to 50% in patients with schizophrenia or bipolar disorder with psychosis, but not in those with unipolar depression without psychosis when compared with nonpsychiatric subjects. Group differences were absent for DAB1,GAD 65 and neuron-specific–enolase expression implying that RELN and GAD 67 down-regulations were unrelated to neuronal damage. Reelin and GAD 67 were also unrelated to postmortem intervals, dose, duration, or presence of antipsychotic medication. Conclusions The selective down-regulation of RELN and GAD 67 in prefrontal cortex of patients with schizophrenia and bipolar disorder who have psychosis is consistent with the hypothesis that these parameters are vulnerability factors in psychosis; this plus the loss of the correlation between these 2 parameters that exists in nonpsychotic subjects support the hypothesis that these changes may be liability factors underlying psychosis.
1,180 citations
TL;DR: Overall, support exists for the effectiveness of several forms of cognitive rehabilitation for persons with stroke and TBI, and specific recommendations can be made for remediation of language and perception after left and right hemisphere stroke.
1,154 citations
TL;DR: Two G protein‐coupled receptors have been identified that bind corticotropin‐releasing factor (CRF) and urocortin (UCN) with high affinity and hybridization histochemical methods were used to shed light on controversies concerning their localization in rat brain, and to provide normative distributional data in mouse.
Abstract: Two G protein-coupled receptors have been identified that bind corticotropin-releasing factor (CRF) and urocortin (UCN) with high affinity. Hybridization histochemical methods were used to shed light on controversies concerning their localization in rat brain, and to provide normative distributional data in mouse, the standard model for genetic manipulation in mammals. The distribution of CRF-R1 mRNA in mouse was found to be fundamentally similar to that in rat, with expression predominating in the cerebral cortex, sensory relay nuclei, and in the cerebellum and its major afferents. Pronounced species differences in distribution were few, although more subtle variations in the relative strength of R1 expression were seen in several forebrain regions. CRF-R2 mRNA displayed comparable expression in rat and mouse brain, distinct from, and more restricted than that of CRF-R1. Major neuronal sites of CRF-R2 expression included aspects of the olfactory bulb, lateral septal nucleus, bed nucleus of the stria terminalis, ventromedial hypothalamic nucleus, medial and posterior cortical nuclei of the amygdala, ventral hippocampus, mesencephalic raphe nuclei, and novel localizations in the nucleus of the solitary tract and area postrema. Several sites of expression in the limbic forebrain were found to overlap partially with ones of androgen receptor expression. In pituitary, rat and mouse displayed CRF-R1 mRNA signal continuously over the intermediate lobe and over a subset of cells in the anterior lobe, whereas CRF-R2 transcripts were expressed mainly in the posterior lobe. The distinctive expression pattern of CRF-R2 mRNA identifies additional putative central sites of action for CRF and/or UCN. Constitutive expression of CRF-R2 mRNA in the nucleus of the solitary tract, and stress-inducible expression of CRF-R1 transcripts in the paraventricular nucleus may provide a basis for understanding documented effects of CRF-related peptides at a loci shown previously to lack a capacity for CRF-R expression or CRF binding. Other such "mismatches" remain to be reconciled.
1,028 citations
TL;DR: This statement summarizes the consensus achieved in discussions to develop a consensus defining the criteria for cure of acromegaly.
Abstract: In February 1999, a workshop was held in Cortina, Italy to develop a consensus defining the criteria for cure of acromegaly. The workshop was sponsored by the University of Brescia and hosted by the Italian Society of Endocrinology. Invited international participants included endocrinologists, neurosurgeons, and radiotherapists skilled in the management of acromegaly. This statement summarizes the consensus achieved in these discussions.
984 citations
TL;DR: In this paper, the authors investigate how corporate governance systems of large public U.S. corporations vary with information properties of numbers produced by their financial accounting systems and find that in firms whose current accounting numbers do a relatively poor job of capturing the effects of the firm's current activities and outcomes on shareholder value, the accounting numbers are less effective in the governance setting.
Abstract: The purpose of this paper is to investigate how governance systems of large public U.S. corporations vary with information properties of numbers produced by their financial accounting systems. We argue that in firms whose current accounting numbers do a relatively poor job of capturing the effects of the firm's current activities and outcomes on shareholder value, the accounting numbers are less effective in the governance setting. We predict that such firms will substitute costly governance mechanisms to compensate for their less useful accounting numbers. We explore whether governance systems vary with the timeliness of earnings by examining the cross-sectional relation between proxies for earnings timeliness and subsequent corporate governance systems of 784 firms in the Fortune 1000. The governance systems we consider include board composition, stockholdings of inside and outside directors, ownership concentration and the structure of executive compensation. Our results support a significant negative relation between our timeliness metrics and subsequent costly corporate governance mechanisms after controlling for other firm characteristics.
920 citations
TL;DR: The strengths and weaknesses of three approaches to measurement: managerial perceptions, firm behaviors, and resource allocations are examined, and it is suggested that measurement accuracy can be improved by using a triangulation of methods.
883 citations
TL;DR: In patients with glaucoma with office IOP in the normal range, large fluctuations in diurnal IOP are a significant risk factor, independent of parameters obtained in the office.
Abstract: Purpose:To study the risk associated with diurnal intraocular pressure (IOP) variations in patients with open-angle glaucoma.Patients and Methods:Sixty-four patients (105 eyes) from the practices of two glaucoma specialists successfully performed home tonometry with a self-tonometer five times a day
TL;DR: Investigations suggest that the pyrazole triols prefer to bind to ERalpha with their C(3)-phenol in the estradiol A-ring binding pocket and that binding selectivity results from differences in the interaction of thePyrazole core and C(4)-propyl group with portions of the receptor where ERalpha has a smaller residue than ERbeta.
Abstract: We have found that certain tetrasubstituted pyrazoles are high-affinity ligands for the estrogen receptor (ER) (Fink et al Chem Biol 1999, 6, 205-219) and that one pyrazole is considerably more potent as an agonist on the ERalpha than on the ERbeta subtype (Sun et al Endocrinology 1999, 140, 800-804) To investigate what substituent pattern provides optimal ER binding affinity and the greatest enhancement of potency as an ERalpha-selective agonist, we prepared a number of tetrasubstituted pyrazole analogues with defined variations at certain substituent positions Analysis of their binding affinity pattern shows that a C(4)-propyl substituent is optimal and that a p-hydroxyl group on the N(1)-phenyl group also enhances affinity and selectivity for ERalpha The best compound in this series, a propylpyrazole triol (PPT, compound 4g), binds to ERalpha with high affinity (ca 50% that of estradiol), and it has a 410-fold binding affinity preference for ERalpha It also activates gene transcription only through ERalpha Thus, this compound represents the first ERalpha-specific agonist We investigated the molecular basis for the exceptional ERalpha binding affinity and potency selectivity of pyrazole 4g by a further study of structure-affinity relationships in this series and by molecular modeling These investigations suggest that the pyrazole triols prefer to bind to ERalpha with their C(3)-phenol in the estradiol A-ring binding pocket and that binding selectivity results from differences in the interaction of the pyrazole core and C(4)-propyl group with portions of the receptor where ERalpha has a smaller residue than ERbeta These ER subtype-specific interactions and the ER subtype-selective ligands that can be derived from them should prove useful in defining those biological activities in estrogen target cells that can be selectively activated through ERalpha
TL;DR: The crystal structure of the protease domain of human memapsin 2 complexed to an eight-residue inhibitor at 1.9 angstrom resolution is determined and it is found that the active site of memapin 2 is more open and less hydrophobic than that of other human aspartic proteases.
Abstract: Memapsin 2 (beta-secretase) is a membrane-associated aspartic protease involved in the production of beta-amyloid peptide in Alzheimer's disease and is a major target for drug design. We determined the crystal structure of the protease domain of human memapsin 2 complexed to an eight-residue inhibitor at 1.9 angstrom resolution. The active site of memapsin 2 is more open and less hydrophobic than that of other human aspartic proteases. The subsite locations from S4 to S2' are well defined. A kink of the inhibitor chain at P2' and the change of chain direction of P3' and P4' may be mimicked to provide inhibitor selectivity.
TL;DR: It is shown that activation of nAChRs on presynaptic terminals in the VTA enhances glutamatergic inputs to DA neurons, which can explain the long-term excitation of brain reward areas induced by a brief nicotine exposure.
TL;DR: In this paper, the authors investigate the value of active mutual fund management by examining the stockholdings and trades of mutual funds and find that stocks widely held by funds do not outperform other stocks.
Abstract: We investigate the value of active mutual fund management by examining the stockholdings and trades of mutual funds. We find that stocks widely held by funds do not outperform other stocks. However, stocks purchased by funds have significantly higher returns than stocks they sell-this is true for large stocks as well as small stocks, and for value stocks as well as growth stocks. We find that growth-oriented funds exhibit better stock-selection skills than income-oriented funds. Finally, we find only weak evidence that funds with the best past performance have better stock-picking skills than funds with the worst past performance.
TL;DR: The unique patterning characteristic of vasculogenic mimicry provides an opportunity to design noninvasive imaging techniques to detect highly aggressive neoplasms and their metastases.
Abstract: Tumors require a blood supply for growth and hematogenous dissemination. Much attention has been focused on the role of angiogenesis—the recruitment of new vessels into a tumor from pre-existing vessels. However, angiogenesis may not be the only mechanism by which tumors acquire a microcirculation. Highly aggressive and metastatic melanoma cells are capable of forming highly patterned vascular channels in vitro that are composed of a basement membrane that stains positive with the periodic acid-Schiff (PAS) reagent in the absence of endothelial cells and fibroblasts. These channels formed in vitro are identical morphologically to PAS-positive channels in histological preparations from highly aggressive primary uveal melanomas, in the vertical growth phase of cutaneous melanomas, and in metastatic uveal and cutaneous melanoma. The generation of microvascular channels by genetically deregulated, aggressive tumor cells was termed “vasculogenic mimicry” to emphasize their de novo generation without participation by endothelial cells and independent of angiogenesis. Techniques designed to identify the tumor microcirculation by the staining of endothelial cells may not be applicable to tumors that express vasculogenic mimicry. Although it is not known if therapeutic strategies targeting endothelial cells will be effective in tumors whose blood supply is formed by tumor cells in the absence of angiogenesis, the biomechanical and molecular events that regulate vasculogenic mimicry provide opportunities for the development of novel forms of tumor-targeted treatments. The unique patterning characteristic of vasculogenic mimicry provides an opportunity to design noninvasive imaging techniques to detect highly aggressive neoplasms and their metastases.
TL;DR: In this article, the authors examined how the risks of accelerated internationalization of businesses can be mitigated and how the internationalization will accelerate in the 21st century, using the Organisation for Economic Co-operation and Development (OECD).
Abstract: The Organisation for Economic Co-operation and Development predicts that the internationalization of businesses will accelerate in the 21st century. Our study examined how the risks of accelerated ...
TL;DR: In this paper, the authors examined whether two key audit committee characteristics combined, activity and independence, reduce likely fraud or aggressive financial statement actions and concluded future research may be required regarding young and mature firms.
Abstract: Examines whether two key audit committee characteristics combined, activity and independence, reduce likely fraud or aggressive financial statement actions. Utilizes evidence on potential of Blue Ribbon Committee (1999) recommendations regarding composition of audit committees, and further involves a sample of 156 firms — 78 subject to SEC Accounting and Auditing Enforcement Releases and 78 similar sized non‐sanctioned firms. Closes by stating future research may be required regarding young and mature firms ‐ that could affect monitoring.
TL;DR: BETA2/NeuroD1 is the first gene to be shown to regulate neuronal and sensory cell development in both the cochlear and vestibular systems.
Abstract: BETA2/NeuroD1 is a bHLH transcription factor that is expressed during development in the mammalian pancreas and in many locations in the central and peripheral nervous systems. During inner ear ontogenesis, it is present in both sensory ganglion neurons and sensory epithelia. Although studies have shown that BETA2/NeuroD1 is important in the development of the hippocampal dentate gyrus and the cerebellum, its functions in the peripheral nervous system and in particular in the inner ear are unclear. Mice carrying a BETA2/NeuroD1 null mutation exhibit behavioral abnormalities suggestive of an inner ear defect, including lack of responsiveness to sound, hyperactivity, head tilting, and circling. Here we show that these defects can be explained by a severe reduction of sensory neurons in the cochlear-vestibular ganglion (CVG). A developmental study of CVG formation in the null demonstrates that BETA2/NeuroD1 does not play a primary role in the proliferation of neuroblast precursors or in their decision to become neuroblasts. Instead, the reduction in CVG neuron number is caused by a combination both of delayed or defective delamination of CVG neuroblast precursors from the otic vesicle epithelium and of enhanced apoptosis both in the otic epithelium and among those neurons that do delaminate to form the CVG. There are also defects in differentiation and patterning of the cochlear duct and sensory epithelium and loss of the dorsal cochlear nucleus. BETA2/NeuroD1 is, thus, the first gene to be shown to regulate neuronal and sensory cell development in both the cochlear and vestibular systems.
TL;DR: The respiratory failure risk index is a validated model for identifying patients at risk for developing PRF and may be useful for guiding perioperative respiratory care.
Abstract: Objective
To develop and validate a preoperative risk index for predicting postoperative respiratory failure (PRF).
TL;DR: The expression of ARR5 in the apical meristems was confirmed by whole mount in situ analysis of seedlings and is consistent with a role for cytokinin in regulating cell division in vivo, and is due, at least in part, to increased transcription.
Abstract: We examined the expression of a family of Arabidopsis response regulators (ARR) and found that the steady-state levels of RNA for most are elevated very rapidly by cytokinin. Using nuclear run-on assays we demonstrated that this increase in ARR transcript levels in response to cytokinin is due, at least in part, to increased transcription. The start site of transcription for the ARR5 gene was identified using primer extension analysis. A DNA fragment comprised of 1.6 kb upstream of the ARR5 transcript start site conferred cytokinin-inducible gene expression when fused to a beta-glucuronidase reporter, confirming that the transcription rate of ARR5 is elevated by cytokinin. This reporter construct was also used to examine the spatial pattern of ARR5 expression. The highest levels of expression were observed in the root and shoot apical meristems, at the junction of the pedicle and the silique, and in the central portion of mature roots. The expression of ARR5 in the apical meristems was confirmed by whole mount in situ analysis of seedlings and is consistent with a role for cytokinin in regulating cell division in vivo.
TL;DR: Empirical studies of predictors of transitions in stages of smoking progression are reviewed, and similarities and differences related to predictor of stages and transitions across studies are identified.
TL;DR: It is shown that two chimaeric enhancers, constructed by swapping the 5′ and 3′ halves of the native stripe 2 elements of two species, no longer drive expression of a reporter gene in the wild-type pattern.
Abstract: Eukaryotic gene expression is mediated by compact cis-regulatory modules, or enhancers, which are bound by specific sets of transcription factors. The combinatorial interaction of these bound transcription factors determines time- and tissue-specific gene activation or repression. The even-skipped stripe 2 element controls the expression of the second transverse stripe of even-skipped messenger RNA in Drosophila melanogaster embryos, and is one of the best characterized eukaryotic enhancers. Although even-skipped stripe 2 expression is strongly conserved in Drosophila, the stripe 2 element itself has undergone considerable evolutionary change in its binding-site sequences and the spacing between them. We have investigated this apparent contradiction, and here we show that two chimaeric enhancers, constructed by swapping the 5' and 3' halves of the native stripe 2 elements of two species, no longer drive expression of a reporter gene in the wildtype pattern. Sequence differences between species have functional consequences, therefore, but they are masked by other co-evolved differences. On the basis of these results, we present a model for the evolution of eukaryotic regulatory sequences.
TL;DR: Olanzapine demonstrated greater efficacy than placebo in the treatment of acute bipolar mania and was generally well tolerated.
Abstract: Background We compared the efficacy and safety of olanzapine vs placebo for the treatment of acute bipolar mania Methods Four-week, randomized, double-blind, parallel study A total of 115 patients with aDSM-IVdiagnosis of bipolar disorder, manic or mixed, were randomized to olanzapine, 5 to 20 mg/d (n = 55), or placebo (n = 60) The primary efficacy measure was the Young–Mania Rating Scale (Y-MRS) total score Response and euthymia were defined, a priori, as at least a 50% improvement from baseline to end point and as a score of no less than 12 at end point in the Y-MRS total score, respectively Safety was assessed using adverse events, Extrapyramidal Symptom (EPS) rating scales, laboratory values, electrocardiograms, vital signs, and weight change Results Olanzapine-treated patients demonstrated a statistically significant greater mean (± SD) improvement in Y-MRS total score than placebo-treated patients (−148 ± 125 and −81 ± 127, respectively;P Conclusion Olanzapine demonstrated greater efficacy than placebo in the treatment of acute bipolar mania and was generally well tolerated
TL;DR: Findings suggest that restrictions on smoking at home, more extensive bans on smoking in public places, and enforced bans onsmoking at school may reduce teenage smoking.
Abstract: Objective: To determine the relation between extent of restrictions on smoking at home, at school, and in public places and smoking uptake and smoking prevalence among school students. Design: Cross sectional survey with merged records of extent of restrictions on smoking in public places. Setting: United States. Participants: 17 287 high school students. Main outcome measures: Five point scale of smoking uptake; 30 day smoking prevalence. Results: More restrictive arrangements on smoking at home were associated with a greater likelihood of being in an earlier stage of smoking uptake (P Conclusions: These findings suggest that restrictions on smoking at home, more extensive bans on smoking in public places, and enforced bans on smoking at school may reduce teenage smoking.
TL;DR: It is shown that rapid evolution of male reproductive genes is observable in primates and is quite notable in the lineages to human and chimpanzee, and that positive darwinian selection is often the driving force behind this rapid evolution.
Abstract: A diverse body of morphological and genetic evidence has suggested that traits pertaining to male reproduction may have evolved much more rapidly than other types of character1,2,3. Recently, DNA sequence comparisons have also shown a very high level of divergence in male reproductive proteins between closely related Drosophila species4,5,6, among marine invertebrates7,8 and between mouse and rat9. Here we show that rapid evolution of male reproductive genes is observable in primates and is quite notable in the lineages to human and chimpanzee. Nevertheless, rapid evolution by itself is not necessarily an indication of positive darwinian selection; relaxation of negative selection is often equally compatible with the DNA sequence data. By taking three statistical approaches, we show that positive darwinian selection is often the driving force behind this rapid evolution. These results open up opportunities to test the hypothesis that sexual selection plays some role in the molecular evolution of higher primates.
06 Sep 2000
TL;DR: This paper systematically compare four popular metamodeling techniques —Polynomial Regression, Multivariate Adaptive Regression Splines, Radial Basis Functions, and Kriging —based on multiple performance criteria using fourteen test problems representing different classes of problems.
Abstract: Despite the advances in computer capacity, the enormous computational cost of complex engineering simulations makes it impractical to rely exclusively on simulation for the purpose of design optimization. To cut down the cost, surrogate models, also known as metamodels, are constructed from and then used in lieu of the actual simulation models. In the paper, we systematically compare four popular metamodeling techniques —Polynomial Regression, Multivariate Adaptive Regression Splines, Radial Basis Functions, and Kriging —based on multiple performance criteria using fourteen test problems representing different classes of problems. Our objective in th is study is to investigate the advantages and disadvantages these four metamodeling techniques using multiple modeling criteria and multiple test problems rather than a single measure of merit and a single test problem.
TL;DR: Findings suggest that there is an upregulation of collagenase 1 and 2 and gelatinases A and B, and an increase in endothelial and epithelial cell death, which may contribute to the pathogenesis of COPD through the remodeling of airways and alveolar structures.
TL;DR: In this article, the authors apply the theory of hyperbolic spaces and groups to algorithmic questions for the Mapping Class Group and geometric properties of Kleinian representations of Harvey's Complex of Curves.
Abstract: This paper continues a geometric study of Harvey's Complex of Curves, whose ultimate goal is to apply the theory of hyperbolic spaces and groups to algorithmic questions for the Mapping Class Group and geometric properties of Kleinian representations. The authors' previous result that the complex is delta-hyperbolic was hard to apply because the complex is not locally finite; in this paper some tools are developed for overcoming this problem, and a combinatorial mechanism introduced which describes sequences of elementary moves in the graph of markings on a surface. These tools are applied to give a family of quasi-geodesic words in the Mapping Class Group, and a linear bound on the shortest word conjugating two conjugate pseudo-Anosov elements.
A basic tool in the analysis is a family of subsurface projections, which are roughly analogous to closest-point projections to horoballs in classical hyperbolic space. These projections have a strong contraction property which makes it possible to tie together the geometry of the complex and that of the (infinite) subcomplexes that arise as links of vertices. The resulting layered structure of the complex is controlled by means of a combinatorial device called a hierarchy of geodesics, which is the central construction of the paper.
TL;DR: A partial model now exists that facilitates the study of structure-function relationships of the native enzyme, and of natural and engineered mutants, and overexpression of the human LCAT gene in mice and rabbits has been used to examine the physiologic role of LCAT in vivo and its protective effect against diet induced atherosclerosis.