Showing papers by "Yale University published in 2004"
TL;DR: Recognition of microbial infection and initiation of host defense responses is controlled by multiple mechanisms and recent studies have provided important clues about the mechanisms of TLR-mediated control of adaptive immunity orchestrated by dendritic cell populations in distinct anatomical locations.
Abstract: Recognition of microbial infection and initiation of host defense responses is controlled by multiple mechanisms. Toll-like receptors (TLRs) have recently emerged as a key component of the innate immune system that detect microbial infection and trigger antimicrobial host defense responses. TLRs activate multiple steps in the inflammatory reactions that help to eliminate the invading pathogens and coordinate systemic defenses. In addition, TLRs control multiple dendritic cell functions and activate signals that are critically involved in the initiation of adaptive immune responses. Recent studies have provided important clues about the mechanisms of TLR-mediated control of adaptive immunity orchestrated by dendritic cell populations in distinct anatomical locations.
4,108 citations
TL;DR: It is shown that commensal bacteria are recognized by TLRs under normal steady-state conditions, and this interaction plays a crucial role in the maintenance of intestinal epithelial homeostasis and protection from injury.
3,972 citations
TL;DR: An overview of established NF-kappaB signaling pathways is provided with focus on the current state of research into the mechanisms that regulate IKK activation and NF- kappaB transcriptional activity.
Abstract: The transcription factor NF-kappaB has been the focus of intense investigation for nearly two decades. Over this period, considerable progress has been made in determining the function and regulation of NF-kappaB, although there are nuances in this important signaling pathway that still remain to be understood. The challenge now is to reconcile the regulatory complexity in this pathway with the complexity of responses in which NF-kappaB family members play important roles. In this review, we provide an overview of established NF-kappaB signaling pathways with focus on the current state of research into the mechanisms that regulate IKK activation and NF-kappaB transcriptional activity.
3,829 citations
TL;DR: It is shown that the strong coupling regime can be attained in a solid-state system, and the concept of circuit quantum electrodynamics opens many new possibilities for studying the strong interaction of light and matter.
Abstract: The interaction of matter and light is one of the fundamental processes occurring in nature, and its most elementary form is realized when a single atom interacts with a single photon. Reaching this regime has been a major focus of research in atomic physics and quantum optics1 for several decades and has generated the field of cavity quantum electrodynamics2,3. Here we perform an experiment in which a superconducting two-level system, playing the role of an artificial atom, is coupled to an on-chip cavity consisting of a superconducting transmission line resonator. We show that the strong coupling regime can be attained in a solid-state system, and we experimentally observe the coherent interaction of a superconducting two-level system with a single microwave photon. The concept of circuit quantum electrodynamics opens many new possibilities for studying the strong interaction of light and matter. This system can also be exploited for quantum information processing and quantum communication and may lead to new approaches for single photon generation and detection.
3,452 citations
TL;DR: The prevalence of the metabolic syndrome is high among obese children and adolescents, and it increases with worsening obesity, particularly in severely obese youngsters.
Abstract: background The prevalence and magnitude of childhood obesity are increasing dramatically. We examined the effect of varying degrees of obesity on the prevalence of the metabolic syndrome and its relation to insulin resistance and to C-reactive protein and adiponectin levels in a large, multiethnic, multiracial cohort of children and adolescents. methods We administered a standard glucose-tolerance test to 439 obese, 31 overweight, and 20 nonobese children and adolescents. Baseline measurements included blood pressure and plasma lipid, C-reactive protein, and adiponectin levels. Levels of triglycerides, high-density lipoprotein cholesterol, and blood pressure were adjusted for age and sex. Because the body-mass index varies according to age, we standardized the value for age and sex with the use of conversion to a z score. results The prevalence of the metabolic syndrome increased with the severity of obesity and reached 50 percent in severely obese youngsters. Each half-unit increase in the bodymass index, converted to a z score, was associated with an increase in the risk of the metabolic syndrome among overweight and obese subjects (odds ratio, 1.55; 95 percent confidence interval, 1.16 to 2.08), as was each unit of increase in insulin resistance as assessed with the homeostatic model (odds ratio, 1.12; 95 percent confidence interval, 1.07 to 1.18 for each additional unit of insulin resistance). The prevalence of the metabolic syndrome increased significantly with increasing insulin resistance (P for trend, <0.001) after adjustment for race or ethnic group and the degree of obesity. C-reactive protein levels increased and adiponectin levels decreased with increasing obesity. conclusions The prevalence of the metabolic syndrome is high among obese children and adolescents, and it increases with worsening obesity. Biomarkers of an increased risk of adverse cardiovascular outcomes are already present in these youngsters.
3,277 citations
TL;DR: In this paper, a realizable architecture using one-dimensional transmission line resonators was proposed to reach the strong coupling limit of cavity quantum electrodynamics in superconducting electrical circuits.
Abstract: We propose a realizable architecture using one-dimensional transmission line resonators to reach the strong-coupling limit of cavity quantum electrodynamics in superconducting electrical circuits. The vacuum Rabi frequency for the coupling of cavity photons to quantized excitations of an adjacent electrical circuit (qubit) can easily exceed the damping rates of both the cavity and qubit. This architecture is attractive both as a macroscopic analog of atomic physics experiments and for quantum computing and control, since it provides strong inhibition of spontaneous emission, potentially leading to greatly enhanced qubit lifetimes, allows high-fidelity quantum nondemolition measurements of the state of multiple qubits, and has a natural mechanism for entanglement of qubits separated by centimeter distances. In addition it would allow production of microwave photon states of fundamental importance for quantum communication.
2,633 citations
TL;DR: A graphical method is developed, the X-tile plot, that illustrates the presence of substantial tumor subpopulations and shows the robustness of the relationship between a biomarker and outcome by construction of a two dimensional projection of every possible subpopulation.
Abstract: The ability to parse tumors into subsets based on biomarker expression has many clinical applications; however, there is no global way to visualize the best cut-points for creating such divisions. We have developed a graphical method, the X-tile plot that illustrates the presence of substantial tumor subpopulations and shows the robustness of the relationship between a biomarker and outcome by construction of a two dimensional projection of every possible subpopulation. We validate X-tile plots by examining the expression of several established prognostic markers (human epidermal growth factor receptor-2, estrogen receptor, p53 expression, patient age, tumor size, and node number) in cohorts of breast cancer patients and show how X-tile plots of each marker predict population subsets rooted in the known biology of their expression.
2,551 citations
TL;DR: This article found that most indicators of institutional quality used to establish the proposition that institutions cause growth are constructed to be conceptually unsuitable for that purpose and also found that some of the instrumental variable techniques used in the literature are flawed.
Abstract: We revisit the debate over whether political institutions cause economic growth, or whether, alternatively, growth and human capital accumulation lead to institutional improvement. We find that most indicators of institutional quality used to establish the proposition that institutions cause growth are constructed to be conceptually unsuitable for that purpose. We also find that some of the instrumental variable techniques used in the literature are flawed. Basic OLS results, as well as a variety of additional evidence, suggest that (a) human capital is a more basic source of growth than are the institutions, (b) poor countries get out of poverty through good policies, often pursued by dictators, and (c) subsequently improve their political institutions.
2,543 citations
TL;DR: The ENCyclopedia Of DNA Elements (ENCODE) Project is organized as an international consortium of computational and laboratory-based scientists working to develop and apply high-throughput approaches for detecting all sequence elements that confer biological function.
Abstract: The ENCyclopedia Of DNA Elements (ENCODE) Project aims to identify all functional elements in the human genome sequence. The pilot phase of the Project is focused on a specified 30 megabases (∼1%) of the human genome sequence and is organized as an international consortium of computational and laboratory-based scientists working to develop and apply high-throughput approaches for detecting all sequence elements that confer biological function. The results of this pilot phase will guide future efforts to analyze the entire human genome.
2,248 citations
TL;DR: It is found that online conversations may offer an easy and cost-effective opportunity to measure word of mouth and it is shown that a measure of the dispersion of conversations across communities has explanatory power in a dynamic model of TV ratings.
Abstract: Managers are very interested in word-of-mouth communication because they believe that a product's success is related to the word of mouth that it generates. However, there are at least three significant challenges associated with measuring word of mouth. First, how does one gather the data? Because the information is exchanged in private conversations, direct observation traditionally has been difficult. Second, what aspect of these conversations should one measure? The third challenge comes from the fact that word of mouth is not exogenous. While the mapping from word of mouth to future sales is of great interest to the firm, we must also recognize that word of mouth is an outcome of past sales. Our primary objective is to address these challenges. As a context for our study, we have chosen new television (TV) shows during the 1999-2000 seasons. Our source of word-of-mouth conversations is Usenet, a collection of thousands of newsgroups with diverse topics. We find that online conversations may offer an easy and cost-effective opportunity to measure word of mouth. We show that a measure of the dispersion of conversations across communities has explanatory power in a dynamic model of TV ratings.
2,247 citations
TL;DR: Adding aspirin to clopidogrel in high-risk patients with recent ischaemic stroke or transient ischaemia attack is associated with a non-significant difference in reducing major vascular events, however, the risk of life-threatening or major bleeding is increased by the addition of aspirin.
TL;DR: The hypothesis that insulin resistance in the skeletal muscle of insulin-resistant offspring of patients with type 2 diabetes is associated with dysregulation of intramyocellular fatty acid metabolism is supported, possibly because of an inherited defect in mitochondrial oxidative phosphorylation.
Abstract: Background Insulin resistance appears to be the best predictor of the development of diabetes in the children of patients with type 2 diabetes, but the mechanism responsible is unknown. Methods We performed hyperinsulinemic–euglycemic clamp studies in combination with infusions of [6,6-2H2]glucose in healthy, young, lean, insulin-resistant offspring of patients with type 2 diabetes and insulin-sensitive control subjects matched for age, height, weight, and physical activity to assess the sensitivity of liver and muscle to insulin. Proton (1H) magnetic resonance spectroscopy studies were performed to measure intramyocellular lipid and intrahepatic triglyceride content. Rates of whole-body and subcutaneous fat lipolysis were assessed by measuring the rates of [2H5]glycerol turnover in combination with microdialysis measurements of glycerol release from subcutaneous fat. We performed 31P magnetic resonance spectroscopy studies to assess the rates of mitochondrial oxidative-phosphorylation activity in muscle....
TL;DR: In this article, the authors presented a theory, finding, and implications of emotional intelligence, and found that emotional intelligence can be classified into three categories: positive, negative, and neutral.
Abstract: (2004). TARGET ARTICLES: 'Emotional Intelligence: Theory, Findings, and Implications' Psychological Inquiry: Vol. 15, No. 3, pp. 197-215.
TL;DR: It is shown that TLR7 recognizes the single-stranded RNA viruses, vesicular stomatitis virus and influenza virus, and insights into the pathways used by the innate immune cells in the recognition of viral pathogens are provided.
Abstract: Viral infection of mammalian host results in the activation of innate immune responses. Toll-like receptors (TLRs) have been shown to mediate the recognition of many types of pathogens, including viruses. The genomes of viruses possess unique characteristics that are not found in mammalian genomes, such as high CpG content and double-stranded RNA. These genomic nucleic acids serve as molecular signatures associated with viral infections. Here we show that TLR7 recognizes the single-stranded RNA viruses, vesicular stomatitis virus and influenza virus. The recognition of these viruses by plasmacytoid dendritic cells and B cells through TLR7 results in their activation of costimulatory molecules and production of cytokines. Moreover, this recognition required intact endocytic pathways. Mice deficient in either the TLR7 or the TLR adaptor protein MyD88 demonstrated reduced responses to in vivo infection with vesicular stomatitis virus. These results demonstrate microbial ligand recognition by TLR7 and provide insights into the pathways used by the innate immune cells in the recognition of viral pathogens.
TL;DR: Although the total number of trial participants increased during the study period, the representation of racial and ethnic minorities decreased and were less likely to enroll in cooperative group cancer trials than were whites, men, and younger patients, respectively.
Abstract: ContextDespite the importance of diversity of cancer trial participants with
regard to race, ethnicity, age, and sex, there is little recent information
about the representation of these groups in clinical trials.ObjectiveTo characterize the representation of racial and ethnic minorities,
the elderly, and women in cancer trials sponsored by the National Cancer Institute.Design, Setting, and PatientsCross-sectional population-based analysis of all participants in therapeutic
nonsurgical National Cancer Institute Clinical Trial Cooperative Group breast,
colorectal, lung, and prostate cancer clinical trials in 2000 through 2002.
In a separate analysis, the ethnic distribution of patients enrolled in 2000
through 2002 was compared with those enrolled in 1996 through 1998, using
logistic regression models to estimate the relative risk ratio of enrollment
for racial and ethnic minorities to that of white patients during these time
periods.Main Outcome MeasureEnrollment fraction, defined as the number of trial enrollees divided
by the estimated US cancer cases in each race and age subgroup.ResultsCancer research participation varied significantly across racial/ethnic
and age groups. Compared with a 1.8% enrollment fraction among white patients,
lower enrollment fractions were noted in Hispanic (1.3%; odds ratio [OR] vs
whites, 0.72; 95% confidence interval [CI], 0.68-0.77; P<.001) and black (1.3%; OR, 0.71; 95% CI, 0.68-0.74; P<.001) patients. There was a strong relationship between age and
enrollment fraction, with trial participants 30 to 64 years of age representing
3.0% of incident cancer patients in that age group, in comparison to 1.3%
of 65- to 74-year-old patients and 0.5% of patients 75 years of age and older.
This inverse relationship between age and trial enrollment fraction was consistent
across racial and ethnic groups. Although the total number of trial participants
increased during our study period, the representation of racial and ethnic
minorities decreased. In comparison to whites, after adjusting for age, cancer
type, and sex, patients enrolled in 2000 through 2002 were 24% less likely
to be black (adjusted relative risk ratio, 0.76; 95% CI, 0.65-0.89; P<.001). Men were more likely than women to enroll in
colorectal cancer trials (enrollment fractions: 2.1% vs 1.6%, respectively;
OR, 1.30; 95% CI, 1.24-1.35; P<.001) and lung
cancer trials (enrollment fractions: 0.9% vs 0.7%, respectively; OR, 1.23;
95% CI, 1.16-1.31; P<.001).ConclusionsEnrollment in cancer trials is low for all patient groups. Racial and
ethnic minorities, women, and the elderly were less likely to enroll in cooperative
group cancer trials than were whites, men, and younger patients, respectively.
The proportion of trial participants who are black has declined in recent
years.
TL;DR: A large fraction of the Caenorhabditis elegans interactome network is mapped, starting with a subset of metazoan-specific proteins, and more than 4000 interactions were identified from high-throughput, yeast two-hybrid screens.
Abstract: To initiate studies on how protein-protein interaction (or "interactome") networks relate to multicellular functions, we have mapped a large fraction of the Caenorhabditis elegans interactome network. Starting with a subset of metazoan-specific proteins, more than 4000 interactions were identified from high-throughput, yeast two-hybrid (HT=Y2H) screens. Independent coaffinity purification assays experimentally validated the overall quality of this Y2H data set. Together with already described Y2H interactions and interologs predicted in silico, the current version of the Worm Interactome (WI5) map contains approximately 5500 interactions. Topological and biological features of this interactome network, as well as its integration with phenome and transcriptome data sets, lead to numerous biological hypotheses.
TL;DR: This paper forms a control problem with a communication channel connecting the sensor to the controller, and provides upper and lower bounds on the channel rate required to achieve different control objectives.
Abstract: There is an increasing interest in studying control systems employing multiple sensors and actuators that are geographically distributed. Communication is an important component of these distributed and networked control systems. Hence, there is a need to understand the interactions between the control components and the communication components of the distributed system. In this paper, we formulate a control problem with a communication channel connecting the sensor to the controller. Our task involves designing the channel encoder and channel decoder along with the controller to achieve different control objectives. We provide upper and lower bounds on the channel rate required to achieve these different control objectives. In many cases, these bounds are tight. In doing so, we characterize the "information complexity" of different control objectives.
Space Telescope Science Institute1, Johns Hopkins University2, Pennsylvania State University3, Centre national de la recherche scientifique4, European Southern Observatory5, Yale University6, California Institute of Technology7, Goddard Space Flight Center8, Max Planck Society9, University of California, Davis10, European Space Agency11, University of California, Santa Cruz12, University of Arizona13, University of Bonn14, University of California, Berkeley15, University of Oxford16
TL;DR: The GOODS survey as mentioned in this paper is based on multiband imaging data obtained with the Hubble Space Telescope and the Advanced Camera for Surveys (ACS) and covers roughly 320 arcmin2 in the ACS F435W, F606w, F814W, and F850LP bands, divided into two well-studied fields.
Abstract: This special issue of the Astrophysical Journal Letters is dedicated to presenting initial results from the Great Observatories Origins Deep Survey (GOODS) that are primarily, but not exclusively, based on multiband imaging data obtained with the Hubble Space Telescope and the Advanced Camera for Surveys (ACS). The survey covers roughly 320 arcmin2 in the ACS F435W, F606W, F814W, and F850LP bands, divided into two well-studied fields. Existing deep observations from the Chandra X-Ray Observatory and ground-based facilities are supplemented with new, deep imaging in the optical and near-infrared from the European Southern Observatory and from the Kitt Peak National Observatory. Deep observations with the Space Infrared Telescope Facility are scheduled. Reduced data from all facilities are being released worldwide within 3-6 months of acquisition. Together, this data set provides two deep reference fields for studies of distant normal and active galaxies, supernovae, and faint stars in our own Galaxy. This Letter serves to outline the survey strategy and describe the specific data that have been used in the accompanying letters, summarizing the reduction procedures and sensitivity limits.
TL;DR: Botero et al. as discussed by the authors investigated the regulation of labor markets through employment, collective relations, and social security laws in 85 countries and found that the political power of the left is associated with more stringent labor regulations and more generous social security systems, and that socialist, French and Scandinavian legal origin countries have sharply higher levels of labor regulation than do common law countries.
Abstract: Author(s): Botero, Juan; Djankov, Simeon; La Porta, Rafael; Lopez-de-Silanes, Florencio; Shleifer, Andrei | Abstract: We investigate the regulation of labor markets through employment, collective relations, and social security laws in 85 countries. We find that the political power of the left is associated with more stringent labor regulations and more generous social security systems, and that socialist, French and Scandinavian legal origin countries have sharply higher levels of labor regulation than do common law countries. However, the effects of legal origins are larger, and explain more of the variation in regulations, than those of politics. Heavier regulation of labor is associated with lower labor force participation and higher unemployment, especially of the young. These results are most naturally consistent with legal theories, according to which countries have pervasive regulaory styles inherited from the transplantation of legal systems.
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TL;DR: The authors found that most indicators of institutional quality used to establish the proposition that institutions cause economic growth are conceptually unsuitable for that purpose and also found that some of the instrumental variable techniques used in the literature are flawed.
Abstract: We revisit the debate over whether political institutions cause economic growth, or whether, alternatively, growth and human capital accumulation lead to institutional improvement We find that most indicators of institutional quality used to establish the proposition that institutions cause growth are constructed to be conceptually unsuitable for that purpose We also find that some of the instrumental variable techniques used in the literature are flawed Basic OLS results, as well as a variety of additional evidence, suggest that a) human capital is a more basic source of growth than are the institutions, b) poor countries get out of poverty through good policies, often pursued by dictators, and c) subsequently improve their political institutions
TL;DR: The diagnostic accuracy of PCT markers was higher than that of CRP markers among patients hospitalized for suspected bacterial infections and had a higher positive likelihood ratio and lower negative likelihood ratio than didCRP markers in both groups.
Abstract: A meta-analysis was performed to evaluate the accuracy of determination of procalcitonin (PCT) and C-reactive protein (CRP) levels for the diagnosis of bacterial infection. The analysis included published studies that evaluated these markers for the diagnosis of bacterial infections in hospitalized patients. PCT level was more sensitive (88% [95% confidence interval [CI], 80%-93%] vs. 75% [95% CI, 62%-84%]) and more specific (81% [95% CI, 67%-90%] vs. 67% [95% CI, 56%-77%]) than CRP level for differentiating bacterial from noninfective causes of inflammation. The Q value for PCT markers was higher (0.82 vs. 0.73). The sensitivity for differentiating bacterial from viral infections was also higher for PCT markers (92% [95% CI, 86%-95%] vs. 86% [95% CI, 65%-95%]); the specificities were comparable (73% [95% CI, 42%-91%] vs. 70% [95% CI, 19%-96%]). The Q value was higher for PCT markers (0.89 vs. 0.83). PCT markers also had a higher positive likelihood ratio and lower negative likelihood ratio than did CRP markers in both groups. On the basis of this analysis, the diagnostic accuracy of PCT markers was higher than that of CRP markers among patients hospitalized for suspected bacterial infections.
TL;DR: An update of the TG-43 protocol for calculation of dose-rate distributions around photon-emitting brachytherapy sources is presented, and a unified approach to comparing reference dose distributions derived from different investigators to develop a single critically evaluated consensus dataset is recommended.
Abstract: Since publication of the American Association of Physicists in Medicine (AAPM) Task Group No. 43 Report in 1995 (TG-43), both the utilization of permanent source implantation and the number of low-energy interstitial brachytherapy source models commercially available have dramatically increased. In addition, the National Institute of Standards and Technology has introduced a new primary standard of air-kerma strength, and the brachytherapy dosimetry literature has grown substantially, documenting both improved dosimetry methodologies and dosimetric characterization of particular source models. In response to these advances, the AAPM Low-energy Interstitial Brachytherapy Dosimetry subcommittee (LIBD) herein presents an update of the TG-43 protocol for calculation of dose-rate distributions around photon-emitting brachytherapy sources. The updated protocol (TG-43U1) includes (a) a revised definition of air-kerma strength; (b) elimination of apparent activity for specification of source strength; (c) elimination of the anisotropy constant in favor of the distance-dependent one-dimensional anisotropy function; (d) guidance on extrapolating tabulated TG-43 parameters to longer and shorter distances; and (e) correction for minor inconsistencies and omissions in the original protocol and its implementation. Among the corrections are consistent guidelines for use of point- and line-source geometry functions. In addition, this report recommends a unified approach to comparing reference dose distributions derived from different investigators to develop a single critically evaluated consensus dataset as well as guidelines for performing and describing future theoretical and experimental single-source dosimetry studies. Finally, the report includes consensus datasets, in the form of dose-rate constants, radial dose functions, and one-dimensional (1D) and two-dimensional (2D) anisotropy functions, for all low-energy brachytherapy source models that met the AAPM dosimetric prerequisites [Med. Phys. 25, 2269 (1998)] as of July 15, 2001. These include the following 125I sources: Amersham Health models 6702 and 6711, Best Medical model 2301, North American Scientific Inc. (NASI) model MED3631-A/M, Bebig/Theragenics model I25.S06, and the Imagyn Medical Technologies Inc. isostar model IS-12501. The 103Pd sources included are the Theragenics Corporation model 200 and NASI model MED3633. The AAPM recommends that the revised dose-calculation protocol and revised source-specific dose-rate distributions be adopted by all end users for clinical treatment planning of low energy brachytherapy interstitial sources. Depending upon the dose-calculation protocol and parameters currently used by individual physicists, adoption of this protocol may result in changes to patient dose calculations. These changes should be carefully evaluated and reviewed with the radiation oncologist preceding implementation of the current protocol.
TL;DR: In this paper, the authors investigate the role of information uncertainty in short-term CAPM anomalies and cross-sectional variations in stock returns, and show that greater information uncertainty produces relatively higher expected returns following good news and relatively lower expected return following bad news.
Abstract: There is substantial evidence of short-term stock price continuation, which prior literature often attributes to investor behavioral biases such as underreaction to new information. This paper investigates the role of information uncertainty in short-term CAPM anomalies and cross-sectional variations in stock returns. If short-term price continuation is due to investor behavioral biases, we should observe greater price drift when there is greater information uncertainty. As a result, greater information uncertainty produces relatively higher expected returns following good news and relatively lower expected returns following bad news. The evidence presented in this paper supports this hypothesis.
TL;DR: An overview is given on the diverse uses of computational chemistry in drug discovery, with particular emphasis on virtual screening, de novo design, evaluation of drug-likeness, and advanced methods for determining protein-ligand binding.
Abstract: An overview is given on the diverse uses of computational chemistry in drug discovery. Particular emphasis is placed on virtual screening, de novo design, evaluation of drug-likeness, and advanced methods for determining protein-ligand binding.
TL;DR: Mixed-effects models use all available data, can properly account for correlation between repeated measurements on the same subject, have greater flexibility to model time effects, and can handle missing data more appropriately makes them the preferred choice for the analysis of repeated-measures data.
Abstract: Background The analysis of repeated-measures data presents challenges to investigators and is a topic for ongoing discussion in the Archives of
General Psychiatry. Traditional methods of statistical analysis (end-point analysis and univariate and multivariate repeated-measures analysis of variance [rANOVA and rMANOVA, respectively]) have known disadvantages. More sophisticated mixed-effects models provide flexibility, and recently developed software makes them available to researchers. Objectives To review methods for repeated-measures analysis and discuss advantages and potential misuses of mixed-effects models. Also, to assess the extent of the shift from traditional to mixed-effects approaches in published reports in the Archives of General Psychiatry . Data Sources The Archives of General Psychiatry from 1989 through 2001, and the Department of Veterans Affairs Cooperative Study 425. Study Selection Studies with a repeated-measures design, at least 2 groups, and a continuous response variable. Data Extraction The first author ranked the studies according to the most advanced statistical method used in the following order: mixed-effects model, rMANOVA, rANOVA, and end-point analysis. Data Synthesis The use of mixed-effects models has substantially increased during the last 10 years. In 2001, 30% of clinical trials reported in the Archives of General Psychiatry used mixed-effects analysis. Conclusions Repeated-measures ANOVAs continue to be used widely for the analysis of repeated-measures data, despite risks to interpretation. Mixed-effects models use all available data, can properly account for correlation between repeated measurements on the same subject, have greater flexibility to model time effects, and can handle missing data more appropriately. Their flexibility makes them the preferred choice for the analysis of repeated-measures data.
TL;DR: In this article, the authors examine the received wisdom of services marketing and challenge the validity and continued usefulness of its core paradigm, namely, the assertion that four specific characteristics (i.e.,
Abstract: This article examines the received wisdom of services marketing and challenges the validity and continued usefulness of its core paradigm, namely, the assertion that four specific characteristics—i...
TL;DR: The hypothesis hepatic steatosis leads to hepatic insulin resistance by stimulating gluconeogenesis and activating PKC-ϵ and JNK1, which may interfere with tyrosine phosphorylation of IRS-1 and IRS-2 and impair the ability of insulin to activate glycogen synthase is supported.
TL;DR: This paper showed that although most programs have indeed resisted retrenchment, U.S. social policy has also offered increasingly incomplete risk protection in an era of dramatic social change, and argued that the declining scope of risk protection also reflects deliberate and theoretically explicable strategies of reform adopted by welfare state opponents in the face of popular and changeresistant policies.
Abstract: Over the last decade, students of the welfare state have produced an impressive body of research on retrenchment, the dominant thrust of which is that remarkably few welfare states have experienced fundamental shifts. This article questions this now-conventional wisdom by reconsidering the post-1970s trajectory of the American welfare state, long considered the quintessential case of social policy stability. I demonstrate that although most programs have indeed resisted retrenchment, U.S. social policy has also offered increasingly incomplete risk protection in an era of dramatic social change. Although some of this disjuncture is inadvertent—an unintended consequence of the very political stickiness that has stymied retrenchment—I argue that the declining scope of risk protection also reflects deliberate and theoretically explicable strategies of reform adopted by welfare state opponents in the face of popular and change-resistant policies, a finding that has significant implications for the study of institutional change more broadly.
TL;DR: Most adolescents engaged in SMB for automatic reinforcement, although a sizable portion endorsed social reinforcement functions as well, and the results supported the structural validity and reliability of the hypothesized functional model of SMB.
Abstract: This study applied a functional approach to the assessment of self-mutilative behavior (SMB) among adolescent psychiatric inpatients On the basis of past conceptualizations of different forms of self-injurious behavior, the authors hypothesized that SMB is performed because of the automatically reinforcing (ie, reinforced by oneself; eg, emotion regulation) and/or socially reinforcing (ie, reinforced by others; eg, attention, avoidance-escape) properties associated with such behaviors Data were collected from 108 adolescent psychiatric inpatients referred for self-injurious thoughts or behaviors Adolescents reported engaging in SMB frequently, using multiple methods, and having an early age of onset Moreover, the results supported the structural validity and reliability of the hypothesized functional model of SMB Most adolescents engaged in SMB for automatic reinforcement, although a sizable portion endorsed social reinforcement functions as well These findings have direct implications for the understanding, assessment, and treatment of SMB