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Showing papers by "Radboud University Nijmegen published in 2004"


Journal ArticleDOI
TL;DR: In this article, a systematic review of the effectiveness and costs of different guideline development, dissemination and implementation strategies was carried out with key informants from primary and secondary care in the UK.
Abstract: OBJECTIVES: To undertake a systematic review of the effectiveness and costs of different guideline development, dissemination and implementation strategies. To estimate the resource implications of these strategies. To develop a framework for deciding when it is efficient to develop and introduce clinical guidelines. DATA SOURCES: MEDLINE, Healthstar, Cochrane Controlled Trial Register, EMBASE, SIGLE and the specialised register of the Cochrane Effective Practice and Organisation of Care (EPOC) group. REVIEW METHODS: Single estimates of dichotomous process variables were derived for each study comparison based upon the primary end-point or the median measure across several reported end-points. Separate analyses were undertaken for comparisons of different types of intervention. The study also explored whether the effects of multifaceted interventions increased with the number of intervention components. Studies reporting economic data were also critically appraised. A survey to estimate the feasibility and likely resource requirements of guideline dissemination and implementation strategies in UK settings was carried out with key informants from primary and secondary care. RESULTS: In total, 235 studies reporting 309 comparisons met the inclusion criteria; of these 73% of comparisons evaluated multifaceted interventions, although the maximum number of replications of a specific multifaceted intervention was 11 comparisons. Overall, the majority of comparisons reporting dichotomous process data observed improvements in care; however, there was considerable variation in the observed effects both within and across interventions. Commonly evaluated single interventions were reminders, dissemination of educational materials, and audit and feedback. There were 23 comparisons of multifaceted interventions involving educational outreach. The majority of interventions observed modest to moderate improvements in care. No relationship was found between the number of component interventions and the effects of multifaceted interventions. Only 29.4% of comparisons reported any economic data. The majority of studies only reported costs of treatment; only 25 studies reported data on the costs of guideline development or guideline dissemination and implementation. The majority of studies used process measures for their primary end-point, despite the fact that only three guidelines were explicitly evidence based (and may not have been efficient). Respondents to the key informant survey rarely identified existing budgets to support guideline dissemination and implementation strategies. In general, the respondents thought that only dissemination of educational materials and short (lunchtime) educational meetings were generally feasible within current resources. CONCLUSIONS: There is an imperfect evidence base to support decisions about which guideline dissemination and implementation strategies are likely to be efficient under different circumstances. Decision makers need to use considerable judgement about how best to use the limited resources they have for clinical governance and related activities to maximise population benefits. They need to consider the potential clinical areas for clinical effectiveness activities, the likely benefits and costs required to introduce guidelines and the likely benefits and costs as a result of any changes in provider behaviour. Further research is required to: develop and validate a coherent theoretical framework of health professional and organisational behaviour and behaviour change to inform better the choice of interventions in research and service settings, and to estimate the efficiency of dissemination and implementation strategies in the presence of different barriers and effect modifiers.

2,733 citations


Book
01 Jan 2004
TL;DR: In this paper, the authors provide an overview of research into tone and intonation, discussing why speakers vary their pitch, what pitch variations mean, and how they are integrated into our grammars.
Abstract: Tone and Intonation are two types of pitch variation, which are used by speakers of all languages in order to give shape to utterances. More specifically, tone encodes segments and morphemes, and intonation gives utterances a further discoursal meaning that is independent of the meanings of the words themselves. In this comprehensive survey, Carlos Gussenhoven provides an overview of research into tone and intonation, discussing why speakers vary their pitch, what pitch variations mean, and how they are integrated into our grammars. He also explains why intonation in part appears to be universally understood, while at other times it is language-specific and can lead to misunderstandings. After eight chapters on general topics relating to pitch modulation, the book's central arguments are illustrated with comprehensive phonological descriptions - partly in Optimality Theory - of the tonal and intonational systems of six languages, including Japanese, Dutch, and English.

1,099 citations


Journal ArticleDOI
TL;DR: Caspofungin is as effective as and generally better tolerated than liposomal amphotericin B when given as empirical antifungal therapy in patients with persistent fever and neutropenia.
Abstract: Background Patients with persistent fever and neutropenia often receive empirical therapy with conventional or liposomal amphotericin B for the prevention and early treatment of invasive fungal infections. Caspofungin, a member of the new echinocandin class of compounds, may be an effective alternative that is better tolerated than amphotericin B. Methods In this randomized, double-blind, multinational trial, we assessed the efficacy and safety of caspofungin as compared with liposomal amphotericin B as empirical antifungal therapy. At study entry, patients were stratified according to risk and according to whether they had previously received antifungal prophylaxis. A successful outcome was defined as the fulfillment of all components of a five-part composite end point. Results Efficacy was evaluated in 1095 patients (556 receiving caspofungin and 539 receiving liposomal amphotericin B). After adjustment for strata, the overall success rates were 33.9 percent for caspofungin and 33.7 percent for liposoma...

850 citations


Journal ArticleDOI
01 Dec 2004-Proteins
TL;DR: A new force field called YAMBER (Yet Another Model Building and Energy Refinement force field), which is shown to do significantly less damage to X‐ray structures, often move homology models in the right direction, and occasionally make them look like experimental structures.
Abstract: Today's energy functions are not able yet to distinguish reliably between correct and almost correct protein models. Improving these near-native models is currently a major bottle-neck in homology modeling or experimental structure determination at low resolution. Increasingly accurate energy functions are required to complete the "last mile of the protein folding problem," for example during a molecular dynamics simulation. We present a new approach to reach this goal. For 50 high resolution X-ray structures, the complete unit cell was reconstructed, including disordered water molecules, counter ions, and hydrogen atoms. Simulations were then run at the pH at which the crystal was solved, while force-field parameters were iteratively adjusted so that the damage done to the structures was minimal. Starting with initial parameters from the AMBER force field, the optimization procedure converged at a new force field called YAMBER (Yet Another Model Building and Energy Refinement force field), which is shown to do significantly less damage to X-ray structures, often move homology models in the right direction, and occasionally make them look like experimental structures. Application of YAMBER during the CASP5 structure prediction experiment yielded a model for target 176 that was ranked first among 150 submissions. Due to its compatibility with the well-established AMBER format, YAMBER can be used by almost any molecular dynamics program. The parameters are freely available from www.yasara.org/yamber.

798 citations


Journal ArticleDOI
TL;DR: The structure, assembly, interactions, stability and post-translational modifications of the crystallins are reviewed, not only in isolation but also as part of a multi-component system.
Abstract: The alpha-, beta- and gamma-crystallins are the major protein components of the vertebrate eye lens, alpha-crystallin as a molecular chaperone as well as a structural protein, beta- and gamma-crystallins as structural proteins. For the lens to be able to retain life-long transparency in the absence of protein turnover, the crystallins must meet not only the requirement of solubility associated with high cellular concentration but that of longevity as well. For proteins, longevity is commonly assumed to be correlated with long-term retention of native structure, which in turn can be due to inherent thermodynamic stability, efficient capture and refolding of non-native protein by chaperones, or a combination of both. Understanding how the specific interactions that confer intrinsic stability of the protein fold are combined with the stabilizing effect of protein assembly, and how the non-specific interactions and associations of the assemblies enable the generation of highly concentrated solutions, is thus of importance to understand the loss of transparency of the lens with age. Post-translational modification can have a major effect on protein stability but an emerging theme of the few studies of the effect of post-translational modification of the crystallins is one of solubility and assembly. Here we review the structure, assembly, interactions, stability and post-translational modifications of the crystallins, not only in isolation but also as part of a multi-component system. The available data are discussed in the context of the establishment, the maintenance and finally, with age, the loss of transparency of the lens. Understanding the structural basis of protein stability and interactions in the healthy eye lens is the route to solve the enormous medical and economical problem of cataract.

796 citations


Journal ArticleDOI
TL;DR: In this article, the authors explore the evolution in power of black holes of all masses, and their associated jets, within the scheme of an accretion rate-dependent state transition, and show that hard and quiescent state x-ray binaries, LINERs, FR I radio galaxies, and BL Lacs can be unified and fall on a common radio/x-ray correlation.
Abstract: We explore the evolution in power of black holes of all masses, and their associated jets, within the scheme of an accretion rate-dependent state transition. Below a critical value of the accretion rate all systems are assumed to undergo a transition to a state where the dominant accretion mode is optically thin and radiatively inefficient. In these significantly sub-Eddington systems, the spectral energy distribution is predicted to be dominated by non-thermal emission from a relativistic jet whereas near-Eddington black holes will be dominated instead by emission from the accretion disk. Reasonable candidates for such a sub-Eddington state include x-ray binaries in the hard and quiescent states, the Galactic Center (Sgr A*), LINERs, FR I radio galaxies, and a large fraction of BL Lac objects. Standard jet physics predicts non-linear scaling between the optically thick (radio) and optically thin (optical or x-ray) emission of these systems, which has been confirmed recently in x-ray binaries. We show that this scaling relation is also a function of black hole mass and only slightly of the relativistic Doppler factor. Taking the scaling into account we show that indeed hard and quiescent state x-ray binaries, LINERs, FR I radio galaxies, and BL Lacs can be unified and fall on a common radio/x-ray correlation. This suggests that jet domination is an important stage in the luminosity evolution of accreting black hole systems.

793 citations


Journal ArticleDOI
TL;DR: A large French family including members affected by nonspecific X-linked mental retardation, with or without autism or pervasive developmental disorder in affected male patients, has been found to have a 2-base-pair deletion in the Neuroligin 4 gene (NLGN4) located at Xp22.33.
Abstract: A large French family including members affected by nonspecific X-linked mental retardation, with or without autism or pervasive developmental disorder in affected male patients, has been found to have a 2–base-pair deletion in the Neuroligin 4 gene (NLGN4) located at Xp22.33. This mutation leads to a premature stop codon in the middle of the sequence of the normal protein and is thought to suppress the transmembrane domain and sequences important for the dimerization of neuroligins that are required for proper cell-cell interaction through binding to β-neurexins. As the neuroligins are mostly enriched at excitatory synapses, these results suggest that a defect in synaptogenesis may lead to deficits in cognitive development and communication processes. The fact that the deletion was present in both autistic and nonautistic mentally retarded males suggests that the NLGN4 gene is not only involved in autism, as previously described, but also in mental retardation, indicating that some types of autistic disorder and mental retardation may have common genetic origins.

737 citations


Journal ArticleDOI
TL;DR: This article examined the connections between attitudes, group norms, and students' behaviour in bullying situations (bullying others, assisting the bully, reinforcing a bully, defending the victim, or staying outside bullying situations).
Abstract: We examined the connections between attitudes, group norms, and students’ behaviour in bullying situations (bullying others, assisting the bully, reinforcing the bully, defending the victim, or staying outside bullying situations). The participants were 1220 elementary school children (600 girls and 620 boys) from 48 school classes from Grades four, five, and six, i.e., 9–10, 10–11, and 11–12 years of age. Whereas attitudes did predict behaviour at the student level in most cases (although the effects were moderate after controlling for gender), the group norms could be used in explaining variance at the classroom level, especially in the upper grades. The class context (even if not classroom norms specifically) had more effect on girls’ than on boys’ bullying-related behaviours.

689 citations


Journal ArticleDOI
TL;DR: Testing for anti-CCP antibodies in UA allows accurate prediction of a substantial number of patients who will fulfill the ACR criteria for RA.
Abstract: Objective Rheumatoid arthritis (RA) is a common, severe, chronic inflammatory joint disease. Since the disease may initially be indistinguishable from other forms of arthritis, early diagnosis can be difficult. Autoantibodies seen in RA can be detected years before clinical symptoms develop. In an inception cohort of patients with recent-onset arthritis, we undertook this study to assess the predictive value of RA-specific autoantibodies to cyclic citrullinated peptides (CCPs) in patients with undifferentiated arthritis (UA). Methods Anti-CCP2 antibody tests were performed at baseline in 936 consecutive, newly referred patients with recent-onset arthritis. Patients who could not be properly classified 2 weeks after inclusion were categorized as having UA. Patients with UA were followed up for 3 years and evaluated for progression of their disease to RA as defined by the American College of Rheumatology (ACR) 1987 revised criteria. Results Three hundred eighteen of 936 patients with recent-onset arthritis were classified as having UA and were available for analysis. After 3 years of followup, 127 of 318 UA patients (40%) had been classified as having RA. RA had developed in 63 of 249 patients (25%) with a negative anti-CCP test and in 64 of 69 patients (93%) with a positive anti-CCP test (odds ratio 37.8 [95% confidence interval 13.8–111.9]). Multivariate analysis of the presence of anti-CCP antibodies and parameters from the ACR criteria identified polyarthritis, symmetric arthritis, erosions on radiographs, and anti-CCP antibodies as significant predictors of RA. Conclusion Testing for anti-CCP antibodies in UA allows accurate prediction of a substantial number of patients who will fulfill the ACR criteria for RA.

645 citations


Journal ArticleDOI
TL;DR: The results suggest that the effects of mimicry are not simply due to increased liking for the mimicker, but are due toincreased prosocial orientation in general.
Abstract: Recent studies have shown that mimicry occurs unintentionally and even among strangers. In the present studies, we investigated the consequences of this automatic phenomenon in order to learn more about the adaptive function it serves. In three studies, we consistently found that mimicry increases prosocial behavior. Participants who had been mimicked were more helpful and generous toward other people than were nonmimicked participants. These beneficial consequences of mimicry were not restricted to behavior directed toward the mimicker, but included behavior directed toward people not directly involved in the mimicry situation. These results suggest that the effects of mimicry are not simply due to increased liking for the mimicker, but are due to increased prosocial orientation in general.

625 citations


Journal ArticleDOI
TL;DR: Among patients with RA for whom previous DMARD treatment had failed, adalimumab monotherapy achieved significant, rapid, and sustained improvements in disease activity and improved physical function and was safe and well tolerated.
Abstract: Objective: To evaluate the efficacy and safety of monotherapy with adalimumab in patients with RA for whom previous DMARD treatment has failed. Methods: In a 26 week, double blind, placebo controlled, phase III trial, 544 patients with RA were randomised to monotherapy with adalimumab 20 mg every other week, 20 mg weekly, 40 mg every other week, 40 mg weekly, or placebo. The primary efficacy end point was ≥20% improvement in the ACR core criteria (ACR20 response). Secondary efficacy end points included ACR50, ACR70, EULAR responses, and the Disability Index of the Health Assessment Questionnaire (HAQ DI). Results: After 26 weeks, patients treated with adalimumab 20 mg every other week, 20 mg weekly, 40 mg every other week, and 40 mg weekly had significantly better response rates than those treated with placebo: ACR20 (35.8%, 39.3%, 46.0%, 53.4%, respectively v 19.1%; p⩽0.01); ACR50 (18.9%, 20.5%, 22.1%, 35.0% v 8.2%; p⩽0.05); ACR70 (8.5%, 9.8%, 12.4%, 18.4% v 1.8%; p⩽0.05). Moderate EULAR response rates were significantly greater with adalimumab than with placebo (41.5%, 48.2%, 55.8%, 63.1% v 26.4%; p⩽0.05). Patients treated with adalimumab achieved better improvements in mean HAQ DI than those receiving placebo (−0.29, −0.39, −0.38, −0.49 v −0.07; p⩽0.01). No significant differences were found between adalimumab and placebo treated patients for serious adverse events, serious infections, or malignancies. Injection site reaction occurred in 10.6% and 0.9% of adalimumab and placebo treated patients, respectively (p⩽0.05). Conclusion: Among patients with RA for whom previous DMARD treatment had failed, adalimumab monotherapy achieved significant, rapid, and sustained improvements in disease activity and improved physical function and was safe and well tolerated.

Journal ArticleDOI
TL;DR: In this article, the Coulomb interaction was calculated from first principles, using the random-phase approximation, and an expression for the frequency-dependent Coulomb interactions was derived for the case of nickel.
Abstract: We propose a systematic procedure for constructing effective models of strongly correlated materials. The parameters, in particular the on-site screened Coulomb interaction $U$, are calculated from first principles, using the random-phase approximation. We derive an expression for the frequency-dependent $U(\ensuremath{\omega})$ and show, for the case of nickel, that its high-frequency part has significant influence on the spectral functions. We propose a scheme for taking into account the energy dependence of $U(\ensuremath{\omega})$, so that a model with an energy-independent local interaction can still be used for low-energy properties.

Journal ArticleDOI
24 Jun 2004-Nature
TL;DR: It is shown that, using a short laser pulse, the spins of the antiferromagnet TmFeO3 can indeed be manipulated on a timescale of a few picoseconds, in contrast to the hundreds of picoseConds in a ferromagnets.
Abstract: All magnetically ordered materials can be divided into two primary classes: ferromagnets and antiferromagnets. Since ancient times, ferromagnetic materials have found vast application areas, from the compass to computer storage and more recently to magnetic random access memory and spintronics. In contrast, antiferromagnetic (AFM) materials, though representing the overwhelming majority of magnetically ordered materials, for a long time were of academic interest only. The fundamental difference between the two types of magnetic materials manifests itself in their reaction to an external magnetic field-in an antiferromagnet, the exchange interaction leads to zero net magnetization. The related absence of a net angular momentum should result in orders of magnitude faster AFM spin dynamics. Here we show that, using a short laser pulse, the spins of the antiferromagnet TmFeO3 can indeed be manipulated on a timescale of a few picoseconds, in contrast to the hundreds of picoseconds in a ferromagnet. Because the ultrafast dynamics of spins in antiferromagnets is a key issue for exchange-biased devices, this finding can expand the now limited set of applications for AFM materials.

Journal ArticleDOI
TL;DR: The reliability and validity of the Attachment Q Sort (AQS) was tested in a series of meta-analyses on 139 studies with 13,835 children and it was concluded that the observer AQS, but not the self-reported AQs, is a valid measure of attachment.
Abstract: The reliability and validity of the Attachment Q Sort (AQS; Waters & Deane, 1985) was tested in a series of meta-analyses on 139 studies with 13,835 children. The observer AQS security score showed convergent validity with Strange Situation procedure (SSP) security (r = .31) and excellent predictive validity with sensitivity measures (r = .39). Its association with temperament was weaker (r = .16), which supports the discriminant validity of the observer AQS. Studies on the stability of the observer AQS are still relatively scarce but they have yielded promising results (mean r = .28; k = 4, n = 162). It is concluded that the observer AQS, but not the self-reported AQS, is a valid measure of attachment.

Journal ArticleDOI
TL;DR: Citrullinated vimentin is an interesting candidate autoantigen in RA and may provide new insights into the potential role of citrullination synovial antigens and the antibodies directed to them in the pathophysiology of RA.
Abstract: Antibodies directed to the Sa antigen are highly specific for rheumatoid arthritis (RA) and can be detected in approximately 40% of RA sera. The antigen, a doublet of protein bands of about 50 kDa, is present in placenta and in RA synovial tissue. Although it has been stated that the Sa antigen is citrullinated vimentin, experimental proof for this claim has never been published. In this study, we investigated the precise nature of the antigen. Peptide sequences that were obtained from highly purified Sa antigen were unique to vimentin. Recombinant vimentin, however, was not recognized by anti-Sa reference sera. In vivo, vimentin is subjected to various post-translational modifications, including citrullination. Since antibodies to citrullinated proteins are known to be highly specific for RA, we investigated whether Sa is citrullinated and found that Sa indeed is citrullinated vimentin. Anti-Sa antibodies thus belong to the family of anticitrullinated protein/peptide antibodies. The presence of the Sa antigen in RA synovial tissue, and the recent observation that vimentin is citrullinated in dying human macrophages, make citrullinated vimentin an interesting candidate autoantigen in RA and may provide new insights into the potential role of citrullinated synovial antigens and the antibodies directed to them in the pathophysiology of RA.

Journal ArticleDOI
TL;DR: A sedentary lifestyle during healthy aging is associated with decreased left ventricular compliance, leading to diminished diastolic performance, which may contribute to the high incidence of heart failure in the elderly.
Abstract: Background— Left ventricular compliance appears to decrease with aging, which may contribute to the high incidence of heart failure in the elderly. However, whether this change is an inevitable consequence of senescence or rather secondary to reduced physical activity is unknown. Methods and Results— Twelve healthy sedentary seniors (69.8±3 years old; 6 women, 6 men) and 12 Masters athletes (67.8±3 years old; 6 women, 6 men) underwent pulmonary artery catheterization to define Starling and left ventricular pressure-volume curves. Data were compared with those obtained in 14 young but sedentary control subjects (28.9±5 years old; 7 women, 7 men). Pulmonary capillary wedge pressures and left ventricular end-diastolic volumes by use of echocardiography were measured at baseline, during decreased cardiac filling by use of lower-body negative pressure (−15 and −30 mm Hg), and after saline infusion (15 and 30 mL/kg). Stroke volume for any given filling pressure was greater in Masters athletes compared with the ...

Journal ArticleDOI
TL;DR: Recent developments in the field include increasing awareness of the importance of the protein surface for stability, as well as the notion that normally a very limited number of mutations can yield a large increase in stability.

Journal ArticleDOI
V. M. Abazov1, Brad Abbott2, M. Abolins3, Bobby Samir Acharya4  +601 moreInstitutions (73)
TL;DR: In this article, the authors reported the observation of the X(3872) in the J/psipi(+)pi(-) channel with decaying to mu(+)mu(-), in p (p) over bar collisions at roots=1.96 TeV.
Abstract: We report the observation of the X(3872) in the J/psipi(+)pi(-) channel, with J/psi decaying to mu(+)mu(-), in p (p) over bar collisions at roots=1.96 TeV. Using approximately 230 pb(-1) of data collected with the Run II D0 detector, we observe 522+/-100 X(3872) candidates. The mass difference between the X(3872) state and the J/psi is measured to be 774.9+/-3.1(stat)+/-3.0(syst) MeV/c(2). We have investigated the production and decay characteristics of the X(3872) and find them to be similar to those of the psi(2S) state.

Journal ArticleDOI
TL;DR: PAD2 and PAD4 are the most likely candidate PAD isotypes for thecitrullination of synovial proteins in RA and the results indicate that citrullinated vimentin is a candidate autoantigen in RA.
Abstract: Background: Antibodies directed to proteins containing the non-standard amino acid citrulline, are extremely specific for rheumatoid arthritis (RA). Peptidylcitrulline can be generated by post-translational conversion of arginine residues. This process, citrullination, is catalysed by a group of calcium dependent peptidylarginine deiminase (PAD) enzymes. Objective: To investigate the expression and activity of four isotypes of PAD in peripheral blood and synovial fluid cells of patients with RA. Results: The data presented here show that citrullination of proteins by PAD enzymes is a process regulated at three levels: transcription—in peripheral blood PAD2 and PAD4 mRNAs are expressed predominantly in monocytes; PAD4 mRNA is not detectable in macrophages, translation—translation of PAD2 mRNA is subject to differentiation stage-specific regulation by its 3' UTR, and activation—the PAD proteins are only activated when sufficient Ca2+ is available. Such high Ca2+ concentrations are normally not present in living cells. In macrophages, which are abundant in the inflamed RA synovium, vimentin is specifically citrullinated after Ca2+ influx. Conclusion: PAD2 and PAD4 are the most likely candidate PAD isotypes for the citrullination of synovial proteins in RA. Our results indicate that citrullinated vimentin is a candidate autoantigen in RA.

Journal ArticleDOI
TL;DR: In this paper, a stable tree topology with four major groups of placental mammals is proposed, and the emerging tree has revealed numerous instances of convergent evolution and suggests a role for plate tectonics in the early evolutionary history of this group.
Abstract: Deciphering relationships among the orders of placental mammals remains an important problem in evolutionary biology and has implications for understanding patterns of morphological character evolution, reconstructing the ancestral placental genome, and evaluating the role of plate tectonics and dispersal in the biogeographic history of this group. Until recently, both molecular and morphological studies provided only a limited and questionable resolution of placental relationships. Studies based on larger and more diverse molecular datasets, and using an array of methodological approaches, are now converging on a stable tree topology with four major groups of placental mammals. The emerging tree has revealed numerous instances of convergent evolution and suggests a role for plate tectonics in the early evolutionary history of placental mammals. The reconstruction of mammalian phylogeny illustrates both the pitfalls and the powers of molecular systematics.


Journal ArticleDOI
TL;DR: Investigating the relationship between HLA class II gene polymorphisms and RA-specific IgG antibodies against cyclic citrullinated peptides found that more severe disease progression is found in RA patients with both anti-CCP antibodies and SE alleles.
Abstract: Objective. The functional role of HLA class II molecules in the pathogenesis of rheumatoid arthritis (RA) is unclear. HLA class II molecules are involved in the interaction between T and B lymphocytes required for long-lived B cell responses and generation of high-affinity IgG antibodies. We undertook this study to investigate the relationship between HLA class II gene polymorphisms and RA-specific IgG antibodies against cyclic citrullinated peptides (anti-CCP antibodies). Methods. High-resolution HLA-DR and DQ typing and anti-CCP-2 antibody testing were performed on 268 RA patients from the Early Arthritis Clinic cohort at the Department of Rheumatology of the Leiden University Medical Center. The presence of anti-CCP antibodies was analyzed in carriers of the different DR and DQ alleles. Disease progression was measured over a period of 4 years by scoring radiographs of the hands and feet using the Sharp/van der Heijde method. Results. Carriership of the individual alleles HLA-DRBt*0401, DRB1*1001, DQB1*0302, and DQBI*0501 was associated with the presence of antiCCP antibodies. Carriers of DQ-DR genotypes containing proposed RA susceptibility alleles were significantly more often anti-CCP antibody positive. Carriership of one or two HLA-DRB1 shared epitope (SE) alleles was significantly associated with production of anti-CCP antibodies (odds ratio [OR] 3.3, 95% confidence interval [95% CI] 1.8-6.0 and OR 13.3, 95% CI 4.6-40.4, respectively). An increased rate of joint destruction was observed in SE+, anti-CCP+ patients (mean Sharp score 7.6 points per year) compared with that in SE-, anti-CCP+ patients (2.4 points per year) (P = 0.04), SE+, anti-CCP- patients (1.6 points per year) (P < 0.001), and SE-, anti-CCP- patients (1.6 points per year) (11 < 0.001). Conclusion. HLA class II RA susceptibility alleles are associated with production of anti-CCP antibodies. Moreover, more severe disease progression is found in RA patients with both anti-CCP antibodies and SE alleles.

Journal ArticleDOI
TL;DR: The results show that normalization procedures that use information across multiple vowels to normalize a single vowel token performed better than those that include only information contained in the vowel token itself ("vowel-intrinsic" information).
Abstract: An evaluation of vowel normalization procedures for the purpose of studying language variation is presented. The procedures were compared on how effectively they (a) preserve phonemic information, (b) preserve information about the talker's regional background (or sociolinguistic information), and (c) minimize anatomical/physiological variation in acoustic representations of vowels. Recordings were made for 80 female talkers and 80 male talkers of Dutch. These talkers were stratified according to their gender and regional background. The normalization procedures were applied to measurements of the fundamental frequency and the first three formant frequencies for a large set of vowel tokens. The normalization procedures were evaluated through statistical pattern analysis. The results show that normalization procedures that use information across multiple vowels ("vowel-extrinsic" information) to normalize a single vowel token performed better than those that include only information contained in the vowel token itself ("vowel-intrinsic" information). Furthermore, the results show that normalization procedures that operate on individual formants performed better than those that use information across multiple formants (e.g., "formant-extrinsic" F2-F1).

Journal ArticleDOI
TL;DR: In this paper, the authors propose a framework to analyse power in policy practices based on the so-called policy arrangement approach, which combines elements of the old and new policy vocabularies.
Abstract: During the last few decades, both policy practices and policy idioms have drastically changed. Concepts such as interactive planning, network management, stakeholder dialogue, deliberative democracy, policy discourses, governance, etc. have replaced older ones such as public administration, policy programmes, interest groups, institutions, power, and the like. Although we recognise the relevance and importance of this shift in vocabulary, we also regret related ‘losses’. We particularly regret that the concept of power has – in our view – become an ‘endangered species’ in the field of public policy analysis. We therefore will develop a framework to analyse power – being a multi-layered concept – in policy practices in this article. We will do so on the basis of the so-called policy arrangement approach, which combines elements of the old and new policy vocabularies. In addition, we draw upon different power theories in developing our argument and model. As a result, we hope to combine the best of two worlds, of the ‘old’ and the ‘new’ idioms in policy studies, and to achieve our two aims: to bring back in the concept of power in current policy analysis and to expand the policy arrangement approach from a power perspective.

Journal ArticleDOI
TL;DR: This article examined consumer attitudes towards the purchase of foreign cars and TVs in the Netherlands and found that consumer ethnocentrism and feelings of animosity have an important impact on the evaluation of foreign products, even when no domestic brands are available.

Journal ArticleDOI
TL;DR: In this paper, the dual-process model of work-home interference (WHI) is introduced, which claims that job characteristics can be categorized in two broad categories, job demands and job resources, that are differentially related to job-related outcomes and WHI measures.
Abstract: This article introduces the dual-process model of work-home interference (WHI), which claims that job characteristics can be categorized in two broad categories, job demands and job resources, that are differentially related to job-related outcomes and WHI measures. The model proposes that job demands are primarily related to feelings of exhaustion, whereas job resources are primarily related to work-related flow. The central hypothesis of the current study among 1,090 employees was that exhaustion and flow, in turn, are related to negative and positive WHI, respectively. A series of structured equation modeling (SEM) analyses provided strong evidence for the dual-process model of WHI. The implications for WHI research and practice are discussed.

Journal ArticleDOI
TL;DR: The UISS is an accurate predictor of survival for patients with localized RCC applicable to external databases and may be less accurate in this subset of patients due to the heterogeneity of patients and treatments.
Abstract: Purpose To evaluate ability of the University of California Los Angeles Integrated Staging System (UISS) to stratify patients with localized and metastatic renal cell carcinoma (RCC) into risk groups in an international multicenter study. Patients and Methods 4,202 patients from eight international academic centers were classified according to the UISS, which combines TNM stage, Fuhrman grade, and Eastern Cooperative Oncology Group performance status. Distribution of the UISS categories was assessed in the overall population and in each center. Results The UISS stratified both localized and metastatic RCC into three different risk groups (P < .001). For localized RCC, the 5-year survival rates were 92%, 67%, and 44% for low-, intermediate-, and high-risk groups, respectively. A trend toward a higher risk of death was observed in all centers for increasing UISS risk category. For metastatic RCC, the 3-year survival rates were 37%, 23%, and 12% for low-, intermediate-, and high-risk groups, respectively; in...

Journal ArticleDOI
TL;DR: The interplay of correlation effects and cation covalency (GdFeO3-type distortions) is found to suppress orbital fluctuations in LaTiO3 and even more in Y TiO3, and to favor the transition to the insulating state.
Abstract: Using t(2g) Wannier functions, a low-energy Hamiltonian is derived for orthorhombic 3d(1) transition-metal oxides. Electronic correlations are treated with a new implementation of dynamical mean-field theory for noncubic systems. Good agreement with photoemission data is obtained. The interplay of correlation effects and cation covalency (GdFeO3-type distortions) is found to suppress orbital fluctuations in LaTiO3 and even more in YTiO3, and to favor the transition to the insulating state.

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TL;DR: In this paper, the authors compared the performance of Partial Least Squares (PLS) and Support Vector Machines (SVM) for two spectral regression applications and found that SVM outperformed PLS.

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TL;DR: Shleifer et al. as mentioned in this paper presented behavioral finance as an alternative to the efficient market hypothesis that has dominated finance for many years, in particular, Shleifer demonstrated the oversimplification of the efficient model.
Abstract: Behavioral economics and its focus on the interrelations between economics and psychology is attracting increasing attention and recognition. In 1998, the Journal of Economic Literature published an article offering an overview of the connections between economics and psychology (Rabin 1998). In defense of his focus on the relevance of psychological findings for economics, the author noted: “Because psychology systematically explores human judgment, behavior, and well-being, it can teach us important facts about how humans differ from the way they are traditionally described by economists” (11). A year later, in 1999, Andrei Shleifer of Harvard University was awarded the John Bates Clark medal of the American Economic Association, which is a prize granted every other year to an exceptional economist under the age of forty. Shleifer was selected for the award for his research on securities markets and on the role of government in regulating markets and in fostering economic growth. In this work, he presented behavioral finance as an alternative to the efficient market hypothesis that has dominated finance for many years (Shleifer 2000). In particular, Shleifer demonstrated the oversimplification of the efficient