bluuebunny/crossref_metadata_2025_split huggingface dataset:
Model selection for multi‐component frailty models
Authors: Ha Il Do , Lee Youngjo , MacKenzie Gilbert 
Published: May 2007

AbstractVarious frailty models have been developed and are now widely used for analysing multivariate survival data. It is therefore important to develop an information criterion for model selection. However, in frailty models there are several alternative ways of forming a criterion and the particular criterion chosen may not be uniformly best. In this paper, we study an Akaike information criterion (AIC) on selecting a frailty structure from a set of (possibly) non‐nested frailty models. We propose two new AIC criteria, based on a conditional likelihood and an extended restricted likelihood (ERL) given by Lee and Nelder (J. R. Statist. Soc. B1996;58:619–678). We compare their performance using well‐known practical examples and demonstrate that the two criteria may yield rather different results. A simulation study shows that the AIC based on the ERL is recommended, when attention is focussed on selecting the frailty structure rather than the fixed effects. Copyright © 2007 John Wiley & Sons, Ltd.
Performance of the trim and fill method in the presence of publication bias and between‐study heterogeneity
Authors: Peters Jaime L. , Sutton Alex J. , Jones David R. , Abrams Keith R. , Rushton Lesley 
Published: May 2007

AbstractThe trim and fill method allows estimation of an adjusted meta‐analysis estimate in the presence of publication bias. To date, the performance of the trim and fill method has had little assessment. In this paper, we provide a more comprehensive examination of different versions of the trim and fill method in a number of simulated meta‐analysis scenarios, comparing results with those from usual unadjusted meta‐analysis models and two simple alternatives, namely use of the estimate from: (i) the largest; or (ii) the most precise study in the meta‐analysis. Findings suggest a great deal of variability in the performance of the different approaches. When there is large between‐study heterogeneity the trim and fill method can underestimate the true positive effect when there is no
publication bias. However, when publication bias is present the trim and fill method can give estimates that are less biased than the usual meta‐analysis models. Although results suggest that the use of the estimate from the largest or most precise study seems a reasonable approach in the presence of publication bias, when between‐study heterogeneity exists our simulations show that these estimates are quite biased. We conclude that in the presence of publication bias use of the trim and fill method can help to reduce the bias in pooled estimates, even though the performance of this method is not ideal. However, because we do not know whether funnel plot asymmetry is truly caused by publication bias, and because there is great variability in the performance of different trim and fill estimators and models in various meta‐analysis scenarios, we recommend use of the trim and fill method as a form of sensitivity analysis as intended by the authors of the method. Copyright © 2007 John Wiley & Sons, Ltd.
Constructing multiple test procedures for partially ordered hypothesis sets
Authors: Edwards David , Madsen Jesper 
Published: May 2007

AbstractA popular method to control multiplicity in confirmatory clinical trials is to use a so‐called hierarchical, or fixed sequence, test procedure. This requires that the null hypotheses are ordered a priori, for example, in order of clinical importance. The procedure tests the hypotheses in this order using α‐level tests until one is not rejected. It then stops, so that no subsequent hypotheses are eligible for rejection. This procedure strongly controls the familywise error rate (FWE), that is to say, the probability that any true hypotheses are rejected.This paper describes a simple generalization of this approach in which the null hypotheses are partially ordered. It is convenient to display the partial ordering in a directed acyclic graph (DAG). We consider sequentially rejective procedures based on the partial ordering, in which a hypothesis is tested only when all preceding hypotheses have been tested and rejected. In general such procedures do not control the FWE, but it is shown that when certain intersection hypotheses are added, strong control of the FWE is obtained. The purpose of the method is to construct inference strategies for confirmatory clinical trials that better reflect the trial objectives. Copyright © 2007 John Wiley &
Sons, Ltd.
Inferences on the mean response in a log‐regression model: The generalized variable approach
Authors: Tian Lili , Wu Jianrong 
Published: May 2007

AbstractThis paper proposes a novel approach for the confidence interval estimation and hypothesis testing of the mean response in a log‐regression model using the concept of generalized variable. Simulation studies demonstrate that the proposed confidence intervals have satisfying coverage probabilities. The proposed approach can be simply carried out by a few simulation steps. Therefore, it is an ideal candidate for making inferences about the mean response in a log‐regression model. Copyright © 2007 John Wiley & Sons, Ltd.
Analysis, synthesis, systems thinking and the scientific method: rediscovering the importance of open systems
Authors: Barton John , Haslett Tim 
Published: May 2007

AbstractThis paper reconsiders the role of systems thinking in science and addresses an issue raised by Peter Checkland some 25 years ago, that of the relationship between systems thinking, analysis and the scientific method. The paper argues that the scientific method is most usefully interpreted as a dialectic between analysis and synthesis supported by the triadic logic of C.S. Peirce, and that the role of systems thinking is to frame this dialectic. Three generic forms of the system concept are identified—closed systems, input‐output systems and open systems. Consequently, systems thinking is shown to play a central role in mainstream science. The paper concludes that a system is best defined as a cognitive construct for making sense of complexity and the organization of knowledge and that contemporary system thinking is best identified as the ethical, scientific pursuit of knowledge using the socio‐ecological (open) systems frame. Copyright © 2007 John Wiley & Sons, Ltd.
Verification of clock synchronization algorithms: experiments on a combination of deductive tools
Authors: Barsotti Damián , Nieto Leonor Prensa , Tiu Alwen 
Published: May 2007

Abstract
We report on an experiment in combining the theorem prover Isabelle with automatic first-order arithmetic provers to increase automation on the verification of distributed protocols. As a case study for the experiment we verify several averaging clock synchronization algorithms. We present a formalization of Schneider’s generalized clock synchronization protocol [Sch87] in Isabelle/HOL. Then, we verify that the convergence functions used in two clock synchronization algorithms, namely, the Interactive Convergence Algorithm (ICA) of Lamport and Melliar-Smith [LMS85] and the Fault-tolerant Midpoint algorithm of Lundelius–Lynch [LL84], satisfy Schneider’s general conditions for correctness. The proofs are completely formalized in Isabelle/HOL. We identify parts of the proofs which are not fully automatically proven by Isabelle built-in tactics and show that these proofs can be handled by automatic first-order provers with support for arithmetics.
Estimates of biomass and primary productivity in a high‐altitude maple forest of the west central Himalayas
Authors: Garkoti S. C. 
Published: May 2007

AbstractThe paper describes the biomass and productivity of maple (Acer cappadocicum) forest occurring at an altitude of 2,750 m in the west central Himalayas. Total vegetation biomass was 308.3 t ha−1, of which the tree layer contributed the most, followed by herbs and shrubs. The seasonal forest‐floor litter mass varied between 5.4 t ha−1(in rainy season) and 6.6 t ha−1(in winter season). The annual litter fall was 6.2 t ha−1, of which leaf litter contributed the largest part (59% of the total litter fall). Net primary productivity of total vegetation was 19.5 t ha−1year−1. The production efficiency of leaves (net primary productivity/leaf mass) was markedly higher (2.9 g g−1foliage mass year−1) than those of the low‐altitude forests of the region.
Prevacuolar compartment morphology in vps mutants of Saccharomyces cerevisiae
Authors: Hedman Jamie M. , Eggleston Matthew D. , Attryde Amanda L. , Marshall Pamela A. 
Published: May 2007

AbstractOver 60 genes have been identified that affect protein sorting to the lysosome‐like vacuole in Saccharomyces cerevisiae. Cells with mutations in these vacuolar protein sorting (vps) genes fall into seven general classes based upon their vacuolar morpholology. Class A mutants have a morphologically wild type vacuole, while Class B mutants have a fragmented vacuole. There is no discernable vacuolar structure in Class C mutants. Class D mutants have a slightly enlarged vacuole, but Class E mutants have a normal looking vacuole with an enlarged prevacuolar compartment (PVC), which is analogous to the mammalian late endosome. Class F mutants have a wild type appearing vacuole as well as fragmented vacuolar structures. vps mutants have also been found with a tubulo‐vesicular vacuole structure. vps mutant morphology is pertinent, as mutants of the same class may work together and/or have a block in the same general step in the vacuolar protein sorting pathway. We probed PVC morphology and location microscopically in live cells of several null vps mutants using a GFP fusion protein of Nhx1p, an Na+/H+ exchanger normally localized to the PVC. We show that cell strains deleted for VPS proteins that have been previously shown to work together, regardless of VPS Class, have the same PVC morphology. Cell strains lacking VPS genes that have not been implicated in the same pathway show different PVC morphologies, even if the mutant strains are in the same VPS Class. These new studies indicate that PVC morphology is another tier of classification that may more accurately identify proteins that function together in vacuolar protein sorting than the original vps mutation classes.
The Objective Burden in Partners of Heart Failure Patients; Development and Initial Validation of the Dutch Objective Burden Inventory
Authors: Luttik Marie Louise , Jaarsma Tiny , Tijssen Jan G.P. , van Veldhuisen Dirk J. , Sanderman Robbert 
Published: May 2007

Background: Measures on objective caregiver burden in partners of Heart Failure patients are hardly available and never include HF specific aspects. Aim: The main objective of our study was to develop an inventory that assesses the objective caregiver burden of partners of HF patients, including the full range of potential care giving demands. Methods: To develop the inventory, six domains of caregiving demands were identified. Items for the domains were generated from the literature, expert opinion and existing scales. The original 50-items self-report inventory was administered to 321 partners of HF patients. Demographic data of HF partners were collected by questionnaire. Clinical data of the HF patients were collected by chart review. Results: Component analysis led to exclusion of 12 original items and to a meaningful four-factor solution with a total explained variance of 43%. The components reflected four different kinds of care giving tasks; personal care, emotional, motivational and practical (treatment related) support. They demonstrated good internal consistency and initial validity was supported by a pattern of meaningful associations with external variables. Conclusion: The Objective Burden Inventory is a promising inventory to assess objective care giving tasks performed by HF partners, including emotional and motivational support. It provides information on the caregiver situation that may help to develop effective interventions.
Exercise training reduces sympathetic nerve activity in heart failure patients treated with carvedilol
Authors: Fraga Raffael , Franco Fábio G. , Roveda Fabiana , de Matos Luciana N.J. , Braga Ana M.F.W. , Rondon Maria U.P.B. , Rotta Daniel R. , Brum Patricia C. , Barretto Antonio C.P. , Middlekauff Holly R. , Negrão Carlos E. 
Published: May 2007

AbstractBackground:Evidence suggests that carvedilol decreases muscle sympathetic nerve activity (MSNA) in patients with heart failure (HF) but carvedilol fails to improve forearm vascular resistance and overall functional capacity. Exercise training in HF reduces MSNA and improves forearm vascular resistance and functional capacity.Aims:To investigate whether the beneficial effects exercise training on MSNA are maintained in the presence of carvedilol.Methods and results:Twenty seven HF patients, NYHA Class II–III, EF <35%, peak VO2 <20 ml/kg/min, treated with carvedilol were randomly divided into two groups: exercise training (n=15) and untrained (n=12). MSNA was recorded by microneurography. Forearm blood flow (FBF) was measured by venous occlusion plethysmography. The four‐month training program consisted of three 60‐min exercise/week on a cycloergometer. Baseline parameters were similar between groups. Exercise training reduced MSNA (–14±3.3 bursts/100 HB, p=0.001) and increased forearm blood flow (0.6±0.1 mL/min/100 g.p p>0.001) in HF patients on carvedilol. In addition, exercise training improved peak VO2 in HF patients (20±6%, p=0.002). MSNA, FBF and peak VO2 were unchanged in untrained HF patients on carvedilol.Conclusion:Exercise training reduces MSNA in heart failure patients treated with carvedilol. In addition, the beneficial effects of exercise training on muscle blood flow and functional capacity are still realized in patients on carvedilol.
Constant differences: Friedrich Wilhelm Bessel, the concept of the observer in early nineteenth-century practical astronomy and the history of the personal equation
Authors: HOFFMANN CHRISTOPH 
Published: May 2007

AbstractIn 1823 the astronomer Friedrich Wilhelm Bessel gave notice of an observational error which is now known as the personal equation. Bessel, however, never used this phrase to characterize the finding that when noting the time of a certain event observers show a considerable ‘involuntary constant difference’. From this starting point the paper develops two arguments. First, these involuntary differences subverted the concept of the ‘observing observer’. What had previously been defined as a reference point of trust and precision turned into a source of an error that resisted any wilful intervention. Second, and contrary to later suggestions, Bessel's findings did not initially lead to discussions and measures of permanent control. In everyday astronomical work the influence of such differences could be avoided by comparatively simple means. Taking this into account offers a new perspective both on the history of the personal equation and on the significance of Bessel's findings. Whereas the former has to be read as the history of a rather particular reaction to the phenomenon of constant differences, the latter is connected with a rather fundamental transition in the epistemology of the observer.
A psychosocial skills training approach in Mexican out-patients with schizophrenia
Authors: VALENCIA MARCELO , RASCON MARIA LUISA , JUAREZ FRANCISCO , MUROW ESTHER 
Published: May 2007

ABSTRACTBackgroundThe effectiveness of a psychosocial skills training (PSST) approach applied to chronic out-patients with schizophrenia was examined. We hypothesized that the PSST programme, which included treatment as usual (TAU), PSST and family therapy (FT), would reduce positive and negative symptoms, prevent relapse and rehospitalization, and improve psychosocial functioning (PSF), global functioning and treatment adherence.MethodEighty-two patients were randomly assigned to receive either TAU [antipsychotic medication (AP); n=39] or the PSST approach (TAU+PSST+FT; n=43). The two groups were assessed at intake and after completion of 1 year of treatment.ResultsThere were statistically significant differences between the two groups. Patients in the PSST group improved their symptomatology, psychosocial and global functioning (symptoms and psychological, social and occupational functioning), showed lower relapse, rehospitalization and drop-out rates, a higher level of compliance with AP medication, and a high level of therapeutic adherence in comparison with TAU patients, whose symptoms also improved although they showed no improvement in any of the clinical or psychosocial variables. A comparison of the standardized effect sizes showed a medium and a large effect size of PSF and global functioning for the PSST group and a non-effect size for the TAU group.ConclusionsA higher level of effectiveness was demonstrated when combining TAU, PSST and FT in comparison with AP medication alone. The PSST approach should be recommended for clinical practice.
The role of perinatal problems in risk of co-morbid psychiatric and medical disorders in adulthood
Authors: NOMURA YOKO , BROOKS-GUNN JEANNE , DAVEY CHARLES , HAM JACOB , FIFER WILLIAM P. 
Published: May 2007

ABSTRACTBackgroundPerinatal problems may be associated with an increased risk for psychological and physical health problems in adulthood, although it is unclear which perinatal problems (low birthweight, preterm birth, low Apgar scores, and small head circumference), or what clusters of problems, are more likely to be associated with later health problems. It is also not known whether perinatal problems (singly or together) are associated with co-morbidity between psychological and physical health problems.MethodA regional random sample (from Baltimore) of mothers and their children (n=1525) was followed from birth to adulthood (mean age 29 years). Perinatal conditions were measured at delivery. Psychological problems (depression and suicidal ideation) were measured with the General Health Questionnaire-28 (GHQ-28) and physical problems (asthma and hypertension) with the RAND-36 Health Status Inventory.ResultsChildren with perinatal problems were generally at increased risk for depression, suicidal ideation and hypertension, and co-morbid depression and hypertension even after controlling for confounders. One possible underlying condition, preterm low birthweight (LBW), extracted by cluster analysis, considering all of the four perinatal problems, was associated with increased risk for psychological and physical health outcomes as well as co-morbidity of the two.ConclusionsLBW, preterm birth and small head circumference singly increased the risk for both psychological and physical health problems, as well as co-morbid depression and hypertension, while low Apgar scores were only associated with psychological problems. Delineating different etiological processes, such as preterm LBW, considering various perinatal problems simultaneously, might be of benefit to understanding the fetal origin of adult illness and co-morbidity.
Probing the folding intermediate of Rd‐apocyt b562 by protein engineering and infrared T‐jump
Authors: Wang Ting , Zhou Zheng , Bunagan Michelle R. , Du Deguo , Bai Yawen , Gai Feng 
Published: May 2007

AbstractSmall proteins often fold in an apparent two‐state manner with the absence of detectable early‐folding intermediates. Recently, using native‐state hydrogen exchange, intermediates that exist after the rate‐limiting transition state have been identified for several proteins. However, little is known about the folding kinetics from these post‐transition intermediates to their corresponding native states. Herein, we have used protein engineering and a laser‐induced temperature‐jump (T‐jump) technique to investigate this issue and have applied it to Rd‐apocyt b562, a four‐helix bundle protein. Previously, it has been shown that Rd‐apocyt b562 folds via an on‐pathway hidden intermediate, which has only the N‐terminal helix unfolded. In the present study, a double mutation (V16G/I17A) in the N‐terminal helix of Rd‐apocyt b562 was made to further increase the relative population of this intermediate state at high temperature by selectively destabilizing the native state. In the circular dichroism thermal melting experiment, this mutant showed apparent two‐state folding behavior. However, in the T‐jump experiment, two kinetic phases were observed. Therefore, these results are in agreement with the idea that a folding intermediate is populated on the folding pathway of Rd‐apocyt b562. Moreover, it was found that the exponential growth rate of the native state from this intermediate state is roughly (25 μsec)−1 at 65°C.
Conformational change of the methionine 20 loop of Escherichia coli dihydrofolate reductase modulates pKa of the bound dihydrofolate
Authors: Khavrutskii Ilja V. , Price Daniel J. , Lee Jinhyuk , Brooks Charles L. 
Published: May 2007

AbstractWe evaluate the pKa of dihydrofolate (H2F) at the N5 position in three ternary complexes with Escherichia coli dihydrofolate reductase (ecDHFR), namely ecDHFR(NADP+:H2F) in the closed form (1), and the Michaelis complexes ecDHFR(NADPH:H2F) in the closed (2) and occluded (3) forms, by performing free energy perturbation with molecular dynamics simulations (FEP/MD). Our simulations suggest that in the Michaelis complex the pKa is modulated by the Met20 loop fluctuations, providing the largest pKa shift in substates with a “tightly closed” loop conformation; in the “partially closed/open” substates, the pKa is similar to that in the occluded complex. Conducive to the protonation, tightly closing the Met20 loop enhances the interactions of the cofactor and the substrate with the Met20 side chain and aligns the nicotinamide ring of the cofactor coplanar with the pterin ring of the substrate. Overall, the present study favors the hypothesis that N5 is protonated directly from solution and provides further insights into the mechanism of the substrate protonation.
Structural determinants of nitroxide motion in spin‐labeled proteins: Tertiary contact and solvent‐inaccessible sites in helix G of T4 lysozyme
Authors: Guo Zhefeng , Cascio Duilio , Hideg Kálmán , Kálái Támás , Hubbell Wayne L. 
Published: May 2007

AbstractA nitroxide side chain (R1) has been substituted at single sites along a helix–turn–helix motif in T4 lysozyme (residues 114–135). Together with previously published data, the new sites reported complete a continuous scan through the motif. Mutants with R1 at sites 115 and 118 were selected for crystallographic analysis to identify the structural origins of the corresponding two‐component EPR spectra. At 115, R1 is shown to occupy two rotamers in the room temperature crystal structure, one of which has not been previously reported. The two components in the EPR spectrum apparently arise from differential interactions of the two rotamers with the surrounding structure, the most important of which is a hydrophobic interaction of the nitroxide ring. Interestingly, the crystal structure at 100 K reveals a single rotamer, emphasizing the possibility of rotamer selection in low‐temperature crystal structures. Residue 118 is at a solvent‐inaccessible site in the protein core, and the structure of 118R1, the first reported for the R1 side chain at a buried site, reveals how the side chain is accommodated in an overpacked core.