Different Degrees Of Association Research Articles

NMR Spectroscopy of the Hydrated Layer of Composite Particles Based on Nanosized Al2O3 and Vitreous Humor

The hydrated layer of composite particles prepared using Al2O3 and cattle vitreous humor was investigated using NMR spectroscopy. It was found that water bound to Al2O3 nanoparticles was present in the form of clusters with different degrees of association and energies of interaction with the surface. Water bound to the surface of the Al2O3/vitreous humor composite became more uniform upon immobilization of vitreous humor components on the surface of the Al2O3. With this, the clusters of adsorbed water had characteristics that were close to those found in air and weakly polar CHCl3 media. Addition of polar CH3CN led to the formation of very small water clusters. PMR spectra of the surface of the Al2O3/vitreous humor composite in the presence of trifluoroacetic acid differentiated four types of hydrated structures that differed in the degree of water association.

Environmental and social factors account for Mexican maize richness and distribution: A data mining approach

Food security is a key topic for human welfare worldwide. In this context, the agrobiodiversity in centers of origin and diversification (COD) for the world's staple crops will be critical for feeding the world under changing environmental and social conditions. Maize is one of the most widely cultivated cereal and is the staple food for African and Latin-American countries, including its COD: Mexico, harboring more than 60% of the world's diversity for this crop. In this study we implemented a data mining approach that allowed us to evaluate spatial relationships of environmental (altitude, climate, slope and soil) and social factors (education and ethnic groups) with the spatial distribution of Mexican races, as well as the areas that can potentially harbor the highest number of races (PRA). In contrast to commonly used species distribution approaches, the data mining method implemented here allowed the integration of contrasting types of variables and their spatial relationships with the focal entity. Our results indicate that altitude, which is related with climate, was the factor with highest predictive power for most races. However, different factors showed different degrees of association with the spatial distribution of particular races. In any case, the performance of the model increased when using all evaluated factors. In our example study case, the highly vulnerable race Palomero Tolqueño was mainly influenced by climate, implying that climate change might threaten its preservation by reducing the areas with favorable conditions for its cultivation. Importantly, however, for this and other eleven races analyzed in detail, is that the ethnic group was the factor with the greatest predictive power. This finding further reinforces the key importance of in situ conservation by supporting local indigenous communities who are in charge of preserving, adapting to changing challenges and cultivating local races.

Microfluidic devices for continuous production of pDNA/cationic liposome complexes for gene delivery and vaccine therapy

To evaluate the process parameters for the production of plasmid DNA/cationic liposome (pDNA/CL) complexes in microfluidic systems, we studied two microfluidic devices: one with simple straight hydrodynamic flow focusing (SMD) and a second one with barriers in the mixing microchannel (patterned walls, PMD). A conventional bulk mixing method was used as a comparison to microfluidic mixing. The CL and the pDNA were combined at a molar positive/negative charge ratio of 6. The results showed that incorporating pDNA into the liposomal structures was different for the two microfluidic devices and that the temperature influenced the average size of complexes produced by the simple microfluidic device, while it did not influence the average complex size in the patterned wall device. Differences were also observed in pDNA probe accessibility in the complexes. The SMD yielded a similar quantity of non-electrostatic bound pDNA as that provided by the bulk mixing method. The complexes produced by the PMD had their pDNA probe accessibility decreased in 40% and achieved lower in vitro transfection levels in HeLa cells than the bulk mixing and simple microfluidic complexation methods. These differences are most likely due to different degrees of association between pDNA and CL, as controlled by the microfluidic devices. This study contributes to the development of rational strategies for controlling the formation of pDNA/CL complexes for further applications in gene and vaccine therapy.

A drought resistance-promoting microbiome is selected by root system under desert farming.

BackgroundTraditional agro-systems in arid areas are a bulwark for preserving soil stability and fertility, in the sight of “reverse desertification”. Nevertheless, the impact of desert farming practices on the diversity and abundance of the plant associated microbiome is poorly characterized, including its functional role in supporting plant development under drought stress.Methodology/Principal FindingsWe assessed the structure of the microbiome associated to the drought-sensitive pepper plant (Capsicum annuum L.) cultivated in a traditional Egyptian farm, focusing on microbe contribution to a crucial ecosystem service, i.e. plant growth under water deficit. The root system was dissected by sampling root/soil with a different degree of association to the plant: the endosphere, the rhizosphere and the root surrounding soil that were compared to the uncultivated soil. Bacterial community structure and diversity, determined by using Denaturing Gradient Gel Electrophoresis, differed according to the microhabitat, indicating a selective pressure determined by the plant activity. Similarly, culturable bacteria genera showed different distribution in the three root system fractions. Bacillus spp. (68% of the isolates) were mainly recovered from the endosphere, while rhizosphere and the root surrounding soil fractions were dominated by Klebsiella spp. (61% and 44% respectively). Most of the isolates (95%) presented in vitro multiple plant growth promoting (PGP) activities and stress resistance capabilities, but their distribution was different among the root system fractions analyzed, with enhanced abilities for Bacillus and the rhizobacteria strains. We show that the C. annuum rhizosphere under desert farming enriched populations of PGP bacteria capable of enhancing plant photosynthetic activity and biomass synthesis (up to 40%) under drought stress.Conclusions/SignificanceCrop cultivation provides critical ecosystem services in arid lands with the plant root system acting as a “resource island” able to attract and select microbial communities endowed with multiple PGP traits that sustain plant development under water limiting conditions.

Reducing uncertainty about objective functions in adaptive management

This paper extends the uncertainty framework of adaptive management to include uncertainty about the objectives to be used in guiding decisions. Adaptive decision making typically assumes explicit and agreed-upon objectives for management, but allows for uncertainty as to the structure of the decision process that generates change through time. Yet it is not unusual for there to be uncertainty (or disagreement) about objectives, with different stakeholders expressing different views not only about resource responses to management but also about the appropriate management objectives. In this paper I extend the treatment of uncertainty in adaptive management, and describe a stochastic structure for the joint occurrence of uncertainty about objectives as well as models, and show how adaptive decision making and the assessment of post-decision monitoring data can be used to reduce uncertainties of both kinds. Different degrees of association between model and objective uncertainty lead to different patterns of learning about objectives.

Abstract 11: Predicting Angina for Stable Coronary Patients with or Without Percutaneous Coronary Intervention

Background: Relief of angina and improvement in quality of life is the most common indication for percutaneous coronary intervention (PCI) in stable ischemic heart disease (SIHD). Given that there are alternative strategies for treating angina, (e.g. intensifying optimal medical therapy (OMT) or PCI), predicting angina severity as a function of alternative treatment options can serve as a foundation for shared decision-making and the elicitation of patients’ preferences. Methods: Using data from the 2,287 SIHD patients in COURAGE trial, where PCI was randomized, we built multivariable linear regression models of Seattle Angina Questionnaire (SAQ)-assessed angina, physical function and quality of life at 6 and 12 months, using baseline SAQ scores, treatment, and all demographic and clinical characteristics available at the time of randomization. Results: At baseline, there were no significant differences between PCI and OMT groups for any SAQ domain. The strongest predictors of 6- and 12-month SAQ scores were patients’ baseline scores. Different characteristics had different degrees of association with angina, physical function and quality of life domains, with PCI being associated with 1.9-5.3-point greater improvement in SAQ scores, depending upon the domain and time frame. The adjusted R 2 of final models varied from 0.38-0.62. The results (regression coefficients with standard errors and adjusted R 2 ) of patients characteristics associated with SAQ scores for 6-month and 1-year are presented in table. Conclusions: Prediction models can be created to estimate patient-centered health status outcomes and could be used as an evidence-based foundation for supporting shared medical decision-making in SIHD. The impact of such models on treatment decisions needs to be assessed in future studies. Patient Characteristics associated with Seattle Angina Questionnaire Scores 1 Domain Time Frame Physical limitation Angina Frequency Quality of Life Factor β(SE) Factor β(SE) Factor β(SE) 6-month SAQ scores Baseline Score * Age(<65) * Gender(F) PreviousPCI E-F 3 Hypertension * MI * PCI * Diabetes * 0.51(0.02) 5.21(1.10) -1.32(1.56) -0.10(1.45) 0.15(1.40) 2.87(1.08) 2.87(1.15) 5.07(1.01) 5.22(1.14) Baseline Score * Age(<65) Gender(F) PreviousPCI E-F 3 Hypertension MI PCI * diabetes 0.28(0.02) 1.09(1.09) 0.43(1.48) 2.14(1.71) 0.98(1.42) -0.28(1.14) 1.49(1.14) 4.75(1.02) 1.56(1.11) Baseline Score * Age(<65) Gender(F) PreviousPCI E-F 3 Hypertension MI PCI * Diabetes * 0.36(0.02) -0.40(1.13) 1.12(1.53) 2.69(1.62) 1.64(1.48) -0.20(1.16) 1.95(1.19) 5.30(1.07)3.13(1.16) Adjusted R 2 0.62 Adjusted R 2 0.43 Adjusted R 2 0.42 1-year SAQ scores Baseline Score * Age(<65) * Gender(F) PreviousPCI E-F 3 Hypertension * MI PCI Diabetes * 0.46(0.03) 3.91(1.17) -0.34(1.62) 1.10(1.66) 2.21(1.57) 3.14(1.16) 2.02(1.21) 1.88(1.11) 4.64(1.22) Baseline Score * Age(<65) * Gender(F) PreviousPCI E-F 3 Hypertension MI PCI * Diabetes * 0.26(0.02) 2.12(1.05) -0.54(1.48) 0.15(1.61) 1.06(1.35) 0.51(1.11) 0.84(1.118) 3.65(0.98) 4.29(1.11) Baseline Score * Age(<65) Gender(F) PreviousPCI E-F 3 Hypertension MI PCI * Diabetes * 0.29(0.02) -1.85(1.11) 0.06(1.58) 0.94(1.65) 0.75(1.53) 0.39(1.16) 1.59(1.18) 3.12(1.08) 2.81(1.19) Adjusted R 2 0.48 Adjusted R 2 0.38 Adjusted R 2 0.41 1 Scale: 0-100; * With p <0.05; . 2 E-F: Ejection Fraction; 3 MI: Myocardial Infarction.

On the occurrence of postmidnight equatorialFregion irregularities during the June solstice

[1] Postmidnight equatorial F region irregularities (EFIs) are known to develop mainly during the solstitial months. However, it is not well understood whether they occur at all longitudes and what process causes their occurrence at different longitude sectors. In this study, we use the GPS total electron content (TEC) fluctuations obtained from a global GPS network and spread F in ionograms from Jicamarca (283°E, 12°S, Dip 1°N) in the American longitude sector and Kwajalein (167°E, 9°N, Dip 4°N), Bac Lieu (106°E, 9°N, Dip 2°N), and Chumphon (99°E, 11°N, Dip 3°N) in the Pacific and Asian longitude sectors during 2000–2009, to investigate the EFI characteristics during June solstice. Results from global TEC fluctuations show that at solar maximum, the occurrence rate of postmidnight EFIs is high in African and Pacific regions, moderate in the Southeast Asian region, and low in the Peruvian region and that most postmidnight EFIs are the continuation of postsunset EFIs. During solar minimum the postmidnight EFIs were rarely observed in TEC but were very frequent in ionograms. The latter had more frequent postmidnight onsets over Peru, whereas they were initiated during late postsunset hours in Pacific and Southeast Asian longitudes. In both longitudes the postsunset layer rise occurred with some delay. The layer rise was more prominent on spread F nights over Jicamarca and less so over Pacific longitudes. The results showing different degrees of association at the different longitudes between the postsunset/postmidnight EFIs and F layer heights highlight the influence of other factors in the late-night EFI development. Perturbation seeds and plasma drifts/neutral winds, in particular, are discussed as strong candidates for causing these irregularities in the June solstitial months of solar minimum years.

Synthesis and Characterization of Alkynyl Complexes of Groups 1 and 2

The synthesis of N-heterocyclic carbene adducts of alkynyl lithium and magnesium is achieved, and different degrees of association are observed. Reaction of strontium amide nacnacSrN(SiMe(3))(2)(thf) (nacnac = CH(CMe2,6-iPr(2)C(6)H(3)N)(2)) with PhC[triple bond]CH in THF yields the dimeric alkynyl complex [nacnacSr(thf)(mu-C[triple bond]CPh)](2) which shows an interesting coordination geometry around the metal center. The compound retains the THF molecules, unlike its lighter congener, even in hydrocarbon solvents.

Temperature-Induced Dissociation of A β Monomers from Amyloid Fibril

Using all-atom molecular dynamics, we study the temperature-induced dissociation of A β monomers from the fibril protofilament. To accelerate conformational sampling, simulations are performed at elevated temperatures and peptide concentrations. By computing free energy disconnectivity graphs we mapped the free energy landscape of monomers on the surface of A β fibril. We found that A β monomers sample diverse sets of low free energy states with different degrees of association with the fibril. Some of these states have residual amounts of fibril interactions, whereas others lack fibril-like content. Generally, A β monomers with partially formed fibril-like interactions have the lowest free energies, but their backbone conformations may differ considerably from those in the fibril interior. Overall, A β amyloid protofilaments seem to be highly resistant to thermal dissociation. Monomer dissociation from the fibril edge proceeds via multiple stages and pathways. Our simulation findings are discussed in the context of recent experimental results.

Response projected clustering for direct association with physiological and clinical response data

BackgroundMicroarray gene expression data are often analyzed together with corresponding physiological response and clinical metadata of biological subjects, e.g. patients' residual tumor sizes after chemotherapy or glucose levels at various stages of diabetic patients. Current clustering analysis cannot directly incorporate such quantitative metadata into the clustering heatmap of gene expression. It will be quite useful if these clinical response data can be effectively summarized in the high-dimensional clustering display so that important groups of genes can be intuitively discovered with different degrees of relevance to target disease phenotypes.ResultsWe introduced a novel clustering analysis approach, response projected clustering (RPC), which uses a high-dimensional geometrical projection of response data to the gene expression space. The projected response vector, which becomes the origin in the projected space, is then clustered together with the projected gene vectors based on their different degrees of association with the response vector. A bootstrap-counting based RPC analysis is also performed to evaluate statistical tightness of identified gene clusters. Our RPC analysis was applied to the in vitro growth-inhibition and microarray profiling data on the NCI-60 cancer cell lines and the microarray gene expression study of macrophage differentiation in atherogenesis. These RPC applications enabled us to identify many known and novel gene factors and their potential pathway associations which are highly relevant to the drug's chemosensitivity activities and atherogenesis.ConclusionWe have shown that RPC can effectively discover gene networks with different degrees of association with clinical metadata. Performed on each gene's response projected vector based on its degree of association with the response data, RPC effectively summarizes individual genes' association with metadata as well as their own expression patterns. Thus, RPC greatly enhances the utility of clustering analysis on investigating high-dimensional microarray gene expression data with quantitative metadata.

Outcomes at 12 Months in a Population of Elderly Patients Discharged From a Rehabilitation Unit

This study investigates the cognitive, functional, and clinical variables associated with the risk of institutionalization, rehospitalization, and death at 12 months among a population of elderly discharged from a Rehabilitation and Aged Care Unit (RACU) within a 1-year period (May 1, 2004 to April 30, 2005). The RACU is a relatively new setting of care providing intensive rehabilitation and clinical support to elderly with highly heterogeneous reasons for admission. There were 1303 patients (> or =65 years old) contacted 12 months after discharge from the RACU. We obtained information about institutionalization, rehospitalization, and death. Predictors were all the demographic and clinical variables potentially related to these outcomes. The relationship among predictors and outcomes was tested with multiple stepwise logistic regression models. Among the 1072 patients alive at the 12-month follow-up, 90 (8.4%) were institutionalized (3.4% early at discharge and 4.9% within the next period). The logistic regression analysis showed that 2 ranges of age (78 to 83 years and 84 years or more), living alone, occurrence of delirium, cognitive impairment (Mini Mental State Examination lower or equal to 20/30), and poor functional status at discharge (Barthel Index scores ranging from 69 to 85 and Barthel Index scores lower than 68/100) were independently and significantly associated with the risk of institutionalization during the 12 months following discharge from the RACU. Three hundred and twenty-three (30.1%) patients had been rehospitalized once and 86 (8.0%) patients twice at the 12-month follow-up. In the multivariate analysis, comorbidity (Charlson Index scores ranging from 2 to 3 and Charlson Index scores higher than 4) and delirium were significantly and independently associated with this outcome. One hundred and thirty-six (11.3%) patients had died by the 12-month follow-up. The stepwise logistic regression analysis showed that age greater than 83 years, poor functional status (Barthel Index lower than 60/100 at discharge), high comorbidity (Charlson Index scores ranging from 3 to 4 and Charlson Index scores higher than 4, respectively), and albumin serum levels ranging from 3.2 to 2.9 mg/dL and lower than 2.9 mg/dL independently and significantly predicted the 12-month risk of death. Absence of depressive symptoms (Geriatric Depression Scale <2/15) had instead a protective effect. Variables related to the sociodemographic, cognitive, functional, and health status predicted, with different degree of association, the 12-month risk of institutionalization, rehospitalization, and death among a population of elderly patients discharged from a RACU. Accordingly, various clinical and organizational approaches may be planned for prevention.

A Meta-Analysis of the Association Between Stress and Health in Taiwan

This study adopted the meta-analysis technique to analyze 354 journal articles, theses, and dissertations that had investigated the association between stress and health in Taiwan between January 1980 and December 2003. This study was conducted with the purpose of understanding the association between general stress and general health, the discrepant associations between different stress types and health facets, and the possible moderators between general stress and general health. A computer search for relevant studies was conducted on several databases using the key words "stress" and "life event". For each eligible study, the important study characteristics were recorded, and the effect sizes of the relationship between stress and health were computed. Furthermore, in order to investigate the moderating effects of the study characteristics on the stress-health relationship, the methods of categorical model analysis and correlation analysis were employed. The results of this study revealed that: (1) the correlations between general stress and general health as well as between general stress and various health facets fell between medium and high; (2) there existed different degrees of association between various stress types and health facets; and (3) none of the demographic and methodologic variables could by itself moderate the relationship between general stress and general health as the moderator effects were not sufficient and strong enough. This study presents a multidimensional framework of the issues on the relationship between stress and health, and it provides guiding references for future research. No evidence was found for moderating effects of social support, coping strategies, and personality traits on the stress-health relationship. Such findings may be due to methodologic limitations. This suggests that further investigation is needed.

Lack of Agreement Between Cervicography and Cytology and the Effect of Human Papillomavirus Infection and Viral Load

Cohort studies of the natural history of human papillomavirus (HPV) infection and cervical squamous intraepithelial lesions with repeated screening allow the comparison of different macroscopic and microscopic diagnostic methods. Concurrent visual inspection using cervicography and conventional Pap cytology tests were performed during multiple visits in a cohort of women attending a maternal and child health clinic in São Paulo, Brazil. HPV infection status at the same visits was determined by polymerase chain reaction followed by typing with specific oligonucleotide probing and viral load quantification. Information on reproductive health and hygiene habits was also collected at each visit. Overall agreement between cervicography and cytology was low (kappa = 0.046), which increased only slightly when high oncogenic-risk HPV types (kappa = 0.120) or high viral burden (>100 copies/cell) (kappa = 0.170) was present. Analysis of reproductive health and hygiene habits revealed somewhat different risk factors for cervical lesions detected by these tests. However, presence of oncogenic HPV DNA (odds ratio = 36.0, 95% CI = 16.6-77.8) and high viral burden (odds ratio = 67.34; 95% CI = 27.1-167.0) were strongly associated with lesions detected by cytology but not by cervicography. Although changes in the cervix (because of age, gravidity, or hormonal effects) may influence the performance of morphology-based screening tests, the lack of agreement and the different degrees of association with HPV infection measures indicate that a visual inspection method such as cervicography may detect different cervical abnormalities relative to cytology.

Sulfate-Reducing Bacteria in Floating Macrophyte Rhizospheres from an Amazonian Floodplain Lake in Bolivia and Their Association with Hg Methylation

Five subgroups of sulfate-reducing bacteria (SRB) were detected by PCR in three macrophyte rhizospheres (Polygonum densiflorum, Hymenachne donacifolia, and Ludwigia helminthorriza) and three subgroups in Eichhornia crassipes from La Granja, a floodplain lake from the upper Madeira basin. The SRB community varied according to the macrophyte species but with different degrees of association with their roots. The rhizosphere of the C4 plant Polygonum densiflorum had higher frequencies of SRB subgroups as well as higher mercury methylation potentials (27.5 to 36.1%) and carbon (16.06 +/- 5.40%), nitrogen (2.03 +/- 0.64%), Hg (94.50 +/- 6.86 ng Hg g(-1)), and methylmercury (8.25 +/- 1.45 ng Hg g(-1)) contents than the rhizosphere of the C3 plant Eichhornia crassipes. Mercury methylation in Polygonum densiflorum and Eichhornia crassipes was reduced when SRB metabolism was inhibited by sodium molybdate.

Patient satisfaction with health care providers in South Africa: the influences of race and socioeconomic status

The first democratic government elected in South Africa in 1994 inherited huge inequalities in health status and health provision across all sections of the population. This study set out to assess, 4 years later, the influence of race and socioeconomic status (SES) on perceived quality of care from health care providers. A 1998 countrywide survey of 3820 households assessed many aspects of health care delivery, including levels of satisfaction with health care providers among different segments of South African society. Fifty-one percent (n = 1953) of the respondents had attended a primary care facility in the year preceding the interview and were retained in the analysis. Both race and SES were significant predictors of levels of satisfaction with the services of the health care provider, after adjusting for gender, age, and type of facility visited. White and high SES respondents were about 1.5 times more likely to report excellent service compared with Black and low SES respondents, respectively. In South Africa, race and SES are not synonymous and can no longer be considered reliable proxy indicators of one another. Each has distinct and significant but different degrees of association with client satisfaction. Any assessment of equity-driven health policy in South Africa should consider the impacts of both race and SES on client satisfaction as one of the indicators of success.

Development of radiology prediction models using feature analysis 1

This article provides an introduction to prediction models and their application in diagnostic imaging research. Prediction models capitalize on the different degrees of association among variables to make a prediction of a health state, formulate a rule, or quantify individual contributions of various predictor variables. The purpose of this article is to elucidate the rationale, implication, and interpretation of prediction models using imaging features. The techniques and challenges of developing, testing, and implementing prediction models are described. Prediction model development methods are similar to data-mining techniques. Learning objectives are to review prediction rule (model) methods, learn how prediction models may be applied to feature analysis, and understand the challenges of developing, testing, and implementing prediction models.

Soil–fungi transfer coefficients: Importance of the location of mycelium in soil and of the differential availability of radionuclides in soil fractions

Soil–fungus transfer coefficients are usually defined as the ratio between the content of the fruiting bodies and that of the soil. Since, however, the methodology of how to determine the soil content is not firmly established, there exist a variety of definitions in the literature. We analyzed the 137Cs, 90Sr, 40K, and 226Ra content of mushroom and soil samples from two pine-wood ecosystems in Spain. The location of the mycelium in the soil profiles of these ecosystems was determined by means of the ergosterol concentration. The results showed the mycelium to generally be localized in the surface layer of soil (0–5 cm). We also carried out a speciation procedure for this layer of soil to determine the different degrees of association of the radionuclides in the soil. The results led us to propose some variations to the traditional definition used in quantifying radionuclide transfer. With these modifications, we were able to analyze Cs–K competition in several species of mycorrhizal and saprophytic fungi.

Repetition Priming in Adults With Williams Syndrome: Age-Related Dissociation Between Implicit and Explicit Memory

We examined implicit and explicit memory in adults with Williams syndrome. An age-related dissociation was found; repetition priming (reflecting implicit memory) did not show change with age, but free recall (reflecting explicit memory) was markedly reduced. We also compared the performance of adults with Williams syndrome to adults with Down syndrome and those with unspecified mental retardation. A similar dissociation was observed in adults with Down syndrome but not in adults with unspecified mental retardation. An IQ-related dissociation was also found. Implicit and explicit memory, therefore, show different degrees of association with age and IQ, supporting theories of these memory processes. Results also suggest that Williams syndrome, similar to Down syndrome, may be associated with precocious aging, resulting in the loss of some cognitive abilities.

Choice of time‐scale in Cox's model analysis of epidemiologic cohort data: a simulation study

Cox's regression model is widely used for assessing associations between potential risk factors and disease occurrence in epidemiologic cohort studies. Although age is often a strong determinant of disease risk, authors have frequently used time-on-study instead of age as the time-scale, as for clinical trials. Unless the baseline hazard is an exponential function of age, this approach can yield different estimates of relative hazards than using age as the time-scale, even when age is adjusted for. We performed a simulation study in order to investigate the existence and magnitude of bias for different degrees of association between age and the covariate of interest. Age to disease onset was generated from exponential, Weibull or piecewise Weibull distributions, and both fixed and time-dependent dichotomous covariates were considered. We observed no bias upon using age as the time-scale. Upon using time-on-study, we verified the absence of bias for exponentially distributed age to disease onset. For non-exponential distributions, we found that bias could occur even when the covariate of interest was independent from age. It could be severe in case of substantial association with age, especially with time-dependent covariates. These findings were illustrated on data from a cohort of 84,329 French women followed prospectively for breast cancer occurrence. In view of our results, we strongly recommend not using time-on-study as the time-scale for analysing epidemiologic cohort data.

The order-restricted association model: Two estimation algorithms and issues in testing

This paper presents a row-column (RC) association model in which the estimated row and column scores are forced to be in agreement with an a priori specified ordering. Two efficient algorithms for finding the order-restricted maximum likelihood (ML) estimates are proposed and their reliability under different degrees of association is investigated by a simulation study. We propose testing order-restricted RC models using a parametric bootstrap procedure, which turns out to yield reliablep values, except for situations in which the association between the two variables is very weak. The use of order-restricted RC models is illustrated by means of an empirical example.