Related Covariates Research Articles

Predictors of risk for relapse in patients with schizophrenia or schizoaffective disorder during olanzapine drug therapy

Purpose To evaluate the relationship of dose decrease, symptom worsening, and baseline covariates on subsequent relapse during olanzapine treatment in patients with schizophrenia or schizoaffective disorder. Methods In two 28-week, randomized, double-blind clinical trials, a Cox proportional hazards model was used to determine potential correlates of relapse (defined as ⩾20% worsening on PANSS total and CGI-Severity ⩾3) among patients ( N = 271) who responded to 8 weeks of olanzapine treatment (10–20 mg/day). Variables examined included: demographics, illness characteristics, baseline symptoms, symptom change, dose, adverse events, and functioning. Results Patients with a lower last dose relative to the preceding visit interval were 4 times more likely to relapse during that visit interval than other patients ( p < .001). A similar finding was observed for a decrease in interval modal dose, although this variable was more predictive of relapse in the visit interval immediately following dose decrease ( p = .027). In a subgroup analysis by gender, there was a significantly greater incidence of relapse in men with a dose decrease, whereas a dose decrease in women did not correlate with relapse. Relapse was also correlated with the emergence or worsening of a psychiatric adverse event during the same ( p < .001) and preceding ( p = .007) visit intervals, and with increased rating scale measures of psychopathology. The occurrence of a non-psychiatric adverse event was not associated with relapse. Conclusion Dose decrease is a significant predictor of relapse in male but not female patients. Psychiatric adverse events also predicted relapse. Patients should be periodically reassessed to determine the need for maintenance treatment with appropriate dose.

Boundary Conditions for Limited-Area Ensemble Kalman Filters

Abstract One aspect of implementing a limited-area ensemble Kalman filter (EnKF) involves the specification of a suitable ensemble of lateral boundary conditions. Two classes of methods to populate a boundary condition ensemble are proposed. In the first class, the ensemble of boundary conditions is provided by an EnKF on a larger domain and is approximately a random draw from the probability distribution function for the forecast (or analysis) on the limited-area domain boundary. The second class perturbs around a deterministic estimate of the state using assumed spatial and temporal covariance relationships. Methods in the second class are relatively flexible and easy to implement. Experiments that test the utility of these methods are performed for both an idealized low-dimensional model and limited-area simulations using the Weather Research and Forecasting (WRF) model; all experiments employ simulated observations under the perfect model assumption. The performance of the ensemble boundary condition methods is assessed by comparing the results of each experiment against a control “global” EnKF that extends beyond the limited-area domain. For all methods tested, results show that errors for the limited-area EnKF are larger near the lateral boundaries than those from a control EnKF, but decay inside the limited-area domain so that errors there are comparable to the control case. The relatively larger errors near the boundaries in the limited-area EnKF originate from not assimilating observations outside the limited-area domain and, in the second class of methods, from deficiencies in boundary spatial and temporal covariances. Overall, these experiments suggest that for observation densities typical in numerical weather prediction models, ensemble boundary conditions can be specified in the absence of a global ensemble without significant penalty in the domain interior by perturbing around an ensemble mean.

Population pharmacokinetics of darbepoetin alfa in haemodialysis and peritoneal dialysis patients after intravenous administration

To characterize the pharmacokinetics of darbepoetin alfa and covariate relationships in haemodialysis (HD) and peritoneal dialysis (PD) patients. Data were collected from 131 (63 HD and 68 PD) patients who received darbepoetin alfa intravenously. A total of 917 serum concentrations were available. The data were analysed by nonlinear mixed effect modelling using NONMEM with a model including endogenous erythropoietin production. In addition, the final model was evaluated using bootstrap resampling. The selected basic model was a two-compartment model with a combination of additive and the constant coefficient of variation error models. The significant covariates were weight (WT) for clearance (CL) and the volume of central compartment (V(1)), and the dialysis technique (DIA) for V(1). The typical values of CL and V(1) were 0.0807 l h(-1) and 2.51 l, respectively. V(1) in PD patients was 17% higher than in HD patients. With the introduction of WT in CL and WT and DIA in V(1), interindividual variability decreased from 27.1% to 20.6% in CL and from 29.1% to 21.8% in V(1). The mean parameter estimates from the bootstrap datasets were similar to those from the original dataset. Evaluation by bootstrapping showed that the final model was stable. The results of the present analysis suggest no dosage regimen change is warranted for darbepoetin alfa in HD and PD patients over the range of distribution of covariates included in this study.

Linkage Analysis Using Co-Phenotypes in the BRIGHT Study Reveals Novel Potential Susceptibility Loci for Hypertension

Identification of the genetic influences on human essential hypertension and other complex diseases has proved difficult, partly because of genetic heterogeneity. In many complex-trait resources, additional phenotypic data have been collected, allowing comorbid intermediary phenotypes to be used to characterize more genetically homogeneous subsets. The traditional approach to analyzing covariate-defined subsets has typically depended on researchers' previous expectations for definition of a comorbid subset and leads to smaller data sets, with a concomitant attrition in power. An alternative is to test for dependence between genetic sharing and covariates across the entire data set. This approach offers the advantage of exploiting the full data set and could be widely applied to complex-trait genome scans. However, existing maximum-likelihood methods can be prohibitively computationally expensive, especially since permutation is often required to determine significance. We developed a less computationally intensive score test and applied it to biometric and biochemical covariate data, from 2,044 sibling pairs with severe hypertension, collected by the British Genetics of Hypertension (BRIGHT) study. We found genomewide-significant evidence for linkage with hypertension and several related covariates. The strongest signals were with leaner-body-mass measures on chromosome 20q (maximum LOD = 4.24) and with parameters of renal function on chromosome 5p (maximum LOD = 3.71). After correction for the multiple traits and genetic locations studied, our global genomewide P value was .046. This is the first identity-by-descent regression analysis of hypertension to our knowledge, and it demonstrates the value of this approach for the incorporation of additional phenotypic information in genetic studies of complex traits.

Modeling Genotype × Environment Interaction Using Additive Genetic Covariances of Relatives for Predicting Breeding Values of Wheat Genotypes

In plant breeding, multienvironment trials (MET) may include sets of related genetic strains. In self‐pollinated species the covariance matrix of the breeding values of these genetic strains is equal to the additive genetic covariance among them. This can be expressed as an additive relationship matrix, A, multiplied by the additive genetic variance. Using Mixed Model Methodology, the genetic covariance matrix can be estimated and Best Linear Unbiased Predictors (BLUPs) of the breeding values obtained. The effectiveness of exploiting relationships among strains tested in METs and usefulness of these BLUPs of breeding values for simultaneously modeling the main effects of genotypes and genotype × environment interaction (GE) have not been thoroughly studied. In this study, we obtained BLUPs of breeding values using genetic variance–covariance structures constructed as the Kroneker product (direct product) of a structured matrix of genetic variances and covariances for sites and a matrix of genetic relationships between strains, A. Results are compared with those from traditional fixed effects and random effects models for studying GE ignoring genetic relationships. A CIMMYT international wheat trial was used for illustration. Results showed that direct products of factor analytic structures with matrix A efficiently model the main effects of genotypes and GE. These models showed the lowest standard error of the BLUPs [SE(BLUP)] of breeding values. Genotypes that were related to other genotypes had small SE(BLUP). Related genotypes can clearly be visualized in biplots.

Salinity Assimilation Using S(T): Covariance Relationships

Abstract Assimilation of salinity into ocean and climate general circulation models is a very important problem. Argo data now provide far more salinity observations than ever before. In addition, a good analysis of salinity over time in ocean reanalyses can give important results for understanding climate change. Here it is shown from the historical ocean database that over large regions of the globe (mainly midlatitudes and lower latitudes) variance of salinity on an isotherm S(T) is often less than variance measured at a particular depth S(z). It is also shown that the dominant temporal variations in S(T) occur more slowly than variations in S(z), based on power spectra from the Bermuda time series. From ocean models it is shown that the horizontal spatial covariance of S(T) often has larger scales than S(z). These observations suggest an assimilation method based on analyzing S(T). An algorithm for assimilating salinity data on isotherms is then presented, and it is shown how this algorithm produces orthogonal salinity increments to those produced during the assimilation of temperature profiles. It is argued that the larger space and time scales can be used for the S(T) assimilation, leading to better use of scarce salinity observations. Results of applying the salinity assimilation algorithm to a single analysis time within the ECMWF seasonal forecasting ocean model are also shown. The separate salinity increments coming from temperature and salinity data are identified, and the independence of these increments is demonstrated. Results of an ocean reanalysis with this method will appear in a future paper.

Population analysis of the pharmacokinetics and the haematological toxicity of the fluorouracil-epirubicin-cyclophosphamide regimen in breast cancer patients

The aims of the study were (a) to characterise the pharmacokinetics (PK), including inter-individual variability (IIV) and inter-occasion variability (IOV) as well as covariate relationships and (b) to characterise the relationship between the PK and the haematological toxicity of the component drugs of the fluorouracil (5-FU)-epirubicin (EPI)-cyclophosphamide (CP) regimen in breast cancer patients. Data from 140 breast cancer patients, either within one of different studies or in routine clinical management, were included in the analyses. The patients were all treated with the fluorouracil-epirubicin-cyclophosphamide (FEC) regimen every third week for 3-12 courses, either in standard doses, i.e. 600/60/600 mg/m(2) of 5-FU, EPI and CP, respectively, or according to a dose escalation/reduction protocol (tailored dosing). PK data were available from 84 of the patients, whereas time-courses of haematological toxicity were available from 87 patients. The data analysis was carried out using mixed effects models within the NONMEM program. The PK of 5-FU, EPI and 4-hydroxy-cyclophosphamide (4-OHCP), the active metabolite of CP, were described with a one-compartment model with saturable elimination, a three-compartment linear model and a two-compartment linear model, respectively. No clinical significant correlation was found between PK across drugs. The unexplained variability in clearance was found to be less within patients, between courses (inter-occasion variability, IOV) than between patients (inter-individual variability, IIV) for EPI and 5-FU. For 4-OHCP, however, the IIV diminished by approximately 45% when significant covariates were included and the final population model predicts an IIV that is equal to IOV. Significant covariates for elimination capacity parameters were serum albumin (5-FU, EPI and 4-OHCP), creatinine clearance (5-FU), bilirubin (EPI) and body surface area (BSA) (4-OHCP). Elimination capacity of 5-FU and EPI was not related to BSA and for none of the studied drugs did body weight explain the PK variability. The time-course of haematological toxicity after treatment was well described by a semi-physiological model that assumes additive haematological toxicity between CP and EPI with negligible contribution from 5-FU. The influence of G-CSF could be incorporated into the model in a mechanistic manner as shortening the maturation time to 43% of the normal duration and increasing the mitotic activity to 269% of normal activity. The models presented describe the dose-concentration-toxicity relationships for the FEC therapy and may provide a basis for implementation and comparison of different individualisation strategies based on covariates, therapeutic drug monitoring and/or pharmacodynamic (PD) feedback. The PD model extends on previous semi-mechanistic models in that it also takes G-CSF administration into account.

The Impact of Tax Credits on Labour Supply

One of the principle aims of the Working Families' Tax Credit in the UK was to increase the participation of single mothers. The literature to date concludes there was approximately a five-percentage-point increase in employment of single mothers. The differences-in-differences methodology that is typically used compares single mother with single women without children. However, the characteristics of these groups are very different, and change over time in relative covariates are likely to violate the identifying assumption. We find that when we control for differential trends between women with and without children, the employment effect of the policy falls significantly. Moreover, the effect is borne solely by those working full-time (30 hours or more), while having no effect on inducing people into the labor market from inactivity. Looking closely at important covariates over time, we can see sizeable changes in the relative returns to employment between the treatment and control groups.

A Bayesian approach for population pharmacokinetic modelling of sirolimus

To explore a Bayesian approach for the pharmacokinetic analysis of sirolimus concentration data arising from therapeutic drug monitoring (poorly informative concentration-time point design), and to explore possible covariate relationships for sirolimus pharmacokinetics. Sirolimus concentration-time data were available as part of routine clinical care from 25 kidney transplant recipients. Most samples were taken at or near the trough time point at steady state. The data were analyzed using a fully conditional Bayesian approach with PKBUGS (v 1.1)/WinBUGS (v 1.3). Features of the data included noncompliance and missing concentration measurements below the limit of sensitivity of the assay. Informative priors were used. A two-compartment model with proportional residual error provided the best fit to the data (consisting of 315 sirolimus concentration-time points). The typical value for the apparent clearance (CL/F ) was 12.5 l h(-1) at the median age of 44 years. Apparent CL was found to be inversely related to age with a posterior probability of a clinically significant effect of 0.734. A population pharmacokinetic model was developed for sirolimus using a novel approach. Bayesian modelling with informative priors allowed interpretation of a significant covariate relationship, even using poorly informative data.

Ordered subset analysis supports a glaucoma locus at GLC1I on chromosome 15 in families with earlier adult age at diagnosis

Open angle glaucoma (OAG) is a complex disorder with varying etiologies due to multiple genes and environmental effects. This genetic heterogeneity can confound efforts to map loci. Increased homogeneity in a sample can be achieved using either ordered subset analysis (OSA) which groups families, or individual OSA (IOSA), which groups individuals based on disease related covariates. Recently, GLC1I was mapped to 15q11–13 in families with early adult onset of OAG. We tested for linkage to GLC1I in an independent sample of 167 individuals in 25 multiplex OAG families of European descent. We carried out nonparametric linkage analysis on the complete set of 25 families and obtained a maximum LOD score of 1.00 at 9.0 cM. Using mean age at diagnosis (AAD) across the affected individuals within each family to order the families as a proxy for age at onset, we found a maximum OSA LOD score of 2.09 ( p=0.021) at 26.1 cM. The mean (± s. d.) AAD across the 14 earlier AAD families that contributed to the OSA LOD score was 50.6 years (±5.38); the mean AAD for the other 1210 later AAD families that did not contribute to the OSA LOD score (the high-AAD) was 61.7 years (±3.50). We also ran IOSA on our families using AAD as our covariate on which to subset affected individuals. The maximum LOD score was 1.01 at 14.3 cM when ordering subjects from early to late AAD. Ordered subset analysis of this sample has provided evidence of linkage close to the previously identified GLC1I glaucoma locus on 15q11–13 in families with middle-aged mean age at diagnosis.

The Relationship of Longitudinal Change in Reproductive Hormones and Vasomotor Symptoms during the Menopausal Transition

The relationship of reproductive hormones to vasomotor symptoms (VMS) has been incompletely explored, although an increase in such symptoms at midlife and their reduction with hormone therapy suggest a strong and direct relationship. Vasomotor symptoms are reported by 65-76% of women traversing the menopausal transition and are a primary reason for medical intervention during this life stage. The purpose of this report was to relate longitudinal serum concentrations of the reproductive hormones estradiol (E2), FSH, testosterone (T), dehydroepiandrosterone sulfate (DHEAS), and SHBG and the free hormone indices free E2 index (FEI) and free T index (FTI) with the occurrence of VMS in women traversing the menopausal transition. The Study of Women's Health Across the Nation is a multisite, longitudinal, cohort study of the menopausal transition being conducted in community-based groups of women. At baseline, 3302 menstruating women who belonged to one of five ethnic/racial groups were recruited and followed up with annual visits. Frequencies of symptoms (hot flashes, night sweats) for the prior 2 wk and measures of other covariates as well as potentially confounding variables were self-reported in the annual interview. Serum was obtained annually, on d 2-5 of a spontaneous cycle in cycling women or within 90 d of the anniversary of the baseline study visit in noncycling women and assayed for FSH, E2, T, SHBG, and DHEAS. FTI and FEI were calculated. This analysis incorporated available longitudinal data from 3293 women, excluding information collected at or after first report of hormone therapy use or hysterectomy. Data were analyzed using longitudinal marginal logistic regression models and a partial proportional odds model. After adjusting for age, body mass index, and other related covariates, VMS prevalence increased with higher (log)FSH concentrations, and the increase was greater when blood was drawn more than 5 d after menses began. FSH concentrations were positively associated with the frequency of either hot flashes or night sweats, and higher FSH concentrations were associated with greater odds of reporting more frequent symptoms. Vasomotor symptom prevalence decreased with higher (log)E2, (sqrt)SHBG, and (log)FEI but only when these hormone values were modeled independently of (log)FSH values and the specimens were obtained outside the d 2-5 window. When modeled simultaneously with (log)FSH, (log)E2, (sqrt)SHBG, and (log)FEI were no longer significantly associated with symptom prevalence. (Cubic root)T and (sqrt)DHEAS concentrations and (log)FTI were not associated with the prevalence of VMS. Annual serum FSH concentrations, but not E2, T, DHEAS, FTI, or FEI when collectively modeled longitudinally, are associated with both the prevalence and frequency of VMS in women at midlife.

The Effect of Diabetes on Disability in Middle-Aged and Older Adults

Physical disability is increasingly recognized as an adverse health consequence of type 2 diabetes in older adults. We studied the effect of diabetes on disability in middle-aged and older adults to: 1) characterize the association of diabetes with physical disability in middle-aged adults, and 2) determine the extent to which the effect of diabetes is explained by related covariates in either or both age groups. We used data from two parallel national panel studies of middle-aged and older adults to study the effect of self-reported diabetes at baseline on disability 2 years later, adjusting for baseline covariates. Diabetes was strongly associated with subsequent physical disability (measured by a composite variable combining activities of daily living, mobility, and strength tasks) in middle-aged and older adults. Controlling for socioeconomic characteristics and common diabetes-related and unrelated comorbidities and conditions reduced the diabetes effect substantially, but it remained a significant predictor of disability in both groups. Our analyses demonstrated that disability is an important diabetes-related health outcome in middle-aged and older adults that should be prevented or mitigated through appropriate diabetes management.

Homelessness and HIV Risk Behaviors Among Drug Injectors in Puerto Rico

This report examines associations between homelessness and HIV risk behaviors among injection drug users (IDUs) in Puerto Rico. The study sample consisted of 557 IDUs who were not in treatment, recruited in inner-city neighborhoods of the North Metro Health Care Region. Subjects were categorized into three groups by residential status (last 30 days): housed, transitionally housed (living with friends, family, or others but considering themselves homeless), and on-the-street homeless (living on the street or in a shelter). Multiple logistic regression models were fitted to assess effects of residential status on each HIV risk behavior after adjusting for sociodemographic and drug-use related covariates. Transitionally housed and on-the-street homeless subjects made up 16% of the total sample. On-the-street homeless IDUs were more likely to test positive for HIV than were transitionally housed and housed IDUs. In the adjusted analysis, on-the-street homeless subjects were significantly more likely to share needles, share rinse water, and practice back loading than the other two groups. Sexual risk behaviors (last 30 days) were not significantly associated with residential status after adjustment. Findings from this study present an added challenge to drug treatment and HIV prevention and treatment programs, to provide services that can address the additional needs of drug users suffering the stressors of homelessness.

Quality of Life Profile – Adolescent Version: Assessing the relationship of covariates to scale scores using structural equation modeling

This study investigates the effects of covariates on adolescent quality of life (QOL) using structural equation modeling (SEM). The Quality of Life Profile--Adolescent Version, a generic 54 item self-reported questionnaire, was administered to 363 adolescents aged between 10 and 18 years who were enrolled in 20 secondary schools within metropolitan Perth, the capital of Western Australia. Previous results based on a second-order SEM provided preliminary support for measuring adolescent QOL in terms of physical health, psychological, social, environment and opportunities for growth and development. The second-order model is further enhanced in this study by incorporating covariates age, presence of a chronic condition, amount of control and perception of health. The amount of control the adolescent perceived had a significant positive impact on QOL, whereas poorer reports of health had a negative impact. However, the presence of a chronic condition was found to have little effect on QOL, while the modest inverse relationship between age and QOL was not statistically significant.

Semiparametric Estimation of Proportional Mean Residual Life Model in Presence of Censoring

A mean residual life function is the average remaining life of a surviving subject, as it varies with time. The proportional mean residual life model was proposed by Oakes and Dasu (1990, Biometrika77, 409-410) in regression analysis to study its association with related covariates in absence of censoring. In this article, we develop some semiparametric estimation procedures to take censoring into account. The proposed methodology is evaluated via simulation studies, and further applied to a clinical trial of chemotherapy in postoperative radiotherapy of lung cancer patients.

Development and evaluation of a population pharmacokinetic (PK) model for darbepoetin alfa in healthy subjects

Aims Darbepoetin alfa (DA) is a novel erythropoiesis stimulating protein with longer half-life, which allows for less frequent dosing. DA is approved for treatment of anemia associated with chemotherapy and chronic kidney disease. We describe the development and evaluation of a population PK model of DA in healthy subjects. Methods Serum DA concentration data were gathered from 50 healthy subjects (age 53–88 years) after intravenous and/or subcutaneous doses ranging from 0.75 to 9 μg/kg. Intensive PK profiles were obtained after single doses in all subjects. Results A population PK model, including first order absorption, two-compartment disposition, and first order elimination, provided adequate description of data. The drug exhibited flip-flop kinetics after SC administration. The influence of baseline covariates such as age, body weight, height, baseline hemoglobin, and gender on the model parameters was evaluated to obtain the final model, which was tested with posterior predictive and bootstrap tests. Simulations were performed using the final model to compare the PK after fixed versus weight-based DA dosing. Conclusions A population PK model which describes the inter-individual and intra-individual variability in DA PK and PK parameter-baseline covariate relationships was developed using robust modeling methodologies. The model is being used to predict PKPD response of DA in various therapeutic settings. Clinical Pharmacology & Therapeutics (2005) 77, P76–P76; doi: 10.1016/j.clpt.2004.12.182

Frame-based and frameless stereotactic hematoma puncture and subsequent fibrinolytic therapy for the treatment of spontaneous intracerebral hemorrhage

Comparison of two minimally invasive procedures for the treatment of intracerebral hemorrhage and subsequent lysis with regard to technical implications and clinical outcome of the patients. Retrospective analysis of 126 patients with spontaneous supratentorial intracerebral hemorrhage treated by frame-based (n=53) or frameless (n=75) hematoma aspiration and subsequent fibrinolysis with recombinant tissue plasminogen activator (rt-PA). Data were analysed for the whole group as well as for the two subsets of patients with regard to hematoma reduction, procedure-related complications, and the early and long term clinical outcome of the patients. Functional outcome was rated using the Glasgow Outcome Scale (GOS) and Barthel-Index (median follow-up 178 weeks). The prognostic impact of patient related covariates on the GOS was analysed using logistic regression analysis. 49 out of 126 patients (38.9 %) died, 25 of them in the early postoperative period. Only 22/126 (17.5 %) had a favorable long term outcome (GOS >3). Age > 65 years was significantly (p<0.03, OR 3.6) associated with a higher risk for an unfavorable long term outcome (GOS < or = 3). Treatment had no impact on outcome. Both techniques were highly effective in reducing the intracerebral blood volume by 75.8+/-21.4% of the initial hematoma volume in frame-based and 64.8+/-25.4 % in frameless stereotaxy within 2 days of rt-PA-therapy. Malpositioning of the catheter occurred more often in the frameless group (21.3% vs. 9.4 % in the frame-based procedure) without gaining statistical significance. Frame-based and frameless stereotactic hematoma aspirations with subsequent fibrinolysis are effective in volume reduction of intracerebral hemorrhage with comparable clinical outcome. The frameless procedure is associated with a higher risk for malpositioning of the catheter. Despite effective hematoma reduction with both techniques, the percentage of patients with a good clinical outcome remained limited especially in the elder subpopulation.

Lifestyle behaviors associated with lower risk of having the metabolic syndrome

The metabolic syndrome is a cluster of risk factors that predisposes individuals to cardiovascular disease (CVD) and diabetes and is present in almost one fourth of adult Americans. Risk factors involved with the metabolic syndrome can be altered via modifiable lifestyle factors, such as diet, physical activity, and smoking and drinking habits. The objective of this study was to examine the extent to which these modifiable lifestyle behaviors are associated with the risk of having the metabolic syndrome. Data from the Third National Health and Nutrition Examination Survey (NHANES III), conducted between 1988 and 1994, were used to measure the risk of having the metabolic syndrome in healthy adult Americans who follow certain lifestyle behaviors, such as dietary practices, levels of physical activity, smoking and drinking habits. Low physical activity level, high carbohydrate (CHO) intake, and current smoking habits were all significantly associated with an increased risk of having the metabolic syndrome, even after adjusting for other related covariates. Relative to physically inactive subjects, being physically active was associated with lower odds ratio (OR) (0.36, confidence interval [CI] 0.21 to 0.68, P < .01) in overweight men and in normal weight (0.36, CI 0.18 to 0.70, P < .01) and overweight (0.61, CI 0.38 to 0.97, P < .05) women. Although the type of CHO could not be distinguished, relative to a high CHO diet, men having a low or moderate CHO intake had a lower risk of having the metabolic syndrome with respective ORs of 0.41 (CI 0.24 to 0.67, P < .01) and 0.44 (CI 0.25 to 0.77, P < .01); no effect of dietary CHO was observed in women. Moderate alcohol consumption was not significantly related to the risk of having the metabolic syndrome in men, but was associated with a lower OR in women (0.76, CI 0.61 to 0.95, P < .05). Regression models indicate a reduced risk of having the metabolic syndrome when selected low-risk lifestyle factors are present in combination, particularly in subjects with body mass index (BMI) < 30 kg/m2. According to our cross-sectional logistic models, the risk of having the metabolic syndrome is substantially lower in individuals who are physically active, nonsmoking, have a relatively low CHO intake and moderate alcohol consumption, and who maintain a BMI in the non-obese range. These observations have potentially important value for public health recommendations.

Insulin-like growth factor 1 as a predictor of ischemic stroke outcome in the elderly

To examine whether serum insulin-like growth factor 1 (IGF-1) and IGF binding protein 3 (IGFBP-3) concentrations, determined early after the onset of stroke, are predictive of clinical outcome in elderly patients. The sample comprised 85 patients (mean [+/- SD] age, 83 +/- 7.4 years; range, 67 to 99 years; 34% male) who were admitted with acute stroke to a geriatric ward between January 1998 and June 2000, and 88 control patients who were similar in age and sex. Clinical and laboratory assessments, computed tomographic scan of the head, carotid ultrasonography, and electrocardiography were employed to define the clinical and etiologic stroke subtype. Fasting blood samples were collected within 24 hours of admission for IGF-I and IGFBP-3 measurement. Univariate and multiple logistic regression analyses, with adjustment for other related clinical covariates, were used to assess the relation of IGF-I and IGFBP-3 to poor outcome, defined as severe disability (Barthel index <60/100) or death, at 1 month (or at discharge), 3 months, and 6 months. Mean (+/- SD) IGF-1 levels were lower in patients with stroke than in controls (69 +/- 45 ng/mL vs. 102 +/- 67 ng/mL, P adjusted for age = 0.001). The mean IGF-1/IGFBP-3 molar ratio was also lower in stroke patients (0.12 +/- 0.07 vs. 0.19 +/- 0.09, P adjusted for age <0.0001). However, there was no relation of hormone levels to either the clinical subtype of stroke or the extent of neurologic impairment. IGF-1 levels were inversely related to poor outcome (mainly death) at 3 and 6 months, independent of other clinical covariates that were highly predictive of outcome, such as age and stroke scale score on admission (hazard ratio for death at 6 months for each 20-ng/mL increase = 0.7; 95% confidence interval: 0.5 to 0.9). An independent association of the molar ratio with death at 3 and 6 months was also found. Low levels of circulating IGF-1 may predict the clinical outcome of stroke in elderly patients.

Nonlocality and short-range wetting phenomena.

We propose a nonlocal interfacial model for 3D short-range wetting at planar and nonplanar walls. The model is characterized by a binding-potential functional depending only on the bulk Ornstein-Zernike correlation function, which arises from different classes of tubelike fluctuations that connect the interface and the substrate. The theory provides a physical explanation for the origin of the effective position-dependent stiffness and binding potential in approximate local theories and also obeys the necessary classical wedge covariance relationship between wetting and wedge filling. Renormalization group and computer simulation studies reveal the strong nonperturbative influence of nonlocality at critical wetting, throwing light on long-standing theoretical problems regarding the order of the phase transition.