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PubMed1997

[Longitudinal study of cognitive aging in non-demented elderly subjects].

BACKGROUND: The aim of this study is to describe and compare the course of the score of two psychometric tests during a five-year period in a cohort of non-demented elderly subjects. We studied a timed test of simple logical reasoning (the Digit Symbol Substitution Test of Wechsler) and a test of short-term visual memory (the Benton Visual Retention Test). Then we compared the course of these two tests with the course of the Mini-Mental State Examination (MMSE) which evaluates the general cognitive functioning and which has been studied previously. METHODS: The sample consisted of 2792 subjects aged 65 years and older living at home at the beginning of the study (the Paquid cohort in Gironde). Subjects were interviewed at home by a psychologist at the baseline visit and one year, 3 years and 5 years after the baseline visit. All subjects who were diagnosed as demented at any of the four examinations were excluded from this study (218 subjects). The statistical analysis was performed using a mixed effects linear model and an additional analysis was performed to study sensitivity of the results to hypotheses regarding missing data mechanism. RESULTS: Among the three tests studied, only the score of the Digit Symbol Substitution Test declined over the five years (by -1.15 points for subjects aged 65 years to -3.4 points for subjects aged 85 years). We observed an improvement of the score between the first two visits which is sharper for the test of Benton and the MMSE than for the Digit Symbol Substitution Test and which reflects a stress effect at the baseline visit or a learning effect at the second visit. The difference between the cross-sectional measure of age effect and the longitudinal measure of time effect suggests either a cohort effect or a practice effect which would persist during the five years. CONCLUSIONS: The cognitive change in a non-demented elderly population is different according to the psychometric test used. Among the three tests studied, only the score of the Digit Symbol Substitution Test which has a a speed component declined over the five years.

Age Factors↗

PubMed1997

Effect of prolonged topotecan infusion on topoisomerase 1 levels: a phase I and pharmacodynamic study.

Topoisomerase 1 (topo-1) inhibitors act on the target enzyme by forming "cleavable complex," a high molecular weight DNA protein adduct. The formation of such cleavable complexes results in depletion of the Mr 100,000 "free" topo-1 band detectable by Western blot. The objectives of this study were to determine the maximally tolerated dose of prolonged topotecan infusion in previously untreated and minimally pretreated patients. A secondary objective was to measure the effect of prolonged topotecan infusion on topo-1 levels in peripheral blood mononuclear cells (PBMCs) as a pharmacodynamic end point. In a prior Phase I study of 21-day topotecan infusion (H. Hochster et al., J. Clin. Oncol., 12: 553-559, 1994), the maximum tolerated dose for patients treated previously was 0.53 mg/m2/day for 21 days every 28 days. In this study, patients with no prior therapy were treated similarly at 0.7 mg/m2/day for 21 days, and doses were escalated in 0.1 mg/m2/day increments. Patients who had one prior chemotherapy regimen or radiation therapy to a portal of </=20 cm2 were entered at the 0.6 mg/m2/day level. Cohorts of four patients were entered until the maximum tolerated dose was determined. Peripheral blood was sampled weekly to obtain plasma topotecan drug levels and topo-1 levels in PBMCs by Western Blot. For previously untreated patients, the dose-limiting toxicity was myelosuppression at the dose of 0.8 mg/m2/day. Anemia was seen as a cumulative effect. Unexpected nonhematological toxicity was not observed. topo-1 level analysis by Western blot in 11 cycles with weekly measurements showed progressive decrement in the percentage of free topo-1 (compared to baseline value) during weeks 1, 2, and 3. The median percentage of decrease from baseline was 26% (P, not significant; Wilcoxon signed rank test) at week 1, 45% (P = 0.10) at week 2, and 77% (P = 0.016) at week 3. At week 4, off drug treatment, the median percentage of decrease from baseline was only 14%. Additional analysis of free topo-1 level as a function of both area under the curve (P = 0.005) and day of infusion (P = 0.003) demonstrated a significant relationship by regression analysis using a linear mixed effects model. In this Phase I study of topotecan prolonged infusion, hematological toxicity remained dose limiting without evidence of previously described nonhematological toxicity. The recommended Phase II dose is 0.7 mg/m2/day for 21 days every 28 days for previously untreated patients and 0.6 mg/m2/day for those with limited prior therapy. Western blot analysis of noncomplexed topo-1 in PBMCs sampled weekly showed a progressive depletion of free topo-1 over the 21 days of infusion, which reached statistical significance by week 3. Within 1 week of stopping infusion, topo-1 levels return to baseline. A strong correlation of topo-1 level with area under the curve and duration of infusion was demonstrated. These data suggest that prolonged administration of topo-1 inhibitory drugs results in sustained depletion of free topo-1 enzyme as measured by Western Blot analysis, which may be an important consideration in the clinical use of these agents. Direct randomized, comparative trials will be necessary to determine whether such schedules will improve therapeutic index and efficacy.

Adult↗

PubMed2005

APOE alleles predict the rate of cognitive decline in Alzheimer disease: a nonlinear model.

BACKGROUND: The APOE genotype predicts the age at onset of Alzheimer disease (AD) and neuropathologic progression. However, studies relating APOE alleles to the rate of cognitive decline have been inconclusive. This may stem from their use of linear statistical analyses. OBJECTIVE: To model relations of APOE alleles to the rate of cognitive decline in AD, nonlinearly. METHODS: Serial measures of cognitive ability were obtained using the cognitive scale of the Cambridge Examination for Mental Disorders of the Elderly in 218 patients with AD. The relations of these serial scores to APOE alleles were tested using nonlinear and linear mixed-effects models. RESULTS: In the non-linear model, possession of an APOE epsilon4 allele related to earlier and faster cognitive decline, but possession of an APOE epsilon2 related to slower decline. Patients homozygous for APOE epsilon4 showed faster cognitive decline than heterozygotes. The linear model was less sensitive and did not detect differences between APOE epsilon4 homo- and heterozygotes. CONCLUSIONS: APOE genotype strongly predicts the rate of cognitive decline in Alzheimer disease. The decline shows a dose-response relation with the APOE epsilon4 allele, but the APOE epsilon2 allele is protective. The nonlinear model yielded larger estimates of the maximal rate of decline than the linear.

Aged↗

PubMed1998

The relationship of obesity and the development of coronary heart disease to longitudinal changes in systolic blood pressure.

In an investigation of the relationship of obesity and the development of coronary heart disease (CHD) to longitudinal changes in systolic blood pressure (SBP), a sample of 1029 male participants from the Baltimore Longitudinal Study of Baltimore (BLSA), who were free of CHD at the beginning of the study, were examined with a total of 4111 examinations (mean of four examinations per person) conducted during the study period. The mean follow-up time was 8.1 years with a maximum of 16 examinations and 30.9 years of follow-up. During the follow-up period, 192 participants developed CHD, and these participants' data collected after the CHD event were excluded from the analysis. A proportional hazards regression model was used to calculate the relative risk of developing CHD for several CHD risk factors. Both simple and multiple proportional hazards regression models indicate a strong association between body mass index (BMI), cholesterol, cigarette smoking, and systolic blood pressure (SBP) with the risk of developing CHD. In addition, a linear mixed-effects model was used to examine changes in SBP measurements over time and to identify factors, including the age at first examination and time in study, that are related to that change. The results from the linear mixed-effects model analysis indicate that those in the obese group (BMI > or = 30 kg/m2) have SBP measurements that are on average 9.0 mm Hg higher than those in the normal group (20 < or = BMI < 25). Also, SPB measurements were on average 6.6 mm Hg higher in those who developed CHD during the study period than those who remained free of disease. In addition, SPB showed a quadratic relationship with time, and its patterns of change with time were different among the different age groups. Also, the relationship between changes in SBP with respect to cholesterol was dependent on time in the study as well.

Adult↗

PubMed2004

Remifentanil by bolus injection: a safety, pharmacokinetic, pharmacodynamic, and age effect investigation in human volunteers.

BACKGROUND: Although remifentanil's short-acting pharmacokinetic profile makes it well suited for procedures during which a brief period of intense analgesia is required, setting up an infusion pump for brief procedures is inconvenient. The clinical pharmacology of remifentanil administered by bolus injection, a more convenient alternative, has not been explored in detail. The primary aim of this study was to examine the safety of single bolus doses of remifentanil in conscious, healthy, adult volunteers breathing room air. Secondary aims included the evaluation of remifentanil pharmacokinetics and analgesic effects after bolus injection and a comparison of these issues in younger vs older adults. METHODS: Using a randomized, double-blind, placebo-controlled, dose-escalation, crossover study design, 64 subjects (16 over 60 years old) received remifentanil or placebo by bolus injection in a fixed unit dose separated by a 1 h washout period. Respiratory effects were assessed using a respiratory intervention scale. Analgesic effects were assessed using pressure algometry. A population pharmacokinetic model was constructed using non-linear, mixed-effects modelling techniques based on arterial blood samples. Computer simulations were performed to illustrate the clinical application of the pharmacokinetic model. RESULTS: Dose-related increases in both respiratory and analgesic effects were observed. In general, the respiratory depression observed was mild and easily treated with requests to breathe or the administration of oxygen, although the older cohort (and some younger subjects) experienced more substantial respiratory depression at lower doses. The pharmacokinetics of bolus-dose remifentanil were adequately described by a two-compartment model. The pharmacokinetic simulations illustrated the potential utility of bolus-dose remifentanil. CONCLUSIONS: Bolus injection could potentially be a safe and effective means of administering remifentanil in clinical situations requiring a brief period of intense analgesia. Because some subjects, both old and young, experienced significant respiratory depression even at low doses, careful monitoring of respiratory function is essential.

Adult↗

PubMed1996

Halogen-Bridged Mixed-Valence Linear-Chain Complexes: Molecular Orbital Model of Electron Localization.

A simple tight-binding model is used to study electronic distributions and Peierls distortions in a series of mixed-valence linear-chain complexes [M(II)(LL)(2)][M(IV)(LL)(2)X(2)] (M = Ni, Pd, Pt; X = Cl, Br, I; LL = 1,2-diaminoethane, 1,3-diaminopropane). The calculated values of Peierls distortions for complexes with known structure are in good agreement with the experimental data. For the whole series, the model is employed as a qualitative tool to analyze structural and electronic properties. It is shown that charge disproportionation occurs in the related dimers. Thus, our quantum chemical calculations as well as previous phenomenological approaches indicate that, in metal-halogen chains, one deals with the interplay of local and cooperative effects.

Journal Article↗

PubMed2002

Constrained four parameter logistic model.

The constrained four parameter logistic model has found wide application in describing dose response relationships across many assay systems. This discussion examines the basic model and its practical application to potency testing in the context of the 96 well plate. A two step procedure is recommended for the analysis: (i) the constrained logistic model to generate potency estimates, (ii) a linear mixed-effects model to account for within-plate and between plate variability for producing the final combined estimate of potency. The method is outlined in a case study. Design issues related to possible location effects on the plate may be ameliorated by use of a Latin square design.

Biological Assay↗

PubMed2004

Fluoxetine, comprehensive cognitive behavioral therapy, and placebo in generalized social phobia.

BACKGROUND: Generalized social phobia is common, persistent, and disabling and is often treated with selective serotonin reuptake inhibitor drugs or cognitive behavioral therapy. OBJECTIVE: We compared fluoxetine (FLU), comprehensive cognitive behavioral group therapy (CCBT), placebo (PBO), and the combinations of CCBT/FLU and CCBT/PBO. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: Two academic outpatient psychiatric centers. PATIENTS: Subjects meeting a primary diagnosis of generalized social phobia were recruited via advertisement. Seven hundred twenty-two were screened, and 295 were randomized and available for inclusion in an intention-to-treat efficacy analysis; 156 (52.9%) were male, 226 (76.3%) were white, and mean age was 37.1 years. INTERVENTIONS: Treatment lasted for 14 weeks. Fluoxetine and PBO were administered at doses from 10 mg/d to 60 mg/d (or equivalent). Group comprehensive cognitive behavioral therapy was administered weekly for 14 sessions. MAIN OUTCOME MEASURES: An independent blinded evaluator assessed response with the Brief Social Phobia Scale and Clinical Global Impressions scales as primary outcomes. A videotaped behavioral assessment served as a secondary outcome, using the Subjective Units of Distress Scale. Adverse effects were measured by self-rating. Each treatment was compared by means of chi2 tests and piecewise linear mixed-effects models. RESULTS: Clinical Global Impressions scales response rates in the intention-to-treat sample were 29 (50.9%) (FLU), 31 (51.7%) (CCBT), 32 (54.2%) (CCBT/FLU), 30 (50.8%) (CCBT/PBO), and 19 (31.7%) (PBO), with all treatments being significantly better than PBO. On the Brief Social Phobia Scale, all active treatments were superior to PBO. In the linear mixed-effects models analysis, FLU was more effective than CCBT/FLU, CCBT/PBO, and PBO at week 4; CCBT was also more effective than CCBT/FLU and CCBT/PBO. By the final visit, all active treatments were superior to PBO but did not differ from each other. Site effects were found for the Subjective Units of Distress Scale assessment, with FLU and CCBT/FLU superior to PBO at Duke University Medical Center, Durham, NC. Treatments were well tolerated. CONCLUSIONS: All active treatments were superior to PBO on primary outcomes. Combined treatment did not yield any further advantage. Notwithstanding the benefits of treatment, many patients remained symptomatic after 14 weeks.

Adult↗

PubMed2006

Patterns of growth and body proportions after total-body irradiation and hematopoietic stem cell transplantation during childhood.

Patterns of growth and body proportions were studied in 75 children receiving total-body irradiation (TBI) and hematopoietic stem cell transplantation (SCT) before onset of puberty. Of the 19 patients receiving GH, only data obtained before onset of GH were included. Thirty-two patients reached final height (FH). Median change in height SD score (SDS) between SCT and FH was -1.7 in boys and -1.1 in girls. Peak height velocity (PHV) was decreased in the majority of the patients (median PHV 5.7 cm/y in boys and 5.3 cm/y in girls), even though it occurred at appropriate ages. Changes in body proportions were analyzed by linear mixed-effects models. Decrease in sitting height SDS did not differ between boys and girls. In boys, decrease in leg length SDS was of comparable magnitude, whereas, in girls, decrease in leg length was less pronounced, leading to a significant decrease in SDS for sitting height/height ratio in girls only. The sex-specific effects of several variables on height SDS were analyzed by linear mixed-effects modeling, showing a slightly faster decrease in younger children and a more pronounced decrease during puberty in boys compared with girls. We conclude that 1) younger children are more susceptible to growth retardation after TBI and SCT, 2) pubertal growth is more compromised in boys, and 3) leg growth is relatively less affected in girls, possibly due to a high incidence of gonadal failure in girls.

Adolescent↗

PubMed2004

Methodology for estimating regional and global trends of child malnutrition.

BACKGROUND: Child malnutrition is an important indicator for monitoring progress towards the Millennium Development Goals (MDG). This paper describes the methodology developed by the World Health Organization (WHO) to derive global and regional trends of child stunting and underweight, and reports trends in prevalence and numbers affected for 1990-2005. METHODS: National prevalence data from 139 countries were extracted from the WHO Global Database on Child Growth and Malnutrition. A total of 419 and 388 survey data points were available for underweight and stunting, respectively. To estimate trends we used linear mixed-effect models allowing for random effects at country level and for heterogeneous covariance structures. One model was fitted for each United Nation's region using the logit transform of the prevalence and results back-transformed to the original scale. Best models were selected based on explicit statistical and graphical criteria. RESULTS: During 1990-2000 global stunting and underweight prevalences declined from 34% to 27% and 27% to 22%, respectively. Large declines were achieved in Eastern and South-eastern Asia, while South-central Asia continued to suffer very high levels of malnutrition. Substantial improvements were also made in Latin America and the Caribbean, whereas in Africa numbers of stunted and underweight children increased from 40 to 45, and 25 to 31 million, respectively. CONCLUSION: Linear mixed-effect models made best use of all available information. Trends are uneven across regions, with some showing a need for more concerted and efficient interventions to meet the MDG of reducing levels of child malnutrition by half between 1990 and 2015.

Child↗

PubMed2006

Pain control: opioid dosing, population kinetics and side-effects.

Neonates undergoing invasive procedures, postoperative pain or ventilatory support commonly receive opioids for treating pain and stress. Randomized clinical trials have examined the benefits and adverse effects of morphine or fentanyl for ventilated neonates and other indications. This paper summarizes the current evidence for opioid dosing in newborns, reviews their side-effects and explains the use of population kinetics and non-linear mixed-effects modeling to analyze the data from clinical trials. Opioid use should be reserved for severe pain postoperatively or during intensive care in neonates, using continuous infusions rather than intermittent boluses. The safety and efficacy data from prolonged opioid use, particularly on the long-term outcomes of neonates, is still lacking. The pharmacodynamics and pharmacogenetics of opioid use in infancy needs further investigation, using non-linear mixed-effects models to drive individualized therapy. The current interest in opioid research will reap rich dividends in providing pain relief for neonates and avoiding dangerous side effects.

Analgesics, Opioid↗

PubMed2003

Heart rate increases linearly in response to acute isovolemic anemia.

BACKGROUND: The cardiovascular response to acute isovolemic anemia in humans is thought to differ from that of other species. Studies of anesthetized humans have found either no change or a decreased heart rate. A previous study showed that in 32 healthy unmedicated humans, heart rate increased during acute isovolemic anemia. The hypothesis that heart rate in humans increases in response to acute isovolemic anemia and that the increase is affected by gender was tested. STUDY DESIGN AND METHODS: Acute isovolemic anemia to a Hb concentration of approximately 5 g per dL in 95 unmedicated healthy humans was produced by simultaneous withdrawal of blood and IV replacement with 5-percent HSA and autologous platelet-rich plasma. The relationship between heart rate and Hb concentration was examined using a mixed-effects linear regression model that allowed each person to have a fitted line with its own slope and intercept. Cubic and quadratic terms were added to determine if these improved the goodness of fit. The effect of gender was tested by including it and its interactions with Hb in the mixed model. RESULTS: The relationship between heart rate and Hb concentration was linear (p < 0.001) and consistent among the population studied: heart rate = 116.0-4.0 [Hb] (slope 95% CI: -4.2 to -3.8 beats/min/g Hb). Adding a cubic or quadratic term did not significantly improve the goodness of fit of the mathematical expression to the data, confirming the linear nature of the relationship between heart rate and Hb concentration. For women, the slope of the heart rate response was significantly greater than it was for males (difference +/- SE: 0.70 +/- 0.23, p < 0.005). CONCLUSION: In 95 unmedicated, healthy humans, heart rate was a linear function of Hb during acute isovolemic anemia. Females had a significantly greater slope of increase in heart rate with decreasing Hb concentration than did males. The relationship is consistent among individuals, is similar to that reported for conscious dogs, and differs from that found previously in anesthetized humans.

Acute Disease↗

PubMed2007

Power analyses for longitudinal study designs with missing data.

Existing methods for power analysis for longitudinal study designs are limited in that they do not adequately address random missing data patterns. Although the pattern of missing data can be assessed during data analysis, it is unknown during the design phase of a study. The random nature of the missing data pattern adds another layer of complexity in addressing missing data for power analysis. In this paper, we model the occurrence of missing data with a two-state, first-order Markov process and integrate the modelling information into the power function to account for random missing data patterns. The Markov model is easily specified to accommodate different anticipated missing data processes. We develop this approach for the two most popular longitudinal models: the generalized estimating equations (GEE) and the linear mixed-effects model under the missing completely at random (MCAR) assumption. For GEE, we also limit our consideration to the working independence correlation model. The proposed methodology is illustrated with numerous examples that are motivated by real study designs.

Adolescent↗

PubMed2005

Group sequential clinical trials for longitudinal data with analyses using summary statistics.

Longitudinal endpoints are used in clinical trials, and the analysis of the results is often conducted using within-individual summary statistics. When these trials are monitored, interim analyses that include subjects with incomplete follow-up can give incorrect decisions due to bias by non-linearity in the true time trajectory of the treatment effect. Linear mixed-effects models can be used to remove this bias, but there is a lack of software to support both the design and implementation of monitoring plans in this setting. This paper considers a clinical trial in which the measurement time schedule is fixed (at least for pre-trial design), and the scientific question is parameterized by a contrast across these measurement times. This setting assures generalizable inference in the presence of non-linear time trajectories. The distribution of the treatment effect estimate at the interim analyses using the longitudinal outcome measurements is given, and software to calculate the amount of information at each interim analysis is provided. The interim information specifies the analysis timing thereby allowing standard group sequential design software packages to be used for trials with longitudinal outcomes. The practical issues with implementation of these designs are described; in particular, methods are presented for consistent estimation of treatment effects at the interim analyses when outcomes are not measured according to the pre-trial schedule. Splus/R functions implementing this inference using appropriate linear mixed-effects models are provided. These designs are illustrated using a clinical trial of statin treatment for the symptoms of peripheral arterial disease.

Humans↗

PubMed2026

Webcam-Based Real-Time Visual Feedback During Baduanjin Practice in Older Adults: 6-Week Pilot Randomized Study.

BACKGROUND: Baduanjin qigong is a traditional mind-body exercise used to support balance and physical health in older adults. Age-related changes in proprioception may make accurate self-directed performance difficult without external guidance. OBJECTIVE: The aim of this study is to explore whether webcam-based real-time visual feedback delivered during supervised laboratory sessions was associated with differences in webcam-derived 2D pose discrepancy and movement consistency during Baduanjin practice in older adults. METHODS: A total of 31 older adults were enrolled, and 28 participants with complete analyzable records were included in this complete-case dataset (feedback group, n=14; nonfeedback group, n=14). All sessions were conducted face-to-face in a supervised motion-analysis laboratory. Weekly 2D pose-discrepancy values were analyzed using a linear mixed-effects model with fixed effects for group, categorical week, and the group-by-week interaction and a participant-specific random intercept. Joint- and movement-specific participant-level 6-week means were analyzed exploratorily using Welch independent-samples t tests. Holm correction was applied across 24 exploratory contrasts (6 week-specific, 8 joint-specific, and 10 movement-specific comparisons), and Hedges g and 95% CIs were reported. Participant-specific weekly slopes and within-participant variability were additionally examined to directly assess longitudinal error drift. RESULTS: The linear mixed-effects model showed no significant group-by-week interaction (Wald χ25=1.09; P=.96) and no significant overall week effect (Wald χ25=6.40; P=.27). Averaged across 6 weeks, the feedback group had an estimated mean 2D pose discrepancy 1.20° lower than the nonfeedback group (95% CI -2.38° to -0.02°; P=.046), although this marginal pilot finding was sensitive to an analytic approach. No week-specific contrast remained significant after Holm adjustment. Nominal right elbow, right shoulder, and right knee differences did not survive global Holm correction. Form 3 showed a lower mean discrepancy in the feedback group (mean difference -3.70°, 95% CI -5.86° to -1.54°; Hedges g=-1.30; unadjusted P=.002; Holm-adjusted P=.04). Direct analyses of participant-specific slopes and within-participant SDs did not support a significant between-group difference in longitudinal error drift. CONCLUSIONS: In this small exploratory pilot study conducted under supervised laboratory conditions, the 6-week trajectories did not differ significantly between groups. A marginally lower average 2D pose discrepancy was observed in the feedback group across the 6 weeks, but no individual week- or joint-specific comparison remained significant after multiplicity adjustment. Form 3 was the only exploratory contrast that remained significant after global Holm correction. Direct longitudinal analyses did not demonstrate prevention of error drift. Larger studies using validated reference measurements, prespecified outcomes, and adequately powered longitudinal designs are required.

Humans↗

PubMed2026

Polygenic Profiles Are Associated with Multidomain Biochemical Adaptations Across a Competitive Season in Professional Football Players: A Longitudinal Observational Study.

Background/Objectives: The physiological adaptations required to sustain elite football performance are influenced by both genetic background and dynamic biochemical responses, although their interaction across a full competitive season remains insufficiently characterized. This study aimed to examine the association between polygenic profiles and longitudinal biochemical adaptations in professional football players. Methods: Forty male professional football players competing in the Spanish league were monitored across two consecutive seasons. Blood samples were collected at six time points representing different phases of the competitive cycle. Biomarkers related to muscle metabolism, iron status, and hepatic function were analyzed. Polygenic profiles were calculated using Total Genotype Scores (TGS) for muscle performance, hepatic resilience, and metabolic efficiency. Associations were initially explored using Pearson correlations and subsequently evaluated using linear mixed-effects models accounting for repeated measurements within subjects. Results: Exploratory correlation analyses identified several associations between polygenic profiles and biochemical markers. Muscle performance TGS was inversely associated with serum iron (r = -0.36, p = 0.017) and positively associated with CK (r = 0.32, p = 0.041), Hb (r = 0.29, p = 0.046), and Hct (r = 0.33, p = 0.024). Hepatic resilience TGS showed inverse associations with ALT (r = -0.39, p = 0.012), urea (r = -0.51, p = 0.011), and BUN (r = -0.51, p = 0.011). Metabolic efficiency TGS was negatively associated with AST (r = -0.43, p = 0.044), ALT (r = -0.33, p = 0.025), and GGT across multiple time points (p = 0.001-0.013). However, although several nominal associations emerged in linear mixed-effects models accounting for repeated measurements, none remained statistically significant after false discovery rate correction. These findings should therefore be interpreted as exploratory and hypothesis-generating. Conclusions: Polygenic profiles may be associated with inter-individual variability in biochemical adaptations throughout a competitive season. These findings suggest the integration of genomic and biochemical data in precision athlete monitoring, while highlighting causal relationships and predictive applications require further investigation.

Humans↗

PubMed2005

Exposure to oil mist and oil vapour during offshore drilling in norway, 1979-2004.

OBJECTIVES: To describe personal exposure to airborne hydrocarbon contaminants (oil mist and oil vapour) from 1979 to 2004 in the mud-handling areas of offshore drilling facilities operating on the Norwegian continental shelf when drilling with oil-based muds. METHODS: Qualitative and quantitative information was gathered during visits to companies involved in offshore oil and gas production in Norway. Monitoring reports on oil mist and oil vapour exposure covered 37 drilling facilities. Exposure data were analysed using descriptive statistics and by constructing linear mixed-effects models. RESULTS: Samples had been taken during the use of three generations of hydrocarbon base oils, namely diesel oils (1979-1984), low-aromatic mineral oils (1985-1997) and non-aromatic mineral oils (1998-2004). Sampling done before 1984 showed high exposure to diesel vapour (arithmetic mean, AM = 1217 mg m(-3)). When low-aromatic mineral oils were used, the exposure to oil mist and oil vapour was 4.3 and 36 mg m(-3), and the respective AMs for non-aromatic mineral oils were reduced to 0.54 and 16 mg m(-3). Downward time trends were indicated for both oil mist (6% per year) and oil vapour (8% per year) when the year of monitoring was introduced as a fixed effect in a linear mixed-effects model analysis. Rig type, technical control measures and mud temperature significantly determined exposure to oil mist. Rig type, type of base oil, viscosity of the base oil, work area, mud temperature and season significantly determined exposure to oil vapour. Major decreases in variability were found for the between-rig components. CONCLUSIONS: Exposure to oil mist and oil vapour declined over time in the mud-handling areas of offshore drilling facilities. Exposure levels were associated with rig type, mud temperature, technical control measures, base oil, viscosity of the base oil, work area and season.

Aerosols↗

PubMed1993

A modeling approach to hospital location for effective marketing.

This paper develops a mixed integer linear programming model for locating health care facilities. The parameters of the objective function of this model are based on factor rating analysis and grid method. Subjective and objective factors representative of the real life situations are incorporated into the model in a unique way permitting a trade-off analysis of certain factors pertinent to the location of hospitals. This results in a unified approach and a single model whose credibility is further enhanced by inclusion of geographical and demographical factors.

Algorithms↗