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Physical activity and magnetic field exposure in pregnancy.

BACKGROUND: Peak magnetic field exposure was associated with increased risk of miscarriage in 2 recent studies. Reduced physical activity levels in healthy pregnancies may affect measured exposure and thus bias results. METHODS: We recruited 100 pregnant women to wear an Actigraph accelerometer and EMDEX magnetic field monitor for a 7-day period. We evaluated the association between physical activity and magnetic field exposure (peaks and time-weighted average) using generalized estimating equations and linear mixed models. RESULTS: We found a positive association between level of activity and likelihood of incurring elevated exposure in the person-day analysis, most strongly for cutpoints of 16 or 20 mG, for both working and nonworking women among whom odds ratios in the uppermost quartile ranged from 2.1 to 2.6. A positive association was found using person-minutes only among nonworking women. CONCLUSION: Physical activity may affect peak magnetic field exposure. If the early nausea and later cumbersomeness of healthy pregnancies leads to reduced physical activity, this could distort measured magnetic field-health outcome associations.

Adult↗

Familial aggregation of small-for-gestational-age births: the importance of fetal genetic effects.

OBJECTIVE: This study was undertaken to disentangle the maternal genetic, fetal genetic, and environmental effects for the risk of having small-for-gestational-age (SGA) offspring. STUDY DESIGN: By cross-linking the population-based Swedish Multi-Generation and Medical Birth Registers, we extracted 2,193,142 births between 1973 and 2001 with both parents identified. Odds ratios (OR) were calculated to estimate the relative risks, and generalized linear mixed models were used to estimate the contribution of genetic and environmental effects. RESULTS: Women whose full sisters had an offspring born SGA had a significantly increased risk of having a SGA offspring themselves (OR = 1.8, 95% CI 1.7-1.9), whereas the corresponding risk for brothers was lower (OR = 1.3, 95% CI 1.2-1.4). Thirty-seven percent of the liability was explained by fetal (including both maternal and paternal) genetic effects and 9% by maternal genetic effects. CONCLUSION: Genetic factors account for almost half of the liability to have SGA births. These effects are primarily caused by fetal genes.

Female↗

Near vision impairment predicts cognitive decline: data from the Hispanic Established Populations for Epidemiologic Studies of the Elderly.

OBJECTIVES: To estimate the association between sensory impairment and cognitive decline in older Mexican Americans. DESIGN: A prospective cohort study. SETTING: The Hispanic Established Populations for Epidemiologic Studies of the Elderly from five southwestern states. PARTICIPANTS: The sample consisted of 2,140 noninstitutionalized Mexican Americans aged 65 and older followed from 1993/1994 until 2000/2001. MEASUREMENTS: The outcome, cognitive function decline, was assessed using the Mini-Mental State Examination blind version (MMSE-blind) at baseline and at 2, 5, and 7 years of follow-up. Other variables were near vision, distance vision, hearing, demographics (age, sex, marital status, living arrangements, and education), depressive symptoms, hypertension, diabetes mellitus, stroke, heart attack, and functional status. A general linear mixed model was used to estimate cognitive decline at follow-up. RESULTS: In a fully adjusted model, MMSE-blind scores of subjects with near vision impairment decreased 0.62 points (standard error (SE)=0.29, P=.03) over 2 years and decreased (slope of decline) 0.13 points (SE=0.07, P=.045) more per year than scores of subjects with adequate near vision. Other independent predictors of cognitive decline were baseline MMSE-blind score, age, education, marital status, depressive symptoms, and number of activity of daily living limitations. CONCLUSION: Near vision impairment, but not distance vision or hearing impairments, was associated with cognitive decline in older Mexican Americans.

Aged↗

Is the P300 wave an endophenotype for schizophrenia? A meta-analysis and a family study.

INTRODUCTION: We assessed the usefulness of the P300 wave as endophenotype for schizophrenia by means of a meta-analysis of the literature as well as our own family study. METHOD: Meta-analysis: We conducted a systematic search for articles published between 1983 and 2003 that reported P300 measures in non-psychotic relatives of schizophrenic patients and in healthy controls. Meta-regression analyses were performed using a random effects procedure. The pooled standardized effect size (PSES) was calculated as the difference between the means of the two groups divided by the common standard deviation. Local study: We examined the P300 wave with a standard two-tone oddball paradigm in 30 patients with schizophrenia, 40 non-psychotic relatives, and 40 controls using linear mixed models. RESULTS: Meta-analysis: We pooled 472 relatives and 513 controls. The P300 amplitude was significantly reduced in relatives (PSES = 0.61; 95% CI: 0.30 to 0.91; P < 0.001). The P300 latency was significantly delayed in relatives (PSES of -0.50; 95% CI: -0.88 to -0.13; P = 0.009]. Local study: The patients showed a trend for amplitude reductions (P = 0.06) and significant latency delays (P < 0.01). The relatives displayed normal amplitude but had significant latency delays (P = 0.01). The P300 amplitude and especially the P300 latency are promising alternative phenotypes for genetic research into schizophrenia.

Adolescent↗

Factors associated with suckling piglet average daily gain.

Low piglet weight at weaning implies a loss of income for the farmer and might influence the welfare of the affected animals negatively. The objective of our cohort study was to identify risk factors in the farrowing section associated with average daily weight gain (ADG) of piglets from birth to weaning. The study was done in 3 Danish farrow-to-finish herds and included 581 sows, 277 pens, 814 farrowings, and 8241 piglets. The data were analysed with a linear mixed model where the response was ADG, and sow and litter were random effects. Piglet treatments for arthritis (-38 g per day), diarrhoea (-8 g per day) and other infections (-21 g per day) were the major infectious contributors to lower ADG. Forelimb-skin abrasions on a piglet (-5 g per day), weak pasterns of sows on concrete slats (-34 g per day), suckling a sow with poor milking 3 weeks after farrowing (-14 g per day), low birth weight (-8.4 g per day per 100 g), male compared to female (-4 g per day) also were associated with lower ADG in the suckling period.

Animal Feed↗

The effect of crash experience on changes in risk taking among urban and rural young people.

A 20-month prospective study was conducted to investigate the effect of motorcycle crash experience on changes in risk taking among 2514 urban and 2304 rural students in Taiwan. Risk taking was assessed using a 14-item self-administered questionnaire at the beginning and end of the study. A risk-taking score for each student at the initial and the last follow-up assessments was generated from adding up points across all 14 items. For exposure variables, the study documented past motorcycle crash history at the initial assessment and collected detailed information about any motorcycle crash involvement that occurred during the study period. A general linear mixed model was applied to assess the effects of prior and recent crash involvements on the path of risk-taking behavior. The results show that at the initial assessment, students with crash experience had higher risk-taking levels than those without crash experience. However, crash experience, irregardless of whether it was measured in terms of crash history prior to the study, crash frequency, time elapsed since the last crash, or crash severity, did not significantly change the risk-taking path among students, even though its effect differed between urban and rural areas.

Accidents, Traffic↗

Comparison of software tools to improve the detection of carcinogen induced changes in the rat liver proteome by analyzing SELDI-TOF-MS spectra.

A common animal model of chemical hepatocarcinogenesis was used to demonstrate the potential identification of carcinogenicity related protein signatures/biomarkers. Therefore, an animal study in which rats were treated with the known liver carcinogen N-nitrosomorpholine (NNM) or the corresponding vehicle was evaluated. Histopathological investigation as well as SELDI-TOF-MS analysis was performed. SELDI-TOF-MS is an affinity-based mass spectrometry method in which subsets of proteins from biological samples are selectively adsorbed to a chemically modified surface. The proteins are subsequently analyzed with respect to their mass-charge ratios (m/z) by a time of flight (TOF) mass spectrometry (MS) approach. As data preprocessing of SELDI-TOF-MS spectra is essential, baseline correction, normalization, peak detection, and alignment of raw spectra were performed using either the Ciphergen ProteinChip Software 3.1 or functions implemented in the library PROcess of the BioConductor Project. Baseline correction and normalization algorithms of both tools lead to comparable results, whereas results after peak detection and alignment steps differed. Variability between technical and biological replicates was investigated. A linear mixed model with factors experimental group and time point was applied for each protein peak, taking into account the different correlation structure of technical and biological replicates. Alternatively, only median intensity values of technical replicates were used. Results of both models were similar and correlated well with those of the histopathological evaluation of the study. In conclusion, statistical analyses lead to comparable results, whereas parameter settings for preprocessing proved to be crucial.

Animals↗

Changes in 3D joint dynamics during the first 5 months after the onset of independent walking: a longitudinal follow-up study.

A longitudinal follow-up study of 10 normally developing children was performed in order to identify changes in mechanical control of gait during the first months after initiation of independent walking. Changes in spatio-temporal parameters and kinematics were recorded (336 trials spread over 83 recording sessions) and linked to kinetic features of gait. At the onset of independent walking, all children in our study group showed the same walking strategy: a dominance of the extending moments around the lower extremity joints was observed and could be linked to the flexed position of the hip and knee during stance. In a subset of our study population, the dominance of the extending moments disappeared with increasing walking experience, though reversal to immature patterns was frequently observed. A linear mixed model showed that with increasing walking experience, there was an increase in dimensionless walking speed, dimensionless cadence and dimensionless stride length (without correction for the increase in speed). Maximal hip extension in stance, knee flexion and ankle plantar flexion at foot contact also increased (even when the increase in speed is taken into account). Dimensionless step width, duty factor, double support time, maximal hip flexion in swing and hip abduction significantly decreased (with correction for speed). Important changes were also observed in ground reaction force patterns, evolving towards a double "hump". No significant changes could be observed in other kinetic parameters, probably due to the high degree of variability.

Ankle Joint↗

Associations between olfactory identification and verbal memory in patients with schizophrenia, first-degree relatives, and non-psychiatric controls.

OBJECTIVE: Olfactory identification deficits and verbal memory impairments may represent trait markers for schizophrenia. The aims of this study were to: (1) assess olfactory identification in patients, first-degree relatives, and non-psychiatric controls, (2) determine differences in verbal memory functioning in these three groups, and (3) study correlations between olfactory identification and three specific verbal memory domains. METHOD: A total of 106 participants-41 patients with schizophrenia or related disorders, 27 relatives, and 38 controls-were assessed with the University of Pennsylvania Smell Identification Test (UPSIT) and the Wechsler Memory Scale-Third Edition. Linear mixed models, accounting for clustering within families and relevant covariates, were used to compare scores across groups and to examine associations between olfactory identification ability and the three verbal memory domains. RESULTS: A group effect was apparent for all four measures, and relatives scored midway between patients and controls on all three memory domains. UPSIT scores were significantly correlated with all three forms of verbal memory. Age, verbal working memory, and auditory recognition delayed memory were independently predictive of UPSIT scores. CONCLUSIONS: Impairments in olfactory identification and verbal memory appear to represent two correlated risk markers for schizophrenia, and frontal-temporal deficits likely account for both impairments.

Adult↗

Reduced intellectual development in children with prenatal lead exposure.

OBJECTIVE: Low-level postnatal lead exposure is associated with poor intellectual development in children, although effects of prenatal exposure are less well studied. We hypothesized that prenatal lead exposure would have a more powerful and lasting impact on child development than postnatal exposure. DESIGN: We used generalized linear mixed models with random intercept and slope to analyze the pattern of lead effect of the cohort from pregnancy through 10 years of age on child IQ from 6 to 10 years. We statistically evaluated dose-response nonlinearity. PARTICIPANTS: A cohort of 175 children, 150 of whom had complete data for all included covariates, attended the National Institute of Perinatology in Mexico City from 1987 through 2002. EVALUATIONS/MEASUREMENTS: We used the Wechsler Intelligence Scale for Children-Revised, Spanish version, to measure IQ. Blood lead (BPb) was measured by a reference laboratory of the Centers for Disease Control and Prevention (CDC) quality assurance program for BPb. RESULTS: Geometric mean BPb during pregnancy was 8.0 microg/dL (range, 1-33 microg/dL), from 1 through 5 years was 9.8 microg/dL (2.8-36.4 microg/dL), and from 6 through 10 years was 6.2 microg/dL (2.2-18.6 microg/dL). IQ at 6-10 years decreased significantly only with increasing natural-log third-trimester BPb (beta=-3.90; 95% confidence interval, -6.45 to -1.36), controlling for other BPb and covariates. The dose-response BPb-IQ function was log-linear, not linear-linear. CONCLUSIONS: Lead exposure around 28 weeks gestation is a critical period for later child intellectual development, with lasting and possibly permanent effects. There was no evidence of a threshold; the strongest lead effects on IQ occurred within the first few micrograms of BPb. RELEVANCE TO CLINICAL PRACTICE: Current CDC action limits for children applied to pregnant women permit most lead-associated child IQ decreases measured over the studied BPb range.

Child↗

Longitudinal relationships of depressive symptoms to pain intensity and functional disability among children with disease-related pain.

OBJECTIVE: To examine the longitudinal relationship between depressive symptoms at study entry (T1) on pain intensity (PI) and functional disability over a 1-year period among children with either sickle cell disease (SCD) or juvenile idiopathic arthritis (JIA). METHODS: 119 children, ages 8-17 years, completed measures of depression at T1 as well as pain and functional disability at T1, 6-month (T2), and 12-month (T3) follow-ups. Caregivers also rated their child's pain and disability at each time point. General linear mixed modeling was employed to examine longitudinal relationships between study variables. RESULTS: For children with JIA, T1 pain significantly moderated the effects of T1-depressive symptoms on T2 and T3 pain where T1-depressive symptoms predicted future child-reported pain only when T1 pain was relatively mild. Similarly, T1-depressive symptoms predicted future child-reported disability only when initial reports of disability were relatively low. Only family income significantly predicted T2 and T3 pain in children with SCD. CONCLUSIONS: Study findings suggest that T1-depressive symptoms play a role in the longitudinal course of pain symptoms in children with JIA but not in children with SCD.

Activities of Daily Living↗

Paratuberculosis in dairy cattle: variation of the antibody response in offspring attributable to the dam.

The objective of this study was to examine transmission of paratuberculosis in dairy cattle attributable to the dam. Milk samples were collected from 8131 cows in 110 Danish dairy herds. The level of antibodies to Mycobacterium avium subspecies paratuberculosis was determined by use of an ELISA. Information on dam and sire was obtained from the Danish Cattle database. The following two data sets were analyzed: Data set A contained all cows < or = 400 days in milk (n = 7410); data set B contained 1056 dam-daughter pairs present simultaneously in herds at the day of sampling. Cows > 400 days in milk were excluded. Linear mixed models were used to obtain variance components for the effect of sire in data set A and the effect of sire and dam-daughter pairs in data set B. Models for both data sets A and B included information previously shown to confound antibody level and information of the relative prevalence of paratuberculosis in the herd. In data set A, the effect explained by sire was 1.9%, whereas it was 6.3% in data set B. The effect from dam-daughter pairs was 7.7%. Those effects were all significant. It was concluded that the parental contribution was significant, and both heritability of susceptibility and vertical transmission should be considered in any control programs on paratuberculosis in dairy cattle.

Animals↗

A generalized estimating equations approach to quantitative trait locus detection of non-normal traits.

To date, most statistical developments in QTL detection methodology have been directed at continuous traits with an underlying normal distribution. This paper presents a method for QTL analysis of non-normal traits using a generalized linear mixed model approach. Development of this method has been motivated by a backcross experiment involving two inbred lines of mice that was conducted in order to locate a QTL for litter size. A Poisson regression form is used to model litter size, with allowances made for under- as well as over-dispersion, as suggested by the experimental data. In addition to fixed parity effects, random animal effects have also been included in the model. However, the method is not fully parametric as the model is specified only in terms of means, variances and covariances, and not as a full probability model. Consequently, a generalized estimating equations (GEE) approach is used to fit the model. For statistical inferences, permutation tests and bootstrap procedures are used. This method is illustrated with simulated as well as experimental mouse data. Overall, the method is found to be quite reliable, and with modification, can be used for QTL detection for a range of other non-normally distributed traits.

Animals↗

Salad and satiety: energy density and portion size of a first-course salad affect energy intake at lunch.

OBJECTIVE: We tested the effect on meal intake of varying the energy density and portion size of a compulsory first-course salad. DESIGN: The study used a randomized crossover design. SUBJECTS/SETTING: Forty-two women from the State College, PA, university community ate lunch in the laboratory once per week for 7 weeks. INTERVENTION: Lunch comprised one of six first-course salads, or no salad in the control condition, followed by a main course of pasta. Subjects were required to consume the entire salad, but ate as much pasta as they wanted. The salads varied in energy density (0.33, 0.67, or 1.33 kcal/g) and portion size (150 or 300 g). The energy density of the salad was reduced by changing the amount and type of dressing and cheese. MAIN OUTCOME MEASURES: Energy intake and ratings of hunger, satiety, and food characteristics were measured. STATISTICAL ANALYSES PERFORMED: Outcomes were analyzed using a linear mixed model with repeated measures. RESULTS: Compared with having no first course, consuming the low-energy-dense salads reduced meal energy intake (by 7% for the small portion and 12% for the large), and consuming the high-energy-dense salads increased intake (by 8% for the small portion and 17% for the large). When two salads with the same number of calories were compared, meal intake was decreased when the large portion of the lower-energy-dense salad was consumed. CONCLUSIONS: Eating a low-energy-dense first course enhances satiety and reduces meal energy intake. Consuming a large portion of a low-energy-dense food at the start of a meal may be an effective strategy for weight management.

Adult↗

Restricted maximum likelihood estimation of genetic principal components and smoothed covariance matrices.

Principal component analysis is a widely used 'dimension reduction' technique, albeit generally at a phenotypic level. It is shown that we can estimate genetic principal components directly through a simple reparameterisation of the usual linear, mixed model. This is applicable to any analysis fitting multiple, correlated genetic effects, whether effects for individual traits or sets of random regression coefficients to model trajectories. Depending on the magnitude of genetic correlation, a subset of the principal component generally suffices to capture the bulk of genetic variation. Corresponding estimates of genetic covariance matrices are more parsimonious, have reduced rank and are smoothed, with the number of parameters required to model the dispersion structure reduced from k(k+1)/2 to m(2k-m+1)/2 for k effects and m principal components. Estimation of these parameters, the largest eigenvalues and pertaining eigenvectors of the genetic covariance matrix, via restricted maximum likelihood using derivatives of the likelihood, is described. It is shown that reduced rank estimation can reduce computational requirements of multivariate analyses substantially. An application to the analysis of eight traits recorded via live ultrasound scanning of beef cattle is given.

Analysis of Variance↗

MRI measures and progression of cognitive decline in nondemented elderly attending a memory clinic.

OBJECTIVE: To investigate whether MRI-based volumes of whole brain, medial temporal lobe and white matter hyperintensities (WMH) predict progression of cognitive decline in a sample of nondemented elderly. METHODS: Thirty-seven nondemented elderly attending a memory clinic and 28 elderly controls participated in this follow-up study. The average follow-up period was 1.8 years. Cognitive function was measured at baseline and follow-up with the Cambridge Cognitive Examination (CAMCOG). Baseline Magnetic Resonance Imaging (MRI) provided quantitative measures of whole brain, medial temporal lobe and WMH. Linear mixed models controlled for age and sex were used to assess the independent associations between MRI measures, baseline cognition, and annual decline in cognition. RESULTS: Medial temporal lobe volume was independently associated with baseline CAMCOG score (p < 0.01), whereas whole brain volume (p < 0.01) and WMH (p < 0.05) were associated with annual decline in CAMCOG score. CONCLUSIONS: These data suggest that regional damage to the medial temporal lobes underlies initial mild cognitive impairment, whereas more global brain changes, such as whole brain atrophy and WMH, contribute to further progression of cognitive decline.

Aged↗

In vitro peripheral blood mononuclear cell proliferation in a crossbred cattle population.

Immune function measured by Staphylococcus aureus- and phytohemagglutinin- (PHA-) induced cell proliferation was assessed in a population of 445 genetically defined, F2 and backcross Charolais-Holstein crossbred cattle when the animals were approximately 5 mo of age. Variation in Staph. aureus-induced, PHA-induced, and control proliferation [peripheral blood mononuclear cell (PBMC) and media only] was observed at d 2, 3, 4, 5, 9, and 10 of in vitro culture. The levels of Staph. aureus-induced, PHA-induced, and control proliferation were strongly positively correlated between days of culture within-assay (e.g., between d 2 and d 3 or between d 4 and d 5). Responses were also positively correlated when the same individuals were resampled and the assay repeated within 3 mo. Analyses fitting linear mixed models using REML showed that Staph. aureus-induced and PHA-induced proliferation was significantly associated with control proliferation and the year of birth. The age of the animal at sampling influenced only Staph. aureus-induced proliferation, with Staph. aureus-induced proliferation increasing with the age of the animal. Control proliferation was influenced by a sex x cross interaction, although in this study, sex was confounded by management, as female cattle were housed and reared differently from male cattle. All 3 measures of immune function were influenced by sire, demonstrating that these traits are partially under genetic control, and indicating that it may ultimately be possible to identify quantitative trait loci for these measures of immunity.

Animals↗

Do angiographic results from symptom-directed studies reflect true graft patency?

BACKGROUND: Coronary artery graft patency results have been obtained from repeat angiograms in patients who presented with evidence of ischemia. The purpose of this study is to compare protocol-directed angiographic results from a randomized clinical trial with symptom-directed angiography in nontrial patients. METHODS: Repeat angiography after primary isolated coronary artery bypass grafting was performed in 337 of 2,259 patients between July 1996 and September 2004. Patients were divided into two groups: 596 graft angiograms in 192 trial patients were compared with 389 graft angiograms in 142 nontrial patients. The mean interval from surgery was 1,306 +/- 800 days versus 1,119 +/- 777 days, respectively. Grafting techniques were similar in both groups except that the right internal thoracic artery was used almost exclusively as a free graft in the trial patients. Angiographic outcomes were defined as patent (stenosis <80%) or failure (stenosis > or =80%, occlusion, or the string sign). Comparisons of trial versus nontrial grafts were made using a generalized linear mixed model. Five-year estimates of graft patency were made using survival analyses accounting for interval censoring. RESULTS: The odds ratio for graft failure for nontrial compared with trial patient grafts was 2.6 (95% confidence interval, 1.6 to 4.3; p < 0.001). Cumulative patency estimates for all grafts at 5 years were trial 91% versus nontrial 83%, p = 0.004. Five-year estimates for individual conduits were left internal thoracic artery, 99% versus 92%, p = 0.002; right internal thoracic artery, 86% versus 87%, p = 0.8; radial artery, 87% versus 86%, p = 0.6; and saphenous vein, 86% versus 56%, p = 0.003. CONCLUSIONS: Graft patency rates were superior in the trial compared with nontrial patients. Symptom-directed graft failure rates were approximately double those of trial patients.

Clinical Protocols↗