Latent variable mixture modeling in psychiatric research--a review and application.

Latent variable mixture modeling represents a flexible approach to investigating population heterogeneity by sorting cases into latent but non-arbitrary subgroups that are more homogeneous. The purpose of this selective review is to provide a non-technical introduction to mixture modeling in a cross-sectional context. Latent class analysis is used to classify individuals into homogeneous subgroups (latent classes). Factor mixture modeling represents a newer approach that represents a fusion of latent class analysis and factor analysis. Factor mixture models are adaptable to representing categorical and dimensional states of affairs. This article provides an overview of latent variable mixture models and illustrates the application of these methods by applying them to the study of the latent structure of psychotic experiences. The flexibility of latent variable mixture models makes them adaptable to the study of heterogeneity in complex psychiatric and psychological phenomena. They also allow researchers to address research questions that directly compare the viability of dimensional, categorical and hybrid conceptions of constructs.

How do changes in body mass index in infancy and childhood associate with cardiometabolic profile in adulthood? Findings from the Northern Finland Birth Cohort 1966 Study.

BACKGROUND/OBJECTIVE: Postnatal growth patterns leading to obesity may have adverse influences on future cardiometabolic health. This study evaluated age and body mass index (BMI) at infant BMI peak (BMIP) and childhood BMI rebound (BMIR) in relation to adult cardiometabolic outcomes in the Northern Finland Birth Cohort 1966. METHODS: BMI at various ages was calculated from frequent height and weight measurements obtained from child health and welfare clinical records. Age and BMI at BMIP and BMIR were derived from random effect models fitted at >0-1.5 years (N=3 265) and >1.5-13 years (N=4 121). Cardiometabolic outcomes were obtained from a clinical examination at age 31 years. Multiple regression models were used to analyse associations between the derived growth parameters and cardiometabolic outcomes. RESULTS: Age and BMI at BMIP were positively associated with adult BMI and waist circumference (WC), independently of birth weight and infant height growth (P<0.05). Later BMIR was associated with a better cardiometabolic profile: adult BMI and insulin were 14% lower, WC and triglycerides were 10% lower and the odds of metabolic syndrome (MetS) were 74% lower per 2 s.d. (1.86 years) higher age at BMIR (P<0.0001). BMI at rebound had generally weaker associations with cardiometabolic outcomes, which attenuated after adjustment for age at BMIR. CONCLUSIONS: Age and BMI at infant BMIP were associated with adult adiposity but not with other cardiometabolic outcomes. Earlier timing of BMIR was a risk factor of an adverse cardiometabolic profile, independently of early growth or BMI at rebound. Identifying growth patterns harmful to cardiovascular health will give opportunities for early interventions.

Automatic detection and analysis of cell motility in phase-contrast time-lapse images using a combination of maximally stable extremal regions and Kalman filter approaches.

Phase-contrast illumination is simple and most commonly used microscopic method to observe nonstained living cells. Automatic cell segmentation and motion analysis provide tools to analyze single cell motility in large cell populations. However, the challenge is to find a sophisticated method that is sufficiently accurate to generate reliable results, robust to function under the wide range of illumination conditions encountered in phase-contrast microscopy, and also computationally light for efficient analysis of large number of cells and image frames. To develop better automatic tools for analysis of low magnification phase-contrast images in time-lapse cell migration movies, we investigated the performance of cell segmentation method that is based on the intrinsic properties of maximally stable extremal regions (MSER). MSER was found to be reliable and effective in a wide range of experimental conditions. When compared to the commonly used segmentation approaches, MSER required negligible preoptimization steps thus dramatically reducing the computation time. To analyze cell migration characteristics in time-lapse movies, the MSER-based automatic cell detection was accompanied by a Kalman filter multiobject tracker that efficiently tracked individual cells even in confluent cell populations. This allowed quantitative cell motion analysis resulting in accurate measurements of the migration magnitude and direction of individual cells, as well as characteristics of collective migration of cell groups. Our results demonstrate that MSER accompanied by temporal data association is a powerful tool for accurate and reliable analysis of the dynamic behaviour of cells in phase-contrast image sequences. These techniques tolerate varying and nonoptimal imaging conditions and due to their relatively light computational requirements they should help to resolve problems in computationally demanding and often time-consuming large-scale dynamical analysis of cultured cells.

Tumor tissue inhibitor of metalloproteinases-1 (TIMP-1) in hormone-independent breast cancer might originate in stromal cells, and improves stratification of prognosis together with nodal status.

Tissue inhibitor of metalloproteinases-1 (TIMP-1) is shown to be a potential marker for poor prognosis in breast cancer, but the biology of TIMP-1 is only partially understood. In this study, TIMP-1 production was studied in a co-culture model of hormone-independent breast cancer cell lines and mesenchymal stem cells mimicking the stromal components of the tumor. In addition, the prognostic value of TIMP-1 was histologically evaluated in a clinical material of 168 patients with hormone-independent breast tumors. The hormone-independent breast cancer (BC) cell lines MDA-MB-231, M4A4 and NM2C5 did not produce TIMP-1 protein in measureable quantities. Six tested primary mesenchymal stem cell lines all produced TIMP-1. Co-culturing of mesenchymal stem cells and breast cancer cells resulted in positive immunocytochemical diffuse staining for TIMP-1 for both cell types. Culturing breast cancer cells with MSC-conditioned media resulted in a positive cytoplasmic immunoreactivity for TIMP-1, and TIMP-1 protein concentration in cell lysates increased 2.7-fold (range 1.1-4.7). The TIMP-1 mRNA levels remained unaffected in BC cells. This might suggest that breast cancer cells can take up TIMP-1 produced by stromal cells and are thus displaying cellular immunoreactivity. In addition, TIMP-1 was shown to improve stratification of prognosis in clinical material.

Maternal weight gain during the first half of pregnancy and offspring obesity at 16 years: a prospective cohort study.

OBJECTIVE: To assess the association between maternal gestational weight gain (GWG) during the first 20 weeks of gestation and overweight/obesity and abdominal obesity of offspring at the age of 16 years. DESIGN: A prospective cohort study. SETTING: The two northernmost provinces of Finland. POPULATION: Mothers and their adolescent offspring born from singleton pregnancies (3265 boys; 3372 girls) in the Northern Finland Birth Cohort 1986. METHODS: Maternal weight at 20 weeks of gestation was measured in municipal maternity clinics. Maternal GWG was based on the difference between the measured weight and self-reported pre-pregnancy weight, and was classified into quartiles. Offspring weight, height and waist circumference were measured by study nurses during a clinical examination. Logistic regression analyses [with and without adjustment for maternal pre-pregnancy body mass index (BMI), glucose metabolism, education level, haemoglobin, smoking status, parity, and gender of offspring] were performed. MAIN OUTCOME MEASURE: Offspring overweight/obesity, based on BMI and abdominal obesity at 16 years. RESULTS: The highest quartile of maternal weight gain (>7.0 kg during the first 20 weeks of gestation) was independently associated with BMI-based overweight/obesity and abdominal obesity in the 16-year-old offspring (OR 1.46, 95% CI 1.16-1.83, and OR 1.37, 95% CI 1.10-1.72, respectively). Among all covariates, maternal pregravid obesity showed the highest odds for both overweight/obesity and abdominal obesity (OR 4.57, 95% CI 3.18-6.57, and OR 4.43, 95% CI 3.10-6.34, respectively). CONCLUSIONS: Maternal overnutrition during the first half of gestation predicts offspring overweight/obesity and abdominal obesity in adolescence, yet a high pregravid BMI appears to be a more important determinant of both outcomes.

Physical activity and fitness in adolescents at risk for psychosis within the Northern Finland 1986 Birth Cohort.

BACKGROUND: Literature regarding physical activity and fitness among subjects at risk for psychosis especially in adolescents is scarce. This study evaluated the level of physical activity and cardio-respiratory fitness among subjects at risk for psychosis in a relatively large birth cohort sample. METHODS: The study population consisted of the Northern Finland Birth Cohort 1986 including 6987 adolescents who self-reported their physical activity by responding to a postal inquiry in 2001-2002 at the age of 15-16 years. Their cardiorespiratory fitness was measured in a clinical examination by a submaximal cycle ergometer test. Vulnerability to psychosis was defined in three ways: having a parent with a history of psychosis, having prodromal symptoms of psychosis measured by PROD-screen questionnaire at the age of 15-16 years or having actually developed psychosis after the field study (in 2002-2005). The Finnish Hospital Discharge Register was used to find out about parental and the individual's own psychosis. RESULTS: Those individuals who developed psychosis were more likely to be physically inactive (OR 3.3; CI 95% (1.4-7.9) adjusted for gender, parental socio-economic status, family structure and parents' physical activity) and to have poor cardiorespiratory fitness (OR 2.2; 95% CI 0.6-7.8 adjusted for parental socio-economic status, family structure and parents' physical activity) compared to those who did not develop psychosis. CONCLUSIONS: Adolescents who would actually develop psychosis had a relatively low level of physical activity compared to their age mates. General recommendations for physical activity would be important for subjects at risk for developing psychosis in order to avoid detrimental effect of physical inactivity on overall health.

Is prenatal alcohol exposure related to inattention and hyperactivity symptoms in children? Disentangling the effects of social adversity.

BACKGROUND: Studies concerning whether exposure to low levels of maternal alcohol consumption during fetal development is related to child inattention and hyperactivity symptoms have shown conflicting results. We examine the contribution of covariates related to social adversity to resolve some inconsistencies in the extant research by conducting parallel analyses of three cohorts with varying alcohol consumption and attitudes towards alcohol use. METHODS: We compare three population-based pregnancy-offspring cohorts within the Nordic Network on ADHD from Denmark and Finland. Prenatal data were gathered via self-report during pregnancy and birth outcomes were abstracted from medical charts. A total of 21,678 reports concerning inattention and hyperactivity symptoms in children were available from the Strengths and Difficulties Questionnaire or the Rutter Scale completed by parents and/or teachers. RESULTS: Drinking patterns differed cross-nationally. Women who had at least some social adversity (young, low education, or being single) were more likely to drink than those better off in the Finnish cohort, but the opposite was true for the Danish cohorts. Prenatal alcohol exposure was not related to risk for a high inattention-hyperactivity symptom score in children across cohorts after adjustment for covariates. In contrast, maternal smoking and social adversity during pregnancy were independently and consistently associated with an increase in risk of child symptoms. CONCLUSIONS: Low doses of alcohol consumption during pregnancy were not related to child inattention/hyperactivity symptoms once social adversity and smoking were taken into account.

Effects of low-intensity training on dihydropyridine and ryanodine receptor content in skeletal muscle of mouse

To evaluate low-intensity exercise training induced changes in the expression of dihydropyridine (DHP) and ryanodine (Ry) receptors both mRNA and protein levels were determined by quantitative RT-PCR and immunoblot analysis from gastrocnemius (GAS) and rectus femoris (RF) muscles of mice subjected to a 15-week aerobic exercise program. The level of muscular work was assayed by changes in myosin heavy chain (MHC) content, myoglobin (Mb) expression and muscle size. The mRNA expression and optical density of DHP receptor increased significantly in GAS by 66.8 and 39.5%, respectively. The expression of Ry receptor, on the other hand, was not up-regulated. In RF, there was a significant increase of 38.4% in the mRNA expression of DHP receptor, although the protein level remained the same. No changes in Ry receptor expression was observed. The training resulted in a 1.58% increase in the amount of MHC IIa and a 2.34% decrease in that of IIb and IId in GAS. A significant 8.3% increase in the Mb content was observed. In RF, no significant changes in MHC or in Mb content were noted. Our results show that an evident increase in the mRNA and protein expression of DHP receptor was induced in GAS even by a relatively low-intensity exercise. Surprisingly, contrast to DHP receptor expression, no changes in Ry receptor mRNA, or protein levels were found, indicating more abundant demand for DHP receptor after increased muscle activity (AU)

Para evaluar los cambios inducidos en la expresión de los receptores de dihidropiridina (DHPR) y rianodina (RyR) por el entrenamiento con ejercicio de baja intensidad, se determinan los niveles de mRNA y de proteína mediante el análisis de RT-PCR cuantitativa e inmunoblot de los músculos gastrocnemius (GAS) y rectus femoris (RF) de ratón sometido a un programa de ejercicio aeróbico durante 15 semanas. El nivel de trabajo muscular fue determinado por los cambios en contenido de cadena pesada de miosina (MHC), expresión de mioglobina (Mb) y tamaño del músculo. La cantidad de mRNA y de proteína de DHPR aumentó significativamente en un 66,8 y 39,5% respectivamente. La expresión de RyR, por otro lado, no se vio incrementada. En RF hubo un aumento significativo del 22,7% en la expresión del mRNA de DHPR, aunque los niveles de proteína permanecieron inalterados. Tampoco se observaron cambios en la expresión de RyR en RF. El entrenamiento dio lugar a un aumento del 1,58% en la cantidad de MHC IIa y disminución del 2,34% en MHC IIb y IId en GAS, con incremento significativo del 8,3% en el contenido de Mb. En RF no se detectaron cambios significativos en el contenido en MHC ni en Mb. Nuestros resultados muestran que se induce un evidente aumento en el nivel de RNAm y de proteína DHPR en GAS mediante un ejercicio de relativamente baja intensidad. Sorprendentemente, en contraste con la expresión de DHPR, no se encontraron cambios en los niveles de mRNA ni de proteína de RyR, indicando mayor demanda de DHPR al incrementar la actividad muscular (AU)

Effects of low-intensity training on dihydropyridine and ryanodine receptor content in skeletal muscle of mouse.

To evaluate low-intensity exercise training induced changes in the expression of dihydropyridine (DHP) and ryanodine (Ry) receptors both mRNA and protein levels were determined by quantitative RT-PCR and immunoblot analysis from gastrocnemius (GAS) and rectus femoris (RF) muscles of mice subjected to a 15-week aerobic exercise program. The level of muscular work was assayed by changes in myosin heavy chain (MHC) content, myoglobin (Mb) expression and muscle size. The mRNA expression and optical density of DHP receptor increased significantly in GAS by 66.8 and 39.5%, respectively. The expression of Ry receptor, on the other hand, was not up-regulated. In RF, there was a significant increase of 38.4% in the mRNA expression of DHP receptor, although the protein level remained the same. No changes in Ry receptor expression was observed. The training resulted in a 1.58% increase in the amount of MHC IIa and a 2.34% decrease in that of IIb and IId in GAS. A significant 8.3% increase in the Mb content was observed. In RF, no significant changes in MHC or in Mb content were noted. Our results show that an evident increase in the mRNA and protein expression of DHP receptor was induced in GAS even by a relatively low-intensity exercise. Surprisingly, contrast to DHP receptor expression, no changes in Ry receptor mRNA, or protein levels were found, indicating more abundant demand for DHP receptor after increased muscle activity.