Evaluation of an early detection tool for social-emotional and behavioral problems in toddlers: The Brief Infant Toddler Social and Emotional Assessment - A cluster randomized trial

Background: The prevalence of social-emotional and behavioral problems is estimated to be 8 to 9% among preschool children. Effective early detection tools are needed to promote the provision of adequate care at an early stage. The Brief Infant-Toddler Social and Emotional Assessment (BITSEA) was developed for this purpose. This study evaluates the effectiveness of the BITSEA to enhance social-emotional and behavioral health of preschool children. Methods and Design: A cluster randomized controlled trial is set up in youth health care centers in the larger Rotterdam area in the Netherlands, to evaluate the BITSEA. The 31 youth health care centers are randomly allocated to either the control group or the intervention group. The intervention group uses the scores on the BITSEA and cut-off points to evaluate a child's social-emotional and behavioral health and to decide whether or not the child should be referred. The control group provides care as usual, which involves administering a questionnaire that structures the conversation between child health professionals and parents. At a one year follow-up measurement the social-emotional and behavioral health of all children included in the study population will be evaluated. Discussion: It is hypothesized that better results will be found, in terms of social-emotional and behavioral health in the intervention group, compared to the control group, due to more adequate early detection, referral and more appropriate and timely care

Evaluation of computer-tailored health education ('E-health4Uth') combined with personal counselling ('E-health4Uth + counselling') on adolescents' behaviours and mental health status: Design of a three-armed cluster randomised controlled trial

Background: About 15% of adolescents in the Netherlands have mental health problems and many also have health risk behaviours such as excessive alcohol consumption, cigarette smoking, use of drugs, and having unsafe sex. Mental health problems and health risk behaviours may have adverse effects on the short and longer term. Therefore, in the Netherlands there is a considerable support for an additional public health examination at age 15-16 years. The study evaluates the effect of two options for such an additional examination. Adolescents in the 'E-health4Uth' group receive internet-based tailored health messages on their health behaviour and well-being. Adolescents in the 'E-health4Uth + counselling' group receive the computer-tailored messages combined with personal counselling for adolescents at risk of mental health problems. Methods and design. A three-arm cluster randomised controlled trial will be conducted in the Netherlands among fourth-grade secondary school students. School classes are the unit of randomisation. Both intervention groups complete the computer-tailored program during one class session; the program focuses on nine topics related on health behaviour and well-being. For each topic a score is computed that can be compared with the Dutch health norms for adolescents. Based on the score, a message is presented that reflects the person's current behaviour or well-being, the Dutch health norm, and offers advise to change unhealthy behaviour or to talk to a person they trust. Adolescents in the 'E-health4Uth + counselling' group are also invited for an appointment to see the nurse when they are at risk of mental health problems. The control group receives 'care as usual'. The primary outcome measures are health behaviour (alcohol, drugs, smoking, safe sex) and mental health status. The secondary outcome measure is health-related quality of life. Data will be collected with a questionnaire at baseline and at 4-months follow-up. A process evaluation will also be conducted. Discussion. It is hypothesized that at follow-up adolescents in the 'E-health4Uth' group and adolescents in the 'E-health4Uth + counselling' group will show fewer mental health problems and less risky behaviour compared to the control group. Trial registration. Current Controlled Trials NTR3596

Differentiation of Glioma and Radiation Injury in Rats Using In Vitro Produce Magnetically Labeled Cytotoxic T-Cells and MRI

A limitation with current imaging strategies of recurrent glioma undergoing radiotherapy is that tumor and radiation injury cannot be differentiated with post contrast CT or MRI, or with PET or other more complex parametric analyses of MRI data. We propose to address the imaging limitation building on emerging evidence indicating that effective therapy for recurrent glioma can be attained by sensitized T-cells following vaccination of primed dendritic cells (DCs). The purpose of this study was to determine whether cord blood T-cells can be sensitized against glioma cells (U-251) and if these sensitized cytotoxic T-cells (CTLs) can be used as cellular magnetic resonance imaging probes to identify and differentiate glioma from radiation necrosis in rodent models.Cord blood T and CD14+ cells were collected. Isolated CD14+ cells were then converted to dendritic cells (DCs), primed with glioma cell lysate and used to sensitize T-cells. Phenotypical expression of the generated DCs were analyzed to determine the expression level of CD14, CD86, CD83 and HLA-DR. Cells positive for CD25, CD4, CD8 were determined in generated CTLs. Specificity of cytotoxicity of the generated CTLs was also determined by lactate dehydrogenase (LDH) release assay. Secondary proliferation capacity of magnetically labeled and unlabeled CTLs was also determined. Generated CTLs were magnetically labeled and intravenously injected into glioma bearing animals that underwent MRI on days 3 and 7 post- injection. CTLs were also administered to animals with focal radiation injury to determine whether these CTLs accumulated non-specifically to the injury sites. Multi-echo T2- and T2*-weighted images were acquired and R2 and R2* maps created. Our method produced functional, sensitized CTLs that specifically induced U251 cell death in vitro. Both labeled and unlabeled CTLs proliferated equally after the secondary stimulation. There were significantly higher CD25 positive cells (p = <0.006) in CTLs. In addition, T2- and T2*-weighted MR images showed increased low signal intensity areas in animals that received labeled CTLs as compared to the images from animals that received control cells. Histological analysis confirmed the presence of iron positive cells in sites corresponding to MRI low signal intensity regions. Significant differences (p = <0.001) in tumor R2 and R2* values were observed among the groups of animals. Animals with radiation injury exhibited neither MRI hypointense areas nor presence of iron positive cells.Our results indicate that T-cells can be effectively sensitized by in vitro methods and used as cellular probes to identify and differentiate glioma from radiation necrosis

Responses of marine benthic microalgae to elevated CO<inf>2</inf>

Increasing anthropogenic CO2 emissions to the atmosphere are causing a rise in pCO2 concentrations in the ocean surface and lowering pH. To predict the effects of these changes, we need to improve our understanding of the responses of marine primary producers since these drive biogeochemical cycles and profoundly affect the structure and function of benthic habitats. The effects of increasing CO2 levels on the colonisation of artificial substrata by microalgal assemblages (periphyton) were examined across a CO2 gradient off the volcanic island of Vulcano (NE Sicily). We show that periphyton communities altered significantly as CO2 concentrations increased. CO2 enrichment caused significant increases in chlorophyll a concentrations and in diatom abundance although we did not detect any changes in cyanobacteria. SEM analysis revealed major shifts in diatom assemblage composition as CO2 levels increased. The responses of benthic microalgae to rising anthropogenic CO2 emissions are likely to have significant ecological ramifications for coastal systems. © 2011 Springer-Verlag

Vascular time-activity variation in patients undergoing 123I-MIBG myocardial scintigraphy: implications for quantification of cardiac and mediastinal uptake

For the quantification of cardiac (123)I-metaiodobenzylguanidine (MIBG) uptake, the mediastinum is commonly used as a reference region reflecting nonspecific background activity. However, variations in the quantity of vascular structures in the mediastinum and the rate of renal clearance of (123)I-MIBG from the blood pool may contribute to increased interindividual variation in uptake. This study examined the relationship between changes in heart (H) and mediastinal (M) counts and the change in vascular (123)I-MIBG activity, including the effect of renal function. Fifty-one subjects with ischemic heart disease underwent early (15 min) and late (4 h) anterior planar images of the chest following injection of (123)I-MIBG. Vascular (123)I-MIBG activity was determined from venous blood samples obtained at 2 min, 15 min, 35 min, and 4 h post-injection. From the vascular clearance curve of each subject, the mean blood counts/min per ml at the time of each acquisition and the slope of the clearance curve were determined. Renal function was expressed as the estimated creatinine clearance (e-CC) and the estimated glomerular filtration rate (e-GFR). Relations between H and M region of interest (ROI) counts/pixel, vascular activity, and renal function were then examined using linear regression. Changes in ROI activity ratios between early and late planar images could not be explained by blood activity, the slope of the vascular clearance curves, or estimates of renal function. At most 3% of the variation in image counts could be explained by changes in vascular activity (p = 0.104). The e-CC and e-GFR could at best explain approximately 1.5% of the variation in the slopes of the vascular clearance curve (p = 0.194). The change in measured H and M counts between early and late planar (123)I-MIBG images is unrelated to intravascular levels of the radiopharmaceutical. This suggests that changes in M counts are primarily due to decrease in soft tissue activity and scatter from the adjacent lung

Effectiveness of a web-based tailored intervention (E-health4Uth) and consultation to promote adolescents' health: Randomized controlled trial

Background: To promote well-being and health behaviors among adolescents, 2 interventions were implemented at 12 secondary schools. Adolescents in the E-health4Uth group received Web-based tailored messages focused on their health behaviors and well-being. Adolescents in the E-health4Uth and consultation group received the same tailored messages, but were subsequently referred to a school nurse for a consultation if they were at risk of mental health problems. Objective: This study evaluated the effect of E-health4Uth and E-health4Uth and consultation on well-being (ie, mental health status and health-related quality of life) and health behaviors (ie, alcohol and drug use, smoking, safe sex). Methods: A cluster randomized controlled trial was conducted among third- and fourth-year secondary school students (mean age 15.9, SD 0.69). School classes (clusters) were randomly assigned to (1) E-health4Uth group, (2) E-health4Uth and consultation group, or (3) control group (ie, care as usual). Adolescents completed a questionnaire at baseline and at 4-month follow-up assessing alcohol consumption, smoking, drug use, condom use, mental health via the Strengths and Difficulties Questionnaire (SDQ) and the Youth Self Report (YSR; only measured at follow-up), and health-related quality of life. Multilevel logistic, ordinal, and linear regression analyses were used to reveal differences in health behavior and well-being between the intervention groups and the control group at follow-up. Subsequently, it was explored whether demographics moderated the effects. Results: Data from 1256 adolescents were analyzed. Compared to the control intervention, the E-health4Uth intervention, as a standalone intervention, showed minor positive results in health-related quality of life (B=2.79, 95% CI 0.72-4.87) and condom use during intercourse among adolescents of Dutch ethnicity (OR 3.59, 95% CI 1.71-7.55) not replicated in the E-health4Uth and consultation group. The E-health4Uth and consultation intervention showed minor positive results in the mental health status of adolescents (SDQ: B=?0.60, 95% CI ?1.17 to ?0.04), but a negative effect on drug use among boys (OR 0.36, 95% CI 0.13-0.96). In the subgroup of adolescents who were at risk of mental health problems at baseline (and referred for a consultation with the nurse), the E-health4Uth and consultation group showed minor to moderate positive results in mental health status (SDQ: B=?1.79, 95% CI ?3.35 to ?0.22; YSR: B=?9.11, 95% CI ?17.52 to ?0.71) and health-related quality of life (B=7.81, 95% CI 2.41-13.21) at follow-up compared to adolescents in the control group who were at risk of mental health problems at baseline. Conclusions: Findings from this study support the use of the E-health4Uth and consultation intervention in promoting the well-being of adolescents at risk of mental health problems. Future research is needed to further evaluate the effects of the consultation as a standalone intervention, and the dual approach of further tailored eHealth messages and a consultation

Reliability and Validity of the KIPPPI: An Early Detection Tool for Psychosocial Problems in Toddlers

Background: The KIPPPI (Brief Instrument Psychological and Pedagogical Problem Inventory) is a Dutch questionnaire that measures psychosocial and pedagogical problems in 2-year olds and consists of a KIPPPI Total score, Wellbeing scale, Competence scale, and Autonomy scale. This study examined the reliability, validity, screening accuracy and clinical application of the KIPPPI. Methods: Parents of 5959 2-year-old children in the Rotterdam area, the Netherlands, were invited to participate in the study. Parents of 3164 children (53.1% of all invited parents) completed the questionnaire. The internal consistency was evaluated and in subsamples the test-retest reliability and concurrent validity with regard to the Child Behavioral Checklist (CBCL). Discriminative validity was evaluated by comparing scores of parents who worried about their child's upbringing and parent's that did not. Screening accuracy of the KIPPPI was evaluated against the CBCL by calculating the Receiver Operating Characteristic (ROC) curves. The clinical application was evaluated by the relation between KIPPPI scores and the clinical decision made by the child health professionals. Results: Psychometric properties of the KIPPPI Total score, Wellbeing scale, Competence scale and Autonomy scale were respectively: Cronbach's alphas: 0.88, 0.86, 0.83, 0.58. Test-rete

Single-molecule imaging reveals receptor-G protein interactions at cell surface hot spots

G-protein-coupled receptors mediate the biological effects of many hormones and neurotransmitters and are important pharmacological targets. They transmit their signals to the cell interior by interacting with G proteins. However, it is unclear how receptors and G proteins meet, interact and couple. Here we analyse the concerted motion of G-protein-coupled receptors and G proteins on the plasma membrane and provide a quantitative model that reveals the key factors that underlie the high spatiotemporal complexity of their interactions. Using two-colour, single-molecule imaging we visualize interactions between individual receptors and G proteins at the surface of living cells. Under basal conditions, receptors and G proteins form activity-dependent complexes that last for around one second. Agonists specifically regulate the kinetics of receptor-G protein interactions, mainly by increasing their association rate. We find hot spots on the plasma membrane, at least partially defined by the cytoskeleton and clathrin-coated pits, in which receptors and G proteins are confined and preferentially couple. Imaging with the nanobody Nb37 suggests that signalling by G-protein-coupled receptors occurs preferentially at these hot spots. These findings shed new light on the dynamic interactions that control G-protein-coupled receptor signalling

Diverse tick-borne microorganisms identified in free-living ungulates in Slovakia

Background: Free-living ungulates are hosts of ixodid ticks and reservoirs of tick-borne microorganisms in central Europe and many regions around the world. Tissue samples and engorged ticks were obtained from roe deer, red deer, fallow deer, mouflon, and wild boar hunted in deciduous forests of south-western Slovakia. DNA isolated from these samples was screened for the presence of tick-borne microorganisms by PCR-based methods. Results: Ticks were found to infest all examined ungulate species. The principal infesting tick was Ixodes ricinus, identified on 90.4% of wildlife, and included all developmental stages. Larvae and nymphs of Haemaphysalis concinna were feeding on 9.6% of wildlife. Two specimens of Dermacentor reticulatus were also identified. Ungulates were positive for A. phagocytophilum and Theileria spp. Anaplasma phagocytophilum was found to infect 96.1% of cervids, 88.9% of mouflon, and 28.2% of wild boar, whereas Theileria spp. was detected only in cervids (94.6%). Importantly, a high rate of cervids (89%) showed mixed infections with both these microorganisms. In addition to A. phagocytophilum and Theileria spp., Rickettsia helvetica, R. monacensis, unidentified Rickettsia sp., Coxiella burnetii, "Candidatus Neoehrlichia mikurensis", Borrelia burgdorferi (s.l.) and Babesia venatorum were identified in engorged I. ricinus. Furthermore, A. phagocytophilum, Babesia spp. and Theileria spp. were detected in engorged H. concinna. Analysis of 16S rRNA and groEL gene sequences revealed the presence of five and two A. phagocytophilum variants, respectively, among which sequences identified in wild boar showed identity to the sequence of the causative agent of human granulocytic anaplasmosis (HGA). Phylogenetic analysis of Theileria 18S rRNA gene sequences amplified from cervids and engorged I. ricinus ticks segregated jointly with sequences of T. capreoli isolates into a moderately supported monophyletic clade. Conclusions: The findings indicate that free-living ungulates are reservoirs for A. phagocytophilum and Theileria spp. and engorged ixodid ticks attached to ungulates are good sentinels for the presence of agents of public and veterinary concern. Further analyses of the A. phagocytophilum genetic variants and Theileria species and their associations with vector ticks and free-living ungulates are required.Fil: Kazimírová, Mária. Slovak Academy of Sciences. Institute of Zoology; EslovaquiaFil: Hamšíková, Zuzana. Slovak Academy of Sciences. Institute of Zoology; EslovaquiaFil: Spitalská, Eva. Slovak Academy of Sciences. Institute of Virology. Biomedical Research Center,; EslovaquiaFil: Minichová, Lenka. Slovak Academy of Sciences. Institute of Virology. Biomedical Research Center,; EslovaquiaFil: Mahríková, Lenka. Slovak Academy of Sciences. Institute of Zoology; EslovaquiaFil: Caban, Radoslav. Široká ; EslovaquiaFil: Sprong, Hein. National Institute for Public Health and Environment.Laboratory for Zoonoses and Environmental Microbiology; Países BajosFil: Fonville, Manoj. National Institute for Public Health and Environment.Laboratory for Zoonoses and Environmental Microbiology; Países BajosFil: Schnittger, Leonhard. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Patobiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Kocianová, Elena. Slovak Academy of Sciences. Institute of Virology. Biomedical Research Center,; Eslovaqui

Fast Statistical Alignment

We describe a new program for the alignment of multiple biological sequences that is both statistically motivated and fast enough for problem sizes that arise in practice. Our Fast Statistical Alignment program is based on pair hidden Markov models which approximate an insertion/deletion process on a tree and uses a sequence annealing algorithm to combine the posterior probabilities estimated from these models into a multiple alignment. FSA uses its explicit statistical model to produce multiple alignments which are accompanied by estimates of the alignment accuracy and uncertainty for every column and character of the alignment—previously available only with alignment programs which use computationally-expensive Markov Chain Monte Carlo approaches—yet can align thousands of long sequences. Moreover, FSA utilizes an unsupervised query-specific learning procedure for parameter estimation which leads to improved accuracy on benchmark reference alignments in comparison to existing programs. The centroid alignment approach taken by FSA, in combination with its learning procedure, drastically reduces the amount of false-positive alignment on biological data in comparison to that given by other methods. The FSA program and a companion visualization tool for exploring uncertainty in alignments can be used via a web interface at http://orangutan.math.berkeley.edu/fsa/, and the source code is available at http://fsa.sourceforge.net/