Three-stage contingent screening for down syndrome

Objective To demonstrate the potential value of three-stage sequential screening for Down syndrome. Methods Protocols were considered in which maternal serum pregnancy associated plasma protein-A (PAPP-A) and free -human chorionic gonadotropin (hCG) measurements were taken on all women in the first trimester. Those women with very low Down syndrome risks were screened negative at that stage and nuchal translucency (NT) was measured on the remainder and the risk reassessed. Those with very low risk were then screened negative and those with very high risk were offered early diagnostic testing. Those with intermediate risks received second-trimester maternal serum -fetoprotein, free -hCG, unconjugated estriol and inhibin-A. Risk was then reassessed and those with high risk were offered diagnosis. Detection rates and false-positive rates were estimated by multivariate Gaussian modelling using Monte-Carlo simulation. Results The modelling suggests that, with full adherence to a three-stage policy, overall detection rates of nearly 90% and false-positive rates below 2.0% can be achieved. Approximately two-thirds of pregnancies are screened on the basis of first-trimester biochemistry alone, five out of six women complete their screening in the first trimester, and the first-trimester detection rate is over 60%. Conclusion Three-stage contingent sequential screening is potentially highly effective for Down syndrome screening. The acceptability of this protocol and its performance in practice, should be tested in prospective studies. Copyright © 2006 John Wiley & Sons, Ltd.

A Hybrid Forward Algorithm for RBF Neural Network Construction

This paper proposes a novel hybrid forward algorithm (HFA) for the construction of radial basis function (RBF) neural networks with tunable nodes. The main objective is to efficiently and effectively produce a parsimonious RBF neural network that generalizes well. In this study, it is achieved through simultaneous network structure determination and parameter optimization on the continuous parameter space. This is a mixed integer hard problem and the proposed HFA tackles this problem using an integrated analytic framework, leading to significantly improved network performance and reduced memory usage for the network construction. The computational complexity analysis confirms the efficiency of the proposed algorithm, and the simulation results demonstrate its effectiveness

New binary direction aftereffect does not add up

Neural adaptation and inhibition are pervasive characteristics of the primate brain, and are probably understood better within the context of visual processing than any other sensory modality. These processes are thought to underlie illusions in which one motion affects the perceived direction of another, such as the direction aftereffect (DAE) and direction repulsion. The DAE describes how, following prolonged viewing of motion in one direction, the direction of a subsequently viewed test pattern is misperceived. In the case of direction repulsion, the direction difference between two transparently moving surfaces is over-estimated. Explanations of the DAE appeal to neural adaptation whilst direction repulsion is accounted for through lateral inhibition. Here we report on a new illusion, the Binary DAE, in which superimposed slow and fast dots moving in the same direction are perceived to move in different directions following adaptation to a mixed-speed stimulus. This new phenomenon is essentially a combination of the DAE and direction repulsion. Interestingly the magnitude of the binary DAE is greater than would be expected simply through a linear combination of the DAE and direction repulsion, suggesting that the mechanisms underlying these two phenomena interact in a non-linear fashion.

Characterization of a spontaneous mouse retinal pigment epithelial cell line B6-RPE07.

PURPOSE. A spontaneously arising retinal pigment epithelial (RPE) cell line (B6-RPE07) was cloned from a primary culture of mouse RPE cells and maintained in culture for more than 18 months. Morphologic and functional properties of this cell line have been characterized.

METHODS. The morphology of the B6-RPE07 cells was examined by phase-contrast light microscopy, electron microscopy, and confocal microscopy. Barrier properties were measured by the flux of fluorescence from the apical to the basolateral compartment of culture chambers. The abilities of the cells to bind/phagocytose photoreceptor outer segments (POS) were determined by confocal microscopy, electron microscopy, and flow cytometry. Cytokine/chemokine secretion was measured by cytometric bead array. The expression of visual cycle proteins was determined by RT-PCR and Western blotting.

RESULTS. In standard culture conditions, B6-RPE07 cells display cobblestone morphology. When cultured on three-dimensional (3D) collagen gel–coated membranes, B6-RPE07 cells exhibit a monolayer epithelial polarization with apical surface microvilli. Immunohistochemistry of B6-RPE07 cultures revealed a high expression of pan-cytokeratin. B6-RPE07 cells also expressed the retinal pigment epithelium-specific marker CRALBP, but not RPE65. Cell junction proteins ZO-1 and ß-catenin, but not claudin-1/3 or occludin-1, were observed in B6-RPE07 cells. B6-RPE07 cells are able to bind, phagocytose, and digest POS. Finally, B6-RPE07 cells produce high levels of IL-6 and CCL2.

CONCLUSIONS. This is the first report of a mouse RPE cell line with morphology, phenotype, and function similar to those of in vivo mouse RPE cells. This cell line will be a valuable resource for future RPE studies, in particular for in vivo gene modification and transplantation studies.

Do development and learning really decrease memory? On similarity and category-based induction in adults and children

In a recently published study, Sloutsky and Fisher [Sloutsky, V. M., & Fisher, A.V. (2004a). When development and learning decrease memory: Evidence against category-based induction in children. Psychological Science, 15, 553-558; Sloutsky, V. M., & Fisher, A. V. (2004b). Induction and categorization in young children: A similarity-based model. Journal of Experimental Psychology: General, 133, 166-188.] demonstrated that children have better memory for the items that they generalise to than do adults. On the basis of this finding, they claim that children and adults use different mechanisms for inductive generalisations;whereas adults focus on shared category membership, children project properties on the basis of perceptual similarity. Sloutsky & Fisher attribute children's enhanced recognition memory to the more detailed processing required by this similarity-based mechanism. In Experiment I we show that children look at the stimulus items for longer than adults. In Experiment 2 we demonstrate that although when given just 250 ms to inspect the items children remain capable of making accurate inferences, their subsequent memory for those items decreases significantly. These findings suggest that there are no necessary conclusions to be drawn from Sloutsky & Fisher's results about developmental differences in generalisation strategy. (C) 2007 Elsevier B.V. All rights reserved.

Testing the role of expansion in the prospective control of locomotion

The constant bearing angle (CBA) strategy is a prospective strategy that permits the interception of moving objects. The purpose of the present study is to test this strategy. Participants were asked to walk through a virtual environment and to change, if necessary, their walking speed so as to intercept approaching targets. The targets followed either a rectilinear or a curvilinear trajectory and target size was manipulated both within trials (target size was gradually changed during the trial in order to bias expansion) and between trials (targets of different sizes were used). The curvature manipulation had a large effect on the kinematics of walking, which is in agreement with the CBA strategy. The target size manipulations also affected the kinematics of walking. Although these effects of target size are not predicted by the CBA strategy, quantitative comparisons of observed kinematics and the kinematics predicted by the CBA strategy showed good fits. Furthermore, predictions based on the CBA strategy were deemed superior to predictions based on a required velocity (V-REQ) model. The role of target size and expansion in the prospective control of walking is discussed.

Out-of-field cell survival following exposure to intensity-modulated radiation fields

PURPOSE:
To determine the in-field and out-of-field cell survival of cells irradiated with either primary field or scattered radiation in the presence and absence of intercellular communication.
METHODS AND MATERIALS:
Cell survival was determined by clonogenic assay in human prostate cancer (DU145) and primary fibroblast (AGO1552) cells following exposure to different field configurations delivered using a 6-MV photon beam produced with a Varian linear accelerator.
RESULTS:
Nonuniform dose distributions were delivered using a multileaf collimator (MLC) in which half of the cell population was shielded. Clonogenic survival in the shielded region was significantly lower than that predicted from the linear quadratic model. In both cell lines, the out-of-field responses appeared to saturate at 40%-50% survival at a scattered dose of 0.70 Gy in DU-145 cells and 0.24 Gy in AGO1522 cells. There was an approximately eightfold difference in the initial slopes of the out-of-field response compared with the a-component of the uniform field response. In contrast, cells in the exposed part of the field showed increased survival. These observations were abrogated by direct physical inhibition of cellular communication and by the addition of the inducible nitric oxide synthase inhibitor aminoguanidine known to inhibit intercellular bystander effects. Additional studies showed the proportion of cells irradiated and dose delivered to the shielded and exposed regions of the field to impact on response.
CONCLUSIONS:
These data demonstrate out-of-field effects as important determinants of cell survival following exposure to modulated irradiation fields with cellular communication between differentially irradiated cell populations playing an important role. Validation of these observations in additional cell models may facilitate the refinement of existing radiobiological models and the observations considered important determinants of cell survival.

Social capital at work as a predictor of employee health: Multilevel evidence from work units in Finland

The majority of previous research on social capital and health is limited to social capital in residential neighborhoods and communities. Using data from the Finnish 10-Town study we examined social capital at work as a predictor of health in a cohort of 9524 initially healthy local government employees in 1522 work units, who did not change their work unit between 2000 and 2004 and responded to surveys measuring social capital at work and health at both time-points. We used a validated tool to measure social capital with perceptions at the individual level and with co-workers' responses at the work unit level. According to multilevel modeling, a contextual effect of work unit social capital on self-rated health was not accounted for by the individual's socio-demographic characteristics or lifestyle. The odds for health impairment were 1.27 times higher for employees who constantly worked in units with low social capital than for those with constantly high work unit social capital. Corresponding odds ratios for low and declining individual-level social capital varied between 1.56 and 1.78. Increasing levels of individual social capital were associated with sustained good health. In conclusion, this longitudinal multilevel study provides support for the hypothesis that exposure to low social capital at work may be detrimental to the health of employees. (c) 2007 Elsevier Ltd. All rights reserved.

When did Britain industrialise? The sectoral distribution of the labour force and labour productivity in Britain, 1381-1851

Britain's labour force industrialised early. The industrial and service sectors already accounted for 40% of the labour force in 1381, and a substantial further shift of labour out of agriculture occurred between 1522 and 1700. From the early seventeenth century rising agricultural labour productivity underpinned steadily increasing employment in industry and services, so that by 1759 agriculture's share of the labour force had shrunk to 37% and industry's grown to 34%. Thereafter, industry's output acceleration during the Industrial Revolution owed more to gains in labour productivity consequent upon mechanisation than the expansion of employment.

In-vitro investigation of out-of-field cell survival following the delivery of conformal, intensity-modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT) plans

The aim of this work is to determine the out-of-field survival of cells irradiated with either the primary field or scattered radiation in the presence and absence of intercellular communication following delivery of conformal, IMRT and VMAT treatment plans. Single beam, conformal, IMRT and VMAT plans were created to deliver 3 Gy to half the area of a T80 flask containing either DU-145 or AGO-1522 cells allowing intercellular communication between the in-and out-of-field cell populations. The same plans were delivered to a similar custom made phantom used to hold two T25 culture flasks, one flask in-field and one out-of-field to allow comparison of cell survival responses when intercellular communication is physically inhibited. Plans were created for the delivery of 8 Gy to the more radio-resistant DU-145 cells only in the presence and absence of intercellular communication. Cell survival was determined by clonogenic assay. In both cell lines, the out-of-field survival was not statistically different between delivery techniques for either cell line or dose. There was however, a statistically significant difference between survival out-of-field when intercellular communication was intact (single T80 culture flask) or inhibited (multiple T25 culture flasks) to in-field for all plans. No statistically significant difference was observed in-field with or without cellular communication to out-of-field for all plans. These data demonstrate out-of-field effects as important determinants of cell survival following exposure to modulated irradiation fields when cellular communication between differentially irradiated cell populations is present. This data is further evidence that refinement of existing radiobiological models to include indirect cell killing effects is required.

Job search monitoring intensity, unemployment exit and job entry: Quasi-experimental evidence from the UK

Because unemployment benefit reforms tend to package together changes to job search requirements, monitoring and assistance, few existing studies have been able to empirically isolate the effects of job search monitoring intensity on the behaviour of unemployment benefit claimants. This paper exploits periods where monitoring has been temporarily withdrawn during a series of Benefit Office refurbishments - with the regime otherwise unchanged - to allow such identification. During these periods of zero monitoring the hazard rates for exits from claimant unemployment and for job entry both fall. © 2008 Elsevier B.V. All rights reserved.