Problems in the coupling of eye and hand in the sequential movements of children with developmental coordination disorder

Background: Shifting gaze and attention ahead of the hand is a natural component in the performance of skilled manual actions. Very few studies have examined the precise co-ordination between the eye and hand in children with Developmental Coordination Disorder (DCD). Methods This study directly assessed the maturity of eye-hand co-ordination in children with DCD. A double-step pointing task was used to investigate the coupling of the eye and hand in 7-year-old children with and without DCD. Sequential targets were presented on a computer screen, and eye and hand movements were recorded simultaneously. Results There were no differences between typically developing (TD) and DCD groups when completing fast single-target tasks. There were very few differences in the completion of the first movement in the double-step tasks, but differences did occur during the second sequential movement. One factor appeared to be the propensity for the DCD children to delay their hand movement until some period after the eye had landed on the target. This resulted in a marked increase in eye-hand lead during the second movement, disrupting the close coupling and leading to a slower and less accurate hand movement among children with DCD. Conclusions In contrast to skilled adults, both groups of children preferred to foveate the target prior to initiating a hand movement if time allowed. The TD children, however, were more able to reduce this foveation period and shift towards a feedforward mode of control for hand movements. The children with DCD persevered with a look-then-move strategy, which led to an increase in error. For the group of DCD children in this study, there was no evidence of a problem in speed or accuracy of simple movements, but there was a difficulty in concatenating the sequential shifts of gaze and hand required for the completion of everyday tasks or typical assessment items.

How active gaze informs the hand in sequential pointing movements

Visual information is vital for fast and accurate hand movements. It has been demonstrated that allowing free eye movements results in greater accuracy than when the eyes maintain centrally fixed. Three explanations as to why free gaze improves accuracy are: shifting gaze to a target allows visual feedback in guiding the hand to the target (feedback loop), shifting gaze generates ocular-proprioception which can be used to update a movement (feedback-feedforward), or efference copy could be used to direct hand movements (feedforward). In this experiment we used a double-step task and manipulated the utility of ocular-proprioceptive feedback from eye to head position by removing the second target during the saccade. We confirm the advantage of free gaze for sequential movements with a double-step pointing task and document eye-hand lead times of approximately 200 ms for both initial movements and secondary movements. The observation that participants move gaze well ahead of the current hand target dismisses foveal feedback as a major contribution. We argue for a feedforward model based on eye movement efference as the major factor in enabling accurate hand movements. The results with the double-step target task also suggest the need for some buffering of efference and ocular-proprioceptive signals to cope with the situation where the eye has moved to a location ahead of the current target for the hand movement. We estimate that this buffer period may range between 120 and 200 ms without significant impact on hand movement accuracy.

Sequential extraction and single-step cold-acid extraction: A feasibility study for use with freshwater-canal sediments

This investigation examines metal release from freshwater sediment using sequential extraction and single-step cold-acid leaching. The concentrations of Cd, Cr, Cu, Fe, Ni, Pb and Zn released using a standard 3-step sequential extraction (Rauret et al., 1999) are compared to those released using a 0.5 M HCl; leach. The results show that the three sediments behave in very different ways when subject to the same leaching experiments: the cold-acid extraction appears to remove higher relative concentrations of metals from the iron-rich sediment than from the other two sediments. Cold-acid extraction appears to be more effective at removing metals from sediments with crystalline iron oxides than the "reducible" step of the sequential extraction. The results show that a single-step acid leach can be just as effective as sequential extractions at removing metals from sediment and are a great deal less time-consuming.

The effect of consumption volume on profile and liking of oral nutritional supplements of varied sweetness: sequential profiling and boredom tests

Oral nutrition supplements (ONS) are routinely prescribed to those with, or at risk of, malnutrition. Previous research identified poor compliance due to taste and sweetness. This paper investigates taste and hedonic liking of ONS, of varying sweetness and metallic levels, over consumption volume; an important consideration as patients are prescribed large volumes of ONS daily. A sequential descriptive profile was developed to determine the perception of sensory attributes over repeat consumption of ONS. Changes in liking of ONS following repeat consumption were characterised by a boredom test. Certain flavour (metallic taste, soya milk flavour) and mouthfeel (mouthdrying, mouthcoating) attributes built up over increased consumption volume (p 0.002). Hedonic liking data from two cohorts, healthy older volunteers (n = 32, median age 73) and patients (n = 28, median age 85), suggested such build-up was disliked. Efforts made to improve the palatability of ONS must take account of the build up of taste and mouthfeel characteristics over increased consumption volume.

'To move or not to move': Reflections on the resettlement of artisanal miners in the western region of Ghana

This article critically reflects upon the shortcomings of the 'Prestea Action Plan', an ambitious initiative undertaken to facilitate the resettlement of artisanal miners operating in the Western Region of Ghana. The aim of the exercise was to identify viable areas for the thousands of operators who were working illegally in the town of Prestea, an area under concession to the US-based multinational, Golden Star Resources Ltd. At the time of its launch, it was one of the few support initiatives to target artisanal miners, whose claims to land are generally not recognized by governments. It was a particularly significant exercise in Ghana because it suggested that the authorities, who traditionally have exercised a policy of non-negotiation with such groups, had finally recognized that dialogue was needed if the growing rift between the country's indigenous artisanal miners, foreign mining companies and government bodies was to be bridged. It soon emerged, however, that despite its commendable policy objectives, the Plan was fundamentally flawed-problems which would undermine the entire exercise.

An adaptive approach to implementing bivariate group sequential clinical trial designs

In clinical trials, situations often arise where more than one response from each patient is of interest; and it is required that any decision to stop the study be based upon some or all of these measures simultaneously. Theory for the design of sequential experiments with simultaneous bivariate responses is described by Jennison and Turnbull (Jennison, C., Turnbull, B. W. (1993). Group sequential tests for bivariate response: interim analyses of clinical trials with both efficacy and safety endpoints. Biometrics 49:741-752) and Cook and Farewell (Cook, R. J., Farewell, V. T. (1994). Guidelines for monitoring efficacy and toxicity responses in clinical trials. Biometrics 50:1146-1152) in the context of one efficacy and one safety response. These expositions are in terms of normally distributed data with known covariance. The methods proposed require specification of the correlation, ρ between test statistics monitored as part of the sequential test. It can be difficult to quantify ρ and previous authors have suggested simply taking the lowest plausible value, as this will guarantee power. This paper begins with an illustration of the effect that inappropriate specification of ρ can have on the preservation of trial error rates. It is shown that both the type I error and the power can be adversely affected. As a possible solution to this problem, formulas are provided for the calculation of correlation from data collected as part of the trial. An adaptive approach is proposed and evaluated that makes use of these formulas and an example is provided to illustrate the method. Attention is restricted to the bivariate case for ease of computation, although the formulas derived are applicable in the general multivariate case.

Point estimates and confidence regions for sequential trials involving selection

A number of authors have proposed clinical trial designs involving the comparison of several experimental treatments with a control treatment in two or more stages. At the end of the first stage, the most promising experimental treatment is selected, and all other experimental treatments are dropped from the trial. Provided it is good enough, the selected experimental treatment is then compared with the control treatment in one or more subsequent stages. The analysis of data from such a trial is problematic because of the treatment selection and the possibility of stopping at interim analyses. These aspects lead to bias in the maximum-likelihood estimate of the advantage of the selected experimental treatment over the control and to inaccurate coverage for the associated confidence interval. In this paper, we evaluate the bias of the maximum-likelihood estimate and propose a bias-adjusted estimate. We also propose an approach to the construction of a confidence region for the vector of advantages of the experimental treatments over the control based on an ordering of the sample space. These regions are shown to have accurate coverage, although they are also shown to be necessarily unbounded. Confidence intervals for the advantage of the selected treatment are obtained from the confidence regions and are shown to have more accurate coverage than the standard confidence interval based upon the maximum-likelihood estimate and its asymptotic standard error.

Sequential designs for phase III clinical trials incorporating treatment selection

Most statistical methodology for phase III clinical trials focuses on the comparison of a single experimental treatment with a control. An increasing desire to reduce the time before regulatory approval of a new drug is sought has led to development of two-stage or sequential designs for trials that combine the definitive analysis associated with phase III with the treatment selection element of a phase II study. In this paper we consider a trial in which the most promising of a number of experimental treatments is selected at the first interim analysis. This considerably reduces the computational load associated with the construction of stopping boundaries compared to the approach proposed by Follman, Proschan and Geller (Biometrics 1994; 50: 325-336). The computational requirement does not exceed that for the sequential comparison of a single experimental treatment with a control. Existing methods are extended in two ways. First, the use of the efficient score as a test statistic makes the analysis of binary, normal or failure-time data, as well as adjustment for covariates or stratification straightforward. Second, the question of trial power is also considered, enabling the determination of sample size required to give specified power. Copyright © 2003 John Wiley & Sons, Ltd.

The sequential analysis of repeated binary responses: a score test for the case of three time points

In this paper a robust method is developed for the analysis of data consisting of repeated binary observations taken at up to three fixed time points on each subject. The primary objective is to compare outcomes at the last time point, using earlier observations to predict this for subjects with incomplete records. A score test is derived. The method is developed for application to sequential clinical trials, as at interim analyses there will be many incomplete records occurring in non-informative patterns. Motivation for the methodology comes from experience with clinical trials in stroke and head injury, and data from one such trial is used to illustrate the approach. Extensions to more than three time points and to allow for stratification are discussed. Copyright © 2005 John Wiley & Sons, Ltd.

Incorporating data received after a sequential trial has stopped into the final analysis: implementation and comparison of methods

In a sequential clinical trial, accrual of data on patients often continues after the stopping criterion for the study has been met. This is termed “overrunning.” Overrunning occurs mainly when the primary response from each patient is measured after some extended observation period. The objective of this article is to compare two methods of allowing for overrunning. In particular, simulation studies are reported that assess the two procedures in terms of how well they maintain the intended type I error rate. The effect on power resulting from the incorporation of “overrunning data” using the two procedures is evaluated.

An adaptive group sequential design for phase II/III clinical trials that select a single treatment from several

There is increasing interest in combining Phases II and III of clinical development into a single trial in which one of a small number of competing experimental treatments is ultimately selected and where a valid comparison is made between this treatment and the control treatment. Such a trial usually proceeds in stages, with the least promising experimental treatments dropped as soon as possible. In this paper we present a highly flexible design that uses adaptive group sequential methodology to monitor an order statistic. By using this approach, it is possible to design a trial which can have any number of stages, begins with any number of experimental treatments, and permits any number of these to continue at any stage. The test statistic used is based upon efficient scores, so the method can be easily applied to binary, ordinal, failure time, or normally distributed outcomes. The method is illustrated with an example, and simulations are conducted to investigate its type I error rate and power under a range of scenarios.

A practical comparison of group-sequential and adaptive designs

Sequential methods provide a formal framework by which clinical trial data can be monitored as they accumulate. The results from interim analyses can be used either to modify the design of the remainder of the trial or to stop the trial as soon as sufficient evidence of either the presence or absence of a treatment effect is available. The circumstances under which the trial will be stopped with a claim of superiority for the experimental treatment, must, however, be determined in advance so as to control the overall type I error rate. One approach to calculating the stopping rule is the group-sequential method. A relatively recent alternative to group-sequential approaches is the adaptive design method. This latter approach provides considerable flexibility in changes to the design of a clinical trial at an interim point. However, a criticism is that the method by which evidence from different parts of the trial is combined means that a final comparison of treatments is not based on a sufficient statistic for the treatment difference, suggesting that the method may lack power. The aim of this paper is to compare two adaptive design approaches with the group-sequential approach. We first compare the form of the stopping boundaries obtained using the different methods. We then focus on a comparison of the power of the different trials when they are designed so as to be as similar as possible. We conclude that all methods acceptably control type I error rate and power when the sample size is modified based on a variance estimate, provided no interim analysis is so small that the asymptotic properties of the test statistic no longer hold. In the latter case, the group-sequential approach is to be preferred. Provided that asymptotic assumptions hold, the adaptive design approaches control the type I error rate even if the sample size is adjusted on the basis of an estimate of the treatment effect, showing that the adaptive designs allow more modifications than the group-sequential method.