When an object appears unexpectedly: foot placement during obstacle circumvention in children and adults with Developmental Coordination Disorder.

Adjustments to locomotion to avoid an obstacle require a change to the usual pattern of foot placement, i.e. changes to step length and/or step width. Previous studies have demonstrated a difficulty in individuals with Developmental Coordination Disorder (DCD) in controlling stability while both stepping over and while circumventing an obstacle. In a previous study, we have considered the way in which individuals with DCD prepare for the possibility of an obstacle appearing (Wilmut and Barnett in Exp Brain Res 235:1531-1340, 2017). Using a parallel data set from this same task on the same individuals, the aim of the current study was to investigate the exact nature of changes in foot placement during obstacle avoidance, as this was not clear from previous work. Children and adults aged from 7 to 34 years of age took part in the study. Forty-four met the criteria for a diagnosis of DCD and there were 44 typically developing (TD) age and gender-matched controls. Participants walked at a comfortable pace down an 11 m walkway; on 6 out of 36 trials a 'gate' closed across their pathway which required circumvention. These 6 'gate close' trials were analysed for this study. The number and magnitude of step length and step width adjustments were similar across the DCD and TD groups, however, the younger children (7-11 years) made a greater number of early adjustments compared to the older children and adults (12-34 years of age). In contrast the adults made a greater number of adjustments later in the movement compared to the children. In terms of foot placement adjustments a clear preference was seen across all participants to use adjustments which resulted in reducing step length, stepping away from the obstacle and a combination of these. Apart from subtle differences, the individuals with DCD make step placements to circumvent an obstacle in line with their peers. It is suggested that the choice of foot placement strategy in individuals with DCD, although in line with their peers, may not be optimal for their level of motor ability.

When an object appears unexpectedly: anticipatory movement and object circumvention in individuals with and without Developmental Coordination Disorder.

Obstacles often appear unexpectedly in our pathway and these require us to make adjustments to avoid collision. Previous research has demonstrated that healthy adults will make anticipatory adjustments to gait where they have been told there is the possibility of an obstacle appearing. One population that may find this type of anticipatory movement difficult is individuals with Developmental Coordination Disorder (DCD). The current study considered how individuals with and without DCD adjust to the possibility of an obstacle appearing which would require circumvention. Fortyfour individuals with DCD and 44 age-matched controls (aged from 7 to 34 years of age) walked down an 11 m walkway under three conditions. Initially they were told this was a clear pathway and nothing in the environment would change (1, no possibility of an obstacle, no obstacle). They then performed a series of trials in which a gate may (2, possibility of an obstacle, obstacle) or may not (3, possibility of an obstacle, no obstacle) partially obstruct their pathway. We found that all participants increased medio-lateral trunk acceleration when there was the possibility of an obstacle but before the obstacle appeared, in addition the typical adults and older children also increased step width. When describing circumvention we found that the younger children showed an increase in trunk velocity and acceleration in all three directions compared to older children and adults. We also found that the individuals with DCD adjusted their path sooner and deviated more than their peers. The degree of adjustment to step width in anticipation of an obstacle was related to later medio-lateral velocity and timing of the deviation. Therefore, the lack of 'readying' the system where there is the possibility of an obstacle appearing seen in the individuals with DCD and the younger typical children may explain the increased medio-lateral velocity seen during circumvention.

Gait symmetry in individuals with and without Developmental Coordination Disorder.

BACKGROUND: Symmetry between the left and right side of the body during locomotion is key in a coordinated gait cycle and is also thought to be important in terms of efficiency. Although previous studies have identified aspects of the gait cycle which are atypical in children and adults with Developmental Coordination Disorder (DCD), studies have not considered whether this could be explained by asymmetrical gait. METHOD AND PROCEDURE: The current study included 62 participants with and 62 without DCD (aged 7-34 years). Participants were asked to walk continuously for 1min up and down a walkway while movement was captured using an optical tracking system. Measures of step length and step time were taken for both the right and the left leg and symmetry ratios were calculated. RESULTS: The DCD group showed significantly higher symmetry ratios for both measures compared to the typically developing (TD) group, with approximately a third of DCD participants falling outside the normative range for symmetry. Furthermore, a relationship was found between movement variability and degree of asymmetry. CONCLUSIONS: These findings demonstrate an asymmetry in the gait of individuals with DCD which, despite improving with age, does not reach the same level as that shown by TD individuals.

Adaptations to walking on an uneven terrain for individuals with and without Developmental Coordination Disorder.

Given the importance of walking in everyday life, understanding why this is challenging for some populations is particularly important. Studies focusing on gait patterns of individuals with Developmental Coordination Disorder (DCD) have shown that whilst increased variability is characteristic of walking patterns for this group, differences in spatio-temporal gait variables seem only to arise when task demands increase. However, these differences occur under rather artificial conditions, for example using a treadmill. The aim of this study, therefore was to examine the step characteristics of individuals with and without DCD whilst walking along an irregular terrain. Thirty-five individuals with DCD aged 8-32years and 35 age and gender-matched controls participated in this study. Participants were divided into 3 age groups; 8-12years (n=12), 13-17years (n=12) and 18-32years (n=11). Participants walked up and down a 6m walkway for two minutes on two terrains: level and irregular. VICON 3D motion analysis was used to extract measures of foot placement, velocity and angle of the head and trunk. Results showed that both groups adapted their gait to negotiate the irregular terrain, but the DCD group was more affected than their TD peers; walking significantly slower with shorter, wider steps and inclining their head more towards the ground. This suggests an adaptive approach used by individuals with DCD to preserve stability and increase visual sampling whilst negotiating an irregular terrain.

Gait patterns in children with Developmental Coordination Disorder.

Previous research has shown that adults with Developmental Coordination Disorder (DCD) show increased variability of foot placement measures and movement of the centre of mass (CoM) while walking. The current study considered the gait patterns of young and older children with DCD. Fourteen young children with DCD (7-12 years), 15 older children with DCD (12-17 years) and 29 age- and gender-matched typically developing children took part. Children were asked to walk up and down a flat 10-m-long pathway for 1 min, while the movement of their feet and trunk was recorded using motion analysis. The gait pattern of children with DCD was characterised by wider steps, elevated variability in the time spent in double support and stride time and greater medio-lateral velocity and acceleration compared to their peers. An elevated variability in medio-lateral acceleration was also seen in the young but not the older children with DCD. In addition, the young children showed a greater variability in velocity and acceleration in all three directions compared to the older children. The data suggest that the high incidence of trips and falls seen in children with DCD may be due to differences in the control of the CoM.

Constraints and facilitators to participation in physical activity in teenagers with Developmental Co-ordination Disorder: an exploratory interview study.

BACKGROUND: Despite their movement difficulties, youngsters with Developmental Co-ordination Disorder (DCD) generally have sufficient capability for physical activity. However, they tend to be less physically active and less physically fit than their well co-ordinated age peers. The aim of this study was to use qualitative research methods to understand which factors constrain and facilitate participation in physical activity in teenagers with DCD, in order to help inform future health promotion programmes. METHOD: Semi-structured interviews were conducted with eight teenagers with DCD (aged 13-15) and their parents. The interviews focused on how much physical activity was typically undertaken by the child and the perceived constraints and facilitators to being physically active. Interviews were transcribed and subjected to categorical-content analysis. RESULTS: Half of the children and all but one of the parents reported that the children did little physical activity. Although most children disliked competitive team games, they reported many physical activities that they did enjoy and they reported wanting to be more physically active. Perceived internal constraints to participation included poor motor skill, lack of motivation and reports of fatiguing easily. Perceived external constraints included difficulty travelling to activities, negative comments from peers and teachers' lack of understanding of DCD. CONCLUSIONS: Reports of low levels of physical activity support previous literature and are a cause for concern for this group. The teenagers expressed the desire to be more active, yet the interviews revealed both personal and environmental constraints to engagement in physical activity. It is clear that these factors interact in a dynamic way and that teachers, schools and communities play an important role in creating a motivational environment for youngsters with DCD to engage in physical activity and learn to maintain an active lifestyle as they move into adulthood.

Sleep behaviour in children with developmental co-ordination disorder.

BACKGROUND: Children with developmental co-ordination disorder (DCD) experience significant difficulty in the performance of everyday movement skills in the absence of obvious neurological, sensory or intellectual impairment. They often underachieve academically and have higher rates of anxiety than their typically developing peers. Such factors are known to be associated with sleep problems in other clinical populations but the sleep patterns of children with DCD have not been examined. Information about the frequency and nature of sleep problems in DCD will aid our understanding of this developmental disorder. It may also be clinically helpful, alerting clinicians to potential difficulties so that these can be identified early and appropriate support offered. OBJECTIVE: To examine sleep behaviour of children with DCD compared with typically developing control children. METHODS: Two groups of 16 boys aged 8 to 12 years (M = 10.28, SD = 1.28) participated: (1) the DCD group had Movement ABC-2 Checklist scores below the 5th percentile; (2) an age-matched control group of typically developing children had Movement ABC-2 Checklist scores above the 15th percentile. Parents of children from both groups completed the Children's Sleep Habits Questionnaire. RESULTS & DISCUSSION: The total sleep disturbance score was significantly higher for children with DCD compared with the control group (U= 24, P < 0.001). Subscale scores indicated particular problems with bedtime resistance (U= 77.5, P < 0.05), parasomnias (U= 28.5, P < 0.001) and daytime sleepiness (U= 58.00, P < 0.01). There were no differences between the groups for sleep onset delay, sleep duration, night wakings and sleep-disordered breathing. These preliminary results suggest that sleep patterns of children with DCD may be of clinical relevance and are worthy of further investigation.

Can the Griffiths scales predict neuromotor and perceptual-motor impairment in term infants with neonatal encephalopathy?

AIMS: To examine the predictive value of early developmental testing for identifying neuromotor and perceptual-motor impairment at school age in children with neonatal encephalopathy (NE). METHODS: Eighty full term infants with NE were followed longitudinally. Where possible, children were tested on the Griffiths scales at 1 and 2 years and at 5-6 years, on the Touwen Examination, Movement ABC, and WPPSI. The relation between the Griffiths scores and later outcome measures was examined using correlation coefficients and sensitivity and specificity values. RESULTS: By 2 years, 25 children with cerebral palsy were too severely impaired to be formally assessed and remained so at 5-6 years. Abnormal Griffiths scores were obtained by 12% and 7% of the children at 1 and 2 years respectively. At 5-6 years, 33% had poor Movement ABC scores and 15% poor WPPSI scores. The highest correlation between Griffiths scores and the outcome measures was for the Movement ABC (0.72), although this accounted for only 50% of the variance. Sensitivity scores for the Movement ABC were below 70% but specificity was 100%. CONCLUSIONS: A poor score on the Griffiths scales at 1 and/or 2 years is a good predictor of impairment at school age. However, a normal score in the early years cannot preclude later neurological, perceptual-motor, or cognitive abnormalities.

Visual function at school age in children with neonatal encephalopathy and low Apgar scores.

OBJECTIVE: To assess different aspects of visual function at school age in children who suffered from neonatal encephalopathy. METHOD: Thirty nine full term infants with neonatal encephalopathy, low Apgar scores, and early neonatal imaging were studied using a battery of tests assessing different aspects of visual function (crowding acuity, stereopsis, visual fields) at school age. The results were compared with brain magnetic resonance imaging (MRI) findings and, when possible, with the results of the assessment of visual function performed at 5 and 12 months, available in 24 of the 39 children examined at school age. RESULTS: Sixteen of the 39 children (41%) had abnormal results at school age in at least one of the visual tests used. Seven of these 16 were untestable on all tests. The remaining 23 children (59%) had normal results. CONCLUSIONS: The presence and severity of visual impairment was related to the severity of brain lesions. Moderate or severe basal ganglia lesions and severe white matter changes were always associated with abnormal visual function. Infants with normal MRI, minimal basal ganglia lesions, and minimal or moderate white matter involvement tended to have normal vision. It was also found that the assessment of visual function performed in the first year was a reliable indicator of visual function at school age. With two exceptions, the results on the 5 month visual assessment were predictive of visual outcome at school age. In the remaining two cases, a normal visual outcome at 5 years was associated with visual abnormalities at 5 months but these had already normalised by the age of 1 year.

Clumsiness, dyspraxia and developmental co-ordination disorder: how do health and educational professionals in the UK define the terms?

At the turn of the century, the idea that there might be a discrete childhood syndrome, which had 'clumsiness' of movement as its defining symptom, began to emerge. Since then numerous labels have been applied to the syndrome. In spite of recent attempts to standardise the terminology used, variation continues to compromise inter-professional communication and interpretation of research. The aim of this study was to determine how the three terms 'Clumsy', 'Dyspraxia' and 'Developmental Co-ordination Disorder (DCD)' are viewed by health and educational professionals in the UK. Two hundred and thirty-four adults (57% from the health professions and 43% from education) provided a written definition of each term. Content analysis of the 702 definitions was used to determine: (1) the extent to which the terms were familiar/acceptable to the respondents; and (2) to capture differences in the meaning of the term being defined. The results indicated that the terms 'DCD' and 'Dyspraxia' were less familiar than the term 'clumsy' which was, however, least acceptable. Amongst those professionals who were familiar with all three terms, there was general agreement that all were used to describe some sort of overall movement difficulty. Beyond that point, divergence of understanding and inter-professional differences in emphasis emerged. The implications of these differences for clinical and educational practice, research and policy making are discussed.

Receptor binding transforms the surface subunit of the mammalian C-type retrovirus envelope protein from an inhibitor to an activator of fusion.

The envelope protein (Env) of murine leukemia viruses (MLVs) is composed of a surface subunit (SU) and a transmembrane subunit (TM), which mediates membrane fusion, resulting in infection. SU contains a discrete N-terminal receptor binding domain (RBD) that is connected to the remainder of Env by a short, proline-rich segment. Previous studies suggest that after receptor binding, the RBD interacts directly with the remainder of Env to trigger fusion (A. L. Barnett, R. A. Davey, and J. M. Cunningham, Proc. Natl. Acad. Sci. USA 98:4113-4118, 2001). To investigate the role of the RBD in activating fusion, we compared infection by several MLVs that are defective unless rescued in trans by the addition of soluble RBD to the culture medium. Infection by MLV lacking a critical histidine residue near the N terminus of the viral RBD is dependent on the expression of receptors for both the RBD in the viral Env and the soluble RBD supplied in trans. However, infection by MLVs in which the RBD has been deleted or replaced by the ligand erythropoietin are dependent only on expression of the receptor for the soluble RBD. We were able to expand the host range of xenotropic MLV to nonpermissive murine fibroblasts only if the RBD was deleted from the xenotropic viral envelope and the soluble RBD from ecotropic Friend MLV was supplied to the culture medium. These findings indicate that receptor binding transforms the RBD from an inhibitor to an activator of the viral fusion mechanism and that viruses lacking the critical histidine residue at the N terminus of the RBD are impaired at the activation step.

Modular organization of the Friend murine leukemia virus envelope protein underlies the mechanism of infection.

Retrovirus infection is initiated by receptor-dependent fusion of the envelope to the cell membrane. The modular organization of the envelope protein of C type retroviruses has been exploited to investigate how binding of the surface subunit (SU) to receptor triggers fusion mediated by the transmembrane (TM) subunit. We show that deletion of the receptor-binding domain (RBD) from SU of Friend murine leukemia virus (Fr-MLV) abolishes infection that is restored by supplying RBD as a soluble protein. Infection by this mechanism remains dependent on receptor expression. When membrane attachment of the virus lacking RBD is reestablished by inserting the hormone erythropoietin, infection remains dependent on the RBD/receptor complex. However, infection increases 50-fold to 5 x 10(5) units/ml on cells that also express the erythropoietin receptor. Soluble RBD from Fr-MLV also restores infection by amphotropic and xenotropic MLVs in which RBD is deleted. These experiments demonstrate that RBD has two functions: mediating virus attachment and activating the fusion mechanism. In addition, they indicate that receptor engagement triggers fusion by promoting a subgroup-independent functional interaction between RBD and the remainder of SU and/or TM.

The Movement Assessment Battery for Children: a comparison of 4-year-old to 6-year-old children from Hong Kong and the United States.

OBJECTIVE: There is little information available on the appropriateness of tests developed in the West for children of different ethnicities. The aim of this study was to examine the suitability of the Movement Assessment Battery for Children (Movement ABC) for use with Hong Kong Chinese preschool children. METHOD: The performance of 255 Hong Kong Chinese children between the ages of 4 years and 6 years was compared with that of the 493 children of the same age from the United States who took part in the most recent standardization of the Movement ABC. RESULTS: The test content was found to be suitable for use with Hong Kong Chinese children. However, cross-cultural differences were found on a number of the test items. Chinese children performed significantly better on items contained in the manual dexterity and dynamic balance sections, whereas American children were better at the projection and reception of moving objects. CONCLUSION: These findings highlight the need to ensure that norms for all tests are appropriate for the specific cultural groups being assessed.

In vitro host range of Autographa californica nucleopolyhedrovirus recombinants lacking functional p35, iap1 or iap2.

We have examined the host range in different insect cell lines of Autographa californica nucleopolyhedrovirus (AcMNPV) recombinants lacking p35, iap1 or iap2. These genes encode, or are predicted to encode, anti-apoptotic proteins. Abrogation of p35 reduced the ability of AcMNPV to replicate in permissive cell lines derived from Spodoptera frugiperda insects by inducing apoptosis. In semi-permissive cell lines, such as Lymantria dispar and Spodoptera littoralis cells, we observed cytopathic effects after infection with AcMNPV but little virus production. Infection of these cells by AcMNPV lacking p35 resulted in apoptosis. However, p35-deficient viruses were still able to replicate normally in Trichoplusia ni, Mamestra brassicae and Panolis flammea cell lines. Disruption of AcMNPV iap1 and iap2 was found not to affect virus replication in any of the cell lines. It was also possible to disrupt both iap1 and iap2 in the same virus without loss of infectivity. A virus without iap1 and p35 demonstrated identical growth characteristics and host range to a virus lacking p35. We conclude that in cells which respond to AcMNPV infection by initiating programmed cell death, the p35 gene product alone is sufficient to inhibit apoptosis. Removal of iap1 or iap2 has no effect on virus replication, even in cell lines which do not undergo apoptosis in response to AcMNPV infection. Our results with two semi-permissive cell lines further indicate that whilst p35 is important in blocking block apoptosis, other factors are involved in restricting AcMNPV replication within these cells.

Specific biological effects of an anti-rat PMN antiserum intraperitoneally infected into f344/n rats.

Neutropenia can be produced with antimitotic chemicals, but this method lacks specificity. An alternative is to use antibody-dependent cytotoxicity to produce neutropenia; however, this method has not been completely evaluated with respect to efficacy, specificity, and potential collateral damage, especially to constituents of bone marrow. This study used in vitro and in vivo methods to evaluate specific biological effects of a commercially available rabbit anti-rat neutrophil (PMN) antiserum in F344/N rats. The viability of rat pulmonary alveolar macrophages (PAMs), PMNs, and lymphocytes in vitro was quantified using a trypan blue dye exclusion test. Amounts of antiserum in vitro that rendered PMNs 100% nonviable did not decrease the viability or phagocytic ability of the PAMs and did not decrease the viability of the lymphocytes. Intraperitoneal (IP) injection of the antiserum into rats resulted in complete depletion of the PMNs and about a 50% depletion of the lymphocytes in circulating blood within 24 hours. The numbers of both cell types remained lowered for 5 days, but returned to control values by Day 6 after the IP injection. The antiserum had no effect on the numbers of PAMs or lymphocytes in the pulmonary alveolar airspaces, as determined by quantifying the numbers of these cell types in bronchoalveolar lavage fluid (BALF). The numbers of PMNs in BALF, however, decreased on Days 3 and 4 after IP injection of antiserum, but were not different from control values by Day 5. The viability of the PAMs in BALF of treated rats was not different from control values at any time point. There were no morphological indications that the injected antiserum damaged lung tissue or stem cells in bone marrow. Results demonstrate that the anti-rat PMN antiserum administered IP to F344/N rats depletes circulating PMNs and partially depletes lymphocytes for a period of about 6 days without adversely affecting the precursors of red or white blood cells in bone marrow. We concluded that the antiserum is a relatively specific way to temporarily render rats neutropenic without damaging precursor cells in bone marrow.

Skin fibroblast beta-adrenergic receptor function in manic-depressive illness.

Beta-adrenergic receptor function was assessed in cultured skin fibroblasts obtained from bipolar patients and normal volunteers by measurement of the cyclic adenosine monophosphate (cAMP) response to isoproterenol. No group differences were observed. To assess regulation of receptor desensitization, fibroblasts were incubated for 24 hr with isoproterenol, and then the cAMP response to isoproterenol was determined. Subsensitivity to rechallenge with isoproterenol did not distinguish bipolar patients from controls.

Controlled primary functionalization of agarose affinity supports by carboxymethylation and subsequent addition of spacer units.

Experimental details are given for the O-carboxymethylation of cross-linked agarose beads with chloroacetate in aqueous sodium hydroxide, formation of a tandem 2-amino-ethylamide derivative, and coupling of beta-alanine residues to the aminoethyl groups using a new reagent, N-phthalimidyl N'-ethylsulfonylethoxycarbonyl-beta-alaninate. An ideal support for attaching affinity ligands results. Extent of derivatization was controlled by the time and temperature of the first reaction. Functional group densities were estimated by using hydrogen ion binding measurements for carboxyls and a new reagent, N-succinimidyl 3-[2-(4-nitrophenylamino)ethyldithio]propionate, for assaying reactive amino groups on solid supports. Synthesis and use of the new reagents are described.

Beta-adrenoceptor function in human adult skin fibroblasts: a study of manic-depressive illness.

Catecholamine theories of affective illness provide a rationale for the study of beta-adrenoceptor function in these disorders. Skin fibroblasts were grown in tissue culture from skin biopsies of normal volunteers and manic-depressive subjects for measurement of isoprenaline-stimulated production of cyclic AMP. Monolayers of fibroblasts in wells were incubated for 3 min with or without 0.5 microM-isoprenaline. The cyclic AMP was isolated by ion-exchange chromatography and quantitated by radioimmunoassay. The isoprenaline-stimulated levels of cyclic AMP in manic-depressive subjects (n = 12) were no different from those in normal volunteers (n = 13). Thus, no evidence was found for abnormal beta-adrenoceptor function in manic-depressive illness.

Liquid-chromatographic study of fluorescent compounds in hemodialysate solutions.

We have separated and identified three endogenous, naturally fluorescent substances in uremic hemodialysate by using reversed-phase liquid chromatography with fluorescence detection. Co-chromatography with authentic standards, monitoring peak shifts after enzymic treatment, and spectrofluorescence measurements were used to confirm the identity of indican, tryptophan, and indole-3-acetic acid. Concentrations of indican were about 1.5 those of tryptophan and considerably greater than those of indole-3-acetic acid in hemodialysate samples from 12 renal patients. These three compounds, as well as eight unidentified components, were consistently present in dialysate samples from each of the 12 patients.