Adults with intellectual disabilities experience high rates of obesity. Despite this higher risk, there is little evidence on the effectiveness of weight-loss interventions for adults with intellectual disabilities and obesity. The present study examined the effectiveness of the TAKE 5 multi-component weight-loss intervention. Adults with obesity were invited using specialist intellectual disability services to participate in the study. Obesity was defined as a BMI of 30 kg/m 2 or greater. TAKE 5 included a daily energy-deficit diet of 2510 kJ (600 kcal), achieved via a personalised dietary prescription. Participants' body weight, BMI, waist circumference and levels of physical activity and sedentary behaviour were measured before and after the intervention. A total of fifty-four individuals consented to participate, of which forty-seven (87 %) completed the intervention in the study period. There was a significant decrease in body weight (mean difference 24·47 (95 % CI 25·91, 2 3·03) kg; P,0·0001), BMI (21·82 (95 % CI 2 2·36, 2 1·29) kg/m 2 ; P,0·0001), waist circumference (26·29 (95 % CI 2 7·85, 24·73) cm; P,0·0001) and daily sedentary behaviour of participants (2 41·40 (95 % CI 2 62·45, 220·35) min; P¼ 0·00 034). Of the participants who completed the intervention, seventeen (36·2 %) lost 5 % or more of their initial body weight. Findings from the study suggest that TAKE 5 is an effective weight-loss intervention for adults with intellectual disabilities and obesity. The effectiveness of TAKE 5 should be examined further in a controlled study.

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People with intellectual disabilities experience significant health inequalities compared with the general population, including a shorter life expectancy and high levels of unmet health needs. Another accepted measure of health inequalities, the prevalence of obesity, has been shown to be higher in adults with intellectual disabilities than in the general population. While the factors contributing to the increased prevalence among adults with intellectual disabilities are not well understood, the high rates of obesity among younger adults highlight the need for further research involving children and adolescents with intellectual disabilities. To take forward the priorities for research and the development of effective, accessible services, there is a need for collaboration between professionals working in the fields of intellectual disabilities and obesity.

Tacrolimus is a substrate for P-glycoprotein (P-gp) and cytochrome (CYP) P4503A. P-gp is encoded by the multiple drug resistance gene MDR1 and CYP3A is the major enzyme responsible for tacrolimus metabolism. Both MDR1 and CYP3A5 genes have multiple single nucleotide polymorphisms. The objective of this study was to evaluate whether the MDR1 exon21 and exon26 polymorphisms and the CYP3A5 polymorphism are associated with tacrolimus disposition in pediatric heart transplant patients. At 3, 6 and 12 months post transplantation, a significant difference in tacrolimus blood level per dose/kg/day was found between the CYP3A5 *1/*3 (CYP3A5 expressor) vs. *3/*3 (nonexpressor) genotypes with the *1/*3 patients requiring a larger tacrolimus dose to maintain the same blood concentration. There were no significant differences in tacrolimus blood level per dose/kg/day between MDR1 exon21 G2677T and exon 26 C3435T at 3 months, but both were found to have a significant association with tacrolimus blood level per dose/kg/day at 6 and 12 months. We conclude that specific genotypes of MDR1 and CYP3A5 in pediatric heart transplant patients require larger tacrolimus doses to maintain their tacrolimus blood concentration, and that this information could be used prospectively to manage patient's immunosuppressive therapy.

SUMMARY1. The responses evoked by non-invasive electromagnetic and surface anodal electrical stimulation of the scalp (scalp stimulation) have been studied in the monkey. Conventional recording and stimulating electrodes, placed in the corticospinal pathway in the hand area of the left motor cortex, left medullary pyramid and the right spinal dorsolateral funiculus (DLF), allowed comparison of the actions of non-invasive stimuli and conventional electrical stimulation.2. Responses to electromagnetic stimulation (with the coil tangential to the skull) were studied in four anaesthetized monkeys. In each case short-latency descending volleys were recorded in the contralateral DLF at threshold. In two animals later responses were also seen at higher stimulus intensities. Both early and late responses were of corticospinal origin since they could be completely collided by appropriately timed stimulation of the pyramidal tract. The latency of the early response in the DLF indicated that it resulted from direct activation of corticospinal neurones: its latency was the same as the latency of the antidromic action potentials evoked in the motor cortex from the recording site in the DLF.3. Scalp stimulation, which was also investigated in three of the monkeys, evoked short-latency volleys at threshold and at higher stimulus intensities these were followed by later waves. The short-latency volleys could be collided from the pyramid and, at threshold, had latencies compatible with direct activation of corticospinal neurones. The longer latency volleys were also identified as corticospinal in origin.4. The latency of the early volley evoked by electromagnetic stimulation remained constant with increasing stimulus intensities. In contrast, with scalp stimulation above threshold the latency of the early volleys decreased considerably, indicating remote activation of the corticospinal pathway below the level of the motor cortex. In two monkeys both collision and latency data suggest activation of the corticospinal pathway as far caudal as the medulla.5. The majority of fast corticospinal fibres could be excited by scalp stimulation with intensities of 20% of maximum stimulator output. Electromagnetic MS 8118 S. A. EDGLEY AND OTHERS stimulation at maximum stimulator output elicited a volley of between 70 and 90 % of the size of the maximal volley evoked from the pyramidal electrodes.6. Electromagnetic stimulation was also investigated in one awake monkey during the performance of a precision grip task. Short-latency EMG responses were evoked in hand and forearm muscles. The onsets of these responses were approximately 0-8 ms longer than the responses evoked by electrical stimulation of the pyramid. Furthermore, they were comparable in latency to the fastest post-spike facilitation produced in the same muscles by identified cortico-motoneuronal cells.7. It is concluded that in the monkey, both electromagnetic and scalp stimulation of the motor cortex can activate corticospinal neurones directly, but that suprathreshold scalp stim...