Harmonizing analytical chemistry and clinical epidemiology for human biomonitoring studies. A case-study of plastic product chemicals in urine.

There is an interdisciplinary interface between analytical chemistry and epidemiology studies with respect to the design, execution, and analysis of environmental epidemiology cohorts and studies. Extracting meaningful results linking chemical exposure to human health outcomes begins at study design and spans the entire workflow. Here we discuss analytical experimental design from an exposure science perspective, and propose a reporting checklist for the design of human biomonitoring studies. We explain key analytical chemistry concepts of blanks and limits of reporting and present a case series of plastic product chemical exposure in prenatal urine specimens from the Barwon Infant Study.

Movement Disorders and Syndromic Autism: A Systematic Review.

Movement disorders are reported in idiopathic autism but the extent to which comparable movement disorders are found in syndromic/co-morbid autism is unknown. A systematic search of Medline, Embase, PsychINFO and CINAHL on the prevalence of specific movement disorder in syndromic autism associated with specific genetic syndromes identified 16 papers, all relating to Angelman syndrome or Rett syndrome. Prevalence rates of 72.7-100% and 25.0-27.3% were reported for ataxia and tremor, respectively, in Angelman syndrome. In Rett syndrome, prevalence rates of 43.6-50% were reported for ataxia and 27.3-48.3% for tremor with additional reports of dystonia, rigidity and pyramidal signs. However, reliable assessment measures were rarely used and recruitment was often not described in sufficient detail.

Anatomical redistribution of endogenous copper in embryonic mice overexpressing SOD1.

Mutations in the copper (Cu)- and zinc (Zn)-binding metalloenzyme Cu/Zn-superoxide dismutase (SOD1) cause familial forms of amyotrophic lateral sclerosis (ALS), a fatal adult-onset neurodegenerative disorder of the central nervous system (CNS). Transgenic over-expression of mutant SOD1 produces a robust ALS-like phenotype in mice. Despite being ubiquitously expressed from the moment of conception, the mechanisms underlying the CNS-selective phenotype of mutant SOD1 expression remain poorly understood. We have previously shown that the physiological requirement for copper in SOD1 is unsatiated in the CNS of adult mice overexpressing mutant SOD1 and that suboptimal delivery of Cu to SOD1 in these mice progressively worsens with age. An age-related impediment to Cu availability may therefore contribute to the adult onset of disease in cases of ALS caused by mutant SOD1. Here, we have extended the age-related investigation of Cu in SOD1 overexpressing transgenic mice to the embryonic stage of development. We used the quantitative in situ elemental imaging method, laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS), to assess the endogenous distribution of Cu, Zn and other endogenous elements (carbon, phosphorus, sulphur, magnesium, manganese and iron) in the embryonic day 14 (E14) embryos of transgenic mice overexpressing wild-type human SOD1 (hSOD1Wt) or mutant human SOD1 (hSOD1G37R). We show that in contrast to adult mice, SOD1 overexpression (both wild-type and mutant) is associated with an overt redistribution of Cu from the liver to the CNS during embryonic development. Also in contrast to adult mice, Zn redistribution to the CNS in response to SOD1 over-expression is relatively modest in embryonic mice, being limited to the brainstem. No other elemental changes between genotypes were observed. Our application of quantitative LA-ICP-MS in situ imaging details the first anatomical mapping of endogenous elements in embryonic mice. The observed redistribution of Cu from the liver to the CNS in response to SOD1 overexpression during embryogenesis indicates that the impediment of Cu delivery to SOD1, which is evident in adult mutant SOD1 overexpressing mice, only occurs at a later stage in life.

Symptoms of Autism Spectrum Disorder (ASD) in Individuals with Mucopolysaccharide Disease Type III (Sanfilippo Syndrome): A Systematic Review.

The prevalence of autism spectrum disorder (ASD) in many genetic disorders is well documented but not as yet in Mucopolysaccharidosis type III (MPS III). MPS III is a recessively inherited metabolic disorder and evidence suggests that symptoms of ASD present in MPS III. This systematic review examined the extant literature on the symptoms of ASD in MPS III and quality assessed a total of 16 studies. Results indicated that difficulties within speech, language and communication consistent with ASD were present in MPS III, whilst repetitive and restricted behaviours and interests were less widely reported. The presence of ASD-like symptoms can result in late diagnosis or misdiagnosis of MPS III and prevent opportunities for genetic counselling and the provision of treatments.

Whole-brain metallomic analysis of the common marmoset (Callithrix jacchus).

Despite the importance of transition metals for normal brain function, relatively little is known about the distribution of these elemental species across the different tissue compartments of the primate brain. In this study, we employed laser ablation-inductively coupled plasma-mass spectrometry on PFA-fixed brain sections obtained from two adult common marmosets. Concurrent cytoarchitectonic, myeloarchitectonic, and chemoarchitectonic measurements allowed for identification of the major neocortical, archaecortical, and subcortical divisions of the brain, and precise localisation of iron, manganese, and zinc concentrations within each division. Major findings across tissue compartments included: (1) differentiation of white matter tracts from grey matter based on manganese and zinc distribution; (2) high iron concentrations in the basal ganglia, cortex, and substantia nigra; (3) co-localization of high concentrations of iron and manganese in the primary sensory areas of the cerebral cortex; and (4) high manganese in the hippocampus. The marmoset has become a model species of choice for connectomic, aging, and transgenic studies in primates, and the application of metallomics to these disciplines has the potential to yield high translational and basic science value.

The nature and prevalence of catatonic symptoms in young people with autism.

BACKGROUND: A proportion of young people with autism are reported to show catatonic-like symptoms in adolescence. The aetiology and prevalence of such presentations is unknown but include a set of behaviours that can best be described as attenuated. METHOD: The current study empirically investigated the presence and nature of such attenuated behaviours in children and adolescents with autism using a newly developed 34-item third party report measure, the Attenuated Behaviour Questionnaire. Caregivers or parents of young people with autism reported on the presentation of symptoms via the online completion of the Attenuated Behaviour Questionnaire and two established clinical measures of repetitive behaviour and depression. RESULTS: Initial results indicate that the Attenuated Behaviour Questionnaire is a workable clinical measure in this population with a degree of discriminant validity with regard to catatonia. Attenuated behaviour indicative of catatonia was relatively common in young people with autism with up to 20.2% having an existing diagnosis of catatonia and evidence of a relationship between attenuated behaviours and measures of depression and repetitive and restricted behaviours. CONCLUSION: Catatonic symptoms are more prevalent in young people with autism than previously thought, and the Attenuated Behaviour Questionnaire has potential as a clinical and research tool.

Glutathione peroxidase 4: a new player in neurodegeneration?

Glutathione peroxidase 4 (GPx4) is an antioxidant enzyme reported as an inhibitor of ferroptosis, a recently discovered non-apoptotic form of cell death. This pathway was initially described in cancer cells and has since been identified in hippocampal and renal cells. In this Perspective, we propose that inhibition of ferroptosis by GPx4 provides protective mechanisms against neurodegeneration. In addition, we suggest that selenium deficiency enhances susceptibility to ferroptotic processes, as well as other programmed cell death pathways due to a reduction in GPx4 activity. We review recent studies of GPx4 with an emphasis on neuronal protection, and discuss the relevance of selenium levels on its enzymatic activity.

Clinical psychologists' attitudes towards the biology and 'new genetics' of intellectual and developmental disabilities: a pilot study using Q-methodology.

BACKGROUND: The current study investigated how ideas and models from the 'New Genetics' and associated fields of developmental neuroscience and behavioural phenotypes are perceived by clinical psychologists working with people with intellectual and developmental disabilities (IDD). As well as examining the take-up and influence of such ideas, it also examines barriers, both personal and institutional, to the widespread adoption of such concepts and research findings in services for people with IDD. METHODS: A Q-methodology study was undertaken with 31 qualified and 16 trainee clinical psychologists in the North West of England using a specifically developed 81-item Q set. RESULTS: Three factors were identified and labelled Integration of social and medical models, Social model of disability is more helpful and Genetic advances in conflict with recognising the value of people with IDD. CONCLUSION: There was a lack of consensus in clinical psychologists working with people with IDD, with amount and type of professional experience affecting the factor loadings, which may need to be considered in developing clinical applications of genetic IDD research.

Behavioural phenotypes of the mucopolysaccharide disorders: a systematic literature review of cognitive, motor, social, linguistic and behavioural presentation in the MPS disorders.

BACKGROUND: The mucopolysaccharide disorders (MPS) are a group of recessively inherited metabolic disorders resulting in progressive physical and cognitive decline. MATERIALS AND METHODS: MEDLINE, PsycINFO and Embase databases were searched, alongside manual screening, to identify relevant literature. Papers were included in the review if they were published in a peer reviewed journal and conducted empirical research into cognitive, motor, social or linguistic development or behaviour in one or more MPS disorders. RESULTS: Twenty-five papers were reviewed. Two papers used methodology of a sufficiently high standard to demonstrate a behavioural phenotype; both found sleep disturbance to be part of the phenotype of MPS III. Fearfulness and sleep disturbance were frequently observed in people with MPS I and II. Cognitive and motor impairment and decline, and challenging behaviour were highly prevalent in the severe form of MPS II. Cognitive decline and severe behavioural problems relating to aggression, hyperactivity, orality, unusual affect and temper tantrums were seen in MPS III. CONCLUSIONS: Sleep disturbance is part of the behavioural phenotype of MPS III, and challenging behaviour is highly prevalent in MPS II and MPS III, therefore the efficacy of behavioural interventions for these populations should be investigated. Further research into the behaviour and adaptive skills of children with MPS III and MPS IV is required.

The feasibility of Dementia Care Mapping (DCM) on a neurorehabilitation ward.

Person-centred care (PCC) is recommended when working with patients with neurological difficulties. Despite this, to date there has been no appropriate methodology for assessing or developing PCC in neurorehabilitation settings. Dementia Care Mapping (DCM) is a well-established tool for assessing and developing PCC in dementia settings and the current study investigated the feasibility of applying DCM on an acute neurorehabilitation ward. DCM procedure and coding required minor adaptations for use in this setting and further recommended adaptations were subsequently identified. It was found that the DCM coding system was generally suitable and could identify strengths, weaknesses and areas for development in ward care. Q-methodology identified that staff views endorsed the feasibility of using DCM in neurorehabilitation, with staff reporting that they found DCM useful and relevant to their work. DCM could be further developed for this setting by amendments to the behaviour coding system, concept and coding of person-centred care, and a population-specific manual. DCM is a promising methodology to develop and promote PCC in neurorehabilitation.

Attitudes of relatives and staff towards family intervention in forensic services using Q methodology.

Attitudes about family interventions have been identified as a possible reason for the poor implementation of such treatments. The current study used Q methodology to investigate the attitudes of relatives of forensic service users and clinical staff towards family interventions in medium secure forensic units, particularly when facilitated by a web camera. Eighteen relatives and twenty-nine staff completed a sixty-one item Q sort to obtain their idiosyncratic views about family intervention. The results indicated that relatives and staff mostly held positive attitudes towards family intervention. Relatives showed some uncertainty towards family intervention that may reflect the lack of involvement they receive from the forensic service. Staff highlighted key barriers to successful implementation such as lack of dedicated staff time for family work and few staff adequately trained in family intervention. Despite agreement with the web-based forensic family intervention technique and its benefits, both staff and relatives predicted problems in the technique.

The use of melatonin to treat sleep disorder in adults with intellectual disabilities in community settings - the evaluation of three cases using actigraphy.

BACKGROUND: Sleep disorders are known to be very prevalent in adults with intellectual disabilities (ID) but to date there has been limited objective assessment of either sleep disorders or of interventions such as the use of melatonin. METHODOLOGY: A protocol-driven assessment and intervention procedure was followed with three people with moderate to severe ID identified as having a possible sleep disorder. Actigraphic assessment was used to determine the nature of the sleep disorder, after which sleep hygiene advice and then individual treatment with melatonin were provided, following which further actigraphic assessment was carried out. Behavioural disturbance was formally assessed before and after the intervention phase. RESULTS: Following treatment with melatonin, changes in circadian rhythm were noted, together with improvements in challenging behaviour, but no significant effects were noted with regard to either quantity or quality of sleep. CONCLUSIONS: A standardised procedure for assessment and treatment of sleep disorders in people with ID was established. Although no apparent effects on sleep quantity or quality were noted, this may reflect factors inherent in the sample, rather than the relative efficacy of melatonin treatment per se.

The conceptualisation of dreams by adults with intellectual disabilities: relationship with theory of mind abilities and verbal ability.

BACKGROUND: Empirical studies suggest that individuals with intellectual disabilities (ID) have difficulties in conceptualising dreams as perceptually private, non-physical, individuated and potentially fictional entities. The aim of the current study was to replicate the results found by Stenfert Kroese et al. using a comparative sample size, and to examine putative cognitive correlates of accurate dream conceptualisation [receptive language and 1st order theory of mind (ToM) abilities]. METHOD: Conceptualisation of dreams, real objects and photographs was assessed with a structured closed-question interview schedule, together with receptive language, and ToM abilities. RESULTS: Findings from the current study replicated those of previous research, finding that many adults with ID tend to think that dreams take place around them, can be witnessed by others, can be touched and manipulated, can be shared by others and are about real events. The ability to accurately conceptualise dreams was found to increase along with receptive language ability, and there was a non-significant association between ToM ability and the ability to understand that dreams can be about potentially fictional entities. CONCLUSIONS: Some individuals with ID have a different understanding of mental phenomena such as dreams, which has implications for several aspects of care and support, particularly relating to mental health and therapeutic work.

Objective investigation of the sleep-wake cycle in adults with intellectual disabilities and autistic spectrum disorders.

BACKGROUND: Disturbances in circadian rhythm functioning, as manifest in abnormal sleep-wake cycles, have been postulated to be present in people with autistic spectrum disorders (ASDs). To date, research into the sleep-wake cycle in people with ASDs has been primarily dependant on third-party data collection. METHOD: The utilization of non-invasive objective recording technologies such as actigraphy permits investigation of both sleep and circadian rhythm functioning in people with ASDs, together with the collection of data on daytime activity. RESULTS: Data were collected from 31 participants with intellectual disabilities living in supported community-based residential provision aged between 20 and 58 years, of whom 14 had an ASD. Analysis indicated that there were no significant differences in sleep patterns and circadian rhythm function between those participants with an ASD and those without. CONCLUSIONS: The mean scores of the participants as a whole indicated abnormalities in the two key circadian rhythm parameters of interdaily stability and intradaily variability. The implications of these findings for both clinical practice and theory are discussed.

The response to challenging behaviour by care staff: emotional responses, attributions of cause and observations of practice.

BACKGROUND: Previous studies have attempted to apply Weiner's attributional model of helping behaviour to care staff who work with service users with intellectual disabilities and challenging behaviours by using studies based on vignettes. The aims of the current study were to investigate the application of Weiner's model to 'real' service users with intellectual disabilities and challenging behaviours and to observe the care staff's actual responses to challenging behaviours displayed by service users. Also, to compare care staff attributions, emotions, optimism, willingness to help and observed helping behaviours for self-injurious behaviours in comparison to other forms of challenging behaviours. METHOD: A total of 27 care staff completed two sets of measures, one set regarding a self-injurious behaviour and the other regarding other forms of challenging behaviour. An additional 16 staff completed one set of measures. The measures focused on care staff attributions, emotions, optimism and willingness to help. Also, 16 of the care staff were observed interacting with the service users to collect data regarding their responses to challenging behaviours. RESULTS: For both self-injurious behaviours and other forms of challenging behaviour, associations were found between the care staff internal, stable and uncontrollable attribution scores and care staff negative emotion scores. However, no associations were found between the care staff levels of emotion, optimism and willingness to help. Some associations were found between the care staff levels of willingness to help and observed helping behaviours. There were significant differences between the care staff attribution scores with higher scores being obtained for uncontrollable and stable attributions for other forms of challenging behaviours. No significant differences were found between the care staff emotions, optimism, willingness to help and observed helping behaviours. CONCLUSIONS: The results did not provide support for Weiner's attributional model of helping behaviour. However, a preliminary model of negative care staff behaviour was derived from the exploratory analyses completed. This model proposes that there are associations between internal, stable and uncontrollable attributions and negative emotions in care staff and also between negative emotions and negative behaviours displayed by care staff in response to the actions of service users.

Theory of mind, causal attribution and paranoia in Asperger syndrome.

Theory of mind (ToM) deficits are central to autistic spectrum disorders, including Asperger syndrome. Research in psychotic disorders has developed a cognitive model of paranoid delusions involving abnormal causal attributions for negative events. Possible aetiologies of these include deficits in social reasoning, specifically ToM. The present study investigated this attributional model of paranoia in Asperger syndrome. Participants diagnosed with Asperger syndrome scored significantly higher on a measure of paranoia and lower on a measure of ToM, compared with the control group. They did not differ in self-concept and causal attributions, contrary to the attributional model of paranoia. A regression analysis highlighted private self-consciousness as the only predictor of paranoia. The theoretical and clinical implications of these findings are discussed.

Carotid endarterectomy under local anaesthesia.

Carotid endarterectomy has been widely used for the surgical treatment of carotid stenosis, and may be performed under either general or local anaesthesia. This article examines the relative merits of both techniques for carotid endarterectomy, and describes the local anaesthetic technique used by the authors for this procedure.