Rethinking functional outcome measures: the development of an upper limb test to assess basal ganglia dysfunction

The basal ganglia is implicated in a wide range of motor, cognitive and behavioural activities required for normal function. This region is predominantly affected in Huntington’s disease (HD), meaning that functional ability progressively worsens. However, functional outcome measures for HD, particularly those for the upper limb, are limited meaning there is an imperative for well-defined, quantitative measures. Here we describe the development and evaluation of the Moneybox test (MBT). This novel, functional upper limb assessment was developed in accordance with translational neuroscience and physiological principles for people with a broad disease manifestation, such as HD. Participants with HD (n=64) and healthy controls (n=21) performed the MBT, which required subjects to transfer tokens into a container in order of size (Baseline Transfer), value (Complex Transfer) with and without reciting the alphabet (Dual Transfer). Disease specific measures of motor, cognition, behaviour and function were collected. HD patients were grouped into disease stage, from which, discriminative and convergent validity was assessed using Analysis of Variance and Pearson’s correlation respectively. Manifest HD participants were slower than pre-manifest and control participants, and achieved significantly lower MBT total scores. Performance in the Complex Transfer and Dual Transfer tasks were significantly different between pre-manifest and stage 1 HD. All MBT performance variables significantly correlated with routinely used measures of motor, cognition, behaviour and function. The MBT provides a valid, sensitive and affordable functional outcome measure. Unlike current assessments, MBT performance significantly distinguished the subtle differences between the earliest disease stages of HD, which are the populations typically targeted in clinical trials

Identification of the neural correlates underlying conflict resolution performance using a rodent analogue of the Stroop tests

The Stroop test is a widely used neuropsychological test measuring attention and conflict resolution, which shows sensitivity across a range of diseases, including Alzheimer’s, Parkinson’s and Huntington’s diseases. A rodent analogue of the Stroop test, the Response-Conflict task (rRCT), allows for systematic investigation of the neural systems underpinning performance in this test. Little is known about the involvement of the basal ganglia in this neural process. The aim of this study was to use the rRCT to determine whether striatal subregions are recruited during conflict resolution processing. To achieve this, rats were exposed to Congruent or Incongruent stimuli in the rRCT and the expression patterns of the immediate early gene Zif268 were analysed throughout cortical, hippocampal and basal ganglia subregions. The results confirmed the previously reported involvement of prefrontal cortical and hippocampal regions, as well as identifying a specific role for the dysgranular (but not granular) retrosplenial cortex in conflict resolution. Finally, performance accuracy correlated significantly with reduced neural activation in the dorsomedial striatum. Involvement of the basal ganglia in this neural process has not previously been reported. These data demonstrate that the cognitive process of conflict resolution requires not only prefrontal cortical regions, but also recruits the dysgranular retrosplenial cortex and the medial region of the neostriatum. These data have implications for understanding the neuroanatomical changes that underpin impaired Stroop performance in people with neurological disorders

Socio-cultural influences on the behaviour of South Asian women with diabetes in pregnancy: qualitative study using a multi-level theoretical approach

BACKGROUND: Diabetes in pregnancy is common in South Asians, especially those from low-income backgrounds, and leads to short-term morbidity and longer-term metabolic programming in mother and offspring. We sought to understand the multiple influences on behaviour (hence risks to metabolic health) of South Asian mothers and their unborn child, theorise how these influences interact and build over time, and inform the design of culturally congruent, multi-level interventions. METHODS: Our sample for this qualitative study was 45 women of Bangladeshi, Indian, Sri Lankan, or Pakistani origin aged 21-45 years with a history of diabetes in pregnancy, recruited from diabetes and antenatal services in two deprived London boroughs. Overall, 17 women shared their experiences of diabetes, pregnancy, and health services in group discussions and 28 women gave individual narrative interviews, facilitated by multilingual researchers, audiotaped, translated, and transcribed. Data were analysed using the constant comparative method, drawing on sociological and narrative theories. RESULTS: Key storylines (over-arching narratives) recurred across all ethnic groups studied. Short-term storylines depicted the experience of diabetic pregnancy as stressful, difficult to control, and associated with negative symptoms, especially tiredness. Taking exercise and restricting diet often worsened these symptoms and conflicted with advice from relatives and peers. Many women believed that exercise in pregnancy would damage the fetus and drain the mother's strength, and that eating would be strength-giving for mother and fetus. These short-term storylines were nested within medium-term storylines about family life, especially the cultural, practical, and material constraints of the traditional South Asian wife and mother role and past experiences of illness and healthcare, and within longer-term storylines about genetic, cultural, and material heritage - including migration, acculturation, and family memories of food insecurity. While peer advice was familiar, meaningful, and morally resonant, health education advice from clinicians was usually unfamiliar and devoid of cultural meaning. CONCLUSIONS: 'Behaviour change' interventions aimed at preventing and managing diabetes in South Asian women before and during pregnancy are likely to be ineffective if delivered in a socio-cultural vacuum. Individual education should be supplemented with community-level interventions to address the socio-material constraints and cultural frames within which behavioural 'choices' are made

The evidence base for chiropractic treatment of musculoskeletal conditions in children and adolescents: The emperor's new suit?

Five to ten percent of chiropractic patients are children and adolescents. Most of these consult because of spinal pain, or other musculoskeletal complaints. These musculoskeletal disorders in early life not only affect the quality of children's lives, but also seem to have an impact on adult musculoskeletal health. Thus, this is an important part of the chiropractors' scope of practice, and the objective of this review is to assess the evidence base for manual treatment of musculoskeletal disorders in children and adolescents

The effectiveness of a multidisciplinary intervention strategy for the treatment of symptomatic joint hypermobility in childhood:A randomised, single Centre parallel group trial (The Bendy Study)

Introduction: Joint hypermobility is common in childhood and can be associated with musculoskeletal pain and dysfunction. Current management is delivered by a multidisciplinary team, but evidence of effectiveness is limited. This clinical trial aimed to determine whether a structured multidisciplinary, multisite intervention resulted in improved clinical outcomes compared with standard care. Method: A prospective randomised, single centre parallel group trial comparing an 8-week individualised multidisciplinary intervention programme (bespoke physiotherapy and occupational therapy in the clinical, home and school environment) with current standard management (advice, information and therapy referral if deemed necessary). The primary endpoint of the study was between group difference in child reported pain from baseline to 12 months as assessed using the Wong Baker faces pain scale. Secondary endpoints were parent reported pain (100 mm visual analogue scale), parent reported function (child health assessment questionnaire), child reported quality of life (child health utility 9-dimensional assessment), coordination (movement assessment battery for children version 2) and grip strength (handheld dynamometer). Results: 119 children aged 5 to 16 years, with symptomatic hypermobility were randomised to receive an individualised multidisciplinary intervention (I) (n = 59) or standard management (S) (n = 60). Of these, 105 completed follow up at 12 months. No additional significant benefit could be shown from the intervention compared to standard management. However, there was a statistically significant improvement in child and parent reported pain, coordination and grip strength in both groups. The response was independent of the degree of hypermobility. Conclusion: This is the first randomised controlled trial to compare a structured multidisciplinary, multisite intervention with standard care in symptomatic childhood hypermobility. For the majority, the provision of education and positive interventions aimed at promoting healthy exercise and self-management was associated with significant benefit without the need for more complex interventions. Trial registration: The trial was registered prospectively with the national database at the Clinical Research Network (UKCRN Portfolio 9366). The trial was registered retrospectively with ISRCTN (ISRCTN86573140)

The effect of premature extraction of primary teeth on the subsequent need for orthodontic treatment.

AIM: To investigate if premature extraction of primary teeth was associated with orthodontic need in the permanent dentition. STUDY DESIGN: This was a case-control study based on retrospective dental records. METHODS: As part of NHS (UK) Dental Epidemiology Programme a sample of 366, 12-year-old children from Bradford and Airedale were examined. The survey collected data on patient demographics, dental health status including orthodontic need. Data linkage was undertaken for those children participating in the NHS Dental Epidemiology Programme who had previously accessed the local Salaried Dental Service (SDS). For these children, retrospective dental information was collected about premature extraction of primary teeth. RESULTS: From the 366 children who were surveyed, 116 children had received treatment at the local SDS in the past. Significantly more children from ethnic minorities, low socioeconomic backgrounds and high caries rate (p < 0.001) were seen in the SDS. For the 107 children who attended SDS, an increased total number of primary teeth extractions was positively associated with orthodontic need (odds ratio:1.18, CI -1.01 to 1.37). STATISCTICS: Multilevel modelling was undertaken to identify variables associated with orthodontic need. CONCLUSIONS: In the study group, orthodontic need was significantly associated with the number of primary teeth extracted

Portfolio manager ownership and mutual fund performance

This paper examines the association between a mutual fund manager's personal fund investment and mutual fund performance. Newly-released managerial ownership disclosures reveal that fund ownership varies across mutual fund managers and, in many instances, is quite large. I find that mutual fund returns are increasing in the level of managerial fund investment, consistent with managerial ownership realigning decision-maker and shareholder interests. Also consistent with the reduction of agency costs, I find that managerial ownership is inversely related to fund turnover, which could affect both tax and trading costs. However, I do not find any association between portfolio manager ownership and a mutual fund's tax burden