1,930 research outputs found

    An Introduction to Applications of Wavelet Benchmarking with Seasonal Adjustment

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    Summary Before adjustment, low and high frequency data sets from national accounts are frequently inconsistent. Benchmarking is the procedure used by economic agencies to make such data sets consistent. It typically involves adjusting the high frequency time series (e.g. quarterly data) so that they become consistent with the lower frequency version (e.g. annual data). Various methods have been developed to approach this problem of inconsistency between data sets. The paper introduces a new statistical procedure, namely wavelet benchmarking. Wavelet properties allow high and low frequency processes to be jointly analysed and we show that benchmarking can be formulated and approached succinctly in the wavelet domain. Furthermore the time and frequency localization properties of wavelets are ideal for handling more complicated benchmarking problems. The versatility of the procedure is demonstrated by using simulation studies where we provide evidence showing that it substantially outperforms currently used methods. Finally, we apply this novel method of wavelet benchmarking to official data from the UK's Office for National Statistics.Engineering and Physical Sciences Research CouncilThis is the final version of the article. It first appeared from Wiley via https://doi.org/10.1111/rssa.1224

    The development of path integration: combining estimations of distance and heading

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    Efficient daily navigation is underpinned by path integration, the mechanism by which we use self-movement information to update our position in space. This process is well-understood in adulthood, but there has been relatively little study of path integration in childhood, leading to an underrepresentation in accounts of navigational development. Previous research has shown that calculation of distance and heading both tend to be less accurate in children as they are in adults, although there have been no studies of the combined calculation of distance and heading that typifies naturalistic path integration. In the present study 5-year-olds and 7-year-olds took part in a triangle-completion task, where they were required to return to the startpoint of a multi-element path using only idiothetic information. Performance was compared to a sample of adult participants, who were found to be more accurate than children on measures of landing error, heading error, and distance error. 7-year-olds were significantly more accurate than 5-year-olds on measures of landing error and heading error, although the difference between groups was much smaller for distance error. All measures were reliably correlated with age, demonstrating a clear development of path integration abilities within the age range tested. Taken together, these data make a strong case for the inclusion of path integration within developmental models of spatial navigational processing

    Mechanical activation of vinculin binding to talin locks talin in an unfolded conformation

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    The force-dependent interaction between talin and vinculin plays a crucial role in the initiation and growth of focal adhesions. Here we use magnetic tweezers to characterise the mechano-sensitive compact N-terminal region of the talin rod, and show that the three helical bundles R1-R3 in this region unfold in three distinct steps consistent with the domains unfolding independently. Mechanical stretching of talin R1-R3 enhances its binding to vinculin and vinculin binding inhibits talin refolding after force is released. Mutations that stabilize R3 identify it as the initial mechano-sensing domain in talin, unfolding at ~5 pN, suggesting that 5 pN is the force threshold for vinculin binding and adhesion progression

    Is the superior verbal memory span of Mandarin speakers due to faster rehearsal?

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    It is well established that digit span in native Chinese speakers is atypically high. This is commonly attributed to a capacity for more rapid subvocal rehearsal for that group. We explored this hypothesis by testing a group of English-speaking native Mandarin speakers on digit span and word span in both Mandarin and English, together with a measure of speed of articulation for each. When compared to the performance of native English speakers, the Mandarin group proved to be superior on both digit and word spans while predictably having lower spans in English. This suggests that the Mandarin advantage is not limited to digits. Speed of rehearsal correlated with span performance across materials. However, this correlation was more pronounced for English speakers than for any of the Chinese measures. Further analysis suggested that speed of rehearsal did not provide an adequate account of differences between Mandarin and English spans or for the advantage of digits over words. Possible alternative explanations are discussed

    Genetic contributions to visuospatial cognition in Williams syndrome: insights from two contrasting partial deletion patients

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    Background Williams syndrome (WS) is a rare neurodevelopmental disorder arising from a hemizygotic deletion of approximately 27 genes on chromosome 7, at locus 7q11.23. WS is characterised by an uneven cognitive profile, with serious deficits in visuospatial tasks in comparison to relatively proficient performance in some other cognitive domains such as language and face processing. Individuals with partial genetic deletions within the WS critical region (WSCR) have provided insights into the contribution of specific genes to this complex phenotype. However, the combinatorial effects of different genes remain elusive. Methods We report on visuospatial cognition in two individuals with contrasting partial deletions in the WSCR: one female (HR), aged 11 years 9 months, with haploinsufficiency for 24 of the WS genes (up to GTF2IRD1), and one male (JB), aged 14 years 2 months, with the three most telomeric genes within the WSCR deleted, or partially deleted. Results Our in-depth phenotyping of the visuospatial domain from table-top psychometric, and small- and large-scale experimental tasks reveal a profile in HR in line with typically developing controls, albeit with some atypical features. These data are contrasted with patient JB’s atypical profile of strengths and weaknesses across the visuospatial domain, as well as with more substantial visuospatial deficits in individuals with the full WS deletion. Conclusions Our findings point to the contribution of specific genes to spatial processing difficulties associated with WS, highlighting the multifaceted nature of spatial cognition and the divergent effects of genetic deletions within the WSCR on different components of visuospatial ability. The importance of general transcription factors at the telomeric end of the WSCR, and their combinatorial effects on the WS visuospatial phenotype are also discussed

    Maternal neurofascin-specific autoantibodies bind to structures of the fetal nervous system during pregnancy, but have no long term effect on development in the rat

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    Neurofascin was recently reported as a target for axopathic autoantibodies in patients with multiple sclerosis (MS), a response that will exacerbate axonal pathology and disease severity in an animal model of multiple sclerosis. As transplacental transfer of maternal autoantibodies can permanently damage the developing nervous system we investigated whether intrauterine exposure to this neurofascin-specific response had any detrimental effect on white matter tract development. To address this question we intravenously injected pregnant rats with either a pathogenic anti-neurofascin monoclonal antibody or an appropriate isotype control on days 15 and 18 of pregnancy, respectively, to mimic the physiological concentration of maternal antibodies in the circulation of the fetus towards the end of pregnancy. Pups were monitored daily with respect to litter size, birth weight, growth and motor development. Histological studies were performed on E20 embryos and pups sacrificed on days 2, 10, 21, 32 and 45 days post partum. Results: Immunohistochemistry for light and confocal microscopy confirmed passively transferred anti-neurofascin antibody had crossed the placenta to bind to distinct structures in the developing cortex and cerebellum. However, this did not result in any significant differences in litter size, birth weight, or general physical development between litters from control mothers or those treated with the neurofascin-specific antibody. Histological analysis also failed to identify any neuronal or white matter tract abnormalities induced by the neurofascin-specific antibody. Conclusions: We show that transplacental transfer of circulating anti-neurofascin antibodies can occur and targets specific structures in the CNS of the developing fetus. However, this did not result in any pre- or post-natal abnormalities in the offspring of the treated mothers. These results assure that even if anti-neurofascin responses are detected in pregnant women with multiple sclerosis these are unlikely to have a negative effect on their children

    The Change Up Project : using social norming theory with young people to address domestic abuse and promote healthy relationships

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    This paper presents the findings of a secondary analysis of data collected during a pilot project, Change Up, which used a social norming approach (SNA) to address domestic violence and abuse (DVA) with young people aged 13–14. A SNA is based upon a well-articulated theory of behavior and evidence-based methodology for addressing social justice issues. This reflects a paradigm shift focusing upon strengths and positives, rather than pathologizing behaviours. Adopting a SNA, the Change Up project comprised a baseline survey followed by the intervention (workshop and peer-to-peer campaign), ending with a post-intervention survey. It was delivered in two high schools in a UK city between 2015 and 16. A secondary analysis of the survey data collected during the surveys and qualitative data collected at the end of each workshop was undertaken and this is reported here. Change Up data illustrates that most young people in the sample thought that DVA is unacceptable. There was, however, a gender difference in the norms held about the social acceptability of girls using physical violence against boys (and vice versa). The analysis of Change Up data indicates that a social norming approach to DVA programs aimed at young people can be successful in promoting attitude and behaviour change. It also highlights a continuing need for young people’s education about relationships and gender equality

    Identifying unmet clinical need in hypertrophic cardiomyopathy using national electronic health records

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    Introduction: To evaluate unmet clinical need in unselected hypertrophic cardiomyopathy (HCM) patients to determine the risk of a wide range of subsequent cardiovascular disease endpoints and safety endpoints relevant for trial design. Methods: Population based cohort (CALIBER, linked primary care, hospital and mortality records in England, period 1997–2010), all people diagnosed with HCM were identified and matched by age, sex and general practice with ten randomly selected people without HCM. Random-effects Poisson models were used to assess the associations between HCM and cardiovascular diseases and bleeding. Results: Among 3,290,455 eligible people a diagnosis of hypertrophic cardiomyopathy was found in 4 per 10,000. Forty-one percent of the 1,160 individuals with hypertrophic cardiomyopathy were women and the median age was 57 years. The median follow-up was 4.0 years. Compared to general population controls, people with HCM had higher risk of ventricular arrhythmia (incidence rate ratio = 23.53, [95% confidence interval 12.67–43.72]), cardiac arrest or sudden cardiac death (6.33 [3.69–10.85]), heart failure (4.31, [3.30–5.62]), and atrial fibrillation (3.80 [3.04–4.75]). HCM was also associated with a higher incidence of myocardial infarction ([MI] 1.90 [1.27–2.84]) and coronary revascularisation (2.32 [1.46–3.69]).The absolute Kaplan-Meier risks at 3 years were 8.8% for the composite endpoint of cardiovascular death or heart failure, 8.4% for the composite of cardiovascular death, stroke or myocardial infarction, and 1.5% for major bleeding. Conclusions: Our study identified major unmet need in HCM and highlighted the importance of implementing improved cardiovascular prevention strategies to increase life-expectancy of the contemporary HCM population. They also show that national electronic health records provide an effective method for identifying outcomes and clinically relevant estimates of composite efficacy and safety endpoints essential for trial design in rare diseases

    Health-related and overall quality of life of patients with chronic hip and knee complaints in general practice

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    BACKGROUND: Information about quality of life of patients with chronic hip or knee complaints in general practice is scarce. This study describes the health-related and overall quality of life (HRQL) of these complaints. METHODS: Data were obtained from a cohort study in general practice. HRQL at three months follow-up was analysed. HRQL was measured as: symptoms, physical, psychological and social functioning, and general health perceptions, using the Western Ontario and McMaster Universities osteoarthritis index (WOMAC) and the MOS 36-item short-form-health survey (SF-36). Overall quality of life was measured using a 5-point rating scale. RESULTS: The results show that patients with chronic hip or knee complaints have a substantial lower HRQL compared to patients who had recovered from baseline hip or knee complaints. The largest effect was found on symptoms and physical functioning: up to 2.9 standard deviations below patients who had recovered from baseline hip or knee complaints. Scores of patients with both chronic hip and knee complaints were significantly worse than scores of patients with only knee complaints on most subscales. CONCLUSION: In patients with chronic hip or knee complaints the worst scores were seen on scales that measure symptoms and physical functioning, but still a substantially lower score was obtained for overall quality of life. Quality of life was poorer for patients with both chronic hip and knee complaints compared to those with chronic hip or knee complaints onl
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