Cerebellar and brainstem differences in children with developmental coordination disorder: A voxel-based morphometry study

Developmental coordination disorder (DCD) is a neurodevelopmental disorder that significantly impairs a child’s ability to learn motor skills and to perform everyday activities. The cause of DCD is unknown; however, evidence suggests that children with DCD have altered brain structure and function. While the cerebellum has been hypothesised to be involved in developmental coordination disorder, no studies have specifically examined cerebellar structure in this population. The purpose of our study was to examine cerebellar differences in children with DCD compared to typically-developing children. Using voxel-based morphometry, we assessed cerebellar morphology in children 8–12 years of age. Forty-six children (12 typically-developing and 34 with DCD) were investigated using high resolution T1-weighted images, which were then processed using the spatially unbiased atlas template of the cerebellum and brainstem (SUIT) toolbox for a region of interest-based examination of the cerebellum. Results revealed that children with DCD had reduced grey matter volume in several regions, namely: the brainstem, right/left crus I, right crus II, left VI, right VIIb, and right VIIIa lobules. Further, Pearson correlations revealed significant positive associations between the total motor percentile score on the Movement Assessment Battery for Children-2 and regions that had reduced grey matter volume in our cohort (brainstem, left crus I, right VIIb, and right VIIIa). These findings indicate that reductions in cerebellar grey matter volume are associated with poorer motor skills. Given the cerebellum’s involvement in internal models of movement, results of this study may help to explain why children with DCD struggle to learn motor skills

Adapting a practical EPR dosimetry protocol to measure output factors in small fields with alanine.

PURPOSE Modern radiotherapy techniques often deliver small radiation fields. In this work, a practical Electron Paramagnetic Resonance (EPR) dosimetry protocol is adapted and applied to measure output factors (OF) in small fields of a 6 MV radiotherapy system. Correction factors and uncertainties are presented and OFs are compared to the values obtained by following TRS-483 using an ionization chamber (IC). METHODS Irradiations were performed at 10 cm depth inside a water phantom positioned at 90 cm source to surface distance with a 6 MV flattening filter free photon beam of a Halcyon radiotherapy system. OFs for different nominal field sizes (1 × 1, 2 × 2, 3 × 3, 4 × 4, normalized to 10 × 10 cm2 ) were determined with a PinPoint 3D (PTW 31022) IC following TRS-483 as well as with alanine pellets with a diameter of 4 mm and a height of 2.4 mm. EPR readout was performed with a benchtop X-band spectrometer. Correction factors due to volume averaging and due to positional uncertainties were derived from 2D film measurements. RESULTS OFs obtained from both dosimeter types agreed within 0.7% after applying corrections for the volume averaging effect. For the used alanine pellets, volume averaging correction factors of 1.030(2) for the 1 × 1 cm2 field and <1.002 for the larger field sizes were determined. The correction factor for positional uncertainties of 1 mm was in the order of 1.018 for the 1 × 1 cm2 field. Combined relative standard uncertainties uc for the OFs resulting from alanine measurements were estimated to be below 1.5% for all field sizes. For IC measurements, uc was estimated to be below 1.0%. CONCLUSIONS A practical EPR dosimetry protocol is adaptable for precisely measuring OFs in small fields down to 1 × 1 cm2 . It is recommended to consider the effect of positional uncertainties for field sizes <2 × 2 cm2

Robust circadian clocks from coupled protein modification and transcription-translation cycles

The cyanobacterium Synechococcus elongatus uses both a protein phosphorylation cycle and a transcription-translation cycle to generate circadian rhythms that are highly robust against biochemical noise. We use stochastic simulations to analyze how these cycles interact to generate stable rhythms in growing, dividing cells. We find that a protein phosphorylation cycle by itself is robust when protein turnover is low. For high decay or dilution rates (and co mpensating synthesis rate), however, the phosphorylation-based oscillator loses its integrity. Circadian rhythms thus cannot be generated with a phosphorylation cycle alone when the growth rate, and consequently the rate of protein dilution, is high enough; in practice, a purely post-translational clock ceases to function well when the cell doubling time drops below the 24 hour clock period. At higher growth rates, a transcription-translation cycle becomes essential for generating robust circadian rhythms. Interestingly, while a transcription-translation cycle is necessary to sustain a phosphorylation cycle at high growth rates, a phosphorylation cycle can dramatically enhance the robustness of a transcription-translation cycle at lower protein decay or dilution rates. Our analysis thus predicts that both cycles are required to generate robust circadian rhythms over the full range of growth conditions.Comment: main text: 7 pages including 5 figures, supplementary information: 13 pages including 9 figure

Fusion In The Era Of Burning Plasma Studies: Workforce Planning For 2004-2014

This is the final report of a panel set up by the U.S. Department of Energy (DOE) Fusion Energy Sciences Advisory Committee (FESAC) in response to a charge letter from Dr. Raymond Orbach (Appendix A), asking FESAC to addressed the issue of workforce development in the U.S. fusion program. This report, submitted to FESAC March 29, 2004 and subsequently approved by them (Appendix B), presents FESAC\u27s response to that charge

Tract-Based Spatial Statistics in Preterm-Born Neonates Predicts Cognitive and Motor Outcomes at 18 Months.

BACKGROUND AND PURPOSE: Adverse neurodevelopmental outcome is common in children born preterm. Early sensitive predictors of neurodevelopmental outcome such as MR imaging are needed. Tract-based spatial statistics, a diffusion MR imaging analysis method, performed at term-equivalent age (40 weeks) is a promising predictor of neurodevelopmental outcomes in children born very preterm. We sought to determine the association of tract-based spatial statistics findings before term-equivalent age with neurodevelopmental outcome at 18-months corrected age. MATERIALS AND METHODS: Of 180 neonates (born at 24-32-weeks\u27 gestation) enrolled, 153 had DTI acquired early at 32 weeks\u27 postmenstrual age and 105 had DTI acquired later at 39.6 weeks\u27 postmenstrual age. Voxelwise statistics were calculated by performing tract-based spatial statistics on DTI that was aligned to age-appropriate templates. At 18-month corrected age, 166 neonates underwent neurodevelopmental assessment by using the Bayley Scales of Infant Development, 3rd ed, and the Peabody Developmental Motor Scales, 2nd ed. RESULTS: Tract-based spatial statistics analysis applied to early-acquired scans (postmenstrual age of 30-33 weeks) indicated a limited significant positive association between motor skills and axial diffusivity and radial diffusivity values in the corpus callosum, internal and external/extreme capsules, and midbrain (P \u3c .05, corrected). In contrast, for term scans (postmenstrual age of 37-41 weeks), tract-based spatial statistics analysis showed a significant relationship between both motor and cognitive scores with fractional anisotropy in the corpus callosum and corticospinal tracts (P \u3c .05, corrected). Tract-based spatial statistics in a limited subset of neonates (n = 22) scanned at CONCLUSIONS: The strength of the association between fractional anisotropy values and neurodevelopmental outcome scores increased from early-to-late-acquired scans in preterm-born neonates, consistent with brain dysmaturation in this population

Patchy Progress On Obesity Prevention: Emerging Exemplars, Entrenched Barriers, and New Thinking

Although there have been positive pockets of change, no country has yet turned around its obesity epidemic. Preventing an increase in obesity prevalence will require urgent actions from government as well as a broader spectrum of stakeholders than previously emphasized. In this paper, we review a number of regulatory and non-regulatory actions taken around the world to address obesity and discuss some of the reasons for the patchy progress. In addition, we preview the papers in this Lancet series, which each identify priority actions on key obesity issues and challenge some of the entrenched dichotomies that present obesity and its solutions in “either/or” terms. Although obesity is acknowledged as a complex issue, many debates about its causes and solutions are centered around overly simple dichotomies that present seemingly competing perspectives. Examples of such dichotomies explored in this series include: individual versus environmental causes of obesity, personal versus collective responsibilities for actions, supply versus demand explanations for consumption of unhealthy food, government regulation versus industry self-regulation, top down versus bottom up drivers for change, treatment versus prevention priorities, and under versus over nutrition focus. In the current paper, we explore the dichotomy of individual versus environmental drivers of obesity, which lay out two truths: people bear some personal responsibility for their health and environmental factors can readily support or undermine the ability of people to act in their self-interest. We propose a re-framing of obesity that emphasizes the reciprocal nature of the interaction between the environment and individual. Current food environments exploit people’s biological, psychological, social, and economic vulnerabilities, making it easier for them to eat unhealthful foods. This leads to preferences and demands for foods of poor nutritional quality, thus sustaining the unhealthful food environments. Breaking these vicious cycles will need regulatory actions from governments and greater efforts from industry and civil society

Mobilisation of Public Support for Policy Actions to Prevent Obesity

Public mobilisation is needed to enact obesity prevention policies and to mitigate backlash against their implementation. However, current approaches in public health focus primarily on dialogue between public health professionals and political leaders. Strategies to increase popular demand for obesity prevention policies include refining and streamlining public information, identifying effective frames for each population, enhancing media advocacy, building citizen protest and engagement, and developing a receptive political environment with change agents embedded across organisations and sectors. Long-term support and investment in collaboration among diverse stakeholders to create shared value is also important. Each actor in an expanded coalition for obesity prevention can make specific contributions to engaging, mobilising and coalescing the public. Shifting from a top-down to an integrated bottom-up and top-down approach would require an overhaul of current strategies and re-prioritisation of resources