Evaluation of air-displacement plethysmography in children aged 5-7 years using a three-component model of body composition

The aim of the present study was to evaluate air-displacement plethysmography (ADP) in children aged 5-7 years. Body-composition measurements were obtained by ADP, H-2 dilution and anthropometry in twenty-eight children. Calculation of body volume by ADP was undertaken using adult and children's equations for predicting lung volume and surface area. Fat-free mass (FFM) was calculated using a three-component model. Measured FFM hydration was then compared with values from the reference child. Differences between measured and reference hydration were back-extrapolated, to calculate the error in ADP that would account for any disagreement. Propagation of error was used to distinguish the contributions of methodological precision and biological variability to total hydration variability. The use of children's equations influenced the results for lung volume but not surface area. The mean difference between measured and reference hydration was 0.6 (SD 1.7) % (P<0.10), equivalent to an error in body volume of 0.04 (So 0.20) litres (P<0.30), and in percentage fat of 0.4 (SD 1.9) (P<0.28). The limits of agreement in individuals could be attributed to methodological precision and biological variability in hydration. It is concluded that accuracy of ADP was high for the whole group, with a mean bias of <0.5% fat using the three-component model, and after taking into account biological variability in hydration, the limits of agreement were around 2 % fat in individuals. Paediatric rather than adult equations for lung volume estimation should be used

In vitro and in vivo modification of Neisseria gonorrhoeae lipooligosaccharide epitope structure by sialylation.

After growth of gonococci in the presence of cytidine monophospho-N-acetyl-neuraminic acid (CMP-NANA), their 4.5-kD lipooligosaccharide (LOS) component was increased by approximately 400 daltons, whereas the LOS of strains lacking the 4.5-kD component were unaffected. Expression of mAb-defined epitopes on the 4.5-kD component was decreased on LOS of strains grown in CMP-NANA, and treatment of the LOS with neuraminidase reversed this affect. Gonococci incubated with human PMNs also had decreased expression of the 4.5-kD+ epitopes. A detergent extract of gonococci incorporated radiolabeled NANA in the LOS, suggesting the presence of a sialyltransferase in gonococci. Exogenous sialyltransferases also could use LOS as an acceptor

Longest Common Extensions in Sublinear Space

The longest common extension problem (LCE problem) is to construct a data structure for an input string $T$ of length $n$ that supports LCE$(i,j)$ queries. Such a query returns the length of the longest common prefix of the suffixes starting at positions $i$ and $j$ in $T$. This classic problem has a well-known solution that uses $O(n)$ space and $O(1)$ query time. In this paper we show that for any trade-off parameter $1 \leq \tau \leq n$, the problem can be solved in $O(\frac{n}{\tau})$ space and $O(\tau)$ query time. This significantly improves the previously best known time-space trade-offs, and almost matches the best known time-space product lower bound.Comment: An extended abstract of this paper has been accepted to CPM 201

Triggering Cell Stress and Death Using Conventional UV Laser Confocal Microscopy.

Using a standard confocal setup, a UV ablation method can be utilized to selectively induce cellular injury and to visualize single-cell responses and cell-cell interactions in the CNS in real-time. Previously, studying these cell-specific responses after injury often required complicated setups or the transfer of cells or animals into different, non-physiological environments, confounding immediate and short-term analysis. For example, drug-mediated ablation approaches often lack the specificity that is required to study single-cell responses and immediate cell-cell interactions. Similarly, while high-power pulsed laser ablation approaches provide very good control and tissue penetration, they require specialized equipment that can complicate real-time visualization of cellular responses. The refined UV laser ablation approach described here allows researchers to stress or kill an individual cell in a dose- and time-dependent manner using a conventional confocal microscope equipped with a 405-nm laser. The method was applied to selectively ablate a single neuron within a dense network of surrounding cells in the zebrafish spinal cord. This approach revealed a dose-dependent response of the ablated neurons, causing the fragmentation of cellular bodies and anterograde degeneration along the axon within minutes to hours. This method allows researchers to study the fate of an individual dying cell and, importantly, the instant response of cells-such as microglia and astrocytes-surrounding the ablation site

Diffuse axonal injury predicts neurodegeneration after moderate-severe traumatic brain injury

Traumatic brain injury is associated with elevated rates of neurodegenerative diseases such as Alzheimer's disease and chronic traumatic encephalopathy. In experimental models, diffuse axonal injury triggers post-traumatic neurodegeneration, with axonal damage leading to Wallerian degeneration and toxic proteinopathies of amyloid and hyperphosphorylated tau. However, in humans the link between diffuse axonal injury and subsequent neurodegeneration has yet to be established. Here we test the hypothesis that the severity and location of diffuse axonal injury predicts the degree of progressive post-traumatic neurodegeneration. We investigated longitudinal changes in 55 patients in the chronic phase after moderate-severe traumatic brain injury and 19 healthy control subjects. Fractional anisotropy was calculated from diffusion tensor imaging as a measure of diffuse axonal injury. Jacobian determinant atrophy rates were calculated from serial volumetric T1 scans as a measure of measure post-traumatic neurodegeneration. We explored a range of potential predictors of longitudinal post-traumatic neurodegeneration and compared the variance in brain atrophy that they explained. Patients showed widespread evidence of diffuse axonal injury, with reductions of fractional anisotropy at baseline and follow-up in large parts of the white matter. No significant changes in fractional anisotropy over time were observed. In contrast, abnormally high rates of brain atrophy were seen in both the grey and white matter. The location and extent of diffuse axonal injury predicted the degree of brain atrophy: fractional anisotropy predicted progressive atrophy in both whole-brain and voxelwise analyses. The strongest relationships were seen in central white matter tracts, including the body of the corpus callosum, which are most commonly affected by diffuse axonal injury. Diffuse axonal injury predicted substantially more variability in white matter atrophy than other putative clinical or imaging measures, including baseline brain volume, age, clinical measures of injury severity and microbleeds (>50% for fractional anisotropy versus <5% for other measures). Grey matter atrophy was not predicted by diffuse axonal injury at baseline. In summary, diffusion MRI measures of diffuse axonal injury are a strong predictor of post-traumatic neurodegeneration. This supports a causal link between axonal injury and the progressive neurodegeneration that is commonly seen after moderate/severe traumatic brain injury but has been of uncertain aetiology. The assessment of diffuse axonal injury with diffusion MRI is likely to improve prognostic accuracy and help identify those at greatest neurodegenerative risk for inclusion in clinical treatment trials

Chromium isotopes in marine hydrothermal sediments

Hydrothermal chromium (Cr) cycling contributes to marine Cr inventories and their Cr isotopic composition, yet Cr isotope effects associated with this cycling remain poorly documented. Here we determine the distribution, isotopic composition, and diagenetic mobility of Cr in hydrothermal sediments from the distal flank of the South East Pacific Rise (SEPR, DSDP-site 598). We find that Cr is primarily associated with the metalliferous iron (oxyhydr) oxide and detrital components of the sediment (0.4–3.6 mg kg⁻¹), whereas Cr concentrations are much lower in the dominant carbonate phase (80% Cr from the sediment relative to Fe. We propose this loss is tied to oxidation of authigenic Cr(III) to Cr(VI) followed by diagenetic remobilization and efflux from the sediment pile. The bulk δ⁵³Cr composition of the SEPR sediments is isotopically light (−0.24 to −0.57 ± 0.05‰) and the authigenic δ⁵³Cr is as light as −1.2 ± 0.2‰, and we argue that this light Cr isotopic composition results from the partial reduction of oxic seawater-bearing Cr(VI) by reduced hydrothermal vent fluids enriched in Fe(II)aq. Diagenetic oxidation of the reactive Cr pool by Mn-oxides and loss of Cr(VI) from the sediment may further deplete the sediment in ⁵³Cr during diagenesis. The δ⁵³Cr composition of the detrital Cr fraction of the sediment (average δ⁵³Cr composition = −0.05 ± 0.04‰) falls within the igneous silicate earth (ISE) range, revealing that detrital Cr delivered to this region of the Pacific ocean is unfractionated, and has carried a relatively constant δ⁵³Cr composition over the last 5.7 million years. Together our results show that light δ⁵³Cr compositions in hydrothermal sediments are imparted through a combination of processes previously overlooked in the marine Cr biogeochemical cycle, and that the δ⁵³Cr composition of such sediments may provide a rich source of information on paleo-marine redox conditions

Diffuse axonal injury predicts neurodegeneration after moderate–severe traumatic brain injury

Traumatic brain injury is associated with elevated rates of neurodegenerative diseases such as Alzheimer’s disease and chronic traumatic encephalopathy. In experimental models, diffuse axonal injury triggers post-traumatic neurodegeneration, with axonal damage leading to Wallerian degeneration and toxic proteinopathies of amyloid and hyperphosphorylated tau. However, in humans the link between diffuse axonal injury and subsequent neurodegeneration has yet to be established. Here we test the hypothesis that the severity and location of diffuse axonal injury predicts the degree of progressive post-traumatic neurodegeneration. We investigated longitudinal changes in 55 patients in the chronic phase after moderate–severe traumatic brain injury and 19 healthy control subjects. Fractional anisotropy was calculated from diffusion tensor imaging as a measure of diffuse axonal injury. Jacobian determinant atrophy rates were calculated from serial volumetric T1 scans as a measure of measure post-traumatic neurodegeneration. We explored a range of potential predictors of longitudinal post-traumatic neurodegeneration and compared the variance in brain atrophy that they explained. Patients showed widespread evidence of diffuse axonal injury, with reductions of fractional anisotropy at baseline and follow-up in large parts of the white matter. No significant changes in fractional anisotropy over time were observed. In contrast, abnormally high rates of brain atrophy were seen in both the grey and white matter. The location and extent of diffuse axonal injury predicted the degree of brain atrophy: fractional anisotropy predicted progressive atrophy in both whole-brain and voxelwise analyses. The strongest relationships were seen in central white matter tracts, including the body of the corpus callosum, which are most commonly affected by diffuse axonal injury. Diffuse axonal injury predicted substantially more variability in white matter atrophy than other putative clinical or imaging measures, including baseline brain volume, age, clinical measures of injury severity and microbleeds (>50% for fractional anisotropy versus <5% for other measures). Grey matter atrophy was not predicted by diffuse axonal injury at baseline. In summary, diffusion MRI measures of diffuse axonal injury are a strong predictor of post-traumatic neurodegeneration. This supports a causal link between axonal injury and the progressive neurodegeneration that is commonly seen after moderate/severe traumatic brain injury but has been of uncertain aetiology. The assessment of diffuse axonal injury with diffusion MRI is likely to improve prognostic accuracy and help identify those at greatest neurodegenerative risk for inclusion in clinical treatment trials

Electrochemical communication with the inside of cells using micro-patterned vertical carbon nanofibre electrodes

With the rapidly increasing demands for ultrasensitive biodetection, the design and applications of new nano-scale materials for development of sensors based on optical and electrochemical transducers have attracted substantial interest. In particular, given the comparable sizes of nanomaterials and biomolecules, there exist plenty of opportunities to develop functional nanoprobes with biomolecules for highly sensitive and selective biosensing, shedding new light on cellular behaviour. Towards this aim, herein we interface cells with patterned nano-arrays of carbon nanofibers forming a nanosensor-cell construct. We show that such a construct is capable of electrochemically communicating with the intracellular environment.This work was supported by the Leverhulme Trust [grant numbers F/00 094/BD, ECF/2013-603]; the Biotechnology and Biological Sciences Research Council [grant number BB/L017059/1]; the European Research Council [Consolidator Grant, number 614787], the Engineering and Physical Sciences Research Council [EP/K027263/1]; and the NC3Rs [grant number NC/L00058X/1]

Prevalence and Predictors of Vitamin D Insufficiency in Children: A Great Britain Population Based Study

Objectives To evaluate the prevalence and predictors of vitamin D insufficiency (VDI) in children In Great Britain. Design A nationally representative cross-sectional study survey of children (1102) aged 4–18 years (999 white, 570 male) living in private households (January 1997–1998). Interventions provided information about dietary habits, physical activity, socio-demographics, and blood sample. Outcome measures were vitamin D insufficiency (<50 nmol/L). Results Vitamin D levels (mean = 62.1 nmol/L, 95%CI 60.4–63.7) were insufficient in 35%, and decreased with age in both sexes (p<0.001). Young People living between 53–59 degrees latitude had lower levels (compared with 50–53 degrees, p = 0.045). Dietary intake and gender had no effect on vitamin D status. A logistic regression model showed increased risk of VDI in the following: adolescents (14–18 years old), odds ratio (OR) = 3.6 (95%CI 1.8–7.2) compared with younger children (4–8 years); non white children (OR = 37 [95%CI 15–90]); blood levels taken December-May (OR = 6.5 [95%CI 4.3–10.1]); on income support (OR = 2.2 [95%CI 1.3–3.9]); not taking vitamin D supplementation (OR = 3.7 [95%CI 1.4–9.8]); being overweight (OR 1.6 [95%CI 1.0–2.5]); <1/2 hour outdoor exercise/day/week (OR = 1.5 [95%CI 1.0–2.3]); watched >2.5 hours of TV/day/week (OR = 1.6[95%CI 1.0–2.4]). Conclusion We confirm a previously under-recognised risk of VDI in adolescents. The marked higher risk for VDI in non-white children suggests they should be targeted in any preventative strategies. The association of higher risk of VDI among children who exercised less outdoors, watched more TV and were overweight highlights potentially modifiable risk factors. Clearer guidelines and an increased awareness especially in adolescents are needed, as there are no recommendations for vitamin D supplementation in older children

Distinct patterns of neurodegeneration after TBI and in Alzheimer's disease

Introduction Traumatic brain injury (TBI) is a dementia risk factor, with Alzheimer's disease (AD) more common following injury. Patterns of neurodegeneration produced by TBI can be compared to AD and aging using volumetric MRI. Methods A total of 55 patients after moderate to severe TBI (median age 40), 45 with AD (median age 69), and 61 healthy volunteers underwent magnetic resonance imaging over 2 years. Atrophy patterns were compared. Results AD patients had markedly lower baseline volumes. TBI was associated with increased white matter (WM) atrophy, particularly involving corticospinal tracts and callosum, whereas AD rates were increased across white and gray matter (GM). Subcortical WM loss was shared in AD/TBI, but deep WM atrophy was TBI-specific and cortical atrophy AD-specific. Post-TBI atrophy patterns were distinct from aging, which resembled AD. Discussion Post-traumatic neurodegeneration 1.9–4.0 years (median) following moderate-severe TBI is distinct from aging/AD, predominantly involving central WM. This likely reflects distributions of axonal injury, a neurodegeneration trigger. Highlights We compared patterns of brain atrophy longitudinally after moderate to severe TBI in late-onset AD and healthy aging. Patients after TBI had abnormal brain atrophy involving the corpus callosum and other WM tracts, including corticospinal tracts, in a pattern that was specific and distinct from AD and aging. This pattern is reminiscent of axonal injury following TBI, and atrophy rates were predicted by the extent of axonal injury on diffusion tensor imaging, supporting a relationship between early axonal damage and chronic neurodegeneration