White matter hyperintensities and within-person variability in community-dwelling adults aged 60–64 years

Estimates of white matter hyperintensities (WMH) derived from T2-weighted MRI were investigated in relation to cognitive performance in 469 healthy community-dwelling adults aged 60–64 years. Frontal lobe WMH but not WMH from other brain regions (temporal, parietal, and occipital lobes, anterior and posterior horn, periventricular body) were associated with elevated within-person reaction time (RT) variability (trial to trial fluctuations in RT performance) but not performance on several other cognitive tasks including psychomotor speed, memory, and global cognition. The findings are consistent with the view that elevated within-person variability is related to neurobiological disturbance, and that attentional mechanisms supported by the frontal cortex play a key role in this type of variability

Combined modelling and experimental studies of failure in thick laminates under out-of-plane shear

A multi-scale model validated with out-of-plane shear testing is presented to analyse thick composite structural failure. Key features of this multi-scale analysis approach are inclusion of shear non linearity and modelling the response at a sub-laminate level whilst the structural failure is predicted at a ply level. Based on this multi-scale approach, a user-defined FORTRAN subroutine (VUMAT) has been written for ABAQUS/EXPLICIT solver and is used to model the shear nonlinearity and intra-laminar failure. In addition, a cohesive zone model is used to predict the inter-laminar delamination. The modelling has been employed to predict the failure processes for Iosipescu shear test specimens with different fibre orientations. The results show that both the failure mode and the load-displacement trace for finite element simulations agree closely with the experimental findings. This demonstrates the validity of this multi-scale, nonlinear, three-dimensional model for thick laminates. In particular, for the Iosepescu shear test, the effect of the fibres being aligned along the length of the specimen or out-of-plane is investigated as well as different dimensions of the specimen. These simulations are validated by experiments using Digital Image Correlation (DIC)

A provisional database for the silicon content of foods in the United Kingdom

Si may play an important role in bone formation and connective tissue metabolism. Although biological interest in this element has recently increased, limited literature exists on the Si content of foods. To further our knowledge and understanding of the relationship between dietary Si and human health, a reliable food composition database, relevant for the UK population, is required. A total of 207 foods and beverages, commonly consumed in the UK, were analysed for Si content. Composite samples were analysed using inductively coupled plasma&ndash;optical emission spectrometry following microwave-assisted digestion with nitric acid and H2O2. The highest concentrations of Si were found in cereals and cereal products, especially less refined cereals and oat-based products. Fruit and vegetables were highly variable sources of Si with substantial amounts present in Kenyan beans, French beans, runner beans, spinach, dried fruit, bananas and red lentils, but undetectable amounts in tomatoes, oranges and onions. Of the beverages, beer, a macerated whole-grain cereal product, contained the greatest level of Si, whilst drinking water was a variable source with some mineral waters relatively high in Si. The present study provides a provisional database for the Si content of UK foods, which will allow the estimation of dietary intakes of Si in the UK population and investigation into the role of dietary Si in human health.<br /

Modifying the osteoblastic niche with zoledronic acid in vivo - potential implications for breast cancer bone metastasis

INTRODUCTION: Bone metastasis is the most common complication of advanced breast cancer. The associated cancer-induced bone disease is treated with bone-sparing agents like zoledronic acid. Clinical trials have shown that zoledronic acid also reduces breast cancer recurrence in bone; potentially by modifying the bone microenvironment surrounding disseminated tumour cells. We have characterised the early effects of zoledronic acid on key cell types of the metastatic niche in vivo, and investigated how these modify the location of breast tumour cells homing to bone. METHODS: Female mice were treated with a single, clinically achievable dose of zoledronic acid (100μg/kg) or PBS. Bone integrity, osteoclast and osteoblast activity and number/mm trabecular bone on 1, 3, 5 and 10days after treatment were assessed using μCT, ELISA (TRAP, PINP) and bone histomorphometry, respectively. The effect of zoledronic acid on osteoblasts was validated in genetically engineered mice with GFP-positive osteoblastic cells. The effects on growth plate cartilage were visualised by toluidine blue staining. For tumour studies, mice were injected i.c. with DID-labelled MDA-MB-231-NW1-luc2 breast cancer cells 5days after zoledronic acid treatment, followed by assessment of tumour cell homing to bone and soft tissues by multiphoton microscopy, flow cytometry and ex vivo cultures. RESULTS: As early as 3days after treatment, animals receiving zoledronic acid had significantly increased trabecular bone volume vs. control. This rapid bone effect was reflected in a significant reduction in osteoclast and osteoblast number/mm trabecular bone and reduced bone marker serum levels (day 3-5). These results were confirmed in mice expressing GFP in osteoblastic linage cells. Pre-treatment with zoledronic acid caused accumulation of an extra-cellular matrix in the growth plate associated with a trend towards preferential [1] homing of tumour cells to osteoblast-rich areas of bone, but without affecting the total number of tumour cells. The number of circulating tumour cells was reduced in ZOL treated animals. CONCLUSION: A single dose of zoledronic acid caused significant changes in the bone area suggested to contain the metastatic niche. Tumour cells arriving in this modified bone microenvironment appeared to preferentially locate to osteoblast-rich areas, supporting that osteoblasts may be key components of the bone metastasis niche and therefore a potential therapeutic target in breast cancer.Marie-Therese Haider, Ingunn Holen, T. Neil Dear, Keith Hunter, Hannah K. Brow

On the extent of fracture toughness transfer from 1D/2D nanomodified epoxy matrices to glass fibre composites

Abstract: In this study, the effects of adding nanofillers to an epoxy resin (EP) used as a matrix in glass fibre-reinforced plastic (GFRP) composites have been investigated. Both 1D and 2D nanofillers were used, specifically (1) carbon nanotubes (CNTs), (2) few-layer graphene nanoplatelets (GNPs), as well as hybrid combinations of (3) CNTs and boron nitride nanosheets, and (4) GNPs and boron nitride nanotubes (BNNTs). Tensile tests have shown improvements in the transverse stiffness normal to the fibre direction of up to about 25% for the GFRPs using the ‘EP + CNT’ and the ‘EP + BNNT + GNP’ matrices, compared to the composites with the unmodified epoxy (‘EP’). Mode I and mode II fracture toughness tests were conducted using double cantilever beam (DCB) and end-notched flexure (ENF) tests, respectively. In the quasi-static mode I tests, the values of the initiation interlaminar fracture toughness, GICC, of the GFRP composites showed that the transfer of matrix toughness to the corresponding GFRP composite is greatest for the GFRP composite with the GNPs in the matrix. Here, a coefficient of toughness transfer (CTT), defined as the ratio of mode I initiation interlaminar toughness for the composite to the bulk polymer matrix toughness, of 0.68 was recorded. The highest absolute values of the mode I interlaminar fracture toughness at crack initiation were achieved for the GFRP composites with the epoxy matrix modified with the hybrid combinations of nanofillers. The highest value of the CTT during steady-state crack propagation was ~ 2 for all the different types of GFRPs. Fractographic analysis of the composite surfaces from the DCB and ENF specimens showed that failure was by a combination of cohesive (through the matrix) and interfacial (along the fibre/matrix interface) modes, depending on the type of nanofillers used

Access to Drinking-water and Arsenicosis in Bangladesh

The discovery of arsenic contamination in groundwater has challenged efforts to provide safe drinking-water to households in rural Bangladesh. Two nationally-representative surveys in 2000 and 2002 investigated water-usage patterns, water-testing, knowledge of arsenic poisoning, and behavioural responses to arsenic contamination. Knowledge of arsenicosis rose between the two surveys among women from 42% to 64% but awareness of consequences of arsenic remained limited; only 13% knew that it could lead to death. Behavioural responses to arsenic have been limited, probably in part because of the lack of concern but also because households are uncertain of how best to respond and have a strong preference for tubewell water even when wells are known to be contaminated. Further work conducted by the survey team highlighted the difficulties in providing alternative sources of water, with many households switching back to their original sources of water

Dynamics of oligomer populations formed during the aggregation of Alzheimer's Aβ42 peptide

Oligomeric species populated during the aggregation of the Aβ42 peptide have been identified as potent cytotoxins linked to Alzheimer’s disease, but the fundamental molecular pathways that control their dynamics have yet to be elucidated. By developing a general approach that combines theory, experiment and simulation, we reveal, in molecular detail, the mechanisms of Aβ42 oligomer dynamics during amyloid fibril formation. Even though all mature amyloid fibrils must originate as oligomers, we found that most Aβ42 oligomers dissociate into their monomeric precursors without forming new fibrils. Only a minority of oligomers converts into fibrillar structures. Moreover, the heterogeneous ensemble of oligomeric species interconverts on timescales comparable to those of aggregation. Our results identify fundamentally new steps that could be targeted by therapeutic interventions designed to combat protein misfolding diseases

Setting the stage for acute-on-chronic kidney injury

Acute-on-chronic kidney disease will be familiar to many nephrologists. Hsu et al. quantify the risk of acute-on-chronic disease across the stages of preexisting chronic kidney disease. Their study demonstrates the valuable insights that large epidemiological studies can bring to the field of acute kidney injury

DN interaction from meson exchange

A model of the DN interaction is presented which is developed in close analogy to the meson-exchange KbarN potential of the Juelich group utilizing SU(4) symmetry constraints. The main ingredients of the interaction are provided by vector meson (rho, omega) exchange and higher-order box diagrams involving D*N, D\Delta, and D*\Delta intermediate states. The coupling of DN to the pi-Lambda_c and pi-Sigma_c channels is taken into account. The interaction model generates the Lambda_c(2595) resonance dynamically as a DN quasi-bound state. Results for DN total and differential cross sections are presented and compared with predictions of an interaction model that is based on the leading-order Weinberg-Tomozawa term. Some features of the Lambda_c(2595) resonance are discussed and the role of the near-by pi-Sigma_c threshold is emphasized. Selected predictions of the orginal KbarN model are reported too. Specifically, it is pointed out that the model generates two poles in the partial wave corresponding to the Lambda(1405) resonance.Comment: 14 pages, 8 figure