HbA1c, diabetes and cognitive decline: the English Longitudinal Study of Ageing.

AIMS/HYPOTHESIS: The aim of the study was to evaluate longitudinal associations between HbA1c levels, diabetes status and subsequent cognitive decline over a 10 year follow-up period. METHODS: Data from wave 2 (2004-2005) to wave 7 (2014-2015) of the English Longitudinal Study of Ageing (ELSA) were analysed. Cognitive function was assessed at baseline (wave 2) and reassessed every 2 years at waves 3-7. Linear mixed models were used to evaluate longitudinal associations. RESULTS: The study comprised 5189 participants (55.1% women, mean age 65.6 ± 9.4 years) with baseline HbA1c levels ranging from 15.9 to 126.3 mmol/mol (3.6-13.7%). The mean follow-up duration was 8.1 ± 2.8 years and the mean number of cognitive assessments was 4.9 ± 1.5. A 1 mmol/mol increment in HbA1c was significantly associated with an increased rate of decline in global cognitive z scores (-0.0009 SD/year, 95% CI -0.0014, -0.0003), memory z scores (-0.0005 SD/year, 95% CI -0.0009, -0.0001) and executive function z scores (-0.0008 SD/year, 95% CI -0.0013, -0.0004) after adjustment for baseline age, sex, total cholesterol, HDL-cholesterol, triacylglycerol, high-sensitivity C-reactive protein, BMI, education, marital status, depressive symptoms, current smoking, alcohol consumption, hypertension, CHD, stroke, chronic lung disease and cancer. Compared with participants with normoglycaemia, the multivariable-adjusted rate of global cognitive decline associated with prediabetes and diabetes was increased by -0.012 SD/year (95% CI -0.022, -0.002) and -0.031 SD/year (95% CI -0.046, -0.015), respectively (p for trend <0.001). Similarly, memory, executive function and orientation z scores showed an increased rate of cognitive decline with diabetes. CONCLUSIONS/INTERPRETATION: Significant longitudinal associations between HbA1c levels, diabetes status and long-term cognitive decline were observed in this study. Future studies are required to determine the effects of maintaining optimal glucose control on the rate of cognitive decline in people with diabetes

Large deformation of spherical vesicle studied by perturbation theory and Surface evolver

With tangent angle perturbation approach the axial symmetry deformation of a spherical vesicle in large under the pressure changes is studied by the elasticity theory of Helfrich spontaneous curvature model.Three main results in axial symmetry shape: biconcave shape, peanut shape, and one type of myelin are obtained. These axial symmetry morphology deformations are in agreement with those observed in lipsome experiments by dark-field light microscopy [Hotani, J. Mol. Biol. 178, (1984) 113] and in the red blood cell with two thin filaments (myelin) observed in living state (see, Bessis, Living Blood Cells and Their Ultrastructure, Springer-Verlag, 1973). Furthermore, the biconcave shape and peanut shape can be simulated with the help of a powerful software, Surface Evolver [Brakke, Exp. Math. 1, 141 (1992) 141], in which the spontaneous curvature can be easy taken into account.Comment: 16 pages, 6 EPS figures and 2 PS figure

Imprint of the stochastic nature of photon emission by electrons on the proton energy spectra in the laser-plasma interaction

The impact of stochasticity effects (SEs) in photon emissions on the proton energy spectra during laser-plasma interaction is theoretically investigated in the quantum radiation-dominated regime, which may facilitate SEs experimental observation. We calculate the photon emissions quantum mechanically and the plasma dynamics semiclassically via two-dimensional particle-in-cell simulations. An ultrarelativistic plasma generated and driven by an ultraintense laser pulse head-on collides with another strong laser pulse, which decelerates the electrons due to radiation-reaction effect and results in a significant compression of the proton energy spectra because of the charge separation force. In the considered regime the SEs are demonstrated in the shift of the mean energy of the protons up to hundreds of MeV. This effect is robust with respect to the laser and target parameters and measurable in soon available strong laser facilities

PBRM1 acts as a p53 lysine-acetylation reader to suppress renal tumor growth.

p53 acetylation is indispensable for its transcriptional activity and tumor suppressive function. However, the identity of reader protein(s) for p53 acetylation remains elusive. PBRM1, the second most highly mutated tumor suppressor gene in kidney cancer, encodes PBRM1. Here, we identify PBRM1 as a reader for p53 acetylation on lysine 382 (K382Ac) through its bromodomain 4 (BD4). Notably, mutations on key residues of BD4 disrupt recognition of p53 K382Ac. The mutation in BD4 also reduces p53 binding to promoters of target genes such as CDKN1A (p21). Consequently, the PBRM1 BD4 mutant fails to fully support p53 transcriptional activity and is defective as a tumor suppressor. We also find that expressions of PBRM1 and p21 correlate with each other in human kidney cancer samples. Our findings uncover a tumor suppressive mechanism of PBRM1 in kidney cancer and provide a mechanistic insight into the crosstalk between p53 and SWI/SNF complexes

Multistage Random Growing Small-World Networks with Power-law degree Distribution

In this paper, a simply rule that generates scale-free networks with very large clustering coefficient and very small average distance is presented. These networks are called {\bf Multistage Random Growing Networks}(MRGN) as the adding process of a new node to the network is composed of two stages. The analytic results of power-law exponent $\gamma=3$ and clustering coefficient $C=0.81$ are obtained, which agree with the simulation results approximately. In addition, the average distance of the networks increases logarithmical with the number of the network vertices is proved analytically. Since many real-life networks are both scale-free and small-world networks, MRGN may perform well in mimicking reality.Comment: 3 figures, 4 page

Magnetoconductivity of Dirac fermions in graphene under charged impurity scatterings

On the basis of self-consistent Born approximation, we solve the Bethe-Salpeter matrix equations for Cooperon propagator of the Dirac fermions in graphene under the charged impurity scatterings and a weak external magnetic field. In the absence of the magnetic field, the quantum interference effect in the electric conductivity from the contribution of Cooperon propagator will be studied and possible weak localization in the system is discussed in terms of the sample length and temperature. The magnetoconductivity stemming from the quantum interference effect is calculated, and the obtained results are in good agreement with experimental measurements.Comment: 13 pages, 9 figure