Predictors of risky alcohol consumption in schoolchildren and their implications for preventing alcohol-related harm

BACKGROUND: While alcohol-related health and social problems amongst youths are increasing internationally, both consumption and associated harms are particularly high in British youth. Youth drinking patterns, including bingeing, frequent drinking and drinking in public spaces, are associated with increased risks of acute (e.g. violence) and long-term (e.g. alcohol-dependence) health problems. Here we examine economic, behavioural and demographic factors that predict these risky drinking behaviours among 15-16 year old schoolchildren who consume alcohol. A cross-sectional survey was conducted among schoolchildren in North West England (n = 10,271) using an anonymous questionnaire delivered in school settings. Analysis utilised logistic regression to identify independent predictors of risky drinking behaviour. RESULTS: Of all respondents, 87.9% drank alcohol. Of drinkers, 38.0% usually binged when drinking, 24.4% were frequent drinkers and 49.8% drank in public spaces. Binge, frequent and public drinking were strongly related to expendable income and to individuals buying their own alcohol. Obtaining alcohol from friends, older siblings and adults outside shops were also predictors of risky drinking amongst drinkers. However, being bought alcohol by parents was associated with both lower bingeing and drinking in public places. Membership of youth groups/teams was in general protective despite some association with bingeing. CONCLUSION: Although previous studies have examined predictors of risky drinking, our analyses of access to alcohol and youth income have highlighted eradicating underage alcohol sales and increased understanding of children's spending as key considerations in reducing risky alcohol use. Parental provision of alcohol to children in a family environment may also be important in establishing child-parent dialogues on alcohol and moderating youth consumption. However, this will require supporting parents to ensure they develop only moderate drinking behaviours in their children and only when appropriate

Neuropsychological profiles of vascular disease and risk of dementia: implications for defining vascular cognitive impairment no dementia (VCI-ND)

$\textbf{Background}$ vascular cognitive impairment no dementia (VCI-ND) defines a preclinical phase of cognitive decline associated with vascular disorders. The neuropsychological profile of VCI-ND may vary according to different vascular conditions. $\textbf{Objective}$ to determine the neuropsychological profile of individuals with no dementia and vascular disorders, including hypertension, peripheral vascular disease (PVD), coronary heart disease (CHD), diabetes and stroke. Risk of 2-year incident dementia in individuals with disease and cognitive impairment was also tested. $\textbf{Methods}$ participants were from the Cognitive Function and Ageing Study. At baseline, 13,004 individuals aged ≥65 years were enrolled into the study. Individuals were grouped by baseline disorder status (present, absent) for each condition. Cognitive performance was assessed using the Mini Mental State Examination (MMSE) and the Cambridge Cognitive Examination (CAMCOG). Dementia was assessed at 2 years. $\textbf{Results}$ in the cross-sectional analysis, hypertension, PVD and CHD were not associated with cognitive impairment. Stroke was associated with impaired global (MMSE) and CAMCOG sub-scale (including memory and non-memory) scores. Diabetes was associated with impairments in global cognitive function (MMSE) and abstract thinking. In the longitudinal analysis, cognitive impairments were associated with incident dementia in all groups. $\textbf{Conclusion}$ the neuropsychological profile in individuals with vascular disorders depends on the specific condition investigated. In all conditions cognitive impairment is a risk factor for dementia. A better understanding of which cognitive domains are affected in different disease groups could help improve operationalisation of the neuropsychological criteria for VCI-ND and could also aid with the development of dementia risk prediction models in persons with vascular disease.MRC CFAS has been funded by the Medical Research Council (G9901400) and Department of Health

An evaluation of the clinical and cost-effectiveness of alternative care locations for critically ill adult patients with acute traumatic brain injury.

BACKGROUND: For critically ill adult patients with acute traumatic brain injury (TBI), we assessed the clinical and cost-effectiveness of: (a) Management in dedicated neurocritical care units versus combined neuro/general critical care units within neuroscience centres. (b) 'Early' transfer to a neuroscience centre versus 'no or late' transfer for those who present at a non-neuroscience centre. METHODS: The Risk Adjustment In Neurocritical care (RAIN) Study included prospective admissions following acute TBI to 67 UK adult critical care units during 2009-11. Data were collected on baseline case-mix, mortality, resource use, and at six months, Glasgow Outcome Scale Extended (GOSE), and quality of life (QOL) (EuroQol 5D-3L). We report incremental effectiveness, costs and cost per Quality-Adjusted Life Year (QALY) of the alternative care locations, adjusting for baseline differences with validated risk prediction models. We tested the robustness of results in sensitivity analyses. FINDINGS: Dedicated neurocritical care unit patients (N = 1324) had similar six-month mortality, higher QOL (mean gain 0.048, 95% CI -0.002 to 0.099) and increased average costs compared with those managed in combined neuro/general units (N = 1341), with a lifetime cost per QALY gained of £14,000. 'Early' transfer to a neuroscience centre (N = 584) was associated with lower mortality (odds ratio 0.52, 0.34-0.80), higher QOL for survivors (mean gain 0.13, 0.032-0.225), but positive incremental costs (£15,001, £11,123 to £18,880) compared with 'late or no transfer' (N = 263). The lifetime cost per QALY gained for 'early' transfer was £11,000. CONCLUSIONS: For critically ill adult patients with acute TBI, within neuroscience centres management in dedicated neurocritical care units versus combined neuro/general units led to improved QoL and higher costs, on average, but these differences were not statistically significant. This study finds that 'early' transfer to a neuroscience centre is associated with reduced mortality, improvement in QOL and is cost-effective

Intracranial V. cholerae Sialidase Protects against Excitotoxic Neurodegeneration

Converging evidence shows that GD3 ganglioside is a critical effector in a number of apoptotic pathways, and GM1 ganglioside has neuroprotective and noötropic properties. Targeted deletion of GD3 synthase (GD3S) eliminates GD3 and increases GM1 levels. Primary neurons from GD3S−/− mice are resistant to neurotoxicity induced by amyloid-β or hyperhomocysteinemia, and when GD3S is eliminated in the APP/PSEN1 double-transgenic model of Alzheimer's disease the plaque-associated oxidative stress and inflammatory response are absent. To date, no small-molecule inhibitor of GD3S exists. In the present study we used sialidase from Vibrio cholerae (VCS) to produce a brain ganglioside profile that approximates that of GD3S deletion. VCS hydrolyzes GD1a and complex b-series gangliosides to GM1, and the apoptogenic GD3 is degraded. VCS was infused by osmotic minipump into the dorsal third ventricle in mice over a 4-week period. Sensorimotor behaviors, anxiety, and cognition were unaffected in VCS-treated mice. To determine whether VCS was neuroprotective in vivo, we injected kainic acid on the 25th day of infusion to induce status epilepticus. Kainic acid induced a robust lesion of the CA3 hippocampal subfield in aCSF-treated controls. In contrast, all hippocampal regions in VCS-treated mice were largely intact. VCS did not protect against seizures. These results demonstrate that strategic degradation of complex gangliosides and GD3 can be used to achieve neuroprotection without adversely affecting behavior

THE RHYTHM OF FAIRALL 9. I. OBSERVING THE SPECTRAL VARIABILITY WITH XMM-NEWTON AND NuSTAR

© 2016. The American Astronomical Society. All rights reserved. We present a multi-epoch X-ray spectral analysis of the Seyfert 1 galaxy Fairall 9. Our analysis shows that Fairall 9 displays unique spectral variability in that its ratio residuals to a simple absorbed power law in the 0.5-10 keV band remain constant with time in spite of large variations in flux. This behavior implies an unchanging source geometry and the same emission processes continuously at work at the timescale probed. With the constraints from NuSTAR on the broad-band spectral shape, it is clear that the soft excess in this source is a superposition of two different processes, one being blurred ionized reflection in the innermost parts of the accretion disk, and the other a continuum component such as a spatially distinct Comptonizing region. Alternatively, a more complex primary Comptonization component together with blurred ionized reflection could be responsible

DISK–WIND CONNECTION DURING THE HEARTBEATS OF GRS 1915+105

Disk and wind signatures are seen in the soft state of Galactic black holes, while the jet is seen in the hard state. Here we study the disk–wind connection in the ρ class of variability in GRS 1915+105 using a joint NuSTAR–Chandra observation. The source shows 50 s limit cycle oscillations. By including new information provided by the reflection spectrum and using phase-resolved spectroscopy, we find that the change in the inner disk inferred from the blackbody emission is not matched by reflection measurements. The latter is almost constant, independent of the continuum model. The two radii are comparable only if the disk temperature color correction factor changes, an effect that could be due to the changing opacity of the disk caused by changes in metal abundances. The disk inclination is similar to that inferred from the jet axis, and oscillates by ~10°. The simultaneous Chandra data show the presence of two wind components with velocities between 500 and 5000 km s⁻¹, and possibly two more with velocities reaching 20,000 km s⁻¹ (~0.06 c). The column densities are ~5 × 10²² cm⁻². An upper limit to the wind response time of 2 s is measured, implying a launch radius of <6 × 10¹° cm. The changes in wind velocity and absorbed flux require the geometry of the wind to change during the oscillations, constraining the wind to be launched from a distance of 290–1300 r _g from the black hole. Both data sets support fundamental model predictions in which a bulge originates in the inner disk and moves outward as the instability progresses.This work made use of data from the NuSTAR mission, a project led by the California Institute of Technology, managed by the Jet Propulsion Laboratory, and funded by the National Aeronautics and Space Administration. This work is also based on observations made by the Chandra X-ray Observatory

Solution NMR assignment of the C-terminal domain of human chTOG

The microtubule regulatory protein colonic and hepatic tumor overexpressed gene (chTOG), also known as cytoskeleleton associated protein 5 (CKAP5) plays an important role in organizing the cytoskeleton and in particular in the assembly of k-fibres in mitosis. Recently, we dissected the hitherto poorly understood C-terminus of this protein by discovering two new domains—a cryptic TOG domain (TOG6) and a smaller, helical domain at the very C-terminus. It was shown that the C-terminal domain is important for the interaction with the TACC domain in TACC3 during the assembly of k-fibres in a ternary complex that also includes clathrin. Here we now present the solution NMR assignment of the chTOG C-terminal domain which confirms our earlier prediction that it is mainly made of α-helices. However, the appearance of the 1H–15N HSQC spectrum is indicative of the presence of a considerable amount of unstructured and possibly flexible portions of protein in the domain

NuSTAR observations of Mrk 766: Distinguishing reflection from absorption

We present two new NuSTAR observations of the narrow line Seyfert 1 (NLS1) galaxy Mrk 766 and give constraints on the two scenarios previously proposed to explain its spectrum and that of other NLS1s: relativistic reflection and partial covering. The NuSTAR spectra show a strong hard (> 15 keV) X-ray excess, while simultaneous soft X-ray coverage of one of the observations provided by XMM-Newton constrains the ionised absorption in the source. The pure reflection model requires a black hole of high spin (a > 0.92) viewed at a moderate inclination (i = 46 +1 −4 ). The pure partial covering model requires extreme parameters: the cut-off of the primary continuum is very low (22 +7 −5 keV) in one observation and the intrinsic X-ray emission must provide a large fraction (75%) of the bolometric luminosity. Allowing a hybrid model with both partial covering and reflection provides more reasonable absorption parameters and relaxes the constraints on reflection parameters. The fractional variability reduces around the iron K band and at high energies including the Compton hump, suggesting that the reflected emission is less variable than the continuum

The corona of the broad-line radio galaxy 3C 390.3

We present the results from a joint Suzaku/NuSTAR broad-band spectral analysis of 3C 390.3. The high quality data enables us to clearly separate the primary continuum from the reprocessed components allowing us to detect a high energy spectral cut-off ($E_\text{cut}=117_{-14}^{+18}$ keV), and to place constraints on the Comptonization parameters of the primary continuum for the first time. The hard over soft compactness is 69$_{-24}^{+124}$ and the optical depth 4.1$_{-3.6}^{+0.5}$, this leads to an electron temperature of $30_{-8}^{+32}$ keV. Expanding our study of the Comptonization spectrum to the optical/UV by studying the simultaneous Swift-UVOT data, we find indications that the compactness of the corona allows only a small fraction of the total UV/optical flux to be Comptonized. Our analysis of the reprocessed emission show that 3C 390.3 only has a small amount of reflection (R~0.3), and of that the vast majority is from distant neutral matter. However we also discover a soft X-ray excess in the source, which can be described by a weak ionized reflection component from the inner parts of the accretion disk. In addition to the backscattered emission, we also detect the highly ionized iron emission lines Fe XXV and Fe XXVI