APOE genotype and entorhinal cortex volume in non-demented community-dwelling adults in midlife and early old age

Copyright © 2012 IOS PressThis article has been made available through the Brunel Open Access Publishing Fund.The apolipoprotein E (APOE) ε4 allele is a risk factor for the neuropathological decline accompanying Alzheimer's disease (AD) while, conversely, the ε2 allele offers protection. One of the brain structures exhibiting the earliest changes associated with the disease is the entorhinal cortex. We therefore investigated the volumes of the entorhinal cortex and other structures in the medial temporal lobe including the parahippocampal gyrus, temporal pole, and inferior, middle, and superior temporal cortices, in relation to APOE genotype. Our main objectives were to determine if (a) volumes systematically varied according to allele in a stepwise fashion, ε2 > ε3 > ε4, and (b) associations varied according to age. We investigate this association in 627 non-demented community-dwelling adults in middle age (44 to 48 years; n = 314) and older age (64 to 68 years; n = 313) who underwent structural MRI scans. We found no evidence of APOE-related variation in brain volumes in the age groups examined. We conclude that if a ε2 > ε3 > ε4 pattern in brain volumes does emerge in non-demented adults living in the community in old age, it is not until after the age of 68 years.This study was funded by the UK Leverhulme Trust, the British Academy, the NHMRC Research Fellowship No. 471501, the NHMRC Research Fellowship No.#1002560, the National Health and Medical Research Council of Australia Unit Grant No. 973302, Program Grant No. 179805, Project grant No. 157125; Program grant no. 350833, and the National Computational Infrastructure. This article is made available through the Brunel Open Access Publishing Fund

A phase III, multi-centre, double-masked randomised controlled trial of adjunctive intraocular and peri-ocular steroid (triamcinolone acetonide) versus standard treatment in eyes undergoing vitreoretinal surgery for open globe trauma (ASCOT): statistical analysis plan.

BACKGROUND: Open globe ocular trauma complicated by intraocular scarring (proliferative vitreoretinopathy) is a relatively rare, blinding, but potentially treatable condition for which, at present, surgery is often unsatisfactory and visual results frequently poor. To date, no pharmacological adjuncts to surgery have been proven to be effective. The aim of the Adjunctive Steroid Combination in Ocular Trauma (ASCOT) randomised controlled trial is to determine whether adjunctive steroid (triamcinolone acetonide), given at the time of surgery, can improve the outcome of vitreoretinal surgery in patients with open globe ocular trauma. This article presents the statistical analysis plan for the main publication as approved and signed off by the Trial Steering Committee prior to the first data extraction for the Data Monitoring Committee meeting report. METHODS/DESIGN: ASCOT is a pragmatic, multi-centre, parallel-group, double-masked randomised controlled trial. The aim of the study is to recruit from 20-25 centres in the United Kingdom and randomise 300 eyes (from 300 patients) into two treatment arms. Both groups will receive standard surgical treatment and care; the intervention arm will additionally receive a pre-operative steroid combination (triamcinolone acetonide) into the vitreous cavity consisting of 4 mg/0.1 ml and 40 mg/1 ml sub-Tenon's. Participants will be followed for 6 months post-surgery. The primary outcome is the proportion of patients achieving a clinically meaning improvement in visual acuity in the study eye at 6 months after initial surgery, defined as a 10 letter score improvement in the ETDRS (the standard scale to test visual acuity). TRIAL REGISTRATION: ISRCTN30012492 . Registered on 5 September 2014. EudraCT2014-002193-37 . Registered on 5 September 2014

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

Intra-individual reaction time variability and all-cause mortality over 17 years: A community-based cohort study

Background: very few studies have examined the association between intra-individual reaction time variability and subsequent mortality. Furthermore, the ability of simple measures of variability to predict mortality has not been compared with more complex measures. Method: a prospective cohort study of 896 community-based Australian adults aged 70+ were interviewed up to four times from 1990 to 2002, with vital status assessed until June 2007. From this cohort, 770–790 participants were included in Cox proportional hazards regression models of survival. Vital status and time in study were used to conduct survival analyses. The mean reaction time and three measures of intra-individual reaction time variability were calculated separately across 20 trials of simple and choice reaction time tasks. Models were adjusted for a range of demographic, physical health and mental health measures. Results: greater intra-individual simple reaction time variability, as assessed by the raw standard deviation (raw SD), coefficient of variation (CV) or the intra-individual standard deviation (ISD), was strongly associated with an increased hazard of all-cause mortality in adjusted Cox regression models. The mean reaction time had no significant association with mortality. Conclusion: intra-individual variability in simple reaction time appears to have a robust association with mortality over 17 years. Health professionals such as neuropsychologists may benefit in their detection of neuropathology by supplementing neuropsychiatric testing with the straightforward process of testing simple reaction time and calculating raw SD or CV

The impact of in-cylinder charge motion on lean limit extension and in-pre-chamber mixture preparation in a homogeneous ultra-lean engine

The perpetual desire to conserve fuel is driving strong demand for increased efficiency in spark ignited (SI) engines. A method being increasingly explored to accomplish this goal is lean combustion. Homogeneous ultra-lean combustion with λ > 1.6 has demonstrated the ability to both increase thermal efficiency and significantly reduce engine-out nitrogen oxides (NOx) emissions due to the colder cylinder temperatures innate to combustion with high levels of dilution. The major limitation in developing lean and ultra-lean combustion systems is the less favorable ignition quality of the mixture. This has necessitated the development of higher energy ignition sources. A pre-chamber combustor application known as jet ignition is one such technology, having been researched extensively. Differing types and magnitudes of charge motion are incorporated in SI engines to aid with mixture preparation. The influence of charge motion over lean SI combustion however is less well understood. Additionally, charge motion introduced in the main combustion chamber has the potential to translate to the pre-chamber, thereby affecting pre-chamber mixing and combustion. The effect of charge motion on mixing and combustion comprehensively throughout the engine cycle is unknown and has not been investigated. This study seeks to evaluate the impact of charge motion on mixture preparation and combustion processes in a jet ignition engine. Experimental engine testing is undertaken to quantify the impact of differing levels and types of induced charge motion on pre-chamber and main chamber combustion. An analysis of high speed pressure data from the pre-chamber provides insight into how charge motion affects pre-chamber combustion stability, and how instabilities cascade to the main chamber combustion event. A set of simulations, matched to experimental engine results, is used to develop an understanding of charge motion influence over the complexities of in-pre-chamber phenomena that are not easily observed experimentally. From the synthesis of these data sets, a clear understanding of the role that charge motion plays in homogeneous highly dilute jet ignition engines emerges. This study quantifies the impact that charge motion has on lean limit extension and engine efficiency, identifies optimal charge motion type, and provides a roadmap for engine system optimization

Effects of silvoarable agroforestry on profitability and environmental indicators

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Comparison of bacterial biofilm communities using barcoded pyrosequencing and analysis to determine origin of biofilm fouling of reverse osmosis membranes in a full scale desalination system

Biofouling is the single most important issue in reverse osmosis sea water desalination worldwide (Ridgway et al., 1999) and may account for up to 50% of energy use. Which species are responsible and their origin is unclear. With the advent of next generation sequencing, species diversity and transience can be examined at orders of magnitude greater detail than was previously possible. We found many similarities in bacterial families across source water, prefiltration units and membranes in this study and in the few other studies available, despite disparate locations and seasons. Key groups included members of the Bacteroidetes (e. Flavobacteriaceae), Planctomycetes, Alphaproteobacteria (eg. Rhodobacteraceae, Sphingomonadales), Betaproteobacteria (eg. Burkholderia) and Gammaproteobacteria (eg. Oceanospirillales, Xanthomonadaceae). Despite similarities in families, the predominant fouling species on reverse osmosis (RO) membranes appear to differ between studies. This seems likely to reflect a common origin (seawater) but subsequent adaptation or selective pressures in different niches, particularly on RO membranes under high pressure and salt concentration. We can now select environmental isolates from our culture collection representing key bacterial groups responsible for biofouling in seawater systems. This will enable more accurate evaluation of the effectiveness of anti-fouling strategies

Is it real? The development of judgments about authenticity and ontological status

We examined children's judgments of the real/not-real status of fictional characters given that such judgments can be based either on the ontological status of the character or on the authenticity of a representation of the character. Sixty 3 - 5 year-olds and 20 adults were shown paired photographs of fictional characters (e.g., Bob the Builder) and people dressing up as those characters (e.g., a person wearing a Bob the Builder costume). They were asked whether each depicted character lives in ‘the real world’ (ontology question) and whether each character is ‘the real’ fictional character (authenticity question), and why. As expected, younger children, and to some extent older children, made more accurate authenticity judgments than ontology judgments about the characters, whereas adults made accurate judgments in reply to both questions. Furthermore, younger children did not differentiate between the two questions in their justifications, unlike the older children and adults. Implications for the development of children's ability to make reality judgments about fictional characters are discussed

Use of tobacco and e-cigarettes among youth in Great Britain in 2022: analysis of a cross sectional survey

Introduction: Although e-cigarettes can be an effective form of nicotine substitution for adults attempting to quit smoking, their use among children and young people is a concern. Accurate data about this are needed to inform debates over policy and regulation in the UK and elsewhere. Methods: Using data from an online survey of 2613 youth aged 11–18 years, conducted by the market research company YouGov in March 2022, we present prevalence estimates of e-cigarette and tobacco use. We use logistic regression models to assess differences in e-cigarette use, tobacco use and use of disposable e-cigarettes across a range of covariates including age, sex, tobacco smoking status, social class, and country. Results: Among the 18.0% of those surveyed who reported ever having smoked a cigarette, 83.9% were not regular (at least once per week) smokers and 16.1% were (15.1% and 2.9% of the total sample, respectively). Among the 19.2% of those surveyed who had ever used an e-cigarette, 79.2% were not regular users, while 20.8% were (15.2% and 4.0% of the total sample, respectively). Regular e-cigarette use was more common than regular tobacco smoking (4.0% vs 2.9%). E-cigarette use was more common among those who also smoked tobacco, with 9.0% of never e-cigarette users ever smoking tobacco, compared with 89.4% of regular e-cigarette users. Both smoking and e-cigarette use were associated with increasing age and use by others within the home, but not with social class. Use of disposable e-cigarettes was reported by 53.8% of those who have ever used an e-cigarette, and more common among females than males. Conclusions: Regular e-cigarette use is now more common than smoking in children and youth, though the majority of this is among those who have also smoked tobacco. Measures to reduce the appeal of both e-cigarettes and tobacco to children and young people are warranted