403 research outputs found

    Examination of homogeneity of selected Irish pooling groups

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    Flood frequency analysis is a necessary and important part of flood risk assessment and management studies. Regional flood frequency methods, in which flood data from groups of catchments are pooled together in order to enhance the precision of flood estimates at project locations, is an accepted part of such studies. This enhancement of precision is based on the assumption that catchments so pooled together are homogeneous in their flood producing properties. If homogeneity is assured then a homogeneous pooling group of sites lead to a reduction in the error of quantile estimates, relative to estimators based on single at-site data series alone. Homogeneous pooling groups are selected by using a previously nominated rule and this paper examines how effective one such rule is in selecting homogeneous groups. In this paper a study, based on annual maximum series obtained from 85 Irish gauging stations, examines how successful a common method of identifying pooling group membership is in selecting groups that actually are homogeneous. Each station has its own unique pooling group selected by use of a Euclidean distance measure in catchment descriptor space, commonly denoted <i>d</i><i><sub>ij</sub></i> and with a minimum of 500 station years of data in the pooling group. It was found that <i>d</i><i><sub>ij</sub></i> could be effectively defined in terms of catchment area, mean rainfall and baseflow index. The study then investigated how effective this selected method is in selecting groups of catchments that are actually homogenous as indicated by their L-Cv values. The sampling distribution of L-CV (<i>t</i><sub>2</sub>) in each pooling group and the 95% confidence limits about the pooled estimate of <i>t</i><sub>2</sub> are obtained by simulation. The <i>t</i><sub>2</sub> values of the selected group members are compared with these confidence limits both graphically and numerically. Of the 85 stations, only 1 station's pooling group members have all their <i>t</i><sub>2</sub> values within the confidence limits, while 7, 33 and 44 of them have 1, 2 or 3 or more, <i>t</i><sub>2</sub> values outside the confidence limits. The outcomes are also compared with the heterogeneity measures H1 and H2. The H1 values show an upward trend with the ranges of <i>t</i><sub>2</sub> values in the pooling group whereas the H2 values do not show any such dependency. A selection of 27 pooling groups, found to be heterogeneous, were further examined with the help of box-plots of catchment descriptor values and one particular case is considered in detail. Overall the results show that even with a carefully considered selection procedure, it is not certain that perfectly homogeneous pooling groups are identified

    Hyperactivation of monocytes and macrophages in MCI patients contributes to the progression of Alzheimer's disease

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    Background: Alzheimer’s disease (AD) is the most common neurodegenerative disease ultimately manifesting as clinical dementia. Despite considerable effort and ample experimental data, the role of neuroinflammation related to systemic inflammation is still unsettled. While the implication of microglia is well recognized, the exact contribution of peripheral monocytes/macrophages is still largely unknown, especially concerning their role in the various stages of AD. Objectives: AD develops over decades and its clinical manifestation is preceded by subjective memory complaints (SMC) and mild cognitive impairment (MCI); thus, the question arises how the peripheral innate immune response changes with the progression of the disease. Therefore, to further investigate the roles of monocytes/macrophages in the progression of AD we assessed their phenotypes and functions in patients at SMC, MCI and AD stages and compared them with cognitively healthy controls. We also conceptualised an idealised mathematical model to explain the functionality of monocytes/macrophages along the progression of the disease. Results: We show that there are distinct phenotypic and functional changes in monocyte and macrophage populations as the disease progresses. Higher free radical production upon stimulation could already be observed for the monocytes of SMC patients. The most striking results show that activation of peripheral monocytes (hyperactivation) is the strongest in the MCI group, at the prodromal stage of the disease. Monocytes exhibit significantly increased chemotaxis, free radical production, and cytokine production in response to TLR2 and TLR4 stimulation. Conclusion: Our data suggest that the peripheral innate immune system is activated during the progression from SMC through MCI to AD, with the highest levels of activation being in MCI subjects and the lowest in AD patients. Some of these parameters may be used as biomarkers, but more holistic immune studies are needed to find the best period of the disease for clinical intervention

    Plasma response to fish oil in the elderly

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    Little information is available concerning whether incorporation of dietary omega-3 fatty acids into plasma lipids changes during healthy aging. Elderly (74 ± 4 years old) and young (24 ± 2 years old) adults were given a fish oil supplement for 3 weeks that provided 680 mg/day of docosahexaenoic acid and 320 mg/day of eicosapentaenoic acid, followed by a 2 week wash-out period. Compliance was monitored by spiking the capsules with carbon-13 glucose, the excretion of which was measured in breath CO2. In response to the supplement, plasma docosahexaenoic acid rose 42% more in the elderly but eicosapentaenoic responded similarly in both groups. Despite raising docosahexaenoic acid intake by five to tenfold, the supplement did not raise plasma free docosahexaenoic acid (% or mg/dL) in either group. We conclude that healthy aging is accompanied by subtle but significant changes in DHA incorporation into plasma lipids

    Challenges to determining whether DHA can protect against age-related cognitive decline

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    DHA, an omega-3 fatty acid, is an important constituent of brain membranes and has a key role in brain development and function. This review aims to highlight recent research on DHA’s role during age-related cognitive decline and Alzheimer’s disease. Animal and in vitro studies have provided some interesting mechanistic leads, especially on brain glucose metabolism, that may be involved in neuroprotection by DHA. However, results from human studies are more mitigated, perhaps due to changing DHA metabolism during aging. Recent innovative tools such as 13C-DHA for metabolic studies and 11C-DHA for PET provide interesting opportunities to study factors that affect DHA homeostasis during aging and to better understand whether and how to use DHA to delay or treat Alzheimer’s disease

    Disturbance in uniformly 13C-labelled DHA metabolism in elderly human subjects carrying the apoE ε4 allele

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    Carrying the apoE ε4 allele (E4+) is the most important genetic risk for Alzheimer's disease. Unlike non-carriers (E4 − ), E4+ seem not to be protected against Alzheimer's disease when consuming fish. We hypothesised that this may be linked to a disturbance in n-3 DHA metabolism in E4+. The aim of the present study was to evaluate [13C]DHA metabolism over 28 d in E4+v. E4 − . A total of forty participants (twenty-six women and fourteen men) received a single oral dose of 40 mg [13C]DHA, and its metabolism was monitored in blood and breath over 28 d. Of the participants, six were E4+ and thirty-four were E4 − . In E4+, mean plasma [13C]DHA was 31 % lower than that in E4 − , and cumulative β-oxidation of [13C]DHA was higher than that in E4 − 1–28 d post-dose (P≤ 0·05). A genotype × time interaction was detected for cumulative β-oxidation of [13C]DHA (P≤ 0·01). The whole-body half-life of [13C]DHA was 77 % lower in E4+ compared with E4 − (P≤ 0·01). In E4+ and E4 − , the percentage dose of [13C]DHA recovered/h as 13CO2 correlated with [13C]DHA concentration in plasma, but the slope of linear regression was 117 % steeper in E4+ compared with E4 − (P≤ 0·05). These results indicate that DHA metabolism is disturbed in E4+, and may help explain why there is no association between DHA levels in plasma and cognition in E4+. However, whether E4+ disturbs the metabolism of 13C-labelled fatty acids other than DHA cannot be deduced from the present study

    Being punk in higher education: subcultural strategies for academic practice

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    Since its beginnings in the late 1970s, punk culture has been associated with counter-mainstream ideology and anti-institutional antagonism. In particular, formal education has been criticised in punk for sustaining oppressive social and conceptual orders and associated behavioural norms. Drawing on literature and interviews, this paper focuses on the experiences of higher education teachers who self-identify as punks, and considers how they negotiate and reconcile their subcultural and academic identities in their academic practice. The findings reveal that participants’ affiliations with punk subculture give rise to counter-cultural pedagogies in which both the ethics and aesthetics of punk are applied in classroom contexts. Furthermore, the participants draw upon subcultural ethical and epistemological narratives to formulate and rationalise their responses to the state of contemporary UK higher education

    European Food Safety Authority; Outcome of the Public consultation on the Draft Opinion of the Scientific Panel on Dietetic products, Nutrition, and Allergies (NDA) on Dietary Reference Values for fats, including saturated fatty acids, polyunsaturated fatty acids, monounsaturated fatty acids, trans fatty acids, and cholesterol

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    On 2 July 2009, the EFSA Panel on Dietetic products, Nutrition and Allergies (NDA) endorsed a draft Opinion on Dietary Reference Values for fats to be released for public consultation. This Scientific Report summarises the comments received through the public consultation and outlines how these were taken into account in the final opinion. EFSA had received contributions from 40 interested parties (individuals, non-governmental organisations, industry organisations, academia and national assessment bodies). The main comments which were received during the public consultation related to: the availability of more recent data, the nomenclature used, the use of a non-European food composition data base, the impact of genetic factors in modulating the absorption, metabolism and health effects of different fatty acids, the definition of “nutritionally adequate diet”, the use of Dietary Reference Values in the labelling of foods, the translation of advice into food-based dietary guidelines, nutrient goals and recommendations, certain risk management issues, and to Dietary Reference Values of fats, individual fatty acids, and cholesterol. All the public comments received that related to the remit of EFSA were assessed and the Opinion on Dietary Reference Values for fats has been revised taking relevant comments into consideration

    The PLIN4 Variant rs8887 Modulates Obesity Related Phenotypes in Humans through Creation of a Novel miR-522 Seed Site

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    PLIN4 is a member of the PAT family of lipid storage droplet (LSD) proteins. Associations between seven single nucleotide polymorphisms (SNPs) at human PLIN4 with obesity related phenotypes were investigated using meta-analysis followed by a determination if these phenotypes are modulated by interactions between PLIN4 SNPs and dietary PUFA. Samples consisted of subjects from two populations of European ancestry. We demonstrated association of rs8887 with anthropometrics. Meta-analysis demonstrated significant interactions between the rs8887 minor allele with PUFA n3 modulating anthropometrics. rs884164 showed interaction with both n3 and n6 PUFA modulating anthropometric and lipid phenotypes. In silico analysis of the PLIN4 3′UTR sequence surrounding the rs8887 minor A allele predicted a seed site for the human microRNA-522 (miR-522), suggesting a functional mechanism. Our data showed that a PLIN4 3′UTR luciferase reporter carrying the A allele of rs8887 was reduced in response to miR-522 mimics compared to the G allele. These results suggest variation at the PLIN4 locus, and its interaction with PUFA as a modulator of obesity related phenotypes, acts in part through creation of a miR-522 regulatory site
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