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A higher intake of food rich in flavonoids such as quercetin can reduce the risk of CVD. Enzymatically modified isoquercitrin (EMIQ®) has a bioavailability 17-fold higher than quercetin aglycone and has shown potential CVD moderating effects in animal studies. The present study aimed to determine whether acute ingestion of EMIQ® improves endothelial function, blood pressure (BP) and cognitive function in human volunteers at risk of CVD. Twenty-five participants (twelve males and thirteen females) with at least one CVD risk factor completed this randomised, controlled, crossover study. In a random order, participants were given EMIQ® (2 mg aglycone equivalent)/kg body weight or placebo alongside a standard breakfast meal. Endothelial function, assessed by flow-mediated dilatation (FMD) of the brachial artery was measured before and 1·5 h after intervention. BP, arterial stiffness, cognitive function, BP during cognitive stress and measures of quercetin metabolites, oxidative stress and markers of nitric oxide (NO) production were assessed post-intervention. After adjustment for pre-treatment measurements and treatment order, EMIQ® treatment resulted in a significantly higher FMD response compared with the placebo (1·80 (95 % CI 0·23, 3·37) %; P = 0·025). Plasma concentrations of quercetin metabolites were significantly higher (P < 0·001) after EMIQ® treatment compared with the placebo. No changes in BP, arterial stiffness, cognitive function or biochemical parameters were observed. In this human intervention study, the acute administration of EMIQ® significantly increased circulating quercetin metabolites and improved endothelial function. Further clinical trials are required to assess whether health benefits are associated with long-term EMIQ® consumption.
Decreases in Fe status have been reported in military women during initial training periods of 8–10 weeks. The present study aimed to characterise Fe status and associations with physical performance in female New Zealand Army recruits during a 16-week basic combat training (BCT) course. Fe status indicators – Hb, serum ferritin (sFer), soluble transferrin receptor (sTfR), transferrin saturation (TS) and erythrocyte distribution width (RDW) – were assessed at the beginning (baseline) and end of BCT in seventy-six volunteers without Fe-deficiency non-anaemia (sFer <12 µg/l; Hb ≥120 g/l) or Fe-deficiency anaemia (sFer <12 µg/l; Hb <120 g/l) at baseline or a C-reactive protein >10 mg/l at baseline or end. A timed 2·4 km run followed by maximum press-ups were performed at baseline and midpoint (week 8) to assess physical performance. Changes in Fe status were investigated using paired t tests and associations between Fe status and physical performance evaluated using Pearson correlation coefficients. sFer (56·6 (sd 33·7) v. 38·4 (sd 23·8) µg/l) and TS (38·8 (sd 13·9) v. 34·4 (sd 11·5) %) decreased (P<0·001 and P=0·014, respectively), while sTfR (1·21 (sd 0·27) v. 1·39 (sd 0·35) mg/l) and RDW (12·8 (sd 0·6) v. 13·2 (sd 0·7) %) increased (P<0·001) from baseline to end. Hb (140·6 (sd 7·5) v. 142·9 (sd 7·9) g/l) increased (P=0·009) during BCT. At end, sTfR was positively (r 0·29, P=0·012) and TS inversely associated (r –0·32, P=0·005) with midpoint run time. There were no significant correlations between Fe status and press-ups. Storage and functional Fe parameters indicated a decline in Fe status in female recruits during BCT. Correlations between tissue-Fe indicators and run times suggest impaired aerobic fitness. Optimal Fe status appears paramount for enabling success in female recruits during military training.
Walking ability recently emerged as a sub-clinical marker of cognitive decline. Hence, the relationship between baseline gait and future cognitive decline was examined in geriatric patients. Because a “loss of complexity” (LOC) is a key phenomenon of the aging process that exhibits in multiple systems, we propose the idea that age- and cognition-related LOC may also become manifested in gait function. The LOC theory suggests that even healthy aging is associated with a (neuro)physiological breakdown of system elements that causes a decline in variability and an overall LOC. We used coordination dynamics as a conceptual framework and hypothesized that a LOC is reflected in dynamic gait outcomes (e.g. gait regularity, complexity, stability) and that such outcomes could increase the specificity of the gait-cognition link.
19 geriatric patients (age 80.0±5.8) were followed for 14.4±6.6 months. An iPod collected three-dimensional (3D) trunk accelerations while patients walked for 3 minutes. Cognition was evaluated with the Mini-Mental State Examination (MMSE) and the Seven-Minute screen (7MS) test. The Reliable Change Index (RCI) quantified the magnitude of cognitive change. Spearman's Rho coefficients (ρ) indexed correlations between baseline gait and future cognitive change.
Seven patients showed reliable cognitive decline (“Cognitive Decline” group), and 12 patients remained cognitively stable (“Cognitive Stable” group) over time. Future cognitive decline was correlated with a more regular (ρ = 0.579*) and predictable (ρ = 0.486*) gait pattern, but not with gait speed.
The increase in gait regularity and predictability possibly reflects a LOC due to age- and cognition-related (neuro)physiological decline. Because dynamic versus traditional gait outcomes (i.e. gait speed and (variability of) stride time) were more strongly correlated with future cognitive decline, the use of wearable sensors in predicting and monitoring cognitive and physical health in vulnerable geriatric patients can be considered promising. However, our results are preliminary and do require replication in larger cohorts.
A discordant twin gestation, in which one fetus is significantly growth restricted, compared to the other normal twin, is a unique model that can be used to elucidate the mechanism(s) by which the intrauterine environment affects fetal growth. In many model systems, placental transcription factor genes regulate fetal growth. Transcription factors regulate growth through their activation or repression of downstream target genes that mediate important cell functions. The objective of this study was to determine the expression of the placental HLX homeobox gene transcription factor and its downstream target genes in dizygotic twins with growth discordance. In this cross-sectional study, HLX and its downstream target genes’ retinoblastoma 1 (RB1) and cyclin kinase D (CDKN1C) expression levels were determined in placentae obtained from dichorionic diamniotic twin pregnancies (n = 23) where one of the twins was growth restricted. Fetal growth restriction (FGR) was defined as small for gestational age with abnormal umbilical artery Doppler indices when compared with the normal control co-twin. Homeobox gene HLX expression was significantly decreased at both the mRNA and protein levels in FGR twin placentae compared with the normal control co-twin placentae (p < .05). Downstream target genes CDKN1C and RB1 were also significantly decreased and increased, respectively, at both the mRNA and protein levels in FGR twin placentae compared with normal control co-twin placentae (p < .05). Together, these observations suggest an important association between HLX transcription factor expression and abnormal human placental development in discordant twin pregnancies.
West Antarctic climate and surface mass balance (SMB) records are sparse. To fill this gap, regional atmospheric climate modelling is useful, providing that such models are employed at sufficiently high horizontal resolution and coupled with a snow model. Here we present the results of a high-resolution (5.5 km) regional atmospheric climate model (RACMO2) simulation of coastal West Antarctica for the period 1979–2015. We evaluate the results with available in situ weather observations, remote-sensing estimates of surface melt, and SMB estimates derived from radar and firn cores. Moreover, results are compared with those from a lower-resolution version, to assess the added value of the resolution. The high-resolution model resolves small-scale climate variability invoked by topography, such as the relatively warm conditions over ice-shelf grounding zones, and local wind speed accelerations. Surface melt and SMB are well reproduced by RACMO2. This dataset will prove useful for picking ice core locations, converting elevation changes to mass changes, for driving ocean, ice-sheet and coupled models, and for attributing changes in the West Antarctic Ice Sheet and shelves to changes in atmospheric forcing.
Arterial wall thickening, stimulated by low-grade systemic inflammation, underlies many cardiovascular events. As diet is a significant moderator of systemic inflammation, the dietary inflammatory index (DIITM) has recently been devised to assess the overall inflammatory potential of an individual’s diet. The primary objective of this study was to assess the association of the DII with common carotid artery–intima-media thickness (CCA–IMT) and carotid plaques. To substantiate the clinical importance of these findings we assessed the relationship of DII score with atherosclerotic vascular disease (ASVD)-related mortality, ischaemic cerebrovascular disease (CVA)-related mortality and ischaemic heart disease (IHD)-related mortality more. The study was conducted in Western Australian women aged over 70 years (n 1304). Dietary data derived from a validated FFQ (completed at baseline) were used to calculate a DII score for each individual. In multivariable-adjusted models, DII scores were associated with sub-clinical atherosclerosis: a 1 sd (2·13 units) higher DII score was associated with a 0·013-mm higher mean CCA–IMT (P=0·016) and a 0·016-mm higher maximum CCA–IMT (P=0·008), measured at 36 months. No relationship was seen between DII score and carotid plaque severity. There were 269 deaths during follow-up. High DII scores were positively associated with ASVD-related death (per sd, hazard ratio (HR): 1·36; 95 % CI 1·15, 1·60), CVA-related death (per sd, HR: 1·30; 95 % CI 1·00, 1·69) and IHD-related death (per sd, HR: 1·40; 95 % CI 1·13, 1·75). These results support the hypothesis that a pro-inflammatory diet increases systemic inflammation leading to development and progression of atherosclerosis and eventual ASVD-related death.
The Numeniini is a tribe of 13 wader species (Scolopacidae, Charadriiformes) of which seven are Near Threatened or globally threatened, including two Critically Endangered. To help inform conservation management and policy responses, we present the results of an expert assessment of the threats that members of this taxonomic group face across migratory flyways. Most threats are increasing in intensity, particularly in non-breeding areas, where habitat loss resulting from residential and commercial development, aquaculture, mining, transport, disturbance, problematic invasive species, pollution and climate change were regarded as having the greatest detrimental impact. Fewer threats (mining, disturbance, problematic native species and climate change) were identified as widely affecting breeding areas. Numeniini populations face the greatest number of non-breeding threats in the East Asian-Australasian Flyway, especially those associated with coastal reclamation; related threats were also identified across the Central and Atlantic Americas, and East Atlantic flyways. Threats on the breeding grounds were greatest in Central and Atlantic Americas, East Atlantic and West Asian flyways. Three priority actions were associated with monitoring and research: to monitor breeding population trends (which for species breeding in remote areas may best be achieved through surveys at key non-breeding sites), to deploy tracking technologies to identify migratory connectivity, and to monitor land-cover change across breeding and non-breeding areas. Two priority actions were focused on conservation and policy responses: to identify and effectively protect key non-breeding sites across all flyways (particularly in the East Asian- Australasian Flyway), and to implement successful conservation interventions at a sufficient scale across human-dominated landscapes for species’ recovery to be achieved. If implemented urgently, these measures in combination have the potential to alter the current population declines of many Numeniini species and provide a template for the conservation of other groups of threatened species.
Recognising the scarcity of glacier mass-balance data in the Southern Hemisphere, a mass-balance measurement programme was started at Brewster Glacier in the Southern Alps of New Zealand in 2004. Evolution of the measurement regime over the 11 years of data recorded means there are differences in the spatial density of data obtained. To ensure the temporal integrity of the dataset a new geostatistical approach is developed to calculate mass balance. Spatial co-variance between elevation and snow depth allows a digital elevation model to be used in a co-kriging approach to develop a snow depth index (SDI). By capturing the observed spatial variability in snow depth, the SDI is a more reliable predictor than elevation and is used to adjust each year of measurements consistently despite variability in sampling spatial density. The SDI also resolves the spatial structure of summer balance better than elevation. Co-kriging is used again to spatially interpolate a derived mean summer balance index using SDI as a co-variate, which yields a spatial predictor for summer balance. The average glacier-wide surface winter, summer and annual balances over the period 2005–15 are 2484, −2586 and −102 mm w.e., respectively, with changes in summer balance explaining most of the variability in annual balance.
Integral field unit spectrographs allow the 2D exploration of the kinematics and stellar populations of galaxies, although they are generally restricted to small fields-of-view. Using the large field-of-view of the DEIMOS multislit spectrograph on Keck and our Stellar Kinematics using Multiple Slits technique, we are able to extract sky-subtracted stellar light spectra to large galactocentric radii. Here, we present a new DEIMOS mask design named SuperSKiMS that explores large spatial scales without sacrificing high spatial sampling. We simulate a set of observations with such a mask design on the nearby galaxy NGC 1023, measuring stellar kinematics and metallicities out to where the galaxy surface brightness is orders of magnitude fainter than the sky. With this technique we also reproduce the results from literature integral field spectroscopy in the innermost galaxy regions. In particular, we use the simulated NGC 1023 kinematics to model its total mass distribution to large radii, obtaining comparable results with those from published integral field unit observation. Finally, from new spectra of NGC 1023, we obtain stellar 2D kinematics and metallicity distributions that show good agreement with integral field spectroscopy results in the overlapping regions. In particular, we do not find a significant offset between our Stellar Kinematics using Multiple Slits and the ATLAS3D stellar velocity dispersion at the same spatial locations.
Higher fruit intake is associated with lower risk of all-cause and disease-specific mortality. However, data on individual fruits are limited, and the generalisability of these findings to the elderly remains uncertain. The objective of this study was to examine the association of apple intake with all-cause and disease-specific mortality over 15 years in a cohort of women aged over 70 years. Secondary analyses explored relationships of other fruits with mortality outcomes. Usual fruit intake was assessed in 1456 women using a FFQ. Incidence of all-cause and disease-specific mortality over 15 years was determined through the Western Australian Hospital Morbidity Data system. Cox regression was used to determine the hazard ratios (HR) for mortality. During 15 years of follow-up, 607 (41·7 %) women died from any cause. In the multivariable-adjusted analysis, the HR for all-cause mortality was 0·89 (95 % CI 0·81, 0·97) per sd (53 g/d) increase in apple intake, HR 0·80 (95 % CI 0·65, 0·98) for consumption of 5–100 g/d and HR 0·65 (95 % CI 0·48, 0·89) for consumption of >100 g/d (an apple a day), compared with apple intake of <5 g/d (Pfor trend=0·03). Our analysis also found that higher apple intake was associated with lower risk for cancer mortality, and that higher total fruit and banana intakes were associated lower risk of CVD mortality (P<0·05). Our results support the view that regular apple consumption may contribute to lower risk of mortality.
A growing body of literature has explored the influence of physical activity on brain structure and function. While the mechanisms of this relationship remain largely speculative, recent research suggests that one of the effects of physical exercise is an increase in synaptic long-term potentiation (LTP). This has not yet been explored directly in humans due to the difficulty of measuring LTP non-invasively. However, we have previously established that LTP-like changes in visual-evoked potentials (VEPs) can be measured in humans. Here, we investigated whether physical fitness status affects the degree of visual sensory LTP. Using a self-report measure of physical activity, participants were split into two groups: a high-activity group, and a low-activity group. LTP was measured and compared between the two groups using the previously established electroencephalography-LTP paradigm, which assesses the degree to which the N1b component of the VEP elicited by a sine grating is potentiated (enhanced) following a rapid “tetanic” presentation of that grating. Both groups demonstrated increased negativity in the amplitude of the N1b component of the VEP immediately after presentation of the visual “tetanus,” indicating potentiation. However, after a 30-min rest period, the N1b for the high-activity group remained potentiated while the N1b for the low-activity group returned to baseline. This study presents the first evidence for the impact of self-reported levels of physical activity on LTP in humans, and sheds light on potential neurological mechanisms underlying the relationship between physical fitness and cognition. (JINS, 2015, 21, 831–840)
Food liking-disliking patterns may strongly influence food choices and health. Here we assess: (1) whether food preference patterns are genetic/environmentally driven; and (2) the relationship between metabolomics profiles and food preference patterns in a large population of twins. 2,107 individuals from TwinsUK completed an online food and lifestyle preference questionnaire. Principle components analysis was undertaken to identify patterns of food liking-disliking. Heritability estimates for each liking pattern were obtained by structural equation modeling. The correlation between blood metabolomics profiles (280 metabolites) and each food liking pattern was assessed in a subset of 1,491 individuals and replicated in an independent subset of monozygotic twin pairs discordant for the liking pattern (65 to 88 pairs). Results from both analyses were meta-analyzed. Four major food-liking patterns were identified (Fruit and Vegetable, Distinctive Tastes, Sweet and High Carbohydrate, and Meat) accounting for 26% of the total variance. All patterns were moderately heritable (Fruit and Vegetable, h2[95% CI]: 0.36 [0.28; 0.44]; Distinctive Tastes: 0.58 [0.52; 0.64]; Sweet and High Carbohydrate: 0.52 [0.45, 0.59] and Meat: 0.44 [0.35; 0.51]), indicating genetic factors influence food liking-disliking. Overall, we identified 14 significant metabolite associations (Bonferroni p < 4.5 × 10−5) with Distinctive Tastes (8 metabolites), Sweet and High Carbohydrate (3 metabolites), and Meat (3 metabolites). Food preferences follow patterns based on similar taste and nutrient characteristics and these groupings are strongly determined by genetics. Food preferences that are strongly genetically determined (h2 ≥ 0.40), such as for meat and distinctive-tasting foods, may influence intakes more substantially, as demonstrated by the metabolomic associations identified here.
Hypertension is associated with an increased risk of dementia and
depression with uncertain longitudinal associations with brain
To examine lifetime blood pressure as a predictor of brain structure in
A total of 190 participants (mean age 69.3 years) from the Whitehall II
study were screened for hypertension six times (1985–2013). In 2012–2013,
participants had a 3T-magnetic resonance imaging (MRI) brain scan. Data
from the MRI were analysed using automated and visual measures of global
atrophy, hippocampal atrophy and white matter hyperintensities.
Longitudinally, higher mean arterial pressure predicted increased
automated white matter hyperintensities (P<0.002).
Cross-sectionally, hypertensive participants had increased automated
white matter hyperintensities and visually rated deep white matter
hyperintensities. There was no significant association with global or
Long-term exposure to high blood pressure predicts hyperintensities,
particularly in deep white matter. The greatest changes are seen in those
with severe forms of hypertension, suggesting a dose–response
Multi-annual records of glacier surface meteorology and energy balance are necessary to resolve glacier–climate interactions but remain sparse, especially in the Southern Hemisphere. To address this, we present a record from the ablation zone of Brewster Glacier, New Zealand, between October 2010 and September 2012. The mean air temperature was 1.2°C at 1760 m a.s.l., with only a moderate temperature difference between the warmest and coldest months (∼8°C). Long-term annual precipitation was estimated to exceed 6000 mm a−1, with the majority of precipitation falling within a few degrees of the freezing level. The main melt season was between November and March (83% of annual ablation), but melt events occurred during all months. Annually, net radiation was positive (a source of energy) and supplied 64% of the melt energy, driven primarily by net shortwave radiation. Net longwave radiation was often positive during cloudy conditions in summer, demonstrating the radiative importance of clouds during melt. Turbulent sensible and latent heat fluxes were directed towards the surface in the summer months, accounting for just over a third of the energy for melt (34%). The energy gain associated with rainfall was small except during heavy events in summer.
We present a data-assimilation technique based on a variational formulation and a Lagrange multipliers approach to enforce the Navier–Stokes equations. A general operator (referred to as the measure operator) is defined in order to mathematically describe an experimental measure. The presented method is applied to the case of mean flow measurements. Such a flow can be described by the Reynolds-averaged Navier–Stokes (RANS) equations, which can be formulated as the classical Navier–Stokes equations driven by a forcing term involving the Reynolds stresses. The stress term is an unknown of the equations and is thus chosen as the control parameter in our study. The data-assimilation algorithm is derived to minimize the error between a mean flow measurement and the measure performed on a numerical solution of the steady, forced Navier–Stokes equations; the optimal forcing is found when this error is minimal. We demonstrate the developed data-assimilation framework on a test case: the two-dimensional flow around an infinite cylinder at a Reynolds number of
. The mean flow is computed by time-averaging instantaneous flow fields from a direct numerical simulation (DNS). We then perform several ‘measures’ on this mean flow and apply the data-assimilation method to reconstruct the full mean flow field. Spatial interpolation, extrapolation, state vector reconstruction and noise filtering are considered independently. The efficacy of the developed identification algorithm is quantified for each of these cases and compared with more traditional methods when possible. We also analyse the identified forcing in terms of unsteadiness characterization, present a way to recover the second-order statistical moments of the fluctuating velocities and finally explore the possibility of pressure reconstruction from velocity measurements.
Formal grammars such as L-systems have long been used to describe plant growth dynamics. In this article, they are used for a new purpose. The aim is to build a symbolic method that enables the computation of the stochastic distribution associated with the number of complex structures in plants whose organogenesis is driven by a multitype branching process. For that purpose, a new combinatorial framework is set in which plant structure is coded by a Dyck word. Moreover, organogenesis is represented by stochastic F0L-systems. In doing so, the problem is equivalent to determining the distribution of patterns in random words generated by a stochastic F0L-system. This method finds interesting applications in the parameter identification of stochastic models of plant development.
Fluid balance and renal function can be difficult to manage in the postoperative infant with tetralogy of Fallot. High fluid volumes are often needed to maintain cardiac output.
To stratify patients at risk for advanced renal support following tetralogy of Fallot repair.
Retrospective analysis of all consecutive tetralogy of Fallot cases operated at a single centre in a 3-year period.
A total of 41 children were identified. All cases had loop diuretics administered. Of the cases, 17% required support with a peritoneal dialysis catheter, with only one complication of peritoneal dialysis catheter blockage. The mean length of paediatric intensive care unit stay in those receiving peritoneal dialysis catheter insertion was prolonged by an additional mean of 6 days (p<0.001). No statistical significance was found between those children requiring peritoneal dialysis and those who did not when considering patient age and weight at time of repair, cardiopulmonary bypass and aortic cross clamp times, the presence of a transannular patch, or junctional ectopic tachycardia. However, volume requirement of more than 35 ml/kg in the first 12 hours following repair did increase the likelihood to need peritoneal dialysis (p<0.0001). Furthermore, the higher the peak creatinine, the longer the stay on intensive care (p<0.01).
Peritoneal dialysis is an effective method of dealing with fluid balance in children after tetralogy of Fallot repair, with minimal complications. Early consideration should be given to peritoneal dialysis when it is clear that high fluid volumes are required postoperatively.
Poor maternal nutrition predisposes offspring to metabolic disease. This predisposition is modified by various postnatal factors. We hypothesised that coupled to the initial effects of developmental programming due to a maternal low-protein diet, a second hit resulting from increased offspring postnatal sugar consumption would lead to additional changes in metabolism and adipose tissue function. The objective of the present study was to determine the effects of sugared water consumption (5 % sucrose in the drinking-water) on adult offspring adiposity as a ‘second hit’ following exposure to maternal protein restriction during pregnancy. We studied four offspring groups: (1) offspring of mothers fed the control diet (C); (2) offspring of mothers fed the restricted protein diet (R); (3) offspring of control mothers that drank sugared water (C-S); (4) offspring of restricted mothers that drank sugared water (R-S). Maternal diet in pregnancy was considered the first factor and sugared water consumption as the second factor – the second hit. Body weight and total energy consumption, before and after sugared water consumption, were similar in all the groups. Sugared water consumption increased TAG, insulin and cholesterol concentrations in both the sexes of the C-S and R-S offspring. Sugared water consumption increased leptin concentrations in the R-S females and males but not in the R offspring. There was also an interaction between sugared water and maternal diet in males. Sugared water consumption increased adipocyte size and adiposity index in both females and males, but the interaction with maternal diet was observed only in females. Adiposity index and plasma leptin concentrations were positively correlated in both the sexes. The present study shows that a second hit during adulthood can amplify the effects of higher adiposity arising due to poor maternal pregnancy diet in an offspring sex dependent fashion.