Flavonoid-rich fruits and vegetables improve microvascular reactivity and inflammatory status in men at risk of cardiovascular disease – FLAVURS: a randomized controlled trial

BACKGROUND: Observed associations between increased fruit and vegetable (F&V) consumption, particularly those F&Vs that are rich in flavonoids, and vascular health improvements require confirmation in adequately powered randomized controlled trials. OBJECTIVE: This study was designed to measure the dose-response relation between high-flavonoid (HF), low-flavonoid (LF), and habitual F&V intakes and vascular function and other cardiovascular disease (CVD) risk indicators. DESIGN: A single-blind, dose-dependent, parallel randomized controlled dietary intervention study was conducted. Male and female low-F&V consumers who had a ≥1.5-fold increased risk of CVD (n = 174) were randomly assigned to receive an HF F&V, an LF F&V, or a habitual diet, with HF and LF F&V amounts sequentially increasing by 2, 4, and 6 (+2, +4, and +6) portions/d every 6 wk over habitual intakes. Microvascular reactivity (laser Doppler imaging with iontophoresis), arterial stiffness [pulse wave velocity, pulse wave analysis (PWA)], 24-h ambulatory blood pressure, and biomarkers of nitric oxide (NO), vascular function, and inflammation were determined at baseline and at 6, 12, and 18 wk. RESULTS: In men, the HF F&V diet increased endothelium-dependent microvascular reactivity (P = 0.017) with +2 portions/d (at 6 wk) and reduced C-reactive protein (P = 0.001), E-selectin (P = 0.0005), and vascular cell adhesion molecule (P = 0.0468) with +4 portions/d (at 12 wk). HF F&Vs increased plasma NO (P = 0.0243) with +4 portions/d (at 12 wk) in the group as a whole. An increase in F&Vs, regardless of flavonoid content in the groups as a whole, mitigated increases in vascular stiffness measured by PWA (P = 0.0065) and reductions in NO (P = 0.0299) in the control group. CONCLUSION: These data support recommendations to increase F&V intake to ≥6 portions daily, with additional benefit from F&Vs that are rich in flavonoids, particularly in men with an increased risk of CVD. This trial was registered at www.controlled-trials.com as ISRCTN47748735.

A library at Antium?

This chapter considers the implications of accepting the 'Antium' crux in Galen's recently discovered Peri Alphas ( = De Indolentia). It examines what we know about the Roman imperial villa library at Antium, and what this new testimony can add.

Toward a scholarly edition of Beckett's critical writings

This essay outlines the case for a new, scholarly edition of Beckett's critical writings, one that would be complete and with critical annotation. For the most part these texts (critical writings, tributes, in memoria and epigraphs) have been published in a range of places. As well as in the magazines, newspapers, books and special-issue publications in which pieces originally appeared, a number were collected in Disjecta (Calder 1983 & Grove 1984). This volume, however, is not exhaustive; it misses out a number of important texts (not least Proust) and contains some textual inaccuracies. Furthermore, Beckett's critical writings are currently not available from the UK publishers Faber and the Grove Press Centenary Edition of Beckett's works, the fourth volume of which contains a section entitled ‘Criticism’, presents only three works of criticism by Beckett (Proust, ‘Dante … Bruno . Vico . . Joyce’ and ‘Three Dialogues’). In this essay, we give a brief (and far from exhaustive) overview of the publication history of Beckett's non-fiction prose texts, before outlining some of the editorial challenges they pose. Although Beckett tended to be dismissive of these works, they form an integral part of his canon.

Carotenoids but not flavonoids are associated with improvements in spatial working memory in younger adults in a flavonoid-rich v. -poor fruit and vegetable intervention study

Findings from animal studies suggest that components of fruit and vegetables (F&V) may protect against, and even reverse, age-related decline(1,2) in aspects of cognitive functioning such as spatial working memory (SWM). Human subjects in vivo and in vitro studies indicate that anti-inflammatory, anti-oxidant and cell-signalling properties of flavonoids and carotenoids, non-nutrient components of F&V, may underpin this protective effect(3–5). The Flavonoid University of Reading Study (FLAVURS), designed to explore the dose-response relationship between dietary F&V flavonoids and CVD, enabled the investigation of such an association with SWM. FLAVURS is an 18-week parallel three-arm randomised controlled dietary intervention trial with four time points, measured at 6-weekly intervals from baseline. Low F&V consumers at risk of CVD aged 26–70 years were randomly assigned to high flavonoid (HF), low flavonoid (LF) or control group. F&V intake increased by two daily 80 g portions every 6 weeks, with either HF or LF F&V, in addition to each participant's habitual diet, while controls maintained their habitual diet. At each visit, participants completed a cognitive test battery with SWM as the primary outcome. The HF group showed significantly higher levels of urinary flavonoids than LF or controls at 12 weeks (P<0.001) as expected, but surprisingly only higher levels than LF at 18 weeks (P<0.01). The LF group showed higher levels of plasma carotenoids than the other groups at 18 weeks (P<0.001). No group differences were found for SWM overall, however, age-group sub-analyses (26–50 and 51–70 years of age) showed differences from 0 to 18 weeks for younger adults, with LF improving significantly more than the other two groups on SWM (P<0.05). As nutritional absorption is known to decrease with age, separate stepwise regressions were performed on the two age groups irrespective of dietary group, with urinary flavonoids and plasma carotenoids as predictors. For younger adults, improved SWM performance from 0 to 18 weeks was associated with higher carotenoid levels, β=0.28, t(55)=2.10, P<0.05, accounting for 7.5% of the variance, R2=0.075, F(1,54)=4.41, P=0.040. For older adults, no between-group SWM differences were found. Findings suggest that F&V-based flavonoids and carotenoids may provide benefits for cognitive function, and that carotenoids in particular may improve cognitive performance in SWM. Given that these benefits were restricted to younger adults, future work is needed to test the reliability of this finding, as well as determine the mechanisms by which age-dependent differences in F&V responsiveness occur.

Towards improving the framework for probabilistic forecast evaluation

The evaluation of forecast performance plays a central role both in the interpretation and use of forecast systems and in their development. Different evaluation measures (scores) are available, often quantifying different characteristics of forecast performance. The properties of several proper scores for probabilistic forecast evaluation are contrasted and then used to interpret decadal probability hindcasts of global mean temperature. The Continuous Ranked Probability Score (CRPS), Proper Linear (PL) score, and IJ Good’s logarithmic score (also referred to as Ignorance) are compared; although information from all three may be useful, the logarithmic score has an immediate interpretation and is not insensitive to forecast busts. Neither CRPS nor PL is local; this is shown to produce counter intuitive evaluations by CRPS. Benchmark forecasts from empirical models like Dynamic Climatology place the scores in context. Comparing scores for forecast systems based on physical models (in this case HadCM3, from the CMIP5 decadal archive) against such benchmarks is more informative than internal comparison systems based on similar physical simulation models with each other. It is shown that a forecast system based on HadCM3 out performs Dynamic Climatology in decadal global mean temperature hindcasts; Dynamic Climatology previously outperformed a forecast system based upon HadGEM2 and reasons for these results are suggested. Forecasts of aggregate data (5-year means of global mean temperature) are, of course, narrower than forecasts of annual averages due to the suppression of variance; while the average “distance” between the forecasts and a target may be expected to decrease, little if any discernible improvement in probabilistic skill is achieved.

Mapping power law distributions in digital health social networks: methods, interpretations, and practical implications

BACKGROUND: Social networks are common in digital health. A new stream of research is beginning to investigate the mechanisms of digital health social networks (DHSNs), how they are structured, how they function, and how their growth can be nurtured and managed. DHSNs increase in value when additional content is added, and the structure of networks may resemble the characteristics of power laws. Power laws are contrary to traditional Gaussian averages in that they demonstrate correlated phenomena. OBJECTIVES: The objective of this study is to investigate whether the distribution frequency in four DHSNs can be characterized as following a power law. A second objective is to describe the method used to determine the comparison. METHODS: Data from four DHSNs—Alcohol Help Center (AHC), Depression Center (DC), Panic Center (PC), and Stop Smoking Center (SSC)—were compared to power law distributions. To assist future researchers and managers, the 5-step methodology used to analyze and compare datasets is described. RESULTS: All four DHSNs were found to have right-skewed distributions, indicating the data were not normally distributed. When power trend lines were added to each frequency distribution, R(2) values indicated that, to a very high degree, the variance in post frequencies can be explained by actor rank (AHC .962, DC .975, PC .969, SSC .95). Spearman correlations provided further indication of the strength and statistical significance of the relationship (AHC .987. DC .967, PC .983, SSC .993, P<.001). CONCLUSIONS: This is the first study to investigate power distributions across multiple DHSNs, each addressing a unique condition. Results indicate that despite vast differences in theme, content, and length of existence, DHSNs follow properties of power laws. The structure of DHSNs is important as it gives insight to researchers and managers into the nature and mechanisms of network functionality. The 5-step process undertaken to compare actor contribution patterns can be replicated in networks that are managed by other organizations, and we conjecture that patterns observed in this study could be found in other DHSNs. Future research should analyze network growth over time and examine the characteristics and survival rates of superusers.

Targeting medication non-adherence behavior in selected autoimmune diseases: a systematic approach to digital health program development

Background 29 autoimmune diseases, including Rheumatoid Arthritis, gout, Crohn’s Disease, and Systematic Lupus Erythematosus affect 7.6-9.4% of the population. While effective therapy is available, many patients do not follow treatment or use medications as directed. Digital health and Web 2.0 interventions have demonstrated much promise in increasing medication and treatment adherence, but to date many Internet tools have proven disappointing. In fact, most digital interventions continue to suffer from high attrition in patient populations, are burdensome for healthcare professionals, and have relatively short life spans. Objective Digital health tools have traditionally centered on the transformation of existing interventions (such as diaries, trackers, stage-based or cognitive behavioral therapy programs, coupons, or symptom checklists) to electronic format. Advanced digital interventions have also incorporated attributes of Web 2.0 such as social networking, text messaging, and the use of video. Despite these efforts, there has not been little measurable impact in non-adherence for illnesses that require medical interventions, and research must look to other strategies or development methodologies. As a first step in investigating the feasibility of developing such a tool, the objective of the current study is to systematically rate factors of non-adherence that have been reported in past research studies. Methods Grounded Theory, recognized as a rigorous method that facilitates the emergence of new themes through systematic analysis, data collection and coding, was used to analyze quantitative, qualitative and mixed method studies addressing the following autoimmune diseases: Rheumatoid Arthritis, gout, Crohn’s Disease, Systematic Lupus Erythematosus, and inflammatory bowel disease. Studies were only included if they contained primary data addressing the relationship with non-adherence. Results Out of the 27 studies, four non-modifiable and 11 modifiable risk factors were discovered. Over one third of articles identified the following risk factors as common contributors to medication non-adherence (percent of studies reporting): patients not understanding treatment (44%), side effects (41%), age (37%), dose regimen (33%), and perceived medication ineffectiveness (33%). An unanticipated finding that emerged was the need for risk stratification tools (81%) with patient-centric approaches (67%). Conclusions This study systematically identifies and categorizes medication non-adherence risk factors in select autoimmune diseases. Findings indicate that patients understanding of their disease and the role of medication are paramount. An unexpected finding was that the majority of research articles called for the creation of tailored, patient-centric interventions that dispel personal misconceptions about disease, pharmacotherapy, and how the body responds to treatment. To our knowledge, these interventions do not yet exist in digital format. Rather than adopting a systems level approach, digital health programs should focus on cohorts with heterogeneous needs, and develop tailored interventions based on individual non-adherence patterns.

Production of acid whey hydrolysates applying an integrative process: effect of calcium on process performance

High ionic calcium concentration and the absence of caseinmacropeptides (CMP) in acid whey could influence the production of angiotensin-I-converting enzyme (ACE)-inhibitory hydrolysate and its bioactivity through the application of the integrative process. Therefore, the aim of the present study was to produce a hydrolysate from acid whey applying the integrative process. Process performance was evaluated based on protein adsorption capacity and conversion in relation to ACE-inhibitory activity (ACEi%) and ionic calcium concentration. Hydrolysates with high potency of their biological activity were produced (IC50 = 206-353 μg mL-1). High ionic calcium concentration in acid whey contributed to ACE-inhibitory activity. However, low β-lactoglobulin adsorption and conversion was observed. Optimisation of the resin volume increased the adsorption of β-lactoglobulin significantly but with lower selectivity. The changes in conversion value were not significant even at higher concentration of enzyme. Several ACE inhibitors derived from β-lactoglobulin that were identified before in sweet whey hydrolysates such as, IIAEKT, IIAE, IVTQ, LIVTQ, LIVTQT, LDAQ and LIVT were found. New peptides such as, SNICNI and ECCHGD derived from α-lactalbumin and BSA respectively were identified.

Behavioral economics, wearable devices, and cooperative games: results from a population-based intervention to increase physical activity

Background: Health care literature supports the development of accessible interventions that integrate behavioral economics, wearable devices, principles of evidence-based behavior change, and community support. However, there are limited real-world examples of large scale, population-based, member-driven reward platforms. Subsequently, a paucity of outcome data exists and health economic effects remain largely theoretical. To complicate matters, an emerging area of research is defining the role of Superusers, the small percentage of unusually engaged digital health participants who may influence other members. Objective: The objective of this preliminary study is to analyze descriptive data from GOODcoins, a self-guided, free-to-consumer engagement and rewards platform incentivizing walking, running and cycling. Registered members accessed the GOODcoins platform through PCs, tablets or mobile devices, and had the opportunity to sync wearables to track activity. Following registration, members were encouraged to join gamified group challenges and compare their progress with that of others. As members met challenge targets, they were rewarded with GOODcoins, which could be redeemed for planet- or people-friendly products. Methods: Outcome data were obtained from the GOODcoins custom SQL database. The reporting period was December 1, 2014 to May 1, 2015. Descriptive self-report data were analyzed using MySQL and MS Excel. Results: The study period includes data from 1298 users who were connected to an exercise tracking device. Females consisted of 52.6% (n=683) of the study population, 33.7% (n=438) were between the ages of 20-29, and 24.8% (n=322) were between the ages of 30-39. 77.5% (n=1006) of connected and active members met daily-recommended physical activity guidelines of 30 minutes, with a total daily average activity of 107 minutes (95% CI 90, 124). Of all connected and active users, 96.1% (n=1248) listed walking as their primary activity. For members who exchanged GOODcoins, the mean balance was 4,000 (95% CI 3850, 4150) at time of redemption, and 50.4% (n=61) of exchanges were for fitness or outdoor products, while 4.1% (n=5) were for food-related items. Participants were most likely to complete challenges when rewards were between 201-300 GOODcoins. Conclusions: The purpose of this study is to form a baseline for future research. Overall, results indicate that challenges and incentives may be effective for connected and active members, and may play a role in achieving daily-recommended activity guidelines. Registrants were typically younger, walking was the primary activity, and rewards were mainly exchanged for fitness or outdoor products. Remaining to be determined is whether members were already physically active at time of registration and are representative of healthy adherers, or were previously inactive and were incentivized to change their behavior. As challenges are gamified, there is an opportunity to investigate the role of superusers and healthy adherers, impacts on behavioral norms, and how cooperative games and incentives can be leveraged across stratified populations. Study limitations and future research agendas are discussed.

Attention bias to emotional faces varies by IQ and anxiety in Williams syndrome

Individuals with Williams syndrome (WS) often experience significant anxiety. A promising approach to anxiety intervention has emerged from cognitive studies of attention bias to threat. To investigate the utility of this intervention in WS, this study examined attention bias to happy and angry faces in individuals with WS (N=46). Results showed a significant difference in attention bias patterns as a function of IQ and anxiety. Individuals with higher IQ or higher anxiety showed a significant bias toward angry, but not happy faces, whereas individuals with lower IQ or lower anxiety showed the opposite pattern. These results suggest that attention bias interventions to modify a threat bias may be most effectively targeted to anxious individuals with WS with relatively high IQ.

Urinary metabolomic profiling to identify biomarkers of a flavonoid-rich and flavonoid-poor fruits and vegetables diet: the FLAVURS trial in adults: the FLAVURS trial

The present study aims to investigate the dose dependent effects of consuming diets enriched in flavonoid-rich and flavonoid-poor fruits and vegetables on the urine metabolome of adults who had a C1.5 fold increased risk of cardiovascular diseases. A single-blind, dose-dependent, parallel randomized controlled dietary intervention was conducted where volunteers (n = 126) were randomly assigned to one of three diets: high flavonoid diet, low flavonoid diet or habitual diet as a control for 18 weeks. High resolution LC– MS untargeted metabolomics with minimal sample cleanup was performed using an Orbitrap mass spectrometer. Putative biomarkers which characterize diets with high and low flavonoid content were selected by state-of-the-art data analysis strategies and identified by HR-MS and HR-MS/MS assays. Discrimination between diets was observed by application of two linear mixedmodels: one including a diet-time interaction effect and the second containing only a time effect. Valerolactones, phenolic acids and their derivatives were among sixteen biomarkers related to the high flavonoid dietary exposure. Four biomarkers related to the low flavonoid diet belonged to the family of phenolic acids. For the first time abscisic acid glucuronide was reported as a biomarker after a dietary intake, however its origins have to be examined by future hypothesis driven experiments using a more targeted approach. This metabolomic analysis has identified a number of dose dependent urinary biomarkers (i.e. proline betaine or iberin-N-acetyl cysteine), which can be used in future observation and intervention studies to assess flavonoids and nonflavonoid phenolic intakes and compliance to fruit and vegetable intervention.

Probing the 2D kinematic structure of early-type galaxies out to three effective radii

We detail an innovative new technique for measuring the two-dimensional (2D) velocity moments (rotation velocity, velocity dispersion and Gauss-Hermite coefficients h(3) and h(4)) of the stellar populations of galaxy haloes using spectra from Keck DEIMOS (Deep Imaging Multi-Object Spectrograph) multi-object spectroscopic observations. The data are used to reconstruct 2D rotation velocity maps. Here we present data for five nearby early-type galaxies to similar to three effective radii. We provide significant insights into the global kinematic structure of these galaxies, and challenge the accepted morphological classification in several cases. We show that between one and three effective radii the velocity dispersion declines very slowly, if at all, in all five galaxies. For the two galaxies with velocity dispersion profiles available from planetary nebulae data we find very good agreement with our stellar profiles. We find a variety of rotation profiles beyond one effective radius, i.e. rotation speed remaining constant, decreasing and increasing with radius. These results are of particular importance to studies which attempt to classify galaxies by their kinematic structure within one effective radius, such as the recent definition of fast- and slow-rotator classes by the Spectrographic Areal Unit for Research on Optical Nebulae project. Our data suggest that the rotator class may change when larger galactocentric radii are probed. This has important implications for dynamical modelling of early-type galaxies. The data from this study are available on-line.

Satellite Rainfall Estimates Over South America - Possible Applicability to the Water Management of Large Watersheds1

This work analyzes high-resolution precipitation data from satellite-derived rainfall estimates over South America, especially over the Amazon Basin. The goal is to examine whether satellite-derived precipitation estimates can be used in hydrology and in the management of larger watersheds of South America. High spatial-temporal resolution precipitation estimates obtained with the CMORPH method serve this purpose while providing an additional hydrometeorological perspective on the convective regime over South America and its predictability. CMORPH rainfall estimates at 8-km spatial resolution for 2003 and 2004 were compared with available rain gauge measurements at daily, monthly, and yearly accumulation time scales. The results show the correlation between satellite-derived and gauge-measured precipitation increases with accumulation period from daily to monthly, especially during the rainy season. Time-longitude diagrams of CMORPH hourly rainfall show the genesis, strength, longevity, and phase speed of convective systems. Hourly rainfall analyses indicate that convection over the Amazon region is often more organized than previously thought, thus inferring that basin scale predictions of rainfall for hydrological and water management purposes have the potential to become more skillful. Flow estimates based on CMORPH and the rain gauge network are compared to long-term observed average flow. The results suggest this satellite-based rainfall estimation technique has considerable utility. Other statistics for monthly accumulations also suggest CMORPH can be an important source of rainfall information at smaller spatial scales where in situ observations are lacking.