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Despite population-wide recommendations by the U.S. Dietary Guidelines for Americans and others to encourage health-promoting dietary patterns, the proportion of Americans following dietary recommendations remains low. The gaps in the adoption and integration of evidence-based dietary interventions, practices, programs, and policies (EBIs) into community and clinical settings signal the need to strengthen efforts in implementation science (IS) in nutrition research to understand and alleviate barriers to adopting and sustaining healthy dietary behaviors and practices. Equally important is the translation of this research into practice in a variety of settings and across the diversity of populations. Recognizing this need, the U.S. National Institutes of Health (NIH) 2020-2030 Strategic Plan for NIH Nutrition Research calls for the expansion of IS as a key opportunity to advancing nutrition research. This commentary highlights three scientific opportunities to stimulate IS in nutrition research and provides examples for each opportunity. These include: (a) Advance consideration of implementation and dissemination early in the design of interventions to facilitate opportunities for equitable scale-up and sustainability of EBIs, (b) Develop and test strategies for equitable implementation of nutrition and diet EBIs in health care and community settings, and (c) Build and strengthen the infrastructure, capacity, and expertise needed to increase use of IS in clinical and community nutrition research to swiftly move the research into practice. By advancing the three opportunities identified in this commentary, the scientific community has the potential to advance the field of nutrition research and IS with the ultimate goal of improving public health.While dietary guidelines have proven effective in clinical studies, most Americans do not follow these tested guidelines. More work is needed to bring research into practice so that all populations can benefit from the research. The U.S. National Institutes of Health recognizes this need and highlights it as a key opportunity in its 2020–2030 Strategic Plan for NIH Nutrition Research. This commentary describes three scientific opportunities that can help to stimulate the research needed to move research into practice, toward the ultimate goal of improving public health.

PDF - 73K, Supplementary Table S1. Effects of Various NSAIDs on Urinary 11-α-hydroxy-9, 15-dioxo-2, 3, 4, 5-tetranor-prostane-1, 20-dioic acid (PGE-M) levels.

PDF file - 40K, Effect of Erlotinib (6 mg/kg BW/day) on Time of Appearance of Methylnitrosourea- Induced Mammary Cancers in Female Sprague-Dawley Rats.

PDF - 982K, Supplementary figure 2. Common gene network for NO-naproxen and naproxen treated rat liver.

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Urinary bladder cancer prevention studies were performed with the nonsteroidal anti-inflammatory drugs (NSAID) naproxen (a standard NSAID with a good cardiovascular profile), sulindac, and their nitric oxide (NO) derivatives. In addition, the effects of the ornithine decarboxylase inhibitor, difluoromethylornithine (DFMO), alone or combined with a suboptimal dose of naproxen or sulindac was examined. Agents were evaluated at their human equivalent doses (HED), as well as at lower doses. In the hydroxybutyl(butyl)nitrosamine (OH-BBN) model of urinary bladder cancer, naproxen (400 or 75 ppm) and sulindac (400 ppm) reduced the incidence of large bladder cancers by 82%, 68%, and 44%, respectively, when the agents were initially given 3 months after the final dose of the carcinogen; microscopic cancers already existed. NO-naproxen was highly effective, whereas NO-sulindac was inactive. To further compare naproxen and NO-naproxen, we examined their effects on gene expression in rat livers following a 7-day exposure. Limited, but similar, gene expression changes in the liver were induced by both agents, implying that the primary effects of both are mediated by the parent NSAID. When agents were initiated 2 weeks after the last administration of OH-BBN, DFMO at 1,000 ppm had limited activity, a low dose of naproxen (75 ppm) and sulindac (150 ppm) were highly and marginally effective. Combining DFMO with suboptimal doses of naproxen had minimal effects, whereas the combination of DMFO and sulindac was more active than either agent alone. Thus, naproxen and NO-naproxen were highly effective, whereas sulindac was moderately effective in the OH-BBN model at their HEDs. Cancer Prev Res; 7(2); 246–54. ©2013 AACR.

Background Gene therapy based on viral vectors is a promising new approach and offers great potential for the study and the treatment of cardiac diseases. Nucleic acid-based transfection of human heart tissue could be considered a valid and translational alternative to the use of transgenic animal models in cardiovascular research. Purpose Here we explore the use of Living Myocardial Slices (LMS) as a platform for nucleic acid-based therapies. Rat LMS and Adeno-Associated viruses (AAV) were used to optimise and analyse gene transfer efficiency, viability, tissue functionality, and cell tropism in cardiac tissue. Human cardiac samples from failing (dilated cardiomyopathy) hearts were also used to validate the human model. In addition, we transfected and tested for the first time the regenerative effect of AAV-miR-199a in both healthy and pathologically overloaded LMS. Methods LMS (300 μm thick) were prepared and glued to PTFE-coated holders, mounted on custom stretchers, and cultured at physiological sarcomere length for 72-hours under electrical stimulation. Two recombinant AAV serotypes (AAV-6 and AAV-9) at different multiplicity of infection (MOI) expressing green fluorescent protein (GFP) or the miR-199 transgene were added to the surface of the LMS. Results AAV6 proved to be the most suitable serotype and 20,000 MOI the most efficient dose, as these conditions were proven not to affect LMS contractility and to have the highest transduction and penetrability efficiency. This serotype exhibited preferential cell tropism to cardiomyocytes and stromal cells (40% of transduction in both) in rat LMS, with lower efficiency in endothelial cells, (20% of transduction). In contrast, AAV6 in human failing LMS showed higher transduction efficiency in endothelial cells and myofibroblasts. Treatment with miR-199a significantly increased the active force of pathologically overstretched LMS, downregulated the expression of its target genes, and affected the proliferative capacity of LMS. Conclusion LMS can be used as a model for nucleic acid-based therapies and their transfection protocol can be adapted to samples obtained from failing human hearts. With great translational relevance, this model would accelerate preclinical studies of novel nucleic acid-based therapies for heart failure. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): British Heart Foundation

Background Nutrition plays a major role in the prevention and treatment of cardiovascular and other chronic diseases; hence, nutrition research is a priority for the National Heart, Lung, and Blood Institute (NHLBI). The purpose of this analysis is to describe the scope of NHLBI-funded extramural nutrition research grants over the past decade and offer insights into future opportunities for nutrition research relevant to NHLBI's mission. Methods Data were extracted using the Research, Condition, and Disease Categorization spending categories from the publicly available NIH Research Portfolio Online Reporting Tool Expenditures and Results. New 2018 and 2019 grants were coded into categories and mapped to the 2016 NHLBI Strategic Vision priorities. Results Approximately 90% of nutrition research funds supported extramural grants, particularly through investigator-initiated R series grants (69.6%). Of these, 19.8% were classified as clinical trials. Consistent nutrition-related topics, including physical activity, weight loss, fatty acids, metabolic syndrome, childhood obesity, and other topics such as gut microbiota, arterial stiffness, sleep duration, and meal timing, emerged in 2014-2019. Mapping of the NHLBI Strategic Vision objectives revealed that 32% of newly funded grants focused on pathobiological mechanisms important to the onset and progression of heart, lung, blood, and sleep disorders, with opportunities including developing novel diagnostic and therapeutic strategies and clinical and implementation science research. Discussion The findings show the breadth of NHLBI-funded nutrition research and highlight potential research opportunities for nutrition scientists.

Very-high Energy (VHE) gamma-ray astroparticle physics is a relatively young field, and observations over the past decade have surprisingly revealed almost two hundred VHE emitters which appear to act as cosmic particle accelerators. These sources are an important component of the Universe, influencing the evolution of stars and galaxies. At the same time, they also act as a probe of physics in the most extreme environments known - such as in supernova explosions, and around or after the merging of black holes and neutron stars. However, the existing experiments have provided exciting glimpses, but often falling short of supplying the full answer. A deeper understanding of the TeV sky requires a significant improvement in sensitivity at TeV energies, a wider energy coverage from tens of GeV to hundreds of TeV and a much better angular and energy resolution with respect to the currently running facilities. The next generation gamma-ray observatory, the Cherenkov Telescope Array Observatory (CTAO), is the answer to this need. In this talk I will present this upcoming observatory from its design to the construction, and its potential science exploitation. CTAO will allow the entire astronomical community to explore a new discovery space that will likely lead to paradigm-changing breakthroughs. In particular, CTA has an unprecedented sensitivity to short (sub-minute) timescale phenomena, placing it as a key instrument in the future of multi-messenger and multi-wavelength time domain astronomy. I will conclude the talk presenting the first scientific results obtained by the LST-1, the prototype of one CTAO telescope type - the Large-Sized Telescope, that is currently under commission., PoS: Proceedings of Science, 395, ISSN:1824-8039, Proceedings of 37th International Cosmic Ray Conference (ICRC2021)

Few studies have derived data-driven dietary patterns in youth in the USA. This study examined data-driven dietary patterns and their associations with BMI measures in predominantly low-income, racial/ethnic minority US youth. Data were from baseline assessments of the four Childhood Obesity Prevention and Treatment Research (COPTR) Consortium trials: NET-Works (534 2–4-year-olds), GROW (610 3–5-year-olds), GOALS (241 7–11-year-olds) and IMPACT (360 10–13-year-olds). Weight and height were measured. Children/adult proxies completed three 24-h dietary recalls. Dietary patterns were derived for each site from twenty-four food/beverage groups using k-means cluster analysis. Multivariable linear regression models examined associations of dietary patterns with BMI and percentage of the 95th BMI percentile. Healthy (produce and whole grains) and Unhealthy (fried food, savoury snacks and desserts) patterns were found in NET-Works and GROW. GROW additionally had a dairy- and sugar-sweetened beverage-based pattern. GOALS had a similar Healthy pattern and a pattern resembling a traditional Mexican diet. Associations between dietary patterns and BMI were only observed in IMPACT. In IMPACT, youth in the Sandwich (cold cuts, refined grains, cheese and miscellaneous) compared with Mixed (whole grains and desserts) cluster had significantly higher BMI (β= 0·99 (95 % CI 0·01, 1·97)) and percentage of the 95th BMI percentile (β= 4·17 (95 % CI 0·11, 8·24)). Healthy and Unhealthy patterns were the most common dietary patterns in COPTR youth, but diets may differ according to age, race/ethnicity or geographic location. Public health messages focused on healthy dietary substitutions may help youth mimic a dietary pattern associated with lower BMI.

The National Heart, Lung, and Blood Institute convened a multidisciplinary working group of hypertension researchers on December 6 to 7, 2018, in Bethesda, MD, to share current scientific knowledge in hypertension and to identify barriers to translation of basic into clinical science/trials and implementation of clinical science into clinical care of patients with hypertension. The goals of the working group were (1) to provide an overview of recent discoveries that may be ready for testing in preclinical and clinical studies; (2) to identify gaps in knowledge that impede translation; (3) to highlight the most promising scientific areas in which to pursue translation; (4) to identify key challenges and barriers for moving basic science discoveries into translation, clinical studies, and trials; and (5) to identify roadblocks for effective dissemination and implementation of basic and clinical science in real-world settings. The working group addressed issues that were responsive to many of the objectives of the National Heart, Lung, and Blood Institute Strategic Vision. The working group identified major barriers and opportunities for translating research to improved control of hypertension. This review summarizes the discussion and recommendations of the working group.

While conventional nutrition research has yielded biomarkers such as doubly labeled water for energy metabolism and 24-h urinary nitrogen for protein intake, a critical need exists for additional, equally robust biomarkers that allow for objective assessment of specific food intake and dietary exposure. Recent advances in high-throughput MS combined with improved metabolomics techniques and bioinformatic tools provide new opportunities for dietary biomarker development. In September 2018, the NIH organized a 2-d workshop to engage nutrition and omics researchers and explore the potential of multiomics approaches in nutritional biomarker research. The current Perspective summarizes key gaps and challenges identified, as well as the recommendations from the workshop that could serve as a guide for scientists interested in dietary biomarkers research. Topics addressed included study designs for biomarker development, analytical and bioinformatic considerations, and integration of dietary biomarkers with other omics techniques. Several clear needs were identified, including larger controlled feeding studies, testing a variety of foods and dietary patterns across diverse populations, improved reporting standards to support study replication, more chemical standards covering a broader range of food constituents and human metabolites, standardized approaches for biomarker validation, comprehensive and accessible food composition databases, a common ontology for dietary biomarker literature, and methodologic work on statistical procedures for intake biomarker discovery. Multidisciplinary research teams with appropriate expertise are critical to moving forward the field of dietary biomarkers and producing robust, reproducible biomarkers that can be used in public health and clinical research.

Introduction Mechanical load is a determinant of the healthy-to-failing myocardium transition. Extracellular vesicles (EVs) found in the range of 30–200 nm contain bioactive cargoes such as DNA, miRNA and proteins, and thus are considered important mediators of the paracrine crosstalk between cells in health and disease. Living myocardial slices (LMS) are 300μm layers of myocardial tissue that allow modelling of the intercellular communication in the heart. Purpose To assess whether secretion of EVs derived from physiological or pathological mechanically-loaded LMS regulate changes in myocardial contractility. Methods LMS were prepared from adult male Sprague-Dawley rats' left ventricle using a vibratome. LMS were stretched uniaxially using customised stretchers at a sarcomere length of 2.2μm and 2.4μm to recapitulate a physiological (P) and an overload (O) condition, respectively. LMS were cultured for 48-hours under electromechanical stimulation in M-199 media with Earls' salts, catecholamines, dexamethasone and triiodothyronine. After culture, media was harvested and processed for exosomes isolation by size exclusion chromatography. Particle size and concentration was assessed by nanoparticle tracking analysis. To validate the different phenotypes in LMS, force-stretch relationship was assessed after 48-hours culture. EVs isolated from P and O LMS were then used to treat physiologically loaded LMS (1x107 particles/LMS) and the force-stretch relationship was assessed after 48-hours culture. Results No significant difference in contractility was found between P and O LMS at any stretch increment (5.99±1.10 vs 2.82±0.92 mN/mm2 max force), whilst a significant increase in the passive tension of myocardial tissue was observed at 25% (15.90±2.77 vs 4.67±0.37 mN/mm2; p Conclusions EVs derived from physiologically loaded LMS improve the contractility of healthy LMS after 48-hours culture compared to PBS-treated LMS. Understanding how mechanical load correlates with specific loading of cargoes in EVs may reveal interesting therapeutic targets for the treatment of heart failure. Funding Acknowledgement Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): British Heart Foundation Physiological and overloaded phenotypesContractility of EVs treated LMS

Background Through the systematic large-scale profiling of metabolites, metabolomics provides a tool for biomarker discovery and improving disease monitoring, diagnosis, prognosis, and treatment response, as well as for delineating disease mechanisms and etiology. As a downstream product of the genome and epigenome, transcriptome, and proteome activity, the metabolome can be considered as being the most proximal correlate to the phenotype. Integration of metabolomics data with other -omics data in multi-omics analyses has the potential to advance understanding of human disease development and treatment. Aim of review To understand the current funding and potential research opportunities for when metabolomics is used in human multi-omics studies, we cross-sectionally evaluated National Institutes of Health (NIH)-funded grants to examine the use of metabolomics data when collected with at least one other -omics data type. First, we aimed to determine what types of multi-omics studies included metabolomics data collection. Then, we looked at those multi-omics studies to examine how often grants employed an integrative analysis approach using metabolomics data. Key scientific concepts of review We observed that the majority of NIH-funded multi-omics studies that include metabolomics data performed integration, but to a limited extent, with integration primarily incorporating only one other -omics data type. Some opportunities to improve data integration may include increasing confidence in metabolite identification, as well as addressing variability between -omics approach requirements and -omics data incompatibility.

Food insecurity, defined as a lack of consistent access to enough food for an active, healthy life, is a major public health concern with 11.8% of U.S. households (15.0 million) estimated to be affected at some point in 2017 according to the United States Department of Agriculture Economic Research Service. While the link between food insecurity, diet quality, and obesity is well documented in the literature, additional research and policy considerations are needed to better understand underlying mechanisms, associated risks, and effective strategies to mitigate the adverse impact of obesity related food insecurity on health. With its Strategic Plan for NIH Obesity Research, the NIH has invested in a broad spectrum of obesity research over the past 10 years to understand the multifaceted factors that contribute to the disease. The issue of food insecurity, obesity and nutrition is cross-cutting and relates to many activities and research priorities of the institutes and centers within the NIH. Several research gaps exist, including the mechanisms and pathways that underscore the complex relationship between food insecurity, diet, and weight outcomes, the impacts on pregnant and lactating women, children, and other vulnerable populations, its cumulative impact over the life course, and the development of effective multi-level intervention strategies to address this critical social determinant of health. Challenges and barriers such as the episodic nature of food insecurity and the inconsistencies of how food insecurity is measured in different studies also remain. Overall, food insecurity research aligns with the upcoming release of the Strategic Plan for NIH Nutrition Research and will continue to be prioritized in order to enhance health, lengthen life, reduce illness and disability and health disparities.

Introduction Mechanical overload plays an important role in the progression of chronic heart failure (CHF). Beside the numerous neurohormonal and chemical stimuli that contribute to structural and functional changes in the myocardium, intercellular communication mediated by extracellular vesicles (EVs), also plays a pivotal role in disease progression. Exosomes are a subset of EVs ranging between 30–150 nm; these mediators carry molecular cargoes such as miRNAs, mRNAs, DNA and several proteins. However, it is still unclear how specific pathological stimuli may induce a change in their release from tissues or a difference in their cargo content. Living myocardial slices (LMS) are ultra-thin sections of heart tissue, ranging from 100–400 μm in thickness. They retain the multicellularity, electromechanical physiology, biochemistry and extracellular matrix of the adult heart. Purpose To investigate whether mechanical load influences both the released amount and content of LMS-derived exosomes after 24 hours culture. Methods and results LMS were prepared from the left ventricle of male Sprague Dawley rats using a high precision vibratome. LMS were stretched in the direction of the muscle fibers at a sarcomere length (SL) of 2.2 μm to recapitulate physiological preload, and at 2.4 μm SL to recapitulate a condition of volume overload. LMS were cultured for 24 hours under electromechanical stimulation. Media containing LMS-derived exosomes was harvested after culture and processed for exosome isolation by size exclusion chromatography columns. Particle size and concentration were assessed by nanoparticle tracking analysis and protein quantity by microBCA assay. There was no significant difference in the size of exosomes between overload and physiological conditions, with an average mean size of 113.475±8.35 nm for the physiological and 129.3±16.35 nm for the overload condition (p=0.61; n=4 physiological; n=3 overload). Although there was not significant difference in exosome amount between physiological and overload condition, (7.00E+10±2.53E+09 vs 1.04E+11±5.77E+09 particles/ml) (p=0.57; n=4 physiological; n=3 overload), exosomes released from overloaded LMS showed a significant increase in protein content compared to physiologically loaded LMS (150.57±25.682 vs 66.045±9.855 μg/ml) (p=0.04; n=3 overload; n=2 physiological). Conclusions Mechanical load influences the cargo content of EVs secreted from LMS after 24 hours culture under electromechanical stimulation. Understanding how mechanical load correlates with specific cargoes in EVs will reveal novel therapeutic targets for the treatment of CHF. Funding Acknowledgement Type of funding source: Private grant(s) and/or Sponsorship. Main funding source(s): British Heart Foundation (BHF)

Applying the Behavior Change Technique Taxonomy has the potential to facilitate identification of effective childhood obesity intervention components. This article evaluates the feasibility of coding Childhood Obesity Prevention and Treatment Consortium interventions and compares reliability between external taxonomy-familiar coders and internal intervention-familiar coders. After training, coder pairs independently coded prespecified portions of intervention materials. An adjudication process was used to explore coding discrepancies. Reliability between internal and external coders was moderate (prevalence and bias-adjusted kappa .38 to .55). Reliability for specific target behaviors varied with substantial agreement for physical activity (.63 to .76) and moderate for dietary intake (.44 to .63). Applying the taxonomy to these interventions was feasible, but agreement was modest. Coding discrepancies highlight the importance of refining coding to capture the complexities of childhood obesity interventions, which often engage multiple recipients (e.g., parents and/or children) and address multiple behaviors (e.g., diet, physical activity, screen time).

Hispanics/Latinos are expected to constitute 25% of the U.S. population by 2060. Differences in the prevalence of health risk factors, chronic diseases, and access to and utilization of health-care services between Hispanics/Latinos and other populations in the U.S. have been documented. This study aimed to describe and analyze the landscape of Research Program Grants (RPGs) funded by the National Institutes of Health (NIH) between 2008 and 2015 involving Hispanic/Latino health research in six health condition areas—asthma, cancer, dementia, diabetes, liver/gallbladder disease, and obesity—and to identify opportunities for continued research in these areas. Using an NIH internal search engine, we identified new and renewal Hispanic/Latino health RPGs searching for specific Hispanic/Latino identifiers in the Title, Abstract, and Specific Aims. We used descriptive statistics to examine the distribution of funded RPGs by NIH disease-based classification codes for the six health condition areas of interest, and other selected characteristics. The most prominent clusters of research subtopics were identified within each health condition area, and performance sites were mapped at the city level. Within the selected time frame, 3,221 Hispanic/Latino health-related unique RPGs were funded (constituting 4.4% of all funded RPGs), and of those 625 RPGs were eligible for review and coding in the present study. Cancer and obesity were the most commonly studied health condition areas (72%), while studies on mechanisms of disease—biological and non-biological—(72.6%), behavioral research (42.1%) and epidemiological studies (38.1%) were the most common types of research. Most of the primary performance sites were in California, Texas, the northeastern U.S., and Illinois. The predominance of mechanistic, behavioral, and epidemiological studies in our analysis poses opportunities to evaluate knowledge gained and their clinical application, explore new research questions, or to update some methods or instruments. The findings of the present study suggest opportunities to expand research in understudied mechanisms of disease that could explain differences in prevalence of conditions like diabetes and cancer among different heritage groups. In addition, our findings suggest that the impact of interventions or policies designed to reduce health disparities, innovative multi-level interventions, implementation and dissemination studies, the role of health information technology on health outcomes, and the intersectionality of individual, sociocultural, geographic, and other factors on health outcomes, among others, are understudied approaches, which could potentially advance research in Hispanic/Latino health and contribute to the achievement of better health outcomes in this diverse population.

No robust detection of prompt electromagnetic counterparts to fast radio bursts (FRBs) has yet been obtained, in spite of several multi-wavelength searches carried out so far. Specifically, X/gamma-ray counterparts are predicted by some models. We planned on searching for prompt gamma-ray counterparts in the Insight-Hard X-ray Modulation Telescope (Insight-HXMT) data, taking advantage of the unique combination of large effective area in the keV-MeV energy range and of sub-ms time resolution. We selected 39 FRBs that were promptly visible from the High-Energy (HE) instrument aboard Insight-HXMT. After calculating the expected arrival times at the location of the spacecraft, we searched for a significant excess in both individual and cumulative time profiles over a wide range of time resolutions, from several seconds down to sub-ms scales. Using the dispersion measures in excess of the Galactic terms, we estimated the upper limits on the redshifts. No convincing signal was found and for each FRB we constrained the gamma-ray isotropic-equivalent luminosity and the released energy as a function of emission timescale. For the nearest FRB source, the periodic repeater FRB180916.J0158+65, we find $L_{\gamma,iso}, Comment: 15 pages, 3 figures, 6 tables, accepted by A&A

Background The influence of community characteristics on the effectiveness of childhood obesity prevention efforts is not well understood. Objective Examine the interaction of community characteristics with the relationship between community programmes and policies (CPPs) and dietary intake. Methods An observational study of 5138 children in grades K-8 in 130 US communities was conducted in 2013-2015. Key informant interviews identified and characterized CPPs. CPP scores were generated for the number of target behaviours (CPP-Behav) and the number of behaviour change strategies (CPP-Strat) addressed by all CPPs and CPPs with nutrition goals over the prior 6 years in each community. Dietary intake was assessed by dietary screener and included intake of sugar from sugar-sweetened beverages; energy-dense foods; fruits and vegetables; whole grains; and fibre. Multivariate statistical models assessed the interactions between US region, urbanicity, community-level income, and community-level race/ethnicity and CPP scores in relation to dietary intake. Results CPP-Strat was positively associated with healthier dietary intakes in the Northeast and West, and in high Hispanic communities; the reverse was true in the South, and in high African-American and low-income communities. The CPP-Behav was positively associated with healthier dietary intakes in the South and rural areas, and the reverse was true in the West. Conclusion The relationships between CPP index scores and dietary intake were most strongly influenced by region and urbanicity and to a lesser extent by community-level race/ethnicity and income. Findings suggest that different considerations may be needed for childhood obesity prevention efforts in communities with different characteristics.

Wire + Arc Additive Manufacturing (WAAM) is a promising manufacturing process for producing large aerospace components. Based on welding technology, the process is highly affordable, has a very high deposition rate and is not limited by chamber size. Ti-6Al-4V is a promising candidate material for this technology given that it is extensively used in aerospace applications and some large, high buy-fly ratio components can be more efficiently produced by WAAM than via the conventional machining from billet approach. There is currently limited knowledge about whether additional post processes including heat treatments and hot isostatic pressing are necessary to unlock the optimal mechanical properties of Ti-6Al-4V components produced by WAAM. This work explores a range of different post process treatments and the effects on the microstructure and tensile properties of Ti-6Al-4V components produced by WAAM. The relatively slow cooling rate (10-20Ks(-1)) during the beta-alpha transformation produced Widmanstatten-alpha and offered an optimal balance between strength and ductility. Hot Isostatic Pressing (HIPing) removed gas porosity but was not effective in improving strength or ductility. Residual tensile stresses in as-built components severely impair ductility and should be removed through stress relief treatments. (C) 2018 Elsevier B.V. All rights reserved.

Background Individual variability in response to multiple modalities of obesity treatment is well documented, yet our understanding of why some individuals respond while others do not is limited. The etiology of this variability is multifactorial; however, at present, we lack a comprehensive evidence base to identify which factors or combination of factors influence treatment response. Objectives This paper provides an overview and rationale of the Accumulating Data to Optimally Predict obesity Treatment (ADOPT) Core Measures Project, which aims to advance the understanding of individual variability in response to adult obesity treatment. This project provides an integrated model for how factors in the behavioral, biological, environmental, and psychosocial domains may influence obesity treatment responses and identify a core set of measures to be used consistently across adult weight-loss trials. This paper provides the foundation for four companion papers that describe the core measures in detail. Significance The accumulation of data on factors across the four ADOPT domains can inform the design and delivery of effective, tailored obesity treatments. ADOPT provides a framework for how obesity researchers can collectively generate this evidence base and is a first step in an ongoing process that can be refined as the science advances.

Background The ability to identify and measure behaviors that are related to weight loss and the prevention of weight regain is crucial to understanding the variability in response to obesity treatment and the development of tailored treatments. Objectives The overarching goal of the Accumulating Data to Optimally Predict obesity Treatment (ADOPT) Core Measures Project is to provide obesity researchers with guidance on a set of constructs and measures that are related to weight control and that span and integrate obesity-related behavioral, biological, environmental, and psychosocial domains. This article describes how the behavioral domain subgroup identified the initial list of high-priority constructs and measures to be included, and it describes practical considerations for assessing the following four behavioral areas: eating, activity, sleep, and self-monitoring of weight. Challenges and considerations for advancing the science related to weight loss and maintenance behaviors are also discussed. Significance Assessing a set of core behavioral measures in combination with those from other ADOPT domains is critical to improve our understanding of individual variability in response to adult obesity treatment. The selection of behavioral measures is based on the current science, although there continues to be much work needed in this field.

Context A review of interventions addressing obesity disparities could reveal gaps in the literature and provide guidance on future research, particularly for populations with a high prevalence of obesity and obesity-related cardiometabolic risk. Evidence acquisition A systematic review of clinical trials in obesity disparities research that were published in 2011–2016 in PubMed/MEDLINE resulted in 328 peer-reviewed articles. Articles were excluded if they had no BMI, weight, or body composition measure as primary outcome or were foreign ( n =201); were epidemiologic or secondary data analyses of clinical trials ( n =12); design or protocol papers ( n =54); systematic reviews ( n =3); or retracted or duplicates ( n =9). Forty-nine published trials were summarized and supplemented with a review of ongoing obesity disparities grants being funded by the National, Heart, Lung and Blood Institute. Evidence synthesis Of the 49 peer-reviewed trials, 27 targeted adults and 22 children only or parent–child dyads (5 of 22). Interventions were individually focused; mostly in single settings (e.g., school or community); of short duration (mostly ≤12 months); and primarily used behavioral modification (e.g., self-monitoring) strategies. Many of the trials had small sample sizes and moderate to high attrition rates. A meta-analysis of 13 adult trials obtained a pooled intervention effect of BMI –1.31 (95% CI=–2.11, –0.52, p =0.0012). Institutional review identified 140 ongoing obesity-related health disparities grants, but only 19% ( n =27) were clinical trials. Conclusions The reviews call for cardiovascular-related obesity disparities research that is long term and includes population research, and multilevel, policy, and environmental, or "whole of community," interventions.

Objective:To describe snacking characteristics and patterns in children and examine associations with diet quality and BMI.Design:Children’s weight and height were measured. Participants/adult proxies completed multiple 24 h dietary recalls. Snack occasions were self-identified. Snack patterns were derived for each sample using exploratory factor analysis. Associations of snacking characteristics and patterns with Healthy Eating Index-2010 (HEI-2010) score and BMI were examined using multivariable linear regression models.Setting:Childhood Obesity Prevention and Treatment Research (COPTR) Consortium, USA: NET-Works, GROW, GOALS and IMPACT studies.Participants:Predominantly low-income, racial/ethnic minorities: NET-Works (n534, 2–4-year-olds); GROW (n610, 3–5-year-olds); GOALS (n241, 7–11-year-olds); IMPACT (n360, 10–13-year-olds).Results:Two snack patterns were derived for three studies: a meal-like pattern and a beverage pattern. The IMPACT study had a similar meal-like pattern and a dairy/grains pattern. A positive association was observed between meal-like pattern adherence and HEI-2010 score (Pfor trend < 0⋅01) and snack occasion frequency and HEI-2010 score (βcoefficient (95 % CI): NET-Works, 0⋅14 (0⋅04, 0⋅23); GROW, 0⋅12 (0⋅02, 0⋅21)) among younger children. A preference for snacking while using a screen was inversely associated with HEI-2010 score in all studies except IMPACT (βcoefficient (95 % CI): NET-Works, −3⋅15 (−5⋅37, −0⋅92); GROW, −2⋅44 (−4⋅27, −0⋅61); GOALS, −5⋅80 (−8⋅74, −2⋅86)). Associations with BMI were almost all null.Conclusions:Meal-like and beverage patterns described most children’s snack intake, although patterns for non-Hispanic Blacks or adolescents may differ. Diets of 2–5-year-olds may benefit from frequent meal-like pattern snack consumption and diets of all children may benefit from decreasing screen use during eating occasions.

As we commemorate the 70th anniversary of the National Heart, Lung, and Blood Institute and celebrate important milestones that have been achieved by the division of cardiovascular sciences, it is imperative that division of cardiovascular sciences and the Extramural Research community at-large continue to address critical public health challenges that persist within the area of cardiovascular diseases. The National Heart, Lung, and Blood Institute Strategic Vision, developed with extensive input from the extramural research community and published in 2016, included overarching goals and strategic objectives that serve to provide a general blueprint for sustaining the legacy of the institute by leveraging opportunities in emerging scientific areas (eg, regenerative medicine, omics technology, data science, precision medicine, and mobile health), finding new ways to address enduring challenges (eg, social determinants of health, health inequities, prevention, and health promotion), and training the next generation of heart, lung, blood, and sleep researchers. Division of cardiovascular sciences has developed a strategic vision implementation plan to provide a cardiovascular framing for the pursuit of the institutes overarching goals and strategic objectives garnered from the input of the broader National Heart, Lung, and Blood Institute community. This plan highlights 6 scientific focus areas that demonstrate a cross-cutting and multifaceted approach to addressing cardiovascular sciences, including (1) addressing social determinants of cardiovascular health and health inequities, (2) enhancing resilience, (3) promoting cardiovascular health and preventing cardiovascular diseases across the lifespan, (4) eliminating hypertension-related cardiovascular diseases, (5) reducing the burden of heart failure, and (6) preventing vascular dementia. These priorities will guide our efforts in institute-driven activities in the coming years but will not exclude development of other novel ideas or the support of investigator-initiated grant awards. The Division of Cardiovascular Sciences strategic vision implementation plan is a living document that will evolve with iterative dialogue with the National Heart, Lung, and Blood Institute community and adapt as the dynamic scientific landscape changes to seize emerging opportunities.

Nutrition plays an important role in health promotion and disease prevention and treatment across the lifespan. Physicians and other healthcare professionals are expected to counsel patients about nutrition, but recent surveys report minimal to no improvements in medical nutrition education in US medical schools. A workshop sponsored by the National Heart, Lung, and Blood Institute addressed this gap in knowledge by convening experts in clinical and academic health professional schools. Representatives from the National Board of Medical Examiners, the Accreditation Council for Graduate Medical Education, the Liaison Committee on Medical Education, and the American Society for Nutrition provided relevant presentations. Reported is an overview of lessons learned from nutrition education efforts in medical schools and health professional schools including interprofessional domains and competency-based nutrition education. Proposed is a framework for coordinating activities of various entities using a public-private partnership platform. Recommendations for nutrition research and accreditation are provided.

Objective To describe and elucidate the time trends of the academic productivity of NHLBI's obesity-related research funding via bibliometric analysis of 30 years of NHLBI-supported obesity-related publications. Methods In total, 3,545 NHLBI-funded obesity-related publications were identified in the Thomson Reuters InCites™ database. Shared references in a community detection algorithm were used to identify publication topics. Characteristics of publications and topical communities were analyzed based on citation count and percentile rank. A percentile rank >90 was considered “highly cited.” Results Obesity-related publications increased more than 10-fold over 30 years, whereas NHLBI-funded publications only increased twofold NHLBI-funded obesity publications were cited a median of 23 times (IQR 8-55, range 0-2,047, mean 52). Thirty percent of these publications were highly cited compared to the expected ten percent. Six topical communities were present in 1983 compared to 16 in 2013. The most highly cited topical areas were sleep (n = 199 publications, 38% highly cited), cardiovascular morbidity and mortality (n = 277, 36%), obesity correlates and consequences (n = 588, 35%), and asthma and inflammation (n = 283, 35%). Conclusions NHLBI-funded obesity publications have contributed substantially to the obesity literature, with many highly cited. Publications grew in number and topical diversity over 30 years and grew at a faster rate than total NHLBI publications.

The ability to identify and measure behaviors that are related to weight loss and the prevention of weight regain is crucial to understanding the variability in response to obesity treatment and the development of tailored treatments.The overarching goal of the Accumulating Data to Optimally Predict obesity Treatment (ADOPT) Core Measures Project is to provide obesity researchers with guidance on a set of constructs and measures that are related to weight control and that span and integrate obesity-related behavioral, biological, environmental, and psychosocial domains. This article describes how the behavioral domain subgroup identified the initial list of high-priority constructs and measures to be included, and it describes practical considerations for assessing the following four behavioral areas: eating, activity, sleep, and self-monitoring of weight. Challenges and considerations for advancing the science related to weight loss and maintenance behaviors are also discussed.Assessing a set of core behavioral measures in combination with those from other ADOPT domains is critical to improve our understanding of individual variability in response to adult obesity treatment. The selection of behavioral measures is based on the current science, although there continues to be much work needed in this field.

Background: One-half of US adults report using a dietary supplement. NHANES has traditionally assessed dietary supplement use via a 30-d questionnaire but in 2007 added a supplement module to the 24-h dietary recall (24HR). Objective: We compared these 2 dietary assessment methods, examined potential biases in the methods, and determined the effect that instrument choice had on estimates of prevalence of multivitamin/multimineral dietary supplement (MVMM) use. Methods: We described prevalence of dietary supplement use by age, sex, and assessment instrument in 12,285 adults in the United States (>19 y of age) from NHANES 2007–2010. Results: When using data from the questionnaire alone, 29.3% ± 1.0% of men and 35.5% ± 1.0% of women were users of MVMMs, whereas data from the 24HR only produced prevalence estimates of 26.3% ± 1.1% for men and 33.2% ± 1.0% for women. When using data from both instruments combined, 32.3% ± 1.2% of men and 39.5% ± 1.1% of women were classified as MVMM users. Prevalence estimates were significantly higher by 2–9% in all age–sex groups when using information from both instruments combined than when using data from either instrument individually. A digit preference bias and flattened slope phenomenon were observed in responses to the dietary supplement questionnaire. A majority (67%) of MVMMs were captured on both instruments, whereas 19% additional MVMMs were captured on the questionnaire and 14% additional on the 24HR. Of those captured only on the 24HR, 26% had missing label information, whereas only 12% and 9% of those captured on the questionnaire or both, respectively, had missing information. Conclusions: Use of both the dietary supplement questionnaire and the 24HR can provide advantages to researchers over the use of a single instrument and potentially capture a larger fraction of dietary supplement users.

BackgroundThe impact of community-based obesity prevention efforts on child nutrition has not been adequately studied.ObjectiveExamine relationships between number, type and intensity of community programs and policies (CPPs) and child nutrition.MethodsAn observational study of 5138 children (grades K-8) in 130 U.S. communities was conducted in 2013-2015. CPPs were identified by 10-14 key informant interviews per community. CPPs were characterized based on: count, intensity, number of different strategies used and number of different behaviours targeted. Scores for the prior 6years were calculated separately for CPPs that addressed primarily nutrition, primarily physical activity (PA) or total combined. Child intakes were calculated from a dietary screener and dietary behaviours were based on survey responses. Multi-level statistical models assessed associations between CPP indices and nutrition measures, adjusting for child and community-level covariates.ResultsImplementing more types of strategies across all CPPs was related to lower intakes of total added sugar (when CPPs addressed primarily PA), sugar-sweetened beverages (for nutrition and PA CPPs) and energy-dense foods of minimal nutritional value (for total CPPs). Addressing more behaviours was related to higher intakes of fruit and vegetables (for nutrition and total CPPs) and fibre (total CPPs). Higher count and intensity (PA and total CPPs) were related to more consumption of lower fat compared with higher fat milk. A higher count (PA CPPs) was related to fewer energy-dense foods and whole grains. No other relationships were significant at P&nbsp

Urinary bladder cancer prevention studies were performed with the nonsteroidal anti-inflammatory drugs (NSAID) naproxen (a standard NSAID with a good cardiovascular profile), sulindac, and their nitric oxide (NO) derivatives. In addition, the effects of the ornithine decarboxylase inhibitor, difluoromethylornithine (DFMO), alone or combined with a suboptimal dose of naproxen or sulindac was examined. Agents were evaluated at their human equivalent doses (HED), as well as at lower doses. In the hydroxybutyl(butyl)nitrosamine (OH-BBN) model of urinary bladder cancer, naproxen (400 or 75 ppm) and sulindac (400 ppm) reduced the incidence of large bladder cancers by 82%, 68%, and 44%, respectively, when the agents were initially given 3 months after the final dose of the carcinogen; microscopic cancers already existed. NO-naproxen was highly effective, whereas NO-sulindac was inactive. To further compare naproxen and NO-naproxen, we examined their effects on gene expression in rat livers following a 7-day exposure. Limited, but similar, gene expression changes in the liver were induced by both agents, implying that the primary effects of both are mediated by the parent NSAID. When agents were initiated 2 weeks after the last administration of OH-BBN, DFMO at 1,000 ppm had limited activity, a low dose of naproxen (75 ppm) and sulindac (150 ppm) were highly and marginally effective. Combining DFMO with suboptimal doses of naproxen had minimal effects, whereas the combination of DMFO and sulindac was more active than either agent alone. Thus, naproxen and NO-naproxen were highly effective, whereas sulindac was moderately effective in the OH-BBN model at their HEDs. Cancer Prev Res; 7(2); 246–54. ©2013 AACR.

ARGO-YBJ is a “full coverage” air shower detector consisting of Resistive Plate Chambers(RPCs) at the Yangbajing High Altitude Cosmic Ray Laboratory (Tibet, China) at 4300 m a.s.l. (lat=30.11° N, long=90.53° E). Using the data collected with a carpet of RPCs (1900 m 2 , about 1/3 of the whole ARGO-YBJ detector), the cosmic ray shadowing effect due to the Moon was studied. The 50% angular resolution is found to be ∼1.2° with the Chess-board method and the Moon shadow with a significance of 4.9 σ is found displaced by 0.7° westward and 0.5° northward with respect to the expected position by the equi-zenith angle Method.

OBJECTIVES: The recent release of the Strategic Plan for NIH Nutrition Research (SPNR) provides a unique opportunity for advancements in nutrition science and research through investigator-initiated efforts. This presentation provides a broad overview of the nutrition measures collected in NHLBI cohort studies and presents information on available resources through the NHLBI Biologic Specimen and Data Repository Information Coordinating Center (BioLINCC). Leveraging existing NHLBI cohort studies, which include diverse study populations, is a cost-effective approach for investigators, including early stage investigators, to develop new research questions. METHODS: A landscape analysis was conducted to evaluate the nutrition measures collected in eight, multi-site NHLBI-funded cohort studies including over 163,000 participants (ages 18 −100 y+). These datasets include the Coronary Artery Risk Development in Young Adults (CARDIA), the Framingham Heart Study, the Jackson Heart Study (JHS), the Women's Health Initiative (WHI), the Multi-Ethnic Study of Atherosclerosis (MESA), the Atherosclerosis Risk in Communities Study (ARIC), the Hispanics Community Health Study/Study of Latinos (SOL), and the Cardiovascular Health Study (CHS). Information from BioLINCC provided an additional resource to identify nutrition measures collected. RESULTS: Most of the cohort studies used food frequency questionnaires to assess diet, with a smaller number using 24-hr recall methodology. Concentration biomarkers largely varied by study, including carotenoid and vitamin D concentrations to serum calcium and potassium levels. Lipids and blood pressure measurements were consistently collected across all cohort studies and some studies collected inflammatory markers (e.g., C reactive protein, interleukin-6) and used more invasive and costly cardiac imaging outcomes (e.g., carotid IMT, coronary calcium). CONCLUSIONS: This preliminary study identified variable nutrition measures and nutrition-related clinical outcomes in NHLBI-funded cohort studies, which are available on BioLINCC for future analysis by investigators. Additionally, these findings can help with implementation of the NIH SPNR by identifying key research gaps and possible focus areas for future research. FUNDING SOURCES: National Institutes of Health.

3,3′-Diindolylmethane (DIM), an indole derivative from vegetables of the Brassica genus, has antiproliferative activity in breast cancer cells. Part of this activity is thought to be due to DIM inhibition of Akt signaling, but an upstream mechanism of DIM-induced Akt inhibition has not been described. The goals of this study were to investigate the kinetics of inhibition of Akt by physiologically relevant concentrations of DIM and to identify an upstream factor that mediates this effect. Here we report that DIM (5–25 μM) inhibited Akt activation from 30 min to 24 h in tumorigenic MDA-MB-231 cells but did not inhibit Akt activation in non-tumorigenic preneoplastic MCF10AT cells. DIM inhibited hepatocyte growth factor (HGF)-induced Akt activation by up to 46%, cell migration by 66% and cell proliferation by up to 54%, but did not inhibit induction of Akt by epidermal growth factor or insulin-like growth factor-1. DIM decreased phosphorylation of the HGF receptor, c-Met, at tyrosines 1234 and 1235, indicating decreased activation of the receptor. This decrease was reversed by pretreatment with inhibitors of p38 or calcineurin. Our results demonstrate the important role of HGF and c-Met in DIM's anti-proliferative effect on breast cancer cells and suggest that DIM could have preventive or clinical value as an inhibitor of c-Met signaling.

To describe and elucidate the time trends of the academic productivity of NHLBI's obesity-related research funding via bibliometric analysis of 30 years of NHLBI-supported obesity-related publications.In total, 3,545 NHLBI-funded obesity-related publications were identified in the Thomson Reuters InCites™ database. Shared references in a community detection algorithm were used to identify publication topics. Characteristics of publications and topical communities were analyzed based on citation count and percentile rank. A percentile rank90 was considered "highly cited."Obesity-related publications increased more than 10-fold over 30 years, whereas NHLBI-funded publications only increased twofold NHLBI-funded obesity publications were cited a median of 23 times (IQR 8-55, range 0-2,047, mean 52). Thirty percent of these publications were highly cited compared to the expected ten percent. Six topical communities were present in 1983 compared to 16 in 2013. The most highly cited topical areas were sleep (n = 199 publications, 38% highly cited), cardiovascular morbidity and mortality (n = 277, 36%), obesity correlates and consequences (n = 588, 35%), and asthma and inflammation (n = 283, 35%).NHLBI-funded obesity publications have contributed substantially to the obesity literature, with many highly cited. Publications grew in number and topical diversity over 30 years and grew at a faster rate than total NHLBI publications.

Small research grants, or R03 grants, provide limited, short-term support for individual research projects. R03s may be an excellent means of support for projects by nutrition scientists at all stages in their careers. The National Cancer Institute (NCI) has awarded roughly one-half of all nutrition-related NIH R03 grants in the period from 2005 to 2010. A detailed review of the recent NCI grant portfolio identified potential strategies for successful applications. Projects that addressed important nutrition and cancer issues had feasible and appropriate specific aims, were innovative, and were based on sound concepts were most positively viewed by reviewers. Furthermore, applicants with suitable expertise, training, mentorship, and records of accomplishment who, when appropriate, collaborated with investigators with complementary knowledge and skills were more likely to receive higher priority scores.

Metabolomics platforms allow for the measurement of hundreds to thousands of unique small chemical entities, as well as offer extensive coverage of metabolic markers related to obesity, diet, smoking, and other exposures of high interest to health scientists. Nevertheless, its potential use as a tool in population-based study design has not been fully explored. As the field of metabolomics continues to mature, and in part, accelerate through the National Institutes of Health (NIH) investment of ≤65 million in the Common Fund’s Metabolomics Program (https://common fund.nih.gov/metabolomics/index), it is time to consider those challenges most pertinent to epidemiologic studies.

The ARGO-YBJ experiment is designed for the detection of Extensive Air Showers (EAS) in the primary energy range 100 GeV–10 TeV. Its full-coverage feature allows to lower the energy threshold about one order of magnitude with respect to sampling EAS detectors. Here the performance of the RPC array is described and the current status of the experiment is presented.

We describe the scientific motivations, the mission concept and the instrumentation of SPACE, a class-M mission proposed for concept study at the first call of the ESA Cosmic-Vision 2015-2025 planning cycle. SPACE aims to produce the largest three-dimensional evolutionary map of the Universe over the past 10 billion years by taking near-IR spectra and measuring redshifts for more than half a billion galaxies at 0, Comment: 27 pages, Experimental Astronomy, in press. The SPACE team complete list is available at http://urania.bo.astro.it/cimatti/space . The article with full resolution figures is available at http://urania.bo.astro.it/cimatti/space/publications.htm

The Allium genus includes garlic, onions, shallots, leeks, and chives. These vegetables are popular in cuisines worldwide and are valued for their potential medicinal properties. Epidemiologic studies, while limited in their abilities to assess Allium consumption, indicate some associations of Allium vegetable consumption with decreased risk of cancer, particularly cancers of the gastrointestinal tract. Limited intervention studies have been conducted to support these associations. The majority of supportive evidence on Allium vegetables cancer-preventive effects comes from mechanistic studies. These studies highlight potential mechanisms of individual sulfur-containing compounds and of various preparations and extracts of these vegetables, including decreased bioactivation of carcinogens, antimicrobial activities, and redox modification. Allium vegetables and their components have effects at each stage of carcinogenesis and affect many biologic processes that modify cancer risk. This review discusses the cancer-preventive effects of Allium vegetables, particularly garlic and onions, and their bioactive sulfur compounds and highlights research gaps. Cancer Prev Res; 8(3); 181–9. ©2015 AACR.

The Selenium and Vitamin E Cancer Prevention Trial (SELECT) was conducted to assess the efficacy of selenium and vitamin E alone and in combination on the incidence of prostate cancer. In this randomized, double-blind, placebo-controlled, 2 × 2 factorial design clinical trial, neither selenium nor vitamin E reduced the incidence of prostate cancer after seven years, and in fact, vitamin E was associated with a 17% increased risk of prostate cancer compared to placebo. The null findings were initially surprising given the preclinical and clinical evidence suggesting chemopreventive activity of selenium. These findings suggest that selenium and vitamin E do not prevent prostate cancer. Other potential explanations for the null findings include the agent formulation and dose, the characteristics of the cohort, and the study design. It is likely that only specific subpopulations may benefit from selenium supplementation; therefore, future studies should consider the baseline selenium status of the participants, age of the cohort, and genotype of specific selenoproteins, among other characteristics, in order to determine the activity of selenium in cancer prevention.