Circulating Inflammatory and Oxidative Stress Responses to Steady-State Moderate-Intensity and High-Intensity Interval Exercise in Mid-Spectrum Chronic Kidney Disease

Inflammation and oxidative stress can be potent modulators of vascular function. These factors may transiently respond to moderate-intensity steady state exercise (SSE) in a manner that improves post-exercise vascular function in healthy adults. Whether exercise imparts similar effects in adults with Stage 3 or 4 chronic kidney disease (CKD) remains understudied. Moreover, a comparison of SSE and high-intensity interval exercise (HIIE) may add to clinically-relevant findings for improving vascular function in mid-spectrum CKD. PURPOSE: To determine the influence of SSE and a comparable amount of HIIE on post-exercise inflammation and oxidative stress in patients diagnosed with secondary Stage 3 or 4 CKD. METHODS: Twenty participants (n = 6 men; n = 14 women; age 62.0 + 9.9 yr; weight 80.9 + 16.2 kg; body fat 37.3 + 8.5% of weight; VO2max 19.4 + 4.7 ml/kg/min) completed 30 min of SSE at 65% VO2reserve or HIIE by treadmill walking (90% and 20% of VO2reserve in 3:2 min ratio) in a randomized crossover design. Both exercise conditions averaged ~ 65% VO2reserve. Blood samples were obtained by the same technician under standardized conditions just before, 1hr and 24hrs after exercise. Total antioxidant capacity (TAC), paraoxonase1 (PON1), asymmetric dimethylarginine (ADMA), 3nitrotyrosine (3NT) and interleukin-6 (IL6) responses were analyzed using 2 (condition) by 3 (sample point) repeated measures ANOVAs. RESULTS: Relative to pre-exercise measures: TAC increased by 4.3% 24hr after exercise (p = 0.012). PON1 was maintained 1hr and elevated by 6.1% 24hr after SSE, but not HIIE (p = 0.035). When corrected for plasma volume shifts, ADMA increased 30 ng/ml at 1hr but was 58 ng/ml lower 24hrs after exercise (p = 0.0006). 3NT and IL6 remained stable in the hours after exercise (p \u3e 0.05). CONCLUSION: Modest inflammatory and oxidative stress marker responses to either SSE and HIIE may contribute to improved vascular function in mid-spectrum CKD

Concert recording 2017-11-06

[Track 1]. Sebben crudele / Antonio Caldara -- [Track 2]. Orpheus with his lute / William Schuman -- [Track 3]. Heaven help my heart -- [Track 4]. Little elegy / John Duke -- [Track 5]. Bel piacere / G.F. Handel -- [Track 6]. I dreamed a dream from Les Miserables / Claude-Michel Schönberg -- [Track 7]. In questa tomba oscura / Ludwig van Beethoven -- [Track 8]. Lasst mich nur auf meinem Sattel gelten! from Freisinn / Robert Shumann -- [Track 9]. Für Musik / Robert Franz -- [Track 10]. Edelweiss from The sound of music / Rodgers & Hammerstein -- [Track 11]. Tu lo sai / Giuseppe Torelli -- [Track 12]. Glück / Max Reger -- [Track 13] Le colibri / Ernest Chausson -- [Track 14] Der Der Schäfer / Hugo Wolf -- [Track 15]. A route to the sky / Jake Heggie -- [Track 16]. Ich liebe dich / Edvard Grieg -- [Track 17]. When it all fall down from Chaplin / Christopher Curtis -- [Track 18]. Voyage a Paris / Francis Poulenc -- [Track 19]. Crucifixion / arr. Hall Johnson -- [Track 20]. Bright is the ring of words / Ralph Vaughan Williams -- [Track 21]. Non t\u27amo piu / Francesco Paolo Tosti -- [Track 22]. Se tu m\u27ami / Alessandro Parisotti -- [Track 23]. I love the way from Something\u27s rotten / Kirkpatrick & Kirkpatrick -- [Track 24]. A madrigal / Herbert Howells -- [Track 25]. El majo discrete / Enrique Granados -- [Track 26]. The roadside fire / Ralph Vaughan Williams -- [Track 27]. Che fiero costume / Giovanni Legrenzi -- [Track 28]. An die Musik / Franz Shubert -- [Track 29]. I will sing new songs of gladness / Anton Dvorak -- [Track 30]. Full fathom five from The tempest / Henry Purcell -- [Track 31]. Nimmerstate Libe / Hugo Wolf -- [Track 32]. Deposuit potentes from Magnificat / Johann Sebastian Bach -- [Track 33]. Vaghissima sembiante / Stefano Donaudy -- [Track 34]. Tormani a vaghegghiar from Alcina / G.F. Handel -- [Track 35]. Nobody knows this little rose / John Duke -- [Track 36]. Let beauty awake / Ralph Vaughan Williams -- [Track 37]. Steal away / arr. Hall Johnson -- [Track 38]. Come paride vezzoso from L\u27elisir d\u27amore / Kirkpatrick & Kirkpatrick -- [Track 39]. Dich, teure Halle from Tannhaüser / Richard Wagner -- [Track 40]. Non t\u27accotare all\u27urna / Giuseppe Verdi -- [Track 41]. Zur Rosenzeit / Edvard Grieg

Coastal shoreline change assessments at global scales

During the present era of rapid climate change and sea-level rise, coastal change science is needed at global, regional, and local scales. Essential elements of this science, regardless of scale, include that the methods are defendable and that the results are independently verifiable. The recent contribution by Almar et al.1 does not achieve either of these measures as shown by: (i) the use of an error-prone proxy for coastal shoreline and (ii) analyses that are circular and explain little of the data variance

Rucaparib maintenance treatment for recurrent ovarian carcinoma after response to platinum therapy (ARIEL3): a randomised, double-blind, placebo-controlled, phase 3 trial

Background: Rucaparib, a poly(ADP-ribose) polymerase inhibitor, has anticancer activity in recurrent ovarian carcinoma harbouring a BRCA mutation or high percentage of genome-wide loss of heterozygosity. In this trial we assessed rucaparib versus placebo after response to second-line or later platinum-based chemotherapy in patients with high-grade, recurrent, platinum-sensitive ovarian carcinoma. Methods: In this randomised, double-blind, placebo-controlled, phase 3 trial, we recruited patients from 87 hospitals and cancer centres across 11 countries. Eligible patients were aged 18 years or older, had a platinum-sensitive, high-grade serous or endometrioid ovarian, primary peritoneal, or fallopian tube carcinoma, had received at least two previous platinum-based chemotherapy regimens, had achieved complete or partial response to their last platinum-based regimen, had a cancer antigen 125 concentration of less than the upper limit of normal, had a performance status of 0–1, and had adequate organ function. Patients were ineligible if they had symptomatic or untreated central nervous system metastases, had received anticancer therapy 14 days or fewer before starting the study, or had received previous treatment with a poly(ADP-ribose) polymerase inhibitor. We randomly allocated patients 2:1 to receive oral rucaparib 600 mg twice daily or placebo in 28 day cycles using a computer-generated sequence (block size of six, stratified by homologous recombination repair gene mutation status, progression-free interval after the penultimate platinum-based regimen, and best response to the most recent platinum-based regimen). Patients, investigators, site staff, assessors, and the funder were masked to assignments. The primary outcome was investigator-assessed progression-free survival evaluated with use of an ordered step-down procedure for three nested cohorts: patients with BRCA mutations (carcinoma associated with deleterious germline or somatic BRCA mutations), patients with homologous recombination deficiencies (BRCA mutant or BRCA wild-type and high loss of heterozygosity), and the intention-to-treat population, assessed at screening and every 12 weeks thereafter. This trial is registered with ClinicalTrials.gov, number NCT01968213; enrolment is complete. Findings: Between April 7, 2014, and July 19, 2016, we randomly allocated 564 patients: 375 (66%) to rucaparib and 189 (34%) to placebo. Median progression-free survival in patients with a BRCA-mutant carcinoma was 16·6 months (95% CI 13·4–22·9; 130 [35%] patients) in the rucaparib group versus 5·4 months (3·4–6·7; 66 [35%] patients) in the placebo group (hazard ratio 0·23 [95% CI 0·16–0·34]; p<0·0001). In patients with a homologous recombination deficient carcinoma (236 [63%] vs 118 [62%]), it was 13·6 months (10·9–16·2) versus 5·4 months (5·1–5·6; 0·32 [0·24–0·42]; p<0·0001). In the intention-to-treat population, it was 10·8 months (8·3–11·4) versus 5·4 months (5·3–5·5; 0·36 [0·30–0·45]; p<0·0001). Treatment-emergent adverse events of grade 3 or higher in the safety population (372 [99%] patients in the rucaparib group vs 189 [100%] in the placebo group) were reported in 209 (56%) patients in the rucaparib group versus 28 (15%) in the placebo group, the most common of which were anaemia or decreased haemoglobin concentration (70 [19%] vs one [1%]) and increased alanine or aspartate aminotransferase concentration (39 [10%] vs none). Interpretation: Across all primary analysis groups, rucaparib significantly improved progression-free survival in patients with platinum-sensitive ovarian cancer who had achieved a response to platinum-based chemotherapy. ARIEL3 provides further evidence that use of a poly(ADP-ribose) polymerase inhibitor in the maintenance treatment setting versus placebo could be considered a new standard of care for women with platinum-sensitive ovarian cancer following a complete or partial response to second-line or later platinum-based chemotherapy. Funding: Clovis Oncology

The Long-Baseline Neutrino Experiment: Exploring Fundamental Symmetries of the Universe

The preponderance of matter over antimatter in the early Universe, the dynamics of the supernova bursts that produced the heavy elements necessary for life and whether protons eventually decay --- these mysteries at the forefront of particle physics and astrophysics are key to understanding the early evolution of our Universe, its current state and its eventual fate. The Long-Baseline Neutrino Experiment (LBNE) represents an extensively developed plan for a world-class experiment dedicated to addressing these questions. LBNE is conceived around three central components: (1) a new, high-intensity neutrino source generated from a megawatt-class proton accelerator at Fermi National Accelerator Laboratory, (2) a near neutrino detector just downstream of the source, and (3) a massive liquid argon time-projection chamber deployed as a far detector deep underground at the Sanford Underground Research Facility. This facility, located at the site of the former Homestake Mine in Lead, South Dakota, is approximately 1,300 km from the neutrino source at Fermilab -- a distance (baseline) that delivers optimal sensitivity to neutrino charge-parity symmetry violation and mass ordering effects. This ambitious yet cost-effective design incorporates scalability and flexibility and can accommodate a variety of upgrades and contributions. With its exceptional combination of experimental configuration, technical capabilities, and potential for transformative discoveries, LBNE promises to be a vital facility for the field of particle physics worldwide, providing physicists from around the globe with opportunities to collaborate in a twenty to thirty year program of exciting science. In this document we provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess.Comment: Major update of previous version. This is the reference document for LBNE science program and current status. Chapters 1, 3, and 9 provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess. 288 pages, 116 figure

EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA); Scientific Opinion on Dietary Reference Values for protein

This opinion of the EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) deals with the setting of Dietary Reference Values (DRVs) for protein. The Panel concludes that a Population Reference Intake (PRI) can be derived from nitrogen balance studies. Several health outcomes possibly associated with protein intake were also considered but data were found to be insufficient to establish DRVs. For healthy adults of both sexes, the average requirement (AR) is 0.66 g protein/kg body weight per day based on nitrogen balance data. Considering the 97.5th percentile of the distribution of the requirement and assuming an efficiency of utilisation of dietary protein for maintenance of 47 %, the PRI for adults of all ages was estimated to be 0.83 g protein/kg body weight per day and is applicable both to high quality protein and to protein in mixed diets. For children from six months onwards, age-dependent requirements for growth estimated from average daily rates of protein deposition and adjusted by a protein efficiency for growth of 58 % were added to the requirement for maintenance of 0.66 g/kg body weight per day. The PRI was estimated based on the average requirement plus 1.96 SD using a combined SD for growth and maintenance.For pregnancy, an intake of 1, 9 and 28 g/d in the first, second and third trimesters, respectively, is proposed in addition to the PRI for non-pregnant women. For lactation, a protein intake of 19 g/d during the first six months, and of 13 g/d after six months, is proposed in addition to the PRI for non-lactating women. Data are insufficient to establish a Tolerable Upper Intake Level (UL) for protein. Intakes up to twice the PRI are regularly consumed from mixed diets by some physically active and healthy adults in Europe and are considered safe

Open Data for Global Science

The global science system stands at a critical juncture. On the one hand, it is overwhelmed by a hidden avalanche of ephemeral bits that are central components of modern research and of the emerging ‘cyberinfrastructure’4 for e-Science.5 The rational management and exploitation of this cascade of digital assets offers boundless opportunities for research and applications. On the other hand, the ability to access and use this rising flood of data seems to lag behind, despite the rapidly growing capabilities of information and communication technologies (ICTs) to make much more effective use of those data. As long as the attention for data policies and data management by researchers, their organisations and their funders does not catch up with the rapidly changing research environment, the research policy and funding entities in many cases will perpetuate the systemic inefficiencies, and the resulting loss or underutilisation of valuable data resources derived from public investments. There is thus an urgent need for rationalised national strategies and more coherent international arrangements for sustainable access to public research data, both to data produced directly by government entities and to data generated in academic and not-for-profit institutions with public funding. In this chapter, we examine some of the implications of the ‘data driven’ research and possible ways to overcome existing barriers to accessibility of public research data. Our perspective is framed in the context of the predominantly publicly funded global science system. We begin by reviewing the growing role of digital data in research and outlining the roles of stakeholders in the research community in developing data access regimes. We then discuss the hidden costs of closed data systems, the benefits and limitations of openness as the default principle for data access, and the emerging open access models that are beginning to form digitally networked commons. We conclude by examining the rationale and requirements for developing overarching international principles from the top down, as well as flexible, common-use contractual templates from the bottom up, to establish data access regimes founded on a presumption of openness, with the goal of better capturing the benefits from the existing and future scientific data assets. The ‘Principles and Guidelines for Access to Research Data from Public Funding’ from the Organisation for Economic Cooperation and Development (OECD), reported on in another article by Pilat and Fukasaku,6 are the most important recent example of the high-level (inter)governmental approach. The common-use licenses promoted by the Science Commons are a leading example of flexible arrangements originating within the community. Finally, we should emphasise that we focus almost exclusively on the policy—the institutional, socioeconomic, and legal aspects of data access—rather than on the technical and management practicalities that are also important, but beyond the scope of this article

The ABC130 barrel module prototyping programme for the ATLAS strip tracker

For the Phase-II Upgrade of the ATLAS Detector, its Inner Detector, consisting of silicon pixel, silicon strip and transition radiation sub-detectors, will be replaced with an all new 100 % silicon tracker, composed of a pixel tracker at inner radii and a strip tracker at outer radii. The future ATLAS strip tracker will include 11,000 silicon sensor modules in the central region (barrel) and 7,000 modules in the forward region (end-caps), which are foreseen to be constructed over a period of 3.5 years. The construction of each module consists of a series of assembly and quality control steps, which were engineered to be identical for all production sites. In order to develop the tooling and procedures for assembly and testing of these modules, two series of major prototyping programs were conducted: an early program using readout chips designed using a 250 nm fabrication process (ABCN-25) and a subsequent program using a follow-up chip set made using 130 nm processing (ABC130 and HCC130 chips). This second generation of readout chips was used for an extensive prototyping program that produced around 100 barrel-type modules and contributed significantly to the development of the final module layout. This paper gives an overview of the components used in ABC130 barrel modules, their assembly procedure and findings resulting from their tests.Comment: 82 pages, 66 figure

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data