Identification of physical activity and sedentary behaviour dimensions that predict mortality risk in older adults: Development of a machine learning model in the Whitehall II accelerometer sub-study and external validation in the CoLaus study.

Identification of new physical activity (PA) and sedentary behaviour (SB) features relevant for health at older age is important to diversify PA targets in guidelines, as older adults rarely adhere to current recommendations focusing on total duration. We aimed to identify accelerometer-derived dimensions of movement behaviours that predict mortality risk in older populations. We used data on 21 accelerometer-derived features of daily movement behaviours in 3991 participants of the UK-based Whitehall II accelerometer sub-study (25.8% women, 60-83 years, follow-up: 2012-2013 to 2021, mean = 8.3 years). A machine-learning procedure was used to identify core PA and SB features predicting mortality risk and derive a composite score. We estimated the added predictive value of the score compared to traditional sociodemographic, behavioural, and health-related risk factors. External validation in the Switzerland-based CoLaus study (N = 1329, 56.7% women, 60-86 years, follow-up: 2014-2017 to 2021, mean = 3.8 years) was conducted. In total, 11 features related to overall activity level, intensity distribution, bouts duration, frequency, and total duration of PA and SB, were identified as predictors of mortality in older adults and included in a composite score. Both in the derivation and validation cohorts, the score was associated with mortality (hazard ratio = 1.10 (95% confidence interval = 1.05-1.15) and 1.18 (1.10-1.26), respectively) and improved the predictive value of a model including traditional risk factors (increase in C-index = 0.007 (0.002-0.014) and 0.029 (0.002-0.055), respectively). The identified accelerometer-derived PA and SB features, beyond the currently recommended total duration, might be useful for screening of older adults at higher mortality risk and for diversifying PA and SB targets in older populations whose adherence to current guidelines is low. National Institute on Aging; UK Medical Research Council; British Heart Foundation; Wellcome Trust; French National Research Agency; GlaxoSmithKline; Lausanne Faculty of Biology and Medicine; Swiss National Science Foundation

On the asymptotic giant branch star origin of peculiar spinel grain OC2

Microscopic presolar grains extracted from primitive meteorites have extremely anomalous isotopic compositions revealing the stellar origin of these grains. The composition of presolar spinel grain OC2 is different from that of all other presolar spinel grains. Large excesses of the heavy Mg isotopes are present and thus an origin from an intermediate-mass (IM) asymptotic giant branch (AGB) star was previously proposed for this grain. We discuss the isotopic compositions of presolar spinel grain OC2 and compare them to theoretical predictions. We show that the isotopic composition of O, Mg and Al in OC2 could be the signature of an AGB star of IM and metallicity close to solar experiencing hot bottom burning, or of an AGB star of low mass (LM) and low metallicity suffering very efficient cool bottom processing. Large measurement uncertainty in the Fe isotopic composition prevents us from discriminating which model better represents the parent star of OC2. However, the Cr isotopic composition of the grain favors an origin in an IM-AGB star of metallicity close to solar. Our IM-AGB models produce a self-consistent solution to match the composition of OC2 within the uncertainties related to reaction rates. Within this solution we predict that the 16O(p,g)17F and the 17O(p,a)14N reaction rates should be close to their lower and upper limits, respectively. By finding more grains like OC2 and by precisely measuring their Fe and Cr isotopic compositions, it may be possible in the future to derive constraints on massive AGB models from the study of presolar grains.Comment: 10 pages, 8 figures, accepted for publication on Astronomy & Astrophysic

Scaled solar tracks and isochrones in a large region of the Z-Y plane. II. From 2.5 to 20 solar masses

We extend our theoretical computations for low-mass stars to intermediate-mass and massive stars, for which few databases exist in the literature. Evolutionary tracks and isochrones are computed from 2.50 to 20 solar masses for agrid of 37 chemical compositions with metal content Z between 0.0001 and 0.070 and helium content Y between 0.23 and 0.40. Synthetic TP-AGB models allow stellar tracks and isochrones to be extended until the end of the thermal pulses along the AGB. We provide software tools for the bidimensional interpolation (in Y and Z) of the isochrones. We present tracks for scaled-solar abundances and the corresponding isochrones from very old ages down to about 10 million years. The extension of the blue loops and the instability strip of Cepheid stars are compared and the Cepheid mass-discrepancy is discussed. The location of red supergiants in the H-R diagram is in good agreement with the evolutionary tracks for masses from 10 to 20 solar masses. Tracks and isochrones are available in tabular form for the adopted grid of chemical compositions in the extended plane Z-Y in three photometric systems. An interactive web interface allows users to obtain isochrones of any chemical composition inside the provided Z-Y range and also to simulate stellar populations with different Y(Z) helium-to-metal enrichment laws.Comment: 17 pages, 18 figures, accepted for publication in A&

METALLIC ION DEVELOPMENTS AT GANIL

Radioactive ion beams (RIB) are routinely produced at GANIL by fragmentation of the projectile. A possible way to improve the RIB intensity is to increase the primary beam intensity impinging the target. Although high intensities can be obtained with an ECR ion source for gaseous elements, it is more difficult for metallic elements due to the poor ionization efficiency of the source. This report deals with metallic ion beam production at high intensity. Experimental results for Ca, Ni and Fe are presented. The oven and the MIVOC methods are compared

Convective Core Mixing: a Metallicity Dependence?

The main scope of this paper is to investigate the possible existence of a metallicity dependence of the overshooting from main sequence stars turbulent cores. We focus on objects with masses in the range ~2.5 Msol - ~25 Msol. Basically, evolutionary time scale ratios are compared with star numbers ratios on the main sequence. Star populations are synthesized using grids of evolutionary tracks computed with various overshooting amounts. Observational material is provided by the large and homogeneous photometric database of OGLE 2 project for the Magellanic clouds. Attention is paid to the study of uncertainties: distance modulus, intergalactic and interstellar reddening, IMF slope and average binarity rate. Rotation and chemical composition gradient are also considered. The result for the overshooting distance is l_over(SMC)= 0.40 +0.12-0.06 Hp (Z=0.004) and l_over(LMC)= 0.10+0.17-0.10 Hp (Z=0.008) suggesting a possible dependence of the extent of the mixed central regions with metallicity within the considered mass range. Unfortunately it is not yet possible to fully disentangle effects of mass and chemical composition.Comment: 13 pages, 8 figures, accepted in Astronomy & Astrophysic

Evidence Map of Pancreatic Surgery–A living systematic review with meta-analyses by the International Study Group of Pancreatic Surgery (ISGPS)

Background: Pancreatic surgery is associated with considerable morbidity and, consequently, offers a large and complex field for research. To prioritize relevant future scientific projects, it is of utmost importance to identify existing evidence and uncover research gaps. Thus, the aim of this project was to create a systematic and living Evidence Map of Pancreatic Surgery. Methods: PubMed, the Cochrane Central Register of Controlled Trials, and Web of Science were systematically searched for all randomized controlled trials and systematic reviews on pancreatic surgery. Outcomes from every existing randomized controlled trial were extracted, and trial quality was assessed. Systematic reviews were used to identify an absence of randomized controlled trials. Randomized controlled trials and systematic reviews on identical subjects were grouped according to research topics. A web-based evidence map modeled after a mind map was created to visualize existing evidence. Meta-analyses of specific outcomes of pancreatic surgery were performed for all research topics with more than 3 randomized controlled trials. For partial pancreatoduodenectomy and distal pancreatectomy, pooled benchmarks for outcomes were calculated with a 99% confidence interval. The evidence map undergoes regular updates. Results: Out of 30, 860 articles reviewed, 328 randomized controlled trials on 35, 600 patients and 332 systematic reviews were included and grouped into 76 research topics. Most randomized controlled trials were from Europe (46%) and most systematic reviews were from Asia (51%). A living meta-analysis of 21 out of 76 research topics (28%) was performed and included in the web-based evidence map. Evidence gaps were identified in 11 out of 76 research topics (14%). The benchmark for mortality was 2% (99% confidence interval: 1%–2%) for partial pancreatoduodenectomy and <1% (99% confidence interval: 0%–1%) for distal pancreatectomy. The benchmark for overall complications was 53% (99%confidence interval: 46%–61%) for partial pancreatoduodenectomy and 59% (99% confidence interval: 44%–80%) for distal pancreatectomy. Conclusion: The International Study Group of Pancreatic Surgery Evidence Map of Pancreatic Surgery, which is freely accessible via www.evidencemap.surgery and as a mobile phone app, provides a regularly updated overview of the available literature displayed in an intuitive fashion. Clinical decision making and evidence-based patient information are supported by the primary data provided, as well as by living meta-analyses. Researchers can use the systematic literature search and processed data for their own projects, and funding bodies can base their research priorities on evidence gaps that the map uncovers. © 2021 The Author

DNA-binding regulates site-specific ubiquitination of IRF-1

Understanding the determinants for site-specific ubiquitination by E3 ligase components of the ubiquitin machinery is proving to be a challenge. In the present study we investigate the role of an E3 ligase docking site (Mf2 domain) in an intrinsically disordered domain of IRF-1 [IFN (interferon) regulatory factor-1], a short-lived IFNγ-regulated transcription factor, in ubiquitination of the protein. Ubiquitin modification of full-length IRF-1 by E3 ligases such as CHIP [C-terminus of the Hsc (heat-shock cognate) 70-interacting protein] and MDM2 (murine double minute 2), which dock to the Mf2 domain, was specific for lysine residues found predominantly in loop structures that extend from the DNA-binding domain, whereas no modification was detected in the more conformationally flexible C-terminal half of the protein. The E3 docking site was not available when IRF-1 was in its DNA-bound conformation and cognate DNA-binding sequences strongly suppressed ubiquitination, highlighting a strict relationship between ligase binding and site-specific modification at residues in the DNA-binding domain. Hyperubiquitination of a non-DNA-binding mutant supports a mechanism where an active DNA-bound pool of IRF-1 is protected from polyubiquitination and degradation.</jats:p