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Bone and bone marrow are not only anatomically, but also functionally interdependent. In a systematic review, we examined bone health in patients with hematopoietic disorders and demonstrated that an increased hematopoietic cell proliferation, such as in patients with hemolytic anemias, was associated with bone loss, while bone marrow hypocellularity, such as in patients with chronic myelofibrosis (CMF), was associated with bone gain [Steer K et al. J Bone Miner Res 2017]. Since bone mass in CMF increases at the expense of bone marrow, it contributes to patients' morbidity as it is associated with bone pain, and mortality as it may lead to bone marrow failure. A mouse model with a global knockout of the megakaryocyte (MK) lineage specific inhibitory receptor G6b-B was shown to develop myelofibrosis secondary to aberrant platelet production and function [Mazharian A et al Sci Signal 2012]. Moreover, a group of patients with primary myelofibrosis was identified to have loss-of-function mutations in the G6b-B gene [Hofmann I et al Blood 2018]. The objective of this study was to characterize temporal changes in the skeleton of the G6b-B knockout mice. We examined age- and sex-related changes in 4, 8, 16, and 32 week-old G6b-B+/+, G6b-B-/- female and male mice. Starting from 8 weeks-of-age, spleen progressively increased in female G6b-B-/- mice compared to corresponding G6b-B+/+ mice, reaching 2.9-fold increase at 32 weeks (p < 0.001) (Fig.1A). Micro-computed tomography analysis of femur demonstrated that starting at 8 weeks of age female G6b-B-/- mice had a significantly higher proportion of cortical bone and a respectively lower proportion of marrow (Fig.1B). Starting at 16 weeks of age, female G6b-B-/- mice developed trabecula in the medullary cavity normally occupied by the bone marrow, which by 32 weeks led to a 38-fold increase (p < 0.001) in the proportion of bone to tissue volume compared to G6b-B+/+ (Fig.1C,D). At 32-weeks of age, female G6b-B-/- mice also demonstrated a 7-fold increase in BV/TV (p < 0.001) in the region of metaphysis. While some abnormalities were found in male G6b-B-/- mice, they were considerably less severe compared to females. To establish whether the observed bone phenotype is due to MK and platelet functional defects, we performed microcomputed tomography analysis on femurs of 22 week-old G6b-Bfl/fl;Gp1ba-Cre-/- mice with a MK/platelet-specific knockout of G6b-B. Changes in trabecular bone of G6b-Bfl/fl;Gp1ba-Cre-/- mice recapitulated changes of G6b-B-/- mice. However, periosteal perimeter in male G6b-Bfl/fl;Gp1ba-Cre-/- mice was significantly larger, and in female G6b-Bfl/fl;Gp1ba-Cre-/- mice - significantly smaller than in corresponding control mice, while in global G6b-B-/- mice periosteal perimeter was not affected. Female G6b-B-/- mice demonstrated severe splenomegaly as well as progressive osteosclerosis, which was confirmed in G6b-Bfl/fl;Gp1ba-Cre-/- mice, indicating that trabecular bone gain in G6b-B-/- mice is consequent to a MK disfunction. Dramatic sexual dimorphism suggests that sex-related factors play an important role in the development of osteosclerosis. The differences in cortical bone phenotype between the global and conditional knockout of G6b-B suggest the potential role of G6b-B signaling in osteoclasts or osteoblasts. This study demonstrates that MK-associated myelofibrosis is sufficient to induce osteosclerosis of bone marrow, and that sex hormones play an important role either in protecting male mice from osteosclerosis or in exacerbating osteosclerosis in female mice. Disclosures No relevant conflicts of interest to declare.

A controlled quantum system can alter its environment by feedback, leading to reduced-entropy states of the environment and to improved system coherence. Here, using a quantum-dot electron spin as a control and probe, we prepare the quantum-dot nuclei under the feedback of coherent population trapping and observe their evolution from a thermal to a reduced-entropy state, with the immediate consequence of extended qubit coherence. Via Ramsey interferometry on the electron spin, we directly access the nuclear distribution following its preparation and measure the emergence and decay of correlations within the nuclear ensemble. Under optimal feedback, the inhomogeneous dephasing time of the electron, T_{2}^{*}, is extended by an order of magnitude to 39 ns. Our results can be readily exploited in quantum information protocols utilizing spin-photon entanglement and represent a step towards creating quantum many-body states in a mesoscopic nuclear-spin ensemble. We acknowledge financial support from the European Research Council ERC Consolidator Grant Agreement No. 617985 and the EPSRC National Quantum Technologies Program NQIT EP/M013243/1. G.E-M. acknowledges financial support from NSERC.

Motives underlying sport and exercise involvement have recently been hypothesized as potential factors influencing the positive association between sports/exercises involvement and disturbed eating attitudes and behaviours (DEAB) among adolescents. Nevertheless, very few studies have examined this hypothesis or the moderating role of gender, context of practice, performance levels and sport type on these relationships. In this study, these questions were addressed among 168 male and 167 female French adolescents involved in various types, contexts and performance levels of sport and exercise. Participants were asked to indicate their main motives for involvement in sport practice and to self-report DEAB (generic DEAB, vomiting–purging behaviours, and eating-related control) on a French adaptation of the Eating Attitudes Test-26. The results shared positive associations between body-related sport and exercise motives and most of the DEAB subscales. Furthermore, they show that the relationship between body-related sport and exercise motives and Vomiting–Purging Behaviours differs according to involvement in individual and competitive sports and exercises. Copyright ©2015 John Wiley & Sons, Ltd and Eating Disorders Association.

Strategies for the design optimisation of the Slide-o-Cam transmission. The optimization of the pressure angle in a cam-follower transmission is reported in this paper. This transmission is based on Slide-o-Cam, a cam mechanism with multiple rollers mounted on a common translating follower. The design of Slide-o-Cam; a transmission intended to produce a sliding motion from a turning drive, or vice versa, was reported elsewhere. This transmission provides pure-rolling motion, thereby reducing the friction of rack-and-pinions and linear drives. The pressure angle is a suitable performance index for this transmission because it determines the amount of force transmitted to the load vs. that transmitted to the machine frame. Two alternative design strategies are studied, namely, (i) increase the number of lobes on each cam or (ii) increase the number of cams. This device is intended to replace the current ball-screws in orthoglide, a three-DOF parallel robot for the production of translational motions, currently under development at Ecole Centrale de Nantes for machining applications.

The kidney sessions of the 2017 Banff Conference focused on 2 areas: clinical implications of inflammation in areas of interstitial fibrosis and tubular atrophy (i‐IFTA) and its relationship to T cell–mediated rejection (TCMR), and the continued evolution of molecular diagnostics, particularly in the diagnosis of antibody‐mediated rejection (ABMR). In confirmation of previous studies, it was independently demonstrated by 2 groups that i‐IFTA is associated with reduced graft survival. Furthermore, these groups presented that i‐IFTA, particularly when involving >25% of sclerotic cortex in association with tubulitis, is often a sequela of acute TCMR in association with underimmunosuppression. The classification was thus revised to include moderate i‐IFTA plus moderate or severe tubulitis as diagnostic of chronic active TCMR. Other studies demonstrated that certain molecular classifiers improve diagnosis of ABMR beyond what is possible with histology, C4d, and detection of donor‐specific antibodies (DSAs) and that both C4d and validated molecular assays can serve as potential alternatives and/or complements to DSAs in the diagnosis of ABMR. The Banff ABMR criteria are thus updated to include these alternatives. Finally, the present report paves the way for the Banff scheme to be part of an integrative approach for defining surrogate endpoints in next‐generation clinical trials. The Banff consortium presents revisions to the diagnostic criteria for T cell– and antibody‐mediated kidney transplant rejection, including specific criteria for chronic active T cell–mediated rejection, plus prospects for integrative endpoints in clinical trials. See related articles on pages 321, 364, and 377.

Nuestro informe se interesa en las características de las pequeñas y medias empresas que han alcanzado ganancias de productividad y que han al mismo tiempo puesto en marcha los procesos de diversificación gracias a sus usos del red. En un medioambiente económico en permanente evolución, marcado por la innovación y la competencia, ese doble capacidad aparece como un elemento importante de la viabilidad y de la perennidad de las pequeñas y medias estructuras. Por estas últimas empresas, la diversificación externa practicáda por las grandes firmas más corresponde a una estrategia demasiado costosa que se vuelve, por entonces en la práctica, inaccesible para ellas. La capacidad de obtención de la combinación de esos dos ventajas de competencia, gracias al red y a sus tecnologías conexas, está explicada por un análisis estadístico detallado de los usos de la tecnología pero repuestos en sus contextos de organización e industriales. Notre recherche s’intéresse aux caractéristiques de PME ayant simultanément su atteindre des gains de productivité et mettre en œuvre des processus de diversification grâce à leurs usages d’Internet. Dans un environnement économique en évolution permanente, marqué par l’innovation et la concurrence, cette double capacité apparaît comme un élément important de la viabilité et de la pérennité des petites et moyennes structures pour lesquelles la diversification externe, pratiquée par les grandes organisations, correspond à une stratégie trop coûteuse et donc, dans la pratique, inaccessible. La capacité d’obtention de combinaisons de ces deux avantages concurrentiels grâce aux usages d’Internet et de ses technologies connexes est expliquée par une analyse statistique détaillée des usages de la technologie reconsidérés dans leurs contextes organisationnels et industriels. Unsere Untersuchung interessiert sich für KMU, die gleichzeitig Produktivitäts-gewinne realisiert und Diversifikationsprozesse auf die Beine gestellt haben dank der Nutzung des Internets. In einem ökonomischen Umfeld mit einer ständigen Entwicklung, gekennzeichnet durch Innovation und Konkurrenz, erscheint diese zweifache Fähigkeit als ein wichtiges Element für die Lebensfähigkeit und den Fortbestand der kleinen und mittleren Strukturen. Normalerweise ist die externe Diversifikation, wie sie angewendet wird durch grosse Organisationen, eine zu teure und unerreichbare Strategie für KMU. Durch die Nutzung des Internets und seinen verwandten Technologien können zwei Konkurrenzvorteile kombiniert werden. Dies wird in der Folge erklärt durch eine detaillierte statistische Analyse der Technologie-nutzung in ihrem organisatorischen und industriellen Kontext. The results presented in this paper deal with the characteristics of SME’s capable to benefit, on the bases of their Internet uses, from productivity gains and diversification practices. That double capacity appears to be in a flexible and highly competitive economy as an important mean of viability for SME’s compared to big firms which are able to survive by external diversification. The capacity to obtain simultaneously that two sources of competitive advantage is explained by a precise statistical analysis of the technology uses that are reconsidered in their organizational and industrial contexts.

Abstract We consider solutions of an initial value problem involving the equation ∂ 2 ∂t 2 (x,t)+ ∑ i=0 4 a i (x) ∂ i w ∂x i (x,t) ∑ i=0 2 b i (x) ∂ i+1 w ∂x i ∂t (x,t)=0 for x, t > 0. Here, a4(x) > 0 and is constant outside a compact set, b2(x) ⩽ 0, and the coefficients ai(x) for i ⩽ 3 and bi(x) for i ⩽ 2 vanish outside a compact set. We show that the solutions are given by an integral operator, the kernel of which is an infinitely differentiable function of t for t > 0. In fact, its derivatives satisfy Gevrey-2 bounds.

International audience; Methylation of mercury (Hg) is the crucial process that controls Hg biomagnification along the aquatic food chains. Aquatic sediments are of particular interest because they constitute an essential reservoir where inorganic divalent Hg (HgII) is methylated. Methylmercury (MeHg) concentrations in sediments mainly result from the balance between methylation and demethylation reactions, two opposite natural processes primarily mediated by aquatic microorganisms. Thus, Hg availability and the activity of methylating microbial communities control the MeHg abundance in sediments. Consistently, some studies have reported a significant positive correlation between MeHg and HgII or total Hg (HgT), taken as a proxy for HgII, in aquatic sediments using enzyme-catalyzed methylation/demethylation mechanisms. By compiling 1,442 published and unpublished HgT–MeHg couples from lacustrine, riverine, estuarine and marine sediments covering various environmental conditions, from deep pristine abyssal to heavily contaminated riverine sediments, we show that a Michaelis–Menten type relationship is an appropriate model to relate the two parameters: MeHg = aHgT/(K m + HgT), with a = 0.277 ± 0.011 and K m = 188 ± 15 (R 2 = 0.70, p < 0.001). From K m variations, which depend on the various encountered environmental conditions, it appears that MeHg formation and accumulation are favoured in marine sediments compared to freshwater ones, and under oxic/suboxic conditions compared to anoxic ones, with redox potential and organic matter lability being the governing factors.

Galaxy bias, the unknown relationship between the clustering of galaxies and the underlying dark matter density field is a major hurdle for cosmological inference from large-scale structure. While traditional analyses focus on the absolute clustering amplitude of high-density regions mapped out by galaxy surveys, we propose a relative measurement that compares those to the underdense regions, cosmic voids. On the basis of realistic mock catalogs we demonstrate that cross correlating galaxies and voids opens up the possibility to calibrate galaxy bias and to define a static ruler thanks to the observable geometric nature of voids. We illustrate how the clustering of voids is related to mass compensation and show that volume-exclusion significantly reduces the degree of stochasticity in their spatial distribution. Extracting the spherically averaged distribution of galaxies inside voids from their cross correlations reveals a remarkable concordance with the mass-density profile of voids. 5 pages, 3 figures. Matches PRL published version after minor corrections