Developing a machine learning algorithm to predict the probability of aseptic loosening of the glenoid component after anatomical total shoulder arthroplasty:protocol for a retrospective, multicentre study

INTRODUCTION: Despite technological advancements in recent years, glenoid component loosening remains a common complication after anatomical total shoulder arthroplasty (ATSA) and is one of the main causes of revision surgery. Increasing emphasis is placed on the prevention of glenoid component failure. Previous studies have successfully predicted range of motion, patient-reported outcomes and short-term complications after ATSA using machine learning methods, but an accurate predictive model for (glenoid component) revision is currently lacking. This study aims to use a large international database to accurately predict aseptic loosening of the glenoid component after ATSA using machine learning algorithms.METHODS AND ANALYSIS: For this multicentre, retrospective study, individual patient data will be compiled from previously published studies reporting revision of ATSA. A systematic literature search will be performed in Medline (PubMed) identifying all studies reporting outcomes of ATSA. Authors will be contacted and invited to participate in the Machine Learning Consortium by sharing their anonymised databases. All databases reporting revisions after ATSA will be included, and individual patients with a follow-up less than 2 years or a fracture as the indication for ATSA will be excluded. First, features (predictive variables) will be identified using a random forest feature selection. The resulting features from the compiled database will be used to train various machine learning algorithms (stochastic gradient boosting, random forest, support vector machine, neural network and elastic-net penalised logistic regression). The developed and validated algorithms will be evaluated across discrimination (c-statistic), calibration, the Brier score and the decision curve analysis. The best-performing algorithm will be used to create an open-access online prediction tool.ETHICS AND DISSEMINATION: Data will be collected adhering to the WHO regulation on data sharing. An Institutional Review Board review is not applicable. The study results will be published in a peer-reviewed journal.</p

Lack of detectable chemosynthesis at a sponge dominated subarctic methane seep

We used high-resolution imagery within a Geographic Information System (GIS), free gas and porewater analyses and animal bulk stable isotope measurements to characterize the biotic and abiotic aspects of the newly discovered Vestbrona Carbonate Field (VCF) seep site on the Norwegian shelf (63°28′N, 6° 31′E, ∿270 m water depth). Free gas was mainly composed of microbial methane. Sediment porewater sulfide concentrations were in the millimolar range and thus high enough to sustain seep chemosymbiotrophic animals. Nonetheless, the VCF lacked chemosymbiotrophic animals despite an abundance of methane-derived carbonate crusts which are formed by the same anaerobic processes that sustain chemosymbiotrophic animals at seeps. Furthermore, none of the sampled taxa, across various trophic guilds exhibited a detectable contribution of chemosynthetically fixed carbon to their diets based on bulk stable isotope values, suggesting a predominantly photosynthetic source of carbon to the VCF seep food web. We link the absence of chemosymbiotrophic animals to highly localized methane flow pathways, which may act as a “shunt-bypass” of the anaerobic oxidation of methane (AOM) and by extension sulfide generation, thus leading to sediment sulfide concentrations that are highly heterogeneous over very short lateral distances, inhibiting the successful colonization of chemosymbiotrophic animals at the VCF seep. Instead, the seep hosted diverse biological communities, consisting of heterotrophic benthic fauna, including long lived taxa, such as soft corals (e.g., Paragorgia arborea) and stony corals (i.e., Desmophyllum pertusum, formerly known as Lophelia pertusa). Compared to the surrounding non-seep seafloor, we measured heightened megafaunal density at the seep, which we attribute to increased habitat heterogeneity and the presence of a variety of hard substrates (i.e., methane-derived authigenic carbonates, dropstones and coral rubble), particularly since the most abundant taxa all belonged to the phylum Porifera. Compared to the surrounding non-seep seafloor, marine litter was denser within the VCF seep, which we link to the more variable local topography due to authigenic carbonates, which can rip off parts of bottom trawling nets thereby making the seep act as catchment area for marine litter

The changing culture of silviculture

Changing climates are altering the structural and functional components of forest ecosystems at an unprecedented rate. Simultaneously, we are seeing a diversification of public expectations on the broader sustainable use of forest resources beyond timber production. As a result, the science and art of silviculture needs to adapt to these changing realities. In this piece, we argue that silviculturists are gradually shifting from the application of empirically derived silvicultural scenarios to new sets of approaches, methods and practices, a process that calls for broadening our conception of silviculture as a scientific discipline. We propose a holistic view of silviculture revolving around three key themes: observe, anticipate and adapt. In observe, we present how recent advances in remote sensing now enable silviculturists to observe forest structural, compositional and functional attributes in near-real-time, which in turn facilitates the deployment of efficient, targeted silvicultural measures in practice that are adapted to rapidly changing constraints. In anticipate, we highlight the importance of developing state-of-the-art models designed to take into account the effects of changing environmental conditions on forest growth and dynamics. In adapt, we discuss the need to provide spatially explicit guidance for the implementation of adaptive silvicultural actions that are efficient, cost-effective and socially acceptable. We conclude by presenting key steps towards the development of new tools and practical knowledge that will ensure meeting societal demands in rapidly changing environmental conditions. We classify these actions into three main categories: reexamining existing silvicultural trials to identify key stand attributes associated with the resistance and resilience of forests to multiple stressors, developing technological workflows and infrastructures to allow for continuous forest inventory updating frameworks, and implementing bold, innovative silvicultural trials in consultation with the relevant communities where a range of adaptive silvicultural strategies are tested. In this holistic perspective, silviculture can be defined as the science of observing forest condition and anticipating its development to apply tending and regeneration treatments adapted to a multiplicity of desired outcomes in rapidly changing realities

EVER Proteins, Key Elements of the Natural Anti-Human Papillomavirus Barrier, Are Regulated upon T-Cell Activation

Human papillomaviruses (HPV) cause a variety of mucosal and skin lesions ranging from benign proliferations to invasive carcinomas. The clinical manifestations of infection are determined by host-related factors that define the natural anti-HPV barrier. Key elements of this barrier are the EVER1 and EVER2 proteins, as deficiency in either one of the EVER proteins leads to Epidermodysplasia Verruciformis (EV), a genodermatosis associated with HPV-induced skin carcinoma. Although EVERs have been shown to regulate zinc homeostasis in keratinocytes, their expression and function in other cell types that may participate to the anti-HPV barrier remain to be investigated. In this work, we demonstrate that EVER genes are expressed in different tissues, and most notably in lymphocytes. Interestingly, in contrast to the skin, where EVER2 transcripts are hardly detectable, EVER genes are both abundantly expressed in murine and human T cells. Activation of CD4+ and CD8+ T cells via the TCR triggers a rapid and profound decrease in EVER expression, accompanied by an accumulation of free Zn2+ ions. Thus, EVER proteins may be involved in the regulation of cellular zinc homeostasis in lymphocytes. Consistent with this hypothesis, we show that the concentration of Zn2+ ions is elevated in lymphoblastoid cells or primary T cells from EVER2-deficient patients. Interestingly, we also show that Zn2+ excess blocks T-cell activation and proliferation. Therefore, EVER proteins appear as key components of the activation-dependent regulation of Zn2+ concentration in T cells. However, the impact of EVER-deficiency in T cells on EV pathogenesis remains to be elucidated

Real-Time Online Monitoring of the Ion Range by Means of Prompt Secondary Radiations

International audiencePrompt secondary radiations such as gamma rays and protons can be used for ion-range monitoring during ion therapy either on an energy-slice basis or on a pencil-beam basis. We present a review of the ongoing activities in terms of detector developments, imaging, experimental and theoretical physics issues concerning the correlation between the physical dose and hadronic processe

Association of Gender with Clinical Expression, Quality of Life, Disability, and Depression and Anxiety in Patients with Systemic Sclerosis

OBJECTIVES: To assess the association of gender with clinical expression, health-related quality of life (HRQoL), disability, and self-reported symptoms of depression and anxiety in patients with systemic sclerosis (SSc). METHODS: SSc patients fulfilling the American College of Rheumatology and/or the Leroy and Medsger criteria were assessed for clinical symptoms, disability, HRQoL, self-reported symptoms of depression and anxiety by specific measurement scales. RESULTS: Overall, 381 SSc patients (62 males) were included. Mean age and disease duration at the time of evaluation were 55.9 (13.3) and 9.5 (7.8) years, respectively. One-hundred-and-forty-nine (40.4%) patients had diffuse cutaneous SSc (dcSSc). On bivariate analysis, differences were observed between males and females for clinical symptoms and self-reported symptoms of depression and anxiety, however without reaching statistical significance. Indeed, a trend was found for higher body mass index (BMI) (25.0 [4.1] vs 23.0 [4.5], p = 0.013), more frequent dcSSc, echocardiography systolic pulmonary artery pressure >35 mmHg and interstitial lung disease in males than females (54.8% vs 37.2%, p = 0.010; 24.2% vs 10.5%, p = 0.003; and 54.8% vs 41.2%, p = 0.048, respectively), whereas calcinosis and self-reported anxiety symptoms tended to be more frequent in females than males (36.0% vs 21.4%, p = 0.036, and 62.3% vs 43.5%, p = 0.006, respectively). On multivariate analysis, BMI, echocardiography PAP>35 mmHg, and anxiety were the variables most closely associated with gender. CONCLUSIONS: In SSc patients, male gender tends to be associated with diffuse disease and female gender with calcinosis and self-reported symptoms of anxiety. Disease-associated disability and HRQoL were similar in both groups

Transposable Elements Are a Major Cause of Somatic Polymorphism in Vitis vinifera L.

Through multiple vegetative propagation cycles, clones accumulate mutations in somatic cells that are at the origin of clonal phenotypic diversity in grape. Clonal diversity provided clones such as Cabernet-Sauvignon N°470, Chardonnay N° 548 and Pinot noir N° 777 which all produce wines of superior quality. The economic impact of clonal selection is therefore very high: since approx. 95% of the grapevines produced in French nurseries originate from the French clonal selection. In this study we provide the first broad description of polymorphism in different clones of a single grapevine cultivar, Pinot noir, in the context of vegetative propagation. Genome sequencing was performed using 454 GS-FLX methodology without a priori, in order to identify and quantify for the first time molecular polymorphisms responsible for clonal variability in grapevine. New generation sequencing (NGS) was used to compare a large portion of the genome of three Pinot noir clones selected for their phenotypic differences. Reads obtained with NGS and the sequence of Pinot noir ENTAV-INRA® 115 sequenced by Velasco et al., were aligned on the PN40024 reference sequence. We then searched for molecular polymorphism between clones. Three types of polymorphism (SNPs, Indels, mobile elements) were found but insertion polymorphism generated by mobile elements of many families displayed the highest mutational event with respect to clonal variation. Mobile elements inducing insertion polymorphism in the genome of Pinot noir were identified and classified and a list is presented in this study as potential markers for the study of clonal variation. Among these, the dynamic of four mobile elements with a high polymorphism level were analyzed and insertion polymorphism was confirmed in all the Pinot clones registered in France

Enabling planetary science across light-years. Ariel Definition Study Report

Ariel, the Atmospheric Remote-sensing Infrared Exoplanet Large-survey, was adopted as the fourth medium-class mission in ESA's Cosmic Vision programme to be launched in 2029. During its 4-year mission, Ariel will study what exoplanets are made of, how they formed and how they evolve, by surveying a diverse sample of about 1000 extrasolar planets, simultaneously in visible and infrared wavelengths. It is the first mission dedicated to measuring the chemical composition and thermal structures of hundreds of transiting exoplanets, enabling planetary science far beyond the boundaries of the Solar System. The payload consists of an off-axis Cassegrain telescope (primary mirror 1100 mm x 730 mm ellipse) and two separate instruments (FGS and AIRS) covering simultaneously 0.5-7.8 micron spectral range. The satellite is best placed into an L2 orbit to maximise the thermal stability and the field of regard. The payload module is passively cooled via a series of V-Groove radiators; the detectors for the AIRS are the only items that require active cooling via an active Ne JT cooler. The Ariel payload is developed by a consortium of more than 50 institutes from 16 ESA countries, which include the UK, France, Italy, Belgium, Poland, Spain, Austria, Denmark, Ireland, Portugal, Czech Republic, Hungary, the Netherlands, Sweden, Norway, Estonia, and a NASA contribution

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms