International single-step SNPBLUP beef cattle evaluations for Limousin weaning weight

Background Compared to national evaluations, international collaboration projects further improve accuracies of estimated breeding values (EBV) by building larger reference populations or performing a joint evaluation using data (or proxy of them) from different countries. Genomic selection is increasingly adopted in beef cattle, but, to date, the benefits of including genomic information in international evaluations have not been explored. Our objective was to develop an international beef cattle single-step genomic evaluation and investigate its impact on the accuracy and bias of genomic evaluations compared to current pedigree-based evaluations. Methods Weaning weight records were available for 331,593 animals from seven European countries. The pedigree included 519,740 animals. After imputation and quality control, 17,607 genotypes at a density of 57,899 single nucleotide polymorphisms (SNPs) from four countries were available. We implemented two international scenarios where countries were modelled as different correlated traits: an international genomic single-step SNP best linear unbiased prediction (SNPBLUP) evaluation (ssSNPBLUP(INT)) and an international pedigree-based BLUP evaluation (PBLUPINT). Two national scenarios were implemented for pedigree and genomic evaluations using only nationally submitted phenotypes and genotypes. Accuracies, level and dispersion bias of EBV of animals born from 2014 onwards, and increases in population accuracies were estimated using the linear regression method. Results On average across countries, 39 and 17% of sires and maternal-grand-sires with recorded (grand-)offspring across two countries were genotyped. ssSNPBLUP(INT) showed the highest accuracies of EBV and, compared to PBLUPINT, led to increases in population accuracy of 13.7% for direct EBV, and 25.8% for maternal EBV, on average across countries. Increases in population accuracies when moving from national scenarios to ssSNPBLUP(INT) were observed for all countries. Overall, ssSNPBLUP(INT) level and dispersion bias remained similar or slightly reduced compared to PBLUPINT and national scenarios. Conclusions International single-step SNPBLUP evaluations are feasible and lead to higher population accuracies for both large and small countries compared to current international pedigree-based evaluations and national evaluations. These results are likely related to the larger multi-country reference population and the inclusion of phenotypes from relatives recorded in other countries via single-step international evaluations. The proposed international single-step approach can be applied to other traits and breeds

WASP-80b has a dayside within the T-dwarf range

AHMJT is a Swiss National Science Foundation (SNSF) fellow under grant number P300P2-147773. MG and EJ are Research Associates at the F.R.S-FNRS; LD received the support the support of the F.R.I.A. fund of the FNRS. DE, KH, and SU acknowledge the financial support of the SNSF in the frame of the National Centre for Competence in Research ‘PlanetS’. EH and IR acknowledge support from the Spanish Ministry of Economy and Competitiveness (MINECO) and the ‘Fondo Europeo de Desarrollo Regional’ (FEDER) through grants AYA2012-39612-C03-01 and ESP2013-48391-C4-1-R.WASP-80b is a missing link in the study of exo-atmospheres. It falls between the warm Neptunes and the hot Jupiters and is amenable for characterisation, thanks to its host star's properties. We observed the planet through transit and during occultation with Warm Spitzer. Combining our mid-infrared transits with optical time series, we find that the planet presents a transmission spectrum indistinguishable from a horizontal line. In emission, WASP-80b is the intrinsically faintest planet whose dayside flux has been detected in both the 3.6 and 4.5 $\mu$m Spitzer channels. The depths of the occultations reveal that WASP-80b is as bright and as red as a T4 dwarf, but that its temperature is cooler. If planets go through the equivalent of an L-T transition, our results would imply this happens at cooler temperatures than for brown dwarfs. Placing WASP-80b's dayside into a colour-magnitude diagram, it falls exactly at the junction between a blackbody model and the T-dwarf sequence; we cannot discern which of those two interpretations is the more likely. Flux measurements on other planets with similar equilibrium temperatures are required to establish whether irradiated gas giants, like brown dwarfs, transition between two spectral classes. An eventual detection of methane absorption in transmission would also help lift that degeneracy. We obtained a second series of high-resolution spectra during transit, using HARPS. We reanalyse the Rossiter-McLaughlin effect. The data now favour an aligned orbital solution and a stellar rotation nearly three times slower than stellar line broadening implies. A contribution to stellar line broadening, maybe macroturbulence, is likely to have been underestimated for cool stars, whose rotations have therefore been systematically overestimated. [abridged]Publisher PDFPeer reviewe

The thermal emission of the exoplanets WASP-1b and WASP-2b

We present a comparative study of the thermal emission of the transiting exoplanets WASP-1b and WASP-2b using the Spitzer Space Telescope. The two planets have very similar masses but suffer different levels of irradiation and are predicted to fall either side of a sharp transition between planets with and without hot stratospheres. WASP-1b is one of the most highly irradiated planets studied to date. We measure planet/star contrast ratios in all four of the IRAC bands for both planets (3.6-8.0um), and our results indicate the presence of a strong temperature inversion in the atmosphere of WASP-1b, particularly apparent at 8um, and no inversion in WASP-2b. In both cases the measured eclipse depths favor models in which incident energy is not redistributed efficiently from the day side to the night side of the planet. We fit the Spitzer light curves simultaneously with the best available radial velocity curves and transit photometry in order to provide updated measurements of system parameters. We do not find significant eccentricity in the orbit of either planet, suggesting that the inflated radius of WASP-1b is unlikely to be the result of tidal heating. Finally, by plotting ratios of secondary eclipse depths at 8um and 4.5um against irradiation for all available planets, we find evidence for a sharp transition in the emission spectra of hot Jupiters at an irradiation level of 2 x 10^9 erg/s/cm^2. We suggest this transition may be due to the presence of TiO in the upper atmospheres of the most strongly irradiated hot Jupiters.Comment: 10 pages, submitted to Ap

Phase 2B randomized study of nemolizumab in adults with moderate-to-severe atopic dermatitis and severe pruritus

Background: Nemolizumab targets the IL-31 receptor a subunit involved in atopic dermatitis (AD) pathogenesis. Objective: We sought to evaluate a new dosing strategy of nemolizumab in patients with AD. Methods: We performed a 24-week, randomized, double-blind, multicenter study of nemolizumab (10, 30, and 90 mg) subcutaneous injections every 4 weeks versus placebo, with topical corticosteroids in adults with moderate-to-severe AD, severe pruritus, and inadequate control with topical treatment (n 5 226). The Eczema Area and Severity Index (EASI), the peak pruritus (PP) numeric rating scale (NRS), and the Investigator’s Global Assessment (IGA) were assessed. Standard safety assessments were performed. Results: Nemolizumab improved EASI, IGA, and/or NRS-itch scores, with the 30-mg dose being most effective. Nemolizumab (30 mg) reduced EASI scores versus placebo at week 24 (268.8% vs 252.1%, P 5 .016); significant differences were observed by week 8 (P <_ .01). With significant improvement (P 5 .028) as early as week 4, IGA 0/1 rates were higher for 30 mg of nemolizumab versus placebo at week 16 (33.3% vs 12.3%, P 5 .008) but not week 24 because of an increased placebo/topical corticosteroid effect (36.8% vs 21.1%, P 5 .06). PP-NRS scores were improved for 30 mg of nemolizumab versus placebo at week 16 (268.6% vs 234.3%, P <.0001) and week 24 (267.3% vs 235.8%, P <.0001), with a difference by week 1 (P _4-point decrease) were greater for 30 mg of nemolizumab versus placebo at week 16 (P <_ .001) and week 24 (P <_ .01). Nemolizumab was safe and well tolerated. The most common adverse events were nasopharyngitis and upper respiratory tract infection. Conclusions: Nemolizumab resulted in rapid and sustained improvements in cutaneous signs of inflammation and pruritus in patients with AD, with maximal efficacy observed at 30 mg. Nemolizumab had an acceptable safety profile. (J Allergy Clin Immunol 2020;145:173-82.

Identifying gaps and providing recommendations to address shortcomings in the investigation of acne sequelae by the Personalising Acne: Consensus of Experts panel

Background: The physical sequelae of acne include erythema, hyperpigmentation, and scarring, which are highly burdensome for patients. Early, effective treatment can potentially limit and prevent sequelae development, but there is a need for guidance for and evidence of prevention-oriented management to improve patient outcomes. Objective: To identify unmet needs of acne sequelae and generate expert recommendations to address gaps in clinical guidance. Methods: The Personalizing Acne: Consensus of Experts panel of 13 dermatologists used a modified Delphi approach to achieve a consensus on the clinical aspects of acne sequelae. A consensus was defined as ≥75% of the dermatologists voting agree or strongly agree. All voting was electronic and blinded. Results: The panel identified gaps in current guidance and made recommendations related to acne sequelae. These included identification and classification of sequelae, pertinent points to consider for patient consultations, and management aimed at reducing the development of sequelae. Limitations: The recommendations are based on expert opinion and made in the absence of high-quality evidence. Conclusions: The identified gaps should help inform future research and guideline development for acne sequelae. The consensus-based recommendations should also support the process of consultations throughout the patient journey, helping to reduce the development and burden of acne sequelae through improved risk factor recognition, early discussion, and appropriate management

The Personalised Acne Care Pathway-Recommendations to guide longitudinal management from the Personalising Acne: Consensus of Experts

Background: Acne is a chronic disease with a varying presentation that requires long-term management. Despite this, the clinical guidelines for acne offer limited guidance to facilitate personalized or longitudinal management of patients. Objectives: To generate recommendations to support comprehensive, personalized, long-term patient management that address all presentations of acne and its current and potential future burden. Methods: The Personalising Acne: Consensus of Experts panel consisted of 13 dermatologists who used a modified Delphi approach to reach consensus on statements related to longitudinal acne management. The consensus was defined as ≥75% voting agree or strongly agree. All voting was electronic and blinded. Results: Key management domains, consisting of distinct considerations, points to discuss with patients, and pivot points were identified and incorporated into the Personalised Acne Care Pathway. Long-term treatment goals and expectations and risk of (or fears about) sequelae are highlighted as particularly important to discuss frequently with patients. Limitations: Recommendations are based on expert opinion, which could potentially differ from patients\u27 perspectives. Regional variations in health care systems may not have been captured. Conclusions: The Personalised Acne Care Pathway provides practical recommendations to facilitate the longitudinal management of acne, which can be used by health care professionals to optimize and personalize care throughout the patient journey

How Does BERT Answer Questions? A Layer-Wise Analysis of Transformer Representations

Bidirectional Encoder Representations from Transformers (BERT) reach state-of-the-art results in a variety of Natural Language Processing tasks. However, understanding of their internal functioning is still insufficient and unsatisfactory. In order to better understand BERT and other Transformer-based models, we present a layer-wise analysis of BERT's hidden states. Unlike previous research, which mainly focuses on explaining Transformer models by their attention weights, we argue that hidden states contain equally valuable information. Specifically, our analysis focuses on models fine-tuned on the task of Question Answering (QA) as an example of a complex downstream task. We inspect how QA models transform token vectors in order to find the correct answer. To this end, we apply a set of general and QA-specific probing tasks that reveal the information stored in each representation layer. Our qualitative analysis of hidden state visualizations provides additional insights into BERT's reasoning process. Our results show that the transformations within BERT go through phases that are related to traditional pipeline tasks. The system can therefore implicitly incorporate task-specific information into its token representations. Furthermore, our analysis reveals that fine-tuning has little impact on the models' semantic abilities and that prediction errors can be recognized in the vector representations of even early layers.Comment: Accepted at CIKM 201

The Personalized Acne Treatment Tool - Recommendations to facilitate a patient-centered approach to acne management from the Personalizing Acne: Consensus of Experts

BACKGROUND: Acne, a commonly treated skin disease, requires patient-centered management due to its varying presentations, chronicity, and impact on health-related quality of life. Despite this, evidence-based clinical guidelines focus primarily on clinical severity of facial acne, omitting important patient- and disease-related factors, including ongoing management. OBJECTIVES: To generate recommendations to support patient-centered acne management, which incorporate priority and prognostic factors beyond conventional clinical severity, traditionally defined by grading the appearance and extent of visible lesions. METHODS: The Personalizing Acne: Consensus of Experts consisted of 17 dermatologists who used a modified Delphi approach to reach consensus on statements regarding patient- and treatment-related factors pertaining to patient-centered acne management. Consensus was defined as ≥75% voting agree or strongly agree. RESULTS: Recommendations based on factors such as acne sequelae, location of acne, high burden of disease, and individual patient features were generated and incorporated into the Personalized Acne Treatment Tool. LIMITATIONS: Recommendations are based on expert opinion, which may differ from patients\u27 perspectives. Regional variations in healthcare systems may not be represented. CONCLUSIONS: The Personalizing Acne: Consensus of Experts panel provided practical recommendations to facilitate individualized management of acne, based on patient features, which can be implemented to improve treatment outcomes, adherence, and patient satisfaction