A Jurassic ornithischian dinosaur from Siberia with both feathers and scales

Feathers, not just for the birds? Theropod dinosaurs, thought to be the direct ancestors of birds, sported birdlike feathers. But were they the only feathery dino group? Godefroit et al. describe an early neornithischian dinosaur with both early feathers and scales. This seemingly feathery nontheropod dinosaur shows that feathers were not unique to the ancestors of birds and may even have been quite widespread. Science , this issue p. 451 </jats:p

Neuroimaging of structural pathology and connectomics in traumatic brain injury: Toward personalized outcome prediction.

Recent contributions to the body of knowledge on traumatic brain injury (TBI) favor the view that multimodal neuroimaging using structural and functional magnetic resonance imaging (MRI and fMRI, respectively) as well as diffusion tensor imaging (DTI) has excellent potential to identify novel biomarkers and predictors of TBI outcome. This is particularly the case when such methods are appropriately combined with volumetric/morphometric analysis of brain structures and with the exploration of TBI-related changes in brain network properties at the level of the connectome. In this context, our present review summarizes recent developments on the roles of these two techniques in the search for novel structural neuroimaging biomarkers that have TBI outcome prognostication value. The themes being explored cover notable trends in this area of research, including (1) the role of advanced MRI processing methods in the analysis of structural pathology, (2) the use of brain connectomics and network analysis to identify outcome biomarkers, and (3) the application of multivariate statistics to predict outcome using neuroimaging metrics. The goal of the review is to draw the community's attention to these recent advances on TBI outcome prediction methods and to encourage the development of new methodologies whereby structural neuroimaging can be used to identify biomarkers of TBI outcome

Discovery of Innovative Therapies for Rare Immune-Mediated Inflammatory Diseases via Off-Label Prescription of Biologics: The Case of IL-6 Receptor Blockade in Castleman’s Disease

Biologics have revolutionized the field of clinical immunology and proven to be both effective and safe in common immune-mediated inflammatory diseases (IMIDs) such as rheumatoid arthritis, inflammatory bowel diseases, and various hematological disorders. However, in patients with rare, severe IMIDs failing on standard therapies, it is virtually impossible to conduct randomized controlled trials. Therefore, biologics are usually prescribed off-label in these often severely ill patients. Unfortunately, off-label prescription is sometimes hampered in these diseases due to a lack of reimbursement that is often based on a presumed lack of evidence for effectiveness. In the present article, we will discuss that off-label prescription of biologics can be a good way to discover new treatments for rare diseases. This will be illustrated using a case of multicentric Castleman's disease, an immune-mediated lymphoproliferative disorder, in which off-label tocilizumab (humanized anti-IL-6 receptor blocking antibody) treatment resulted in remarkable clinical improvement. Furthermore, we will give recommendations for monitoring efficacy and safety of biologic treatment in rare IMIDs, including the use of registries. In conclusion, we put forward that innovative treatments for rare IMIDs can be discovered via off-label prescription of biologicals, provided that this is based on rational arguments including knowledge of the pathophysiology of the diseas

Evaluation of the First Year(s) of Physicians Collaboration on an Interdisciplinary Electronic Consultation Platform in the Netherlands:Mixed Methods Observational Study

BACKGROUND: Complexity of health problems and aging of the population create an ongoing burden on the health care system with the general practitioner (GP) being the gatekeeper in primary care. In GPs daily practice, collaboration with specialists and exchange of knowledge from the secondary care play a crucial role in this system. Communication between primary and secondary care has shortcomings for health care workers that want to practice sustainable patient-centered health care. Therefore, a new digital interactive platform was developed: Prisma. OBJECTIVE: This study aims to describe the development of a digital consultation platform (Prisma) to connect GPs with hospital specialists via the Siilo application and to evaluate the first year of use, including consultations, topic diversity, and number of participating physicians. METHODS: We conducted a mixed methods observational study, analyzing qualitative and quantitative data for cases posted on the platform between June 2018 and May 2020. Any GP can post questions to an interdisciplinary group of secondary care specialists, with the platform designed to facilitate discussion and knowledge exchange for all users. RESULTS: In total, 3674 cases were posted by 424 GPs across 16 specialisms. Most questions and answers concerned diagnosis, nonmedical treatment, and medication. Mean response time was 76 minutes (range 44-252). An average of 3 users engaged with each case (up to 7 specialists). Almost half of the internal medicine cases received responses from at least two specialisms in secondary care, contrasting with about one-fifth for dermatology. Of note, the growth in consultations was steepest for dermatology. CONCLUSIONS: Digital consultations offer the possibility for GPs to receive quick responses when seeking advice. The interdisciplinary approach of Prisma creates opportunities for digital patient-centered networking

Reductions in movement-associated fear are dependent upon graded exposure in chronic low back pain : an exploratory analysis of a modified 3-item fear hierarchy

Objective: To explore the effectiveness of a modified fear hierarchy on measuring improvements in movement-associated fear in chronic low back pain. Methods: A modified 3-item fear hierarchy was created and implemented based on principles of graded exposure. This study was an exploratory analysis of the modified 3-item fear hierarchy from a larger clinical trial data set. Both groups received pain education and exercise, either bodyweight or strength training. Both groups performed item one on the hierarchy, the squat. Only the strength training group performed item 2, the deadlift. Neither group performed item 3, the overhead press. Analysis of Covariance and stepwise linear regression were used to explore results. Results: Improvement in movement-associated fear was conditional upon graded exposure. Both groups improved in the squat movement (p ≤ 0.05), which both performed. Only the strength training group improved in the deadlift (p ≤ 0.01), and neither improved in the overhead press (p ≥ 0.05). Conclusion: Reductions in movement-associated fear are conditional upon graded exposure, based on the use of a novel modified 3-item fear hierarchy. Further research is needed to understand the utility of this tool in a patient-led approach to co-designing a graded exposure-based intervention

Reliability of computerized image analysis for the evaluation of serial synovial biopsies in randomized controlled trials in rheumatoid arthritis

Analysis of biomarkers in synovial tissue is increasingly used in the evaluation of new targeted therapies for patients with rheumatoid arthritis (RA). This study determined the intrarater and inter-rater reliability of digital image analysis (DIA) of synovial biopsies from RA patients participating in clinical trials. Arthroscopic synovial biopsies were obtained before and after treatment from 19 RA patients participating in a randomized controlled trial with prednisolone. Immunohistochemistry was used to detect CD3(+ )T cells, CD38(+ )plasma cells and CD68(+ )macrophages. The mean change in positive cells per square millimetre for each marker was determined by different operators and at different times using DIA. Nonparametric tests were used to determine differences between observers and assessments, and to determine changes after treatment. The intraclass correlations (ICCs) were calculated to determine the intrarater and inter-rater reliability. Intrarater ICCs showed good reliability for measuring changes in T lymphocytes (R = 0.87), plasma cells (R = 0.62) and macrophages (R = 0.73). Analysis by Bland–Altman plots showed no systemic differences between measurements. The smallest detectable changes were calculated and their discriminatory power revealed good response in the prednisolone group compared with the placebo group. Similarly, inter-rater ICCs also revealed good reliability for measuring T lymphocytes (R = 0.68), plasma cells (R = 0.69) and macrophages (R = 0.72). All measurements identified the same cell types as changing significantly in the treated patients compared with the placebo group. The measurement of change in total positive cell numbers in synovial tissue can be determined reproducibly for various cell types by DIA in RA clinical trials