A dinosaurian facial deformity and the first occurrence of ameloblastoma in the fossil record

Despite documentation of various types of neoplastic pathologies encountered in the vertebrate fossil record, no ameloblastic tumours have been recognised so far. Ameloblastoma is a benign neoplasic tumour with a strong preponderance for the mandible. Here, we report for the first time the presence of an ameloblastoma neoplasm in the lower jaw of a specimen referred to the derived non-hadrosaurid hadrosauroid dinosaur Telmatosaurus transsylvanicus from the uppermost Cretaceous of the Haeg Basin in Romania. The location, external appearance and internal structure of the pathological outgrowth provide clear evidence for the diagnosis of ameloblastoma in Telmatosaurus. This report extends the range of pathologies encountered in hadrosauroid dinosaurs. In addition, recognition of an ameloblastoma neoplasm in a taxon lying close to the origin of ‘duck-billed’ hadrosaurid dinosaurs confirms the predisposition of this clade towards neoplasia pathologies already in its basal members

Individual learning on environmental vocational education and training courses does not always lead to the workplace application of knowledge and skills

YesEmpirical research on three commercial environmental vocational education and training programmes revealed distinct personal, teaching and work-based presage factors, which influenced individual learning and learning transfer to the workplace. The extent to which behaviour change and learning transfer occurred depended on a diverse range of factors, notably the workplace utility of the course; student’s level of personal commitment and position within the employing organisation; strength of the organisation’s environmental culture; level of post-course managerial/supervisory support available within the workplace; and changing workplace circumstances/priorities

Measurement and determination of encoder disc surface parameters in x-z planes using a conventional optical disc reading head

Non-contact surface measurement methods as well as roughness parameter determination methods are analyzed in the paper. While most of the modern non-contact surface inspection methods require advanced instrumentation and a big budget, this study looks into a novel approach to non-contact encoder disc roughness measurements by using the proposed system attached to the rotary table with an implemented optical disc pick up head and the reference angle encoder. Application of a conventional optical disc laser reading system resulted in a cost effective and compact solution for a non-destructive angle encoder disc surface inspection. Assets and shortcomings as well as detailed analysis of the measurement procedure are explained in the paper. The experimental setup and the measurement results are presented within this article

Preliminary results from a phase I/II study of BDC-1001, a novel HER2 targeting TLR7/8 immune-stimulating antibody conjugate (ISAC), in patients (pts) with advanced HER2-expressing solid tumors

Background: BDC-1001 is a novel ISAC consisting of an investigational trastuzumab biosimilar chemically conjugated to a TLR7/8 agonist with a non-cleavable linker. BDC1001 elicits myeloid activation and enhances antigen presentation leading to antibody-mediated effector functions that promote T-cell activation and a durable adaptive immune response. Methods: A 4-part, phase 1/2 dose-escalation/expansion study was initiated to evaluate BDC-1001 PD-1 inhibitor in pts with previously treated advanced/metastatic HER2-expressing (IHC2/3+) or amplified solid tumors (NCT04278144). Pts received BDC-1001 IV in a 3+3 design. Primary objectives are to evaluate safety, tolerability, dose-limiting toxicities (DLTs), and determine a recommended phase 2 dose (RP2D); secondary and exploratory objectives are to assess pharmacokinetics (PK), pharmacodynamics (PD), and preliminary antitumor activity. Results: From the completed monotherapy dose-escalation (Part 1) will be reported including safety, tolerability, PK, and PD biomarker data. The initial subset of pts enrolled include the following cancer types: breast, biliary, cervical, colorectal, lung, gastroesophageal, salivary, urinary tract, and endometrial. Preliminary results of the first 20 pts indicate that BDC-1001 appears well-tolerated. No DLTs have been observed, and the MTD has not been reached. AEs deemed related to BDC-1001 were grade 1-2, including infusion-related reactions and one event of decreased ejection fraction. Early evidence of clinical activity was observed in a pt with a partial response and other pts with stable disease. Increases in plasma biomarkers associated with TLR7/8 and myeloid cell activation (TNFa, CXCL10, MCP-1, MIP-1a) were observed. BDC-1001 treatment led to an increase in myeloid and T-cell infiltration in a subset of pts. Updated clinical and translational data are anticipated. Conclusions: In this first-in-human study, BDC-1001 appears well-tolerated with early evidence of clinical activity, including pts previously treated with anti-HER2 therapy. Dose escalation is ongoing. Clinical trial identification: NCT04278144

‘Overcoming the Bottleneck’: Knowledge Architectures for Genomic Data Interpretation in Oncology

International audienceIn recent years, oncology transitioned from its traditional, organ-based approach to 'precision oncology' centered on molecular alterations. As a result, it has become to a significant extent a 'data-centric' domain. Its practices increasingly rely on a sophisticated techno-scientific infrastructure that generates massive amounts of data in need of consistent, appropriate interpretations. Attempts to overcome the interpretation bottleneck have led to the establishment of a complex landscape of interrelated resources that, while displaying distinct characteristics and design choices, also entertain horizontal and vertical relations. Although there is no denying that the data-centric nature of contemporary oncology raises a number of key issues related to the production and circulation of data, we suggest that the focus on data use and re-use should be complemented by a focus on interpretation. Oncology practitioners refer to data interpretation resources as 'knowledgebases', an actor's category designed to differentiate them from generic, multipurpose databases. Their major purpose is the definition and identification of clinically actionable alterations. A heavy investment in human curation, of a clinical rather than exclusively scientific nature is needed to make them valuable, but each knowledgebas