Juncture stress fields in multicellular shell structures. Volume III - Stresses and deformations on fixed-edge segmental conical shells Final report

Equations for thin elastic conical shells and digital program for analysis of stress and deformation on fixed edge segmental conical shells - solution by finite difference techniqu

Investigation of juncture stress fields in multicellular shell structures

Discontinuity stress fields in thin elastic multicellular shell structures subject to inertial, pressure, and thermal loadin

Biological maturation and match running performance: A national football (soccer) federation perspective

© 2019 Sports Medicine Australia Objectives: To examine the influence of maturation and its interaction with playing position upon physical match performances in U15 footballers from a national federation. Design: Observational study. Methods: 278 male outfield players competing in a national tournament were assessed for somatic maturity and match physical performances according to playing position. Stature, sitting height, and body mass were measured and entered into an algorithm to estimate the age at peak height velocity (APHV). Players match movements were recorded by Global Positioning System devices (10 Hz), to determine peak speed, and total- (TD), low-speed running (LSR; ≤13.0 km h−1), high-speed running (HSR; 13.1–16.0 km h−1), very high-speed running (VHSR; 16.1–20.0 km h−1) and sprint distances (SPR; >20.0 km h−1) expressed relative to match exposure (m min−1). Results: Linear-mixed models using log transformed response variables revealed a significant contribution of estimated APHV upon TD (1.01; 95% CI: 0.99–1.02 m·min−1; p < 0.001), HSR (1.05; 95% CI: 0.98–1.13 m min−1; p < 0.001) and VHSR (1.07; 95% CI: 1.00–1.14 m min−1; p = 0.047). An increase by one year in APHV was associated with an increase of 0.6, 5.4 and 6.9% in TD, HSR and VHSR respectively. No effects of APHV were observed for LSR, SPR, and peak speed. Further, no APHV effects were observed relative to players’ field position. Conclusions: Later maturing players covered substantially more higher-intensity (HSR and VHSR) running in matches, irrespective of playing position. The greater match intensity of later maturing players may inform talent identification and athletic development processes within a national federation

Notch Antagonists: Potential Modulators of Cancer and Inflammatory Diseases.

Notch is a key player in various developmental processes during the embryonic stage as well as in regulating tissue homeostasis, cell differentiation, and stem cell maintenance in adult life. Activation of Notch signaling occurs following Notch receptor-ligand interaction and subsequent enzymatic proteolysis by the gamma-secretase complex, resulting in the cytoplasmic release of a Notch intracellular domain, which translocates to the nucleus to initiate the downstream transcriptional machinery. Notch activation and its aberrant signaling have been broadly linked to the pathogenesis of cancer and some chronic inflammatory diseases resulting in pathologic fibrotic processes. This review focuses on the molecular basis of Notch-induced signaling and its interaction with other pathways to identify therapeutic targets. We also highlight current efforts to pharmacologically intervene in Notch signaling and discuss promising ongoing experimental and clinical studies

Safety and clinical activity of the Notch inhibitor, crenigacestat (LY3039478), in an open-label phase I trial expansion cohort of advanced or metastatic adenoid cystic carcinoma

Background Deregulated Notch signaling is implicated in multiple cancers. The phase I trial (I6F-MC-JJCA) investigated the safety and anti-tumor activity of crenigacestat (LY3039478), a selective oral Notch inhibitor, in an expansion cohort of patients with adenoid cystic carcinoma (ACC) who received the dose-escalation-recommended phase 2 dose (RP2D), established previously (Massard C, et al., Annals Oncol 2018, 29:1911-17). Methods Patients with advanced or metastatic cancer, measurable disease, ECOG-PS ≤1, and baseline tumor tissue were enrolled. Primary objectives were to identify a safe RP2D, confirm this dose in expansion cohorts, and document anti-tumor activity. Secondary objectives included safety and progression-free survival (PFS). The ACC expansion cohort received the RP2D regimen of 50 mg crenigacestat thrice per week in a 28-day cycle until disease progression or other discontinuation criteria were met. Results Twenty-two patients with ACC were enrolled in the expansion cohort (median age of 60 years). Median treatment duration was 3 cycles with 6 patients remaining on treatment. There were no objective responses; 1 (5%) patient had an unconfirmed partial response. Disease control rate was 73% and 4 patients had stable disease ≥6 months. Median PFS was 5.3 months (95%CI: 2.4-NE)) for the 22 patients; and 7.7 months (95%CI: 4.0-NR) and 2.4 months (95%CI: 1.1-NE) in the subgroup of patients in second-line (n = 7) or ≥ third-line (n = 9), respectively. Frequent treatment-related-adverse events (all grades) included diarrhea, fatigue, vomiting, decreased appetite, dry mouth, and dry skin. There were no new safety signals. Conclusion The crenigacestat RP2D regimen induced manageable toxicity and limited clinical activity, without confirmed responses, in heavily pretreated patients with ACC

Continuous professional development: elevating thoracic oncology education in Europe

The @EuroRespSoc launches a new thoracic oncology continuous professional development programme http://bit.ly/31ShuTp

New Species in the Old World: Europe as a Frontier in Biodiversity Exploration, a Test Bed for 21st Century Taxonomy

The number of described species on the planet is about 1.9 million, with ca. 17,000 new species described annually, mostly from the tropics. However, taxonomy is usually described as a science in crisis, lacking manpower and funding, a politically acknowledged problem known as the Taxonomic Impediment. Using data from the Fauna Europaea database and the Zoological Record, we show that contrary to general belief, developed and heavily-studied parts of the world are important reservoirs of unknown species. In Europe, new species of multicellular terrestrial and freshwater animals are being discovered and named at an unprecedented rate: since the 1950s, more than 770 new species are on average described each year from Europe, which add to the 125,000 terrestrial and freshwater multicellular species already known in this region. There is no sign of having reached a plateau that would allow for the assessment of the magnitude of European biodiversity. More remarkably, over 60% of these new species are described by non-professional taxonomists. Amateurs are recognized as an essential part of the workforce in ecology and astronomy, but the magnitude of non-professional taxonomist contributions to alpha-taxonomy has not been fully realized until now. Our results stress the importance of developing a system that better supports and guides this formidable workforce, as we seek to overcome the Taxonomic Impediment and speed up the process of describing the planetary biodiversity before it is too late