Genomic landscape and clonal architecture of mouse oral squamous cell carcinomas dictate tumour ecology.

To establish whether 4-nitroquinoline N-oxide-induced carcinogenesis mirrors the heterogeneity of human oral squamous cell carcinoma (OSCC), we have performed genomic analysis of mouse tongue lesions. The mutational signatures of human and mouse OSCC overlap extensively. Mutational burden is higher in moderate dysplasias and invasive SCCs than in hyperplasias and mild dysplasias, although mutations in p53, Notch1 and Fat1 occur in early lesions. Laminin-α3 mutations are associated with tumour invasiveness and Notch1 mutant tumours have an increased immune infiltrate. Computational modelling of clonal dynamics indicates that high genetic heterogeneity may be a feature of those mild dysplasias that are likely to progress to more aggressive tumours. These studies provide a foundation for exploring OSCC evolution, heterogeneity and progression

The global burden of adolescent and young adult cancer in 2019: a systematic analysis for the Global Burden of Disease Study 2019

Background: In estimating the global burden of cancer, adolescents and young adults with cancer are often overlooked, despite being a distinct subgroup with unique epidemiology, clinical care needs, and societal impact. Comprehensive estimates of the global cancer burden in adolescents and young adults (aged 15–39 years) are lacking. To address this gap, we analysed results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019, with a focus on the outcome of disability-adjusted life-years (DALYs), to inform global cancer control measures in adolescents and young adults. Methods: Using the GBD 2019 methodology, international mortality data were collected from vital registration systems, verbal autopsies, and population-based cancer registry inputs modelled with mortality-to-incidence ratios (MIRs). Incidence was computed with mortality estimates and corresponding MIRs. Prevalence estimates were calculated using modelled survival and multiplied by disability weights to obtain years lived with disability (YLDs). Years of life lost (YLLs) were calculated as age-specific cancer deaths multiplied by the standard life expectancy at the age of death. The main outcome was DALYs (the sum of YLLs and YLDs). Estimates were presented globally and by Socio-demographic Index (SDI) quintiles (countries ranked and divided into five equal SDI groups), and all estimates were presented with corresponding 95% uncertainty intervals (UIs). For this analysis, we used the age range of 15–39 years to define adolescents and young adults. Findings: There were 1·19 million (95% UI 1·11–1·28) incident cancer cases and 396 000 (370 000–425 000) deaths due to cancer among people aged 15–39 years worldwide in 2019. The highest age-standardised incidence rates occurred in high SDI (59·6 [54·5–65·7] per 100 000 person-years) and high-middle SDI countries (53·2 [48·8–57·9] per 100 000 person-years), while the highest age-standardised mortality rates were in low-middle SDI (14·2 [12·9–15·6] per 100 000 person-years) and middle SDI (13·6 [12·6–14·8] per 100 000 person-years) countries. In 2019, adolescent and young adult cancers contributed 23·5 million (21·9–25·2) DALYs to the global burden of disease, of which 2·7% (1·9–3·6) came from YLDs and 97·3% (96·4–98·1) from YLLs. Cancer was the fourth leading cause of death and tenth leading cause of DALYs in adolescents and young adults globally. Interpretation: Adolescent and young adult cancers contributed substantially to the overall adolescent and young adult disease burden globally in 2019. These results provide new insights into the distribution and magnitude of the adolescent and young adult cancer burden around the world. With notable differences observed across SDI settings, these estimates can inform global and country-level cancer control efforts. Funding: Bill & Melinda Gates Foundation, American Lebanese Syrian Associated Charities, St Baldrick's Foundation, and the National Cancer Institute

The global burden of adolescent and young adult cancer in 2019 : a systematic analysis for the Global Burden of Disease Study 2019

Background In estimating the global burden of cancer, adolescents and young adults with cancer are often overlooked, despite being a distinct subgroup with unique epidemiology, clinical care needs, and societal impact. Comprehensive estimates of the global cancer burden in adolescents and young adults (aged 15-39 years) are lacking. To address this gap, we analysed results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019, with a focus on the outcome of disability-adjusted life-years (DALYs), to inform global cancer control measures in adolescents and young adults. Methods Using the GBD 2019 methodology, international mortality data were collected from vital registration systems, verbal autopsies, and population-based cancer registry inputs modelled with mortality-to-incidence ratios (MIRs). Incidence was computed with mortality estimates and corresponding MIRs. Prevalence estimates were calculated using modelled survival and multiplied by disability weights to obtain years lived with disability (YLDs). Years of life lost (YLLs) were calculated as age-specific cancer deaths multiplied by the standard life expectancy at the age of death. The main outcome was DALYs (the sum of YLLs and YLDs). Estimates were presented globally and by Socio-demographic Index (SDI) quintiles (countries ranked and divided into five equal SDI groups), and all estimates were presented with corresponding 95% uncertainty intervals (UIs). For this analysis, we used the age range of 15-39 years to define adolescents and young adults. Findings There were 1.19 million (95% UI 1.11-1.28) incident cancer cases and 396 000 (370 000-425 000) deaths due to cancer among people aged 15-39 years worldwide in 2019. The highest age-standardised incidence rates occurred in high SDI (59.6 [54.5-65.7] per 100 000 person-years) and high-middle SDI countries (53.2 [48.8-57.9] per 100 000 person-years), while the highest age-standardised mortality rates were in low-middle SDI (14.2 [12.9-15.6] per 100 000 person-years) and middle SDI (13.6 [12.6-14.8] per 100 000 person-years) countries. In 2019, adolescent and young adult cancers contributed 23.5 million (21.9-25.2) DALYs to the global burden of disease, of which 2.7% (1.9-3.6) came from YLDs and 97.3% (96.4-98.1) from YLLs. Cancer was the fourth leading cause of death and tenth leading cause of DALYs in adolescents and young adults globally. Interpretation Adolescent and young adult cancers contributed substantially to the overall adolescent and young adult disease burden globally in 2019. These results provide new insights into the distribution and magnitude of the adolescent and young adult cancer burden around the world. With notable differences observed across SDI settings, these estimates can inform global and country-level cancer control efforts. Copyright (C) 2021 The Author(s). Published by Elsevier Ltd.Peer reviewe

A report card on the management of E-health in Australia: From optimistic assumptions to conflicted success of Telehealth

Dramatically escalating healthcare costs have prompted governments around the world toincrease the rate of investment and the number of health information communicationtechnologies (HICT) projects, also known as E-health projects, in the hope of improvingefficiency and effectiveness of health services. Despite the often-massive expenditures,evidence of E-health projects improving efficiency and effectiveness of service delivery anddelivering positive return on investment is contradictory at best. Reviews of literature on Ehealth programs indicate that there are significant challenges, ranging from low adoption tosustainability, which are closely related to management of E-Health initiatives. This paperconducted a qualitative analysis of 29 telehealth initiatives carried out in Australia between 2009 and 2019, identifying a wide range of problematic project and change management practices in their main areas of scope: technological and non-technological implementation, change management, and user acceptance. The analysis provides a bleak picture of a project focus with high levels of unrealistic optimism regarding these initiatives among managers, resulting in near-universal mixed results indicating “conflicted success’ of such initiatives. We offer insights applying a critical lens to current perspectives on the nature of E-health programs and their management, arguing that the adoption of change management as the main framework will improve the decision making and success levels of E-health initiatives.Keywords: E-health, management, change, Telehealth, healthcare, Australi

Infrared temperature measurement and increasing infrared measurement accuracy in the context of machining process

One of the major challenges in the machining process is measuring the temperature accurately which has a considerable importance in calibrating finite element models and investigating thermodynamic of machining process. In the present paper, one of the effective methods for measuring temperature in the machining processes - i.e. infrared imaging - is used and effective parameters which increase measurement accuracy are investigated. One of the most effective parameter in the temperature measurement accuracy of infrared imaging is extracting and calibrating the emissivity coefficient for different temperature ranges. The obtained results show that the lack of precision calibration of the emissivity for different temperature ranges may cause high error in the measurement results. To measure temperature, several experiments are performed for turning a thin walled workpiece which is made of aluminium alloy Al-7075 and the effects of the machining parameters and tool material - polycrystalline diamond (PCD) and cemented carbide - are studied. Based on the achieved results, it can be concluded that the generated temperature in the cutting area can be decreased significantly by using PCD tools and selecting appropriate machining parameters

Phase equilibria in the aluminium-rich side of the Al-Zr system.

International audienceThe Al-rich phase equilibria in the Al-Zr binary system were investigated experimentally. The phase diagram for compositions up to 40 at.% Zr was determined experimentally by differential thermal analysis and metallography. Three stable intermetallic compounds exist in this region of the diagram: Al3Zr2, Al2Zr, and Al3Zr. The peritectic melting of Al3Zr2 and the congruent melting of Al2Zr were confirmed. Al3Zr, the most Al-rich intermetallic compound, melts peritectically, which contradicts information available in the literature. In addition, the reaction between Al3Zr and the (Al) solid solution seems to be of eutectic nature, in contradiction with previous results found in the literature. Based on these new experimental evidence, a revised phase diagram is drawn