Fostering Inquiry and Creativity in Early Years STEM Education: Policy Recommendations from the <i>Creative Little Scientists</i> Project

Creative Little Scientists was a 30-month (2011-2014) EU/FP7-funded research project focusing on the synergies between early years science and mathematics education and the development of children’s creativity, in response to increasing interest in these areas in European educational policy. Using a variety of methods, including desk research, a teacher survey and classroom-based fieldwork, the research provided insights into whether and how children’s creativity is fostered and appropriate learning outcomes, including children’s interest, emerge. Based on these and ongoing collaboration and dialogue with participants and other stakeholders the project proposed recommendations for policy and teacher education. This paper presents these recommendations and the research on which they were based. Throughout the study, mixed methods were employed, combining quantitative approaches used in surveys of policy and teachers’ views based on a list of factors, alongside qualitative approaches employed in case studies of classroom practice. A strong conceptual framework developed at the start of the project guided data collection and analysis, as well as the presentation of findings and the development of policy recommendations, thus ensuring the latter’s strong and consistent relationship with the relevant theoretical knowledge, the comparative research, analysis of classroom practices and the production of guidelines for teacher education

Human Cytomegalovirus Escapes a Naturally Occurring Neutralizing Antibody by Incorporating It into Assembling Virions

SummaryHuman cytomegalovirus (CMV) is a common but difficult to treat infection of immunocompromised patients. MSL-109 is a human monoclonal IgG isolated from a CMV seropositive individual that recognizes the viral glycoprotein H (gH) surface antigen complexes that mediate entry. Although MSL-109 blocks CMV infection in vitro, it lacked sufficient efficacy in human trials, and CMV isolated from treated patients suggested the evolution of MSL-109 resistance. To understand how CMV escapes MSL-109, we characterized a MSL-109-resistant CMV strain. Our results elucidate a nongenetic escape mechanism in which the antibody is selectively taken up by infected cells and incorporated into assembling virions in a dose-dependent manner. The resistant virus then utilizes the Fc domain of the incorporated antibody to infect naive nonimmune cells. This resistance mechanism may explain the clinical failure of MSL-109, illustrate a general mechanism of viral antibody escape, and inform antiviral vaccine and therapeutic development

A thermostable salmonella phage endolysin, Lys68, with broad bactericidal properties against gram-negative pathogens in presence of weak acids

Resistance rates are increasing among several problematic Gram-negative pathogens, a fact that has encouraged the development of new antimicrobial agents. This paper characterizes a Salmonella phage endolysin (Lys68) and demonstrates its potential antimicrobial effectiveness when combined with organic acids towards Gram-negative pathogens. Biochemical characterization reveals that Lys68 is more active at pH 7.0, maintaining 76.7% of its activity when stored at 4°C for two months. Thermostability tests showed that Lys68 is only completely inactivated upon exposure to 100°C for 30 min, and circular dichroism analysis demonstrated the ability to refold into its original conformation upon thermal denaturation. It was shown that Lys68 is able to lyse a wide panel of Gram-negative bacteria (13 different species) in combination with the outer membrane permeabilizers EDTA, citric and malic acid. While the EDTA/Lys68 combination only inactivated Pseudomonas strains, the use of citric or malic acid broadened Lys68 antibacterial effect to other Gram-negative pathogens (lytic activity against 9 and 11 species, respectively). Particularly against Salmonella Typhimurium LT2, the combinatory effect of malic or citric acid with Lys68 led to approximately 3 to 5 log reductions in bacterial load/CFUs after 2 hours, respectively, and was also able to reduce stationary-phase cells and bacterial biofilms by approximately 1 log. The broad killing capacity of malic/citric acid-Lys68 is explained by the destabilization and major disruptions of the cell outer membrane integrity due to the acidity caused by the organic acids and a relatively high muralytic activity of Lys68 at low pH. Lys68 demonstrates good (thermo)stability properties that combined with different outer membrane permeabilizers, could become useful to combat Gram-negative pathogens in agricultural, food and medical industry.This work was supported by the projects FCOMP-01-0124-FEDER-019446, FCOMP-01-0124-FEDER-027462 and PEst-OE/EQB/LA0023/2013 from "Fundacao para a Ciencia e Tecnologia" (FCT), Portugal. The authors thank the Project "BioHealth - Biotechnology and Bioengineering approaches to improve health quality", Ref. NORTE-07-0124-FEDER-000027, co-funded by the Programa Operacional Regional do Norte (ON. 2 - O Novo Norte), QREN, FEDER. Hugo Oliveira acknowledges the FCT grant SFRH/BD/63734/2009. Maarten Walmagh held a PhD scholarship of the IWT Vlaanderen. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Global, regional, and national burden of respiratory tract cancers and associated risk factors from 1990 to 2019: a systematic analysis for the Global Burden of Disease Study 2019

Background Prevention, control, and treatment of respiratory tract cancers are important steps towards achieving target 3.4 of the UN Sustainable Development Goals (SDGs)—a one-third reduction in premature mortality due to non-communicable diseases by 2030. We aimed to provide global, regional, and national estimates of the burden of tracheal, bronchus, and lung cancer and larynx cancer and their attributable risks from 1990 to 2019. Methods Based on the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 methodology, we evaluated the incidence, mortality, years lived with disability, years of life lost, and disability-adjusted life-years (DALYs) of respiratory tract cancers (ie, tracheal, bronchus, and lung cancer and larynx cancer). Deaths from tracheal, bronchus, and lung cancer and larynx cancer attributable to each risk factor were estimated on the basis of risk exposure, relative risks, and the theoretical minimum risk exposure level input from 204 countries and territories, stratified by sex and Socio-demographic Index (SDI). Trends were estimated from 1990 to 2019, with an emphasis on the 2010–19 period. Findings Globally, there were 2·26 million (95% uncertainty interval 2·07 to 2·45) new cases of tracheal, bronchus, and lung cancer, and 2·04 million (1·88 to 2·19) deaths and 45·9 million (42·3 to 49·3) DALYs due to tracheal, bronchus, and lung cancer in 2019. There were 209 000 (194 000 to 225 000) new cases of larynx cancer, and 123 000 (115 000 to 133 000) deaths and 3·26 million (3·03 to 3·51) DALYs due to larynx cancer globally in 2019. From 2010 to 2019, the number of new tracheal, bronchus, and lung cancer cases increased by 23·3% (12·9 to 33·6) globally and the number of larynx cancer cases increased by 24·7% (16·0 to 34·1) globally. Global age-standardised incidence rates of tracheal, bronchus, and lung cancer decreased by 7·4% (−16·8 to 1·6) and age-standardised incidence rates of larynx cancer decreased by 3·0% (−10·5 to 5·0) in males over the past decade; however, during the same period, age-standardised incidence rates in females increased by 0·9% (−8·2 to 10·2) for tracheal, bronchus, and lung cancer and decreased by 0·5% (−8·4 to 8·1) for larynx cancer. Furthermore, although age-standardised incidence and death rates declined in both sexes combined from 2010 to 2019 at the global level for tracheal, bronchus, lung and larynx cancers, some locations had rising rates, particularly those on the lower end of the SDI range. Smoking contributed to an estimated 64·2% (61·9–66·4) of all deaths from tracheal, bronchus, and lung cancer and 63·4% (56·3–69·3) of all deaths from larynx cancer in 2019. For males and for both sexes combined, smoking was the leading specific risk factor for age-standardised deaths from tracheal, bronchus, and lung cancer per 100 000 in all SDI quintiles and GBD regions in 2019. However, among females, household air pollution from solid fuels was the leading specific risk factor in the low SDI quintile and in three GBD regions (central, eastern, and western sub-Saharan Africa) in 2019. Interpretation The numbers of incident cases and deaths from tracheal, bronchus, and lung cancer and larynx cancer increased globally during the past decade. Even more concerning, age-standardised incidence and death rates due to tracheal, bronchus, lung cancer and larynx cancer increased in some populations—namely, in the lower SDI quintiles and among females. Preventive measures such as smoking control interventions, air quality management programmes focused on major air pollution sources, and widespread access to clean energy should be prioritised in these settings.publishedVersio

Psychosocial impact of undergoing prostate cancer screening for men with BRCA1 or BRCA2 mutations.

OBJECTIVES: To report the baseline results of a longitudinal psychosocial study that forms part of the IMPACT study, a multi-national investigation of targeted prostate cancer (PCa) screening among men with a known pathogenic germline mutation in the BRCA1 or BRCA2 genes. PARTICPANTS AND METHODS: Men enrolled in the IMPACT study were invited to complete a questionnaire at collaborating sites prior to each annual screening visit. The questionnaire included sociodemographic characteristics and the following measures: the Hospital Anxiety and Depression Scale (HADS), Impact of Event Scale (IES), 36-item short-form health survey (SF-36), Memorial Anxiety Scale for Prostate Cancer, Cancer Worry Scale-Revised, risk perception and knowledge. The results of the baseline questionnaire are presented. RESULTS: A total of 432 men completed questionnaires: 98 and 160 had mutations in BRCA1 and BRCA2 genes, respectively, and 174 were controls (familial mutation negative). Participants' perception of PCa risk was influenced by genetic status. Knowledge levels were high and unrelated to genetic status. Mean scores for the HADS and SF-36 were within reported general population norms and mean IES scores were within normal range. IES mean intrusion and avoidance scores were significantly higher in BRCA1/BRCA2 carriers than in controls and were higher in men with increased PCa risk perception. At the multivariate level, risk perception contributed more significantly to variance in IES scores than genetic status. CONCLUSION: This is the first study to report the psychosocial profile of men with BRCA1/BRCA2 mutations undergoing PCa screening. No clinically concerning levels of general or cancer-specific distress or poor quality of life were detected in the cohort as a whole. A small subset of participants reported higher levels of distress, suggesting the need for healthcare professionals offering PCa screening to identify these risk factors and offer additional information and support to men seeking PCa screening

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

The Changing Landscape for Stroke\ua0Prevention in AF: Findings From the GLORIA-AF Registry Phase 2

Background GLORIA-AF (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation) is a prospective, global registry program describing antithrombotic treatment patterns in patients with newly diagnosed nonvalvular atrial fibrillation at risk of stroke. Phase 2 began when dabigatran, the first non\u2013vitamin K antagonist oral anticoagulant (NOAC), became available. Objectives This study sought to describe phase 2 baseline data and compare these with the pre-NOAC era collected during phase&nbsp;1. Methods During phase 2, 15,641 consenting patients were enrolled (November 2011 to December 2014); 15,092 were eligible. This pre-specified cross-sectional analysis describes eligible patients\u2019 baseline characteristics. Atrial fibrillation&nbsp;disease characteristics, medical outcomes, and concomitant diseases and medications were collected. Data were analyzed using descriptive statistics. Results Of the total patients, 45.5% were female; median age was 71 (interquartile range: 64, 78) years. Patients were from Europe (47.1%), North America (22.5%), Asia (20.3%), Latin America (6.0%), and the Middle East/Africa (4.0%). Most had high stroke risk (CHA2DS2-VASc [Congestive heart failure, Hypertension, Age&nbsp; 6575 years, Diabetes mellitus, previous Stroke, Vascular disease, Age 65 to 74 years, Sex category] score&nbsp; 652; 86.1%); 13.9% had moderate risk (CHA2DS2-VASc&nbsp;= 1). Overall, 79.9% received oral anticoagulants, of whom 47.6% received NOAC and 32.3% vitamin K antagonists (VKA); 12.1% received antiplatelet agents; 7.8% received no antithrombotic treatment. For comparison, the proportion of phase 1 patients (of N&nbsp;= 1,063 all eligible) prescribed VKA was 32.8%, acetylsalicylic acid 41.7%, and no therapy 20.2%. In Europe in phase 2, treatment with NOAC was more common than VKA (52.3% and 37.8%, respectively); 6.0% of patients received antiplatelet treatment; and 3.8% received no antithrombotic treatment. In North America, 52.1%, 26.2%, and 14.0% of patients received NOAC, VKA, and antiplatelet drugs, respectively; 7.5% received no antithrombotic treatment. NOAC use was less common in Asia (27.7%), where 27.5% of patients received VKA, 25.0% antiplatelet drugs, and 19.8% no antithrombotic treatment. Conclusions The baseline data from GLORIA-AF phase 2 demonstrate that in newly diagnosed nonvalvular atrial fibrillation patients, NOAC have been highly adopted into practice, becoming more frequently prescribed than VKA in&nbsp;Europe and North America. Worldwide, however, a large proportion of patients remain undertreated, particularly in&nbsp;Asia&nbsp;and North America. (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients With Atrial Fibrillation [GLORIA-AF]; NCT01468701

The global burden of cancer attributable to risk factors, 2010-19 : a systematic analysis for the Global Burden of Disease Study 2019

Background Understanding the magnitude of cancer burden attributable to potentially modifiable risk factors is crucial for development of effective prevention and mitigation strategies. We analysed results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 to inform cancer control planning efforts globally. Methods The GBD 2019 comparative risk assessment framework was used to estimate cancer burden attributable to behavioural, environmental and occupational, and metabolic risk factors. A total of 82 risk-outcome pairs were included on the basis of the World Cancer Research Fund criteria. Estimated cancer deaths and disability-adjusted life-years (DALYs) in 2019 and change in these measures between 2010 and 2019 are presented. Findings Globally, in 2019, the risk factors included in this analysis accounted for 4.45 million (95% uncertainty interval 4.01-4.94) deaths and 105 million (95.0-116) DALYs for both sexes combined, representing 44.4% (41.3-48.4) of all cancer deaths and 42.0% (39.1-45.6) of all DALYs. There were 2.88 million (2.60-3.18) risk-attributable cancer deaths in males (50.6% [47.8-54.1] of all male cancer deaths) and 1.58 million (1.36-1.84) risk-attributable cancer deaths in females (36.3% [32.5-41.3] of all female cancer deaths). The leading risk factors at the most detailed level globally for risk-attributable cancer deaths and DALYs in 2019 for both sexes combined were smoking, followed by alcohol use and high BMI. Risk-attributable cancer burden varied by world region and Socio-demographic Index (SDI), with smoking, unsafe sex, and alcohol use being the three leading risk factors for risk-attributable cancer DALYs in low SDI locations in 2019, whereas DALYs in high SDI locations mirrored the top three global risk factor rankings. From 2010 to 2019, global risk-attributable cancer deaths increased by 20.4% (12.6-28.4) and DALYs by 16.8% (8.8-25.0), with the greatest percentage increase in metabolic risks (34.7% [27.9-42.8] and 33.3% [25.8-42.0]). Interpretation The leading risk factors contributing to global cancer burden in 2019 were behavioural, whereas metabolic risk factors saw the largest increases between 2010 and 2019. Reducing exposure to these modifiable risk factors would decrease cancer mortality and DALY rates worldwide, and policies should be tailored appropriately to local cancer risk factor burden. Copyright (C) 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.Peer reviewe