An interactive flash application as a supplementary teaching tool in higher education

Educational Flash applications have received the attention of researchers and educators in higher education as a result of the evolution of technology, including high-speed Internet, advanced hardware and software, and the seeking of new learning paradigms from the constructivist\u27s point of view. However, existing educational websites utilizing Flash contain limited interactivity, and few websites have been created which adapt valuable educational theories that sustain and enhance the learning processes that suit the Net generation. The purpose of this study is to examine educational theories which are relevant to current educational contexts and learners and to propose a guideline for developing an educational application. In addition, by providing an educational Flash application, the author discovers potential applications using Flash to enhancing the learning process, based on literature which has been previously discussed. To create the educational Flash application, the author selected the subject, learning grid systems for design students in higher education. The validity of this application is examined by learners\u27 evaluations. The guidelines proposed by the author can be utilized by developers and educators to create instructional applications based on valid educational theories. Also, the Flash application as the prototype for this study is an illustration of a higher education use of Flash

Regulation of MEK Signaling and Inhibitor Sensitivity in Melanoma

Melanoma, the deadliest form of skin cancer, is characterized by aberrant hyperactivation of the ERK mitogen-activated protein kinase signaling pathway. Genetic lesions in the core components of the RAS-RAF-MEK-ERK protein kinase cascade as well as its upstream regulators are key features of melanoma progression and drug resistance. MEK, the central kinase within the cascade, is constitutively activated by many upstream oncogenic events and is an important drug target. MEK inhibition in combination with BRAF inhibition is the standard of care for treating BRAFV600E melanoma. However, not all BRAFV600E melanomas respond to these inhibitors, and those that do respond eventually acquire resistance. To better understand mechanisms of MEK inhibitor susceptibility and MEK regulation in BRAFV600E melanoma, I performed a loss-of-function screen to identify kinases and phosphatases that modulate sensitivity to two clinical MEK1/2 inhibitors. In this screen, I identified PPP6C, the catalytic subunit of protein phosphatase 6 (PP6), as a factor promoting sensitivity to MEK inhibition. I established PPP6C as a major MEK phosphatase in cells exhibiting oncogenic ERK pathway activation. Recruitment of MEK to PPP6C occurs through an interaction with its associated regulatory subunits. Loss of PPP6C causes hyperphosphorylation of MEK at both activating and crosstalk phosphorylation sites, promoting signaling through the ERK pathway and decreasing sensitivity to the growth inhibitory effects of MEK inhibitors. Consistent with its role in regulating ERK signaling, PPP6C is frequently mutated in melanoma, as is MEK1. I found that recurrent melanoma-associated PPP6C mutations cause MEK hyperphosphorylation and ERK signaling hyperactivation when expressed in cells. Recurrent MEK1 mutations all promote MEK1 kinase activity but are activated by different mechanisms of action. The elevated MEK activity associated with PPP6C mutations or MEK1 mutations suggests that they promote disease by a common mechanism: activating the core oncogenic pathway driving melanoma. Collectively, our studies identify novel modulators of susceptibility to ERK pathway targeted cancer therapies, including PPP6C, a key negative regulator of ERK signaling, and cancer-associated mutations that influence ERK signaling activation

The effect of a couples intervention to increase breast cancer screening among korean americans.

Purpose/objectivesTo assess the efficacy of Korean Immigrants and Mammography-Culture-Specific Health Intervention (KIM-CHI), an educational program for Korean American (KA) couples designed to improve mammography uptake among KA women.DesignA two-group cluster randomized, longitudinal, controlled design.Setting50 KA religious organizations in the Chicago area.Sample428 married KA women 40 years of age or older who had not had a mammogram in the past year. The women and their husbands were recruited from 50 KA religious organizations.MethodsCouples were randomly assigned to intervention or attention control groups. Those in the KIM-CHI program (n = 211 couples) were compared to an attention control group (n = 217 couples) at baseline, as well as at 6 and 15 months postintervention on mammogram uptake.Main research variablesSociodemographic variables and mammography uptake were measured. Level of acculturation was measured using the Suinn-Lew Asian Self-Identity Acculturation Scale. Researchers asked questions about healthcare resources and use, health insurance status, usual source of care, physical examinations in the past two years, family history of breast cancer, and history of mammography.FindingsThe KIM-CHI group showed statistically significant increases in mammography uptake compared to the attention control group at 6 months and 15 months postintervention.ConclusionsThe culturally targeted KIM-CHI program was effective in increasing mammogram uptake among nonadherent KA women.Implications for nursingNurses and healthcare providers should consider specific health beliefs as well as inclusion of husbands or significant others. They also should target education to be culturally relevant for KA women to effectively improve frequency of breast cancer screening

Justice-Free Zones: U.S. Immigration Detention Under the Trump Administration

In the last three years, the Trump administration has grown the immigration detention system in the United States to an unprecedented size, at times holding more than 56,000 people per day. Since 2017, Immigration and Customs Enforcement (ICE) has anchored this growth in places where immigrants are most likely to be isolated from legal counsel, remain in detention without real opportunity for release, and are more likely to lose their cases. These new detention centers also exhibit patterns of mistreatment and abuse, including medical and mental health care neglect, that have been present since the inception of ICE’s detention system and grown worse as the system has expanded. When ICE was created in 2003, it inherited an immigration detention system that held about 20,000 people per day.1 The immigration detention system has since grown to a sprawling network of more than 200 detention centers nationwide. These facilities range in size and are largely operated by private prison corporations and, in some cases, by local jails. ICE uses these facilities to lock up people who arrive at the border or airports and request asylum, as well as long-time community members who are facing removal because of allegations of criminal conduct or simply because they are undocumented. This report provides a comprehensive examination of changes to the immigration detention system under the Trump administration, including an in-depth examination of the system’s expansion in the last three years and conditions of confinement in new detention facilities opened after January 2017. When this report went to print in April 2020, the COVID-19 coronavirus pandemic had taken hold in the United States. While our findings do not account for conditions in the detention system during the pandemic, they do document the state of a system that was never prepared to safely handle the crisis situation the world now faces. The following findings were particularly concerning in light of the COVID-19 outbreak: • We observed understaffing and cost-cutting measures in medical units which appeared dangerously unprepared for emergencies, posing danger to the health of people in detention even under ordinary circumstances; • We heard stories of immigrants’ lack of access to proper hygiene and witnessed unsanitary conditions in living units, many of which contained beds, dining, and restroom facilities for up to nearly 100 people all in one room. • Asylum seekers described virtually impossible odds for receiving release from detention on parole, an important legal mechanism ICE should be more eager to deploy to draw down its detention population in the face of a health crisis

Behind Closed Doors: Abuse and Retaliation Against Hunger Strikers in U.S. Immigration Detention

The decision to begin a hunger strike in immigration detention is not taken lightly. A detained person's refusal to eat may be the last option available to voice complaint, after all other methods of petition have failed. Detained and imprisoned people worldwide have engaged in hunger strikes to plead for humane conditions of confinement or release from captivity and to bring attention to broader calls for justice.Each day, the United States government unnecessarily locks up thousands of people in civil immigration detention, including children, in over two hundred immigration detention centers around the country.People may be locked up for many months — even years — as they await final adjudication of their cases or deportation. Trapped in a system marked by mistreatment and abuse, medical neglect, and the denial of due process, hundreds of people in immigration detention engage in hunger strikes as a means of protest each year. ICE's failure to provide safe and humane conditions in detention during the COVID-19 pandemic has only raised the stakes for detained people. Although some detained people, on occasion, are able to bring outside attention to their hunger strikes, very little is known of ICE's systemic response to hunger striking detainees.This report provides for the first time an in-depth, nationwide examination of what happens to people who engage in hunger strikes while detained by ICE

Dynamic Profiling of β-Coronavirus 3CL M^proProtease Ligand-Binding Sites

Data availability statement: The trajectories of Mpro simulations and models of the metastable states can be downloaded from 10.5281/zenodo.4782284.β-coronavirus (CoVs) alone has been responsible for three major global outbreaks in the 21st century. The current crisis has led to an urgent requirement to develop therapeutics. Even though a number of vaccines are available, alternative strategies targeting essential viral components are required as a backup against the emergence of lethal viral variants. One such target is the main protease (Mpro) that plays an indispensable role in viral replication. The availability of over 270 Mpro X-ray structures in complex with inhibitors provides unique insights into ligand–protein interactions. Herein, we provide a comprehensive comparison of all nonredundant ligand-binding sites available for SARS-CoV2, SARS-CoV, and MERS-CoV Mpro. Extensive adaptive sampling has been used to investigate structural conservation of ligand-binding sites using Markov state models (MSMs) and compare conformational dynamics employing convolutional variational auto-encoder-based deep learning. Our results indicate that not all ligand-binding sites are dynamically conserved despite high sequence and structural conservation across β-CoV homologs. This highlights the complexity in targeting all three Mpro enzymes with a single pan inhibitor.There was no funding for this wor

Genome-Wide Association Study of Susceptibility to Idiopathic Pulmonary Fibrosis

Rationale: Idiopathic pulmonary fibrosis (IPF) is a complex lung disease characterised by scarring of the lung that is believed to result from an atypical response to injury of the epithelium. Genome-wide association studies have reported signals of association implicating multiple pathways including host defence, telomere maintenance, signalling and cell-cell adhesion. Objectives: To improve our understanding of factors that increase IPF susceptibility by identifying previously unreported genetic associations. Methods and measurements: We conducted genome-wide analyses across three independent studies and meta-analysed these results to generate the largest genome-wide association study of IPF to date (2,668 IPF cases and 8,591 controls). We performed replication in two independent studies (1,456 IPF cases and 11,874 controls) and functional analyses (including statistical fine-mapping, investigations into gene expression and testing for enrichment of IPF susceptibility signals in regulatory regions) to determine putatively causal genes. Polygenic risk scores were used to assess the collective effect of variants not reported as associated with IPF. Main results: We identified and replicated three new genome-wide significant (P<5×10−8) signals of association with IPF susceptibility (associated with altered gene expression of KIF15, MAD1L1 and DEPTOR) and confirmed associations at 11 previously reported loci. Polygenic risk score analyses showed that the combined effect of many thousands of as-yet unreported IPF susceptibility variants contribute to IPF susceptibility. Conclusions: The observation that decreased DEPTOR expression associates with increased susceptibility to IPF, supports recent studies demonstrating the importance of mTOR signalling in lung fibrosis. New signals of association implicating KIF15 and MAD1L1 suggest a possible role of mitotic spindle-assembly genes in IPF susceptibility

The global, regional, and national burden of adult lip, oral, and pharyngeal cancer in 204 countries and territories:A systematic analysis for the Global Burden of Disease Study 2019

Importance Lip, oral, and pharyngeal cancers are important contributors to cancer burden worldwide, and a comprehensive evaluation of their burden globally, regionally, and nationally is crucial for effective policy planning.Objective To analyze the total and risk-attributable burden of lip and oral cavity cancer (LOC) and other pharyngeal cancer (OPC) for 204 countries and territories and by Socio-demographic Index (SDI) using 2019 Global Burden of Diseases, Injuries, and Risk Factors (GBD) Study estimates.Evidence Review The incidence, mortality, and disability-adjusted life years (DALYs) due to LOC and OPC from 1990 to 2019 were estimated using GBD 2019 methods. The GBD 2019 comparative risk assessment framework was used to estimate the proportion of deaths and DALYs for LOC and OPC attributable to smoking, tobacco, and alcohol consumption in 2019.Findings In 2019, 370 000 (95% uncertainty interval [UI], 338 000-401 000) cases and 199 000 (95% UI, 181 000-217 000) deaths for LOC and 167 000 (95% UI, 153 000-180 000) cases and 114 000 (95% UI, 103 000-126 000) deaths for OPC were estimated to occur globally, contributing 5.5 million (95% UI, 5.0-6.0 million) and 3.2 million (95% UI, 2.9-3.6 million) DALYs, respectively. From 1990 to 2019, low-middle and low SDI regions consistently showed the highest age-standardized mortality rates due to LOC and OPC, while the high SDI strata exhibited age-standardized incidence rates decreasing for LOC and increasing for OPC. Globally in 2019, smoking had the greatest contribution to risk-attributable OPC deaths for both sexes (55.8% [95% UI, 49.2%-62.0%] of all OPC deaths in male individuals and 17.4% [95% UI, 13.8%-21.2%] of all OPC deaths in female individuals). Smoking and alcohol both contributed to substantial LOC deaths globally among male individuals (42.3% [95% UI, 35.2%-48.6%] and 40.2% [95% UI, 33.3%-46.8%] of all risk-attributable cancer deaths, respectively), while chewing tobacco contributed to the greatest attributable LOC deaths among female individuals (27.6% [95% UI, 21.5%-33.8%]), driven by high risk-attributable burden in South and Southeast Asia.Conclusions and Relevance In this systematic analysis, disparities in LOC and OPC burden existed across the SDI spectrum, and a considerable percentage of burden was attributable to tobacco and alcohol use. These estimates can contribute to an understanding of the distribution and disparities in LOC and OPC burden globally and support cancer control planning efforts

Contributions of mean and shape of blood pressure distribution to worldwide trends and variations in raised blood pressure: A pooled analysis of 1018 population-based measurement studies with 88.6 million participants

© The Author(s) 2018. Background: Change in the prevalence of raised blood pressure could be due to both shifts in the entire distribution of blood pressure (representing the combined effects of public health interventions and secular trends) and changes in its high-blood-pressure tail (representing successful clinical interventions to control blood pressure in the hypertensive population). Our aim was to quantify the contributions of these two phenomena to the worldwide trends in the prevalence of raised blood pressure. Methods: We pooled 1018 population-based studies with blood pressure measurements on 88.6 million participants from 1985 to 2016. We first calculated mean systolic blood pressure (SBP), mean diastolic blood pressure (DBP) and prevalence of raised blood pressure by sex and 10-year age group from 20-29 years to 70-79 years in each study, taking into account complex survey design and survey sample weights, where relevant. We used a linear mixed effect model to quantify the association between (probittransformed) prevalence of raised blood pressure and age-group- and sex-specific mean blood pressure. We calculated the contributions of change in mean SBP and DBP, and of change in the prevalence-mean association, to the change in prevalence of raised blood pressure. Results: In 2005-16, at the same level of population mean SBP and DBP, men and women in South Asia and in Central Asia, the Middle East and North Africa would have the highest prevalence of raised blood pressure, and men and women in the highincome Asia Pacific and high-income Western regions would have the lowest. In most region-sex-age groups where the prevalence of raised blood pressure declined, one half or more of the decline was due to the decline in mean blood pressure. Where prevalence of raised blood pressure has increased, the change was entirely driven by increasing mean blood pressure, offset partly by the change in the prevalence-mean association. Conclusions: Change in mean blood pressure is the main driver of the worldwide change in the prevalence of raised blood pressure, but change in the high-blood-pressure tail of the distribution has also contributed to the change in prevalence, especially in older age groups

Repositioning of the global epicentre of non-optimal cholesterol

High blood cholesterol is typically considered a feature of wealthy western countries(1,2). However, dietary and behavioural determinants of blood cholesterol are changing rapidly throughout the world(3) and countries are using lipid-lowering medications at varying rates. These changes can have distinct effects on the levels of high-density lipoprotein (HDL) cholesterol and non-HDL cholesterol, which have different effects on human health(4,5). However, the trends of HDL and non-HDL cholesterol levels over time have not been previously reported in a global analysis. Here we pooled 1,127 population-based studies that measured blood lipids in 102.6 million individuals aged 18 years and older to estimate trends from 1980 to 2018 in mean total, non-HDL and HDL cholesterol levels for 200 countries. Globally, there was little change in total or non-HDL cholesterol from 1980 to 2018. This was a net effect of increases in low- and middle-income countries, especially in east and southeast Asia, and decreases in high-income western countries, especially those in northwestern Europe, and in central and eastern Europe. As a result, countries with the highest level of non-HDL cholesterol-which is a marker of cardiovascular riskchanged from those in western Europe such as Belgium, Finland, Greenland, Iceland, Norway, Sweden, Switzerland and Malta in 1980 to those in Asia and the Pacific, such as Tokelau, Malaysia, The Philippines and Thailand. In 2017, high non-HDL cholesterol was responsible for an estimated 3.9 million (95% credible interval 3.7 million-4.2 million) worldwide deaths, half of which occurred in east, southeast and south Asia. The global repositioning of lipid-related risk, with non-optimal cholesterol shifting from a distinct feature of high-income countries in northwestern Europe, north America and Australasia to one that affects countries in east and southeast Asia and Oceania should motivate the use of population-based policies and personal interventions to improve nutrition and enhance access to treatment throughout the world.Peer reviewe