Patient-Provider Discussions about Lung Cancer Screening Pre- and Post-Guidelines: Health Information National Trends Survey (HINTS)

Objective In 2013, the USPSTF issued a Grade B recommendation that long-term current and former smokers receive lung cancer screening. Shared decision-making is important for individuals considering screening, and patient-provider discussions an essential component of the process. We examined prevalence and predictors of lung cancer screening discussions pre- and post-USPSTF guidelines. Methods Data were obtained from two cycles of the Health Information National Trends Survey (2012; 2014). The analyzed sample comprised screening-eligible current and former smokers with no personal history of lung cancer (n = 746 in 2012; n = 795 in 2014). Descriptive and multiple logistic regression analyses were conducted; patient-reported discussion about lung cancer screening with provider was the outcome of interest. Results Contrary to expectations, patient-provider discussions about lung cancer screening were more prevalent pre-guideline, but overall patient-provider discussions were low in both years (17% in 2012; 10% in 2014). Current smokers were more likely to have had a discussion than former smokers. Significant predictors of patient-provider discussions included family history of cancer and having healthcare coverage. Conclusions The prevalence of patient-provider discussions about lung cancer screening is suboptimal. Practice implications There is a critical need for patient and provider education about shared decision-making and its importance in cancer screening decisions

Smokers' Likelihood to Engage With Information and Misinformation on Twitter About the Relative Harms of e-Cigarette Use:Results From a Randomized Controlled Trial

BACKGROUND: Information and misinformation on the internet about e-cigarette harms may increase smokers’ misperceptions of e-cigarettes. There is limited research on smokers’ engagement with information and misinformation about e-cigarettes on social media. OBJECTIVE: This study assessed smokers’ likelihood to engage with—defined as replying, retweeting, liking, and sharing—tweets that contain information and misinformation and uncertainty about the harms of e-cigarettes. METHODS: We conducted a web-based randomized controlled trial among 2400 UK and US adult smokers who did not vape in the past 30 days. Participants were randomly assigned to view four tweets in one of four conditions: (1) e-cigarettes are as harmful or more harmful than smoking, (2) e-cigarettes are completely harmless, (3) uncertainty about e-cigarette harms, or (4) control (physical activity). The outcome measure was participants’ likelihood of engaging with tweets, which comprised the sum of whether they would reply, retweet, like, and share each tweet. We fitted Poisson regression models to predict the likelihood of engagement with tweets among 974 Twitter users and 1287 non-Twitter social media users, adjusting for covariates and stratified by UK and US participants. RESULTS: Among Twitter users, participants were more likely to engage with tweets in condition 1 (e-cigarettes are as harmful or more harmful than smoking) than in condition 2 (e-cigarettes are completely harmless). Among other social media users, participants were more likely to likely to engage with tweets in condition 1 than in conditions 2 and 3 (e-cigarettes are completely harmless and uncertainty about e-cigarette harms). CONCLUSIONS: Tweets stating information and misinformation that e-cigarettes were as harmful or more harmful than smoking regular cigarettes may receive higher engagement than tweets indicating e-cigarettes were completely harmless. TRIAL REGISTRATION: International Standard Randomized Controlled Trial Number (ISRCTN) 16082420; https://doi.org/10.1186/ISRCTN1608242

Is exposure to e-cigarette communication associated with perceived harms of e-cigarette secondhand vapour? Results from a national survey of US adults

Objectives: E-cigarettes are frequently advertised and portrayed in the media as less harmful compared with regular cigarettes. Earlier surveys reported public perceptions of harms to people using e-cigarettes; however, public perceptions of harms from exposure to secondhand vapour (SHV) have not been studied. We examined associations between self-reported exposure to e-cigarette advertising, media coverage, and interpersonal discussion and perceived harms of SHV. Design: Observational study. Setting: National online sample of US adults aged ≥18 years. Participants: 1449 US adults (mean age 49.5 years), 51.3% female, 76.6% non-Hispanic Caucasian, 7.5% African-American, 10.0% Hispanic and 5.9% other races. Outcomes Perceived harm measures included (1) harmfulness of SHV to one's health, (2) concern about health impact of breathing SHV and (3) comparative harm of SHV versus secondhand smoke (SHS). Predictors were (1) self-reported frequency of exposure to e-cigarette advertising, media coverage and interpersonal discussion (close friends or family) and (2) perceived valence of exposure from each source. Covariates were demographic characteristics, cigarette smoking status and e-cigarette use, and were weighted to the general US adult population. Results: More frequent interpersonal discussion was associated with lower perceived harmfulness of SHV to one's health and lower perceived comparative harm of SHV versus SHS. Frequency of e-cigarette ad and other media exposure were not significant predictors. Perceived negative valence of ad exposure and interpersonal discussion (vs no exposure) was associated with higher perceived harm across all three outcomes, while negative valence of media coverage was associated with higher concern about health impact of breathing SHV. Perceived positive valence (vs no exposure) of interpersonal discussion was associated with lower perceived harm across all three outcomes about health impact of breathing SHV. Conclusions: Exposure to information about e-cigarettes through advertising, media coverage and interpersonal discussion could play a role in shaping public perceptions of the harmfulness of SHV

Designing Shared Decision-Making Interventions for Dissemination and Sustainment: Can Implementation Science Help Translate Shared Decision Making Into Routine Practice

Shared decision making (SDM) is not widely practiced in routine care due to a variety of organizational, provider, patient, and contextual factors. This article explores how implementation science-which encourages attention to the multilevel contextual factors that influence the adoption, implementation, and sustainment of health care practices-can provide useful insights for increasing SDM use in routine practice. We engaged with stakeholders representing different organizations and geographic locations over three phases: 1) multidisciplinary workgroup meeting comprising researchers and clinicians (n = 11); 2) survey among a purposive sample of 47 patient advocates, clinicians, health care system leaders, funders, policymakers, and researchers; and 3) working session among diverse stakeholders (n = 30). The workgroup meeting identified priorities for action and research, which included targeting multiple audiences and levels, shifting culture toward valuing and supporting SDM, and considering contextual factors influencing SDM implementation. Survey respondents provided recommendations for increasing adoption, implementation, and maintenance of SDM in practice including providing tools to support SDM, obtaining stakeholders\u27 involvement, and raising awareness of the importance of SDM. Stakeholders in the working session provided recommendations on the design of a guide for implementation of SDM in clinical settings, strategies to disseminate educational curricula on SDM, and strategies to influence policies to increase SDM use. These specific recommendations serve as a call to action to pursuing specific promising strategies aimed at increasing SDM use in practice and enhance understanding of the perspectives of diverse stakeholders at multiple levels from an implementation science perspective that appear fruitful for further study and application

SIP-based proactive and adaptive mobility management framework for heterogeneous networks

Abstract In this paper, we present and evaluate the performance of a mobility management system called the Proactive and Adaptive Handover (PAHO) system. PAHO is an application-level approach that uses SIP to manage client-initiated connection handoff across heterogeneous networks based on the IEEE 802.21 framework with designated user/configuration policy. Unlike conventional systems which make sub-optimal decision when managing connection handoff due to limited awareness of the relevant context for the application/service being delivered, PAHO defines proper interface to interact with the application as to determine when and to where the handoff and/or codec switching should take place in the event of network performance degradation. The results showed that using the PAHO approach on an audio/video conferencing session helps reducing the overall handover delay from 10.766 s (on non-PAHO system) down to at least 288 ms, and slowing down the degradation of MOS value throughout the entire experiment in the event of signal degradation as well as network congestion. It is also shown that load balancing among the access points (AP) could be achieved with an improved Information Server (IS). r 2007 Elsevier Ltd. All rights reserved

Glutamate Induces Mitochondrial Dynamic Imbalance and Autophagy Activation: Preventive Effects of Selenium

Glutamate-induced cytotoxicity is partially mediated by enhanced oxidative stress. The objectives of the present study are to determine the effects of glutamate on mitochondrial membrane potential, oxygen consumption, mitochondrial dynamics and autophagy regulating factors and to explore the protective effects of selenium against glutamate cytotoxicity in murine neuronal HT22 cells. Our results demonstrated that glutamate resulted in cell death in a dose-dependent manner and supplementation of 100 nM sodium selenite prevented the detrimental effects of glutamate on cell survival. The glutamate induced cytotoxicity was associated with mitochondrial hyperpolarization, increased ROS production and enhanced oxygen consumption. Selenium reversed these alterations. Furthermore, glutamate increased the levels of mitochondrial fission protein markers pDrp1 and Fis1 and caused increase in mitochondrial fragmentation. Selenium corrected the glutamate-caused mitochondrial dynamic imbalance and reduced the number of cells with fragmented mitochondria. Finally, glutamate activated autophagy markers Beclin 1 and LC3-II, while selenium prevented the activation. These results suggest that glutamate targets the mitochondria and selenium supplementation within physiological concentration is capable of preventing the detrimental effects of glutamate on the mitochondria. Therefore, adequate selenium supplementation may be an efficient strategy to prevent the detrimental glutamate toxicity and further studies are warranted to define the therapeutic potentials of selenium in animal disease models and in human

Structural and Functional Profiling of the Human Histone Methyltransferase SMYD3

The SET and MYND Domain (SMYD) proteins comprise a unique family of multi-domain SET histone methyltransferases that are implicated in human cancer progression. Here we report an analysis of the crystal structure of the full length human SMYD3 in a complex with an analog of the S-adenosyl methionine (SAM) methyl donor cofactor. The structure revealed an overall compact architecture in which the “split-SET” domain adopts a canonical SET domain fold and closely assembles with a Zn-binding MYND domain and a C-terminal superhelical 9 α-helical bundle similar to that observed for the mouse SMYD1 structure. Together, these structurally interlocked domains impose a highly confined binding pocket for histone substrates, suggesting a regulated mechanism for its enzymatic activity. Our mutational and biochemical analyses confirm regulatory roles of the unique structural elements both inside and outside the core SET domain and establish a previously undetected preference for trimethylation of H4K20

Genomic Diversity and Introgression in O. sativa Reveal the Impact of Domestication and Breeding on the Rice Genome

The domestication of Asian rice (Oryza sativa) was a complex process punctuated by episodes of introgressive hybridization among and between subpopulations. Deep genetic divergence between the two main varietal groups (Indica and Japonica) suggests domestication from at least two distinct wild populations. However, genetic uniformity surrounding key domestication genes across divergent subpopulations suggests cultural exchange of genetic material among ancient farmers.In this study, we utilize a novel 1,536 SNP panel genotyped across 395 diverse accessions of O. sativa to study genome-wide patterns of polymorphism, to characterize population structure, and to infer the introgression history of domesticated Asian rice. Our population structure analyses support the existence of five major subpopulations (indica, aus, tropical japonica, temperate japonica and GroupV) consistent with previous analyses. Our introgression analysis shows that most accessions exhibit some degree of admixture, with many individuals within a population sharing the same introgressed segment due to artificial selection. Admixture mapping and association analysis of amylose content and grain length illustrate the potential for dissecting the genetic basis of complex traits in domesticated plant populations.Genes in these regions control a myriad of traits including plant stature, blast resistance, and amylose content. These analyses highlight the power of population genomics in agricultural systems to identify functionally important regions of the genome and to decipher the role of human-directed breeding in refashioning the genomes of a domesticated species

DOCK8 deficiency impairs CD8 T cell survival and function in humans and mice

As shown by analysis of mice and humans bearing DOCK8-inactivating mutations, DOCK8 plays a cell-autonomous role in survival of naive CD8 T cells, LFA-1 polarization toward the immune synapse, and CD8 T cell memory and recall responses following viral infection

The genomic and transcriptomic architecture of 2,000 breast tumours reveals novel subgroups.

The elucidation of breast cancer subgroups and their molecular drivers requires integrated views of the genome and transcriptome from representative numbers of patients. We present an integrated analysis of copy number and gene expression in a discovery and validation set of 997 and 995 primary breast tumours, respectively, with long-term clinical follow-up. Inherited variants (copy number variants and single nucleotide polymorphisms) and acquired somatic copy number aberrations (CNAs) were associated with expression in ~40% of genes, with the landscape dominated by cis- and trans-acting CNAs. By delineating expression outlier genes driven in cis by CNAs, we identified putative cancer genes, including deletions in PPP2R2A, MTAP and MAP2K4. Unsupervised analysis of paired DNA–RNA profiles revealed novel subgroups with distinct clinical outcomes, which reproduced in the validation cohort. These include a high-risk, oestrogen-receptor-positive 11q13/14 cis-acting subgroup and a favourable prognosis subgroup devoid of CNAs. Trans-acting aberration hotspots were found to modulate subgroup-specific gene networks, including a TCR deletion-mediated adaptive immune response in the ‘CNA-devoid’ subgroup and a basal-specific chromosome 5 deletion-associated mitotic network. Our results provide a novel molecular stratification of the breast cancer population, derived from the impact of somatic CNAs on the transcriptome