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DATA-DRIVEN IDENTIFICATION OF PHYSIOLOGICAL STRESS RESPONSE PHENOTYPES IN HEALTHY POPULATION
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Characterizing and Modeling Smoking Behavior Using Automatic Smoking Event Detection and Mobile Surveys in Naturalistic Environments: Observational Study
Get PDFBACKGROUND: There are 1.1 billion smokers worldwide, and each year, more than 8 million die prematurely because of cigarette smoking. More than half of current smokers make a serious quit every year. Nonetheless, 90% of unaided quitters relapse within the first 4 weeks of quitting due to the lack of limited access to cost-effective and efficient smoking cessation tools in their daily lives. OBJECTIVE: This study aims to enable quantified monitoring of ambulatory smoking behavior 24/7 in real life by using continuous and automatic measurement techniques and identifying and characterizing smoking patterns using longitudinal contextual signals. This work also intends to provide guidance and insights into the design and deployment of technology-enabled smoking cessation applications in naturalistic environments. METHODS: A 4-week observational study consisting of 46 smokers was conducted in both working and personal life environments. An electric lighter and a smartphone with an experimental app were used to track smoking events and acquire concurrent contextual signals. In addition, the app was used to prompt smoking-contingent ecological momentary assessment (EMA) surveys. The smoking rate was assessed based on the timestamps of smoking and linked statistically to demographics, time, and EMA surveys. A Poisson mixed-effects model to predict smoking rate in 1-hour windows was developed to assess the contribution of each predictor. RESULTS: In total, 8639 cigarettes and 1839 EMA surveys were tracked over 902 participant days. Most smokers were found to have an inaccurate and often biased estimate of their daily smoking rate compared with the measured smoking rate. Specifically, 74% (34/46) of the smokers made more than one (mean 4.7, SD 4.2 cigarettes per day) wrong estimate, and 70% (32/46) of the smokers overestimated it. On the basis of the timestamp of the tracked smoking events, smoking rates were visualized at different hours and were found to gradually increase and peak at 6 PM in the day. In addition, a 1- to 2-hour shift in smoking patterns was observed between weekdays and weekends. When moderate and heavy smokers were compared with light smokers, their ages (P<.05), Fagerström Test of Nicotine Dependence (P=.01), craving level (P<.001), enjoyment of cigarettes (P<.001), difficulty resisting smoking (P<.001), emotional valence (P<.001), and arousal (P<.001) were all found to be significantly different. In the Poisson mixed-effects model, the number of cigarettes smoked in a 1-hour time window was highly dependent on the smoking status of an individual (P<.001) and was explained by hour (P=.02) and age (P=.005). CONCLUSIONS: This study reported the high potential and challenges of using an electronic lighter for smoking annotation and smoking-triggered EMAs in an ambulant environment. These results also validate the techniques for smoking behavior monitoring and pave the way for the design and deployment of technology-enabled smoking cessation applications. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1136/bmjopen-2018-028284.status: Publishe
Prospective validation of pathologic complete response models in rectal cancer: Transferability and reproducibility
Get PDFPurpose: Multiple models have been developed to predict pathologic complete response (pCR) in locally advanced rectal cancer patients. Unfortunately, validation of these models normally omit the implications of cohort differences on prediction model performance. In this work, we will perform a prospective validation of three pCR models, including information whether this validation will target transferability or reproducibility (cohort differences) of the given models. Methods: We applied a novel methodology, the cohort differences model, to predict whether a patient belongs to the training or to the validation cohort. If the cohort differences model performs well, it would suggest a large difference in cohort characteristics meaning we would validate the transferability of the model rather than reproducibility. We tested our method in a prospective validation of three existing models for pCR prediction in 154 patients. Results: Our results showed a large difference between training and validation cohort for one of the three tested models [Area under the Receiver Operating Curve (AUC) cohort differences model: 0.85], signaling the validation leans towards transferability. Two out of three models had a lower AUC for validation (0.66 and 0.58), one model showed a higher AUC in the validation cohort (0.70). Discussion: We have successfully applied a new methodology in the validation of three prediction models, which allows us to indicate if a validation targeted transferability (large differences between training/validation cohort) or reproducibility (small cohort differences)
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Get PDF“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Get PDFWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
WNT5A-ROR2 axis mediates VEGF dependence of BRAF mutant melanoma
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Despite recent advances, approximately 50% of patient with metastatic melanoma eventually succumb to the disease. Patients with melanomas harboring a BRAF mutation (BRAFMut) have a worse prognosis than those with wildtype (BRAFWT) tumors. Unexpectedly, interim AVAST-M Phase III trial data reported benefit from adjuvant anti-VEGF bevacizumab only in the BRAFMut group. We sought to find mechanisms underpinning this sensitivity.
Methods
We investigated this finding in vitro and in vivo using melanoma cell lines and clones generated by BRAFV600E knock-in on a BRAFWT background.
Results
Compared with BRAFWT cells, isogenic BRAFV600E clones secreted more VEGF and exhibited accelerated growth rates as spheroids and xenografts, which were more vascular and proliferative. Recapitulating AVAST-M findings, bevacizumab affected only BRAFV600E xenografts, inducing significant tumor growth delay, reduced vascularity and increased necrosis. We identified 814 differentially expressed genes in isogenic BRAFV600E/BRAFWT clones. Of 61 genes concordantly deregulated in clinical melanomas ROR2 was one of the most upregulated by BRAFV600E. ROR2 was shown to be RAF-MEK regulated in BRAFV600E cells and its depletion suppressed VEGF secretion down to BRAFWT levels. The ROR2 ligand WNT5A was also overexpressed in BRAFMut melanomas, and in ROR2-overexpressing BRAFV600E cells MEK inhibition downregulated WNT5A and VEGF secretion.
Conclusions
These data implicate WNT5A-ROR2 in VEGF secretion, vascularity, adverse outcomes and bevacizumab sensitivity of BRAFMut melanomas, suggesting that this axis has potential therapeutic relevance
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