Modeling the risk of esophageal squamous cell carcinoma and squamous dysplasia in a high risk area in Iran

Background: Identifying people at higher risk of having squamous dysplasia, the precursor lesion for esophageal squamous cell carcinoma (ESCC), would allow targeted endoscopic screening. Methods: We used multivariate logistic regression models to predict ESCC and dysplasia as outcomes. The ESCC model was based on data from the Golestan Case-Control Study (total n = 871; cases = 300), and the dysplasia model was based on data from a cohort of subjects from a gastroenterology clinic in Northeast Iran (total n = 724; cases = 26). In each of these analyses, we fit a model including all risk factors known in this region to be associated with ESCC. Individual risks were calculated using the linear combination of estimated regression coefficients and individual-specific values for covariates. We used cross-validation to determine the area under the curve (AUC) and to find the optimal cut points for each of the models. Results: The model had an area under the curve of 0.77 (95 CI: 0.74-0.80) to predict ESCC with 74 sensitivity and 70.4 specificity for the optimum cut point. The area under the curve was 0.71 (95 CI: 0.64-0.79) for dysplasia diagnosis, and the classification table optimized at 61.5 sensitivity and 69.5 specificity. In this population, the positive and negative predictive values for diagnosis of dysplasia were 6.8 and 97.8, respectively. Conclusion: Our models were able to discriminate between ESCC cases and controls in about 77, and between individuals with and without squamous dysplasia in about 70 of the cases. Using risk factors to predict individual risk of ESCC or squamous dysplasia still has limited application in clinical practice, but such models may be suitable for selecting high risk individuals in research studies, or increasing the pretest probability for other screening strategies

Direct observation of lithium metal dendrites with ceramic solid electrolyte

Dendrite formation, which could cause a battery short circuit, occurs in batteries that contain lithium metal anodes. In order to suppress dendrite growth, the use of electrolytes with a high shear modulus is suggested as an ionic conductive separator in batteries. One promising candidate for this application is Li7La3Zr2O12 (LLZO) because it has excellent mechanical properties and chemical stability. In this work, in situ scanning electron microscopy (SEM) technique was employed to monitor the interface behavior between lithium metal and LLZO electrolyte during cycling with pressure. Using the obtained SEM images, videos were created that show the inhomogeneous dissolution and deposition of lithium, which induce dendrite growth. The energy dispersive spectroscopy analyses of dendrites indicate the presence of Li, C, and O elements. Moreover, the cross-section mapping comparison of the LLZO shows the inhomogeneous distribution of La, Zr, and C after cycling that was caused by lithium loss near the Li electrode and possible side reactions. This work demonstrates the morphological and chemical evolution that occurs during cycling in a symmetrical Li–Li cell that contains LLZO. Although the superior mechanical properties of LLZO make it an excellent electrolyte candidate for batteries, the further improvement of the electrochemical stabilization of the garnet–lithium metal interface is suggested

Characterizing organic particle impacts on inert metal surfaces: Foundations for capturing organic molecules during hypervelocity transits of Enceladus plumes

The presence and accessibility of a sub‐ice‐surface saline ocean at Enceladus, together with geothermal activity and a rocky core, make it a compelling location to conduct further, in‐depth, astrobiological investigations to probe for organic molecules indicative of extraterrestrial life. Cryovolcanic plumes in the south polar region of Enceladus enable the use of remote in situ sampling and analysis techniques. However, efficient plume sampling and the transportation of captured organic materials to an organic analyzer present unique challenges for an Enceladus mission. A systematic study, accelerating organic ice‐particle simulants into soft inert metal targets at velocities ranging 0.5–3.0 km s−1, was carried out using a light gas gun to explore the efficacy of a plume capture instrument. Capture efficiency varied for different metal targets as a function of impact velocity and particle size. Importantly, organic chemical compounds remained chemically intact in particles captured at speeds up to ~2 km s−1. Calibration plots relating the velocity, crater, and particle diameter were established to facilitate future ice‐particle impact experiments where the size of individual ice particles is unknown

Large body size and sedentary lifestyle during childhood and early adulthood and esophageal squamous cell carcinoma in a high-risk population

Background: Little is known about the association of obesity and physical activity at young ages with subsequent risk of esophageal squamous cell carcinoma (ESCC). Patients and methods: Between 2003 and 2007, we conducted a case-control study in a high-risk population in northeastern Iran. Three hundred ESCC cases and 571 matched controls were recruited. Each individual was shown a standard pictogram, to report body size at ages 15 and 30. Demographic and health-related information, including physical activity at these ages was also collected. Results: In the fully adjusted models, very obese body size (last two pictograms) at age 15 odds ratio (OR) 3.2, 95% confidence interval (CI) 1.3-7.7 and age 30 (OR 3.1; 95% CI 1.1-8.5) were associated with ESCC in women, but not in men. Sedentary work at age 15 (OR 3.3, 95% CI 1.3-8.3) and 30 (OR 18.2, 95% CI 3.9-86.2) were also associated with ESCC risk in women only. The increased risk in women at age 15 remained high after later reduction in body size, while women who became very obese only at age 30 did not show a significantly increased risk. Conclusion: These results highlight the importance of early lifestyle modifications in the context of cancer prevention, particularly in women. © Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved

Prevalence, awareness and risk factors of hypertension in a large cohort of Iranian adult population

Background: There is considerable variation in hypertension prevalence and awareness, and their correlates, across different geographic locations and ethnic groups. We performed this cross-sectional analysis on data from the Golestan Cohort Study (GCS). Methods: Enrollment in this study occurred in 2004-2008, and included 50 045 healthy individuals from Golestan Province in northeastern Iran. Hypertension was defined as a SBP at least 140 mmHg, a DBP at least 90 mmHg, a prior diagnosis of hypertension, or the use of antihypertensive drugs. Potential correlates of hypertension and its awareness were analyzed by logistic regression adjusted for sex, age, BMI, place of residence, literacy, ethnicity, physical activity, smoking, black and green tea consumption and wealth score. Results: Of the total cohort participants, 21 350 (42.7) were hypertensive. Age-standardized prevalence of hypertension, using the 2001 WHO standard world population, was 41.8 (95 confidence interval: 38.3-45.2). Hypertension was directly associated with female sex, increased BMI, Turkmen ethnicity, and lack of physical activity, and inversely associated with drinking black tea and wealth score. Among hypertensive patients, 46.2 were aware of their disease, 17.6 were receiving antihypertensive medication, and 32.1 of the treated patients had controlled hypertension. Hypertension awareness was greater among women, the elderly, overweight and obese patients, and those with a higher wealth score. Conclusion: Hypertension is highly prevalent in rural Iran, many of the affected individuals are unaware of their disease, and the rate of control by antihypertensive medications is low. Increasing hypertension awareness and access to health services, especially among less privileged residents are recommended. © Lippincott Williams and Wilkins

Smoking water-pipe, chewing nass and prevalence of heart disease: A cross-sectional analysis of baseline data from the Golestan Cohort Study, Iran

Objective Water-pipe and smokeless tobacco use have been associated with several adverse health outcomes. However, little information is available on the association between water-pipe use and heart disease (HD). Therefore, we investigated the association of smoking water-pipe and chewing nass (a mixture of tobacco, lime and ash) with prevalent HD. Design Cross-sectional study. Setting Baseline data (collected in 2004-2008) from a prospective population-based study in Golestan Province, Iran. Participants 50 045 residents of Golestan (40-75 years old; 42.4 men). Main outcome measures ORs and 95 CIs from multivariate logistic regression models for the association of water-pipe and nass use with HD prevalence. Results A total of 3051 (6.1) participants reported a history of HD, and 525 (1.1) and 3726 (7.5) reported ever water-pipe or nass use, respectively. Heavy water-pipe smoking was significantly associated with HD prevalence (highest level of cumulative use vs never use, OR=3.75; 95 CI 1.52 to 9.22; p for trend=0.04). This association persisted when using different cut-off points, when restricting HD to those taking nitrate compound medications, and among never cigarette smokers. There was no significant association between nass use and HD prevalence (highest category of use vs never use, OR=0.91; 95 CI 0.69 to 1.20). Conclusions Our study suggests a significant association between HD and heavy water-pipe smoking. Although the existing evidence suggesting similar biological consequences of water-pipe and cigarette smoking make this association plausible, results of our study were based on a modest number of water-pipe users and need to be replicated in further studies

Identification of functional genetic variation in exome sequence analysis

Recent technological advances have allowed us to study individual genomes at a base-pair resolution and have demonstrated that the average exome harbors more than 15,000 genetic variants. However, our ability to understand the biological significance of the identified variants and to connect these observed variants with phenotypes is limited. The first step in this process is to identify genetic variation that is likely to result in changes to protein structure and function, because detailed studies, either population based or functional, for each of the identified variants are not practicable. Therefore algorithms that yield valid predictions of a variant’s functional significance are needed. Over the past decade, several programs have been developed to predict the probability that an observed sequence variant will have a deleterious effect on protein function. These algorithms range from empirical programs that classify using known biochemical properties to statistical algorithms trained using a variety of data sources, including sequence conservation data, biochemical properties, and functional data. Using data from the pilot3 study of the 1000 Genomes Project available through Genetic Analysis Workshop 17, we compared the results of four programs (SIFT, PolyPhen, MAPP, and VarioWatch) used to predict the functional relevance of variants in 101 genes. Analysis was conducted without knowledge of the simulation model. Agreement between programs was modest ranging from 59.4% to 71.4% and only 3.5% of variants were classified as deleterious and 10.9% as tolerated across all four programs