Optical Spectral Variability of the Very-High-Energy Gamma-Ray Blazar 1ES 1011+496

We present results of five years of optical (UBVRI) observations of the very-high-energy gamma-ray blazar 1ES 1011+496 at the MDM Observatory. We calibrated UBVRI magnitudes of five comparison stars in the field of the object. Most of our observations were done during moderately faint states of 1ES 1011+496 with R > 15.0. The light curves exhibit moderate, closely correlated variability in all optical wavebands on time scales of a few days. A cross-correlation analysis between optical bands does not show significant evidence for time lags. We find a positive correlation (Pearson's r = 0.57; probability of non-correlation P(>r) ~ 4e-8) between the R-band magnitude and the B - R color index, indicating a bluer-when-brighter trend. Snap-shot optical spectral energy distributions (SEDs) exhibit a peak within the optical regime, typically between the V and B bands. We find a strong (r = 0.78; probability of non-correlation P (>r) ~ 1e-15) positive correlation between the peak flux and the peak frequency, best fit by a relation $\nu F_{\nu}^{\rm pk} \propto \nu_{\rm pk}^k$ with k = 2.05 +/- 0.17. Such a correlation is consistent with the optical (synchrotron) variability of 1ES 1011+496 being primarily driven by changes in the magnetic field.Comment: Accepted for publication in ApJ. 16 pages, including 7 figure

Longer sleep is associated with lower BMI and favorable metabolic profiles in UK adults: Findings from the National Diet and Nutrition Survey

Ever more evidence associates short sleep with increased risk of metabolic diseases such as obesity, which may be related to a predisposition to non-homeostatic eating. Few studies have concurrently determined associations between sleep duration and objective measures of metabolic health as well as sleep duration and diet, however. We therefore analyzed associations between sleep duration, diet and metabolic health markers in UK adults, assessing associations between sleep duration and 1) adiposity, 2) selected metabolic health markers and 3) diet, using National Diet and Nutrition Survey data. Adults (n = 1,615, age 19–65 years, 57.1% female) completed questions about sleep duration and 3 to 4 days of food diaries. Blood pressure and waist circumference were recorded. Fasting blood lipids, glucose, glycated haemoglobin (HbA1c), thyroid hormones, and high-sensitivity C-reactive protein (CRP) were measured in a subset of participants. We used regression analyses to explore associations between sleep duration and outcomes. After adjustment for age, ethnicity, sex, smoking, and socioeconomic status, sleep duration was negatively associated with body mass index (-0.46 kg/m2 per hour, 95% CI -0.69 to -0.24 kg/m2, p < 0.001) and waist circumference (-0.9 cm per hour, 95% CI -1.5 to -0.3cm, p = 0.004), and positively associated with high-density lipoprotein cholesterol (0.03 mmol/L per hour, 95% CI 0.00 to 0.05, p = 0.03). Sleep duration tended to be positively associated with free thyroxine levels and negatively associated with HbA1c and CRP (p = 0.09 to 0.10). Contrary to our hypothesis, sleep duration was not associated with any dietary measures (p ≥ 0.14). Together, our findings show that short-sleeping UK adults are more likely to have obesity, a disease with many comorbidities

Models, measurement and inference in epithelial tissue dynamics

The majority of solid tumours arise in epithelia and therefore much research effort has gone into investigating the growth, renewal and regulation of these tissues. Here we review different mathematical and computational approaches that have been used to model epithelia. We compare different models and describe future challenges that need to be overcome in order to fully exploit new data which present, for the first time, the real possibility for detailed model validation and comparison

Investigating the Bidirectional Associations of Adiposity with Sleep Duration in Older Adults: The English Longitudinal Study of Ageing (ELSA)

Cross-sectional analyses of adiposity and sleep duration in younger adults suggest that increased adiposity is associated with shorter sleep. Prospective studies have yielded mixed findings, and the direction of this association in older adults is unclear. We examined the cross-sectional and potential bi-directional, prospective associations between adiposity and sleep duration (covariates included demographics, health behaviours, and health problems) in 5,015 respondents from the English Longitudinal Study of Ageing (ELSA), at baseline and follow-up. Following adjustment for covariates, we observed no significant cross-sectional relationship between body mass index (BMI) and sleep duration [(unstandardized) B?=??0.28?minutes, (95% Confidence Intervals (CI)?=??0.012; 0.002), p?=?0.190], or waist circumference (WC) and sleep duration [(unstandardized) B?=??0.10?minutes, (95% CI?=??0.004; 0.001), p?=?0.270]. Prospectively, both baseline BMI [B?=??0.42?minutes, (95% CI?=??0.013; ?0.002), p?=?0.013] and WC [B?=??0.18?minutes, (95% CI?=??0.005; ?0.000), p?=?0.016] were associated with decreased sleep duration at follow-up, independently of covariates. There was, however, no association between baseline sleep duration and change in BMI or WC (p?>?0.05). In older adults, our findings suggested that greater adiposity is associated with decreases in sleep duration over time; however the effect was very small

Development of abnormalities at the neuromuscular junction in the SOD1-G93A mouse model of ALS: dysfunction then disruption of postsynaptic structure precede overt motor symptoms

Introduction: The ultimate deficit in amyotrophic lateral sclerosis (ALS) is neuromuscular junction (NMJ) loss, producing permanent paralysis, ultimately in respiratory muscles. However, understanding the functional and structural deficits at NMJs prior to this loss is crucial for therapeutic strategy design. Should early interventions focus on reversing denervation, or supporting largely intact NMJs that are functionally impaired? We therefore determined when functional and structural deficits appeared in diaphragmatic NMJs relative to the onset of hindlimb tremor (the first overt motor symptoms) in vivo in the SOD1-G93A mouse model of ALS.Materials and methods: We employed electrophysiological recording of NMJ postsynaptic potentials for spontaneous and nerve stimulation-evoked responses. This was correlated with fluorescent imaging microscopy of the postsynaptic acetylcholine receptor (AChR) distribution throughout the postnatal developmental timecourse from 2 weeks to early symptomatic ages.Results: Significant reduction in the amplitudes of spontaneous miniature endplate potentials (mEPPs) and evoked EPPs emerged only at early symptomatic ages (in our colony, 18-22 weeks). Reductions in mEPP frequency, number of vesicles per EPP, and EPP rise time were seen earlier, at 16weeks, but this reversed by early symptomatic ages. However, the earliest and most striking impairment was an inability to maintain EPP amplitude during a 20 Hz stimulus train, which appeared 6 weeks before overt in vivo motor symptoms. Despite this, fluorescent α-bungarotoxin labelling revealed no systematic, progressive changes in 11 comprehensive NMJ morphological parameters (area, shape, compactness, number of acetylcholine receptor, AChR, regions, etc.) with disease progression. Rather, while NMJs were largely normally-shaped, from 16 weeks there was a progressive and substantial disruption in AChR concentration and distribution within the NMJ footprint.Discussion: Thus, NMJ functional deficits appear at least 6 weeks before motor symptoms in vivo, while structural deficits occur 4 weeks later, and predominantly within NMJs. These data suggest initial therapies focused on rectifying suboptimal NMJ function could produce effective relief of symptoms of weakness

Handling missing data when estimating causal effects with targeted maximum likelihood estimation

Targeted maximum likelihood estimation (TMLE) is increasingly used for doubly robust causal inference, but how missing data should be handled when using TMLE with data-adaptive approaches is unclear. Based on data (1992-1998) from the Victorian Adolescent Health Cohort Study, we conducted a simulation study to evaluate 8 missing-data methods in this context: complete-case analysis, extended TMLE incorporating an outcome-missingness model, the missing covariate missing indicator method, and 5 multiple imputation (MI) approaches using parametric or machine-learning models. We considered 6 scenarios that varied in terms of exposure/outcome generation models (presence of confounder-confounder interactions) and missingness mechanisms (whether outcome influenced missingness in other variables and presence of interaction/nonlinear terms in missingness models). Complete-case analysis and extended TMLE had small biases when outcome did not influence missingness in other variables. Parametric MI without interactions had large bias when exposure/outcome generation models included interactions. Parametric MI including interactions performed best in bias and variance reduction across all settings, except when missingness models included a nonlinear term. When choosing a method for handling missing data in the context of TMLE, researchers must consider the missingness mechanism and, for MI, compatibility with the analysis method. In many settings, a parametric MI approach that incorporates interactions and nonlinearities is expected to perform well

Hierarchical Bayesian level set inversion

The level set approach has proven widely successful in the study of inverse problems for inter- faces, since its systematic development in the 1990s. Re- cently it has been employed in the context of Bayesian inversion, allowing for the quantification of uncertainty within the reconstruction of interfaces. However the Bayesian approach is very sensitive to the length and amplitude scales in the prior probabilistic model. This paper demonstrates how the scale-sensitivity can be cir- cumvented by means of a hierarchical approach, using a single scalar parameter. Together with careful con- sideration of the development of algorithms which en- code probability measure equivalences as the hierar- chical parameter is varied, this leads to well-defined Gibbs based MCMC methods found by alternating Metropolis-Hastings updates of the level set function and the hierarchical parameter. These methods demon- strably outperform non-hierarchical Bayesian level set methods

Is physical activity related to renal cell carcinoma? A systematic review

Introduction: Relationship between renal cell carcinoma and physical activity is not clear. Objectives: This study aimed to review the relationship between renal cell carcinoma and physical activity. Methods: We searched valid databases such as PubMed/Medline, Web of Science and Scopus for search of English papers by 30/12/2018. Eleven articles were selected for final assessment. We used Kidney cancer, Exercise, Kidney Neoplasm, Renal cancer, Physical activity, Renal cell carcinoma, Physical inactivity and Sedentary Lifestyle or a combination of them in the title/abstracts as the keywords. Results: There were 37,742 subjects reviewed in this systematic review of eleven published papers including five standard case-control, three cohorts and three population-based case-control design. Conclusion: According to the results, physical activity has a reverse relationship with renal cell carcinoma. © 2020 The Author(s); Published by So

A Framework for the Evaluation of Liquefaction Consequences for Shallow-Founded Structures

Performance-based earthquake engineering is increasingly being used to inform decision-making regarding seismic design. Recent research has provided a number of procedures that yield information needed for the development of a performance-based framework for liquefaction engineering. This study proposes a structure for such a framework for application to shallow-founded structures and identifies procedures that are key to its use. Procedures used in such performance-based engineering frameworks must offer a probabilistic estimate of hazard, demand, and/or damage, rather than a simple deterministic estimate. The framework includes analysis of both foundation and structural performance. The foundation may be subject to settlement and residual tilt if subsurface layers of soil liquefy. Although liquefaction generally reduces the acceleration demand on the superstructure, it may still cause significant damage to nonstructural components or lead to casualties. Further, the framework is organized with mitigation decision-making in mind. Mitigation may reduce the impact of foundation damage, but is expected to simultaneously increase the demand on the superstructure. Decisions about whether to mitigate, and how, must consider this tradeoff.This research was supported by the United States Department of Education under award number P200A150042 and by the Civil, Architectural, and Environmental Engineering department at the University of Colorado, Boulder