Nonequilibrium Steady States of Driven Periodic Media

We study a periodic medium driven over a random or periodic substrate. Our work is based on nonequilibrium continuum hydrodynamic equations of motion, which we derive microscopically. We argue that in the random case instabilities will always destroy the LRO of the lattice. In most, if not all, cases, the stable driven ordered state is a transverse smectic, with ordering wavevector perpendicular to the velocity. It consists of a periodic array of flowing liquid channels, with transverse displacements and density (``permeation mode'') as hydrodynamic variables. We present dynamic functional renormalization group calculations in two and three dimensions for an approximate model of the smectic. The finite temperature behavior is much less glassy than in equilibrium, owing to a disorder-driven effective ``heating'' (allowed by the absence of the fluctuation-dissipation theorem). This, in conjunction with the permeation mode, leads to a fundamentally analytic transverse response for $T>0$. Our results are compared to recent experiments and other theoretical work.Comment: 39 PRB pages, RevTex and 9 postscript figures, uses multicol.st

Development of the oral resistome during the first decade of life

Published online: 09 March 2023Antibiotic overuse has promoted the spread of antimicrobial resistance (AMR) with significant health and economic consequences. Genome sequencing reveals the widespread presence of antimicrobial resistance genes (ARGs) in diverse microbial environments. Hence, surveillance of resistance reservoirs, like the rarely explored oral microbiome, is necessary to combat AMR. Here, we characterise the development of the paediatric oral resistome and investigate its role in dental caries in 221 twin children (124 females and 97 males) sampled at three time points over the first decade of life. From 530 oral metagenomes, we identify 309 ARGs, which significantly cluster by age, with host genetic effects detected from infancy onwards. Our results suggest potential mobilisation of ARGs increases with age as the AMR associated mobile genetic element, Tn916 transposase was co-located with more species and ARGs in older children. We find a depletion of ARGs and species in dental caries compared to health. This trend reverses in restored teeth. Here we show the paediatric oral resistome is an inherent and dynamic component of the oral microbiome, with a potential role in transmission of AMR and dysbiosis.Smitha Sukumar, FangWang, Carra A. Simpson, Cali E. Willet, Tracy Chew, Toby E. Hughes, Michelle R. Bockmann, Rosemarie Sadsad, F. ElizabethMartin, Henry W. Lydecker, Gina V. Browne, KylieM. Davis, Minh Bui, ElenaMartinez, Christina J. Adle

Patterns of eye-movements when Male and Female observers judge female attractiveness, body fat and waist-to-hip ratio

Behavioural studies of the perceptual cues for female physical attractiveness have suggested two potentially important features; body fat distribution (the waist-to-hip ratio or WHR) and overall body fat (often estimated by the body mass index or BMI). However none of these studies tell us directly which regions of the stimulus images inform observers’ judgments. Therefore, we recorded the eye-movements of 3 groups of 10 male observers and 3 groups of 10 female observers, when they rated a set of 46 photographs of female bodies. The first sets of observers rated the images for attractiveness, the second sets rated for body fat and the third sets for WHR. If either WHR and/or body fat are used to judge attractiveness, then observers rating attractiveness should look at those areas of the body which allow assessment of these features, and they should look in the same areas when they are directly asked to estimate WHR and body fat. So we are able to compare the fixation patterns for the explicit judgments with those for attractiveness judgments, and infer which features were used for attractiveness. Prior to group analysis of the eye-movement data, the locations of individual eye fixations were transformed into a common reference space to permit comparisons of fixation density at high resolution across all stimuli. This manipulation allowed us to use spatial statistical analysis techniques to show: 1) Observers’ fixations for attractiveness and body fat clustered in the central and upper abdomen and chest, but not the pelvic or hip areas, consistent with the finding that WHR had little influence over attractiveness judgments. 2) The pattern of fixations for attractiveness ratings was very similar to the fixation patterns for body fat judgments. 3) The fixations for WHR ratings were significantly different from those for attractiveness and body fat

Human and mouse essentiality screens as a resource for disease gene discovery

The identification of causal variants in sequencing studies remains a considerable challenge that can be partially addressed by new gene-specific knowledge. Here, we integrate measures of how essential a gene is to supporting life, as inferred from viability and phenotyping screens performed on knockout mice by the International Mouse Phenotyping Consortium and essentiality screens carried out on human cell lines. We propose a cross-species gene classification across the Full Spectrum of Intolerance to Loss-of-function (FUSIL) and demonstrate that genes in five mutually exclusive FUSIL categories have differing biological properties. Most notably, Mendelian disease genes, particularly those associated with developmental disorders, are highly overrepresented among genes non-essential for cell survival but required for organism development. After screening developmental disorder cases from three independent disease sequencing consortia, we identify potentially pathogenic variants in genes not previously associated with rare diseases. We therefore propose FUSIL as an efficient approach for disease gene discovery. Discovery of causal variants for monogenic disorders has been facilitated by whole exome and genome sequencing, but does not provide a diagnosis for all patients. Here, the authors propose a Full Spectrum of Intolerance to Loss-of-Function (FUSIL) categorization that integrates gene essentiality information to aid disease gene discovery

An economic evaluation of adaptive e-learning devices to promote weight loss via dietary change for people with obesity.

BACKGROUND: The prevalence of obesity is over 25 % in many developed countries. Obesity is strongly associated with an increased risk of fatal and chronic conditions such as cardiovascular disease and type 2 diabetes. Therefore it has become a major public health concern for many economies. E-learning devices are a relatively novel approach to promoting dietary change. The new generation of devices are 'adaptive' and use interactive electronic media to facilitate teaching and learning. E-Learning has grown out of recent developments in information and communication technology, such as the Internet, interactive computer programmes, interactive television and mobile phones. The aim of this study is to assess the cost-effectiveness of e-learning devices as a method of promoting weight loss via dietary change. METHODS: An economic evaluation was performed using decision modelling techniques. Outcomes were expressed in terms of Quality-Adjusted Life-Years (QALYs) and costs were estimated from a health services perspective. All parameter estimates were derived from the literature. A systematic review was undertaken to derive the estimate of relative treatment effect. RESULTS: The base case results from the e-Learning Economic Evaluation Model (e-LEEM) suggested that the incremental cost-effectiveness ratio was approximately £102,000 per Quality-Adjusted Life-Year (QALY) compared to conventional care. This finding was robust to most alternative assumptions, except a much lower fixed cost of providing e-learning devices. Expected value of perfect information (EVPI) analysis showed that while the individual level EVPI was arguably negligible, the population level value was between £37 M and £170 M at a willingness to pay between £20,000 to £30,000 per additional QALY. CONCLUSION: The current economic evidence base suggests that e-learning devices for managing the weight of obese individuals are unlikely to be cost-effective unless their fixed costs are much lower than estimated or future devices prove to be much more effective

Effects of oral calcium supplementation on intestinal bile-acids and cytolytic activity of fecal water in patients with adenomatous polyps of the colon

Calcium has been proposed to prevent colon cancer in subjects at risk for this tumour. This effect is supposed to be due at least in part to binding the bile acids to calcium, making them insoluble and harmless. To evaluate the effects of oral calcium supplementation on intestinal bile acids, 19 patients with adenomatous colonic polyps were supplemented with 35.5 mmol Ca2+ daily for 12 weeks. Duodenal bile, 24-h feces and 24-h urine were collected before and at the end of the 12-week period. In duodenal bile proportional concentration of cholic acid increased (38 +/- 4 vs. 51 +/- 3%, P <0.001), whereas that of chenodeoxycholic acid decreased (35 +/- 3 vs. 25 +/- 2%, P <0.01). Total fecal bile acid excretion increased (950 +/- 126 vs. 1218 +/- 137 mumol 24 h-1, P <0.01), with proportional concentrations of the main primary and secondary bile acids remaining the same. Cytolytic activity of fecal water, measured by the degree of lysis of erythrocytes by the water, decreased (45 +/- 8 vs. 30 +/- 7%, P <0.05). Total excretion of calcium increased as expected from the supplementary dose. It is concluded that calcium supplementation markedly affects intestinal bile acids and lytic activity of fecal water and that, in view of similar results during 1-week calcium supplementation in young healthy subjects, these effects remain constant over at least 3 months and occur both in healthy persons and in patients at increased risk for colon cancer