Search

Multifocal contact lenses (MCLs) are one of the solutions to correct presbyopia, but their adoption is not widespread. To address this situation, visual simulators can be used to refine the adaptation process. This study aims to obtain accurate simulations for a visual simulator (SimVis Gekko; 2EyesVision) of daily soft MCL designs from four manufacturers. In-vitro characterization of these MCLs—several powers and additions- was obtained using NIMO TR-1504. From the averaged relative power profiles across powers, phase maps were reconstructed and the Through-Focus Visual Strehl metric was calculated for each MCL design. The SimVis Gekko simulation corresponding to each MCL design was obtained computationally and bench-validated. Finally, the MCL simulations were clinically validated involving presbyopic patients. The clinical validation results show a good agreement between the SimVis Gekko simulations and the real MCLs for through-focus visual acuity (TF-VA) curves and VA at three real distances. All MCL designs showed a partial correlation higher than 0.90 and a Root Mean Square Error below 0.07 logMAR between the TF-VA of simulations and Real MCLs across subjects. The validity of the simulation approach using SimVis Gekko and in-vitro measurements was confirmed in this study, opening the possibility to accelerate the adaptation of MCLs. [ABSTRACT FROM AUTHOR]

Most tunable lenses (TLs) are affected by deviations in optical power induced by external temperature changes or due to internal heating while in use. This study proposes: (1) An experimental characterization method to evaluate the magnitude of the optical power deviations due to internal temperature shifts; (2) three different mathematical models (experimental, polynomial, and optimized) to describe the response of the lens with temperature; (3) predictions of the internal temperature shifts while using the lens in time frames of minutes, seconds, and milliseconds and; (4) a real time optical power compensation tool based on the implementation of the models on a custom voltage electronic driver. The compensation methods were successfully applied to two TL samples in static and dynamic experiments and in hysteresis cycles. After 40 min at a static nominal power of 5 diopters (dpt), the internal temperature exponentially increased by 17 °C, producing an optical power deviation of 1.0 dpt (1.5 dpt when the lens cools down), representing a 20% distortion for heating and 30% for cooling. Modelling and compensation reduced the deviations to 0.2 dpt when heating (0.35 dpt when cooling) and the distortions to 4% and 7%. Similar levels of improvement were obtained in dynamic and hysteresis experiments. Compensation reduced temperature effects by more than 75%, representing a significant improvement in the performance of the lens. [ABSTRACT FROM AUTHOR]

We present a new metric (Multifocal Acceptance Score, MAS-2EV) to evaluate vision with presbyopic corrections. The MAS-2EV is based on a set of images representing natural visual scenes at day and night conditions projected in far and near displays, and a near stereo target. Subjects view and score the images through different binocular corrections (monofocal corrections at far; bifocal corrections; monovision and modified monovision) administered with soft contact lenses (in cyclopleged young subjects) or with a binocular simultaneous vision simulator (in presbyopic and cyclopleged young subjects). MAS-2EV scores are visually represented in the form of polygons, and quantified using different metrics: overall visual quality, visual degradation at far, visual benefit at near, near stereo benefit, visual imbalance near-far, overall visual imbalance and a combined overall performance metric. We have found that the MAS-2EV has sufficient repeatability and sensitivity to allow differentiation across corrections with only two repetitions, and the duration of the psychophysical task (3 min for subject/condition/correction) makes it useable in the clinic. We found that in most subjects binocular bifocal corrections produce the lowest visual imbalance, and the highest near stereo benefit. 46.67% of the subjects ranked binocular bifocal corrections first, and 46.67% of the subjects ranked monovision first. MAS-2EV, particularly in combination with visual simulators, can be applied to select prospective presbyopic corrections in patients prior to contact lens fitting or intraocular lens implantation. [ABSTRACT FROM AUTHOR]

Due to chromatic aberration, blue images are defocused when the eye is focused to the middle of the visible spectrum, yet we normally are not aware of chromatic blur. The eye suffers from monochromatic aberrations which degrade the optical quality of all images projected on the retina. The combination of monochromatic and chromatic aberrations is not additive and these aberrations may interact to improve image quality. Using Adaptive Optics, we investigated the optical and visual effects of correcting monochromatic aberrations when viewing polychromatic grayscale, green, and blue images. Correcting the eye's monochromatic aberrations improved optical quality of the focused green images and degraded the optical quality of defocused blue images, particularly in eyes with higher amounts of monochromatic aberrations. Perceptual judgments of image quality tracked the optical findings, but the perceptual impact of the monochromatic aberrations correction was smaller than the optical predictions. The visual system appears to be adapted to the blur produced by the native monochromatic aberrations, and possibly to defocus in blue. [ABSTRACT FROM AUTHOR]

Interleukin (IL)-6 is a pleiotropic cytokine involved in the regulation of hematological and immune responses. IL-6 is secreted chiefly by stromal cells, but little is known about its precise role in the homeostasis of human mesenchymal stromal cells (hMSCs) and the role it may play in hMSC-mediated immunoregulation. We studied the role of IL-6 in the biology of bone marrow derived hMSC in vitro by silencing its expression using short hairpin RNA targeting. Our results show that IL-6 is involved in immunosuppression triggered by hMSCs. Cells silenced for IL-6 showed a reduced capacity to suppress activated T-cell proliferation. Moreover, silencing of IL-6 significantly blocked the capacity of hMSCs to proliferate. Notably, increasing the intracellular level of IL-6 but not recovering the extracellular level could restore the proliferative impairment observed in IL-6-silenced hMSC. Our data indicate that IL-6 signals in hMSCs by a previously undescribed intracellular mechanism. [ABSTRACT FROM AUTHOR]

Satellite-measured radiances are obviously of great interest for photovoltaic (PV) energy prediction. In this work we will use them together with clear sky irradiance estimates for the nowcasting of PV energy productions over peninsular Spain. We will feed them directly into two linear Machine Learning models, Lasso and linear Support Vector Regression (SVR), and two highly non-linear ones, Deep Neural Networks (in particular, Multilayer Perceptrons, MLPs) and Gaussian SVRs. We shall also use a simple clear sky-based persistence model for benchmarking purposes. We consider prediction horizons of up to 6 h, with Gaussian SVR being statistically better than the other models at each horizon, since its errors increase slowly with time (with an average of 1.92% for the first three horizons and of 2.89% for the last three). MLPs performance is close to that of the Gaussian SVR for the longer horizons (with an average of 3.1%) but less so at the initial ones (average of 2.26%), being nevertheless significantly better than the linear models. As it could be expected, linear models give weaker results (in the initial horizons, Lasso and linear SVR have already an error of 3.21% and 3.46%, respectively), but we will take advantage of the spatial sparsity provided by Lasso to try to identify the concrete areas with a larger influence on PV energy nowcasts. [ABSTRACT FROM AUTHOR]

Aims/hypothesis: Type 1 and type 2 diabetes differ with respect to pathophysiological factors such as beta cell function, insulin resistance and phenotypic appearance, but there may be overlap between the two forms of diabetes. However, there are relatively few prospective studies that have characterised the relationship between autoimmunity and incident diabetes. We investigated associations of antibodies against the 65 kDa isoform of GAD (GAD65) with type 1 diabetes and type 2 diabetes genetic risk scores and incident diabetes in adults in European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct, a case-cohort study nested in the EPIC cohort. Methods: GAD65 antibodies were analysed in EPIC participants (over 40 years of age and free of known diabetes at baseline) by radioligand binding assay in a random subcohort (n = 15,802) and in incident diabetes cases (n = 11,981). Type 1 diabetes and type 2 diabetes genetic risk scores were calculated. Associations between GAD65 antibodies and incident diabetes were estimated using Prentice-weighted Cox regression. Results: GAD65 antibody positivity at baseline was associated with development of diabetes during a median follow-up time of 10.9 years (HR for GAD65 antibody positive vs negative 1.78; 95% CI 1.43, 2.20) after adjustment for sex, centre, physical activity, smoking status and education. The genetic risk score for type 1 diabetes but not type 2 diabetes was associated with GAD65 antibody positivity in both the subcohort (OR per SD genetic risk 1.24; 95% CI 1.03, 1.50) and incident cases (OR 1.97; 95% CI 1.72, 2.26) after adjusting for age and sex. The risk of incident diabetes in those in the top tertile of the type 1 diabetes genetic risk score who were also GAD65 antibody positive was 3.23 (95% CI 2.10, 4.97) compared with all other individuals, suggesting that 1.8% of incident diabetes in adults was attributable to this combination of risk factors. Conclusions/interpretation: Our study indicates that incident diabetes in adults has an element of autoimmune aetiology. Thus, there might be a reason to re-evaluate the present subclassification of diabetes in adulthood. [ABSTRACT FROM AUTHOR]

Content Distribution Networks (CDN) are key for providing worldwide services and content to end-users. In this work, we propose three multiobjective evolutionary algorithms for solving the problem of designing and optimizing cloud-based CDNs. We consider the objectives of minimizing the total cost of the infrastructure (including virtual machines, network, and storage) and the maximization of the quality-of-service provided to end-users. The proposed model considers a multi-tenant approach where a single cloud-based CDN is able to host multiple content providers using a resource sharing strategy. The proposed evolutionary algorithms address the offline problem of provisioning infrastructure resources while a greedy heuristic method is proposed for addressing the online problem of routing contents. The experimental evaluation of the proposed methods is performed over a set of realistic problem instances. Results indicate that the proposed approach is effective for designing and optimizing cloud-based CDNs reducing total costs by up to 10.3% while maintaining an adequate quality of service. [ABSTRACT FROM AUTHOR]

Aim: 6q24-related transient neonatal diabetes mellitus (6q24-TNDM) is a rare imprinting disorder characterized by uncontrolled hyperglycemia during the first 6 months of life. The molecular etiology of 6q24-TNDM is attributable to overexpression of the paternally inherited PLAGL1 and HYMAI genes located on the 6q24 locus. One of these major defects is maternal loss of methylation (LOM) at 6q24. In addition, approximately 50% of TNDM patients that present LOM at 6q24 can also display hypomethylation at additional imprinted loci (multilocus imprinting disturbances, MLID). Interestingly, the majority of these patients carry mutations in the ZFP57 gene, a transcription factor required for the adequate maintenance of methylation during early embryonic development.Methods: Methylation analysis of 6q24 and additional imprinted loci was carried out by MS-MLPA in a Tunisian male patient with clinical diagnosis of TNMD. For the same patient, mutation analysis of the ZFP57 gene was conducted by direct Sanger sequencing.Results: We report a novel nonsense mutation (c.373C > T; p.R125*; ENST00000376883.1) at the ZFP57 gene causing TNDM-MLID and describe detailed phenotype/epigenotype analysis of TNMD patients carrying ZFP57 mutations.Conclusion: We provide additional support to the role of ZFP57 as a genetic determinant cause of MLID in patients with TNMD. [ABSTRACT FROM AUTHOR]

Aims/hypothesis: Gene-macronutrient interactions may contribute to the development of type 2 diabetes but research evidence to date is inconclusive. We aimed to increase our understanding of the aetiology of type 2 diabetes by investigating potential interactions between genes and macronutrient intake and their association with the incidence of type 2 diabetes.Methods: We investigated the influence of interactions between genetic risk scores (GRSs) for type 2 diabetes, insulin resistance and BMI and macronutrient intake on the development of type 2 diabetes in the European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct, a prospective case-cohort study across eight European countries (N = 21,900 with 9742 incident type 2 diabetes cases). Macronutrient intake was estimated from diets reported in questionnaires, including proportion of energy derived from total carbohydrate, protein, fat, plant and animal protein, saturated, monounsaturated and polyunsaturated fat and dietary fibre. Using multivariable-adjusted Cox regression, we estimated country-specific interaction results on the multiplicative scale, using random-effects meta-analysis. Secondary analysis used isocaloric macronutrient substitution.Results: No interactions were identified between any of the three GRSs and any macronutrient intake, with low-to-moderate heterogeneity between countries (I2 range 0-51.6%). Results were similar using isocaloric macronutrient substitution analyses and when weighted and unweighted GRSs and individual SNPs were examined.Conclusions/interpretation: Genetic susceptibility to type 2 diabetes, insulin resistance and BMI did not modify the association between macronutrient intake and incident type 2 diabetes. This suggests that macronutrient intake recommendations to prevent type 2 diabetes do not need to account for differences in genetic predisposition to these three metabolic conditions. [ABSTRACT FROM AUTHOR]

Deep Learning models are recently receiving a large attention because of their very powerful modeling abilities, particularly on inputs that have a intrinsic one- or two-dimensional structure that can be captured and exploited by convolutional layers. In this work we will apply Deep Neural Networks (DNNs) in two problems, wind energy and daily solar radiation prediction, whose inputs, derived from Numerical Weather Prediction systems, have a clear spatial structure. As we shall see, the predictions of single deep models and, more so, of DNN ensembles can improve on those of Support Vector Regression, a Machine Learning method that can be considered the state of the art for regression. [ABSTRACT FROM AUTHOR]

Aging is the main risk factor for many chronic degenerative diseases and cancer. Increased senescent cell burden in various tissues is a major contributor to aging and age-related diseases. Recently, a new class of drugs termed senolytics were demonstrated to extending healthspan, reducing frailty and improving stem cell function in multiple murine models of aging. To identify novel and more optimal senotherapeutic drugs and combinations, we established a senescence associated β-galactosidase assay as a screening platform to rapidly identify drugs that specifically affect senescent cells. We used primary Ercc1-/- murine embryonic fibroblasts with reduced DNA repair capacity, which senesce rapidly if grown at atmospheric oxygen. This platform was used to screen a small library of compounds that regulate autophagy, identifying two inhibitors of the HSP90 chaperone family as having significant senolytic activity in mouse and human cells. Treatment of Ercc1-/Δ mice, a mouse model of a human progeroid syndrome, with the HSP90 inhibitor 17-DMAG extended healthspan, delayed the onset of several age-related symptoms and reduced p16INK4a expression. These results demonstrate the utility of our screening platform to identify senotherapeutic agents as well as identified HSP90 inhibitors as a promising new class of senolytic drugs. [ABSTRACT FROM AUTHOR]

Gravitational domain wall solutions in gauged supergravity are often constructed within truncations that do not include vectors. As a consequence the gauge group is only a global symmetry of this truncation. The consistency of the truncation requires the restriction to solutions with vanishing Noether charge under this global symmetry, since otherwise vector fields are sourced. We show that this has interesting consequences for the orbit structure of the solutions under the global symmetries. We investigate this for CSO( p, q, r)-gaugings in various dimensions with scalar fields truncated to the $$ \mathrm{S}\mathrm{L}\left(n,\mathbb{R}\right)/\mathrm{SO}(n) $$ subcoset. We prove that the seed solution - which generates all other solutions using only global transformations - has a diagonal coset matrix. This means that there exists a transformation at the boundary of the geometry that diagonalises the coset matrix and that this same transformation also diagonalises the whole flow as a consequence of the vanishing charge. [ABSTRACT FROM AUTHOR]

Intra-arterial radiotherapy with yttrium-90 microspheres (radioembolization) is a therapeutic procedure exclusively applied to the liver that allows the direct delivery of high-dose radiation to liver tumors, by means of endovascular catheters, selectively placed within the tumor vasculature. The aim of the study was to describe the distribution of spheres within the precapillaries, inflammatory response, and recannalization characteristics after embolization with nonradioactive resin microspheres in the kidney and liver. We performed a partial embolization of the liver and kidney vessels in nine white pigs. The left renal and left hepatic arteries were catheterized and filled with nonradioactive resin microspheres. Embolization was defined as the initiation of near-stasis of blood flow, rather than total occlusion of the vessels. The hepatic circulation was not isolated so that the effects of reflux of microspheres into stomach could be observed. Animals were sacrificed at 48 h, 4 weeks, and 8 weeks, and tissue samples from the kidney, liver, lung, and stomach evaluated. Microscopic evaluation revealed clusters of 10-30 microspheres (15-30 microm in diameter) in the small vessels of the kidney (the arciform arteries, vasa recti, and glomerular afferent vessels) and liver. Aggregates were associated with focal ischemia and mild vascular wall damage. Occlusion of the small vessels was associated with a mild perivascular inflammatory reaction. After filling of the left hepatic artery with microspheres, there was some evidence of arteriovenous shunting into the lungs, and one case of cholecystitis and one case of marked gastritis and ulceration at the site of arterial occlusion due to the presence of clusters of microspheres. Beyond 48 h, microspheres were progressively integrated into the vascular wall by phagocytosis and the lumen recannalized. Eight-week evaluation found that the perivascular inflammatory reaction was mild. Liver cell damage, bile duct injury, and portal space fibrosis were not observed. In conclusion, resin microspheres (15-30 microm diameter) trigger virtually no inflammatory response in target tissues (liver and kidney). Clusters rather than individual microspheres were associated with a mild to moderate perivascular inflammatory reaction. There was no evidence of either a prolonged inflammatory reaction or fibrosis in the liver parenchyma following recannalization. [ABSTRACT FROM AUTHOR]

Background/objectives: High intakes of unprocessed red or processed meat may increase the risk of stroke. We aimed to examine the association between unprocessed red meat, processed meat and total red meat consumption and risk of total stroke and ischaemic stroke.Subjects/methods: Cox proportional hazards regression analyses were conducted based on the data for 41,020 men and women aged 29-69 years at baseline.Results: During a mean follow-up of 13.8 years, 674 incident cases of stroke (531 ischaemic strokes, 79 haemorrhagic strokes, 42 subarachnoid haemorrhages and 22 mixed or unspecified events) were identified. After multiple adjustment, unprocessed red meat, processed meat and total red meat consumption were not correlated with incidence of total stroke or ischaemic stroke in either men or women. The hazard ratios (HRs) for unprocessed red meat and processed meat and risk of total stroke comparing the highest with the lowest quintiles were, respectively, 0.81 (95% confidence interval (CI) 0.54-1.21; P-trend=0.15) and 0.92 (95% CI 0.64-1.32; P-trend=0.82) in men and 1.21 (95% CI 0.79-1.85; P-trend=0.10) and 0.81 (95% CI 0.51-1.27; P-trend=0.17) in women. The HRs for unprocessed red meat and processed meat and risk of ischaemic stroke were, respectively, 0.80 (95% CI 0.51-1.25; P-trend=0.51) and 0.86 (95% CI 0.57-1.29; P-trend=0.77) in men and 1.24 (95% CI 0.74-2.05; P-trend=0.13) and 0.82 (95% CI 0.47-1.42; P-trend=0.31) in women.Conclusions: In the Spanish European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, unprocessed red meat and processed meat consumption were not associated with risk of stroke in men or women. [ABSTRACT FROM AUTHOR]

Purpose: The strong association between t(14;18) translocation and follicular lymphoma (FL) is well known. However, the determinants of this chromosomal aberration and their role in t(14;18) associated FL remain to be established.Methods: t(14;18) frequency within the B cell lymphoma 2 major breakpoint region was determined for 135 incident FL cases and 251 healthy controls as part of a nested case-control study within the European Prospective Investigation into Cancer cohort. Quantitative real-time PCR was performed in DNA extracted from blood samples taken at recruitment. The relationship between prevalence and frequency of the translocation with baseline anthropometric, lifestyle, and dietary factors in cases and controls was determined. Unconditional logistic regression was used to explore whether the risk of FL associated with these factors differed in t(14;18)(+) as compared to t(14;18)(-) cases.Results: Among incident FL cases, educational level (χ(2) p = 0.021) and height (χ(2) p = 0.025) were positively associated with t(14;18) prevalence, and cases with high frequencies [t(14;18)(HF)] were significantly taller (t test p value = 0.006). These findings were not replicated in the control population, although there were a number of significant associations with dietary variables. Further analyses revealed that height was a significant risk factor for t(14;18)(+) FL [OR 6.31 (95% CI 2.11, 18.9) in the tallest versus the shortest quartile], but not t(14;18)(-) cases.Conclusions: These findings suggest a potential role for lifestyle factors in the prevalence and frequency of the t(14;18) translocation. The observation that the etiology of FL may differ by t(14;18) status, particularly with regard to height, supports the subdivision of FL by translocation status. [ABSTRACT FROM AUTHOR]