Acquired DNA damage in adolescent obesity – a promoter and predictor of cancer?

Introduction Epidemiological evidence linking obesity with increased risk of cancer is steadily growing, although the causative aspects underpinning this association are only partially understood. Obesity coincides with deficiencies in micronutrients such as Vitamin D, a key player in DNA repair processes. As a result, vitamin D deficiency in obesity may have a marked impact on DNA stability and integrity. 8-hydroxyguanosine (8-OHdG) is a well-established marker of oxidative DNA damage that has been identified in higher concentrations in cancer patients. Here we report, preliminary, unpublished findings from our study on acquired DNA damage in childhood obesity. Material and Method Body Mass Index (BMI), Waist to Hip ratio (WHR) and body fat percentage via bioelectrical impedance was assessed in over 70 participants, aged 11-18 and recruited from National Health Service (NHS) obesity clinics and schools in London. A non-invasive, integrated evaluation of urinary 8-OHdG and salivary vitamin D was conducted using ELISA based methods and compared to markers of adiposity. Results and Discussion A BMI percentile >99 was found to be associated with decreased salivary vitamin D and increased urinary 8-OHdG when compared to healthy weight controls (BMI = 5th-85th percentile). Vitamin D levels in saliva were found to be inversely correlated with BMI and body fat percentage. Urinary 8-OHdG positively correlated with body fat percentage and WHR. Most importantly, an inverse correlation between vitamin D in saliva and 8-OHdG in urine was also identified. Recent evidence has suggested vitamin D in obesity to be a consequence of altered behaviour, reduced intestinal absorption, and sequestration of vitamin D into adipose tissue. As a result, DNA repair processes against oxidative DNA damage in obesity may be impaired, resulting in the excess of lesions including 8-OHdG. The effects of excess 8-OHdG lesions have been well researched to include various mutations that can drive carcinogenesis. Conclusion Our results suggest Vitamin D deficiency in obese adolescents may play a significant role in triggering oxidative DNA damage, thus increasing the likelihood of cancer later in life

Full-field and anomaly initialization using a low-order climate model: a comparison and proposals for advanced formulations

Initialization techniques for seasonal-to-decadal climate predictions fall into two main categories; namely full-field initialization (FFI) and anomaly initialization (AI). In the FFI case the initial model state is replaced by the best possible available estimate of the real state. By doing so the initial error is efficiently reduced but, due to the unavoidable presence of model deficiencies, once the model is let free to run a prediction, its trajectory drifts away from the observations no matter how small the initial error is. This problem is partly overcome with AI where the aim is to forecast future anomalies by assimilating observed anomalies on an estimate of the model climate. The large variety of experimental setups, models and observational networks adopted worldwide make it difficult to draw firm conclusions on the respective advantages and drawbacks of FFI and AI, or to identify distinctive lines for improvement. The lack of a unified mathematical framework adds an additional difficulty toward the design of adequate initialization strategies that fit the desired forecast horizon, observational network and model at hand. Here we compare FFI and AI using a low-order climate model of nine ordinary differential equations and use the notation and concepts of data assimilation theory to highlight their error scaling properties. This analysis suggests better performances using FFI when a good observational network is available and reveals the direct relation of its skill with the observational accuracy. The skill of AI appears, however, mostly related to the model quality and clear increases of skill can only be expected in coincidence with model upgrades. We have compared FFI and AI in experiments in which either the full system or the atmosphere and ocean were independently initialized. In the former case FFI shows better and longer-lasting improvements, with skillful predictions until month 30. In the initialization of single compartments, the best performance is obtained when the stabler component of the model (the ocean) is initialized, but with FFI it is possible to have some predictive skill even when the most unstable compartment (the extratropical atmosphere) is observed. Two advanced formulations, least-square initialization (LSI) and exploring parameter uncertainty (EPU), are introduced. Using LSI the initialization makes use of model statistics to propagate information from observation locations to the entire model domain. Numerical results show that LSI improves the performance of FFI in all the situations when only a portion of the system's state is observed. EPU is an online drift correction method in which the drift caused by the parametric error is estimated using a short-time evolution law and is then removed during the forecast run. Its implementation in conjunction with FFI allows us to improve the prediction skill within the first forecast year. Finally, the application of these results in the context of realistic climate models is discussed

The 2.35 year itch of Cyg OB2 #9. II. Radio monitoring

Cyg OB2 #9 is one of a small set of non-thermal radio emitting massive O-star binaries. The non-thermal radiation is due to synchrotron emission in the colliding-wind region. Cyg OB2 #9 was only recently discovered to be a binary system and a multi-wavelength campaign was organized to study its 2011 periastron passage. We report here on the results of the radio observations obtained in this monitoring campaign. We used the Expanded Very Large Array (EVLA) radio interferometer to obtain 6 and 20 cm continuum fluxes. The observed radio light curve shows a steep drop in flux sometime before periastron. The fluxes drop to a level that is comparable to the expected free-free emission from the stellar winds, suggesting that the non-thermal emitting region is completely hidden at that time. After periastron passage, the fluxes slowly increase. We introduce a simple model to solve the radiative transfer in the stellar winds and the colliding-wind region, and thus determine the expected behaviour of the radio light curve. From the asymmetry of the light curve, we show that the primary has the stronger wind. This is somewhat unexpected if we use the astrophysical parameters based on theoretical calibrations. But it becomes entirely feasible if we take into account that a given spectral type - luminosity class combination covers a range of astrophysical parameters. The colliding-wind region also contributes to the free-free emission, which can help to explain the high values of the spectral index seen after periastron passage. Combining our data with older Very Large Array (VLA) data allows us to derive a period P = 860.0 +- 3.7 days for this system. With this period, we update the orbital parameters that were derived in the first paper of this series.Comment: 10 pages, 4 figures, accepted for publication in A&

Simulated synchrotron and Inverse Compton emission from Pulsar Wind Nebulae

We present a complete set of diagnostic tools aimed at reproducing synthetic non-thermal (synchrotron and/or Inverse Compton, IC) emissivity, integrated flux energy, polarization and spectral index simulated maps in comparison to observations. The time dependent relativistic magnetohydrodynamic (RMHD) equations are solved with a shock capturing code together with the evolution of the maximum particles energy. Applications to Pulsar Wind Nebulae (PWNe) are shown.Comment: 3 pages, 7 figures, proceeding of the conference "40 Years of Pulsars ", 12-17 August 2007, Montreal, Canada, submitted to AI

A criterion for optimal management of water distribution networks

The management of water supply systems is based on fundamental principles, set by international and national legislations; the general target for water utilities is to offer a reliable and effective service following efficiency criteria. In this context, losses in distribution networks are one of the main problems to tackle: their reduction implies a general decrease in operational costs and in the need for a limited resource such as water. Numerous solutions have been proposed to reduce non revenue water, from simple leak detection to structural interventions on distribution systems, based on new design criteria which favour district-based networks over redundant ones. The present work proposes a new procedure to restructure a water supply network starting from its hydraulic model, comparing different types of intervention and evaluating their feasibility, limits and effectiveness in terms of the global system efficiency, as measured by the infrastructure leakage index (ILI). The possibility to use excessive pressure in specific parts of a network for the production of electricity is also examined, as it offers an additional resource to improve the system performance. The procedure has been tested for the water network in the municipalities of Tarcento and Magnano in Riviera, near Udine in Italy. Thanks to a specific hydraulic model, simulations were performed to identify the optimal interventions on the system aimed at reducing water losses and improving performances and efficiency

Plasmatic and urinary glycosaminoglycans characterization in mucopolysaccharidosis II Patient treated with enzyme-replacement therapy with Idursulfase

We report the structural characterization of plasmatic and urinary GAGs in a Patient affected by MPS II (Hunter syndrome) before and during the first ten months of enzyme-replacement therapy (ERT). Plasmatic GAGs before ERT were rich in pathological DS consisting of iduronic acid (IdoA) and composed of ~90% \uf044Di4s and trace amounts of disulfated disaccharides. DS was also characterized as the main (~90%) urinary GAG mainly composed of ~90% \uf044Di4s with minor percentages of monosulfated and disulfated disaccharides, in particular \u394Di2,4dis. After 300 days of ERT, plasmatic DS strongly decreased but ~14% of IdoA-rich \uf044Di4s was still detected. Similarly, urinary galactosaminoglycans were mainly composed of 78% \uf044Di4s, ~11% \uf044Di6s and ~4% \uf044Di0s with the persistence of \u394Di2,4dis (~4%). About 40% of IdoA-formed \uf044Di4s were also calculated thus confirming that pathological DS is still present in excreted urinary GAGs during ERT. By considering the % of IdoA, we observed rather similar kinetics of excretion in fluids from the beginning of the treatment. Immediately after the first enzyme infusion, a large amount of abnormal DS is removed from tissues reaching the blood compartment and eliminated via the urine, and this process lasts for about two weeks. After this, the percentage of IdoA-rich material present in biological fluids remains fairly constant over the following nine months of treatment. To date, these are the first data regarding plasmatic and urinary kinetics directly measured on products released by the activity of the recombinant enzyme Idursulfase, iduronate-2-sulfatase, evaluated using specific and sensitive analytical procedures