Epstein-Barr virus: clinical and epidemiological revisits and genetic basis of oncogenesis

Epstein-Barr virus (EBV) is classified as a member in the order herpesvirales, family herpesviridae, subfamily gammaherpesvirinae and the genus lymphocytovirus. The virus is an exclusively human pathogen and thus also termed as human herpesvirus 4 (HHV4). It was the first oncogenic virus recognized and has been incriminated in the causation of tumors of both lymphatic and epithelial nature. It was reported in some previous studies that 95% of the population worldwide are serologically positive to the virus. Clinically, EBV primary infection is almost silent, persisting as a life-long asymptomatic latent infection in B cells although it may be responsible for a transient clinical syndrome called infectious mononucleosis. Following reactivation of the virus from latency due to immunocompromised status, EBV was found to be associated with several tumors. EBV linked to oncogenesis as detected in lymphoid tumors such as Burkitt's lymphoma (BL), Hodgkin's disease (HD), post-transplant lymphoproliferative disorders (PTLD) and T-cell lymphomas (e.g. Peripheral T-cell lymphomas; PTCL and Anaplastic large cell lymphomas; ALCL). It is also linked to epithelial tumors such as nasopharyngeal carcinoma (NPC), gastric carcinomas and oral hairy leukoplakia (OHL). In vitro, EBV many studies have demonstrated its ability to transform B cells into lymphoblastoid cell lines (LCLs). Despite these malignancies showing different clinical and epidemiological patterns when studied, genetic studies have suggested that these EBV- associated transformations were characterized generally by low level of virus gene expression with only the latent virus proteins (LVPs) upregulated in both tumors and LCLs. In this review, we summarize some clinical and epidemiological features of EBV- associated tumors. We also discuss how EBV latent genes may lead to oncogenesis in the different clinical malignancie

Factors Associated with Revision Surgery after Internal Fixation of Hip Fractures

Background: Femoral neck fractures are associated with high rates of revision surgery after management with internal fixation. Using data from the Fixation using Alternative Implants for the Treatment of Hip fractures (FAITH) trial evaluating methods of internal fixation in patients with femoral neck fractures, we investigated associations between baseline and surgical factors and the need for revision surgery to promote healing, relieve pain, treat infection or improve function over 24 months postsurgery. Additionally, we investigated factors associated with (1) hardware removal and (2) implant exchange from cancellous screws (CS) or sliding hip screw (SHS) to total hip arthroplasty, hemiarthroplasty, or another internal fixation device. Methods: We identified 15 potential factors a priori that may be associated with revision surgery, 7 with hardware removal, and 14 with implant exchange. We used multivariable Cox proportional hazards analyses in our investigation. Results: Factors associated with increased risk of revision surgery included: female sex, [hazard ratio (HR) 1.79, 95% confidence interval (CI) 1.25-2.50; P = 0.001], higher body mass index (fo

Improved shallow waters tidal estimates using satellite radar altimetry data and numerical modeling

Satellite observations can help in the retrieval of constituents in shallow waters. Noise contamination, however, makes smaller constituents irretrievable and large sources of error. Throughout shallow areas, the constituent’s relevancy changes. For example, near an amphidromic point where M2 relevance drops, so does the potential of satellite contribution for improving its accuracy. Moreover, shallow waters are generally influenced by many constituents (>100). Accurately retrieving all these constituents with satellite radar altimeter data alone is not possible. Series length requirements imposed by the Rayleigh criteria to separate constituents are still unavailable. Removing unwanted signals from satellite observations improves least-squares-based harmonic estimates, given an inversion matrix with the same condition number. This variance reduction is the core of the remove compute restore approach commonly used. First, residual harmonic sets are computed with the difference between observations and model background estimates through conventional or weighted least-squares. Then, the residual harmonics are added to the background model estimates. Here we implemented a method that extends the typical approach by including model background estimate and error covariance in the least-squares step. This inclusion helps to weigh between constituents well represented in the model and those that must be updated. To test the method, we designed a semi-synthetic experiment. First, we used tide gauge data to generate a satellite equivalent dataset and compared estimations between the two methods listed above and the model estimate. Next, we applied the method to compute tidal estimates along satellite radar altimeter tracks (T/P Jason) in the 2D Dutch Coastal Shelf Model (DCSMv6) domain. Results from the synthetic experiment show that the second method produces consistently better estimates reducing RSS consistently through temporal cross-validation. In addition, it provides an effective way of keeping as many constituents estimates as the model series can resolve, adding the benefits of satellite observations. Finally, results from the North Sea implementation show the new estimates increase the variance reduction of satellite residuals across the whole domain relative to background tidal estimates. The range of improvements varies between 0 and 3cm, which is significant given already very accurate model background estimates. The benefited areas include the English Channel, the Irish Sea, the English North-Sea Coast, the Bay of Biscay, the German Bight, and the North Atlantic region close to the upper boundary of the model domain

The impact of nonlinear tide–surge interaction on satellite radar altimeter-derived tides

Both empirical and assimilative global ocean tidal models are significantly more accurate in the deep ocean than in shelf and coastal waters. In this study, we answered whether this is due to the quality of the models used to reduce tide and surge or the general approach to treat tide and surge as two separate components of the water level obtained from stand-alone models, which ignores the nonlinear tide–surge interaction. In doing so, we used tide gauge observations as partially synthetic altimeter time series, tide–surge water-level time series obtained with the 2D Dutch Continental Shelf Model–Flexible Mesh (DCSM), and tide and surge water-level time series obtained using the DCSM, FES2014 (FES) and the Dynamic Atmospheric Correction (DAC) product. Expressed in the root-sum-square (RSS) of the eight main tidal constituents, we obtained a reduction (Formula presented.) % when removing the DCSM tide–surge water levels compared to when we removed the sum of the DCSM tide and DCSM surge water levels. The RSS obtained in the latter case was only 3.3% lower than with FES and DAC. We conclude that the lower tidal estimates accuracy in shelf-coastal waters derives from the missing nonlinear tide–surge interactions.</p

Improved shallow waters tidal estimates using satellite radar altimetry data and numerical modeling

Satellite observations can help in the retrieval of constituents in shallow waters. Noise contamination, however, makes smaller constituents irretrievable and large sources of error. Throughout shallow areas, the constituent’s relevancy changes. For example, near an amphidromic point where M2 relevance drops, so does the potential of satellite contribution for improving its accuracy. Moreover, shallow waters are generally influenced by many constituents (&gt;100). Accurately retrieving all these constituents with satellite radar altimeter data alone is not possible. Series length requirements imposed by the Rayleigh criteria to separate constituents are still unavailable. Removing unwanted signals from satellite observations improves least-squares-based harmonic estimates, given an inversion matrix with the same condition number. This variance reduction is the core of the remove compute restore approach commonly used. First, residual harmonic sets are computed with the difference between observations and model background estimates through conventional or weighted least-squares. Then, the residual harmonics are added to the background model estimates. Here we implemented a method that extends the typical approach by including model background estimate and error covariance in the least-squares step. This inclusion helps to weigh between constituents well represented in the model and those that must be updated. To test the method, we designed a semi-synthetic experiment. First, we used tide gauge data to generate a satellite equivalent dataset and compared estimations between the two methods listed above and the model estimate. Next, we applied the method to compute tidal estimates along satellite radar altimeter tracks (T/P Jason) in the 2D Dutch Coastal Shelf Model (DCSMv6) domain. Results from the synthetic experiment show that the second method produces consistently better estimates reducing RSS consistently through temporal cross-validation. In addition, it provides an effective way of keeping as many constituents estimates as the model series can resolve, adding the benefits of satellite observations. Finally, results from the North Sea implementation show the new estimates increase the variance reduction of satellite residuals across the whole domain relative to background tidal estimates. The range of improvements varies between 0 and 3cm, which is significant given already very accurate model background estimates. The benefited areas include the English Channel, the Irish Sea, the English North-Sea Coast, the Bay of Biscay, the German Bight, and the North Atlantic region close to the upper boundary of the model domain.Mathematical PhysicsPhysical and Space GeodesyEnvironmental Fluid Mechanic

The potential impact of hydrodynamic leveling on the quality of the European vertical reference frame

The first objective of this paper is to assess by means of geodetic network analyses the impact of adding model-based hydrodynamic leveling data to the Unified European Leveling Network (UELN) data on the precision and reliability of the European Vertical Reference Frame (EVRF). In doing so, we used variance information from the latest UELN adjustment. The model-based hydrodynamic leveling data are assumed to be obtained from not-yet existing hydrodynamic models covering either all European seas surrounding the European mainland or parts of it that provide the required mean water level with uniform precision. A heuristic search algorithm was implemented to identify the set of hydrodynamic leveling connections that provide the lowest median of the propagated height standard deviations. In the scenario in which we only allow for connections between tide gauges located in the same sea basin, all having a precision of 3 cm, the median of the propagated height standard deviations improved by 38 % compared to the spirit leveling-only solution. Except for the countries around the Black Sea, coastal countries benefit the most with a maximum improvement of 60 % for Great Britain. We also found decreased redundancy numbers for the observations in the coastal areas and over the entire Great Britain. Allowing for connections between tide gauges among all European seas increased the impact to 42%. Lowering the precision of the hydrodynamic leveling data lowers the impact. The results show, however, that even in case the assumed precision is 5 cm, the overall improvement is still 29%. The second objective is to identify which tide gauges are most profitable in terms of impact. Our results show that these are the ones located in Sweden in which most height markers are located. The impact, however, hardly depends on the geographic location of the tide gauges within a country.Physical and Space GeodesyMathematical PhysicsEnvironmental Fluid MechanicsAircraft Noise and Climate Effect

An empirical noise model for the benefit of model-based hydrodynamic leveling

The main objective of this study is to develop and analyze an empirical noise model for model-derived coastal summer mean water levels (SMWLs) and use that to obtain a more realistic quality impact of combining hydrodynamic leveling and Unified European Leveling Network (UELN) data in realizing the European Vertical Reference System (EVRS). We considered three state-of-the-art hydrodynamic models for the Northeast Atlantic Ocean, including the North Sea and Wadden Sea; AMM7, DCSMv6-ZUNOv4, and 3D DCSM-FM. Moreover, we assess the spatiotemporal performance of these three models in representing coastal SMWLs. The empirical noise models are determined from the differences between observation- and model-derived SMWLs at coastal tide gauges. All three noise models show that the model noise is indeed correlated over sea distances up to hundreds of kilometers. At the same time, they all show a relatively large discontinuity at the origin (i.e., nugget effect); between 12.1 cm2 (3D DCSM-FM) and 16.3 cm2 (DCSMv6-ZUNOv4). The variance (i.e., covariance at zero sea distance) for these two models is 15.3 cm2 and 21.7 cm2, respectively. Averaging the water levels over three summers, lowered the variance and nugget effect for 3D DCSM-FM to 12.7 cm2 and 10.0 cm2, respectively. Our analysis also showed that between 30 and 50% of the variance has to be attributed to errors in the vertical referencing of the tide gauges. We lacked the information to assess what proportion of the observed noise covariances should be attributed to these errors. The performance assessments revealed significant variations over both space and time as well as among the three hydrodynamic models. The results suggest that there is still room for model improvement. In the final experiments, we used the noise model of the best overall performing model (i.e., 3D DCSM-FM) to reassess the quality impact of combining hydrodynamic leveling and UELN data in realizing the EVRS. The results suggest that not including the noise covariances leads to an overestimation of the total quality impact by 7 % and 8 % , when we average the water levels over one and three summer periods, respectively.Physical and Space GeodesyMathematical PhysicsEnvironmental Fluid MechanicsControl & Operation

The impact of nonlinear tide–surge interaction on satellite radar altimeter-derived tides

Both empirical and assimilative global ocean tidal models are significantly more accurate in the deep ocean than in shelf and coastal waters. In this study, we answered whether this is due to the quality of the models used to reduce tide and surge or the general approach to treat tide and surge as two separate components of the water level obtained from stand-alone models, which ignores the nonlinear tide–surge interaction. In doing so, we used tide gauge observations as partially synthetic altimeter time series, tide–surge water-level time series obtained with the 2D Dutch Continental Shelf Model–Flexible Mesh (DCSM), and tide and surge water-level time series obtained using the DCSM, FES2014 (FES) and the Dynamic Atmospheric Correction (DAC) product. Expressed in the root-sum-square (RSS) of the eight main tidal constituents, we obtained a reduction (Formula presented.) % when removing the DCSM tide–surge water levels compared to when we removed the sum of the DCSM tide and DCSM surge water levels. The RSS obtained in the latter case was only 3.3% lower than with FES and DAC. We conclude that the lower tidal estimates accuracy in shelf-coastal waters derives from the missing nonlinear tide–surge interactions.Mathematical PhysicsPhysical and Space GeodesyEnvironmental Fluid MechanicsControl & Operation

Alternative Approaches to Governance in the EU: EU Social Policy and the European Employment Strategy

Recent actions by the European Union reveal a shift away from traditional, top-down, command and control governance. This can be seen in the structure of traditional tools like directives, as many recent directives, especially in social policy-making, tend to be more open and flexible. But the move to more flexible and participatory approaches can best be seen in areas like the European Employment Strategy (EES), which departs radically from traditional regulatory governance approaches. This article explores the increased use of alternative approaches to governance in the EU by examining the EES as an example of this shift. Copyright Blackwell Publishing Ltd 2003.