A Markov state modeling analysis of sliding dynamics of a 2D model

Non-equilibrium Markov State Modeling (MSM) has recently been proposed by Pellegrini et al. [Phys. Rev. E 94, 053001 (2016)] as a possible route to construct a physical theory of sliding friction from a long steady state atomistic simulation: the approach builds a small set of collective variables, which obey a transition-matrix-based equation of motion, faithfully describing the slow motions of the system. A crucial question is whether this approach can be extended from the original 1D small size demo to larger and more realistic size systems, without an inordinate increase of the number and complexity of the collective variables. Here we present a direct application of the MSM scheme to the sliding of an island made of over 1000 harmonically bound particles over a 2D periodic potential. Based on a totally unprejudiced phase space metric and without requiring any special doctoring, we find that here too the scheme allows extracting a very small number of slow variables, necessary and sufficient to describe the dynamics of island sliding

Specification and site control of the permeability of the cover concrete: the Swiss approach

It is recognized that most damage to reinforced concrete structures is caused by insufficient durability rather than by low strength. In most cases, the quality and thickness of the cover concrete (covercrete) determine the service life of the structure. Since the quality of the covercrete is influenced, not only by the mix composition, but also by the placing and curing conditions, it is appropriate to measure the achieved properties on the structure rather than just on separately cast specimens. Swiss Standard SIA 262 on Concrete Construction recommends checking the impermeability of the cover concrete on site. With that aim, a non-destructive method to measure the air-permeability on site has been standardized (SIA 262/1 Annex E). A team of Swiss experts was appointed by the Swiss Federal Highway Administration (ASTRA) to prepare recommendations for specifying, measuring, and assessing the conformity of the air-permeability kT. This paper describes these recommendations covering: (a) specification of limiting values of kT as function of the exposure class; (b) sampling of the measurement points; (c) testing (including suitable temperature and moisture conditions); (d) evaluation of conformity with specified values; (e) expected impact on service life

Long-term evaluation of infliximab in the treatment of persistently active juvenile idiopathic arthritis refractory to conventional therapy

Objectives: To evaluate, in long-term open label prospective study, infliximab as therapeutic choice for Juvenile Idiopathic Arthritis (JIA) non responsive to conventional therapy. Methods: We enrolled to treat with infliximab 78 JIA patients (66 females, 12 males): the mean age was 20.7±7.1 years (median 20.9, range 5.4-34.9); mean JIA duration was 13.6±7.6 years (median 13.5, range 0.4-31.4). Infliximab, at dose of 3-10 mg/kg/infusion added to weekly subcutaneous Methotrexate or other previous DMARDs, was administered by intravenous infusions at weeks 0, 2, 6 and every 8 weeks thereafter. Chest X-ray, Mantoux's test, electrocardiogram were performed at baseline; laboratory tests and clinical evaluation were performed at each infusion. Response was evaluated according to ACR improvement criteria. Results: Mean treatment period was 21.6 months±18.8 (median 14.7, range 1.4-72.4). Just after first infusion most of patients reported significant improvement in pain, fatigue, morning stiffness. Infliximab is still successfully administered to 23 patients (29.5%); 55 (70.5%) patients suspended because of: inefficacy (7), infusion reactions (17), adverse events (9), disease flare-up after a period of effectiveness on synovitis, pain, and morning stiffness (19), remission (2), lack of compliance to treatment (1). Infusion reactions, like dyspnea, flushing, chills, headache, hypotension, anxiety, throat oedema, were observed in 29 patients (34.5%). Anti-DNA antibodies were present in 7 patients (none developed Systemic Lupus Eritematous). Conclusions: Infliximab showed impressive effectiveness treating refractory JIA, although most of patients had to discontinue treatment because of disease flare-up or adverse events. Infliximab may represent a good therapeutic choice in patients non-responders to Methotrexate

Usefulness of multimodality imaging approach in the diagnosis of mechanical prosthetic valve dysfunction

Background Although the long-term outcome of mechanical mitral and aortic prosthetic valve (M-PV, Ao-PV), PV dysfunction (PVD) remains a very serious complication associated with high morbidity and mortality. Thrombosis/pannus and paravalvular leak are the 2 main mechanisms of PVD. The diagnosis of PVD, based on clinical presentation may be challenging, but it is essential for referring the patient to the optimal treatment (clinical follow-up, thrombolysis, surgery). An integrated multimodality imaging approach, comprising several parameters by transthoracic echocardiography (TTE) and fluoroscopy (F), is mandatory to pursue the correct therapeutic pathway. Purpose This study aims to evaluate the incremental diagnostic value of combined TTE+F over each imaging modality alone in symptomatic pts with Ao-PV or M-PV and high suspicion of PVD. Methods 387 consecutive pts (63\ub111y, 213 Ao-PV, 173 M-PV) suspected for PVD, symptomatic for dyspnea, embolic events, fever or haemolysis were enrolled. All patients were imaged by TTE and F within 2 days after the admission to the hospital. TTE was defined positive for PVD in presence of intra/para-prosthetic regurgitation or high transprosthetic gradient (>20mmHg in Ao-PV, >8mmHg in M-PV) together with altered Doppler parameters (for Ao-PV: DVI <0.25, AT>95ms; for M-PV: Peak Mitral Velocity>2m/sec, VTIPrMV/VTILVO>2.5, PHT>130ms). F was defined positive for PVD when leaflet/s restriction occurs. PVD was confirmed by transoesophageal echocardiography (TOE) or positive response of thrombolysis (T), or surgical inspection (S). Results PVD was found in 46% (99/213) of Ao-PV and in 53% (91/173) of M-PV at TOE/T/S. Sensitivity (SE), specificity (SP), negative predictive value (NPV), positive predictive value (PPV) and diagnostic accuracy (ACC) for TTE, F and combined TTE+F are reported in Table. The integration of TTE+F data significantly improved ACC both for Ao-PV and M-PV. At ROC analysis, the combined model of TTE+F showed the highest AUC for the detection of PVD compared with TTE and F alone (Figure). Table 1. Comparison of diagnostic accuracy between TTE, F, and TTE+F TTE-Ao-PV (n=211) F-Ao_PV (n=204) TTE+F-Ao-PV (n=202) TTE-M-PV (n=172) F-M-PV (n=158) TTE+F-M-PV (n=157) SE / SP / NPV / PPV / ACC (%) 86 / 89 / 88 / 88 / 88 59 / 99 / 72 / 98 / 79 94 / 88 / 94 / 88 / 91 74 / 90 / 75 / 89 / 81 49 / 96 / 60 / 93 / 70 81 / 86 / 78 / 88 / 83 Figure 1. ROC curves Conclusions In patients with clinical suspicion of PVD, TTE and F are both valid tools to evaluate the PV performance. However, the combined model of TTE+F had a significant incremental value over TTE or F alone to diagnose the presence of PVD. This multimodality imaging approach allows to overcome several weaknesses of the TTE or F alone and consequently provides a prompt recognition of PVD even though TOE remains the gold standard to diagnose paravalvular Leak and non-obstructive thrombosis

Side effects of anti-TNFa therapy in juvenile idiopathic arthritis

Aim of the study: To report adverse events registered in our population affected by JIA and treated with anti-TNFαblockers. Methods: Ninety-five patients were enrolled to be treated with Etanercept, median age 14 years (range 4-34); median duration of therapy 12 months (range 1-40). 19 patients were als treated with MTX (median dose 12.5 mg/week).Fifty-six patients were enrolled to be treated with Infliximab associated with MTX (median dose of MTX 8.8mg/week),median age 23.2 years (range 7.8-34.9); median duration of therapy 20.1 months (range 1.4-60.4). All adverse events were divided in definitely, probably and possibly related to the biologic agent. Results: Side effects definitely related to Infliximab were the reactions to infusions and the Anti-dsDNA positivity. Side effects definitely related to Etanercept were severe headache and thrombocytopenia. Side effects probably correlated to both the biological agents were behavioural modifications and pain amplification syndrome. Probably correlated to the treatment with Etanercept was the onset of Crohn’s disease in 3 patients. Possibly correlated to the biological agents were the new onset or flare-up of Chronic Iridocyclitis and single cases of thyroideal cancer, hypoglossal nerve paralysis and a severe Cytomegalovirus pulmonary infection. No case of tuberculosis infection was registered during this study. Conclusions: Treatment with a TNFαantagonist seems to be associated with various adverse events. Some of them,like onset of Crohn’s disease, behavioural modifications are unusual and others, like pain amplification syndrome were never described before. Children and young adults affected by JIA should be monitored very carefully so as to limit as much as possible the risk of serious side effects on anti-TNFα therapy

Using machine learning and Biogeochemical-Argo (BGC-Argo) floats to assess biogeochemical models and optimize observing system design

Numerical models of ocean biogeochemistry are becoming the major tools used to detect and predict the impact of climate change on marine resources and to monitor ocean health. However, with the continuous improvement of model structure and spatial resolution, incorporation of these additional degrees of freedom into fidelity assessment has become increasingly challenging. Here, we propose a new method to provide information on the model predictive skill in a concise way. The method is based on the conjoint use of a k-means clustering technique, assessment metrics, and Biogeochemical-Argo (BGC-Argo) observations. The k-means algorithm and the assessment metrics reduce the number of model data points to be evaluated. The metrics evaluate either the model state accuracy or the skill of the model with respect to capturing emergent properties, such as the deep chlorophyll maximums and oxygen minimum zones. The use of BGC-Argo observations as the sole evaluation data set ensures the accuracy of the data, as it is a homogenous data set with strict sampling methodologies and data quality control procedures. The method is applied to the Global Ocean Biogeochemistry Analysis and Forecast system of the Copernicus Marine Service. The model performance is evaluated using the model efficiency statistical score, which compares the model–observation misfit with the variability in the observations and, thus, objectively quantifies whether the model outperforms the BGC-Argo climatology. We show that, overall, the model surpasses the BGC-Argo climatology in predicting pH, dissolved inorganic carbon, alkalinity, oxygen, nitrate, and phosphate in the mesopelagic and the mixed layers as well as silicate in the mesopelagic layer. However, there are still areas for improvement with respect to reducing the model–data misfit for certain variables such as silicate, pH, and the partial pressure of CO2 in the mixed layer as well as chlorophyll-a-related, oxygen-minimum-zone-related, and particulate-organic-carbon-related metrics. The method proposed here can also aid in refining the design of the BGC-Argo network, in particular regarding the regions in which BGC-Argo observations should be enhanced to improve the model accuracy via the assimilation of BGC-Argo data or process-oriented assessment studies. We strongly recommend increasing the number of observations in the Arctic region while maintaining the existing high-density of observations in the Southern Oceans. The model error in these regions is only slightly less than the variability observed in BGC-Argo measurements. Our study illustrates how the synergic use of modeling and BGC-Argo data can both provide information about the performance of models and improve the design of observing systems.</p