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

Pre-operational short-term forecasts for Mediterranean Sea biogeochemistry

Operational prediction of the marine environment is recognised as a fundamental research issue in Europe. We present a pre-operational implementation of a biogeochem- ical model for the pelagic waters of the Mediterranean Sea, developed within the framework of the MERSEA-IP Euro- pean project. The OPATM-BFM coupled model is the core of a fully automatic system that delivers weekly analyses and forecast maps for the Mediterranean Sea biogeochem- istry. The system has been working in its current configura- tion since April 2007 with successful execution of the fully automatic operational chain in 87% of the cases while in the remaining cases the runs were successfully accomplished af- ter operator intervention. A description of the system devel- oped and also a comparison of the model results with satel- lite data are presented, together with a measure of the model skill evaluated by means of seasonal target diagrams. Future studies will address the implementation of a data assimila- tion scheme for the biogeochemical compartment in order to increase the skill of the model’s performance

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

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

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

Proapoptotic effect of atorvastatin on stimulated rabbit smooth muscle cells

The in vitro and in vivo activity of atorvastatin and other 3-hydroxy-3-methylglutaryl coenzyme A (HMGCoA) reductase inhibitors (fluvastatin, pravastatin and simvastatin) has been investigated. Atorvastatin, fluvastatin, pravastatin and simvastatin caused a significant and dose-dependent (0.1-50 microM) reduction in cell multiplication of vascular smooth muscle cells (SMC) in cultures associated with the retardation of cycling cells in the G1 and G2/M compartments at 24 h, a phenomenon leading to apoptosis (programmed cell death) in several experimental in vitro models. The effects on the cell cycle resulted in a strong inhibition of cell proliferation at 48 h, followed by apoptosis when incubation was prolonged to 72 h as assessed by nuclei morphology and cytofluorimetric analysis of DNA. The apoptotic effect observed for the statins is completely prevented by the addition of exogenous mevalonate at a 100 microm concentration. in vivo SMC proliferation was stimulated by applying a silastic collar to the outside surface of carotid arteries in normocholesterolemic rabbits in the presence of an anatomically intact endothelium. The positioning of the collar promoted apoptosis in control vessels as assessed by Terminal Deoxynucleotidyl Transferase-dUTP-Biotin Nick-End Labeling (TUNEL) assay. The pre-treatment with 5 mg kg-1 per day of atorvastatin before collar insertion strongly increased the number of TUNEL-positive cells, suggesting a pro-apoptotic effect of HMGCoA reductase inhibitors also in vivo, even though cell DNA rearrangement still needs to be excluded. No apoptotic signal was detectable in sham operated arteries with no collar in either control or atorvastatin-treated rabbits. These data indicate that HMGCoA reductase inhibitors effect on the arterial wall may involve the modulation of both cell proliferation and programmed cell deaths supporting a possible role of statins in the prevention of early lesion and restenosis