Stability change of Fourth-Order Resonance with application to Multi-Turn Extraction Schemes

Recently, a novel multi-turn extraction scheme was proposed, based on particle trapping inside stable resonances. Numerical simulations and experimental tests conirmed the feasibility of such a scheme for low order resonances. While the 3rd order resonance is generically unstable and those higher than 4th order are generically stable, the 4th order resonance can be either stable or unstable depending on the details of the system under consideration. By means of the normal form approach a general formula to control the stability of the 4th order resonance is derived. Numerical simulations confirm the analytical results and show that by crossing the unstable 4th order resonance the region around the centre of phase space is depleted and particles are trapped only in the four stable islands. This indicates that a four-turn extraction could be envisaged based on this technique

The social cost of rheumatoid arthritis in Italy: the results of an estimation exercise.

The objective of this study is to estimate the mean annual social cost per adult person and the total social cost of rheumatoid arthritis (RA) in Italy. A literature review was performed by searching primary economic studies on adults in order to collect cost data of RA in Italy in the last decade. The review results were merged with data of institutional sources for estimating - following the methodological steps of the cost of illness analysis - the social cost of RA in Italy. The mean annual social cost of RA was € 13,595 per adult patient in Italy. Affecting 259,795 persons, RA determines a social cost of € 3.5 billions in Italy. Non-medical direct cost and indirect cost represent the main cost items (48% and 31%) of the total social cost of RA in Italy. Based on these results, it appears evident that the assessment of the economic burden of RA solely based on direct medical costs evaluation gives a limited view of the phenomenon

Analysis of Round Off Errors with Reversibility Test as a Dynamical Indicator

We compare the divergence of orbits and the reversibility error for discrete time dynamical systems. These two quantities are used to explore the behavior of the global error induced by round off in the computation of orbits. The similarity of results found for any system we have analysed suggests the use of the reversibility error, whose computation is straightforward since it does not require the knowledge of the exact orbit, as a dynamical indicator. The statistics of fluctuations induced by round off for an ensemble of initial conditions has been compared with the results obtained in the case of random perturbations. Significant differences are observed in the case of regular orbits due to the correlations of round off error, whereas the results obtained for the chaotic case are nearly the same. Both the reversibility error and the orbit divergence computed for the same number of iterations on the whole phase space provide an insight on the local dynamical properties with a detail comparable with other dynamical indicators based on variational methods such as the finite time maximum Lyapunov characteristic exponent, the mean exponential growth factor of nearby orbits and the smaller alignment index. For 2D symplectic maps the differentiation between regular and chaotic regions is well full-filled. For 4D symplectic maps the structure of the resonance web as well as the nearby weakly chaotic regions are accurately described.Comment: International Journal of Bifurcation and Chaos, 201

Perturbation Theory and Control in Classical or Quantum Mechanics by an Inversion Formula

We consider a perturbation of an ``integrable'' Hamiltonian and give an expression for the canonical or unitary transformation which ``simplifies'' this perturbed system. The problem is to invert a functional defined on the Lie- algebra of observables. We give a bound for the perturbation in order to solve this inversion. And apply this result to a particular case of the control theory, as a first example, and to the ``quantum adiabatic transformation'', as another example.Comment: Version 8.0. 26 pages, Latex2e, final version published in J. Phys.

Clinical and biochemical response to neridronate treatment in a patient with osteoporosis-pseudoglioma syndrome (OPPG)

Osteoporosis-pseudoglioma syndrome (OPPG) is a rare autosomal recessive syndrome characterized by juvenile-onset osteoporosis and ocular abnormalities due to a low-density lipoprotein receptor-related protein 5 (LRP5) gene mutation. Treatment with bisphosphonates, particularly with pamidronate and risedronate, has been reported to be of some efficacy in this condition. We report on a patient with OPPG due to an LRP5 gene mutation, who showed an encouraging response after a 36-month period of neridronate therapy. We report a case of a patient treated with bisphosphonates. Bisphosphonates should be administered in OPPG patients as a first-line therapy during early childhood

Serum creatine kinase isoenzymes in children with osteogenesis imperfecta

This study evaluates serum creatine kinase isoenzyme activity in children with osteogenesis imperfecta to determine its usefulness as a biochemical marker during treatment with bisphosphonate. The changes of creatine kinase (CK) isoenzyme activity during and after discontinuation therapy were observed. These results could be useful in addressing over-treatment risk prevention. Introduction The brain isoenzyme of creatine kinase (CKbb) is highly expressed in mature osteoclasts during osteoclastogenesis, thus plays an important role in bone resorption. We previously identified high serum CKbb levels in 18 children with osteogenesis imperfect (OI) type 1 treated for 1 year with bisphosphonate (neridronate). In the present study, serum CK isoenzymes were evaluated in the same children with continuous versus discontinued neridronate treatment over a further 2-year follow-up period. Methods This study included 18 children with OI type 1, 12 with continued (group A) and 6 with ceased (group B) neridronate treatment. Auxological data, serum biochemical markers of bone metabolism, bone mineral density z-score, and serum total CK and isoenzyme activities were determined in both groups. Results Serum CKbb was progressively and significantly increased in group A (p < 0.004) but rapidly decreased to undetectable levels in group B. In both groups, the cardiac muscle creatine kinase isoenzyme (CKmb) showed a marked decrease, while serum C-terminal telopeptide (CTx) levels were almost unchanged. Conclusions This study provides evidence of the cumulative effect of neridronate administration in increasing serum CKbb levels and the reversible effect after its discontinuation. This approach could be employed for verifying the usefulness of serum CKbb as a biochemical marker in patients receiving prolonged bisphosphonate treatment. Moreover, the decreased serum CKmb levels suggest a systemic effect of these drugs

Systemic lupus erythematosus and the economic perspective: a systematic literature review and points to consider

Systemic lupus erythematosus (SLE) is a chronic, disabling, progressive disease, with many associated comorbidities, affecting patients during prime working years resulting in a high economic burden on society, producing high direct, indirect and intangible costs. In this article, our goals are two-fold. First, we review and discuss studies published in the period 2002–2012 concerning costs of SLE and point out gaps in the published literature. Second, we propose further research studies to advance our understanding of the economic perspective in SLE in the current area of new and emerging therapies. The literature evaluating disease costs in SLE remains limited and to date has only included a small number of countries. Despite these limitations, available studies indicate that SLE has significant socio-economic ramifications. Future studies are needed, especially to assess novel biologic therapies which have been made available or currently under investigation for SLE. An interesting approach in these new economic evaluations in SLE may be represented by the selection of the targets of the treatment to include in the cost-effectiveness and cost-utility analyses. Future treat-to-target strategies will likely include evaluation of their pharmacoeconomic implications

3D solutions of the Poisson-Vlasov equations for a charged plasma and particle-core model in a line of FODO cells

We consider a charged plasma of positive ions in a periodic focusing channel of quadrupolar magnets in the presence of RF cavities. The ions are bunched into charged triaxial ellipsoids and their description requires the solution of a fully 3D Poisson-Vlasov equation. We also analyze the trajectories of test particles in the exterior of the ion bunches in order to estimate their diffusion rate. This rate is relevant for a high intensity linac (TRASCO project). A numerical PIC scheme to integrate the Poisson-Vlasov equations in a periodic focusing system in 2 and 3 space dimensions is presented. The scheme consists of a single particle symplectic integrator and a Poisson solver based on FFT plus tri-diagonal matrix inversion. In the 2D version arbitrary boundary conditions can be chosen. Since no analytical self-consistent 3D solution is known, we chose an initial Neuffer-KV distribution in phase space, whose electric field is close to the one generated by a uniformly filled ellipsoid. For a matched (periodic) beam the orbits of test particles moving in the field of an ellipsoidal bunch, whose semi-axis satisfy the envelope equations, is similar to the orbits generated by the self-consistent charge distribition obtained from the PIC simulation, even though it relaxes to a Fermi-Dirac-like distribution. After a transient the RMS radii and emittances have small amplitude oscillations. The PIC simulations for a mismatched (quasiperiodic) beam are no longer comparable with the ellipsoidal bunch model even though the qualitative behavior is the same, namely a stronger diffusion due to the increase of resonances