Temporal trends in the starting of insulin therapy in type 2 diabetes in Italy: data from the AMD Annals initiative.

AIMS: Opportunities and needs for starting insulin therapy in Type 2 diabetes (T2D) have changed overtime. We evaluated clinical characteristics of T2D subjects undergoing the first insulin prescription during a 15-year-observation period in the large cohort of the AMD Annals Initiative in Italy. METHODS: Data on clinical and laboratory variables, complications and concomitant therapies and the effects on glucose control after 12 months were evaluated in T2D patients starting basal insulin as add-on to oral/non-insulin injectable agents, and in those starting fast-acting in add-on to basal insulin therapy in three 5-year periods (2005-2019). RESULTS: We evaluated data from 171.688 T2D subjects who intensified therapy with basal insulin and 137.225 T2D patients who started fast-acting insulin. Overall, intensification with insulin occurred progressively earlier over time in subjects with shorter disease duration. Moreover, the percentage of subjects with HbA1c levels > 8% at the time of basal insulin initiation progressively decreased. The same trend was observed for fast-acting formulations. Clinical characteristics of subjects starting insulin did not change in the three study-periods, although all major risk factors improved overtime. After 12 months from the starting of basal or fast-acting insulin therapy, mean HbA1c levels decreased in all the three investigated time-periods, although mean HbA1c levels remained above the recommended target. CONCLUSIONS: In this large cohort of T2D subjects, a progressively earlier start of insulin treatment was observed during a long observation period, suggesting a more proactive prescriptive approach. However, after 12 months from insulin prescription, in many patients, HbA1c levels were still out-of-target.

Solitons in Inhomogeneous Gauge Potentials: Integrable and Nonintegrable Dynamics.

We introduce an exactly integrable nonlinear model describing the dynamics of spinor solitons in space-dependent matrix gauge potentials of rather general types. The model is shown to be gauge equivalent to the integrable system of vector nonlinear Schrödinger equations known as the Manakov model. As an example we consider a self-attractive Bose-Einstein condensate with random spin-orbit coupling (SOC). If Zeeman splitting is also included, the system becomes nonintegrable. We illustrate this by considering the random walk of a soliton in a disordered SOC landscape. While at zero Zeeman splitting the soliton moves without scattering along linear trajectories in the random SOC landscape; at nonzero splitting it exhibits strong scattering by the SOC inhomogeneities. For a large Zeeman splitting, the integrability is restored. In this sense, the Zeeman splitting serves as a parameter controlling the crossover between two different integrable limits.

Self-Bound Quantum Droplets of Atomic Mixtures in Free Space.

Self-bound quantum droplets are a newly discovered phase in the context of ultracold atoms. In this Letter, we report their experimental realization following the original proposal by Petrov [Phys. Rev. Lett. 115, 155302 (2015)PRLTAO0031-900710.1103/PhysRevLett.115.155302], using an attractive bosonic mixture. In this system, spherical droplets form due to the balance of competing attractive and repulsive forces, provided by the mean-field energy close to the collapse threshold and the first-order correction due to quantum fluctuations. Thanks to an optical levitating potential with negligible residual confinement, we observe self-bound droplets in free space, and we characterize the conditions for their formation as well as their size and composition. This work sets the stage for future studies on quantum droplets, from the measurement of their peculiar excitation spectrum to the exploration of their superfluid nature.

Dynamics of Spin-Orbit Coupled Bose-Einstein Condensates in a Random Potential.

Disorder plays a crucial role in spin dynamics in solids and condensed matter systems. We demonstrate that for a spin-orbit coupled Bose-Einstein condensate in a random potential two mechanisms of spin evolution that can be characterized as "precessional" and "anomalous" are at work simultaneously. The precessional mechanism, typical for solids, is due to the condensate displacement. The unconventional anomalous mechanism is due to the spin-dependent velocity producing the distribution of the condensate spin polarization. The condensate expansion is accompanied by a random displacement and fragmentation, where it becomes sparse, as clearly revealed in the spin dynamics. Thus, different stages of the evolution can be characterized by looking at the condensate spin.

Vibrational mode multiplexing of ultracold atoms.

Sending multiple messages on qubits encoded in different vibrational modes of cold atoms or ions along a transmission waveguide requires us to merge first and then separate the modes at input and output ends. Similarly, different qubits can be stored in the modes of a trap and be separated later. We design the fast splitting of a harmonic trap into an asymmetric double well so that the initial ground vibrational state becomes the ground state of one of two final wells, and the initial first excited state becomes the ground state of the other well. This might be done adiabatically by slowly deforming the trap. We speed up the process by inverse engineering a double-function trap using dynamical invariants. The separation (demultiplexing) followed by an inversion of the asymmetric bias and then by the reverse process (multiplexing) provides a population inversion protocol based solely on trap reshaping.

Observation of subdiffusion in a disordered interacting system.

We study the transport dynamics of matter-waves in the presence of disorder and nonlinearity. An atomic Bose-Einstein condensate that is localized in a quasiperiodic lattice in the absence of atom-atom interaction shows instead a slow expansion with a subdiffusive behavior when a controlled repulsive interaction is added. The measured features of the subdiffusion are compared to numerical simulations and a heuristic model. The observations confirm the nature of subdiffusion as interaction-assisted hopping between localized states and highlight a role of the spatial correlation of the disorder.

Results by motor cortex stimulation in treatment of focal dystonia, Parkinson's disease and post-ictal spasticity. The experience of the Italian Study Group of the Italian Neurosurgical Society.

Extradural motor cortex stimulation has been employed in cases of Parkinson's disease (PD), fixed dystonia (FD) and spastic hemiparesis (SH) following cerebral stroke. Symptoms of PD are improved by EMCS: results were evaluated on the basis of the UPDRS and statistically analysed. In PD EMCS is less efficacious than bilateral subthalamic nucleus (STN) stimulation, but it may be safely employed in patients not eligible for deep brain stimulation (DBS). The most rewarding effect is the improvement, in severely affected patients, of posture and gait. FD, unresponsive to bilateral pallidal stimulation, has been relieved by EDMS. In SH reduction of spasticiy by EMCS allows improvement of the motor function.

Identification of a glucocorticoid response element in the human gamma chain fibrinogen promoter.

The effect of the synthetic glucocorticoid hormone dexamethasone on human gamma chain fibrinogen gene expression was examined. The whole promoter region of 3.8 kb of this gene and progressive 5'-deletions were inserted into a promoterless expression vector, upstream of the luciferase gene and transiently transfected into the human hepatoma HepG2 cells, in the presence or in the absence of dexamethasone stimulation. Deletion analysis allowed to identify a region located between -1359 and -954 bp upstream from the transcription start site, involved in hormone inducibility. On the basis of a computer-assisted analysis, a putative GRE was found in this region at bases -1116 to -1102. Specific point mutations eliminating this putative GRE led to complete loss of glucocorticoid inducibility, thus indicating its functional role. Binding of the rat glucocorticoid receptor to this site was demonstrated by mobility-shift assays.

Collective oscillations of two colliding bose-einstein condensates

Two 87Rb condensates ( F = 2, m(f) = 2, and m(f) = 1) are produced in highly displaced harmonic traps and the collective dynamical behavior is investigated. The mutual interaction between the two condensates is evidenced in the center-of-mass oscillations as a frequency shift of 6.4(3)%. Calculations based on a mean-field theory well describe the observed effects of periodical collisions both on the center-of-mass motion and on the shape oscillations.

Atom interferometry with a weakly interacting Bose-Einstein condensate.

We demonstrate the operation of an atom interferometer based on a weakly interacting Bose-Einstein condensate. We strongly reduce the interaction induced decoherence that usually limits interferometers based on trapped condensates by tuning the s-wave scattering length almost to zero via a magnetic Feshbach resonance. We employ a 39K condensate trapped in an optical lattice, where Bloch oscillations are forced by gravity. The fine-tuning of the scattering length down to 0.1 a_(0) and the micrometric sizes of the atomic sample make our system a very promising candidate for measuring forces with high spatial resolution. Our technique can be in principle extended to other measurement schemes opening new possibilities in the field of trapped atom interferometry.

39K Bose-Einstein condensate with tunable interactions.

We produce a Bose-Einstein condensate of 39K atoms. Condensation of this species with a naturally small and negative scattering length is achieved by a combination of sympathetic cooling with 87Rb and direct evaporation, exploiting the magnetic tuning of both inter- and intraspecies interactions at Feshbach resonances. We explore the tunability of the self-interactions by studying the expansion and the stability of the condensate. We find that a 39K condensate is interesting for future experiments requiring a weakly-interacting Bose gas.

Bose-Einstein condensate in a random potential.

An optical speckle potential is used to investigate the static and dynamic properties of a Bose-Einstein condensate in the presence of disorder. With small levels of disorder, stripes are observed in the expanded density profile and strong damping of dipole and quadrupole oscillations is seen. Uncorrelated frequency shifts of the two modes are measured and are explained using a sum-rules approach and by the numerical solution of the Gross-Pitaevskii equation.

Effect of optical disorder and single defects on the expansion of a Bose-Einstein condensate in a one-dimensional waveguide.

We investigate the one-dimensional expansion of a Bose-Einstein condensate in an optical guide in the presence of a random potential created with optical speckles. With the speckle the expansion of the condensate is strongly inhibited. A detailed investigation has been carried out varying the experimental conditions and checking the expansion when a single optical defect is present. The experimental results are in good agreement with numerical calculations based on the Gross-Pitaevskii equation.

Spatial interference of coherent atomic waves by manipulation of the internal quantum state.

A trapped >(87)Rb Bose-Einstein condensate is initially put into a superposition of two internal states. Under the effect of gravity and by means of a second transition, we prepare two vertically displaced condensates in the same internal state. These constitute two coherent sources of matter waves with adjustable spatial separation. Fringe patterns, observed after free expansion, are associated with the interplay between internal and external degrees of freedom and substantially agree with those for a double-slit experiment.

Two atomic species superfluid.

We produce a quantum degenerate mixture composed by two Bose-Einstein condensates of different atomic species, 41K and 87Rb. We study the dynamics of the superfluid system in an elongated magnetic trap, where off-axis collisions between the two interacting condensates induce scissorlike oscillations.

Time-domain atom interferometry across the threshold for Bose-Einstein condensation.

We have performed time-domain interferometry experiments with matter waves trapped in a harmonic potential above and below the Bose-Einstein phase transition, by means of the method of separated oscillating fields, with a variable time delay T. We observe the oscillations of the population between two internal Zeeman states versus the delay T to be rapidly depleted both below and slightly above Bose-Einstein condensation. We give a quantitative explanation in terms of the phase evolution due to the entanglement between the internal and external degrees of freedom.

Observation of dynamical instability for a Bose-Einstein condensate in a moving 1D optical lattice.

We have experimentally studied the unstable dynamics of a harmonically trapped Bose-Einstein condensate loaded into a 1D moving optical lattice. The lifetime of the condensate in such a potential exhibits a dramatic dependence on the quasimomentum state. This is unambiguously attributed to the onset of dynamical instability, after a comparison with the predictions of the Gross-Pitaevskii theory. Deeply in the unstable region we observe the rapid appearance of complex structures in the atomic density profile, as a consequence of the condensate phase uniformity breakdown.

Optically induced lensing effect on a Bose-Einstein condensate expanding in a moving lattice.

We report the experimental observation of a lensing effect on a Bose-Einstein condensate expanding in a moving 1D optical lattice. The effect of the periodic potential can be described by an effective mass dependent on the condensate quasimomentum. By changing the velocity of the atoms in the frame of the optical lattice, we induce a focusing of the condensate along the lattice direction. The experimental results are compared with the numerical predictions of an effective 1D theoretical model. In addition, a precise band spectroscopy of the system is carried out by looking at the real-space propagation of the atomic wave packet in the optical lattice.

Nerve growth factor cooperates with p185(HER2) in activating growth of human breast carcinoma cells.

Nerve growth factor (NGF) is known to exert a mitogenic effect on human breast cancer cells through proto-TrkA activation. Reverse transcriptase-PCR analysis of proto-TrkA expression in human breast carcinoma specimens and cell lines revealed trkA transcript in 12 of 14 human breast carcinoma specimens and in all of four cell lines tested. While cytofluorimetric and Western blot analysis indicated proto-TrkA expression in three of the four cell lines, NGF stimulated growth in only two of the three positive cell lines. Inhibition of NGF-induced MAPK activation by an antibody directed against the extracellular domain of TrkA but not by an inhibitor of TrkA phosphorylation demonstrated the requirement of NGF binding but not of proto-TrkA kinase activity for MAPK activation, suggesting the recruitment of another kinase for transmission of the mitogenic signaling. Indeed, NGF induced tyrosine phosphorylation and stimulated kinase activity of p185(HER2), a kinase receptor of the HER family. A TrkA phosphorylation inhibitor did not affect this activation. Moreover, the two receptors were coprecipitated by antibodies directed against proto-TrkA and p185(HER2). Down-modulation of p185(HER2) expression in a breast carcinoma line transfected with a construct containing an anti-p185(HER2) antibody sequence and expressing proto-TrkA impaired NGF-induced MAPK activation and proliferation. Together these data show that in cells expressing low levels of TrkA such as breast carcinoma cells, NGF must recruit other overexpressed receptors such as p185(HER2) in order to generate a biological signal that can induce breast cancer cell growth.