Ofatumumab and high-dose methylprednisolone for the treatment of patients with relapsed or refractory chronic lymphocytic leukemia.

Ofatumumab is a humanized anti-CD20 monoclonal antibody that has been approved by the FDA for the treatment of patients with chronic lymphocytic leukemia. We conducted a phase II single-arm study at a single center. Patients received ofatumumab (300 mg then 1000 mg weekly for 12 weeks) and methylprednisolone (1000 mg/m(2) for 3 days of each 28-day cycle). Twenty-one patients enrolled, including 29% with unfavorable cytogenetics (del17p or del11q). Ninety percent of patients received the full course without dose reductions or delays. The overall response rate was 81% (17/21) with 5% complete response, 10% nodular partial response, 67% partial response, 14% stable disease and 5% progressive disease. After a median follow-up of 31 months, the median progression-free survival was 9.9 months and the median time to next treatment was 12.1 months. The median overall survival has not yet been reached. The combination of high-dose methylprednisolone and ofatumumab is an effective and tolerable treatment regimen. This regimen may be useful for patients who are unable to tolerate more aggressive therapies, or have not responded to other treatments

Rituximab in combination with high-dose methylprednisolone for the treatment of chronic lymphocytic leukemia.

We observed that high-dose methylprednisolone (HDMP) and rituximab was well tolerated and had promising activity when used in combination to treat patients with fludarabine-refractory chronic lymphocytic leukemia (CLL). This prompted us to evaluate the use of these agents in frontline therapy. A total of 28 patients with a median age of 65 years enrolled in this study. Patients received HDMP at 1 g/m(2) each day for 3 days during each of the three 4-week cycles together with rituximab and prophylactic antimicrobial therapy. The treatment was well tolerated with few adverse events of grade III or higher. The overall response rate was 96% (N=27). Nine patients (32%) achieved a complete remission (CR), two of which were without detectable minimal residual disease (MRD). Six patients with MRD received consolidation with alemtuzumab; five of these patients achieved an MRD-negative CR. With over 3 years of follow-up median progression-free survival was 30.3 months with only 39% of patients requiring additional therapy, and an overall survival was 96%. This study demonstrates that HDMP and rituximab is an effective nonmyelosuppressive treatment combination for patients with CLL that warrants consideration particularly for patients with limited myeloid reserve that might not tolerate standard treatment regimens

Vestibular loss disrupts visual reactivity in the alpha EEG rhythm.

The alpha rhythm is a dominant electroencephalographic oscillation relevant to sensory-motor and cognitive function. Alpha oscillations are reactive, being for example enhanced by eye closure, and suppressed following eye opening. The determinants of inter-individual variability in reactivity in the alpha rhythm (e.g. changes with amplitude following eye closure) are not fully understood despite the physiological and clinical applicability of this phenomenon, as indicated by the fact that ageing and neurodegeneration reduce reactivity. Strong interactions between visual and vestibular systems raise the theoretical possibility that the vestibular system plays a role in alpha reactivity. To test this hypothesis, we applied electroencephalography in sitting and standing postures in 15 participants with reduced vestibular function (bilateral vestibulopathy, median age = 70 years, interquartile range = 51-77 years) and 15 age-matched controls. We found participants with reduced vestibular function showed less enhancement of alpha electroencephalography power on eye closure in frontoparietal areas, compared to controls. In participants with reduced vestibular function, video head impulse test gain - as a measure of residual vestibulo-ocular reflex function - correlated with reactivity in alpha power across most of the head. Greater reliance on visual input for spatial orientation ('visual dependence', measured with the rod-and-disc test) correlated with less alpha enhancement on eye closure only in participants with reduced vestibular function, and this was partially moderated by video head impulse test gain. Our results demonstrate for the first time that vestibular function influences alpha reactivity. The results are partly explained by the lack of ascending peripheral vestibular input but also by central reorganisation of processing relevant to visuo-vestibular judgements

Classical and Quantum Solitons in the Symmetric Space Sine-Gordon Theories

We construct the soliton solutions in the symmetric space sine-Gordon theories. The latter are a series of integrable field theories in 1+1-dimensions which are associated to a symmetric space F/G, and are related via the Pohlmeyer reduction to theories of strings moving on symmetric spaces. We show that the solitons are kinks that carry an internal moduli space that can be identified with a particular co-adjoint orbit of the unbroken subgroup H of G. Classically the solitons come in a continuous spectrum which encompasses the perturbative fluctuations of the theory as the kink charge becomes small. We show that the solitons can be quantized by allowing the collective coordinates to be time-dependent to yield a form of quantum mechanics on the co-adjoint orbit. The quantum states correspond to symmetric tensor representations of the symmetry group H and have the interpretation of a fuzzy geometric version of the co-adjoint orbit. The quantized finite tower of soliton states includes the perturbative modes at the base.Comment: 53 pages, additional comments and small errors corrected, final journal versio

On the perturbative S-matrix of generalized sine-Gordon models

Motivated by its relation to the Pohlmeyer reduction of AdS_5 x S^5 superstring theory we continue the investigation of the generalized sine-Gordon model defined by SO(N+1)/SO(N) gauged WZW theory with an integrable potential. Extending our previous work (arXiv:0912.2958) we compute the one-loop two-particle S-matrix for the elementary massive excitations. In the N = 2 case corresponding to the complex sine-Gordon theory it agrees with the charge-one sector of the quantum soliton S-matrix proposed in hep-th/9410140. In the case of N > 2 when the gauge group SO(N) is non-abelian we find a curious anomaly in the Yang-Baxter equation which we interpret as a gauge artifact related to the fact that the scattered particles are not singlets under the residual global subgroup of the gauge group

The Relativistic Avatars of Giant Magnons and their S-Matrix

The motion of strings on symmetric space target spaces underlies the integrability of the AdS/CFT correspondence. Although these theories, whose excitations are giant magnons, are non-relativistic they are classically equivalent, via the Polhmeyer reduction, to a relativistic integrable field theory known as a symmetric space sine-Gordon theory. These theories can be formulated as integrable deformations of gauged WZW models. In this work we consider the class of symmetric spaces CP^{n+1} and solve the corresponding generalized sine-Gordon theories at the quantum level by finding the exact spectrum of topological solitons, or kinks, and their S-matrix. The latter involves a trignometric solution of the Yang-Baxer equation which exhibits a quantum group symmetry with a tower of states that is bounded, unlike for magnons, as a result of the quantum group deformation parameter q being a root of unity. We test the S-matrix by taking the semi-classical limit and comparing with the time delays for the scattering of classical solitons. We argue that the internal CP^{n-1} moduli space of collective coordinates of the solitons in the classical theory can be interpreted as a q-deformed fuzzy space in the quantum theory. We analyse the n=1 case separately and provide a further test of the S-matrix conjecture in this case by calculating the central charge of the UV CFT using the thermodynamic Bethe Ansatz.Comment: 33 pages, important correction to S-matrix to ensure crossing symmetr

What do γ\gamma-ray bursts look like?

There have been great and rapid progresses in the field of $\gamma$-ray bursts (denoted as GRBs) since BeppoSAX and other telescopes discovered their afterglows in 1997. Here, we will first give a brief review on the observational facts of GRBs and direct understanding from these facts, which lead to the standard fireball model. The dynamical evolution of the fireball is discussed, especially a generic model is proposed to describe the whole dynamical evolution of GRB remnant from highly radiative to adiabatic, and from ultra-relativistic to non-relativistic phase. Then, Various deviations from the standard model are discussed to give new information about GRBs and their environment. In order to relax the energy crisis, the beaming effects and their possible observational evidences are also discussed in GRB's radiations.Comment: 10 pages, Latex. Invited talk at the Pacific Rim Conference on Stellar Astrophysics, Hong Kong, China, Aug. 199

Local Optical Probe of Motion and Stress in a multilayer graphene NEMS

Nanoelectromechanical systems (NEMSs) are emerging nanoscale elements at the crossroads between mechanics, optics and electronics, with significant potential for actuation and sensing applications. The reduction of dimensions compared to their micronic counterparts brings new effects including sensitivity to very low mass, resonant frequencies in the radiofrequency range, mechanical non-linearities and observation of quantum mechanical effects. An important issue of NEMS is the understanding of fundamental physical properties conditioning dissipation mechanisms, known to limit mechanical quality factors and to induce aging due to material degradation. There is a need for detection methods tailored for these systems which allow probing motion and stress at the nanometer scale. Here, we show a non-invasive local optical probe for the quantitative measurement of motion and stress within a multilayer graphene NEMS provided by a combination of Fizeau interferences, Raman spectroscopy and electrostatically actuated mirror. Interferometry provides a calibrated measurement of the motion, resulting from an actuation ranging from a quasi-static load up to the mechanical resonance while Raman spectroscopy allows a purely spectral detection of mechanical resonance at the nanoscale. Such spectroscopic detection reveals the coupling between a strained nano-resonator and the energy of an inelastically scattered photon, and thus offers a new approach for optomechanics

Long gamma-ray bursts and core-collapse supernovae have different environments

When massive stars exhaust their fuel they collapse and often produce the extraordinarily bright explosions known as core-collapse supernovae. On occasion, this stellar collapse also powers an even more brilliant relativistic explosion known as a long-duration gamma-ray burst. One would then expect that long gamma-ray bursts and core-collapse supernovae should be found in similar galactic environments. Here we show that this expectation is wrong. We find that the long gamma-ray bursts are far more concentrated on the very brightest regions of their host galaxies than are the core-collapse supernovae. Furthermore, the host galaxies of the long gamma-ray bursts are significantly fainter and more irregular than the hosts of the core-collapse supernovae. Together these results suggest that long-duration gamma-ray bursts are associated with the most massive stars and may be restricted to galaxies of limited chemical evolution. Our results directly imply that long gamma-ray bursts are relatively rare in galaxies such as our own Milky Way.Comment: 27 pages, 4 figures, submitted to Nature on 22 August 2005, revised 9 February 2006, online publication 10 May 2006. Supplementary material referred to in the text can be found at http://www.stsci.edu/~fruchter/GRB/locations/supplement.pdf . This new version contains minor changes to match the final published versio