The Emerging Role of Ofatumumab in the Treatment of Chronic Lymphocytic Leukemia

The treatment of chronic lymphocytic leukemia (CLL) has evolved over the past decade. Our better understanding of disease biology and risk stratification has allowed delivering more effective therapies. In fact, front-line chemoimmunotherapy has demonstrated improvement in overall survival when compared to chemotherapy in randomized studies. Yet, treatment of relapsed CLL remains challenging and few agents are effective in that setting. Ofatumumab (Ofa) is a humanized monoclonal antibody targeted against CD20 with demonstrable activity in rituximab-resistant CLL cell lines. This agent was recently approved for the treatment of relapsed/refractory CLL patients who have failed fludarabine and alemtuzumab. In this review, we provide a historical perspective on approaches to CLL as front-line and in the relapsed setting. We further summarize novel anti-CD20 antibodies with specific emphasis on ofa. We review studies that led to ofatumumab’s approval including pre-clinical data, trials using ofa in combination therapies, and adverse events/toxicities reported with this agent

Origins of the Ambient Solar Wind: Implications for Space Weather

The Sun's outer atmosphere is heated to temperatures of millions of degrees, and solar plasma flows out into interplanetary space at supersonic speeds. This paper reviews our current understanding of these interrelated problems: coronal heating and the acceleration of the ambient solar wind. We also discuss where the community stands in its ability to forecast how variations in the solar wind (i.e., fast and slow wind streams) impact the Earth. Although the last few decades have seen significant progress in observations and modeling, we still do not have a complete understanding of the relevant physical processes, nor do we have a quantitatively precise census of which coronal structures contribute to specific types of solar wind. Fast streams are known to be connected to the central regions of large coronal holes. Slow streams, however, appear to come from a wide range of sources, including streamers, pseudostreamers, coronal loops, active regions, and coronal hole boundaries. Complicating our understanding even more is the fact that processes such as turbulence, stream-stream interactions, and Coulomb collisions can make it difficult to unambiguously map a parcel measured at 1 AU back down to its coronal source. We also review recent progress -- in theoretical modeling, observational data analysis, and forecasting techniques that sit at the interface between data and theory -- that gives us hope that the above problems are indeed solvable.Comment: Accepted for publication in Space Science Reviews. Special issue connected with a 2016 ISSI workshop on "The Scientific Foundations of Space Weather." 44 pages, 9 figure

Production and Decay of D_1(2420)^0 and D_2^*(2460)^0

We have investigated $D^{+}\pi^{-}$ and $D^{*+}\pi^{-}$ final states and observed the two established $L=1$ charmed mesons, the $D_1(2420)^0$ with mass $2421^{+1+2}_{-2-2}$ MeV/c$^{2}$ and width $20^{+6+3}_{-5-3}$ MeV/c$^{2}$ and the $D_2^*(2460)^0$ with mass $2465 \pm 3 \pm 3$ MeV/c$^{2}$ and width $28^{+8+6}_{-7-6}$ MeV/c$^{2}$. Properties of these final states, including their decay angular distributions and spin-parity assignments, have been studied. We identify these two mesons as the $j_{light}=3/2$ doublet predicted by HQET. We also obtain constraints on {\footnotesize $\Gamma_S/(\Gamma_S + \Gamma_D)$} as a function of the cosine of the relative phase of the two amplitudes in the $D_1(2420)^0$ decay.Comment: 15 pages in REVTEX format. hardcopies with figures can be obtained by sending mail to: [email protected]

Measurement of the branching fraction for Υ(1S)→τ+τ−\Upsilon (1S) \to \tau^+ \tau^-

We have studied the leptonic decay of the $\Upsilon (1S)$ resonance into tau pairs using the CLEO II detector. A clean sample of tau pair events is identified via events containing two charged particles where exactly one of the particles is an identified electron. We find $B(\Upsilon(1S) \to \tau^+ \tau^-) = (2.61~\pm~0.12~{+0.09\atop{-0.13}})$. The result is consistent with expectations from lepton universality.Comment: 9 pages, RevTeX, two Postscript figures available upon request, CLNS 94/1297, CLEO 94-20 (submitted to Physics Letters B

Measurement of the Decay Asymmetry Parameters in Λc+→Λπ+\Lambda_c^+ \to \Lambda\pi^+ and Λc+→Σ+π0\Lambda_c^+ \to \Sigma^+\pi^0

We have measured the weak decay asymmetry parameters (\aLC ) for two \LC\ decay modes. Our measurements are \aLC = -0.94^{+0.21+0.12}_{-0.06-0.06} for the decay mode $\Lambda_c^+ \to \Lambda\pi^+$ and \aLC = -0.45\pm 0.31 \pm 0.06 for the decay mode $\Lambda_c \to \Sigma^+\pi^0$. By combining these measurements with the previously measured decay rates, we have extracted the parity-violating and parity-conserving amplitudes. These amplitudes are used to test models of nonleptonic charmed baryon decay.Comment: 11 pages including the figures. Uses REVTEX and psfig macros. Figures as uuencoded postscript. Also available as http://w4.lns.cornell.edu/public/CLNS/1995/CLNS95-1319.p

Observation of the Ξc+\Xi_c^+ Charmed Baryon Decays to Σ+K−π+\Sigma^+ K^-\pi^+, Σ+Kˉ∗0\Sigma^+ \bar{K}^{*0}, and ΛK−π+π+\Lambda K^-\pi^+\pi^+

We have observed two new decay modes of the charmed baryon $\Xi_c^+$ into $\Sigma^+ K^-\pi^+$ and $\Sigma^+ \bar{K}^{*0}$ using data collected with the CLEO II detector. We also present the first measurement of the branching fraction for the previously observed decay mode $\Xi_c^+\to\Lambda K^-\pi^+\pi^+$. The branching fractions for these three modes relative to $\Xi_c^+\to\Xi^-\pi^+\pi^+$ are measured to be $1.18 \pm 0.26 \pm 0.17$, $0.92 \pm 0.27 \pm 0.14$, and $0.58 \pm 0.16 \pm 0.07$, respectively.Comment: 12 page uuencoded postscript file, postscript file also available through http://w4.lns.cornell.edu/public/CLN

Spectral and Timing Analysis of NuSTAR and Swift/XRT Observations of the X-Ray Transient MAXI J0637-430

We present results for the first observed outburst from the transient X-ray binary source MAXI J0637-430. This study is based on eight observations from the Nuclear Spectroscopic Telescope Array (NuSTAR) and six observations from the Neil Gehrels Swift Observatory X-Ray Telescope (Swift/XRT) collected from 2019 November 19 to 2020 April 26 as the 3-79 keV source flux declined from 8.2 × 10-10 to 1.4 × 10-12 erg cm-2 s-1. We see the source transition from a soft state with a strong disk-blackbody component to a hard state dominated by a power-law or thermal Comptonization component. NuSTAR provides the first reported coverage of MAXI J0637-430 above 10 keV, and these broadband spectra show that a two-component model does not provide an adequate description of the soft-state spectrum. As such, we test whether blackbody emission from the plunging region could explain the excess emission. As an alternative, we test a reflection model that includes a physical Comptonization continuum. Finally, we also test a spectral component based on reflection of a blackbody illumination spectrum, which can be interpreted as a simple approximation to the reflection produced by returning disk radiation due to the bending of light by the strong gravity of the black hole. We discuss the physical implications of each scenario and demonstrate the value of constraining the source distance