Can the 126 GeV boson be a pseudoscalar?

We test the possibility that the newly-discovered 126 GeV boson is a pseudoscalar by examining the correlations among the loop-induced pseudoscalar decay branching fractions to $\gamma\gamma$, $ZZ^*$, $Z\gamma$, and $WW^*$ final states in a model-independent way. These four decays are controlled by only two effective operators, so that the rates in $Z\gamma$ and $WW^*$ are predicted now that the rates in $\gamma\gamma$ and $ZZ^*,Z\gamma^* \to 4 \ell$ have been measured. We find that the pseudoscalar possibility is disfavored but not conclusively excluded. Experimental exclusion of the $Z\gamma$ decay to well below $\sigma/\sigma_{\rm SM} \sim 170$ or conclusive observation of the $WW^*$ decay near the Standard Model rate would eliminate the pseudoscalar possibility. The $Z\gamma$ exclusion should be possible using existing data. The only loophole in our argument is the possibility that the $4\ell$ signal comes from pseudoscalar decays to a pair of new neutral gauge bosons with mass near the $Z$ pole.Comment: 8 pages, 2 figures, v2: references added, Fig. 1 improved,v3: minor error in numbers on last paragraph of pg5 fixe

Improved Outcomes After Autologous Hematopoietic Cell Transplantation for Light Chain Amyloidosis: A Center for International Blood and Marrow Transplant Research Study

Autologous hematopoietic cell transplantation, or autotransplantation, is effective in light-chain amyloidosis (AL), but it is associated with a high risk of early mortality (EM). In a multicenter randomized comparison against oral chemotherapy, autotransplantation was associated with 24% EM. We analyzed trends in outcomes after autologous hematopoietic cell transplantation for AL in North America

Lenalidomide after Stem-Cell Transplantation for Multiple Myeloma

Data are lacking on whether lenalidomide maintenance therapy prolongs the time to disease progression after autologous hematopoietic stem-cell transplantation in patients with multiple myeloma

Early role of vascular dysregulation on late-onset Alzheimer's disease based on multifactorial data-driven analysis

Multifactorial mechanisms underlying late-onset Alzheimer's disease (LOAD) are poorly characterized from an integrative perspective. Here spatiotemporal alterations in brain amyloid-β deposition, metabolism, vascular, functional activity at rest, structural properties, cognitive integrity and peripheral proteins levels are characterized in relation to LOAD progression. We analyse over 7,700 brain images and tens of plasma and cerebrospinal fluid biomarkers from the Alzheimer's Disease Neuroimaging Initiative (ADNI). Through a multifactorial data-driven analysis, we obtain dynamic LOAD–abnormality indices for all biomarkers, and a tentative temporal ordering of disease progression. Imaging results suggest that intra-brain vascular dysregulation is an early pathological event during disease development. Cognitive decline is noticeable from initial LOAD stages, suggesting early memory deficit associated with the primary disease factors. High abnormality levels are also observed for specific proteins associated with the vascular system's integrity. Although still subjected to the sensitivity of the algorithms and biomarkers employed, our results might contribute to the development of preventive therapeutic interventions

Pilot Study of Bortezomib and Dexamethasone Pre- and Post-Risk-Adapted Autologous Stem Cell Transplantation in AL Amyloidosis

Treatment for AL amyloidosis aims to eradicate clonal plasma cells, thereby disrupting the amyloid deposition causing organ damage. Risk-adapted high-dose melphalan plus autologous stem cell transplantation (RA-ASCT) is an effective therapy. We conducted a prospective pilot analysis of a comprehensive approach using bortezomib and dexamethasone (BD) before and after RA-ASCT in 19 patients. BD induction (up to 3 cycles of bortezomib 1.3 mg/m i.v. and dexamethasone 40 mg orally [p.o.] or i.v. on days 1, 4, 8, and 11) was followed by RA-ASCT and then BD consolidation (6 cycles of bortezomib 1.3 mg/m i.v. and dexamethasone 20 mg p.o. or i.v. weekly for 4 weeks, every 12 weeks). The overall hematologic response rate (partial response or better) was 95%, including 37% minimal residual disease negative [MRD(-)] complete response (CR) by flow cytometry (sensitivity up to 1/10 cells). At 2 years, progression-free survival (PFS) and overall survival were 68% (95% confidence interval [CI], 50% to 93%) and 84% (95% CI, 69% to 99%), respectively, with median duration of follow-up in survivors of 61 months (range, 42 to 84 months). In a landmark analysis, patients achieving MRD(-) CR had superior PFS (P= .008). This approach is safe and yields deep and durable remissions promoting organ recovery. Each treatment phase deepened the response. Future aims include improving the efficacy and toxicity of each phase

The checkpoint kinase inhibitor AZD7762 potentiates chemotherapy-induced apoptosis of p53-mutated multiple myeloma cells

DNA cross-linking agents are frequently used in the treatment of multiple myeloma-generating lesions, which activate checkpoint kinase 1 (Chk1), a critical transducer of the DNA damage response. Chk1 activation promotes cell survival by regulating cell-cycle arrest and DNA repair following genotoxic stress. The ability of AZD7762, an ATP-competitive Chk1/2 inhibitor to increase the efficacy of the DNA-damaging agents bendamustine, melphalan, and doxorubicin was examined using four human myeloma cell lines, KMS-12-BM, KMS-12-PE, RPMI-8226, and U266B1. The in vitro activity of AZD7762 as monotherapy and combined with alkylating agents and the "novel" drug bortezomib was evaluated by studying its effects on cytotoxicity, signaling, and apoptotic pathways. The Chk1/2 inhibitor AZD7762 potentiated the antiproliferative effects of bendamustine, melphalan, and doxorubicin but not bortezomib in multiple myeloma cell lines that were p53-deficient. Increased γH2AX staining in cells treated with bendamustine or melphalan plus AZD7762 indicates a greater degree of DNA damage with combined therapy. Abrogation of the G(2)-M checkpoint by AZD7762 resulted in mitotic catastrophe with ensuing apoptosis evidenced by PARP and caspase-3 cleavage. In summary, the cytotoxic effects of bendamustine, melphalan and doxorubicin on p53-deficient multiple myeloma cell lines were enhanced by the coadministration of AZD7762. These data provide a rationale for testing these combinations in patients with relapsed and/or refractory multiple myeloma