Emergence and propagation of asynchronous states of spontaneous cortical activity

Poste

A Class of Partially Solvable Two-Dimensional Quantum Models with Periodic Potentials

The supersymmetrical approach is used to analyse a class of two-dimensional quantum systems with periodic potentials. In particular, the method of SUSY-separation of variables allowed us to find a part of the energy spectra and the corresponding wave functions (partial solvability) for several models. These models are not amenable to conventional separation of variables, and they can be considered as two-dimensional generalizations of Lame, associated Lame, and trigonometric Razavy potentials. All these models have the symmetry operators of fourth order in momenta, and one of them (the Lame potential) obeys the property of self-isospectrality.Comment: 22 pages; some typos corrected; new reference adde

Two-Dimensional Supersymmetry: From SUSY Quantum Mechanics to Integrable Classical Models

Two known 2-dim SUSY quantum mechanical constructions - the direct generalization of SUSY with first-order supercharges and Higher order SUSY with second order supercharges - are combined for a class of 2-dim quantum models, which {\it are not amenable} to separation of variables. The appropriate classical limit of quantum systems allows us to construct SUSY-extensions of original classical scalar Hamiltonians. Special emphasis is placed on the symmetry properties of the models thus obtained - the explicit expressions of quantum symmetry operators and of classical integrals of motion are given for all (scalar and matrix) components of SUSY-extensions. Using Grassmanian variables, the symmetry operators and classical integrals of motion are written in a unique form for the whole Superhamiltonian. The links of the approach to the classical Hamilton-Jacobi method for related "flipped" potentials are established.Comment: 19 page

Mirror symmetry breaking through an internal degree of freedom leading to directional motion

We analyze here the minimal conditions for directional motion (net flow in phase space) of a molecular motor placed on a mirror-symmetric environment and driven by a center-symmetric and time-periodic force field. The complete characterization of the deterministic limit of the dissipative dynamics of several realizations of this minimal model, reveals a complex structure in the phase diagram in parameter space, with intertwined regions of pinning (closed orbits) and directional motion. This demonstrates that the mirror-symmetry breaking which is needed for directional motion to occur, can operate through an internal degree of freedom coupled to the translational one.Comment: Accepted for publication in Phys. Rev.

Multiple myeloma and SARS-CoV-2 infection : clinical characteristics and prognostic factors of inpatient mortality

There is limited information on the characteristics, prognostic factors, and outcomes of patients with multiple myeloma (MM) hospitalized with COVID-19. This retrospective case series investigated 167 patients reported from 73 hospitals within the Spanish Myeloma Collaborative Group network in March and April, 2020. Outcomes were compared with 167 randomly selected, contemporary, age-/sex-matched noncancer patients with COVID-19 admitted at six participating hospitals. Among MM and noncancer patients, median age was 71 years, and 57% of patients were male; 75 and 77% of patients, respectively, had at least one comorbidity. COVID-19 clinical severity was moderate-severe in 77 and 89% of patients and critical in 8 and 4%, respectively. Supplemental oxygen was required by 47 and 55% of MM and noncancer patients, respectively, and 21%/9% vs 8%/6% required noninvasive/invasive ventilation. Inpatient mortality was 34 and 23% in MM and noncancer patients, respectively. Among MM patients, inpatient mortality was 41% in males, 42% in patients aged >65 years, 49% in patients with active/progressive MM at hospitalization, and 59% in patients with comorbid renal disease at hospitalization, which were independent prognostic factors on adjusted multivariate analysis. This case series demonstrates the increased risk and identifies predictors of inpatient mortality among MM patients hospitalized with COVID-19

Chimeric antigen receptor T-cell therapy for multiple myeloma: a consensus statement from The European Myeloma Network

Adoptive cellular therapy using chimeric antigen receptor T-cell (CART) therapy is currently being evaluated in patients with relapsed / refractory multiple myeloma (MM). The majority of CAR-T cell programs now being tested in clinical trials are targeting B-cell maturation antigen. Several recent phase I / II trials show promising preliminary results in patients with MM progressing on proteasome inhibitors, immunomodulatory drugs and monoclonal antibodies targeting CD38. CAR-T cell therapy is a potentially life-threatening strategy that can only be administered in experienced centers. For the moment, CAR-T cell therapy for MM is still experimental, but once this strateg

Pembrolizumab as Consolidation Strategy in Patients with Multiple Myeloma: Results of the GEM-Pembresid Clinical Trial

PD1 expression in CD4+ and CD8+ T cells is increased after treatment in multiple myeloma patients with persistent disease. The GEM-Pembresid trial analyzed the efficacy and safety of pembrolizumab as consolidation in patients achieving at least very good partial response but with persistent measurable disease after first- or second-line treatment. Moreover, the characteristics of the immune system were investigated to identify potential biomarkers of response to pembrolizumab. One out of the 17 evaluable patients showed a decrease in the amount of M-protein, although a potential late effect of high-dose melphalan could not be ruled out. Fourteen adverse events were considered related to pembrolizumab, two of which (G3 diarrhea and G2 pneumonitis) prompted treatment discontinuation and all resolving without sequelae. Interestingly, pembrolizumab induced a decrease in the percentage of NK cells at cycle 3, due to the reduction of the circulating and adaptive subsets (0.615 vs. 0.43, p = 0.007; 1.12 vs. 0.86, p = 0.02). In the early progressors, a significantly lower expression of PD1 in CD8+ effector memory T cells (MFI 1327 vs. 926, p = 0.03) was observed. In conclusion, pembrolizumab used as consolidation monotherapy shows an acceptable toxicity profile but did not improve responses in this MM patient population. The trial was registered at clinicaltrials.gov with identifier NCT02636010 and with EUDRACT number 2015-003359-23.This study was funded by Fundación Ramón Areces (FRA 16/003). T.P. is supported by a grant from the AECC (INVES18043PAIN). This study received financial support from Merck Sharp & Dohme of Spain, a subsidiary of Merck & Co., Inc., Whitehouse Station, New Jersey, USA

EHA evaluation of the ESMO-Magnitude of Clinical Benefit Scale version 1.1 (ESMO-MCBS v1.1) for haematological malignancies

Objective Value frameworks in oncology have not been validated for the assessment of treatments in haematological malignancies, but to avoid overlaps and duplications it appears reasonable to build up experience on existing value frameworks, such as the European Society for Medical Oncology-Magnitude of Clinical Benefit Scale (ESMO-MCBS). Methods Here we present the results of the first feasibility testing of the ESMO-MCBS v1.1 for haematological malignancies based on the grading of 80 contemporary studies for acute leukaemia, chronic leukaemia, lymphoma, myeloma and myelodysplastic syndromes. The aims were (1) to evaluate the scorability of data, (2) to evaluate the reasonableness of the generated grades for clinical benefit using the current version and (3) to identify shortcomings in the ESMO-MCBS v1.1 that require amendments to improve the efficacy and validity of the scale in grading new treatments in the management of haematological malignancies. Results In general, the ESMO-MCBS v1.1 was found to be widely applicable to studies in haematological malignancies, generating scores that were judged as reasonable by European Hematology Association (EHA) experts. A small number of studies could either not be graded or were not appropriately graded. The reasons, related to the differences between haematological and solid tumour malignancies, are identified and described. Conclusions Based on the findings of this study, ESMO and EHA are committed to develop a version of the ESMO-MCBS that is validated for haematological malignancies. This development process will incorporate all of the usual stringencies for accountability of reasonableness that have characterised the development of the ESMO-MCBS including field testing, statistical modelling, evaluation for reasonableness and openness to appeal and revision. Applying such a scale will support future public policy decision-making regarding the value of new treatments for haematological malignancies and will provide insights that could be helpful in the design of future clinical trials