Noise-induced switching between vortex states with different polarization in classical two-dimensional easy-plane magnets

In the 2-dimensional anisotropic Heisenberg model with XY-symmetry there are non-planar vortices which exhibit a localized structure of the z-components of the spins around the vortex center. We study how thermal noise induces a transition of this structure from one polarization to the opposite one. We describe the vortex core by a discrete Hamiltonian and consider a stationary solution of the Fokker-Planck equation. We find a bimodal distribution function and calculate the transition rate using Langer's instanton theory (1969). The result is compared with Langevin dynamics simulations for the full many-spin model.Comment: 15 pages, 4 figures, Phys. Rev. B., in pres

Polarisation Patterns and Vectorial Defects in Type II Optical Parametric Oscillators

Previous studies of lasers and nonlinear resonators have revealed that the polarisation degree of freedom allows for the formation of polarisation patterns and novel localized structures, such as vectorial defects. Type II optical parametric oscillators are characterised by the fact that the down-converted beams are emitted in orthogonal polarisations. In this paper we show the results of the study of pattern and defect formation and dynamics in a Type II degenerate optical parametric oscillator for which the pump field is not resonated in the cavity. We find that traveling waves are the predominant solutions and that the defects are vectorial dislocations which appear at the boundaries of the regions where traveling waves of different phase or wave-vector orientation are formed. A dislocation is defined by two topological charges, one associated with the phase and another with the wave-vector orientation. We also show how to stabilize a single defect in a realistic experimental situation. The effects of phase mismatch of nonlinear interaction are finally considered.Comment: 38 pages, including 15 figures, LATeX. Related material, including movies, can be obtained from http://www.imedea.uib.es/Nonlinear/research_topics/OPO

Phase-Locked Spatial Domains and Bloch Domain Walls in Type-II Optical Parametric Oscillators

We study the role of transverse spatial degrees of freedom in the dynamics of signal-idler phase locked states in type-II Optical Parametric Oscillators. Phase locking stems from signal-idler polarization coupling which arises if the cavity birefringence and/or dichroism is not matched to the nonlinear crystal birefringence. Spontaneous Bloch domain wall formation is theoretically predicted and numerically studied. Bloch walls connect, by means of a polarization transformation, homogeneous regions of self-phase locked solutions. The parameter range for their existence is analytically found. The polarization properties and the dynamics of walls in one- and two transverse spatial dimensions is explained. Transition from Bloch to Ising walls is characterized, the control parameter being the linear coupling strength. Wall dynamics governs spatiotemporal dynamical states of the system, which include transient curvature driven domain growth, persistent dynamics dominated by spiraling defects for Bloch walls, and labyrinthine pattern formation for Ising walls.Comment: 27 pages, 16 figure

An exploration of parents’ preferences for foot care in juvenile idiopathic arthritis: a possible role for the discrete choice experiment

Background: An increased awareness of patients’ and parents’ care preferences regarding foot care is desirable from a clinical perspective as such information may be utilised to optimise care delivery. The aim of this study was to examine parents’ preferences for, and valuations of foot care and foot-related outcomes in juvenile idiopathic arthritis (JIA).<p></p> Methods: A discrete choice experiment (DCE) incorporating willingness-to-pay (WTP) questions was conducted by surveying 42 parents of children with JIA who were enrolled in a randomised-controlled trial of multidisciplinary foot care at a single UK paediatric rheumatology outpatients department. Attributes explored were: levels of pain; mobility; ability to perform activities of daily living (ADL); waiting time; referral route; and footwear. The DCE was administered at trial baseline. DCE data were analysed using a multinomial-logit-regression model to estimate preferences and relative importance of attributes of foot care. A stated-preference WTP question was presented to estimate parents’ monetary valuation of health and service improvements.<p></p> Results: Every attribute in the DCE was statistically significant (p < 0.01) except that of cost (p = 0.118), suggesting that all attributes, except cost, have an impact on parents’ preferences for foot care for their child. The magnitudes of the coefficients indicate that the strength of preference for each attribute was (in descending order): improved ability to perform ADL, reductions in foot pain, improved mobility, improved ability to wear desired footwear, multidisciplinary foot care route, and reduced waiting time. Parents’ estimated mean annual WTP for a multidisciplinary foot care service was £1,119.05.<p></p> Conclusions: In terms of foot care service provision for children with JIA, parents appear to prefer improvements in health outcomes over non-health outcomes and service process attributes. Cost was relatively less important than other attributes suggesting that it does not appear to impact on parents’ preferences.<p></p&gt

Islands of relationality and resilience: the shifting stakes of the Anthropocene

In recent decades island studies scholars have done much to disrupt static notions of the island form, increasingly foregrounding how islands form part of complex networks of relations, assemblages and flows. In this paper, we shift the terms of debate more explicitly to relationality in the Anthropocene. We consider the implications and challenges that a wider set of debates, particularly surrounding island ‘resilience’, concerning the Anthropocene in the social sciences and humanities pose for island studies

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

LocoMMotion: a prospective, non-interventional, multinational study of real-life current standards of care in patients with relapsed and/or refractory multiple myeloma

Despite treatment advances, patients with multiple myeloma (MM) often progress through standard drug classes including proteasome inhibitors (PIs), immunomodulatory drugs (IMiDs), and anti-CD38 monoclonal antibodies (mAbs). LocoMMotion (ClinicalTrials.gov identifier: NCT04035226) is the first prospective study of real-life standard of care (SOC) in triple-class exposed (received at least a PI, IMiD, and anti-CD38 mAb) patients with relapsed/refractory MM (RRMM). Patients (N = 248; ECOG performance status of 0–1, ≥3 prior lines of therapy or double refractory to a PI and IMiD) were treated with median 4.0 (range, 1–20) cycles of SOC therapy. Overall response rate was 29.8% (95% CI: 24.2–36.0). Median progression-free survival (PFS) and median overall survival (OS) were 4.6 (95% CI: 3.9–5.6) and 12.4 months (95% CI: 10.3–NE). Treatment-emergent adverse events (TEAEs) were reported in 83.5% of patients (52.8% grade 3/4). Altogether, 107 deaths occurred, due to progressive disease (n = 74), TEAEs (n = 19), and other reasons (n = 14). The 92 varied regimens utilized demonstrate a lack of clear SOC for heavily pretreated, triple-class exposed patients with RRMM in real-world practice and result in poor outcomes. This supports a need for new treatments with novel mechanisms of action

Predicting long-term disease control in transplant-ineligible patients with multiple myeloma: impact of an MGUS-like signature

Disease control at 5 years would be a desirable endpoint for elderly multiple myeloma (MM) patients, but biomarkers predicting this are not defined. Therefore, to gain further insights in this endpoint, a population of 498 newly diagnosed transplant-ineligible patients enrolled in two Spanish trials (GEM2005MAS65 and GEM2010MAS65), has been analyzed. Among the 435 patients included in this post-hoc study, 18.6% remained alive and progression free after 5 years of treatment initiation. In these patients, overall survival (OS) rate at 10 years was 60.8% as compared with 11.8% for those progressing within the first 5 years. Hemoglobin (Hb) = 12 g/dl (OR 2.74, p = 0.001) and MGUS-like profile (OR 4.18, p = 0.005) were the two baseline variables associated with long-term disease-free survival. Upon including depth of response (and MRD), Hb = 12 g/dl (OR 2.27) and MGUS-like signature (OR 7.48) retained their predictive value along with MRD negativity (OR 5.18). This study shows that despite the use of novel agents, the probability of disease control at 5 years is still restricted to a small fraction (18.6%) of elderly MM patients. Since this endpoint is associated with higher rates of OS, this study provides important information about diagnostic and post-treatment biomarkers helpful in predicting the likelihood of disease control at 5 years

CAR density influences antitumoral efficacy of BCMA CAR T cells and correlates with clinical outcome

Identification of new markers associated with long-term efficacy in patients treated with CAR T cells is a current medical need, particularly in diseases such as multiple myeloma. In this study, we address the impact of CAR density on the functionality of BCMA CAR T cells. Functional and transcriptional studies demonstrate that CAR T cells with high expression of the CAR construct show an increased tonic signaling with up-regulation of exhaustion markers and increased in vitro cytotoxicity but a decrease in in vivo BM infiltration. Characterization of gene regulatory networks using scRNA-seq identified regulons associated to activation and exhaustion up-regulated in CARHigh T cells, providing mechanistic insights behind differential functionality of these cells. Last, we demonstrate that patients treated with CAR T cell products enriched in CARHigh T cells show a significantly worse clinical response in several hematological malignancies. In summary, our work demonstrates that CAR density plays an important role in CAR T activity with notable impact on clinical response