Ab initio quantum theory of mass defect and time dilation in trapped-ion optical clocks

We derive a Hamiltonian for the external and internal dynamics of an electromagnetically bound, charged two-particle system in external electromagnetic and gravitational fields, including leading-order relativistic corrections. We apply this Hamiltonian to describe the relativistic coupling of the external and internal dynamics of cold ions in Paul traps, including the effects of micromotion, excess micromotion, and trap imperfections. This provides a systematic and fully quantum-mechanical treatment of relativistic frequency shifts in atomic clocks based on single trapped ions. Our approach reproduces well-known formulas for the second-order Doppler shift for thermal states, which were previously derived on the basis of semiclassical arguments. We complement and clarify recent discussions in the literature on the role of time dilation and mass defect in ion clocks

Quadrupole transitions and quantum gates protected by continuous dynamic decoupling

Dynamical decoupling techniques are a versatile tool for engineering quantum states with tailored properties. In trapped ions, nested layers of continuous dynamical decoupling by means of radio-frequency field dressing can cancel dominant magnetic and electric shifts and therefore provide highly prolonged coherence times of electronic states. Exploiting this enhancement for frequency metrology, quantum simulation or quantum computation, poses the challenge to combine the decoupling with laser-ion interactions for the quantum control of electronic and motional states of trapped ions. Ultimately, this will require running quantum gates on qubits from dressed decoupled states. We provide here a compact representation of nested continuous dynamical decoupling in trapped ions, and apply it to electronic $S$ and $D$ states and optical quadrupole transitions. Our treatment provides all effective transition frequencies and Rabi rates, as well as the effective selection rules of these transitions. On this basis, we discuss the possibility of combining continuous dynamical decoupling and M{\o}lmer-S{\o}rensen gates

The Koskobilo (Olazti, Navarre, Northern Iberian Peninsula) paleontological collection: New insights for the Middle and Late Pleistocene in Western Pyrenees

The destroyed site(s) of Koskobilo (Olazti, Navarre, Northern Iberian Peninsula) have yielded unique archaeo-paleontological evidence in the Western Pyrenees region. The quarry uncovered a karstic site with faunal remains in 1940, and fossils were recovered both in situ and from the quarry dump. Ten years later, while the quarry was still working, a new visit to the dump yielded a large lithic assemblage and additional fossil remains with a different taphonomic pattern, which has been interpreted as the remains coming from a different site or zone within the same karst system. Here we re-study the paleontological evidence and provide new dating on a speleothem covering a Stephanorhinus hemitoechus tooth, which has yielded a minimum date of c. 220 ka for part of the assemblage. In total, the fossil assemblage comprises 38 mammal and six avian taxa and three fish remains. The faunal evidence indicates that in 1940 a mix of taxa from both the Middle and Upper Pleistocene were recovered, and it is difficult to assign most of them to a concrete period. However, based on biochronological criteria some of the identified taxa (e.g., Ursus thibetanus, Ursus cf. deningeri, Cuon cf. priscus, Macaca sylvanus, cf. Megaceroides) could be roughly contemporaneous with the dated rhino tooth, which would provide a new window to the Middle Pleistocene of the region, with deposits from MIS 7d and/or older. Despite the difficulties in studying this collection, recovered without stratigraphic context and in a salvage operation, Koskobilo has yielded an important paleontological assemblage which helps to understand the paleoecology of the Middle Pleistocene human occupations in the Western Pyrenees

Comparison of next-generation sequencing (NGS) and next-generation flow (NGF) for minimal residual disease (MRD) assessment in multiple myeloma

Detecting persistent minimal residual disease (MRD) allows the identification of patients with an increased risk of relapse and death. In this study, we have evaluated MRD 3 months after transplantation in 106 myeloma patients using a commercial next-generation sequencing (NGS) strategy (LymphoTrack®), and compared the results with next-generation flow (NGF, EuroFlow). The use of different marrow pulls and the need of concentrating samples for NGS biased the applicability for MRD evaluation and favored NGF. Despite that, correlation between NGS and NGF was high (R = 0.905). The 3-year progression-free survival (PFS) rates by NGS and NGF were longer for undetectable vs. positive patients (NGS: 88.7% vs. 56.6%; NGF: 91.4% vs. 50%; p < 0.001 for both comparisons), which resulted in a 3-year overall survival (OS) advantage (NGS: 96.2% vs. 77.3%; NGF: 96.6% vs. 74.9%, p < 0.01 for both comparisons). In the Cox regression model, NGS and NGF negativity had similar results but favoring the latter in PFS (HR: 0.20, 95% CI: 0.09-0.45, p < 0.001) and OS (HR: 0.21, 95% CI: 0.06-0.75, p = 0.02). All these results reinforce the role of MRD detection by different strategies in patient prognosis and highlight the use of MRD as an endpoint for multiple myeloma treatment

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

Molecular profiling of immunoglobulin heavy-chain gene rearrangements unveils new potential prognostic markers for multiple myeloma patients

Altres ajuts: This work was partially supported by[...] , CIBERONC-CB16/12/00233, and "Una manera de hacer Europa" (Innocampus; CEI-2010-1-0010)". M.G.-A., I.P.-C., and C.J. are supported by the Fundación Española de Hematología y Hemoterapia (FEHH, co-funded by Fundación Cris in the latter case), A.M. by the European Social Fund and the Spanish Education Council through the University of Salamanca, [...]. All Spanish funding is co-sponsored by the European Union FEDER program.Multiple myeloma is a heterogeneous disease whose pathogenesis has not been completely elucidated. Although B-cell receptors play a crucial role in myeloma pathogenesis, the impact of clonal immunoglobulin heavy-chain features in the outcome has not been extensively explored. Here we present the characterization of complete heavy-chain gene rearrangements in 413 myeloma patients treated in Spanish trials, including 113 patients characterized by next-generation sequencing. Compared to the normal B-cell repertoire, gene selection was biased in myeloma, with significant overrepresentation of IGHV3, IGHD2 and IGHD3, as well as IGHJ4 gene groups. Hypermutation was high in our patients (median: 8.8%). Interestingly, regarding patients who are not candidates for transplantation, a high hypermutation rate (≥7%) and the use of IGHD2 and IGHD3 groups were associated with improved prognostic features and longer survival rates in the univariate analyses. Multivariate analysis revealed prolonged progression-free survival rates for patients using IGHD2/IGHD3 groups (HR: 0.552, 95% CI: 0.361−0.845, p = 0.006), as well as prolonged overall survival rates for patients with hypermutation ≥7% (HR: 0.291, 95% CI: 0.137−0.618, p = 0.001). Our results provide new insights into the molecular characterization of multiple myeloma, highlighting the need to evaluate some of these clonal rearrangement characteristics as new potential prognostic markers

Flow cytometry for fast screening and automated risk assessment in systemic light-chain amyloidosis

Early diagnosis and risk stratification are key to improve outcomes in light-chain (AL) amyloidosis. Here we used multidimensional-flow-cytometry (MFC) to characterize bone marrow (BM) plasma cells (PCs) from a series of 166 patients including newly-diagnosed AL amyloidosis (N = 94), MGUS (N = 20) and multiple myeloma (MM, N = 52) vs. healthy adults (N = 30). MFC detected clonality in virtually all AL amyloidosis (99%) patients. Furthermore, we developed an automated risk-stratification system based on BMPCs features, with independent prognostic impact on progression-free and overall survival of AL amyloidosis patients (hazard ratio: ≥ 2.9;P ≤ .03). Simultaneous assessment of the clonal PCs immunophenotypic protein expression profile and the BM cellular composition, mapped AL amyloidosis in the crossroad between MGUS and MM; however, lack of homogenously-positive CD56 expression, reduction of B-cell precursors and a predominantly-clonal PC compartment in the absence of an MM-like tumor PC expansion, emerged as hallmarks of AL amyloidosis (ROC-AUC = 0.74;P < .001), and might potentially be used as biomarkers for the identification of MGUS and MM patients, who are candidates for monitoring pre-symptomatic organ damage related to AL amyloidosis. Altogether, this study addressed the need for consensus on how to use flow cytometry in AL amyloidosis, and proposes a standardized MFC-based automated risk classification ready for implementation in clinical practice

RICORS2040 : The need for collaborative research in chronic kidney disease

Chronic kidney disease (CKD) is a silent and poorly known killer. The current concept of CKD is relatively young and uptake by the public, physicians and health authorities is not widespread. Physicians still confuse CKD with chronic kidney insufficiency or failure. For the wider public and health authorities, CKD evokes kidney replacement therapy (KRT). In Spain, the prevalence of KRT is 0.13%. Thus health authorities may consider CKD a non-issue: very few persons eventually need KRT and, for those in whom kidneys fail, the problem is 'solved' by dialysis or kidney transplantation. However, KRT is the tip of the iceberg in the burden of CKD. The main burden of CKD is accelerated ageing and premature death. The cut-off points for kidney function and kidney damage indexes that define CKD also mark an increased risk for all-cause premature death. CKD is the most prevalent risk factor for lethal coronavirus disease 2019 (COVID-19) and the factor that most increases the risk of death in COVID-19, after old age. Men and women undergoing KRT still have an annual mortality that is 10- to 100-fold higher than similar-age peers, and life expectancy is shortened by ~40 years for young persons on dialysis and by 15 years for young persons with a functioning kidney graft. CKD is expected to become the fifth greatest global cause of death by 2040 and the second greatest cause of death in Spain before the end of the century, a time when one in four Spaniards will have CKD. However, by 2022, CKD will become the only top-15 global predicted cause of death that is not supported by a dedicated well-funded Centres for Biomedical Research (CIBER) network structure in Spain. Realizing the underestimation of the CKD burden of disease by health authorities, the Decade of the Kidney initiative for 2020-2030 was launched by the American Association of Kidney Patients and the European Kidney Health Alliance. Leading Spanish kidney researchers grouped in the kidney collaborative research network Red de Investigación Renal have now applied for the Redes de Investigación Cooperativa Orientadas a Resultados en Salud (RICORS) call for collaborative research in Spain with the support of the Spanish Society of Nephrology, Federación Nacional de Asociaciones para la Lucha Contra las Enfermedades del Riñón and ONT: RICORS2040 aims to prevent the dire predictions for the global 2040 burden of CKD from becoming true

A tandem-flow assembly for the chemiluminometric determination of hydroquinone

A direct chemiluminescent procedure for determination of hydroquinone based on the emergent flow methodology known as multicommutation or tandem-flow is presented for first time. The manifold was based on a set of three channels and three solenoid valves; and, the determination was performed at 60degreesC and at flow-rate of 7.5 ml min(-1). The complete cycle lasted 35 s, which resulted in a sample flow trough of 103 h(-1). The chemical process was the hydroquinone oxidation with the system sulphuric acid-potassium permanganate; and the light emission was clearly enhanced by the presence of quinine sulphate and benzalkonium chloride reaching a detection limit of 30 Rg l(-1). The dynamic interval was over the range 0.1-15.0 mgl(-1) and a large list of interferents were assayed; the chemical robustness was also tested. The method was applied to different type of samples: namely, pharmaceutical formulations, a photographic solution and irrigation and residual superficial waters. (C) 2004 Elsevier B.V. All rights reserved.Gómez-Taylor Corominas, B.; Catalá Icardo, M.; Lahuerta Zamora, L.; García Mateo, JV.; Martínez Calatayud, J. (2004). A tandem-flow assembly for the chemiluminometric determination of hydroquinone. Talanta. 64(3):618-625. doi:10.1016/j.talanta.2004.03.031S61862564