Array of Individual Circular Rydberg Atoms Trapped in Optical Tweezers.

Circular Rydberg atoms (CRAs), i.e., Rydberg atoms with maximal orbital momentum, are highly promising for quantum computation, simulation, and sensing. They combine long natural lifetimes with strong interatomic interactions and coupling to electromagnetic fields. Trapping individual CRAs is essential to harness these unique features. We report the first demonstration of CRAs laser trapping in a programmable array of optical bottle beams. We observe the decay of a trapped rubidium circular level over 5 ms using a novel optical detection method. This first optical detection of alkali CRAs is both spatially and level selective. We finally observe the mechanical oscillations of the CRAs in the traps. This work opens the route to the use of circular levels in quantum devices. It is also promising for quantum simulation and information processing using the full extent of Rydberg manifolds.

Millisecond-Lived Circular Rydberg Atoms in a Room-Temperature Experiment.

Circular Rydberg states are excellent tools for quantum technologies, with large mutual interactions and long lifetimes in the tens of milliseconds range, 2 orders of magnitude larger than those of laser-accessible Rydberg states. However, such lifetimes are observed only at zero temperature. At room temperature, blackbody-radiation-induced transfers cancel this essential asset of circular states, which have thus been used mostly so far in specific, complex cryogenic experiments. We demonstrate here, on a laser-cooled atomic sample, a circular state lifetime of more than 1 millisecond at room temperature for a principal quantum number 60. A simple plane-parallel capacitor efficiently inhibits the blackbody-radiation-induced transfers. One of the capacitor electrodes is fully transparent and provides large optical access to the atoms. This result paves the way to a wide range of quantum metrology and quantum simulation room-temperature experiments with long-lived, trapped circular Rydberg atoms in inhibition capacitors with full optical access.

Assessment of Psychosocial Functioning in a Large Cohort of Patients with Schizophrenia.

BACKGROUND: This study addresses the question of whether psychosocial functioning measured by the Personal and Social Performance (PSP) Scale is related to various psychopathological measures in a cohort of patients with schizophrenia. METHODS: The 'Neuroleptic Strategy Study' (NeSSy) performed at 14 German hospitals between 2010 and 2013 compared two treatment strategies instead of individual drugs. Secondary end-points were the two PSP scales as well as measures of quality of life (SF-36) and the Positive and Negative Syndrome Scale (PANSS). RESULTS: 149 patients were randomised. There was no difference between the two treatment strategies (first-generation versus second-generation antipsychotics) with regard to the PSP. There were differences in doctors' assessments regarding psychosocial functioning compared with patients' own assessments. Furthermore, there were relationships between the PSP and quality of life, level of skills (ICF), and severity of disease (PANSS), level of sexual activities and poor well-being under antipsychotic medication but not with cognitive changes. CONCLUSIONS: The findings on psychosocial functioning of patients with schizophrenia related to severity and skill level could be confirmed. Further findings were the correlation between psychosocial functioning and quality of life, well-being under treatment, and sexuality what emphasizes the substantial importance of a reduced psychosocial functioning.

Targeted bisulfite sequencing: A novel tool for the assessment of DNA methylation with high sensitivity and increased coverage.

DNA methylation analysis is increasingly used in stress research. Available methods are expensive, laborious and often limited by either the analysis of short CpG stretches or low assay sensitivity. Here, we present a cost-efficient next generation sequencing-based strategy for the simultaneous investigation of multiple candidate genes in large cohorts. To illustrate the method, we present analysis of four candidate genes commonly assessed in psychoneuroendocrine research: Glucocorticoid receptor (NR3C1), Serotonin transporter (SLC6A4), FKBP Prolyl isomerase 5 (FKBP5), and the Oxytocin receptor (OXTR). DNA methylation standards (100 %; 75 %; 50 %; 25 % and 0 %) and DNA of a female and male donor were bisulfite treated in three independent trials and were used to generate sequencing libraries for 42 CpGs from the NR3C1 1 F promoter region, 84 CpGs of the SLC6A4 5' regulatory region, 5 CpGs located in FKBP5 intron 7, and additional 12 CpGs located in a potential enhancer element in intron 3 of the OXTR. In addition, DNA of 45 patients with borderline personality disorder (BPD) and 45 healthy controls was assayed. Multiplex libraries of all samples were sequenced on a MiSeq system and analyzed for mean methylation values of all CpG sites using amplikyzer2 software. Results indicated excellent accuracy of the assays when investigating replicates generated from the same bisulfite converted DNA, and very high linearity (R2 > 0.9) of the assays shown by the analysis of differentially methylated DNA standards. Comparing DNA methylation between BPD and healthy controls revealed no biologically relevant differences. The technical approach as described here facilitates targeted DNA methylation analysis and represents a highly sensitive, cost-efficient and high throughput tool to close the gap between coverage and precision in epigenetic research of stress-associated phenotypes.

Laser Trapping of Circular Rydberg Atoms.

Rydberg atoms are remarkable tools for quantum simulation and computation. They are the focus of an intense experimental activity, mainly based on low-angular-momentum Rydberg states. Unfortunately, atomic motion and levels lifetime limit the experimental timescale to about 100 µs. Here, we demonstrate two-dimensional laser trapping of long-lived circular Rydberg states for up to 10 ms. Our method is very general and opens many opportunities for quantum technologies with Rydberg atoms. The 10 ms trapping time corresponds to thousands of interaction cycles in a circular-state-based quantum simulator. It is also promising for quantum metrology and quantum information with Rydberg atoms, by bringing atom-field interaction times into unprecedented regimes.

Preparation of Long-Lived, Non-Autoionizing Circular Rydberg States of Strontium.

Alkaline earth Rydberg atoms are very promising tools for quantum technologies. Their highly excited outer electron provides them with the remarkable properties of Rydberg atoms and, notably, with a huge coupling to external fields or to other Rydberg atoms while the ionic core retains an optically active electron. However, low angular-momentum Rydberg states suffer almost immediate autoionization when the core is excited. Here, we demonstrate that strontium circular Rydberg atoms with a core excited in a 4D metastable level are impervious to autoionization over more than a few millisecond time scale. This makes it possible to trap and laser-cool Rydberg atoms. Moreover, we observe singlet to triplet transitions due to the core optical manipulations, opening the way to a microwave to optical quantum interface.

Quantum Rabi Oscillations in Coherent and in Mesoscopic Cat Field States.

The simple resonant Rabi oscillation of a two-level system in a single-mode coherent field reveals complex features at the mesoscopic scale, with oscillation collapses and revivals. Using slow circular Rydberg atoms interacting with a superconducting microwave cavity, we explore this phenomenon in an unprecedented range of interaction times and photon numbers. We demonstrate the efficient production of cat states, which are the quantum superposition of coherent components with nearly opposite phases and sizes in the range of few tens of photons. We measure cuts of their Wigner functions revealing their quantum coherence and observe their fast decoherence. This experiment opens promising perspectives for the rapid generation and manipulation of nonclassical states in cavity and circuit quantum electrodynamics.

Early Multidisciplinary Intensive-care Therapy can Improve Outcome of Severe Anti-NMDA-receptor Encephalitis Presenting with Extreme Delta Brush.

Anti-N-methyl-D-aspartate receptor encephalitis (Anti-NMDARE) is a synaptic autoimmune encephalitis syndrome mainly affecting young females. An underlying tumor, most commonly ovarian teratomas in young females, may indicate a paraneoplastic syndrome. Prognostic factors of the clinical course of disease and outcome play a central role in view of early administration of second-line immunotherapy and intensive-care therapy. We report a case of severe Anti-NMDARE associated with unfavorable predictors including an extreme delta brush (EDB) electroencephalographic-pattern and high anti-NMDAR-antibody titers in the cerebral spinal fluid (CSF), which necessitated the admission to an intensive care unit. In spite of the poor prognosis, the patient completely recovered; we attribute this to an early escalation to second-line immunotherapy with rituximab and multidisciplinary intensive-care therapy. The present case underlines the relevance of multidisciplinary management for individuals with Anti-NMDARE.

Benchmarking Maximum-Likelihood State Estimation with an Entangled Two-Cavity State.

The efficient quantum state reconstruction algorithm described by Six et al. [Phys. Rev. A 93, 012109 (2016)PLRAAN2469-992610.1103/PhysRevA.93.012109] is experimentally implemented on the nonlocal state of two microwave cavities entangled by a circular Rydberg atom. We use information provided by long sequences of measurements performed by resonant and dispersive probe atoms over timescales involving the system decoherence. Moreover, we benefit from the consolidation, in the same reconstruction, of different measurement protocols providing complementary information. Finally, we obtain realistic error bars for the matrix elements of the reconstructed density operator. These results demonstrate the pertinence and precision of the method, directly applicable to any complex quantum system.

Coherent Transfer between Low-Angular-Momentum and Circular Rydberg States.

We realize a coherent transfer between a laser-accessible low-angular-momentum Rydberg state and the circular Rydberg level with maximal angular momentum. It is induced by a radio frequency field with a high-purity σ^{+} polarization resonant on Stark transitions inside the hydrogenic Rydberg manifold. We observe over a few microseconds more than 20 coherent Rabi oscillations between the initial Rydberg state and the circular level. We characterize these many-Rydberg-level oscillations and find them in perfect agreement with a simple model. This coherent transfer opens the way to hybrid quantum gates bridging the gap between optical communication and quantum information manipulations with microwave cavity and circuit quantum electrodynamics.

[Control of cardiovascular risk factors in coronary patients one year after cardiac rehabilitation]. / Contrôle des facteurs de risque chez les patients coronariens un an après une réadaptation cardiaque.

OBJECTIVE: To assess risk factors monitoring in coronary patients one year after cardiac rehabilitation. METHOD: From 2015 to 2015, cardiac morbidity, total mortality and risk factors data were collected from a 4-week ambulatory cardiac rehabilitation program with a control one year later and were compared with the results of Euroaspire and Reach studies. RESULTS: Out of 1091 (87%) coronary patients, 746 (68%) were re-examined 12months later (aged 60years (ranging from 20 to 85years), 15% women, 44% hypertensive, 36% smokers, 17% diabetics, 74% with dyslipidemia). At the end of the program, management of CV risk factors was improved (BP ≤ 140/90mmHg and BMI > 30: 80 and 20% vs 65 and 25% at the beginning of the program; LDL < 0.7g/L: 42% and smoking: 4% vs 18% when hospitalized for their cardiac event). Unfortunately, this benefit decreased significantly at one year (BP ≤ 140/90mmHg: 63%, LDL < 0.7g/L: 27%; smoking: 6%) but it remains better than in Euroaspire IV study: 57, 20 et 16% respectively). While 54% had insufficient physical activity before cardiac rehabilitation, they were only 23% at 1-year vs 60% in Euroaspire study. We reported a total mortality of 0.6% vs 2.9% in Reach study and 12% cardiac hospitalization (53% for a new coronary event). CONCLUSION: Participation of coronary patients in a cardiac rehabilitation program significantly improves management of CV risk factors, morbidity and mortality. However, the control obtained at the end of the program decreases at one year.

Impact of killer-immunoglobulin-like receptor and human leukocyte antigen genotypes on the efficacy of immunotherapy in acute myeloid leukemia.

Interactions between killer-immunoglobulin-like receptors (KIRs) and their HLA class I ligands are instrumental in natural killer (NK) cell regulation and protect normal tissue from NK cell attack. Human KIR haplotypes comprise genes encoding mainly inhibitory receptors (KIR A) or activating and inhibitory receptors (KIR B). A substantial fraction of humans lack ligands for inhibitory KIRs (iKIRs), that is, a 'missing ligand' genotype. KIR B/x and missing ligand genotypes may thus give rise to potentially autoreactive, unlicensed NK cells. Little is known regarding the impact of such genotypes in untransplanted acute myeloid leukemia (AML). For this study, NK cell phenotypes and KIR/HLA genotypes were determined in 81 AML patients who received immunotherapy with histamine dihydrochloride and low-dose IL-2 for relapse prevention (NCT01347996). We observed that presence of unlicensed NK cells impacted favorably on clinical outcome, in particular among patients harboring functional NK cells reflected by high expression of the natural cytotoxicity receptor (NCR) NKp46. Genotype analyses suggested that the clinical benefit of high NCR expression was restricted to patients with a missing ligand genotype and/or a KIR B/x genotype. These data imply that functional NK cells are significant anti-leukemic effector cells in patients with KIR/HLA genotypes that favor NK cell autoreactivity.

Donor Preconditioning After the Onset of Brain Death With Dopamine Derivate n-Octanoyl Dopamine Improves Early Posttransplant Graft Function in the Rat.

Heart transplantation is the therapy of choice for end-stage heart failure. However, hemodynamic instability, which has been demonstrated in brain-dead donors (BDD), could also affect the posttransplant graft function. We tested the hypothesis that treatment of the BDD with the dopamine derivate n-octanoyl-dopamine (NOD) improves donor cardiac and graft function after transplantation. Donor rats were given a continuous intravenous infusion of either NOD (0.882 mg/kg/h, BDD+NOD, n = 6) or a physiological saline vehicle (BDD, n = 9) for 5 h after the induction of brain death by inflation of a subdural balloon catheter. Controls were sham-operated (n = 9). In BDD, decreased left-ventricular contractility (ejection fraction; maximum rate of rise of left-ventricular pressure; preload recruitable stroke work), relaxation (maximum rate of fall of left-ventricular pressure; Tau), and increased end-diastolic stiffness were significantly improved after the NOD treatment. Following the transplantation, the NOD-treatment of BDD improved impaired systolic function and ventricular relaxation. Additionally, after transplantation increased interleukin-6, tumor necrosis factor TNF-α, NF-kappaB-p65, and nuclear factor (NF)-kappaB-p105 gene expression, and increased caspase-3, TNF-α and NF-kappaB protein expression could be significantly downregulated by the NOD treatment compared to BDD. BDD postconditioning with NOD through downregulation of the pro-apoptotic factor caspase-3, pro-inflammatory cytokines, and NF-kappaB may protect the heart against the myocardial injuries associated with brain death and ischemia/reperfusion.

Androgens in women after allogeneic hematopoietic cell transplantation: impact of chronic GvHD and glucocorticoid therapy.

Low androgen levels may contribute to sexual dysfunction in women after allogeneic hematopoietic cell transplantation (alloHCT). However, data on serum androgens in women after alloHCT are limited. The aim of this study was to assess androgen levels and their association with chronic GvHD (cGvHD) and glucocorticoid (GC) therapy. Included were 65 allografted women, 33 with cGvHD, and 23 of these were on GC therapy. Controls were 94 healthy, age-matched women. Supportive study groups were women after autologous HCT (autoHCT; n=20) and non-transplanted women on GC therapy (n=26). Compared with controls, free testosterone (free T) and dehydroepiandrosterone sulfate (DHEAS) levels were lower in both the alloHCT group and GC groups; P<0.0001 and P<0.05, respectively. Androgens in the autoHCT group were similar or higher than controls. In the subgroup of alloHCT patients without cGvHD, free T was similar to controls (7.2 vs 8.6 pmol/L; P=0.42), whereas DHEAS levels was lower than controls (1.7 vs 2.5 µmol/L; P=0.008). Compared with controls, cGvHD without GC (n=10) was associated with lower free T and DHEAS; P=0.004 and P=0.0004, respectively). The lowest androgen levels were seen in women with both cGvHD and GC therapy. In conclusion, low serum androgens were associated with cGvHD and GC therapy, prompting for studies assessing a possible association between low androgens and sexual dysfunction and quality of life in allografted women.

[Social psychiatry and neurobiology : A long overdue convergence exemplified by schizophrenia]. / Sozialpsychiatrie und Neurobiologie : Eine längst fällige Annäherung am Beispiel der Schizophrenie.

BACKGROUND: The proliferation of biological psychiatry has greatly increased over the last two decades. With the possibility to carry out brain research using modern technical methods, it seemed that social influencing factors would lose importance in the development of mental diseases; however, in actual fact this does not seem to be justified. It is necessary to overcome this separation, in that social factors are incorporated into a conceptual framework in the development of mental diseases, which simultaneously also takes the results of current neurobiological research into consideration. OBJECTIVES AND METHODS: The aims of this review article are to summarize the current state of sociopsychiatric research and to emphasize the perspectives of the biological principles and their validity with respect to the social dimensions of psychiatry, as exemplified by schizophrenic disorders. The article presents the options for a biosocial approach in social psychiatry and gives an overview of the currently available literature. RESULTS AND CONCLUSION: There is an abundance of neurobiological research approaches, which are closely associated with sociopsychiatric topics, such as social cognition. Social psychiatry and biological psychiatry should no longer be considered as diametrically opposed subdisciplines. On the contrary, the options which could emerge from a synthesis must be used in research and clinical practice.

Direct costs in impaired glucose regulation: results from the population-based Heinz Nixdorf Recall study.

OBJECTIVE: For the first time, this population-based study sought to analyze healthcare utilization and associated costs in people with normal fasting glycemia (NFG), impaired fasting glycemia (IFG), as well as previously undetected diabetes and previously diagnosed diabetes linking data from the prospective German Heinz Nixdorf Recall (HNR) study with individual claims data from German statutory health insurances. RESEARCH DESIGN AND METHODS: A total of 1709 participants of the HNR 5-year follow-up (mean age (SD) 64.9 (7.5) years, 44.5% men) were included in the study. Age-standardized and sex-standardized healthcare utilization and associated costs (reported as € for the year 2008, perspective of the statutory health insurance) were stratified by diabetes stage defined by the participants' self-report and fasting plasma glucose values. Cost ratios (CRs) were estimated using two-part regression models, adjusting for age, sex, sociodemographic variables and comorbidity. RESULTS: The mean total direct healthcare costs for previously diagnosed diabetes, previously undetected diabetes, IFG, and NFG were €2761 (95% CI 2378 to 3268), €2210 (1483 to 4279), €2035 (1732 to 2486) and €1810 (1634 to 2035), respectively. Corresponding age-adjusted and sex-adjusted CRs were 1.53 (1.30 to 1.80), 1.16 (0.91 to 1.47), and 1.09 (0.95 to 1.25) (reference: NFG). Inpatient, outpatient and medication costs varied in order between people with IFG and those with previously undetected diabetes. CONCLUSIONS: The study provides claims-based detailed cost data in well-defined glucose metabolism subgroups. CRs of individuals with IFG and previously undetected diabetes were surprisingly low. Data are important for the model-based evaluation of screening programs and interventions that are aimed either to prevent diabetes onset or to improve diabetes therapy as well.

Conjunctival polyploid cells and donor-derived myofibroblasts in ocular GvHD.

After allogeneic hematopoietic stem cell transplantation (allo-SCT), ocular GvHD is a common complication, typical symptoms being dry eye syndrome with features of fibrosis. In this study, we have identified and quantified two cell types-myofibroblasts (MFB) and polyploid (PP) cells-in the conjunctival surface of allo-SCT patients (pts) and have explored their kinetics and association with local and systemic GvHD. Results are compared with control groups of (a) pretransplant samples from allo-SCT patients, (b) recipients of autologous transplantation (auto-SCT) and (c) healthy controls. Imprint cytologies were obtained by pressing the conjunctival surface with a sterile, non-abrasive cellulose acetate filter (Millipore). After retraction, typically a monolayer of the outermost cells of the epithelium were retrieved. MFB were identified by immunofluorescent (IF) staining for alpha-smooth muscle protein. PP cells were detected by aberrant chromosome content analyzed via X/Y-FISH (X/Y fluorescence in situ hybridization). In female pts with a male donor (MF group), donor genotype were identified by sex chromosome detection using FISH methodology. IF and FISH methods were applied in situ on the same filter, and amounts of MFB and PP cells are expressed as the percentage of all cells on the filter. In all, 70 samples from 46 pts were obtained 1-122 months after allo-SCT. The total MFB density (MFB(TOT)) was higher in allo-SCT pts compared with healthy individuals and auto-SCT pts and increased by time after transplantation (P<0.001). In MF recipients, this increase proved to be due to a significant (P<0.001) and gradual elevation of donor-derived MFB (MFB(XY)), whereas recipient-derived MFB (MFB(XX)) did not vary over time. Clinical ocular GvHD correlated with MFB(XY)/MFB(TOT) ratio (P=0.034), whereas no association between MFB(TOT) or MFB(XY) systemic GvHD was observed. In the MF group (n=25), both MFB(XY) and MFB(XX) were detected on 28 of the 37 imprints (76%). In pts >36 months post transplant, on 11/12 imprints, a median of 9.4% (1.4-39%) MFB(XY) and 3.6% (0-11%) MFB(XX) was found. In one patient, 1.6% MFB(XY) were detected at 3 weeks post transplant. PP cells (6-24n), exclusively of recipient origin, were found to a median of 0.6% (0-37%). The PP cell density differed significantly (P<0.001) between time intervals, with a maximum 8.9% (0-35%) of all cells at 3-12 months. No correlation between PP cells and GvHD (ocular or systemic) was observed. The MFB has been indicated as a culprit in chronic inflammation and fibrosis. The observation that MFB(XY)/MFB(TOT) ratio correlated with ocular GvHD suggests a role of donor MFB in GvHD pathogenesis. The constant finding of recipient-derived MFB(XX) cells many years after transplant in pts with 100% donor hematopoiesis indicates that there is a non-hematopoietic differentiation route to MFB. The origin and role of PP cells after allo-SCT remains obscure.