Gaussian versus Non-Gaussian Filtering of Phase-Insensitive Nonclassicality.

Measures of quantum properties are essential to understanding the fundamental differences between quantum and classical systems as well as quantifying resources for quantum technologies. Here, two broad classes of bosonic phase-space functions, which are filtered versions of the Glauber-Sudarshan P function, are compared with regard to their ability to uncover nonclassical effects of light through their negativities. Gaussian filtering of the P function yields the family of s-parametrized quasiprobabilities, while more powerful regularized nonclassicality quasiprobabilities are obtained by non-Gaussian filtering. A method is proposed to directly sample such phase-space functions for the restricted case of phase-independent quantum states from balanced homodyne measurements. This overcomes difficulties of previous approaches that manually append uniformly distributed optical phases to the measured quadrature data. We experimentally demonstrate this technique for heralded single- and two-photon states using balanced homodyne detection with varying efficiency. The s-parametrized quasiprobabilities, which can be directly sampled, are non-negative for detection efficiencies below 0.5. By contrast, we show that significant negativities of non-Gaussian filtered quasiprobabilities uncover nonclassical effects for arbitrarily low efficiencies.

Quantum Correlations beyond Entanglement and Discord.

Dissimilar notions of quantum correlations have been established, each being motivated through particular applications in quantum information science and each competing for being recognized as the most relevant measure of quantumness. In this contribution, we experimentally realize a form of quantum correlation that exists even in the absence of entanglement and discord. We certify the presence of such quantum correlations via negativities in the regularized two-mode Glauber-Sudarshan function. Our data show compatibility with an incoherent mixture of orthonormal photon-number states, ruling out quantum coherence and other kinds of quantum resources. By construction, the quantumness of our state is robust against dephasing, thus requiring fewer experimental resources to ensure stability. In addition, we theoretically show how multimode entanglement can be activated based on the generated, nonentangled state. Therefore, we implement a robust kind of nonclassical photon-photon correlated state with useful applications in quantum information processing.

Detector-Agnostic Phase-Space Distributions.

The representation of quantum states via phase-space functions constitutes an intuitive technique to characterize light. However, the reconstruction of such distributions is challenging as it demands specific types of detectors and detailed models thereof to account for their particular properties and imperfections. To overcome these obstacles, we derive and implement a measurement scheme that enables a reconstruction of phase-space distributions for arbitrary states whose functionality does not depend on the knowledge of the detectors, thus defining the notion of detector-agnostic phase-space distributions. Our theory presents a generalization of well-known phase-space quasiprobability distributions, such as the Wigner function. We implement our measurement protocol, using state-of-the-art transition-edge sensors without performing a detector characterization. Based on our approach, we reveal the characteristic features of heralded single- and two-photon states in phase space and certify their nonclassicality with high statistical significance.

Introducing FDG PET/CT-guided chemoradiotherapy for stage III NSCLC in low- and middle-income countries: preliminary results from the IAEA PERTAIN trial.

PURPOSE: Patients with stage III non-small-cell lung cancer (NSCLC) treated with chemoradiotherapy (CRT) in low- and middle-income countries (LMIC) continue to have a poor prognosis. It is known that FDG PET/CT improves staging, treatment selection and target volume delineation (TVD), and although its use has grown rapidly, it is still not widely available in LMIC. CRT is often used as sequential treatment, but is known to be more effective when given concurrently. The aim of the PERTAIN study was to assess the impact of introducing FDG PET/CT-guided concurrent CRT, supported by training and quality control (QC), on the overall survival (OS) and progression-free survival (PFS) of patients with stage III NSCLC. METHODS: The study included patients with stage III NSCLC from nine medical centres in seven countries. A retrospective cohort was managed according to local practices between January 2010 and July 2014, which involved only optional diagnostic FDG PET/CT for staging (not for TVD), followed by sequential or concurrent CRT. A prospective cohort between August 2015 and October 2018 was treated according to the study protocol including FDG PET/CT in treatment position for staging and multimodal TVD followed by concurrent CRT by specialists trained in protocol-specific TVD and with TVD QC. Kaplan-Meier analysis was used to assess OS and PFS in the retrospective and prospective cohorts. RESULTS: Guidelines for FDG PET/CT image acquisition and TVD were developed and published. All specialists involved in the PERTAIN study received training between June 2014 and May 2016. The PET/CT scanners used received EARL accreditation. In November 2018 a planned interim analysis was performed including 230 patients in the retrospective cohort with a median follow-up of 14 months and 128 patients in the prospective cohort, of whom 69 had a follow-up of at least 1 year. Using the Kaplan-Meier method, OS was significantly longer in the prospective cohort than in the retrospective cohort (23 vs. 14 months, p = 0.012). In addition, median PFS was significantly longer in the prospective cohort than in the retrospective cohort (17 vs. 11 months, p = 0.012). CONCLUSION: In the PERTAIN study, the preliminary results indicate that introducing FDG PET/CT-guided concurrent CRT for patients with stage III NSCLC in LMIC resulted in a significant improvement in OS and PFS. The final study results based on complete data are expected in 2020.

Incomplete Detection of Nonclassical Phase-Space Distributions.

We implement the direct sampling of negative phase-space functions via unbalanced homodyne measurement using click-counting detectors. The negativities significantly certify nonclassical light in the high-loss regime using a small number of detectors which cannot resolve individual photons. We apply our method to heralded single-photon states and experimentally demonstrate the most significant certification of nonclassicality for only two detection bins. By contrast, the frequently applied Wigner function fails to directly indicate such quantum characteristics for the quantum efficiencies present in our setup without applying additional reconstruction algorithms. Therefore, we realize a robust and reliable approach to characterize nonclassical light in phase space under realistic conditions.

Immunologic effects of chronic administration of tofacitinib, a Janus kinase inhibitor, in cynomolgus monkeys and rats - Comparison of juvenile and adult responses.

Tofacitinib, an oral Janus kinase (JAK) inhibitor for treatment of rheumatoid arthritis, targets JAK1, JAK3, and to a lesser extent JAK2 and TYK2. JAK1/3 inhibition impairs gamma common chain cytokine receptor signaling, important in lymphocyte development, homeostasis and function. Adult and juvenile cynomolgus monkey and rat studies were conducted and the impact of tofacitinib on immune parameters (lymphoid tissues and lymphocyte subsets) and function (T-dependent antibody response (TDAR), mitogen-induced T cell proliferation) assessed. Tofacitinib administration decreased circulating T cells and NK cells in juvenile and adult animals of both species. B cell decreases were observed only in rats. These changes and decreased lymphoid tissue cellularity are consistent with the expected pharmacology of tofacitinib. No differences were observed between juvenile and adult animals, either in terms of doses at which effects were observed or differential effects on immune endpoints. Lymphomas were observed in three adult monkeys. Tofacitinib impaired the primary TDAR in juvenile monkeys, although a recall response was generated. Complete or partial reversal of the effects on the immune system was observed.

Renal and Hematologic Comparative Effects of Dissociated Agonist of the Glucocorticoid Receptor and Prednisone in Dogs With and Without Food Restriction.

Glomerulopathy and body weight gain were noted after chronic oral administration of a novel nonsteroidal dissociated agonist of the glucocorticoid receptor compound, fosdagrocorat, to beagle dogs fed an ad libitum diet. To further investigate the role of diet and treatment with either fosdagrocorat or the glucocorticoid comparator, prednisone, on renal safety, a 13-week investigative study was conducted in beagle dogs. Renal histopathology, clinical chemistry, urinalysis, glomerular filtration rate (GFR), body weight, heart rate, blood pressure (BP), and hematology were investigated in restricted- and ad libitum-fed dogs administered prednisone (2.2 mg/kg/d), fosdagrocorat (5 mg/kg/d), or vehicle for 13 weeks. Glomerulopathy was primarily observed in fosdagrocorat- and prednisone-treated ad libitum but not in feed-restricted or ad libitum vehicle-treated dogs. Kidneys in dogs from the prednisone-treated ad libitum had the greatest incidence and severity of tubular degenerative changes. Increased urine volume and decreased urine-specific gravity were present in prednisone- and fosdagrocorat-treated dogs, regardless of diet. These changes were not associated with consistent changes in GFR. Fosdagrocorat or prednisone treatment ad libitum dogs had the greatest increase in body weight gain. Sporadic changes in systolic and diastolic BP were noted in fosdagrocorat- and prednisone-treated groups. Significant reductions in serum cortisol and absolute eosinophils were noted in both ad libitum- and restriction-fed prednisone- and fosdagrocorat-treated dogs. In conclusion, prednisone-treated dogs fed ad libitum had greater glucocorticoid-induced renal effects than those dosed with fosdagrocorat.

Anomalous Quantum Correlations of Squeezed Light.

Three different noise moments of field strength, intensity, and their correlations are simultaneously measured. For this purpose a homodyne cross-correlation measurement [1] is implemented by superimposing the signal field and a weak local oscillator on an unbalanced beam splitter. The relevant information is obtained via the intensity noise correlation of the output modes. Detection details like quantum efficiencies or uncorrelated dark noise are meaningless for our technique. Yet unknown insight in the quantumness of a squeezed signal field is retrieved from the anomalous moment, correlating field strength with intensity noise. A classical inequality including this moment is violated for almost all signal phases. Precognition on quantum theory is superfluous, as our analysis is solely based on classical physics.

Conditional Hybrid Nonclassicality.

We derive and implement a general method to characterize the nonclassicality in compound discrete- and continuous-variable systems. For this purpose, we introduce the operational notion of conditional hybrid nonclassicality which relates to the ability to produce a nonclassical continuous-variable state by projecting onto a general superposition of discrete-variable subsystem. We discuss the importance of this form of quantumness in connection with interfaces for quantum communication. To verify the conditional hybrid nonclassicality, a matrix version of a nonclassicality quasiprobability is derived and its sampling approach is formulated. We experimentally generate an entangled, hybrid Schrödinger cat state, using a coherent photon-addition process acting on two temporal modes, and we directly sample its nonclassicality quasiprobability matrix. The introduced conditional quantum effects are certified with high statistical significance.

Detector-Independent Verification of Quantum Light.

We introduce a method for the verification of nonclassical light which is independent of the complex interaction between the generated light and the material of the detectors. This is accomplished by means of a multiplexing arrangement. Its theoretical description yields that the coincidence statistics of this measurement layout is a mixture of multinomial distributions for any classical light field and any type of detector. This allows us to formulate bounds on the statistical properties of classical states. We apply our directly accessible method to heralded multiphoton states which are detected with a single multiplexing step only and two detectors, which are in our work superconducting transition-edge sensors. The nonclassicality of the generated light is verified and characterized through the violation of the classical bounds without the need for characterizing the used detectors.

Confirmation and next-generation sequencing of allele HLA-B*35:279 found in a family of a leukaemia patient with Western Asia origin.

The confirmation of novel allele HLA-B*35:279 in a family of a leukaemia patient with Western Asia origin is reported. Moreover, next-generation sequencing (NGS) resulted in whole-gene sequence data and revealed the inheritance of HLA-B*35:279 on the paternal haplotype.

Cellular and functional actions of tofacitinib related to the pathophysiology of hibernoma development.

Tofacitinib is an oral JAK inhibitor for the treatment of rheumatoid arthritis. In the 2-year carcinogenicity study with tofacitinib, increased incidence of hibernoma (a neoplasm of brown adipose tissue [BAT]) was noted in female rats at ≥30 mg/kg/day (≥41x human exposure multiples). Thus, signaling pathways within BAT were investigated by measuring BAT: weight, cell proliferation biomarkers, content of basal and prolactin-induced phosphorylated Signal Transducer and Activator of Transcription (STAT), and uncoupling protein 1 (UCP-1). The relationship between cardiovascular hemodynamics and plasma norepinephrine (NE) levels was also investigated. Tofacitinib administered to female rats at doses of 10, 30, or 75 mg/kg/day for 14 days increased BAT weight at 75 mg/kg/day and cell proliferation at ≥30 mg/kg/day. JAK inhibition, observed as lower pSTAT3 and pSTAT5 in BAT, was noted at ≥10 mg/kg/day, while lower activity of BAT was observed as lower UCP-1 protein at ≥30 mg/kg/day. In cultured brown adipocytes, prolactin-induced increase in pSTAT5 and pSTAT3 were inhibited by tofacitinib in a concentration-dependent manner. Tofacitinib lowered blood pressure, increased heart rate, and resulted in dose-dependent increases in circulating NE. Thus, JAK/STAT inhibition in BAT and sympathetic stimulation are two factors which might contribute to the genesis of hibernomas by tofacitinib in rats.

Poststroke Rehabilitation and Restorative Care Utilization: A Comparison Between VA Community Living Centers and VA-contracted Community Nursing Homes.

BACKGROUND: Effective poststroke rehabilitation care can speed patient recovery and minimize patient functional disabilities. Veterans affairs (VA) community living centers (CLCs) and VA-contracted community nursing homes (CNHs) are the 2 major sources of institutional long-term care for Veterans with stroke receiving care under VA auspices. OBJECTIVES: This study compares rehabilitation therapy and restorative nursing care among Veterans residing in VA CLCs versus those Veterans in VA-contracted CNHs. RESEARCH DESIGN: Retrospective observational. SUBJECTS: All Veterans diagnosed with stroke, newly admitted to the CLCs or CNHs during the study period who completed at least 2 Minimum Data Set assessments postadmission. MEASURES: The outcomes were numbers of days for rehabilitation therapy and restorative nursing care received by the Veterans during their stays in CLCs or CNHs as documented in the Minimum Data Set databases. RESULTS: For rehabilitation therapy, the CLC Veterans had lower user rates (75.2% vs. 76.4%, P=0.078) and fewer observed therapy days (4.9 vs. 6.4, P<0.001) than CNH Veterans. However, the CLC Veterans had higher adjusted odds for therapy (odds ratio=1.16, P=0.033), although they had fewer average therapy days (coefficient=-1.53±0.11, P<0.001). For restorative nursing care, CLC Veterans had higher user rates (33.5% vs. 30.6%, P<0.001), more observed average care days (9.4 vs. 5.9, P<0.001), higher adjusted odds (odds ratio=2.28, P<0.001), and more adjusted days for restorative nursing care (coefficient=5.48±0.37, P<0.001). CONCLUSION: Compared with their counterparts at VA-contracted CNHs, Veterans at VA CLCs had fewer average rehabilitation therapy days (both unadjusted and adjusted), but they were significantly more likely to receive restorative nursing care both before and after risk adjustment.

Unbalanced Homodyne Correlation Measurements.

A method is introduced that allows one to measure normal-ordered moments of the displaced photon-number operator up to higher orders, without the need of photon-number resolving detectors. It is based on unbalanced homodyne correlation measurements, with the local oscillator being replaced by a displaced dephased laser. The measured moments yield a simple approximation of quasiprobabilities, representing the full quantum state. Quantum properties of light are efficiently certified through normal-ordered observables directly accessible by our method, which is illustrated for a weakly squeezed vacuum and a single-photon-added thermal state.

Atmospheric Quantum Channels with Weak and Strong Turbulence.

The free-space transfer of high-fidelity optical signals between remote locations has many applications, including both classical and quantum communication, precision navigation, clock synchronization, etc. The physical processes that contribute to signal fading and loss need to be carefully analyzed in the theory of light propagation through the atmospheric turbulence. Here we derive the probability distribution for the atmospheric transmittance including beam wandering, beam shape deformation, and beam-broadening effects. Our model, referred to as the elliptic beam approximation, applies to weak, weak-to-moderate, and strong turbulence and hence to the most important regimes in atmospheric communication scenarios.

Multipartite Entanglement of a Two-Separable State.

We consider a six-partite, continuous-variable quantum state that we have effectively generated by the parametric down-conversion of a femtosecond frequency comb. We show that, though this state is two-separable, i.e., it does not exhibit "genuine entanglement," it is undoubtedly multipartite entangled. The consideration of not only the entanglement of individual mode decompositions, but also of combinations of those, solves the puzzle and exemplifies the importance of studying different categories of multipartite entanglement.

Quantum Correlations from the Conditional Statistics of Incomplete Data.

We study, in theory and experiment, the quantum properties of correlated light fields measured with click-counting detectors providing incomplete information on the photon statistics. We establish a correlation parameter for the conditional statistics, and we derive the corresponding nonclassicality criteria for detecting conditional quantum correlations. Classical bounds for Pearson's correlation parameter are formulated that allow us, once they are violated, to determine nonclassical correlations via the joint statistics. On the one hand, we demonstrate nonclassical correlations in terms of the joint click statistics of light produced by a parametric down-conversion source. On the other hand, we verify quantum correlations of a heralded, split single-photon state via the conditional click statistics together with a generalization to higher-order moments. We discuss the performance of the presented nonclassicality criteria to successfully discern joint and conditional quantum correlations. Remarkably, our results are obtained without making any assumptions on the response function, quantum efficiency, and dark-count rate of photodetectors.

Spectral prediction of sediment chemistry in Lake Okeechobee, Florida.

High-resolution diffuse reflectance spectra in the visible and near-infrared wavelengths were used to predict chemical properties of sediment samples obtained from Lake Okeechobee (FL, USA). Chemometric models yielded highly effective prediction (relative percent difference (RPD) = SD/RMSE >2) for some sediment properties including total magnesium (Mg), total calcium (Ca), total nitrogen (TN), total carbon (TC), and organic matter content (loss on ignition (LOI)). Predictions for iron (Fe), aluminum (Al), and various forms of phosphorus (total P (TP), HCl-extractable P (HCl-P), and KCl-extractable P (KCl-P)) were also sufficiently accurate (RPD > 1.5) to be considered useful; predictions for other P fractions as well as all pore water properties were poor. Notably, scanning wet sediments resulted in only a 7 % decline in RPD scores. Moreover, interpolation maps based on values predicted from wet sediment spectra captured the same spatial patterns for Ca, Mg, TC, TN, and TP as maps derived directly from wet chemistry, suggesting that field scanning of perpetually saturated sediments may be a viable option for expediting sample analysis and greatly reducing mapping costs. Indeed, the accuracy of spectral model predictions compared favorably with the accuracy of kriging model predictions derived from wet chemistry observations suggesting that, for some analytes, higher density spatial sampling enabled by use of field spectroscopy could increase the geographic accuracy of monitoring for changes in lake sediment chemical properties.

How does geographic access affect in-hospital mortality for veterans with acute ischemic stroke?

OBJECTIVE: To examine the relationship between estimated travel time to admitting hospital and mortality for veterans with acute ischemic stroke, controlling for patient demographic, clinical, facility-level variables, as well as select in-hospital treatments and procedures. METHODS: A longitudinal observational population-based study. Information on all veterans discharged from a Veterans Administration Medical Center (VAMC) with an ischemic stroke diagnosis between October 1, 2006 and September 30, 2008 were examined. A total of 10,430 patients met the inclusion criteria for the study. Unadjusted differences between patients who died during the hospital stay versus those patients who were discharged alive, used χ analyses or Student t tests, as appropriate. Multivariable logistic regression was used to control for confounding effects of patient, treatment, and facility characteristics to examine the relationship between travel time and the bivariate outcome of in-hospital mortality. RESULTS: Travel time to the admitting VAMC, our primary variable of interest regarding the effect on in-hospital mortality, after adjusting for the patient, treatment, and facility characteristics showed that longer travel times significantly increased the odds of in-hospital mortality. Travel times ≥ 90 minutes had increased odds of in-hospital mortality (OR=1.476; 95% CI, 1.067-2.042) as compared with <30 minutes. CONCLUSIONS: Even after adjusting for the confounding effects of patient, treatment, and facility characteristics, travel time from home to admitting VAMC was significantly associated with in-hospital mortality.