Category: Statistics

J Clin Oncol. 2023 Jan 6:JCO2200509. doi: 10.1200/JCO.22.00509. Online ahead of print.

ABSTRACT

PURPOSE: To present primary and final analyses from the randomized, double-blind, placebo-controlled, phase III iNTEGRATE study, which evaluated the safety and efficacy of ibrutinib with prednisone in previously untreated patients with chronic graft-versus-host disease (cGVHD).

METHODS: Patients (age ≥ 12 years) with newly diagnosed moderate or severe cGVHD, requiring systemic corticosteroid therapy, and with no prior systemic treatment for cGVHD were randomly assigned 1:1 to receive ibrutinib 420 mg once daily plus prednisone, starting at 1 mg/kg once daily or placebo plus prednisone. The primary end point was response rate at 48 weeks according to 2014 National Institutes of Health Consensus Development Project Criteria. Other end points included event-free survival, duration of response, time to withdrawal of immunosuppressants, improvement in Lee cGVHD Symptom Scale score, overall survival (OS), and safety.

RESULTS: Ninety-five and 98 patients enrolled in the ibrutinib-prednisone and placebo-prednisone arms, respectively. At 48 weeks, response rates were 41% (ibrutinib-prednisone) and 37% (placebo-prednisone; P = .54). At 33 months of follow-up, median duration of response was 19 months (ibrutinib-prednisone) and 10 months (placebo-prednisone; P = .10). Median event-free survival was 15 months (ibrutinib-prednisone) and 8 months (placebo-prednisone; hazard ratio, 0.76; 95% CI, 0.54 to 1.1; P = .11). Improvement in overall Lee cGVHD Symptom Scale was 43% (ibrutinib-prednisone) and 31% (placebo-ibrutinib; P = .07). Median OS was not reached in either arm. The 24-month Kaplan-Meier OS estimates were 80% for both arms (hazard ratio, 1.06; 95% CI, 0.59 to 1.90). Grade ≥ 3 serious adverse events occurred in 49% (ibrutinib-prednisone) and 47% (placebo-prednisone) of patients.

CONCLUSION: There was no statistical difference observed in the primary and secondary end points with ibrutinib-prednisone treatment. No new safety signals were observed with ibrutinib treatment in previously untreated patients with cGVHD. The primary end point of iNTEGRATE was not met.

PMID:36608310 | DOI:10.1200/JCO.22.00509

Expert Opin Drug Saf. 2023 Jan 6. doi: 10.1080/14740338.2023.2166485. Online ahead of print.

ABSTRACT

BACKGROUND: This study aimed to evaluate efficacy and safety of dapagliflozin as a monotherapy glucose lowering drug treatment for older adults with diabetes.

RESEARCH DESIGN & METHODS: Randomised controlled trials (RCTs) reports were retrieved from PubMed, Embase Cochrane Library and Web of Science from database inception to May 8, 2021. Publication bias and heterogeneity were assessed using the Cochrane risk-of-bias tool and the Cochrane Q statistic, respectively.

RESULTS: Compared with placebo, dapagliflozin as a monotherapy glucose lowering drug did improve the control of HbA1c and fasting plasma glucose levels in older adults. Our analysis also confirmed that the body weight of older adults was well controlled under treatment of dapagliflozin as a monotherapy glucose lowering drug. Patients in older adults with diabetes took a higher risk of genital infection and renal impairment or failure after treatment of dapagliflozin. In addition, treatment with dapagliflozin reduced risk of hypoglycemia, and did not reveal increased risk of urinary tract infection and developing fractures compared to placebo in older adults.

CONCLUSION: Dapagliflozin as a monotherapy glucose lowering drug appeared to be an effective treatment for older adults with diabetes, although it might increase risk of genital infection and renal impairment or failure.

PMID:36608279 | DOI:10.1080/14740338.2023.2166485

Phys Rev Lett. 2022 Dec 16;129(25):251103. doi: 10.1103/PhysRevLett.129.251103.

ABSTRACT

We present the measurement of the energy dependence of the boron flux in cosmic rays and its ratio to the carbon flux in an energy interval from 8.4 GeV/n to 3.8 TeV/n based on the data collected by the Calorimetric Electron Telescope (CALET) during ∼6.4 yr of operation on the International Space Station. An update of the energy spectrum of carbon is also presented with an increase in statistics over our previous measurement. The observed boron flux shows a spectral hardening at the same transition energy E_{0}∼200 GeV/n of the C spectrum, though B and C fluxes have different energy dependences. The spectral index of the B spectrum is found to be γ=-3.047±0.024 in the interval 25<E<200 GeV/n. The B spectrum hardens by Δγ_{B}=0.25±0.12, while the best fit value for the spectral variation of C is Δγ_{C}=0.19±0.03. The B/C flux ratio is compatible with a hardening of 0.09±0.05, though a single power-law energy dependence cannot be ruled out given the current statistical uncertainties. A break in the B/C ratio energy dependence would support the recent AMS-02 observations that secondary cosmic rays exhibit a stronger hardening than primary ones. We also perform a fit to the B/C ratio with a leaky-box model of the cosmic-ray propagation in the Galaxy in order to probe a possible residual value λ_{0} of the mean escape path length λ at high energy. We find that our B/C data are compatible with a nonzero value of λ_{0}, which can be interpreted as the column density of matter that cosmic rays cross within the acceleration region.

PMID:36608255 | DOI:10.1103/PhysRevLett.129.251103

Phys Rev Lett. 2022 Dec 16;129(25):258001. doi: 10.1103/PhysRevLett.129.258001.

ABSTRACT

Active nematics can be modeled using phenomenological continuum theories that account for the dynamics of the nematic director and fluid velocity through partial differential equations (PDEs). While these models provide a statistical description of the experiments, the relevant terms in the PDEs and their parameters are usually identified indirectly. We adapt a recently developed method to automatically identify optimal continuum models for active nematics directly from spatiotemporal data, via sparse regression of the coarse-grained fields onto generic low order PDEs. After extensive benchmarking, we apply the method to experiments with microtubule-based active nematics, finding a surprisingly minimal description of the system. Our approach can be generalized to gain insights into active gels, microswimmers, and diverse other experimental active matter systems.

PMID:36608242 | DOI:10.1103/PhysRevLett.129.258001

Phys Rev Lett. 2022 Dec 16;129(25):253602. doi: 10.1103/PhysRevLett.129.253602.

ABSTRACT

We explore the emergence and active control of optical bistability in a two-level atom near a graphene sheet. Our theory incorporates self-interaction of the optically driven atom and its coupling to electromagnetic vacuum modes, both of which are sensitive to the electrically tunable interband transition threshold in graphene. We show that electro-optical bistability and hysteresis can manifest in the intensity, spectrum, and quantum statistics of the light emitted by the atom, which undergoes critical slow-down to steady state. The optically driven atom-graphene interaction constitutes a platform for active control of driven atomic systems in coherent quantum control and atomic physics.

PMID:36608233 | DOI:10.1103/PhysRevLett.129.253602

Phys Rev Lett. 2022 Dec 16;129(25):250501. doi: 10.1103/PhysRevLett.129.250501.

ABSTRACT

Triply degenerate points (TDPs), which correspond to new types of topological semimetals, can support novel quasiparticles possessing effective integer spins while preserving Fermi statistics. Here by mapping the momentum space to the parameter space of a three-level system in a trapped ion, we experimentally explore the transitions between different types of TDPs driven by spin-tensor-momentum couplings. We observe the phase transitions between TDPs with different topological charges by measuring the Berry flux on a loop surrounding the gap-closing lines, and the jump of the Berry flux gives the jump of the topological charge (up to a 2π factor) across the transitions. For the Berry flux measurement, we employ a new method by examining the geometric rotations of both spin vectors and tensors, which lead to a generalized solid angle equal to the Berry flux. The controllability of a multilevel ion offers a versatile platform to study high-spin physics, and our Letter paves the way to explore novel topological phenomena therein.

PMID:36608231 | DOI:10.1103/PhysRevLett.129.250501

Phys Rev Lett. 2022 Dec 16;129(25):250503. doi: 10.1103/PhysRevLett.129.250503.

ABSTRACT

Quantum metrology with entangled resources aims to achieve sensitivity beyond the standard quantum limit by harnessing quantum effects even in the presence of environmental noise. So far, sensitivity has been mainly discussed from the viewpoint of reducing statistical errors under the assumption of perfect knowledge of a noise model. However, we cannot always obtain complete information about a noise model due to coherence time fluctuations, which are frequently observed in experiments. Such unknown fluctuating noise leads to systematic errors and nullifies the quantum advantages. Here, we propose an error-mitigated quantum metrology that can filter out unknown fluctuating noise with the aid of purification-based quantum error mitigation. We demonstrate that our protocol mitigates systematic errors and recovers superclassical scaling in a practical situation with time-inhomogeneous bias-inducing noise. Our result is the first demonstration to reveal the usefulness of purification-based error mitigation for unknown fluctuating noise, thus paving the way not only for practical quantum metrology but also for quantum computation affected by such noise.

PMID:36608222 | DOI:10.1103/PhysRevLett.129.250503

Phys Rev Lett. 2022 Dec 23;129(26):261102. doi: 10.1103/PhysRevLett.129.261102.

ABSTRACT

Rotating or charged classical black holes in isolation possess a special surface in their interior, the Cauchy horizon, beyond which the evolution of spacetime (based on the equations of General Relativity) ceases to be deterministic. In this Letter, we study the effect of a quantum massless scalar field on the Cauchy horizon inside a rotating (Kerr) black hole that is evaporating via the emission of Hawking radiation (corresponding to the field being in the Unruh state). We calculate the flux components (in Eddington coordinates) of the renormalized stress-energy tensor of the field on the Cauchy horizon, as functions of the black hole spin and of the polar angle. We find that these flux components are generically nonvanishing. Furthermore, we find that the flux components change sign as these parameters vary. The signs of the fluxes are important, as they provide an indication of whether the Cauchy horizon expands or crushes (when backreaction is taken into account). Regardless of these signs, our results imply that the flux components generically diverge on the Cauchy horizon when expressed in coordinates which are regular there. This is the first time that irregularity of the Cauchy horizon under a semiclassical effect is conclusively shown for (four-dimensional) spinning black holes.

PMID:36608207 | DOI:10.1103/PhysRevLett.129.261102

Phys Rev Lett. 2022 Dec 23;129(26):263601. doi: 10.1103/PhysRevLett.129.263601.

ABSTRACT

We report on nonlinear squeezing effects of polarization states of light by harnessing the intrinsic correlations from a polarization-entangled light source and click-counting measurements. Nonlinear Stokes operators are obtained from harnessing the click-counting theory in combination with angular-momentum-type algebras. To quantify quantum effects, theoretical bounds are derived for second- and higher-order moments of nonlinear Stokes operators. The experimental validation of our concept is rendered possible by developing an efficient source, using a spectrally decorrelated type-II phase-matched waveguide inside a Sagnac interferometer. Correlated click statistics and moments are directly obtained from an eight-time-bin quasi-photon-number-resolving detection system. Macroscopic Bell states that are readily available with our source show the distinct nature of nonlinear polarization squeezing in up to eighth-order correlations, matching our theoretical predictions. Furthermore, our data certify nonclassical correlations with high statistical significance, without the need to correct for experimental imperfections and limitations. Also, our nonlinear squeezing can identify nonclassicality of noisy quantum states which is undetectable with the known linear polarization-squeezing criterion.

PMID:36608182 | DOI:10.1103/PhysRevLett.129.263601

Neuroreport. 2023 Feb 1;34(2):93-101. doi: 10.1097/WNR.0000000000001864. Epub 2022 Dec 17.

ABSTRACT

Autism spectrum disorder (ASD) frequently occurs accompanied by attention-deficit/hyperactivity disorder (ADHD), which catches increasing attention. The comorbid diagnosis of ASD with ADHD (ASD + ADHD) is permitted in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-V). However, compared to autism spectrum disorder without other symptoms (ASD-only), the special neural underpinnings in ASD+ADHD remain unclear. Therefore, this study aimed to uncover the differences in cortical complexity between ASD + ADHD and ASD-only patients. A total of 114 ASD participants (i.e. containing 40 ASD + ADHD and 74 ASD-only participants) with T1-weighted magnetic resonance images were collected from the Autism Brain Imaging Data Exchange II. Afterward, a surface-based morphometry method was carried out to compare the cortical complexity (i.e. gyrification index, fractal dimension, and sulcal depth) between the ASD + ADHD and ASD-only cohorts. Results showed the increased fractal dimension in the right fusiform gyrus of the ASD + ADHD cohort in comparison to the ASD-only cohort. Moreover, the ASD + ADHD cohort exhibited increased sulcal depth in the left middle temporal gyrus/inferior temporal gyrus and right middle temporal gyrus compared to the ASD-only cohort. Last but not least, the increased gyrification index in the insula/postcentral gyrus was observed in the ASD + ADHD cohort in comparison to the ASD-only cohort. Overall, the present study contributes to the delineation of particular structural abnormalities in ASD + ADHD than ASD-only, enriching the evidence of the combined phenotype of ASD + ADHD.

PMID:36608165 | DOI:10.1097/WNR.0000000000001864