Objective Of Phase Research Articles

Isolation of phase edges using off-axis q-plate filters.

Edge-enhanced microscopes with a q-plate have attracted more attention to enhance the edges of phase-amplitude objects in biological samples due to their capacity for all-directional edge enhancement, while differential interference-contrast microscopy enhances edges in only one-direction. However, the edge-enhanced microscopes cannot distinguish the edges of phase and amplitude objects, as both edges are equally enhanced. This study introduces a novel method for isolating the edge of a phase object from an amplitude object using an off-axis q-plate filter in a 4f system. Herein, we combined off-axis q-plates with four different displacements to isolate the phase object edge from the amplitude object. To demonstrate the proposed method, we conducted experiments using two distinct samples. The first sample comprised a phase test target surrounded by an aperture, and the second sample involved an overlap between the phase test target and a white hair with non-zero transmittance. In the samples, the isolated phase object edge is in good agreement with the theoretical expectations, and the amplitude object edge was reduced by approximately 93%. The proposed method is a novel and effective approach for isolating the edge of a phase object from an amplitude object and can be useful in various biological imaging applications.

Evaluating the Effects of Consecutive Phases of Plyometric Jump Training on Athletic Performance in Male Soccer Players: The Effect of Training Frequency and Volume Manipulations.

Moran, J, Vali, N, Tallent, J, Howe, L, Clemente, FM, Chaabene, H, and Ramirez-Campillo, R. Evaluating the effects of consecutive phases of plyometric jump training on athletic performance in male soccer players: The effect of training frequency and volume manipulations. J Strength Cond Res 38(6): 1082-1089, 2024-This 14-week, 2-phase study aimed to determine the relative effects of 1 day or 2 days of volume-matched plyometric training on athletic performance (10- and 40-m sprints, change of direction [COD], and vertical jump [VJ]) in male soccer players (phase 1). The objective of phase 2 was to determine the relative effects of higher- and lower-volume plyometric training protocols in maintaining any previously attained increases in athletic performance from phase 1. A randomized parallel-group trial design was utilized. In phase 1, subjects ( n = 24; mean age: 19.5 ± 1.2 years; mean height: 179.7 ± 7.1 cm; mean weight: 69.8 ± 6.9 kg) were randomly allocated to 1 of 2 groups to receive either 1 day or 2 days of volume- and intensity-matched plyometric training for a 7-week period. For the second 7-week period (phase 2), half of each group was randomized into either a lower-volume or higher-volume plyometric training group. In phase 1, both the 1-day group and the 2-day group attained comparably significant ( p < 0.001) increases in performance in all fitness tests ranging from effect sizes (ESs) ( d ) of 0.4 (95% confidence interval: 0.11 to 0.70) for 10-m sprint to 1.51 (0.42-2.60) for VJ. There were no significant differences between the performance increases in the 2 groups. In phase 2, neither group increased or decreased performance, maintaining all previously attained increases with only trivial ESs observed (-0.02 [-0.58 to 0.53] to 0.11 [-0.38 to 0.61]). Increases in 10- and 40-m sprint speed, COD speed, and VJ height can be achieved and maintained with as little as 1 plyometric training session per week. Sessions can include 120 jumps to induce increases of the reported magnitudes, with 60 jumps to maintain these increases thereafter, in male soccer players.

3D fluorescence imaging through scattering medium using transport of intensity equation and iterative phase retrieval.

In this paper, we have proposed a method of three-dimensional (3D) fluorescence imaging through a scattering medium. The proposed method combines the numerical digital phase conjugation propagation after measurement of the complex amplitude distribution of scattered light waves by the transport of intensity equation (TIE) with followed iterative phase retrieval to achieve 3D fluorescence imaging through a scattering medium. In the experiment, we present the quantitative evaluation of the depth position of fluorescent beads. In addition, for time-lapse measurement, cell division of tobacco-cultured cells was observed. Numerical results presented the effective range of the phase amount in the scattering medium. From these results, the proposed method is capable of recovering images degraded by a thin scattering phase object beyond a small phase change approximation.

Leveraging the depolarization of scattered light for holography with the Stokes correlation

A correlation holography technique for quantitative phase imaging from scattered depolarized light is proposed and experimentally demonstrated. To implement this technique, we exploit the depolarization of scattered light with the higher-order Stokes correlation. The higher-order Stokes correlation along with the two-step phase-shifting method is utilized to retrieve the complex Fourier coefficient, this subsequently supports the recovery of the phase in the correlation holography with the fourth-order correlation. A detailed theoretical framework is developed and is also supported by numerical simulation and experimental tests. The applicability of the proposed technique is experimentally demonstrated by quantitatively reconstructing different phase objects from the scattered depolarized light.

Spatially-coded Fourier ptychography: flexible and detachable coded thin films for quantitative phase imaging with uniform phase transfer characteristics.

Fourier ptychography (FP) is an enabling imaging technique that produces high-resolution complex-valued images with extended field coverages. However, when FP images a phase object with any specific spatial frequency, the captured images contain only constant values, rendering the recovery of the corresponding linear phase ramp impossible. This challenge is not unique to FP but also affects other common microscopy techniques -- a rather counterintuitive outcome given their widespread use in phase imaging. The underlying issue originates from the non-uniform phase transfer characteristic inherent in microscope systems, which impedes the conversion of object wavefields into discernible intensity variations. To address this challenge, we present spatially-coded Fourier ptychography (scFP), a new method that synergizes FP with spatial-domain coded detection for true quantitative phase imaging. In scFP, a flexible and detachable coded thin film is attached atop the image sensor in a regular FP setup. The spatial modulation of this thin film ensures a uniform phase response across the entire synthetic bandwidth. It improves reconstruction quality and corrects refractive index underestimation issues prevalent in conventional FP and related tomographic implementations. The inclusion of the coded thin film further adds a new dimension of measurement diversity in the spatial domain. The development of scFP is expected to catalyse new research directions and applications for phase imaging, emphasizing the need for true quantitative accuracy with uniform frequency response.

Quantum ghost imaging of a vector field.

Quantum ghost image technique utilizing position or momentum correlations between entangled photons can realize nonlocal reconstruction of the image of an object. In this work, based on polarization entanglement, we experimentally demonstrate quantum ghost imaging of vector images by using a geometric phase object. We also provide a corresponding theoretical analysis. Additionally, we offer a geometrical optics path explanation of ghost imaging for vector fields. The proposed strategy offers new insights into the fundamental development of ghost imaging and also holds great promise for developing complex structured ghost imaging techniques. Our work expanding the principle of ghost imaging to spatially varying vector beams will lead to interesting developments of this field.

Study of phase objects by dynamical diffraction of a spherical X-ray wave in a crystal using a temperature gradient

The possibility of reconstructing the internal structure of a phase object by dynamical diffraction of a spherical X-ray wave in a crystal using a temperature gradient was investigated. It is shown that the use of a temperature gradient directed perpendicular to the crystal surface makes it possible to obtain a focal distribution of all point inhomogeneities in the phase object on the exit surface of the crystal. By moving the phase object along the direction of the diffraction vector and registering the entire map of obtained data, one can restore the additional phase of the wave and the internal structure of the phase object section.

DOP81 Rosnilimab, a novel PD-1 agonist monoclonal antibody, reduces T cell proliferation, inflammatory cytokine secretion, and PD-1high expressing CD4 and CD8 T cells: Results from a Phase 1 healthy volunteer clinical trial

Abstract Background Programmed cell death protein 1 (PD-1) is expressed on activated T cells and is a key co-inhibitory node in immune regulation. By targeting regulatory mechanisms to modulate immune cells driving disease, there is an opportunity to restore immune balance. Rosnilimab is a PD-1 agonist antibody designed to reduce T cell proliferation and inflammatory cytokine secretion and deplete PD-1high T follicular helper, T peripheral helper, and T effector cells. It is being studied for ulcerative colitis (UC), where PD-1+ T cells are prevalent in inflamed lamina propria (&amp;gt;40%) and the periphery. The primary objective of this healthy volunteer Phase 1 study was to assess the safety and tolerability of single ascending doses (SAD) and multiple ascending doses (MAD) of rosnilimab. Findings from pharmacokinetic (PK) and pharmacodynamic (PD) assessments are summarized. Methods This single-centre study included 14 cohorts in SAD and 3 cohorts in MAD. Each cohort had 8 participants (6 active, 2 placebo [PBO]). Cohorts were enrolled sequentially in each phase. Intravenous (IV) and subcutaneous (SC) administration were assessed in SAD; SC route was assessed in MAD. Results A total of 144 participants were enrolled; 90 to active SAD cohorts, 18 to active MAD cohorts, and 30 and 6 to SAD and MAD PBO cohorts, respectively. Rosnilimab was well tolerated with no dose-limiting toxicities or deaths. Two serious adverse events were reported in SAD (deemed unrelated to treatment) and 0 in MAD. PD-1 expressing cells were reduced by ~50% in both CD4+ and CD8+ subsets, in a dose-dependent manner and in correlation with full receptor occupancy (RO) through Day 30 in SAD. PD activity was rapid with sustained reduction in PD-1+ T cells, and ex-vivo stimulation resulted in reduced T cell functional activity. This reduction was maximized on PD-1high expressing T cells: ~90% reduction vs baseline. There was no significant impact on the overall total T cell or regulatory T (Treg) cell numbers, resulting in restoration of T cell composition to a less activated state and a positive shift in the Treg:Teff ratio. An antigen-specific functional T cell assay measuring ex vivo interferon-gamma release in response to antigen challenge was inhibited up to ~90% vs baseline and the response lasted for more than 30 days following a single dose. Rosnilimab had a favourable PK profile consistent with full RO, a 2-week half-life, and dose-proportional exposure in IV and SC dosing. Conclusion Rosnilimab demonstrated favourable safety, PK, and PD activity. The role of PD-1 in UC pathophysiology coupled with these results and translational data, demonstrate proof of mechanism and support progression into a Phase 2 study of rosnilimab in UC. (NCT06127043)

Photo-Aligned Ferroelectric Liquid Crystal Fork Grating-Mediated Fast Switchable Spiral Phase Contrast Imaging

Extensive research has been devoted to spiral phase contrast imaging because of its notable capacity to enhance the edges of both phase and amplitude objects. We demonstrate a setup using ferroelectric liquid crystal (FLC) fork grating (FG) to enable switchable spiral phase contrast imaging within sub-milli-second responses. This system enables the electrical toggling between images featuring edge enhancement and those without it. The specially designed FLC FG generates a vortex beam while in a diffractive state and transmits a Gaussian beam when in a transmissive state. Using a two-step photo-alignment method, the produced FLC FG exhibits exceptional efficiency at approximately 35% and impressively rapid switching at around 307 μs. By introducing this method, we expand the potential applications of spiral phase contrast imaging, particularly in fields such as bio-sensing and photonics.

Polatuzumab vedotin plus rituximab and lenalidomide in patients with relapsed or refractory diffuse large B-cell lymphoma: a cohort of a multicentre, single-arm, phase 1b/2 study

Diffuse large B-cell lymphoma comprises nearly 30% of non-Hodgkin lymphoma cases and patients with relapsed or refractory diffuse large B-cell lymphoma who are ineligible for stem-cell transplantation have few treatment options and poor prognoses. We aimed to determine whether the novel combination of polatuzumab vedotin in combination with rituximab and lenalidomide (Pola+R+Len) would provide a tolerable treatment option with enhanced antitumour response in patients with relapsed or refractory diffuse large B-cell lymphoma. This completed phase 1b/2, open-label, multicentre, single-arm study (GO29834) evaluated the safety and efficacy of Pola+R+Len in patients with relapsed or refractory diffuse large B-cell lymphoma at 19 sites in three countries (USA, Spain, and UK). Patients (≥18 years old) were eligible for inclusion if they had histologically documented CD20-positive relapsed or refractory diffuse large B-cell lymphoma and Eastern Cooperative Oncology Group performance status of 2 or lower, had received at least one previous line of chemoimmunotherapy, including an anti-CD20 agent, and were ineligible for stem-cell transplantation. The dose-escalation phase (1b) used escalating doses of lenalidomide to find the recommended phase 2 dose. Patients received six 28-day cycles of induction treatment with intravenous rituximab 375 mg/m2 and intravenous polatuzumab vedotin 1·8 mg/kg (all cohorts) plus oral lenalidomide at the following doses: 10 mg (cohort A); 15 mg (cohort B); and 20 mg (cohort C). Rituximab and polatuzumab vedotin were administered on day 1 and lenalidomide on days 1-21 of each 28-day cycle. During the dose-expansion phase (2), patients received six 28-day cycles of Pola+R+Len at the recommended phase 2 dose established during dose escalation. In both phases, patients with a complete response or partial response at the end of induction were eligible for post-induction therapy with rituximab 375 mg/m2 on day 1 and lenalidomide 10 mg/day on days 1-21 of each 28-day cycle for a maximum of 6 cycles. The primary safety objective of the dose-escalation phase was identification of the maximum tolerated dose through incidence of dose-limiting toxic effects. The primary efficacy outcome of the dose-expansion phase was Independent Review Committee-assessed complete response rate at end of induction, based on PET-CT. Analyses were conducted in the safety population, which included all patients who received at least one dose of any study drug, and the efficacy population, which included all patients who received at least one dose of any study drug at the recommended phase 2 dose. This study is registered with ClinicalTrials.gov, number NCT02600897. Between July 11, 2017 and Feb 3, 2020, 57 patients were enrolled (median age 71 years [IQR 60-75]; 38 [67%] were male and 19 (33%) were female; 47 [82%] were not Hispanic or Latino; and the median previous lines of therapy was 2 [IQR 1-3]). 18 participants were included in phase 1b and 39 were included in phase 2. Phase 1b confirmed a 20 mg recommended phase 2 dose for lenalidomide. After a median follow-up of 11·8 months (IQR 4·7-25·8), the complete response rate, as assessed by the Independent Review Committee, was 31% (90% CI 20-43). The most common grade 3-4 adverse events were neutropenia (35 [61%] of 57) and thrombocytopenia (eight [14%] of 57). Serious adverse events were reported in 23 (40%) of 57 patients and one patient died due to a treatment-related adverse event (neutropenic sepsis). Although the combination of Pola+R+Len did not meet the prespecified activity threshold, some patients derived clinical benefit and the regimen had a tolerable safety profile in patients with relapsed or refractory diffuse large B-cell lymphoma. Genentech/F Hoffmann-La Roche.

Zooplankton vulnerability to glyphosate exacerbated by global change

Anthropogenic activities generate a severe footprint at a global scale. Intensive agriculture is a global change driver that affects aquatic systems due to the discharge of pollutants. This situation can be modified or aggravated by other aspects, such as the disturbance history and other global change factors. Following our study line, it is necessary to evaluate how the disturbance history combined with temperature changes can affect the functioning of aquatic systems. The objectives of this study were divided into two phases. The objectives of phase 1 were to induce vulnerability in Daphnia magna populations through a disturbance history based on sublethal glyphosate concentration exposure under different temperature conditions (20 °C and 25 °C). In phase 2, vulnerability was assessed through the exposure to subsequent stressors (starvation, increased salinity and paracetamol) combined with changes in temperature. During the glyphosate exposure period in phase 1, differences were observed in the D. magna populations with respect to temperature, with lower abundance at 25 °C than at 20 °C. However, no differences were observed in abundance regarding glyphosate treatment. The results obtained in phase 2 with the new stressors combined with temperature changes in both directions, revealed stronger effects in vulnerable populations than in control populations. In addition, the temperature changes modulated the effects in the starvation and increased salinity tests. Agrochemical sublethal concentrations induce vulnerability in D. magna populations and inflicted temperature changes can act as a modulating factor for this vulnerability, showing the complexity in assessing the responses under the multiple scenarios associated with global change.

Differential interference contrast phase edging net: an all-optical learning system for edge detection of phase objects

Differential interference contrast phase edging net: an all-optical learning system for edge detection of phase objects

Fractional Fourier transform imaging based on untrained neural networks

Fractional Fourier transform is an important branch of optical research, and it is widely used in optical encryption, optical filtering, image watermarking and other fields. The phase retrieval in the case of fractional Fourier transform is widely studied. Also, deep learning has been an intriguing method for optical computational imaging. However, in optical computational imaging, traditional deep learning methods possess some intrinsic disadvantages. In optical imaging experiments, it is often difficult to obtain sufficient quality and quantity of labeled data for training, thus leading to poor robustness of the trained neural network. Even with sufficient datasets, the training time can be particularly long. In recent years, there has been an increase in interest in physic-driven untrained neural networks for computational imaging. Herein we use such a method to study the fractional Fourier transform imaging, which combines neural networks with optical models to achieve phase retrieval of fractional Fourier transform. Unlike the traditional neural network training with the original image as the target, our network framework is used only a single intensity image for the phase retrieval of fractional Fourier transform images. The output image of the neural network will serve as an optical model through fractional Fourier transform, and then the output image of the optical model will be used as a loss function to drive the neural network training with the output image of the neural network. We study the fractional Fourier transform reconstruction for the cases where the fractional order is less than 1 and greater than 1. The simulations and experiments show that the network framework can implement the fractional Fourier transform reconstructions of the intensity objects and phase objects for different fraction orders, in which only 2000 iterations are needed. The experimental results show that the similarity between the reconstructed image and the original image, i.e. the number of normalized correlation coefficient, can reach 99.7%. Therefore, our work offers an efficient scheme for functional Fourier transform reconstruction with physics-enhanced deep neutral network.

Polytypic metal chalcogenide nanocrystals.

By engineering chemically identical but structurally distinct materials into intricate and sophisticated polytypic nanostructures, which often surpass their pure phase objects and even produce novel physical and chemical properties, exciting applications in the fields of photovoltaics, electronics and photocatalysis can be achieved. In recent decades, various methods have been developed for synthesizing a library of polytypic nanocrystals encompassing IV, III-V and II-VI polytypic semiconductors. The exceptional performances of polytypic metal chalcogenide nanocrystals have been observed, making them highly promising candidates for applications in photonics and electronics. However, achieving high-precision control over the morphology, composition, crystal structure, size, homojunctions, and periodicity of polytypic metal chalcogenide nanostructures remains a significant synthetic challenge. This review article offers a comprehensive overview of recent progress in the synthesis and control of polytypic metal chalcogenide nanocrystals using colloidal synthetic strategies. Starting from a concise introduction on the crystal structures of metal chalcogenides, the subsequent discussion delves into the colloidal synthesis of polytypic metal chalcogenide nanocrystals, followed by an in-depth exploration of the key factors governing polytypic structure construction. Subsequently, we provide comprehensive insights into the physical properties of polytypic metal chalcogenide nanocrystals, which exhibit strong correlations with their applications. Thereafter, we emphasize the significance of polytypic nanostructures in various applications, such as photovoltaics, photocatalysis, transistors, thermoelectrics, stress sensors, and the electrocatalytic hydrogen evolution. Finally, we present a summary of the recent advancements in this research field and provide insightful perspectives on the forthcoming challenges, opportunities, and future research directions.

Fuzzy Attention U-Net Architecture Based Localization and YOLOv5 Detection for Fetal Cardiac Ultrasound Images

The importance of early identification of congenital heart disease is highlighted by the fact that it accounts for around 28% of all congenital abnormalities this is the primary reason why fetus die. The necessity of having a thorough understanding of normal cardiac architecture has been highlighted by the quick advancements in fetal heart imaging techniques that have occurred in recent years. Without this information, it is challenging, even impossible, to distinguish the many manifestations of congenital heart illness. This research suggests an immediate fetal cardiac identification technique employing US pictures with the You Only Look Once v5 (YOLOv5) framework and localization using Fuzzy Attention U-Net (FAU-Net) framework in order to enhance the interpretation of the anatomy of the fetal heart through Ultrasound (US) for precise and instantaneous diagnoses. Localization is accomplished using a FU-Net architecture, which limits the training set to image-level plane labels. This is a crucial component of the proposed study since, for big datasets, it would take too much time to produce bounding box annotations, which are not always captured. The FAU-Net design has been optimized for best performance. The YOLOv5 framework is built to function in real-time and deliver the best results for object identification. With the aid of appropriate fine-tuning, it may function effectively to automatically identify tiny fetal cardiac objects in a fast phase. Depending on how much of a detection overlapped with ground-truth bounding boxes, it was determined if it was a genuine positive or a false positive. This research primarily aids medical professionals in the diagnosis of fetal cardiac anatomy. The efficiency of the outcomes is evaluated using metrics including accuracy, memory, average precision (AP), mean average precision (mAP), and F-measure.

RESEARCH BEST PRACTICES TO SUPPORT RESILIENCE IN EYE STROKE VISION REHABILITATION

Abstract While effective rehabilitation exists to promote independence and community participation for age-related vision impairment, no rehabilitation program has been developed specifically for eye stroke impairment. We are adapting a macular degeneration self-management program using input from key partners to inform future intervention. The pilot phase objective was to inform future study design for eye stroke survivors. We conducted semi-structured interviews, and applied the 5T Framework (Target population identification, Team composition, Time considerations, Tips to accommodate older adults, and Tools for inclusive enrollment of older adults) to develop the interview guide. Twenty-five people recruited from clinical settings were consented/interviewed over six months. This included 10 stroke survivors (M age= 66 years; 70% male--90% visual field defect), 4 care partners (M age= 57 years; 100% female--1 mother, 1 sister and 2 spouses), and 11 providers (M age= 37 years; 54.5% female--3 occupational therapists, 4 ophthalmologists, 2 optical technicians, 1 optometrist, 1 physical therapist). The most meaningful outcomes identified were driving and returning to full independence. The most frequently identified “facilitator of recovery” after eye stroke was family support. The most frequently identified barriers to participation in intervention research were lack of accessibility of the research building and transportation. Optimal lighting and scanning strategies were identified as key elements of any future intervention as well as approaches to support enrollment and retention in study activities. Interview data are now being used to inform phase two: adaptation of the self-management program and design of the study that will evaluate its effectiveness.

NUWARD SMR safety approach and licensing objectives for international deployment

Drawing on the deep experience and understanding of the principles of nuclear safety, as well as many years of nuclear power plant design and operation, the EDF led NUWARD SMR Project is developing a design for a Small Modular Reactor (SMR) of 340 MWe composed of two 170 MWe independent units, that will supplement the offering of high-output nuclear reactors, especially in response to specific needs such as replacement of fossil-fuelled power plants. NUWARD SMR is a mix of proven and innovative design features that will make it more commercially competitive, while integrating safety features that comply with the highest international standards. Following the principles of redundancy and diversity and rigorous application of Defence in Depth (DID), with an international view on nuclear safety licensing, the Project also incorporates new safety approaches into its design development.The NUWARD SMR Project has been in development for a number of years, it entered conceptual design formally in mid-2019 and entered Basic Design in 2023. The objective of the concept design phase was to confirm the project technological choices and to define the first design configuration of the NUWARD SMR product, to document it, in order to launch pre-licensing with the French Safety Authority (ASN) and to define its estimated cost and its subsequent development and construction schedules. As a delivery milestone the Safety Options file (called the Dossier d’Options de Sûreté (DOS)) has been submitted to ASN in July 2023 for their opinion.An integral part of the NUWARD SMR Project, is not only to deliver a design suitable for France and to satisfy French regulation, but to develop a product suitable and indeed desirable, for the international market, with a first focus in Europe. In order to achieve its objectives and realise its market potential, the NUWARD SMR Project needs to define and realise its safety approach within an international environment and that is the key subject of this paper. The following paper:• Summarises the foundation principles and technological background which underpin the design;•Contextualises the key design features with regard to the international safety regulatory framework with particular emphasis on innovative passive safety aspects;•Illustrates the Project activities in preparation for first licensing in France, and also a wider international view via the ASN led Joint Early Review of the NUWARD SMR design, including Finnish and Czech Republic regulators, recently joined by the Swedish, Polish and Dutch regulators;•Articulates the collaborative approach to design development from involvement with the Project partners (the Commissariat à l’énergie atomique et aux énergies alternatives (CEA), Naval Group, TechnicAtome, Framatome and Tractebel) to the establishment of the International NUWARD Advisory Board (INAB), to gain greater international insight and advice;•Concludes with the focus on next steps into detailed design development, standardisation of the design and its simplification to enhance its commercial competitiveness in a context of further harmonisation of the nuclear safety and licensing requirements and aspirations.

A Phase 1/2 Study to Evaluate the Safety and Activity of Nivolumab in Combination With Vorolanib, a Vascular Endothelial Growth Factor Tyrosine Kinase Inhibitor, in Patients With Refractory Thoracic Tumors

IntroductionTargeting the tumor microenvironment may enhance response to immunotherapy (immune checkpoint inhibitors) and improve outcomes for patients. This study tested the safety and efficacy of vorolanib, a novel tyrosine kinase inhibitor of vascular endothelial growth factor, platelet-derived growth factor, and c-KIT, in combination with programmed cell death protein 1 blockade using nivolumab for refractory thoracic malignancies. MethodsThis single-arm multicenter study enrolled patients with extensive-stage SCLC, thymic carcinoma, and NSCLC, either naive or had progressed on previous chemotherapy or immune checkpoint inhibitors (either primary or acquired resistance). The primary objective of phase 1 was to determine the maximum tolerated dose, and the primary end point for each dose-expansion cohort was the objective response rate. ResultsA total of 88 patients were enrolled in phase 1 (n = 11) and dose expansion (n = 77) cohorts. Transaminitis was dose-limiting and expansion proceeded with oral vorolanib 200 mg daily combined with intravenous nivolumab 240 mg every 2 weeks. The objective response rate per cohort were as follows: NSCLC naive 33% (five of 15, 95% confidence interval [CI]: 13%–60%), NSCLC primary refractory 5.9% (one of 17, 95% CI: 0%–17.6%), NSCLC acquired resistance 11.1% (two of 18, 95% CI: 0%–27.8%); SCLC 0% (zero of 18), and thymic carcinoma 11% (one of nine, 95% CI: 0%–33%). Disease control rate ranged from 11.1% in SCLC (two of 18, 0%–27.8%) to 66.7 % in thymic carcinoma (six of nine, 95% CI: 33.3%–100%). The most common adverse events were fatigue (32%), aspartate transaminase (27%) and alanine transaminase elevation (25%), and diarrhea (19%). Transaminitis was more common in patients with thymic carcinoma than other tumors. ConclusionsVorolanib plus nivolumab had a manageable safety profile and may have clinical benefits in various thoracic malignancies. The disease control rate in thymic malignancies warrants further assessment.

3D tomographic phase retrieval and unwrapping

This paper develops uniqueness theory for 3D phase retrieval with finite, discrete measurement data for strong phase objects and weak phase objects, including: (i) Unique determination of (phase) projections from diffraction patterns—General measurement schemes with coded and uncoded apertures are proposed and shown to ensure unique reduction of diffraction patterns to the phase projection for a strong phase object (respectively, the projection for a weak phase object) in each direction separately without the knowledge of relative orientations and locations. (ii) Uniqueness for 3D phase unwrapping—General conditions for unique determination of a 3D strong phase object from its phase projection data are established, including, but not limited to, random tilt schemes densely sampled from a spherical triangle of vertexes in three orthogonal directions and other deterministic tilt schemes. (iii) Uniqueness for projection tomography—Unique determination of an object of n 3 voxels from generic n projections or n + 1 coded diffraction patterns is proved. This approach of reducing 3D phase retrieval to the problem of (phase) projection tomography has the practical implication of enabling classification and alignment, when relative orientations are unknown, to be carried out in terms of (phase) projections, instead of diffraction patterns. The applications with the measurement schemes such as single-axis tilt, conical tilt, dual-axis tilt, random conical tilt and general random tilt are discussed.

Does the order of elastic and inelastic scattering affect an image or is there a top bottom effect from inelastic scattering?

Especially for light elements inelastic scattering is more probable than the elastic scattering that conveys the structural information. The question arises as to whether an image using inelastically scattered electrons is different depending on whether the elastic or inelastic scattering happens first, is there a top-bottom effect. We show that since inelastic scattering is concentrated in a narrow range of angles, much less than typical Bragg angles in light element materials, the inelastic and elastic processes are separable and, to a very good approximation, there is no top-bottom effect. For weakly scattering thin biological specimens that are phase objects the separation is exact and there can be no top-bottom effect.