Photon Emission Research Articles

Stimulated Emission of Virtual Photons: Energy Transfer by Light.

Energy-transfer processes can be viewed as being due to the emission of a virtual photon. It is demonstrated that the emission of virtual photons and thus of energy transfer is stimulated by the sheer presence of photons. We concentrate here on interatomic/intermolecular Coulombic decay (ICD) where an excited system relaxes by transferring its excess energy to a neighbor ionizing it. ICD is inactive if this excess energy is insufficiently large. However, in the presence of photons, the long-range interaction between the system and its neighbor can utilize the photon field making ICD active. The properties of this stimulated-ICD mechanism are discussed. The concept can be transferred to other scenarios. We discuss collective-ICD where two excited molecules concertedly transfer their excess energy. Also here, the presence of photons can make the process active if the sum of excess energies were insufficient to do so. Examples with typical molecules and atoms are presented to demonstrate that these stimulated processes can play a role.

Quantitative bone single photon emission computed tomography/computed tomography in symptomatic and asymptomatic foot and ankle osteoarthritis.

The purpose of this study was to evaluate and quantify the prevalence of increased uptake in SPECT/CT in symptomatic and asymptomatic foot and ankle joints in patients with osteoarthritis. In 63 patients with osteoarthritis (OA), the painful symptomatic foot (SF) and asymptomatic contralateral foot (AF) were imaged with bone SPECT/CT. Presence, localization, and maximum standardized uptake value (SUVmax) of the active joints were assessed for SF and AF. CT OA grade (grade 1: mild, grade 2: moderate, grade 3: severe) and presence of five morphological features of OA (joint space narrowing, subchondral sclerosis, subchondral cysts, irregular joint margins, and osteophytes) were evaluated. In total 32 (51%) patients showed additional uptake in the AF, whereas 31 (49%) patients showed it only in the SF. SF showed more active joints than AF (106 vs. 43). CT OA grades positively correlated with SUVmax (Kendall's tau b = 0.62, P < 0.001). SUVmax values (per foot) in SF were higher in patients with uptake in bilateral feet (SF+, AF+) [median (IQR): 17.9 (10.7-23.3)] as compared with patients with active sites only in the SF (SF+, AF-) [10.4 (6.4-19.1); P < 0.001]. Number of active OA joints in SF was higher in patients with bilateral uptake (P = 0.017). In conclusion, half of the patients exhibited increased uptake in the contralateral asymptomatic foot. SUVmax showed a significant correlation to CT osteoarthritis grade, in the symptomatic and asymptomatic foot. Future follow-up studies will provide further insights into the prognostic and therapeutic value of these findings.

Collective photon emission in solid state environments: Concatenating non-Markovian and Markovian dynamics

Collective light emission and multiqubit dynamics of solid-state quantum emitters are affected both by their coupling to the light field and to lattice vibrations. The effect of phonons on quantum emitters is twofold: polaron formation is described by ultrafast non-Markovian dynamics, while slower dephasing is well described by exponential decay. Of the two temperature-dependent processes, the effect of the former on the collective emission and the entanglement decay of emitters is usually not modeled, and also the latter is sometimes neglected. Here we propose and compare two methods that are efficient also for several emitters: the first method concatenates the fast and slow phonon dynamics, and the second is the polaron method. For a single quantum emitter, we show that the dynamical equations are identical in both methods, while predictions for two or more emitters also agree very well. Both of our methods incorporate non-Markovian dynamics due to phonons demonstrating the temperature sensitivity of the collective photon emission. Utilizing a simplified Markovian model instead may not be accurate enough especially for quantum information applications: for example, we show how the Markovian model may considerably overestimate the two-emitter concurrence, except at very low temperatures. Our concatenation and polaron methods can be applied to an arbitrary number and type of quantum emitters, and beyond the bulk GaAs environment that we consider here. Especially the concatenation method can take phonon effects into account at the same computational cost as modeling the emitter-photon interaction alone. Finally, we present approximate analytical expressions for the collective emission spectrum for N emitters on a one-dimensional chain. Published by the American Physical Society 2024

Tunable quantum emitters on large-scale foundry silicon photonics

Controlling large-scale many-body quantum systems at the level of single photons and single atomic systems is a central goal in quantum information science and technology. Intensive research and development has propelled foundry-based silicon-on-insulator photonic integrated circuits to a leading platform for large-scale optical control with individual mode programmability. However, integrating atomic quantum systems with single-emitter tunability remains an open challenge. Here, we overcome this barrier through the hybrid integration of multiple InAs/InP microchiplets containing high-brightness infrared semiconductor quantum dot single photon emitters into advanced silicon-on-insulator photonic integrated circuits fabricated in a 300 mm foundry process. With this platform, we achieve single-photon emission via resonance fluorescence and scalable emission wavelength tunability. The combined control of photonic and quantum systems opens the door to programmable quantum information processors manufactured in leading semiconductor foundries.

Ligand Equilibrium Influences Photoluminescence Blinking in CsPbBr3: A Change Point Analysis of Widefield Imaging Data.

Photoluminescence intermittency remains one of the biggest challenges in realizing perovskite quantum dots (QDs) as scalable single photon emitters. We compare CsPbBr3 QDs capped with different ligands, lecithin, and a combination of oleic acid and oleylamine, to elucidate the role of surface chemistry on photoluminescence intermittency. We employ widefield photoluminescence microscopy to sample the blinking behavior of hundreds of QDs. Using change point analysis, we achieve the robust classification of blinking trajectories, and we analyze representative distributions from large numbers of QDs (Nlecithin = 1308, Noleicacid/oleylamine = 1317). We find that lecithin suppresses blinking in CsPbBr3 QDs compared with oleic acid/oleylamine. Under common experimental conditions, lecithin-capped QDs are 7.5 times more likely to be nonblinking and spend 2.5 times longer in their most emissive state, despite both QDs having nearly identical solution photoluminescence quantum yields. We measure photoluminescence as a function of dilution and show that the differences between lecithin and oleic acid/oleylamine capping emerge at low concentrations during preparation for single particle experiments. From experiment and first-principles calculations, we attribute the differences in lecithin and oleic acid/oleylamine performance to differences in their ligand binding equilibria. Consistent with our experimental data, density functional theory calculations suggest a stronger binding affinity of lecithin to the QD surface compared to oleic acid/oleylamine, implying a reduced likelihood of ligand desorption during dilution. These results suggest that using more tightly binding ligands is a necessity for surface passivation and, consequently, blinking reduction in perovskite QDs used for single particle and quantum light experiments.

Wheat seed quality assessment after thiamethoxam treatment: integrating optical techniques with standard methods

Insecticide treatment of seeds protects against early field pests. Therefore, studies on the physiological and biochemical responses of crops exposed to insecticides are required. Standard (non-optical) tests are used to evaluate the physiological quality of seeds. However, some tests may need to be more sensitive to observe possible differences between the control group and the groups of interest. Optical techniques such as ultra- weak photon emission and Fourier transform infrared spectroscopy have been discovered to aid standard tests. The effects of different doses of Thiamethoxam were evaluated on wheat seeds from the cultivar FPS Certero. Samples were divided into five groups: control and treated with 75, 150, 225, and 300 mL of Thiamethoxam for each 100 kg of seeds. The ultra-weak photon emission results showed that it was possible to classify the treatment doses through the intensity of photon emissions. The Fourier transform infrared spectroscopy analyses can be used for biological analysis but are unrelated to Thiamethoxam seed treatment. Considering the findings, optical techniques can be used as an additional tool for assessing the physiological quality of seeds.

In‐Vivo GIT Distribution Study On 99mTc‐Functionalized Bioactive Glass Through an Oral Route for Biomedical Applications

AbstractBioactive glass (BG) being bioactive, biocompatible, and osteoconductive has been explored as an oral drug carrier. Herein, after bio‐inspired synthesis, radiolabeling of BG is carried out with Technetium (99mTc) to study its biodistribution and analyze its physico‐chemical characteristics. The particles formed were found to be bioactive due to the formation of hydroxyapatite. An in‐vitro cell proliferation assay confirmed the cytocompatibility of BG against Caco‐2 and U2OS cell lines. The cellular uptake studies of BG for caco‐2 cell lines confirms intracellular nanoparticle transport making it suitable oral drug carrier. The radiolabeling efficiency was monitored in‐vitro at different pH levels of gastrointestinal tract (GI) at different time intervals and the efficacy of radiolabeled BG was found to be substantial. Finally, they were orally ingested in a rat model to investigate its biological diffusion. As depicted by SPECT images (Single photon emission computerized tomography), radiolabeled BG were found to be confined in the intestinal (abdomen) region. The goal of this study is to highlight the application of BG as oral drug carrier for the sustained targeted drug delivery to minimize the drug dosage with the least possible side effects.

Modelling Gd-diamond and Gd-SiC neutron detectors

A custom Monte Carlo (MC) computer model was developed to simulate thermal neutron absorption in, and subsequent photon and electron emission from, natural Gd with a view to using the material as a neutron conversion layer for neutron detectors. The MC code also modelled photon and electron detection with two dissimilar detectors: a thick (500 μm) single crystal diamond detector; and a thin (5.15 μm) commercial off the shelf (COTS) 4H–SiC photodiode detector. The detectors’ quantum detection efficiencies (QE) for hard X-rays and γ-rays were relatively low in comparison to their QE for electrons, thus making it possible to collect electron spectra from the Gd layer neutron conversion products which were not overwhelmed by photon emissions from the Gd. The MC code was utilised to determine the optimal thickness of Gd for the efficient detection of a thermal neutron flux. These radiation hard and spectroscopic detectors paired with natural Gd could find utility as robust and compact thermal neutron detectors for nuclear science and engineering, space science, and other applications.

Technological Advances in SPECT and SPECT/CT Imaging.

Single photon emission tomography/computed tomography (SPECT/CT) is a mature imaging technology with a dynamic role in the diagnosis and monitoring of a wide array of diseases. This paper reviews the technological advances, clinical impact, and future directions of SPECT and SPECT/CT imaging. The focus of this review is on signal amplifier devices, detector materials, camera head and collimator designs, image reconstruction techniques, and quantitative methods. Bulky photomultiplier tubes (PMTs) are being replaced by position-sensitive PMTs (PSPMTs), avalanche photodiodes (APDs), and silicon PMs to achieve higher detection efficiency and improved energy resolution and spatial resolution. Most recently, new SPECT cameras have been designed for cardiac imaging. The new design involves using specialised collimators in conjunction with conventional sodium iodide detectors (NaI(Tl)) or an L-shaped camera head, which utilises semiconductor detector materials such as CdZnTe (CZT: cadmium-zinc-telluride). The clinical benefits of the new design include shorter scanning times, improved image quality, enhanced patient comfort, reduced claustrophobic effects, and decreased overall size, particularly in specialised clinical centres. These noticeable improvements are also attributed to the implementation of resolution-recovery iterative reconstructions. Immense efforts have been made to establish SPECT and SPECT/CT imaging as quantitative tools by incorporating camera-specific modelling. Moreover, this review includes clinical examples in oncology, neurology, cardiology, musculoskeletal, and infection, demonstrating the impact of these advancements on clinical practice in radiology and molecular imaging departments.

Incidental Visualization of Gallbladder on Post-therapy [177Lu]Lu-DOTATATE Scintigraphy Mimicking a Liver Metastasis in a Duodenal Neuroendocrine Tumor

AbstractWe present a rare case of physiological uptake of [177Lu]Lu-DOTATATE in the gallbladder, observed post-therapy, in a 47-year-old man with grade I duodenal neuroendocrine tumor (NET), despite no uptake being observed pre-therapy in the somatostatin receptor-positron emission tomography. On planar scintigraphy, the gallbladder uptake could have been misidentified as liver metastasis. By utilizing single photon emission computed tomography/computed tomography imaging, we were able to precisely localize the tracer and obtain anatomical morphological characteristics, thereby averting the potential for misinterpretation of liver metastasis resulting from the gallbladder's physiological uptake of [177Lu]Lu-DOTATATE in NET patients.

Unique algorithm for the evaluation of embryo photon emission and viability

Living cells have spontaneous ultraweak photon emission derived from metabolic reactions associated with physiological conditions. The ORCA-Quest CMOS camera (Hamamatsu Photonics, Japan) is a highly sensitive and essential tool for photon detection; its use with a microscope incubator (Olympus) enables the detection of photons emitted by embryos with the exclusion of harmful visible light. With the application of the second law of thermodynamics, the low-entropy energy absorbed and used by embryos can be distinguished from the higher-entropy energy released and detectable in their environment. To evaluate higher-entropy energy data from embryos, we developed a unique algorithm for the calculation of the entropy-weighted spectral fractal dimension, which demonstrates the self-similar structure of the energy (photons) released by embryos. Analyses based on this structure enabled the distinction of living and degenerated mouse embryos, and of frozen and fresh embryos and the background. This novel detection of ultra-weak photon emission from mouse embryos can provide the basis for the development of a photon emission embryo control system. The ultraweak photon emission fingerprints of embryos may be used for the selection of viable specimens in an ideal dark environment.

Quantitative Investigation of Quantum Emitter Yield in Drop-Casted Hexagonal Boron Nitride Nanoflakes.

Single photon emitters (SPEs) are a key component for their use as pure photon source in quantum technologies. In this study, we investigate the generation of SPEs from drop-casted hexagonal boron nitride (hBN) nanoflakes, examining the influence of the immersion solution and the source of hBN. We show that, depending on the utilized supplier and solution, the number and quality of the emitters change. We perform a comprehensive optical characterization of the deposited nanoflakes to assess the quality of the generated SPEs. Importantly, we provide quantitative data on SPE yields, highlighting significant variations among solvents and different sources of hBN. We find that hBN from Merck drop-casted in acetone provided the best quality emitters with a g (2) < 0.1 and photoluminescence intensities above 300 kCounts/s. Their number of SPEs among all photon emitters was also the highest, with about 14%, rendering a total yield of about 1.25% of all drop-casted flakes. These numbers hold particular significance when evaluating drop-casting as a practical method for the generation of SPEs and their deposition and incorporation within existing nanophotonic systems. By choosing appropriate solvents and source materials' quality and yield of SPEs can be significantly increased, showcasing further optimization potential for the development of future quantum applications.

High-rate intercity quantum key distribution with a semiconductor single-photon source

Quantum key distribution (QKD) enables the transmission of information that is secure against general attacks by eavesdroppers. The use of on-demand quantum light sources in QKD protocols is expected to help improve security and maximum tolerable loss. Semiconductor quantum dots (QDs) are a promising building block for quantum communication applications because of the deterministic emission of single photons with high brightness and low multiphoton contribution. Here we report on the first intercity QKD experiment using a bright deterministic single photon source. A BB84 protocol based on polarisation encoding is realised using the high-rate single photons in the telecommunication C-band emitted from a semiconductor QD embedded in a circular Bragg grating structure. Utilising the 79 km long link with 25.49 dB loss (equivalent to 130 km for the direct-connected optical fibre) between the German cities of Hannover and Braunschweig, a record-high secret key bits per pulse of 4.8 × 10−5 with an average quantum bit error ratio of ~ 0.65% are demonstrated. An asymptotic maximum tolerable loss of 28.11 dB is found, corresponding to a length of 144 km of standard telecommunication fibre. Deterministic semiconductor sources therefore challenge state-of-the-art QKD protocols and have the potential to excel in measurement device independent protocols and quantum repeater applications.

Strain-graded quantum dots with spectrally pure, stable and polarized emission

Structural deformation modifies the bandgap, exciton fine structure and phonon energy of semiconductors, providing an additional knob to control their optical properties. The impact can be exploited in colloidal semiconductor quantum dots (QDs), wherein structural stresses can be imposed in three dimensions while defect formation is suppressed by controlling surface growth kinetics. Yet, the control over the structural deformation of QDs free from optically active defects has not been reached. Here, we demonstrate strain-graded CdSe-ZnSe core-shell QDs with compositionally abrupt interface by the coherent pseudomorphic heteroepitaxy. Resulting QDs tolerate mutual elastic deformation of varying magnitudes at the interface with high structural fidelity, allowing for spectrally stable and pure emission of photons at accelerated rates with near unity luminescence efficiency. We capitalize on the asymmetric strain effect together with the quantum confinement effect to expand emission envelope of QDs spanning the entire visible region and exemplify their use in photonic applications.

Approaching Maximum Resolution in Structured Illumination Microscopy via Accurate Noise Modeling.

Biological images captured by microscopes are characterized by heterogeneous signal-to-noise ratios (SNRs) due to spatially varying photon emission across the field of view convoluted with camera noise. State-of-the-art unsupervised structured illumination microscopy (SIM) reconstruction algorithms, commonly implemented in the Fourier domain, do not accurately model this noise and suffer from high-frequency artifacts, user-dependent choices of smoothness constraints making assumptions on biological features, and unphysical negative values in the recovered fluorescence intensity map. On the other hand, supervised methods rely on large datasets for training, and often require retraining for new sample structures. Consequently, achieving high contrast near the maximum theoretical resolution in an unsupervised, physically principled, manner remains an open problem. Here, we propose Bayesian-SIM (B-SIM), an unsupervised Bayesian framework to quantitatively reconstruct SIM data, rectifying these shortcomings by accurately incorporating known noise sources in the spatial domain. To accelerate the reconstruction process, we use the finite extent of the point-spread-function to devise a parallelized Monte Carlo strategy involving chunking and restitching of the inferred fluorescence intensity. We benchmark our framework on both simulated and experimental images, and demonstrate improved contrast permitting feature recovery at up to 25% shorter length scales over state-of-the-art methods at both high- and low-SNR. B-SIM enables unsupervised, quantitative, physically accurate reconstruction without the need for labeled training data, democratizing high-quality SIM reconstruction and expands the capabilities of live-cell SIM to lower SNR, potentially revealing biological features in previously inaccessible regimes.

Photon emission and radiation reaction effects in surface plasma waves in ultra-high intensities

Manipulating and harnessing plasmonic phenomena in the ultra-relativistic regime reveal promising prospects for the use of surface plasma waves (SPW) to create high-energy particle and radiation sources in the next generation of multi-petawatt lasers. Indeed, relativistic high-charge electron bunches can be produced by SPW excited by ultra-high intensity femtosecond lasers impinging on a periodically modulated solid-density target. In this regime, there is good evidence that SPW excitation survives and that the produced electron bunches experience strong acceleration, thus emitting large amounts of electromagnetic radiation. Therefore, extending the study to ultra-high laser intensities (I&amp;gt;1021 W/cm2), the use of a resonant grating for SPW generation represents an interesting alternative to light sources, as the energy lost by electrons due to radiation emission is transferred to high-energy γ photons. In addition, we show that using a laser with wavefront rotation coupled with a tailored blazed grating improves photon emission in the ultra-relativistic regime of interaction.

Compact hard x-ray flash radiography device based on wire-shorted low-impedance rod pinch diode.

A rod pinch diode (RPD) is a feasible load configuration to generate a high-brightness, small-size hard x-ray radiation source. In this paper, the radiography performance of a wire-shorted low-impedance RPD on a compactly designed table-top driver (WRPD-1) is demonstrated for the first time. The driver consists of four high-power discharge branches connected in parallel, with each branch consisting of two metal-film capacitors and one multigap field-distortion switch in series. The four branches are triggered synchronously to generate a fast-rising current pulse: the inductance of the load section at the short circuit is ∼10 nH, and the short-circuit current amplitude is ∼325kA at ±90kV charging voltage, with a 10%-90% rise time of 110ns. With a low-impedance RPD shorted by an 18-µm-diameter aluminum wire, a quasi-spherical x-ray focal spot with diameter <0.6mm (width of the half-maximum grayscale) and a pulse duration of ∼25ns (half-width of the radiation pulse) is obtained at ±70kV charging voltage, and the imaging resolution excels 10 lp/mm under 1.56× magnification. According to the transmission-absorption x-ray spectrum estimation, the average emitted photon energy is ∼30keV with a distinct peak in the 10-15keV range that corresponds to the L-lines of tungsten, and the total energy of photons >10keV reaches ∼1.16J. The present results show that the device can serve well for the flash radiography diagnosis and potentially as an efficient light source for dynamic x-ray diffraction.

Imageable Radioembolization Microspheres for Treatment of Unresectable Hepatocellular Carcinoma: Interim Results from a First-in-Human Trial

PurposeTo determine 6-month interim safety, effectiveness, and multimodal imageability of imageable glass microsphere yttrium-90 (90Y) radioembolization for unresectable hepatocellular carcinoma (HCC) in a first-in-human trial. Materials and MethodsImageable microspheres (Eye90 Microspheres; ABK Biomedical, Halifax, Nova Scotia, Canada), a U.S. Food and Drug Administration (FDA) Breakthrough-Designated Device consisting of glass radiopaque 90Y microspheres visible on computed tomography (CT) and single photon emission CT (SPECT), were used to treat 6 subjects with unresectable HCC. Patients underwent selective (≤2 segments) treatment in a prospective open-label pilot trial. Key inclusion criteria included liver-only HCC, performance status ≤1, total lesion diameter ≤9 cm, and Child-Pugh A status. Prospective partition dosimetry was utilized. Safety (measured by Common Terminology Criteria for Adverse Events [CTCAE] v5), multimodal imageability on CT and SPECT, and 3- and 6-month imaging response by modified Response Evaluation Criteria in Solid Tumors on magnetic resonance (MR) imaging were evaluated. ResultsSeven tumors in 6 subjects were treated and followed to 180 days. Administration success was 100%. Microsphere distribution measured by radiopacity on CT correlated with SPECT. Ninety-day target lesion complete response (CR) was observed in 3 of 6 subjects (50%) and partial response (PR) in 2 (33.3%). At 180 days, target lesion CR was maintained in 3 subjects (50%) and PR in 1 (16.7%). Two subjects could not be reassessed, having undergone intervening chemoembolization. All subjects reported adverse events (AEs), and 5 reported AEs related to treatment. There were no treatment-related Grade ≥3 AEs. ConclusionsRadioembolization using imageable microspheres was safe and effective in 6 subjects with unresectable HCC at 6-month interim analysis. Microsphere distribution by radiopacity on CT correlated with radioactivity distribution by SPECT, providing previously unavailable CT-based tumor targeting information.

Electron Beam Restructuring of Quantum Emitters in Hexagonal Boron Nitride

AbstractHexagonal boron nitride (hBN) holds promise as a solid state, van der Waals host of single photon emitters for on‐chip quantum photonics. The B‐center defect emitting at 436 nm is particularly compelling as it can be generated by electron beam irradiation. However, the emitter generation mechanism is unknown, the robustness of the method is variable, and it has only been applied successfully to thick flakes of hBN (≫ 10 nm). Here, it is used in situ time‐resolved cathodoluminescence (CL) spectroscopy to investigate the kinetics of B‐center generation. It is shown that the generation of B‐centers is accompanied by quenching of a carbon‐related emission at ≈305 nm and that both processes are rate‐limited by electromigration of defects in the hBN lattice. It identifies problems that limit the efficacy and reproducibility of the emitter generation method and solve them using a combination of optimized electron beam parameters and hBN pre‐and postprocessing treatments. It is achieved B‐center quantum emitters in hBN flakes as thin as 8 nm, elucidate the mechanisms responsible for electron beam restructuring of quantum emitters in hBN, and gain insights toward the identification of the atomic structure of the B‐center quantum emitter.

Simultaneous visualization of changes in perfusion and myocardial function of a transplanted heart in emergency cardiology

Introduction. In conditions of the Emergency Cardiology Department, a timely and differential diagnosis of myocardial pathology is especially important in the absence of visible focal changes and significant coronary artery stenosis. This group of patients includes recipients of a transplanted heart, when it is difficult to count on the high sensitivity of perfusion images alone. This can be explained by the diffuse, balanced distribution of ischemia.Objective. To present the possibilities of perfusion myocardial single photon emission computed tomography synchronized with electrocardiography for a detailed assessment of the functional condition of both ventricles of the transplanted heartMaterial and methods. We have presented three clinical case reports of the patients with different pathology of the transplanted heart who referred themselves to the emergency cardiology clinic and underwent electrocardiographysynchronized perfusion myocardial single photon emission computed tomography for diagnostic purposes.Results. In all the cases presented, the radionuclide study influenced making the diagnosis and changing the treatment tactics. In the first case, it was possible to identify focal myocardial changes, for which coronary angiography and percutaneous coronary intervention with thromboextraction were immediately performed. In the second case, the image analysis reflecting the function of the myocardium (polar maps of wall movement and systolic thickening) allowed us to note a low efficacy of treatment for the transplanted heart rejection. In the third clinical case, the initial single photon emission computed tomography suggested the inflammatory nature of changes in the myocardium, which was verified by the results of endomyocardial biopsy.Conclusion. In the presented clinical cases, the urgently performed electrocardiography-synchronized perfusion myocardial single photon emission computed tomography made it possible to perform invasive interventions in time and thereby contribute to the recovery of the graft functional state and patient's condition improvement.