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Understanding the foraging behavior of marine animals in Antarctica is crucial for assessing their ecological significance and responses to environmental changes, such as seasonal changes in seawater or light hours. However, studying their responses to these seasonal changes remains challenging due to the difficult logistics of conducting observations, particularly during the harsh austral winter months. In this study, we investigated the influence of changes in seawater properties and light conditions on the seasonal foraging behavior of Weddell seals (Leptonychotes weddellii) in the Ross Sea, Antarctica. We affixed 64 Weddell seals with conductivity–temperature–depth tags for 3 consecutive years from 2021 to 2023 to record their locations and dive profiles, including depth, head acceleration, temperature, and salinity. We found that seals foraged more frequently in Modified Shelf Water and Ice Shelf Water than in Antarctic Surface Water. This preference could be connected to greater food availability. Seals also dove to greater depths and displayed increased activity in capturing prey during daylight hours. This behavior may correspond to the diel vertical migration of pelagic prey in response to varying light conditions. Consequently, marine fauna were confronted with distinct seasonal changes in the Antarctic environment and adjusted their foraging behaviors to respond to them. This highlights the importance of extrinsic factors in estimating their seasonal foraging behavior.

Applications of laser-plasma accelerators (LPA) require independent control of electron beam parameters. However, due to the complex coupling of the many variables governing the laser-plasma interaction, precisely tuning these parameters based on simple scalings is often impossible or at least suboptimal. Here, we apply multiobjective Bayesian optimization to derive optimal tuning curves for LPAs, both in simulations and experiments. For electron energies between 150 and 250 MeV, we demonstrate tuning of the charge over a range of nearly 100 pC, while preserving optimal beam loading conditions with energy spreads below 5%. The derived tuning curves can explain the sometimes counterintuitive interplay between laser and plasma control variables that is necessary to find the best trade-off between competing beam properties.

Laser-plasma accelerators (LPAs) now routinely produce electron beams with GeV energies over acceleration lengths on the order of a few centimeters. This capability and the demonstration of multistage coupling make LPAs promising for numerous applications. However, beam quality preservation in multistage accelerators remains an obstacle because of the need to separate the laser pulse from the electron beam. Plasma mirrors can be used to redirect the laser pulse, but their substrate thickness threatens to substantially degrade the electron beam emittance. Ultrathin (∼20 nm) liquid crystal (LC) plasma mirrors are an excellent candidate to address this challenge. This work investigates the robustness of thin LC plasma mirrors in the presence of capillary discharge plasma and an auxiliary heater laser. We find they can be operated ∼10 cm from the capillary exit when a heater laser is used. We then performed a normalized emittance measurement enabled using a 20 nm LC plasma mirror to protect electron beam optics after the LPA. The emittance contribution from scattering through the plasma mirror is calculated to be of order 100 nm, much less than the measured emittance of 4.0 μm. Finally, we develop a model to calculate plasma mirror performance based on the laser polarization and intensity, and plasma mirror thickness.

The present state of progress in laser wakefield acceleration encourages considering it as a practical alternative to conventional particle accelerators. A promising application would be to use a laser-plasma accelerator as an injector for a synchrotron light source. Yet, the energy spread and jitter of the laser-plasma beam pose a significant difficulty for an efficient injection. In this paper, we propose a design of a prototype injector to deliver 500 MeV low-intensity electron bunches to the DESY-II electron synchrotron. The design utilizes presently available conventional accelerator technology, such as a chicane and an X-band radio frequency cavity, to reduce the energy spread and jitter of the electron beam down to a sub-per-mille level.

We describe the development and operation of a regenerative, cryogenically-formed discharge waveguide formed by freezing nitrous oxide gas onto the inner wall of a sapphire capillary. We demonstrate a technique for varying the channel diameter in situ and present guiding of low-power laser pulses through 6-cm long waveguides with channel diameters of 0.7, 0.8, and 1 mm. Measurements and simulations of the output laser fluence showed that the matched spot size could be adjusted with the thickness of the solid nitrous oxide layer.

We propose a short period undulator based on the electromagnetic field pattern in a THz-driven split ring resonator structure. An analytical model is developed that allows us to assess the key performance parameters of the undulator and to estimate the emitted radiation spectrum. Different geometric configurations are compared in detail using numerical simulations. A 100 MeV electron bunch with 5 pC charge is shown to emit narrow band 83 eV photon pulses with a peak brightness of approximately 10^{19} photons/(s mrad^{2} mm^{2} 0.1% BW) when passing through the 100 mm long undulator with a 1 mm period.

We present a study of laser-ion acceleration, where an increased laser spot size leads to sheath field geometries that accelerate ion beams of narrow and achromatic divergence at unprecedented charge densities, resulting from the high aspect ratio of the laser spot size to the acceleration distance. Matching the laser pulse length to the transverse laser spot size mitigated laser sweeping across the target front side and optimized the acceleration, with maximum energies deviating significantly from a linear intensity scaling.

We propose a short period undulator which is based on the alternating electromagnetic field pattern of THz-driven surface plasmons in a thin conductive layer on a dielectric grating. An approximate analytical model allows to assess the key performance parameters of the undulator and to estimate the emitted radiation spectrum. The specific example of a graphene based undulator is simulated in detail. For a moderate electron beam energy of 100 MeV and a bunch charge of 0.5 pC the 40 mm long undulator is shown to emit narrow band 1 keV x-ray pulses with a peak brightness of approximately 10^{16} photons/(s mrad^{2} mm^{2} 0.1% BW). It therefore has potential for a compact and low cost x-ray source.

Active plasma lenses have the potential to enable broad-ranging applications of plasma-based accelerators owing to their compact design and radially symmetric kT/m-level focusing fields, facilitating beam-quality preservation and compact beam transport. We report on the direct measurement of magnetic field gradients in active plasma lenses and demonstrate their impact on the emittance of a charged particle beam. This is made possible by the use of a well-characterized electron beam with 1.4 mm mrad normalized emittance from a conventional accelerator. Field gradients of up to 823 T/m are investigated. The observed emittance evolution is supported by numerical simulations, which suggests the potential for conservation of the core beam emittance in such a plasma lens setup.

Similarly to laser or x-ray beams, the interaction of sufficiently intense particle beams with neutral gases will result in the creation of plasma. In contrast to photon-based ionization, the strong unipolar field of a particle beam can generate a plasma where the electron population receives a large initial momentum kick and escapes, leaving behind unshielded ions. Measuring the properties of the ensuing Coulomb exploding ions—such as their kinetic energy distribution, yield, and spatial distribution—can provide information about the peak electric fields that are achieved in the electron beams. Particle-in-cell simulations and analytical models are presented for high-brightness electron beams of a few femtoseconds or even hundreds of attoseconds, and transverse beam sizes on the micron scale, as generated by today’s free electron lasers. Different density regimes for the utilization as a potential diagnostics are explored, and the fundamental differences in plasma dynamical behavior for e-beam or photon-based ionization are highlighted. By measuring the dynamics of field-induced ions for different gas and beam densities, a lower bound on the beam charge density can be obtained in a single shot and in a noninvasive way. The exponential dependency of the ionization yield on the beam properties can provide unprecedented spatial and temporal resolution, at the submicrometer and subfemtosecond scales, respectively, offering a practical and powerful approach to characterizing beams from accelerators at the frontiers of performance.

In a plasma-accelerator-based linear collider, the density of matched, low-emittance, high-energy particle bunches required for collider applications can be orders of magnitude above the background ion density, leading to ion motion, perturbation of the focusing fields, and, hence, to beam emittance growth. By analyzing the response of the background ions to an ultrahigh density beam, analytical expressions, valid for nonrelativistic ion motion, are derived for the transverse wakefield and for the final (i.e., after saturation) bunch emittance. Analytical results are validated against numerical modeling. Initial beam distributions are derived that are equilibrium solutions, which require head-to-tail bunch shaping, enabling emittance preservation with ion motion.

Control of the properties of laser-plasma-accelerated electron beams that were injected along a shock-induced density downramp through precision tailoring of the density profile was demonstrated using a 1.8 J, 45 fs laser interacting with a mm-scale gas jet. The effects on the beam spatial profile, steering, and absolute energy spread of the density region before the shock and tilt of the shock were investigated experimentally and with particle-in-cell simulations. By adjusting these density parameters, the electron beam quality was controlled and improved while the energy (30–180 MeV) and energy spread (2–11 MeV) were independently tuned. Simple models that are in good agreement with the experimental results are proposed to explain these relationships, advancing the understanding of downramp injection. This technique allows for high-quality electron beams with percent-level energy spread to be tailored based on the application.

Active plasma lenses have attracted interest in novel accelerator applications due to their ability to provide large-field-gradient (short focal length), tunable, and radially symmetric focusing for charged particle beams. However, if the discharge current is not flowing uniformly as a function of radius, one can expect a radially varying field gradient as well as potential emittance degradation. We have investigated this experimentally for a 1-mm-diameter active plasma lens. The measured near-axis field gradient is approximately 35% larger than expected for a uniform current distribution, and at overfocusing currents ring-shaped electron beams are observed. These observations are explained by simulations.

We reply to Terzic and Krafft’s forgoing Comment [Phys. Rev. Accel. Beams, Comment on “Controlling the spectral shape of nonlinear Thomson scattering with proper laser chirping” 19 (2016)PRABCJ2469-9888]. We disagree with the conclusion of the Comment regarding the novelty of solutions and the citations presented in our paper.

The theory of a plasma undulator excited by a short intense laser pulse in a parabolic plasma channel is presented. The undulator fields are generated either by the laser pulse incident off-axis and/or under the angle with respect to the channel axis. Linear plasma theory is used to derive the wakefield structure. It is shown that the electrons injected into the plasma wakefields experience betatron motion and undulator oscillations. Optimal electron beam injection conditions are derived for minimizing the amplitude of the betatron motion, producing narrow-bandwidth undulator radiation. Polarization control is readily achieved by varying the laser pulse injection conditions.

Effects of nonlinearity in Thomson scattering of a high intensity laser pulse from electrons are analyzed. Analytic expressions for laser pulse shaping in frequency (chirping) are obtained which control spectrum broadening for high laser pulse intensities. These analytic solutions allow prediction of the spectral form and required laser parameters to avoid broadening. Results of analytical and numerical calculations agree well. The control over the scattered radiation bandwidth allows narrow bandwidth sources to be produced using high scattering intensities, which in turn greatly improves scattering yield for future x- and gamma-ray sources.

The laser driven acceleration of ions is considered a promising candidate for an ion source for hadron therapy of oncological diseases. Though proton and carbon ion sources are conventionally used for therapy, other light ions can also be utilized. Whereas carbon ions require 400 MeV per nucleon to reach the same penetration depth as 250 MeV protons, helium ions require only 250 MeV per nucleon, which is the lowest energy per nucleon among the light ions (heavier than protons). This fact along with the larger biological damage to cancer cells achieved by helium ions, than that by protons, makes this species an interesting candidate for the laser driven ion source. Two mechanisms (magnetic vortex acceleration and hole-boring radiation pressure acceleration) of PW-class laser driven ion acceleration from liquid and gaseous helium targets are studied with the goal of producing 250 MeV per nucleon helium ion beams that meet the hadron therapy requirements. We show that He^{3} ions, having almost the same penetration depth as He^{4} with the same energy per nucleon, require less laser power to be accelerated to the required energy for the hadron therapy.

The minimum obtainable transverse emittance (thermal emittance) of electron beams generated and trapped in plasma-based accelerators using laser ionization injection is examined. The initial transverse phase space distribution following ionization and passage through the laser is derived, and expressions for the normalized transverse beam emittance, both along and orthogonal to the laser polarization, are presented. Results are compared to particle-in-cell simulations. Ultralow emittance beams can be generated using laser ionization injection into plasma accelerators, and examples are presented showing normalized emittances on the order of tens of nm.

Laser plasma based accelerators have the potential to reduce dramatically the size and cost of future particle colliders and light sources. Production of high quality beams along with reproducibility, tunability, and efficiency are required for many applications. We present design principles for two-pulse colliding laser pulse injection mechanisms, which can meet these requirements. Simulations are used to determine the best conditions for the production of high quality beams: high charge, low energy spread, and low emittance. Simulations also allow access to the internal dynamics of the interaction, providing insight regarding further improvement of the beam quality. We find that a 20 pC beam can be accelerated to 300 MeV in 4 mm with only a few percent energy spread and transverse normalized emittance close to 1 mm mrad, using a 10 TW laser. We demonstrate that this design scales according to linear theory. Control of the laser pulse mode content and subsequent evolution in the plasma channel are shown to be critical for achieving the highest beam quality.

A method to inject electron beams with controllable transverse emittances in a laser-plasma accelerators is proposed and analyzed. It uses two colliding laser pulses that propagate transversely to the plasma wave. For colliding pulses with equal frequencies, a beam with very low emittance is generated when the collision is close to the density peak of the plasma wave. Electrons near the axis are accelerated longitudinally by the ponderomotive force of the colliding pulses, accelerated transversely by the beat wave, and subsequently injected into the second bucket of the wake. Ionization is used to increase the transverse injection area and the final trapped charge. Simulations show that the transverse emittance can be less than the 0.1 mm mrad level, which is important for many applications. For colliding laser pulses with different frequencies, the beat wave can produce asymmetric injection, which can enhance betatron radiation generated by the electron beam.

We reply to Lebedev and Nagaitsev’s foregoing Comment [Phys. Rev. ST Accel. Beams 16, 108001 (2013)PRABFM1098-4402]. We disagree with the conclusion of the Comment that scattering imposes a fundamental limitation on plasma-based accelerator technology. Laser-plasma accelerators are compatible with high-luminosity collider concepts.

The development of models and the “Virtual Detector for Synchrotron Radiation” (vdsr) code that accurately describe the production of synchrotron radiation are described. These models and code are valid in the classical and linear (single-scattering) quantum regimes and are capable of describing radiation produced from laser-plasma accelerators (LPAs) through a variety of mechanisms including betatron radiation, undulator radiation, and Thomson/Compton scattering. Previous models of classical synchrotron radiation, such as those typically used for undulator radiation, are inadequate in describing the radiation spectra from electrons undergoing small numbers of oscillations. This is due to an improper treatment of a mathematical evaluation at the end points of an integration that leads to an unphysical plateau in the radiation spectrum at high frequencies, the magnitude of which increases as the number of oscillation periods decreases. This is important for betatron radiation from LPAs, in which the betatron strength parameter is large but the number of betatron periods is small. The code vdsr allows the radiation to be calculated in this regime by full integration over each electron trajectory, including end-point effects, and this code is used to calculate betatron radiation for cases of experimental interest. Radiation from Thomson scattering and Compton scattering is also studied with vdsr. For Thomson scattering, radiation reaction is included by using the Sokolov method for the calculation of the electron dynamics. For Compton scattering, quantum recoil effects are considered in vdsr by using Monte Carlo methods. The quantum calculation has been benchmarked with the classical calculation in a classical regime.

Beam-beam interaction constraints modify the basic plasma density scalings for a linear collider based on laser-plasma accelerators. In the quantum beamstrahlung regime, it is shown that operating at low plasma density increases beamstrahlung effects, owing to the higher bunch charge and longer bunch length. At high plasma density, the bunch charge is limited by beam loading, and the required power is proportional to the square root of the plasma density. At low plasma density, the bunch charge is limited by beamstrahlung, which, for fixed luminosity, requires operation at higher laser repetition rate and, hence, higher power requirements, or the use of multibunch trains. If round beams are used in a multibunch train format with fixed beam loading, and the collider is constrained by beamstrahlung, then the required collider power is independent of plasma density.

A comprehensive study of charge diagnostics is conducted to verify their validity for measuring electron beams produced by laser plasma accelerators (LPAs). First, a scintillating screen (Lanex) was extensively studied using subnanosecond electron beams from the Advanced Light Source booster synchrotron, at the Lawrence Berkeley National Laboratory. The Lanex was cross calibrated with an integrating current transformer (ICT) for up to the electron energy of 1.5 GeV, and the linear response of the screen was confirmed for charge density and intensity up to 160 pC/mm^{2} and 0.4 pC/(ps mm^{2}), respectively. After the radio-frequency accelerator based cross calibration, a series of measurements was conducted using electron beams from an LPA. Cross calibrations were carried out using an activation-based measurement that is immune to electromagnetic pulse noise, ICT, and Lanex. The diagnostics agreed within ±8%, showing that they all can provide accurate charge measurements for LPAs.

The design and performance are presented of an electromagnetically driven gas valve [M. Krishnan, J. Wright, and T. Ma, Proceedings of the 13th Advanced Accelerator Concepts Workshop, Santa Cruz, CA, AIP Conf. Proc. No. 1086 (AIP, New York, 2008)] that opens in

Higher-order laser modes are analyzed as a method to control focusing forces and improve the electron bunch quality in laser-plasma accelerators. In the linear wake regime, the focusing force is proportional to the transverse gradient of the laser intensity, which can be shaped by a superposition of modes. In particular, the transverse wakefield can be arbitrarily small in a region about the axis by adjusting the laser modes. Plasma channel effects, which prohibit the formation of the controlled-focusing region, can be mitigating by introducing a delay between the modes. Modes with parallel polarization produce a beat interference in the laser intensity, which lead to deflecting forces. This can be avoided by using modes with orthogonal polarization, different frequencies, or short pulses that do not overlap. Particle-in-cell simulations are performed of a laser-plasma accelerator in the quasilinear regime driven by high-order modes. Simulations show that, by including the first-order mode, the matched radius of the electron bunch is substantially increased, which for fixed bunch density and emittance implies an increase in the beam charge.

Physics considerations for a next-generation linear collider based on laser-plasma accelerators are discussed. The ultrahigh accelerating gradient of a laser-plasma accelerator and short laser coupling distance between accelerator stages allows for a compact linac. Two regimes of laser-plasma acceleration are discussed. The highly nonlinear regime has the advantages of higher accelerating fields and uniform focusing forces, whereas the quasilinear regime has the advantage of symmetric accelerating properties for electrons and positrons. Scaling of various accelerator and collider parameters with respect to plasma density and laser wavelength are derived. Reduction of beamstrahlung effects implies the use of ultrashort bunches of moderate charge. The total linac length scales inversely with the square root of the plasma density, whereas the total power scales proportional to the square root of the density. A 1 TeV center-of-mass collider based on stages using a plasma density of 10^{17} cm^{-3} requires tens of J of laser energy per stage (using 1 μm wavelength lasers) with tens of kHz repetition rate. Coulomb scattering and synchrotron radiation are examined and found not to significantly degrade beam quality. A photon collider based on laser-plasma accelerated beams is also considered. The requirements for the scattering laser energy are comparable to those of a single laser-plasma accelerator stage.

Abstract Whole virion inactivated vaccine CoronaVac (C) and Spike (S) mRNA BNT162b2 (B) vaccines differ greatly in their ability to elicit neutralizing antibodies but have somewhat comparable effectiveness in protecting from severe COVID-19. We conducted further analyses for a randomized trial (Cobovax study, NCT05057169) of third dose homologous and heterologous booster vaccination, i.e. four interventions CC-C, CC-B, BB-C and BB-B. Here, we assess vaccine immunogenicity beyond neutralizing function, including S and non-S antibodies with Fc receptor (FcR) binding, antibody avidity and T cell specificity to 6 months post-vaccination. Ancestral and Omicron S-specific IgG and FcR binding are significantly higher by BNT162b2 booster than CoronaVac, regardless of first doses. Nucleocapsid (N) antibodies are only increased in homologous boosted CoronaVac participants (CC-C). CoronaVac primed participants have lower baseline S-specific CD4+ IFNγ+ cells, but are significantly increased by either CoronaVac or BNT162b2 boosters. Priming vaccine content defined T cell peptide specificity preference, with S-specific T cells dominating B primed groups and non-S structural peptides contributing more in C primed groups, regardless of booster type. S-specific CD4+ T cell responses, N-specific antibodies, and antibody effector functions via Fc receptor binding may contribute to protection and compensate for less potent neutralizing responses in CoronaVac recipients.

Abstract Due to high energy density, clean combustion products and abundant resources, natural gas hydrates (NGHs) have been regarded as an important clean energy source with the potential for large-scale development and utilization. However, pilot tests in NGHs show that their production rates are far below commercial needs. Multilateral well technology may lead to a solution to this problem because it can dramatically expand the drainage area of production wells. This paper presents the practical rate transient analysis for multilateral horizontal wells in NGHs. In developing solution to the diffusivity equation of multilateral horizontal wells in NGHs, the superposition principle and reciprocity are applied. We wrote the governing equation in cylindrical coordinates to describe the NGH flow process. We used the moving boundaries and dissociation coefficients to model the solid-to-gas transition process in hydrates. To obtain solutions for flow in hydrate reservoirs, we used Laplace transforms and the Stehfest numerical inversion method. Superposition principle and Gaussian elimination are applied to obtain the desired solution for multilateral horizontal wells. We validated our proposed model with a commercial numerical simulator. By performing sensitivity analyses, effects on production behavior of the number of branches, dissociation coefficient, radius of the region with dissociated hydrate, and dispersion ratio are determined. A synthetic case study is conducted to show the typical production behaviors.

Abstract Introduction Clinicians commonly escalate empiric antibiotic therapy due to poor clinical progress without microbiology guidance. When escalating, they should take account of how resistance to an initial antibiotic affects the probability of resistance to subsequent options. The term "escalation antibiogram" (EA) has been coined to describe this concept. One difficulty when applying the EA concept to clinical practice is understanding the uncertainty in results and how this changes for specific patient subgroups. Methods A Bayesian model was developed to estimate antibiotic resistance rates in Gram-negative bloodstream infections based on phenotypic resistance data. The model generates a series of “credible” curves to fit the resistance data, each with the same probability of representing the true rate given the inherent uncertainty. To avoid overfitting, an integrated penalisation term adaptively smooths the curves given the level of evidence. Results Rates of resistance to empiric first-choice and potential escalation antibiotics were calculated for the whole hospitalised population based on 10,486 individual bloodstream infections, and for a range of specific patient groups, including ICU (intensive care unit), haematolo-oncology, and paediatric patients. The model generated an expected value (posterior mean) with 95% credible interval to illustrate uncertainty, based on the size of the patient subgroup. For example, the posterior means of piperacillin/tazobactam resistance rates in Gram-negative bloodstream infection are different between patients on ICU and the general hospital population: 27.3% (95% CI 18.1–37.2 vs. 13.4% 95% CI 11.0–16.1) respectively. The model can also estimate the probability of inferiority between two antibiotics for a specific patient population. Differences in optimal escalation antibiotic options between specific patient groups were noted. Conclusions EA analysis informed by our Bayesian model is a useful tool to support empiric antibiotic switches, providing an estimate of local resistance rates, and a comparison of antibiotic options with a measure of the uncertainty in the data. We demonstrate that EAs calculated for the whole hospital population cannot be assumed to apply to specific patient group.

Aerosol optical properties have been provided by the Geostationary Environment Monitoring Spectrometer (GEMS), the world's first geostationary-Earth-orbit (GEO) satellite instrument designed for air quality monitoring. This study describes improvements made to the GEMS aerosol retrieval (AERAOD) algorithm, including spectral binning, surface reflectance estimation, cloud masking, and post-processing, along with validation results. These enhancements aim to provide more accurate and reliable aerosol-monitoring results for Asia. The adoption of spectral binning in the lookup table (LUT) approach reduces random errors and enhances the stability of satellite measurements. In addition, we introduced a new high-resolution database for surface reflectance estimation based on the minimum-reflectance method, which was adapted to the GEMS pixel resolution. Monthly background aerosol optical depth (BAOD) values were used to estimate hourly GEMS surface reflectance consistently. Advanced cloud-removal techniques have been implemented to significantly improve the effectiveness of cloud detection and enhance aerosol retrieval quality. An innovative post-processing correction method based on machine learning has been introduced to address artificial diurnal biases in aerosol optical depth (AOD) observations. In this study, we investigated selected aerosol events, highlighting the capability of GEMS in monitoring and providing insights into hourly aerosol optical properties during various atmospheric events. The performance of the GEMS AERAOD products was validated against the Aerosol Robotic Network (AERONET) and Cloud-Aerosol Lidar with Orthogonal Polarization (CALIOP) data for the period from November 2021 to October 2022. GEMS AOD at 443 nm demonstrated a strong correlation with AERONET AOD at 443 nm (R = 0.792). However, it exhibited biased patterns, including the underestimation of high AOD values and overestimation of low-AOD conditions. Different aerosol types (highly absorbing fine aerosols, dust aerosols, and non-absorbing aerosols) exhibited distinct validation results. The retrievals of GEMS single-scattering albedo (SSA) at 443 nm agreed well with the AERONET SSA at 440 nm within reasonable error ranges, with variations observed among aerosol types. For GEMS AOD at 443 nm exceeding 0.4 (1.0), 42.76 % (56.61 %) and 67.25 % (85.70 %) of GEMS SSA data points fell within the ±0.03 and ±0.05 error bounds, respectively. Model-enforced post-processing correction improved GEMS AOD and SSA performance, thereby reducing the diurnal variation in the biases. The validation of the retrievals of GEMS aerosol layer height (ALH) against the CALIOP data demonstrates good agreement, with a mean bias of −0.225 km and 55.29 % (71.70 %) of data points falling within ±1 km (1.5 km).

Nitrogen oxide radicals (NOx≡NO+NO2) emitted by fuel combustion are important precursors of ozone and particulate matter pollution, and NO2 itself is harmful to public health. The Geostationary Environment Monitoring Spectrometer (GEMS), launched in space in 2020, now provides hourly daytime observations of NO2 columns over East Asia. This diurnal variation offers unique information on the emission and chemistry of NOx, but it needs to be carefully interpreted. Here we investigate the drivers of the diurnal variation in NO2 observed by GEMS during winter and summer over Beijing and Seoul. We place the GEMS observations in the context of ground-based column observations (Pandora instruments) and GEOS-Chem chemical transport model simulations. We find good agreement between the diurnal variations in NO2 columns in GEMS, Pandora, and GEOS-Chem, and we use GEOS-Chem to interpret these variations. NOx emissions are 4 times higher in the daytime than at night, driving an accumulation of NO2 over the course of the day, offset by losses from chemistry and transport (horizontal flux divergence). For the urban core, where the Pandora instruments are located, we find that NO2 in winter increases throughout the day due to high daytime emissions and increasing NO2/NOx ratio from entrainment of ozone, partly balanced by loss from transport and with a negligible role of chemistry. In summer, by contrast, chemical loss combined with transport drives a minimum in the NO2 column at 13:00–14:00 local time (LT). Segregation of the GEMS data by wind speed further demonstrates the effect of transport, with NO2 in winter accumulating throughout the day at low winds but flat at high winds. The effect of transport can be minimized in summer by spatially averaging observations over the broader metropolitan scale, under which conditions the diurnal variation in NO2 reflects a dynamic balance between emission and chemical loss.

Theoretical and numerical studies of the transport in vacuum of multi-nC, multi-MeV electron beams are performed using several methods, including envelope models, a novel semianalytic approach using ellipsoidal shell decomposition, a modified electrostatic particle-in-cell method, and a point-to-point interaction model. The effects of space-charge forces on the longitudinal and transverse bunch properties are evaluated for various bunch lengths, energies, energy spreads, and charges. An evaluation of the various methods for studying space-charge effects in large energy spread, high charge beams is summarized. Examples are given for beam distributions typical of those generated by plasma-based accelerators. It is found that, for the highly correlated beams produced in the self-modulated regime, the high energy portion of the beam can gain significant energy while propagating in vacuum due to space-charge effects.

Salmonella enterica serovar Agona (S. Agona) has been increasingly recognised as a prominent cause of gastroenteritis. This serovar is a strong biofilm former that can undergo genome rearrangement and enter a viable but non-culturable state whilst remaining metabolically active. Similar strategies are employed by S. Typhi, the cause of typhoid fever, during human infection, which are believed to assist with the transition from acute infection to chronic carriage. Here we report S. Agona's ability to persist in people and examine factors that might be contributing to chronic carriage. A review of 2233 S. Agona isolates from UK infections (2004-2020) and associated carriage was undertaken, in which 1155 had short-read sequencing data available. A subset of 207 isolates was selected from different stages of acute and persistent infections within individual patients. The subset underwent long-read sequencing and genome structure (GS) analysis, as well as phenotyping assays including carbon source utilisation and biofilm formation. Associations between genotypes and phenotypes were investigated to compare acute infections to those which progress to chronic. GS analysis revealed the conserved arrangement GS1.0 in 195 isolates, and 8 additional GSs in 12 isolates. These rearranged isolates were typically associated with early, convalescent carriage (3 weeks- 3 months). We also identified an increase in SNP variation during this period of infection. We believe this increase in genome-scale and SNP variation reflects a population expansion after acute S. Agona infection, potentially reflecting an immune evasion mechanism which enables persistent infection to become established.

A 48-year-old woman with a complex aortic history, beginning with an acute type A dissection repair 14 years prior to presentation, followed by endovascular repair of her residual type B dissection and thoracoabdominal aortic aneurysm, presented with an incidental finding of a new, aortic pseudoaneurysm originating from her ascending graft. Given the prohibitive risk of redo open surgery, this was successfully repaired using proximal aortic extension cuffs from the TAG-TBE endograft system (W.L. Gore, Flagstaff, AZ) with complete exclusion of the pseudoaneurysm. To our knowledge, this is the first reported use of this newly commercially available thoracic endograft for this application.

Electron bunches produced in self-modulated laser wakefield experiments usually have a broad energy distribution, with most electrons at low energy (1–3 MeV) and only a small fraction at high energy. We propose and investigate further acceleration of such bunches in a channel-guided resonant laser wakefield accelerator. Two-dimensional simulations with and without the effects of self-consistent beam loading are performed and compared. These results indicate that it is possible to trap about 40% of the injected bunch charge and accelerate this fraction to an average energy of about 50 MeV in a plasma channel of a few mm.

We present 2D simulations of both beam-driven and laser-driven plasma wakefield accelerators, using the object-oriented particle-in-cell code XOOPIC, which is time explicit, fully electromagnetic, and capable of running on massively parallel supercomputers. Simulations of laser-driven wakefields with low \(∼10^{16} W/cm^{2}\) and high \(∼10^{18} W/cm^{2}\) peak intensity laser pulses are conducted in slab geometry, showing agreement with theory and fluid simulations. Simulations of the E-157 beam wakefield experiment at the Stanford Linear Accelerator Center, in which a 30 GeV electron beam passes through 1 m of preionized lithium plasma, are conducted in cylindrical geometry, obtaining good agreement with previous work. We briefly describe some of the more significant modifications to XOOPIC required by this work, and summarize the issues relevant to modeling relativistic electron-neutral collisions in a particle-in-cell code.

Abstract Health apps and wearables are touted to improve physical health and mental well-being. However, it is unclear from existing research the extent to which these health technologies are efficacious in improving physical and mental well-being at a population level, particularly for the underserved groups from the perspective of health equity and social determinants. Also, it is unclear if the relationship between health apps and wearables use and physical and mental well-being differs across individualistic, collectivistic, and a mix of individual–collectivistic cultures. A large-scale online survey was conducted in the U.S. (individualist culture), China (collectivist culture), and Singapore (mix of individual–collectivist culture) using quota sampling after obtaining ethical approval from the Institutional Review Board (IRB-2021-262) of Nanyang Technological University (NTU), Singapore. There was a total of 1004 respondents from the U.S., 1072 from China, and 1017 from Singapore. Data were analyzed using multiple regression and negative binomial regression. The study found that income consistently had the strongest relationship with physical and mental well-being measures in all three countries, while the use of health apps and wearables only had a moderate association with psychological well-being only in the US. Health apps and wearables were associated with the number of times people spent exercising and some mental health outcomes in China and Singapore, but they were only positively associated with psychological well-being in the US. The study emphasizes the importance of considering the social determinants, social–cultural context of the population, and the facilitating conditions for the effective use of digital health technologies. The study suggests that the combined use of both health apps and wearables is most strongly associated with better physical and mental health, though this association is less pronounced when individuals use only apps or wearables.

The structure and distribution of sub-glacial water directly influences Antarctic ice mass loss by reducing or enhancing basal shear stress and accelerating grounding line retreat. A common technique for detecting sub-glacial water involves analyzing the spatial variation in reflectivity from an airborne radar echo sounding (RES) survey. Basic RES analysis exploits the high dielectric contrast between water and most other substrate materials, where a reflectivity increase ≥ 15 dB is frequently correlated with the presence of sub-glacial water. There are surprisingly few additional tools to further characterize the size, shape, or extent of hydrological systems beneath large ice masses. We adapted an existing radar backscattering simulator to model RES reflections from sub-glacial water structures using the University of Texas Institute for Geophysics (UTIG) Multifrequency Airborne Radar Sounder with Full-phase Assessment (MARFA) instrument. Our series of hypothetical simulation cases modeled water structures from 5 to 50 m wide, surrounded by bed materials of varying roughness. We compared the relative reflectivity from rounded Röthlisberger channels and specular flat canals, showing both types of channels exhibit a positive correlation between size and reflectivity. Large (> 20 m), flat canals can increase reflectivity by more than 20 dB, while equivalent Röthlisberger channels show only modest reflectivity gains of 8–13 dB. Changes in substrate roughness may also alter observed reflectivity by 3–6 dB. All of these results indicate that a sophisticated approach to RES interpretation can be useful in constraining the size and shape of sub-glacial water features. However, a highly nuanced treatment of the geometric context is necessary. Finally, we compared simulated outputs to actual reflectivity from a single RES flight line collected over Thwaites Glacier in 2022. The flight line crosses a previously proposed Röthlisberger channel route, with an obvious bright bed reflection in the radargram. Through multiple simulations comparing various water system geometries, such as canals and sub-glacial lakes, we demonstrated the important role that topography and water geometry can play in observed RES reflectivity. From the scenarios that we tested, we concluded the bright reflector from our RES flight line cannot be a Röthlisberger channel but could be consistent with a series of flat canals or a sub-glacial lake. However, we note our simulations were not exhaustive of all possible sub-glacial water configurations. The approach outlined here has broad applicability for studying the basal environment of large glaciers. We expect to apply this technique when constraining the geometry and extent of many sub-glacial hydrologic structures in the future. Further research may also include comprehensive investigations of the impact of sub-glacial roughness, substrate heterogeneity, and computational efficiencies enabling more complex and complete simulations.

The basidiomycete fungus Cryptococcus neoformans is a useful model for investigating mechanisms of fungal pathogenesis in mammalian hosts. This pathogen is the causative agent of cryptococcal meningitis in immunocompromised patients and is in the critical priority group of the World Health Organization fungal priority pathogens list. In this study, we employed a mutant lacking the OPI3 gene encoding a methylene-fatty-acyl-phospholipid synthase to characterize the role of phosphatidylcholine (PC) and lipid homeostasis in the virulence of C. neoformans. We first confirmed that OPI3 was required for growth in nutrient limiting conditions, a phenotype that could be rescued with exogenous choline and PC. Additionally, we established that loss of Opi3 and the lack of PC lead to an accumulation of neutral lipids in lipid droplets and alterations in major lipid classes. The growth defect of the opi3Δ mutant was also rescued by sorbitol and polyethylene glycol (PEG), a result consistent with protection of ER function from the stress caused by lipid imbalance. We then examined the impact of Opi3 on virulence and found that the dependence of PC synthesis on Opi3 caused reduced capsule size and this was accompanied by an increase in shed capsule polysaccharide and changes in cell wall composition. Further tests of virulence demonstrated that survival in alveolar macrophages and the ability to cause disease in mice were not impacted by loss of Opi3 despite the choline auxotrophy of the mutant in vitro. Overall, this work establishes the contribution of lipid balance to virulence factor elaboration by C. neoformans and suggests that host choline is sufficient to support proliferation during disease.

IntroductionThe COVID-19 pandemic caused a widespread public health and financial crisis. The rapid vaccine development generated extensive discussions in both mainstream and social media, sparking optimism in the global financial markets. This study aims to explore the key themes from mainstream media’s coverage of COVID-19 vaccines on Facebook and examine how public interactions and responses on Facebook to mainstream media’s posts are associated with daily stock prices and trade volume of major vaccine manufacturers.MethodsWe obtained mainstream media’s coverage of COVID-19 vaccines and major vaccine manufacturers on Facebook from CrowdTangle, a public insights tool owned and operated by Facebook, as well as the corresponding trade volume and daily closing prices from January 2020 to December 2021. Structural topic modelling was used to analyze social media posts while regression analysis was conducted to determine the impact of Facebook reactions on stock prices and trade volume.Results10 diverse topics ranging from vaccine trials and their politicization (note: check that we use American spelling throughout), to stock market discussions were found to evolve over the pandemic. Although Facebook reactions were not consistently associated with vaccine manufacturers’ stock prices, ‘Haha’ and ‘Angry’ reactions showed the strongest association with stock price fluctuations. In comparison, social media reactions had little observable impact on trading volume.DiscussionTopics generated reflect both actual events during vaccine development as well as its political and economic impact. The topics generated in this study reflect both the actual events surrounding vaccine development and its broader political and economic impact. While we anticipated a stronger correlation, our findings suggest a limited relationship between emotional reactions on Facebook and vaccine manufacturers’ stock prices and trading volume. We also discussed potential technical enhancements for future studies, including the integration of large language models.

Small GTPases of the Rab family coordinate multiple membrane fusion and trafficking events in eukaryotes. In fungi, the Rab GTPase, Ypt7, plays a critical role in late endosomal trafficking, and is required for homotypic fusion events in vacuole biogenesis and inheritance. In this study, we identified a putative YPT7 homologue in Cryptococcus neoformans, a fungal pathogen causing life threatening meningoencephalitis in immunocompromised individuals. As part of an ongoing effort to understand mechanisms of iron acquisition in C. neoformans, we established a role for Ypt7 in growth on heme as the sole iron source. Deletion of YPT7 also caused abnormal vacuolar morphology, defective endocytic trafficking and autophagy, and mislocalization of Aph1, a secreted vacuolar acid phosphatase. Ypt7 localized to the vacuolar membrane and membrane contact sites between the vacuole and mitochondria (vCLAMPs), and loss of the protein impaired growth on inhibitors of the electron transport chain. Additionally, Ypt7 was required for robust growth at 39°C, a phenotype likely involving the calcineurin signaling pathway because ypt7 mutants displayed increased susceptibility to the calcineurin-specific inhibitors, FK506 and cyclosporin A; the mutants also had impaired growth in either limiting or high levels of calcium. Finally, Ypt7 was required for survival during interactions with macrophages, and ypt7 mutants were attenuated for virulence in a mouse inhalation model thus demonstrating the importance of membrane trafficking functions in cryptococcosis.

Abstract Agrobacterium‐mediated transient expression methods are widely used to study gene function in both model and non‐model plants. Using a dual‐luciferase assay, we quantified the effect of Agrobacterium‐infiltration parameters on the transient transformation efficiency of Catharanthus roseus seedlings. We showed that transformation efficiency is highly sensitive to seedling developmental state and a pre‐ and post‐infiltration dark incubation and is less sensitive to the Agrobacterium growth stage. For example, 5 versus 6 days of germination in the dark increased seedling transformation efficiency by seven‐ to eight‐fold while a dark incubation pre‐ and post‐infiltration increased transformation efficiency by five‐ to 13‐fold. Agrobacterium in exponential compared with stationary phase increased transformation efficiency by two‐fold. Finally, we quantified the variation in our Agrobacterium‐infiltration method in replicate infiltrations and experiments. Within a given experiment, significant differences of up to 2.6‐fold in raw firefly luciferase (FLUC) and raw Renilla luciferase (RLUC) luminescence occurred in replicate infiltrations. These differences were significantly reduced when FLUC was normalized to RLUC values, highlighting the utility of including a reference reporter to minimize false positives. Including a second experimental replicate further reduced the potential for false positives. This optimization and quantitative validation of Agrobacterium infiltration in C. roseus seedlings will facilitate the study of this important medicinal plant and will expand the application of Agrobacterium‐mediated transformation methods in other plant species.

ABSTRACT Mitochondrial functions are critical for the ability of the fungal pathogen Cryptococcus neoformans to cause disease. However, mechanistic connections between key functions such as the mitochondrial electron transport chain (ETC) and virulence factor elaboration have yet to be thoroughly characterized. Here, we observed that inhibition of ETC complex III suppressed melanin formation, a major virulence factor. This inhibition was partially overcome by defects in Cir1 or HapX, two transcription factors that regulate iron acquisition and use. In this regard, loss of Cir1 derepresses the expression of laccase genes as a potential mechanism to restore melanin, while HapX may condition melanin formation by controlling oxidative stress. We hypothesize that ETC dysfunction alters redox homeostasis to influence melanin formation. Consistent with this idea, inhibition of growth by hydrogen peroxide was exacerbated in the presence of the melanin substrate L-DOPA. In addition, loss of the mitochondrial chaperone Mrj1, which influences the activity of ETC complex III and reduces ROS accumulation, also partially overcame antimycin A inhibition of melanin. The phenotypic impact of mitochondrial dysfunction was consistent with RNA-Seq analyses of WT cells treated with antimycin A or L-DOPA, or cells lacking Cir1 that revealed influences on transcripts encoding mitochondrial functions (e.g., ETC components and proteins for Fe-S cluster assembly). Overall, these findings reveal mitochondria-nuclear communication via ROS and iron regulators to control virulence factor production in C. neoformans.IMPORTANCEThere is a growing appreciation of the importance of mitochondrial functions and iron homeostasis in the ability of fungal pathogens to sense the vertebrate host environment and cause disease. Many mitochondrial functions such as heme and iron-sulfur cluster biosynthesis, and the electron transport chain (ETC), are dependent on iron. Connections between factors that regulate iron homeostasis and mitochondrial activities are known in model yeasts and are emerging for fungal pathogens. In this study, we identified connections between iron regulatory transcription factors (e.g., Cir1 and HapX) and the activity of complex III of the ETC that influence the formation of melanin, a key virulence factor in the pathogenic fungus Cryptococcus neoformans. This fungus causes meningoencephalitis in immunocompromised people and is a major threat to the HIV/AIDS population. Thus, understanding how mitochondrial functions influence virulence may support new therapeutic approaches to combat diseases caused by C. neoformans and other fungi.

Introduction Gaming disorder has become a global concern and it could have a variety of health and social consequences. The trauma model has been applied to the understanding of different types of addictions as behavioral addictions can sometimes be conceptualized as self-soothing strategies to avoid trauma-related stressors or triggers. However, much less is known about the relationship between trauma exposure and gaming disorder. Objectives To inform prevention and intervention strategies and to facilitate further research, we conducted the first scoping review to explore and summarize the literature on the relationship between trauma and gaming disorder. Methods A systematic search was conducted on the Web of Science, Scopus and ProQuest. We looked for original studies published in English that included a measure of trauma exposure and a measure of gaming disorder symptoms, as well as quantitative data regarding the relationship between trauma exposure and gaming disorder. Results The initial search generated 412 articles, of which 15 met the inclusion criteria. All of them were cross-sectional studies, recruiting participants from both clinical and non-clinical populations. Twelve of them (80%) reported significant correlations between trauma exposure and the severity of gaming disorder symptoms (r = 0.18 to 0.46, p < 0.010). Several potential mediators, including depressive symptoms and dissociative experiences, have been identified. One study found that parental monitoring moderated the relationship between trauma and gaming disorder symptoms. No studies reported the prevalence of trauma or trauma-related symptoms among people with gaming disorder. Conclusions There is some evidence supporting the association between trauma and gaming disorder, at small to medium effect sizes. Future studies should investigate the mediators and moderators underlying the relationship between trauma and gaming disorder. The longitudinal relationship between trauma exposure and the development of gaming disorder should be clarified. A trauma-informed approach may be a helpful strategy to alleviate gaming disorder symptoms. Disclosure of Interest None Declared

Introduction Home nursing and medical services have an established role in delivering chronic medical care to populations which face difficulty accessing physical clinics. Those with chronic medical conditions and reduced mobility face a higher likelihood of suffering from psychiatric co-morbidity. However, till date there has been limited research done on home-based psychiatric care in this population. Since 2021, the Psychiatry department of Tan Tock Seng Hospital (TTSH) has been collaborating with TTSH Community Health Team (CHT) to manage potential psychiatric issues in community patients. These patients would be discussed in a weekly multidisciplinary setting. If indicated, home visit by both teams for home-based assessment and treatment would be arranged, allowing for detection and treatment of psychiatric illness. Objectives To demonstrate that the collaboration between the psychiatry team and CHT leads to diagnosis and treatment of psychiatric illness in a population that might otherwise have been unable to access psychiatric services. Methods We performed a retrospective study on all referrals from the CHT to the psychiatry team, within the 2-year period of August 2021 to August 2023. We collected demographic information, psychiatric history prior to referral, reason for referral, outcome of multidisciplinary discussion, and outcome of the home visits (including diagnoses made, and medications initiated). Results A total of 92 patients were referred by the CHT to the psychiatry team. Most were elderly with multiple medical co-morbidities; of note, a history of stroke was present in 24 of the referred patients. Common reasons for referral include suspected mental illness, risk assessment, and management of behavioural issues. 28 of the referred patients did not have a prior psychiatric history at the point of referral. Among these, home visits involving the psychiatric team were done for 16 patients. 11 (68%) of these home visits led to diagnosis of a new psychiatric illness. 9 of these patients were initiated on psychotropic medications in the home setting. Conclusions A significant proportion of patients (68% of home visits without prior psychiatric diagnosis) were newly diagnosed with psychiatric illness, allowing early psychiatric intervention to be delivered. This was achieved in a population with a high prevalence of multiple medical comorbidity and barriers to clinic-based psychiatric evaluation and treatment. We propose future comparative studies into how the collaboration between the psychiatric team and community health team can improve the quality of life and caregiver experience of patients with chronic medical problems, as well as how the service had improved the confidence of the community health team in identifying and managing patients with possible psychiatric issues. Disclosure of Interest None Declared

BackgroundDigital health technologies have the potential to improve health outcomes for older adults, especially for those recovering from stroke. However, there are challenges to developing these technologies, such as data absenteeism (where older adults’ views are often underrepresented in research and development) and technology chauvinism (the belief that sophisticated technology alone is the panacea to addressing health problems), which hinder their effectiveness. ObjectiveIn this study, we aimed to address these challenges by developing a wearable glove integrated with culturally relevant exergames to motivate older adults to exercise and, for those recovering from stroke, to adhere to rehabilitation. MethodsWe conducted a moderated usability study with 19 older adults, of which 11 (58%) had a history of stroke. Our participants engaged in a 30-minute gameplay session with the wearable glove integrated with exergames, followed by a quantitative survey and an in-depth interview. We used descriptive analysis to compare responses to the System Usability Scale between those who had a history of stroke and those who did not. In addition, we analyzed the qualitative interviews using a bottom-up thematic analysis to identify key themes related to the motivations and barriers regarding the use of wearable gloves for rehabilitation and exercise. ResultsOur study generated several key insights. First, making the exergames exciting and challenging could improve exercise and rehabilitation motivation, but it could also have a boomerang effect, where participants may become demotivated if the games were very challenging. Second, the comfort and ease of use of the wearable gloves were important for older adults, regardless of their stroke history. Third, for older adults with a history of stroke, the functionality and purpose of the wearable glove were important in helping them with specific exercise movements. ConclusionsOur findings highlight the importance of providing contextual support for the effective use of digital technologies, particularly for older adults recovering from stroke. In addition to technology and usability factors, other contextual factors such as gamification and social support (from occupational therapists or caregivers) should be considered to provide a comprehensive approach to addressing health problems. To overcome data absenteeism and technology chauvinism, it is important to develop digital health technologies that are tailored to the needs of underserved communities. Our study provides valuable insights for the development of digital health technologies that can motivate older adults recovering from stroke to exercise and adhere to rehabilitation.

IntroductionAlongside the improved survival of nasopharyngeal cancer (NPC), late radiation toxicities are alarmingly hampering survivors’ quality of life. A patient-reported symptom burden survey is lacking to address the unmet need for symptom management among local NPC survivors.MethodsA single-center cross-sectional survey was conducted on 211 NPC survivors who had completed radiation therapy for three to 120 months. We employed the Chinese version M. D. Anderson Symptom Inventory - Head & Neck Module (MDASI-HN-C), Functional Assessment of Cancer Therapy - Head & Neck (FACT-HN-C), and a question extracted from the Cancer Survivors’ Unmet Needs Measure (CaSUN).ResultsTwo hundred valid responses were collected. Participants suffered from at least four moderate to severe symptoms (mean = 4.84, SD = 4.99). The top five severe symptoms were dry mouth, mucus problems, difficulty swallowing or chewing, teeth or gum problems, and memory problems. MDASI-HN-C subscales were negatively correlated with the physical, emotional, functional, and HN-specific domains of the FACT-HN-C. The unmet need for symptom management was positively associated with symptom burden, either general symptoms (Adjusted odds ratio [ORadj] = 1.566, 95% CI = 1.282 – 1.914, p < 0.001) or top-5 symptoms (ORadj = 1.379, 95% CI = 1.185 – 1.604, p < 0.001), while negatively associated with post-RT time (ORadj = 0.981, 95% CI [0.972, 0.991], p < 0.001).ConclusionVirtually all NPC survivors suffer from late toxicities, which interplay with survivors’ perceptions intricately to affect their unmet needs for symptom management. Personalized supportive care strategies with regular assessments and stratifications are warranted.

IntroductionNatural killer/T cell lymphoma (NKTL) is an aggressive malignancy associated with poor prognosis. This is largely due to limited treatment options, especially for relapsed patients. Immunotherapies like immune checkpoint inhibitors (ICI) and anti-CD38 therapies have shown promising but variable clinical efficacies. Combining these therapies has been suggested to enhance efficacy.MethodsWe conducted a case study on a relapsed NKTL patient treated sequentially with anti-CD38 followed by ICI (anti-PD1) using cytometry analyses.Results and DiscussionOur analysis showed an expected depletion of peripheral CD38+ B cells following anti-CD38 treatment. Further analysis indicated that circulating anti-CD38 retained their function for up to 13 weeks post-administration. Anti-PD1 treatment triggered re-activation and upregulation of CD38 on the T cells. Consequently, these anti-PD1-activated T cells were depleted by residual circulating anti-CD38, rendering the ICI treatment ineffective. Finally, a meta-analysis confirmed this counterproductive effect, showing a reduced efficacy in patients undergoing combination therapy. In conclusion, our findings demonstrate that sequential anti-CD38 followed by anti-PD1 therapy leads to a counterproductive outcome in NKTL patients. This suggests that the treatment sequence is antithetic and warrants re-evaluation for optimizing cancer immunotherapy strategies.