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It has been demonstrated experimentally that laser plasma accelerators can produce multi-100 MeV electron bunches with a few percent energy spread, and from these electrons, multi-MeV quasi-monoenergetic photons have been demonstrated based on Compton up-scattering from a counter-propagating laser. This offers the potential of a high-quality, narrow-bandwidth, compact, photon source with broad application. The bandwidth of the resulting photons depends directly on the distribution of the electron bunch and is limited, in particular, by the bunch divergence (i.e., the spread in transverse velocity angle). At the same time, the ability to decelerate electrons after scattering is important to source deployment. We describe a series of plasma structures that expand and then collimate the electron bunch, reducing its divergence and thus reducing the bandwidth of the scattered photons while enabling both high performance scattering and deceleration. These plasma structures are demonstrated in simulations of the accelerator system, showing the potential to reach few-percent photon spread which is important for applications using nuclear resonance fluorescence.

Density transition injection is an effective technique for controllably loading electrons into a trapped phase for laser plasma accelerators. One common technique to achieve the required fluid structure is to impinge a thin blade on the plume of a supersonic nozzle. Density transitions induced in this way are often assumed to be bow shocks and therefore sharp, but simulations and fluorescence measurements presented in this work show that in many cases of interest, the density transition accessible to a laser propagating transverse to the shock is an intercepting shock, and therefore, shock thickness and density vary with pressure, laser height, and blade position. The fluid dynamics of a supersonic nozzle impinged on by a thin, flat object are explored through simulations and relevant features are verified via planar laser-induced fluorescence measurements. The implications of the results for tuning electron beam injectors in laser plasma accelerators are discussed.

Electrically discharged active plasma lenses (APLs) are actively pursued in compact high-brightness plasma-based accelerators due to their high-gradient, tunable, and radially symmetric focusing properties. In this manuscript, the APL is experimentally compared with a conventional quadrupole triplet, highlighting the favorable reduction in the energy dependence (chromaticity) in the transport line. Through transport simulations, it is explored how the non-uniform radial discharge current distribution leads to beam-integrated emittance degradation and a charge density reduction at focus. However, positioning an aperture at the APL entrance will significantly reduce emittance degradation without additional loss of charge in the high-quality core of the beam. An analytical model is presented that estimates the emittance degradation from a short beam driving a longitudinally varying wakefield in the APL. Optimizing laser plasma accelerator operation is discussed where emittance degradation from the non-uniform discharge current (favoring small beams inside the APL) and wakefield effects (favoring larger beam sizes) is minimized.

Laser plasma accelerators (LPA) offer an exciting possibility to deliver high energy, high brightness electrons beams in drastically smaller distance scales than is typical for conventional accelerators. As such, LPAs draw considerable attention as potential drivers for next generation light sources and for a compact linear collider. In order to asses the viability of an LPA source for a particular application, the brightness of the source should be properly characterized. In this paper, we present charge dependent transverse emittance measurements of LPA sources using both ionization injection and shock induced density down ramp injection, with the latter delivering smaller transverse emittances by a factor of two when controlling for charge density. The single shot emittance method is described in detail with a discussion on limitations related to second order transport effects. The direct role of space charge is explored through a series of simulations and found to be consistent with experimental observations.

Single-shot, charge-dependent emittance measurements of electron beams generated by a laser plasma accelerator (LPA) reveal that shock-induced density down-ramp injection produces beams with normalized emittances a factor of 2 smaller than beams produced via ionization injection. Such a comparison is made possible by the tunable LPA setup, which allows electron beams with nearly identical central energy and peak spectral charge density to be produced using the two distinct injection mechanisms. Parametric measurements of this type are essential for the development of LPA-based applications which ultimately require high charge density and low emittance.

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.

Randomized controlled trials have reported a 4-5 times increased risk of heart failure (HF) in breast cancer patients receiving trastuzumab (Herceptin (®) ) compared to patients who do not receive trastuzumab. However, data regarding the cardiac effects of trastuzumab on elderly patients treated in general practice remain very limited. Using the US surveillance, epidemiology, and end results (SEER)-Medicare database, we conducted a retrospective cohort study on the cardiac effects of trastuzumab use in all incident breast cancer patients diagnosed from 1998 to 2007 who were 66 years and older, had no prior recent claims for cardiomyopathy (CM) or HF, and were followed through 2009. We defined our outcome as the first CM/HF event after diagnosis. We performed Cox-proportional hazard models with propensity score adjustment to estimate CM/HF risk associated with trastuzumab use. A total of 6,829 out of 68,536 breast cancer patients (median age: 75) had an incident CM/HF event. Patients who received trastuzumab tended to be younger, non-white, diagnosed more recently, and had a stage IV diagnosis. Trastuzumab use was associated with an increased risk of CM/HF (HR = 2.08, 95 % CI 1.77-2.44, p < 0.001). The trastuzumab-associated CM/HF risk was stronger in patients who were younger (HR = 2.52 for 66-75 years and HR = 1.44 for 76 years and older, p < 0.001) and diagnosed in recent years (HR = 2.58 for 2006-2007 vs. 1.86 for 1998-2005, p = 0.01). The twofold risk of CM/HF associated with trastuzumab remained regardless of patients diagnosis stage, presence of hypertension, cardiovascular comorbidities, or receipt of anthracyclines, taxanes, or radiation. Trastuzumab may double CM/HF risk among elderly breast cancer patients. Our findings reinforce the need to prevent and manage cardiac risk among elderly breast cancer patients receiving trastuzumab.

BACKGROUND: Cardiovascular risk attributable to bevacizumab (Avastin(®), BEV) for treatment of metastatic colorectal cancer (CRC) remains unclear. We conducted a population-based cohort study to assess the safety of BEV use among patients aged ≥ 65. PATIENTS AND METHODS: We identified CRC patients diagnosed from 2005 to 2007 who received chemotherapy and were followed until 31 December 2009. Outcomes were 3-year risk of arterial thromboembolic events (ATEs), cardiomyopathy or congestive heart failure (CM/CHF), and cardiac death (CD) after chemotherapy initiation. We fitted Cox-proportional hazards (PHs) models with inverse-probability-of-treatment-weights and calculated hazard ratios (HRs) for the risk of adverse events. RESULTS: We identified 6803 CRC patients (median age: 73 years). Those with cardiac comorbidity were less likely to receive BEV (P < 0.0001). BEV is associated with an elevated risk of ATEs (HR = 1.82, 95% CI = 1.20-2.76, P < 0.001; rate difference: 3.5 additional cases/1000 person-years). We observed no association between BEV and CD or CM/CHF. CONCLUSIONS: In general practice, the cardiovascular risk of BEV in elderly CRC is modest. The observed ATEs risk is lower than reported in clinical trials, which may be due to careful patient selection. Our findings may facilitate clinical decision-making of BEV use in elderly patients.

Midbrain- and hindbrain-derived GABAergic interneurons are critical for regulation of sleep, respiratory, sensory-motor and motivational processes, and they are implicated in human neurological disorders. However, the precise mechanisms that underlie gener

Chun-Ta Chiu,1 Hsiao-Han Tsai,2 Jing-Yuan Chen,1,3 Che-Ming Jack Hu,2 Hui-Wen Chen1,3 1Department of Veterinary Medicine, National Taiwan University, Taipei, 10617, Taiwan; 2Institute of Biomedical Sciences, Academia Sinica, Taipei, 115, Taiwan; 3Animal Resource Center, National Taiwan University, Taipei, 10617, TaiwanCorrespondence: Hui-Wen Chen, Department of Veterinary Medicine, National Taiwan University, 1 Sec 4 Roosevelt Road, Taipei, 10617, Taiwan, Tel +886 2 33669450, Email winnichen@ntu.edu.twIntroduction: The clinical success of mRNA vaccine during the COVID-19 pandemic has inspired emerging approaches to elevate mRNA vaccine immunogenicity. Among them, antigen fusion protein designs for improved immune cell targeting have been shown to augment humoral immunity against small antigen targets.Methods: This research demonstrates that SARS-CoV-2 receptor binding domain (RBD) fusion with a minimalistic peptide segment of complement component 3b (C3b, residues 727– 767) ligand can improve mRNA vaccine immunogenicity through antigen targeting to complement receptor 1 (CR1). We affirm vaccines’ antigenicity and targeting ability towards specific receptors through Western blot and immunofluorescence assay. Furthermore, mice immunization studies help the investigation of the antibody responses.Results: Using SARS-CoV-2 Omicron RBD antigen, we compare mRNA vaccine formulations expressing RBD fusion protein with mouse C3b peptide (RBD-mC3), RBD fusion protein with mouse Fc (RBD-Fc), and wild-type RBD. Our results confirm the proper antigenicity and normal functionality of RBD-mC3. Upon validating comparable antigen expression by the different vaccine formulations, receptor-targeting capability of the fusion antigens is further confirmed. In mouse immunization studies, we show that while both RBD-mC3 and RBD-Fc elevate vaccine immunogenicity, RBD-mC3 leads to more sustained RBD-specific titers over the RBD-Fc design, presumably due to reduced antigenic diversion by the minimalistic targeting ligand.Conclusion: The study demonstrates a novel C3b-based antigen design strategy for immune cell targeting and mRNA vaccine enhancement. Keywords: vaccinology, nanotechnology, complement component 3b, follicular dendritic cells, complement receptor 1, immune cell targeting