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In minibeam therapy, the sparing of deep-seated normal tissue is limited by transverse beam spread caused by small-angle scattering. Contrary to proton minibeams, helium or carbon minibeams experience less deflection, which potentially reduces side effects. To verify this potential, an irradiation facility for preclinical and clinical studies is needed. This manuscript presents a concept for a carbon minibeam irradiation facility based on a LINAC design for conventional carbon therapy. A quadrupole triplet focuses the LINAC beam to submillimeter minibeams. A scanning and a dosimetry unit are provided to move the minibeam over the target and monitor the applied dose. The beamline was optimized by TRAVEL simulations. The interaction between beam and these components and the resulting beam parameters at the focal plane is evaluated by TOPAS simulations. A transverse beamwidth of < 100 μm (sigma) and a peak-to-valley (energy) dose ratio of > 1000 results for carbon energies of 100 MeV/u and 430 MeV/u (∼ 3 cm and 30 cm range in water) whereby the average beam current is ∼ 30 nA. Therefore, the presented irradiation facility exceeds the requirements for hadron minibeam therapy.

AWAKE is a plasma wakefield acceleration R&D experiment at CERN, where wakefields are driven by relativistic and self-modulated proton bunches. The goal of AWAKE Run 2b is to demonstrate that a correctly placed plasma density step stabilises the wakefield amplitude (after saturation of self-modulation) at a higher value than without the step. This can be demonstrated by accelerating witness particles. It is therefore planned to externally side-inject 19MeV test electrons into the wakefields. In this manuscript, the injection setup for the AWAKE Run 2b experiments is summarised. Challenges on beam transport due to the Earth’s magnetic field upstream of the vapour source entrance are highlighted and uncertainties on the injection location are estimated. Additionally, a new plasma-light-based diagnostic to verify that electrons cross the plasma column is introduced.

The Advanced Wakefield (AWAKE) Experiment is a proof-of-principle experiment demonstrating the acceleration of electron beams via proton-driven plasma wakefield acceleration. AWAKE Run 2 aims to build on the results of Run 1 by achieving higher energies with an improved beam quality. As part of the upgrade to Run 2, the existing proton and electron beamlines will be adapted and a second plasma cell and new 150-MeV electron beamline will be added. The specification for this new 150-MeV beamline will be challenging as it will be required to inject electron bunches with micron-level beam size and stability into the second plasma cell while being subject to tight spatial constraints. In this paper, we describe the techniques used (e.g., numerical optimizers and genetic algorithms) to produce the design of this electron line. We present a comparison of the methods used in this paper with other optimization algorithms commonly used within accelerator physics. Operational techniques are also studied including steering and alignment methods utilizing numerical optimizers and beam measurement techniques employing neural networks. We compare the performance of algorithms for online optimization and beam-based alignment in terms of their efficiency and effectiveness.

Following the successful Run 1 experiment, the Advanced Proton Driven Plasma Wakefield Acceleration Experiment (AWAKE) Run2 experiment requires the design and implementation of a compact electron source. The “high-quality Electron Accelerator driven by a Reliable Laser wakefield for Industrial uses” (EARLI) project aims to design a stand-alone high-quality electron injector based on a laser wakefield accelerator (LWFA) as an alternative proposal to AWAKE’s baseline design of an X-band electron gun. This project is currently in the design phase, including simulations and experimental tests. Exhaustive beam physics studies for conventional accelerators are applied to LWFA physics.

Self-modulation is a beam-plasma instability that is useful to drive large-amplitude wakefields with bunches much longer than the plasma skin depth. We present experimental results showing that, when increasing the ratio between the initial transverse size of the bunch and the plasma skin depth, the instability occurs later along the bunch, or not at all, over a fixed plasma length, because the amplitude of the initial wakefields decreases. We show cases for which self-modulation does not develop and we introduce a simple model discussing the conditions for which it would not occur after any plasma length. Changing bunch size and plasma electron density also changes the growth rate of the instability. We discuss the impact of these results on the design of a particle accelerator based on the self-modulation instability seeded by a relativistic ionization front, such as the future upgrade of the AWAKE experiment.

The vertical plane transverse emittance of accelerated electron bunches at the AWAKE experiment at CERN has been determined, using three different methods of data analysis. This is a proof-of-principle measurement using the existing AWAKE electron spectrometer to validate the measurement technique. Large values of the geometric emittance, compared to that of the injection beam, are observed (\\(\\sim \\SI{0.5}{\\milli\\metre\\milli\\radian}\\) compared with \\(\\sim \\SI{0.08}{\\milli\\metre\\milli\\radian}\\)), which is in line with expectations of emittance growth arising from plasma density ramps and large injection beam bunch size. Future iterations of AWAKE are anticipated to operate in conditions where emittance growth is better controlled, and the effects of the imaging systems of the existing and future spectrometer designs on the ability to measure the emittance are discussed. Good performance of the instrument down to geometric emittances of approximately \\(\\SI{1e-4}{\\milli\\metre\\milli\\radian}\\) is required, which may be possible with improved electron optics and imaging.

Purpose Indeterminate cytology still puzzles clinicians, due to its wide range of oncological risks. According to the Italian SIAPEC–IAP classification, TIR3B cytology holds up to 30% of thyroid cancer, which justifies the surgical indication, even if more than half of cases do not result in a positive histology. The study aim is to identify potential clinical, ultrasound or cytological features able to improve the surgical indication. Methods Retrospective analysis. A consecutive series of TIR3B nodules referred to the Endocrine Unit of Careggi Hospital from 1st May 2014 to 31st December 2021 was considered for the exploratory analysis (Phase 1). Thereafter, a smaller confirmatory sample of consecutive TIR3B diagnosed and referred to surgery from 1st January 2022 to 31st June 2022 was considered to verify the algorithm (Phase 2). The main clinical, ultrasound and cytological features have been collected. A comprehensive stepwise logistic regression was applied to build a prediction algorithm. The histological results represented the final outcome. Results Of 599 TIR3B nodules referred to surgery, 451 cases were included in the exploratory analysis. A final score > 14.5 corresponded to an OR = 4.98 (95% CI 3.24–7.65, p  < 0.0001) and showed a PPV and NPV of 57% and 79%, respectively. The Phase 2 analysis on a confirmatory sample of 58 TIR3B cytology confirmed that a threshold of 14.5 points has a comparable PPV and NPV of 53% and 80%, respectively. Conclusions A predictive algorithm which considers the main clinical, US and cytological features can significantly improve the oncological stratification of TIR3B cytology.

A long, narrow, relativistic charged particle bunch propagating in plasma is subject to the self -modulation (SM) instability. We show that SM of a proton bunch can be seeded by the wakefields driven by a preceding electron bunch. SM timing reproducibility and control are at the level of a small fraction of the modulation period. With this seeding method, we independently control the amplitude of the seed wakefields with the charge of the electron bunch and the growth rate of SM with the charge of the proton bunch. Seeding leads to larger growth of the wakefields than in the instability case.

BackgroundMost studies on minimally invasive pancreatoduodenectomy (MIPD) combine patients with pancreatic and periampullary cancers even though there is substantial heterogeneity between these tumors. Therefore, this study aimed to evaluate the role of MIPD compared to open pancreatoduodenectomy (OPD) in patients with non-pancreatic periampullary cancer (NPPC).MethodsA systematic review of Pubmed, Embase, and Cochrane databases was performed by two independent reviewers to identify studies comparing MIPD and OPD for NPPC (ampullary, distal cholangio, and duodenal adenocarcinoma) (01/2015–12/2021). Individual patient data were required from all identified studies. Primary outcomes were (90-day) mortality, and major morbidity (Clavien-Dindo 3a-5). Secondary outcomes were postoperative pancreatic fistula (POPF), delayed gastric emptying (DGE), postpancreatectomy hemorrhage (PPH), blood-loss, length of hospital stay (LOS), and overall survival (OS).ResultsOverall, 16 studies with 1949 patients were included, combining 928 patients with ampullary, 526 with distal cholangio, and 461 with duodenal cancer. In total, 902 (46.3%) patients underwent MIPD, and 1047 (53.7%) patients underwent OPD. The rates of 90-day mortality, major morbidity, POPF, DGE, PPH, blood-loss, and length of hospital stay did not differ between MIPD and OPD. Operation time was 67 min longer in the MIPD group (P = 0.009). A decrease in DFS for ampullary (HR 2.27, P = 0.019) and distal cholangio (HR 1.84, P = 0.025) cancer, as well as a decrease in OS for distal cholangio (HR 1.71, P = 0.045) and duodenal cancer (HR 4.59, P < 0.001) was found in the MIPD group.ConclusionsThis individual patient data meta-analysis of MIPD versus OPD in patients with NPPC suggests that MIPD is not inferior in terms of short-term morbidity and mortality. Several major limitations in long-term data highlight a research gap that should be studied in prospective maintained international registries or randomized studies for ampullary, distal cholangio, and duodenum cancer separately.Protocol registrationPROSPERO (CRD42021277495) on the 25th of October 2021.

The effects of percutaneous transluminal renal angioplasty (PTRA) on the renal function of stenotic kidneys are usually assessed by evaluating the changes in serum creatinine, which is quite a rough indicator of glomerular filtration rate (GFR). In 27 hypertensive patients with 19 atherosclerotic and 11 fibromuscular significant renal artery stenoses, we investigated with renal scintigraphy the short-term (5 days) and long-term (10 months) effects of a technically successful PTRA (in seven cases combined with a stent implantation) on GFR of the stenotic and contralateral kidneys; these measurements were combined with those of plasma renin activity (PRA) and of angiotensin II (AII). We found that in short-term studies after PTRA GFR rose from 29.7 3.5 to 34.6 ± 3.1 mL/min and from 36.9 ± 4.0 to 45.1 ± 4.3 mL/min, respectively, in atherosclerotic and fibromuscular poststenotic kidneys. In long-term studies GFR further and significantly increased, to 37.8 ± 3.2 mL/min in the former group, whereas it stabilized in the latter group (46.0 ± 3.6 mL/min). In patients with fibromuscular stenosis these changes in GFR were associated with clear-cut reductions in blood pressure (BP), PRA, and AII; these decrements also occurred in patients with atherosclerotic stenosis but to a much lesser extent. We also found that in short- and long-term studies the percent of PTRA-induced increments of GFR in the poststenotic kidneys were inversely correlated with the baseline values of GFR. In addition, the absolute and percent increments of GFR were positively correlated with the basal levels of AII. Thus the time course of the improvement in GFR after angioplasty may differ in kidneys, depending on the etiology of the stenosis, in that in those with fibromuscular stenosis it was entirely apparent within a few days whereas in those with atherosclerotic stenosis it required several months to be fully expressed. Also, it appears that the more compromised kidneys are those that benefit most from the dilatation and that AII levels are useful indicators of the possibility that the stenotic kidney will have a favorable functional outcome in terms of restoration of renal blood flow.