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Electron beam quality is paramount for X-ray pulse production in free-electron-lasers (FELs). State-of-the-art linear accelerators (linacs) can deliver multi-GeV electron beams with sufficient quality for hard X-ray-FELs, albeit requiring km-scale setups, whereas plasma-based accelerators can produce multi-GeV electron beams on metre-scale distances, and begin to reach beam qualities sufficient for EUV FELs. Here we show, that electron beams from plasma photocathodes many orders of magnitude brighter than state-of-the-art can be generated in plasma wakefield accelerators (PWFAs), and then extracted, captured, transported and injected into undulators without significant quality loss. These ultrabright, sub-femtosecond electron beams can drive hard X-FELs near the cold beam limit to generate coherent X-ray pulses of attosecond-Angstrom class, reaching saturation after only 10 metres of undulator. This plasma-X-FEL opens pathways for advanced photon science capabilities, such as unperturbed observation of electronic motion inside atoms at their natural time and length scale, and towards higher photon energies., (© 2023. Crown.)

Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome is a congenital condition characterizing females with absence of the uterus and part of the vagina. Several genetic defects have been correlated with the presence of MRKH; however, the exact etiology is still unknown due to the complexity of the genetic pathways implicated during the embryogenetic development of the Müllerian ducts. A systematic review (SR) of the literature was conducted to investigate the genetic causes associated with MRKH syndrome and Congenital Uterine Anomalies (CUAs). This study aimed to identify the most affected chromosomal areas and genes along with their associated clinical features in order to aid clinicians in distinguishing and identifying the possible genetic cause in each patient offering better genetic counseling. We identified 76 studies describing multiple genetic defects potentially contributing to the pathogenetic mechanism of MRKH syndrome. The most reported chromosomal regions and the possible genes implicated were: 1q21.1 ( RBM8A gene), 1p31-1p35 ( WNT4 gene), 7p15.3 ( HOXA gene), 16p11 ( TBX6 gene), 17q12 ( LHX1 and HNF1B genes), 22q11.21, and Xp22. Although the etiology of MRKH syndrome is complex, associated clinical features can aid in the identification of a specific genetic defect.

Sources of high-energy photons have important applications in almost all areas of research. However, the photon flux and intensity of existing sources is strongly limited for photon energies above a few hundred keV. Here we show that a high-current ultrarelativistic electron beam interacting with multiple submicrometer-thick conducting foils can undergo strong self-focusing accompanied by efficient emission of gamma-ray synchrotron photons. Physically, self-focusing and high-energy photon emission originate from the beam interaction with the near-field transition radiation accompanying the beam-foil collision. This near field radiation is of amplitude comparable with the beam self-field, and can be strong enough that a single emitted photon can carry away a significant fraction of the emitting electron energy. After beam collision with multiple foils, femtosecond collimated electron and photon beams with number density exceeding that of a solid are obtained. The relative simplicity, unique properties, and high efficiency of this gamma-ray source open up new opportunities for both applied and fundamental research including laserless investigations of strong-field QED processes with a single electron beam.

Metre-scale plasma wakefield accelerators have imparted energy gain approaching 10 gigaelectronvolts to single nano-Coulomb electron bunches. To reach useful average currents, however, the enormous energy density that the driver deposits into the wake must be removed efficiently between shots. Yet mechanisms by which wakes dissipate their energy into surrounding plasma remain poorly understood. Here, we report picosecond-time-resolved, grazing-angle optical shadowgraphic measurements and large-scale particle-in-cell simulations of ion channels emerging from broken wakes that electron bunches from the SLAC linac generate in tenuous lithium plasma. Measurements show the channel boundary expands radially at 1 million metres-per-second for over a nanosecond. Simulations show that ions and electrons that the original wake propels outward, carrying 90 percent of its energy, drive this expansion by impact-ionizing surrounding neutral lithium. The results provide a basis for understanding global thermodynamics of multi-GeV plasma accelerators, which underlie their viability for applications demanding high average beam current.

Beam-driven plasma wakefield acceleration (PWFA) has demonstrated significant progress during the past two decades of research. The new Facility for Advanced Accelerator Experimental Tests (FACET) II, currently under construction, will provide 10 GeV electron beams with unprecedented parameters for the next generation of PWFA experiments. In the context of the FACET II facility, we present simulation results on expected betatron radiation and its potential application to diagnose emittance preservation and hosing instability in the upcoming PWFA experiments. This article is part of the Theo Murphy meeting issue 'Directions in particle beam-driven plasma wakefield acceleration'.

This paper discusses the properties of electron beams formed in plasma wakefield accelerators through ionization injection. In particular, the potential for generating a beam composed of co-located multi-colour beamlets is demonstrated in the case where the ionization is initiated by the evolving charge field of the drive beam itself. The physics of the processes of ionization and injection are explored through OSIRIS simulations. Experimental evidence showing similar features are presented from the data obtained in the E217 experiment at the FACET facility of the SLAC National Laboratory. This article is part of the Theo Murphy meeting issue 'Directions in particle beam-driven plasma wakefield acceleration'.

Hollow channel plasma wakefield acceleration is a proposed method to provide high acceleration gradients for electrons and positrons alike: a key to future lepton colliders. However, beams which are misaligned from the channel axis induce strong transverse wakefields, deflecting beams and reducing the collider luminosity. This undesirable consequence sets a tight constraint on the alignment accuracy of the beam propagating through the channel. Direct measurements of beam misalignment-induced transverse wakefields are therefore essential for designing mitigation strategies. We present the first quantitative measurements of transverse wakefields in a hollow plasma channel, induced by an off-axis 20 GeV positron bunch, and measured with another 20 GeV lower charge trailing positron probe bunch. The measurements are largely consistent with theory.

The preservation of emittance of the accelerating beam is the next challenge for plasma-based accelerators envisioned for future light sources and colliders. The field structure of a highly nonlinear plasma wake is potentially suitable for this purpose but has not been yet measured. Here we show that the longitudinal variation of the fields in a nonlinear plasma wakefield accelerator cavity produced by a relativistic electron bunch can be mapped using the bunch itself as a probe. We find that, for much of the cavity that is devoid of plasma electrons, the transverse force is constant longitudinally to within ±3% (r.m.s.). Moreover, comparison of experimental data and simulations has resulted in mapping of the longitudinal electric field of the unloaded wake up to 83 GV m(-1) to a similar degree of accuracy. These results bode well for high-gradient, high-efficiency acceleration of electron bunches while preserving their emittance in such a cavity.

Plasma accelerators driven by particle beams are a very promising future accelerator technology as they can sustain high accelerating fields over long distances with high energy efficiency. They rely on the excitation of a plasma wave in the wake of a drive beam. To generate the plasma, a neutral gas can be field-ionized by the head of the drive beam, in which case the distance of acceleration and energy gain can be strongly limited by head erosion. Here we overcome this limit and demonstrate that electrons in the tail of a drive beam can be accelerated by up to 27 GeV in a high-ionization-potential gas (argon), boosting their initial 20.35 GeV energy by 130%. Particle-in-cell simulations show that the argon plasma is sustaining very high electric fields, of ∼150 GV m(-1), over ∼20 cm. The results open new possibilities for the design of particle beam drivers and plasma sources.

Plasma wakefield accelerators have been used to accelerate electron and positron particle beams with gradients that are orders of magnitude larger than those achieved in conventional accelerators. In addition to being accelerated by the plasma wakefield, the beam particles also experience strong transverse forces that may disrupt the beam quality. Hollow plasma channels have been proposed as a technique for generating accelerating fields without transverse forces. Here we demonstrate a method for creating an extended hollow plasma channel and measure the wakefields created by an ultrarelativistic positron beam as it propagates through the channel. The plasma channel is created by directing a high-intensity laser pulse with a spatially modulated profile into lithium vapour, which results in an annular region of ionization. A peak decelerating field of 230 MeV m(-1) is inferred from changes in the beam energy spectrum, in good agreement with theory and particle-in-cell simulations.

Electrical breakdown sets a limit on the kinetic energy that particles in a conventional radio-frequency accelerator can reach. New accelerator concepts must be developed to achieve higher energies and to make future particle colliders more compact and affordable. The plasma wakefield accelerator (PWFA) embodies one such concept, in which the electric field of a plasma wake excited by a bunch of charged particles (such as electrons) is used to accelerate a trailing bunch of particles. To apply plasma acceleration to electron-positron colliders, it is imperative that both the electrons and their antimatter counterpart, the positrons, are efficiently accelerated at high fields using plasmas. Although substantial progress has recently been reported on high-field, high-efficiency acceleration of electrons in a PWFA powered by an electron bunch, such an electron-driven wake is unsuitable for the acceleration and focusing of a positron bunch. Here we demonstrate a new regime of PWFAs where particles in the front of a single positron bunch transfer their energy to a substantial number of those in the rear of the same bunch by exciting a wakefield in the plasma. In the process, the accelerating field is altered--'self-loaded'--so that about a billion positrons gain five gigaelectronvolts of energy with a narrow energy spread over a distance of just 1.3 metres. They extract about 30 per cent of the wake's energy and form a spectrally distinct bunch with a root-mean-square energy spread as low as 1.8 per cent. This ability to transfer energy efficiently from the front to the rear within a single positron bunch makes the PWFA scheme very attractive as an energy booster to an electron-positron collider.

High-efficiency acceleration of charged particle beams at high gradients of energy gain per unit length is necessary to achieve an affordable and compact high-energy collider. The plasma wakefield accelerator is one concept being developed for this purpose. In plasma wakefield acceleration, a charge-density wake with high accelerating fields is driven by the passage of an ultra-relativistic bunch of charged particles (the drive bunch) through a plasma. If a second bunch of relativistic electrons (the trailing bunch) with sufficient charge follows in the wake of the drive bunch at an appropriate distance, it can be efficiently accelerated to high energy. Previous experiments using just a single 42-gigaelectronvolt drive bunch have accelerated electrons with a continuous energy spectrum and a maximum energy of up to 85 gigaelectronvolts from the tail of the same bunch in less than a metre of plasma. However, the total charge of these accelerated electrons was insufficient to extract a substantial amount of energy from the wake. Here we report high-efficiency acceleration of a discrete trailing bunch of electrons that contains sufficient charge to extract a substantial amount of energy from the high-gradient, nonlinear plasma wakefield accelerator. Specifically, we show the acceleration of about 74 picocoulombs of charge contained in the core of the trailing bunch in an accelerating gradient of about 4.4 gigavolts per metre. These core particles gain about 1.6 gigaelectronvolts of energy per particle, with a final energy spread as low as 0.7 per cent (2.0 per cent on average), and an energy-transfer efficiency from the wake to the bunch that can exceed 30 per cent (17.7 per cent on average). This acceleration of a distinct bunch of electrons containing a substantial charge and having a small energy spread with both a high accelerating gradient and a high energy-transfer efficiency represents a milestone in the development of plasma wakefield acceleration into a compact and affordable accelerator technology.

We present the results of searches for nucleon decay via n→ν[over ¯]π0 and p→ν[over ¯]π+ using data from a combined 172.8  kt·yr exposure of Super-Kamiokande-I,-II, and-III. We set lower limits on the partial lifetime for each of these modes: τn→ν[over ¯]π0>1.1×10(33) years and τp→ν[over ¯]π+>3.9×10(32) years at a 90% confidence level.

A search for the dinucleon decay pp → K+ K+ has been performed using 91.6  kton·yr data from Super-Kamiokande-I. This decay provides a sensitive probe of the R-parity-violating parameter λ112''. A boosted decision tree analysis found no signal candidates in the data. The expected background was 0.28±0.19 atmospheric neutrino induced events and the estimated signal detection efficiency was 12.6%±3.2%. A lower limit of 1.7×10(32)  years has been placed on the partial lifetime of the decay O16 → C14K+ K+ at 90% C.L. A corresponding upper limit of 7.8×10(-9) has been placed on the parameter λ112''.

We show through experiments and supporting simulations that propagation of a highly relativistic and dense electron bunch through a plasma can lead to distributed injection of electrons, which depletes the accelerating field, i.e., beam loads the wake. The source of the injected electrons is ionization of the second electron of rubidium (Rb II) within the wake. This injection of excess charge is large enough to severely beam load the wake, and thereby reduce the transformer ratio T. The reduction of the average T with increasing beam loading is quantified for the first time by measuring the ratio of peak energy gain and loss of electrons while changing the beam emittance. Simulations show that beam loading by Rb II electrons contributes to the reduction of the peak accelerating field from its weakly loaded value of 43  GV/m to a strongly loaded value of 26  GV/m.

Super-Kamiokande atmospheric neutrino data were fit with an unbinned maximum likelihood method to search for the appearance of tau leptons resulting from the interactions of oscillation-generated tau neutrinos in the detector. Relative to the expectation of unity, the tau normalization is found to be 1.42 ± 0.35(stat)(-0.12)(+0.14)(syst) excluding the no-tau-appearance hypothesis, for which the normalization would be zero, at the 3.8σ level. We estimate that 180.1 ± 44.3(stat)(-15.2)(+17.8) (syst) tau leptons were produced in the 22.5 kton fiducial volume of the detector by tau neutrinos during the 2806 day running period. In future analyses, this large sample of selected tau events will allow the study of charged current tau neutrino interaction physics with oscillation produced tau neutrinos.

We present a search for differences in the oscillations of antineutrinos and neutrinos in the Super-Kamiokande-I, -II, and -III atmospheric neutrino sample. Under a two-flavor disappearance model with separate mixing parameters between neutrinos and antineutrinos, we find no evidence for a difference in oscillation parameters. Best-fit antineutrino mixing is found to be at (Δm2,sin2 2θ)=(2.0×10(-3)  eV2, 1.0) and is consistent with the overall Super-K measurement.

The T2K experiment observes indications of ν(μ) → ν(e) appearance in data accumulated with 1.43×10(20) protons on target. Six events pass all selection criteria at the far detector. In a three-flavor neutrino oscillation scenario with |Δm(23)(2)| = 2.4×10(-3)  eV(2), sin(2)2θ(23) = 1 and sin(2)2θ(13) = 0, the expected number of such events is 1.5±0.3(syst). Under this hypothesis, the probability to observe six or more candidate events is 7×10(-3), equivalent to 2.5σ significance. At 90% C.L., the data are consistent with 0.03(0.04) < sin(2)2θ(13) < 0.28(0.34) for δ(CP) = 0 and a normal (inverted) hierarchy.

We have searched for proton decays via p-->e;{+}pi;{0} and p-->micro;{+}pi;{0} using data from a 91.7 kt.yr exposure of Super-Kamiokande-I and a 49.2 kt.yr exposure of Super-Kamiokande-II. No candidate events were observed with expected backgrounds induced by atmospheric neutrinos of 0.3 events for each decay mode. From these results, we set lower limits on the partial lifetime of 8.2 x 10;{33} and 6.6 x 10;{33} years at 90% confidence level for p-->e;{+}pi;{0} and p-->micro;{+}pi;{0} modes, respectively.

Recent evidence implicates the immune system and the clotting mechanisms in the pathophysiology of sickle cell disease (SCD). This study investigates the association of steady state platelet count with the severity of SCD in pregnancy. A total of 40 SCD women who were asymptomatic early in pregnancy were studied retrospectively: 14 remained asymptomatic throughout pregnancy and 26 developed at least one SCD-related complication. The early pregnancy platelet count was compared between the two groups using t-test and its ability to predict SCD-related complications in pregnancy was investigated using Receiver-Operator Characteristics (ROC) curve. Compared with asymptomatic patients, women who developed SCD-related complications had significantly higher early-pregnancy platelet count [328x10(9)/l (95% CI: 268-389) vs 210x10(9)/l (146-275), p < 0.01]. The area under the ROC curve was 76.4% (95% CI 59.7-93.2). These indicate that the platelet count in early pregnancy is significantly higher in SCD patients who subsequently develop SCD-related complications and may be used for screening.

Objective: Increasing epidemiological evidence implicates leukocytosis as a major risk factor for poor outcome in non-pregnant sickle cell disease (SCD) patients. The aim of this study was to investigate whether steady-state white blood cell (WBC) count can predict SCD-related problems in pregnancy., Design: Retrospective observational study of 40 SCD pregnant women who had their antenatal care at Guy's & St Thomas' NHS Trust, London. Twenty-six women developed clinical complications related to SCD during their pregnancy (painful crisis, chest symptoms, infections, severe anaemia requiring blood transfusion, pre-eclampsia, and/or thromboembolism) and 14 remained asymptomatic. The steady-state leukocyte counts early in pregnancy were compared between the two groups and receiver operator characteristics (ROC) curve was plotted for different values of WBC., Results: Compared to asymptomatic patients, women who developed SCD-related complications had significantly higher total WBC count [11.2 x 10(9)L(-1) (SD 3.22) versus 8 x 10(9)L(-1) (2.8), p<0.01], higher lymphocyte count [3 x 10(9)L(-1) (1.62) versus 1.6 x 10(9)L(-1) (0.65), p<0.01] and higher monocyte count [0.8 x 10(9)L(-1) (0.47) versus 0.4 x 10(9)L(-1) (0.21), p<0.01]. The neutrophil count showed a similar trend but the difference did not reach statistical significance [6.6 x 10(9)L(-1) (2.29) versus 5.7 x 10(9)L(-1) (2.15), p=0.22]. The area under the ROC curve was 74% (95% CI: 56-92)., Conclusion: WBC count early in pregnancy was significantly higher in women who subsequently developed clinical problems related to SCD. The WBC may be used as a predictor of the severity of SCD in pregnancy.

A search for the appearance of tau neutrinos from nu(mu) <--> nu(tau) oscillations in the atmospheric neutrinos has been performed using 1489.2 days of atmospheric neutrino data from the Super-Kamiokande-I experiment. A best fit tau neutrino appearance signal of 138+/-48(stat)-32(+15)(syst) events is obtained with an expectation of 78+/-26(syst). The hypothesis of no tau neutrino appearance is disfavored by 2.4 sigma.

Background: The serum CA 125 marker is elevated in 80% of patients with ovarian adenocarcinoma. MDR 1 gene expression has been identified in a variety of tumor types and its expression has been correlated with multidrug resistance. Whether there is a correlation between CA 125 levels and MDR 1 expression has not been sufficiently investigated. Therefore, the aim of this study was to examine whether an association between serum CA 125 levels and MDR 1 expression exists., Patients and Methods: Serum CA 125 levels were measured during the diagnosis of ovarian cancer. Fresh tumor specimens or ascitic fluid samples were studied for MDR 1 expression by the polymerase chain reaction method (PCR)., Results: Forty patients with ovarian cancer were studied, 34 (85%) of whom had elevated CA 125. Twenty-eight out of the 40 patients were tested for MDR 1 expression; 20 expressed the gene and 8 did not. The median level of CA 125 in specimens expressing the MDR1 gene was 327, and in specimens that did not it was 376. There was no correlation between the CA 125 levels and MDR 1 expression (p = 0.484)., Conclusion: There does not seem to be an association between CA 125 levels and expression of the MDR1 gene in patients with ovarian cancer.

Histamine receptors of the H2 type are found on mature hemopoetic cells such as lymphocytes and monocytes. Since little is known about histamine receptors on immature cells, we studied histamine-induced cAMP synthesis in leukemic cells of 51 patients using 73 samples of peripheral blood and/or bone marrow. Histamine-induced cAMP synthesis was found in all cALL (FAB L1, L2), but only occasionally in AML. In 1 out of 11 myelomonocytic leukemias (M4), and also in 2 out of 5 monocytic leukemias (FAB M5), histamine-inducible cAMP synthesis was found, but no induction of cAMP synthesis by histamine was found in 19 cases from the remaining subgroups (FAB M1-M3, M6). The inhibiting action of H2 antagonists on cAMP synthesis indicates that the receptor is of the H2 type. Since H2 receptors were found in all cALL blasts, we assume a compulsory expression of this receptor on immature cells of the B-lymphocytic lineage.