Acceleration of electrons in the plasma wakefield of a proton bunch.

High-energy particle accelerators have been crucial in providing a deeper understanding of fundamental particles and the forces that govern their interactions. To increase the energy of the particles or to reduce the size of the accelerator, new acceleration schemes need to be developed. Plasma wakefield acceleration1-5, in which the electrons in a plasma are excited, leading to strong electric fields (so called 'wakefields'), is one such promising acceleration technique. Experiments have shown that an intense laser pulse6-9 or electron bunch10,11 traversing a plasma can drive electric fields of tens of gigavolts per metre and above-well beyond those achieved in conventional radio-frequency accelerators (about 0.1 gigavolt per metre). However, the low stored energy of laser pulses and electron bunches means that multiple acceleration stages are needed to reach very high particle energies5,12. The use of proton bunches is compelling because they have the potential to drive wakefields and to accelerate electrons to high energy in a single acceleration stage13. Long, thin proton bunches can be used because they undergo a process called self-modulation14-16, a particle-plasma interaction that splits the bunch longitudinally into a series of high-density microbunches, which then act resonantly to create large wakefields. The Advanced Wakefield (AWAKE) experiment at CERN17-19 uses high-intensity proton bunches-in which each proton has an energy of 400 gigaelectronvolts, resulting in a total bunch energy of 19 kilojoules-to drive a wakefield in a ten-metre-long plasma. Electron bunches are then injected into this wakefield. Here we present measurements of electrons accelerated up to two gigaelectronvolts at the AWAKE experiment, in a demonstration of proton-driven plasma wakefield acceleration. Measurements were conducted under various plasma conditions and the acceleration was found to be consistent and reliable. The potential for this scheme to produce very high-energy electron bunches in a single accelerating stage20 means that our results are an important step towards the development of future high-energy particle accelerators21,22.

Experimental Observation of Proton Bunch Modulation in a Plasma at Varying Plasma Densities.

We give direct experimental evidence for the observation of the full transverse self-modulation of a long, relativistic proton bunch propagating through a dense plasma. The bunch exits the plasma with a periodic density modulation resulting from radial wakefield effects. We show that the modulation is seeded by a relativistic ionization front created using an intense laser pulse copropagating with the proton bunch. The modulation extends over the length of the proton bunch following the seed point. By varying the plasma density over one order of magnitude, we show that the modulation frequency scales with the expected dependence on the plasma density, i.e., it is equal to the plasma frequency, as expected from theory.

Experimental Observation of Plasma Wakefield Growth Driven by the Seeded Self-Modulation of a Proton Bunch.

We measure the effects of transverse wakefields driven by a relativistic proton bunch in plasma with densities of 2.1×10^{14} and 7.7×10^{14} electrons/cm^{3}. We show that these wakefields periodically defocus the proton bunch itself, consistently with the development of the seeded self-modulation process. We show that the defocusing increases both along the bunch and along the plasma by using time resolved and time-integrated measurements of the proton bunch transverse distribution. We evaluate the transverse wakefield amplitudes and show that they exceed their seed value (<15 MV/m) and reach over 300 MV/m. All these results confirm the development of the seeded self-modulation process, a necessary condition for external injection of low energy and acceleration of electrons to multi-GeV energy levels.

Proton-driven plasma wakefield acceleration in AWAKE.

In this article, we briefly summarize the experiments performed during the first run of the Advanced Wakefield Experiment, AWAKE, at CERN (European Organization for Nuclear Research). The final goal of AWAKE Run 1 (2013-2018) was to demonstrate that 10-20 MeV electrons can be accelerated to GeV energies in a plasma wakefield driven by a highly relativistic self-modulated proton bunch. We describe the experiment, outline the measurement concept and present first results. Last, we outline our plans for the future. This article is part of the Theo Murphy meeting issue 'Directions in particle beam-driven plasma wakefield acceleration'.

The influence of precompression on elasticity of thyroid nodules estimated by ultrasound shear wave elastography.

OBJECTIVES: To investigate the influence of variations in resting pressure (precompression) on thyroid ultrasound supersonic shear wave elastography (SWE). METHODS: Thirty-five normal thyroid glands (Norm), 55 benign hyperplastic nodules (BHN), and 17 papillary thyroid cancers (PTC) in 96 subjects underwent thyroid SWE. Four precompression levels were applied manually by the operator, ranging from A (baseline, 0 % strain) to D (high, 22-30 % strain). SWE results at each precompression level were compared using ANOVA tests with P < 0.05 indicating significance. RESULTS: SWE indices were highest in PTC, followed by BHN and Norm at each precompression level (P < 0.05). All tissue types showed successive increases in SWE results as precompression increased, although the rate was higher for PTC than BHN and Norm (Ps < 0.05). SWE values (kPa) of Norm, BHN, and PTC at baseline precompression (A) were 10.3 ± 3.3, 17.7 ± 7.6, and 22.2 ± 11.9 compared with 21.1 ± 4.2, 42.3 ± 16.0, and 97.6 ± 46.8 at high precompression (D). SWE index differences between precompression levels A and D were 10.8 kPa for Norm, 24.6 kPa for BHN, and 75.4 kPa for PTC. CONCLUSION: PTCs show greater SWE stiffening than BHN as precompression rises. Precompression effects on thyroid nodules are not negligible and may account for wide discrepancies in published SWE discriminatory performance results for thyroid malignancy. KEY POINTS: • Increases in resting pressure (precompression) applied by the operator increases thyroid stiffness. • Papillary cancers show greater increases in stiffness (strain hardening) than benign nodules. • Precompression may affect the diagnostic performance of shearwave elastography for thyroid malignancy.

A Comparison of the Diagnostic Accuracy and Reliability of Subjective Grading and Computer-Aided Assessment of Intranodal Vascularity in Differentiating Metastatic and Reactive Cervical Lymphadenopathy.

PURPOSE: Ultrasound is a well-established imaging modality in the assessment of malignant cervical lymphadenopathy. With the use of Doppler ultrasound, intranodal vascularity can be evaluated. However, the major limitation of ultrasound is operator dependency. Therefore, this study aimed to evaluate and compare the diagnostic accuracy and reliability of the subjective grading and computer-aided approach in assessing intranodal vascularity for the differentiation of benign and malignant lymph nodes. MATERIALS AND METHODS: The present study retrospectively assessed 99 power Doppler ultrasound images of cervical lymph nodes and evaluated the degree of intranodal vascularity using qualitative subjective grading (QSG) and quantitative computer-aided (QCA) methods. The diagnostic accuracy of the two methods in distinguishing metastatic and reactive nodes and their inter- and intra-rater reliability in assessing intranodal vascularity were evaluated and compared. RESULTS: The results showed that the QCA method was more accurate than the QSG method with a significantly higher sensitivity (67.8 % and 61.9 %, respectively, p < 0.05) and specificity (73.3 % and 57.3 %, respectively, p < 0.05). Using the intranodal vascularity index as determined by the QCA approach, the optimum cut-off to differentiate metastatic and reactive cervical lymph nodes was 32 %. The QCA method showed higher inter- and intra-rater reliability than the QSG method. CONCLUSION: In the assessment of the degree of intranodal vascularity, the QCA method was more accurate and reliable than the QSG method in distinguishing metastatic and reactive lymph nodes.

Molecular Characterization and Computational Modelling of New Delhi Metallo-ß-Lactamase-5 from an Escherichia coli Isolate (KOEC3) of Bovine Origin.

Emergence of antimicrobial resistance mediated through New Delhi metallo-ß-lactamases (NDMs) is a serious therapeutic challenge. Till date, 16 different NDMs have been described. In this study, we report the molecular and structural characteristics of NDM-5 isolated from an Escherichia coli isolate (KOEC3) of bovine origin. Using PCR amplification, cloning and sequencing of full blaNDM gene, we identified the NDM type as NDM-5. Cloning of full gene in E. coli DH5α and subsequent assessment of antibiotic susceptibility of the transformed cells indicated possible role of native promoter in expression blaNDM-5. Translated amino acid sequence had two substitutions (Val88Leu and Met154Leu) compared to NDM-1. Theoretically deduced isoelectric pH of NDM-5 was 5.88 and instability index was 36.99, indicating a stable protein. From the amino acids sequence, a 3D model of the protein was computed. Analysis of the protein structure elucidated zinc coordination and also revealed a large binding cleft and flexible nature of the protein, which might be the reason for broad substrate range. Docking experiments revealed plausible binding poses for five carbapenem drugs in the vicinity of metal ions. In conclusion, results provided possible explanation for wide range of antibiotics catalyzed by NDM-5 and likely interaction modes with five carbapenem drugs.

Shear Wave Elastography--A New Quantitative Assessment of Post-Irradiation Neck Fibrosis.

PURPOSE: Shear wave elastography (SWE) is a new technique which provides quantitative assessment of soft tissue stiffness. The aim of this study was to assess the reliability of SWE stiffness measurements and its usefulness in evaluating post-irradiation neck fibrosis. MATERIALS AND METHODS: 50 subjects (25 patients with previous radiotherapy to the neck and 25 sex and age-matched controls) were recruited for comparison of SWE stiffness measurements (Aixplorer, Supersonic Imagine). 30 subjects (16 healthy individuals and 14 post-irradiated patients) were recruited for a reliability study of SWE stiffness measurements. SWE stiffness measurements of the sternocleidomastoid muscle and the overlying subcutaneous tissues of the neck were made. The cross-sectional area and thickness of the sternocleidomastoid muscle and the overlying subcutaneous tissue thickness of the neck were also measured. The post-irradiation duration of the patients was recorded. RESULTS: The intraclass correlation coefficients for the intraoperator and interoperator reliability of deep and subcutaneous tissue SWE stiffness ranged from 0.90-0.99 and 0.77-0.94, respectively. The SWE stiffness measurements (mean +/- SD) of deep and subcutaneous tissues were significantly higher in the post-irradiated patients (64.6 ± 46.8 kPa and 63.9 ± 53.1 kPa, respectively) than the sex and age-matched controls (19.9 ± 7.8 kPa and 15.3 ± 8.37 respectively) (p < 0.001). The SWE stiffness increased with increasing post-irradiation therapy duration in the Kruskal Wallis test (p < 0.001) and correlated with muscle atrophy and subcutaneous tissue thinning (p < 0.01). CONCLUSION: SWE is a reliable technique and may potentially be an objective and specific tool in quantifying deep and subcutaneous tissue stiffness, which in turn reflects the severity of neck fibrosis.

Dissipation pattern and risk assessment of flubendiamide on chili at different agro-climatic conditions in India.

Dissipation pattern and risk assessment of flubendiamide and its metabolite (desiodo flubendiamide) on chili were studied at four different agro-climatic locations of India at the standard and double dose at 60 and 120 g a.i. ha(-1) at 10 days interval. Quantification of residues was done on a high-performance liquid chromatograph (HPLC) with a photo diode array detector. The limit of quantification (LOQ) of this method was found to be 0.01 mg kg(-1) while limit of detection (LOD) being 0.003 mg kg(-1). Residues of flubendiamide were found to be below the determination limit in 15 days at both the dosages in all locations. Half-life of flubendiamide when applied at 60 and 120 g a.i. ha(-1) ranged from 0.85 to 1.80 and from 0.95 to 2.79 days, respectively. On the basis of data generated under the All India Network Project on Pesticide Residues, a preharvest interval (PHI) of 1 day has been recommended and the flubendiamide 480 SC has been registered for use on chili in India by the Central Insecticide Board and Registration Committee, Ministry of Agriculture, Government of India. The maximum residue limit (MRL) of flubendiamide on chili has been fixed by the Food Safety Standard Authority of India, Ministry of Health and Family Welfare, Government of India, as 0.02 µg g(-1) after its risk assessment.

Residual behavior and risk assessment of flubendiamide on tomato at different agro-climatic conditions in India.

Supervised field trials were conducted at four different agro-climatic zones in India to evaluate the dissipation pattern and risk assessment of flubendiamide on tomato. Flubendiamide 480 SC was sprayed on tomato at 48 and 96 g active ingredient (a.i.) ha(-1). Samples of tomato fruits were drawn at 0, 1, 3, 5, 7, 10, 15, and 20 days after treatment. Quantification of residues was done on a high-performance liquid chromatography (HPLC) device with a photo diode array detector. The limit of quantification (LOQ) of this method was found to be 0.01 mg kg(-1) while limit of detection (LOD) being 0.003 mg kg(-1). Residues of flubendiamide were found below the determination limit of 0.01 mg kg(-1) in 20 days at both the dosages in all the locations. The half-life of flubendiamide at an application rate of 48 g a.i. ha(-1) varied from 0.33 to 3.28 days and at 48-g a.i. ranged from 1.21 to 3.00 days. On the basis of data generated under the All India Network Project on Pesticide Residues, a preharvest interval (PHI) of 1 day has been recommended, and the flubendiamide 480 SC has been registered for its use on tomato by the Central Insecticide Board and Registration Committee, Ministry of Agriculture, Government of India. The maximum residue limit (MRL) of flubendiamide on tomato has been fixed by the Ministry of Health and Family Welfare, Government of India under Food Safety Standard Authority of India, as 0.07 µg g(-1) after its risk assessment.

Safety evaluation of flubendiamide and its metabolites on cabbage and persistence in soil in different agroclimatic zones of India.

Supervised field trials following good agricultural practices were conducted at the research farms of four agricultural universities located at four different agroclimatic zones of India to evaluate the persistence and dissipation of flubendiamide and its metabolite, des-iodo flubendiamide, on cabbage. Two spray applications of flubendiamide 480 SC of standard and double dose at the rate of 24 and 48 g a.i. ha(-1) were given to the crop at a 15-day interval, and the residues of flubendiamide 2 h after spray were found in the range of 0.107-0.33 and 0.20-0.49 mg kg(-1) at respective doses. Residue of des-iodo flubendiamide was not detected in any cabbage sample during study period. No residues were found in the soil samples collected from all treated fields after 15 days of application. On the basis of data generated under All India Network Project on Pesticide Residues, a preharvest interval (PHI) of 10 days has been recommended, and the flubendiamide 480 SC has been registered for its use on cabbage by Central Insecticide Board and Registration Committee, Ministry of Agriculture, Government of India. The maximum residue limit (MRL) of flubendiamide on cabbage has been fixed by the Ministry of Health and Family Welfare, Government of India, under Food Safety Standard Authority of India as 0.05 µg/g after its risk assessment.

Health care providers' and parents' attitudes toward administration of new infant vaccines--a multinational survey.

The New Vaccinations of Infants in Practice online survey in seven countries evaluated vaccination-related attitudes and concerns of parents of infants and health care providers (HCPs) who provide pediatric medical care. The survey showed that HCPs and parents were open to adding new vaccines to the immunization schedule, even if it requires co-administration with current vaccines or introduction of new office visits. Parental disease awareness campaigns would be helpful to achieve widespread acceptance of changes to vaccination schedules. In addition, HCPs would ideally provide disease education to parents to accompany recommendations for a new vaccine.

White matter hyperintensities and quality of life in acute lacunar stroke.

White matter hyperintensities (WMH) are common in stroke. The influence of WMH on health-related quality of life (HRQoL) following a lacunar stroke is unknown. This study evaluated the impact of WMH on HRQoL in acute lacunar stroke. A cohort of 160 patients with acute lacunar stroke admitted to the stroke unit of a university-affiliated regional hospital in Hong Kong was recruited. Three months after the index stroke, a research assistant administered the Short Form-36 (SF-36) to assess HRQoL. The severity of WMH was evaluated with magnetic resonance imaging (MRI). In univariate analysis, the severity of deep WMH (DWMH) negatively correlated with patients' vitality (VT; p < 0.05), social function (SF; p < 0.001), role-emotional (RE; p < 0.01), mental health (MH; p < 0.01), and mental component summary (MCS; p < 0.001) scores of HRQoL. DWMH was independently associated with all of the above five SF-36 scores (p < 0.05) in linear regression analysis. These findings suggest that DWMH has a significant impact on the HRQoL of stroke survivors. The importance of DWMH in the long-term HRQoL in lacunar stroke warrants further investigation.

Unusual parotid gland lesions: a pictorial review.

This is a pictorial essay of unusual parotid gland lesions that may be encountered in routine clinical practice.

A phase II study of concurrent cetuximab-cisplatin and intensity-modulated radiotherapy in locoregionally advanced nasopharyngeal carcinoma.

BACKGROUND: Based on our previous work on the clinical activity of cetuximab in recurrent nasopharyngeal carcinoma (NPC), we evaluated the feasibility of adding cetuximab to concurrent cisplatin and intensity-modulated radiotherapy (IMRT) in locoregionally advanced NPC. PATIENTS AND METHODS: Patients with American Joint Committee on Cancer stage III-IVB NPC were given an initial dose of cetuximab (400 mg/m(2)) 7-10 days before receiving concurrent IMRT, weekly cisplatin (30 mg/m(2)/week) and cetuximab (250 mg/m(2)/week). RESULTS: Thirty patients (median age of 45 years) with stage III (67%), IVA (30%) and IVB (3%) nonkeratinizing NPC were enrolled. Grade 3-4 oropharyngeal mucositis occurred in 26 (87%) patients and 10 (33%) patients required short-term nasogastric feeding. Grade 3 radiotherapy-related dermatitis occurred in six patients (20%) and three patients (10%) had grade 3 cetuximab-related acneiform rash. These grade 3-4 skin and mucosal toxic effects were manageable and reversible. At a median follow-up of 31.8 months [95% confidence interval (CI) 26.2-32.1 months], the 2-year progression-free survival was 86.5% (95% CI 74.3% to 98.8%). CONCLUSIONS: Concurrent administration of cetuximab, weekly cisplatin and IMRT is a feasible strategy against locoregionally advanced NPC. Preliminary survival data compare favorably with historic data and further follow-up is warranted.

Use of end-cutting needles in ultrasound-guided biopsy of neck lesions.

UNLABELLED: The management of a neck mass is dictated by its nature, location and extent. Pathological diagnosis by fine needle aspiration cytology (FNAC) or core biopsy is often required before proceeding to definitive treatment. It is not uncommon for the cytology result to come back as inadequate for various reasons. The unique design of the end-cutting biopsy needle in our experience makes it a good choice for use in obtaining both transcutaneous and intraoral biopsy under ultrasound guidance of neck lesions and serves as a useful alternative or adjunct to FNAC. Although there is, as yet, only a limited evidence base about end-cutting in comparison to side-cutting needles, they carry several potential advantages. KEY POINTS: End-cutting needles are safe to use for lesions close to vital structures. End-cutting needles yield sufficient tissue samples in a single pass. End-cutting biopsy needles are a useful adjunct to FNAC.