Narrow bandwidth, low-emittance positron beams from a laser-wakefield accelerator.

The rapid progress that plasma wakefield accelerators are experiencing is now posing the question as to whether they could be included in the design of the next generation of high-energy electron-positron colliders. However, the typical structure of the accelerating wakefields presents challenging complications for positron acceleration. Despite seminal proof-of-principle experiments and theoretical proposals, experimental research in plasma-based acceleration of positrons is currently limited by the scarcity of positron beams suitable to seed a plasma accelerator. Here, we report on the first experimental demonstration of a laser-driven source of ultra-relativistic positrons with sufficient spectral and spatial quality to be injected in a plasma accelerator. Our results indicate, in agreement with numerical simulations, selection and transport of positron beamlets containing N e + ≥ 10 5 positrons in a 5% bandwidth around 600 MeV, with femtosecond-scale duration and micron-scale normalised emittance. Particle-in-cell simulations show that positron beams of this kind can be guided and accelerated in a laser-driven plasma accelerator, with favourable scalings to further increase overall charge and energy using PW-scale lasers. The results presented here demonstrate the possibility of performing experimental studies of positron acceleration in a laser-driven wakefield accelerator.

Knowledge, Attitudes, and Practices in Antibiotic Dispensing amongst Pharmacists in Trinidad and Tobago: Exploring a Novel Dichotomy of Antibiotic Laws.

The inappropriate consumption, use, and dispensing of antibiotics are problems faced globally, with a pattern of inappropriate consumption differing in higher-income countries due to the ease of accessibility of antibiotics. The main drivers of consumption and inappropriate use are the over-the-counter sales of antibiotics by pharmacies. Trinidad and Tobago (T&T), a twin island state in the Caribbean, has two Acts of Parliament that regulate antibiotics: the Antibiotics Act and the Food and Drug Act, yet the Over-the-Counter (OTC) sale of antibiotics still exists. This study sought to determine the knowledge, attitudes, and practices regarding the OTC dispensing of antibiotics in T&T. A cross-sectional study gathered data from pharmacists in both the private and public sectors of Trinidad over 7 months. The results showed that antibiotic resistance and antibiotic abuse were seen as significant problems. The level of experience, gender (female), and age (younger) were significantly associated with having good overall knowledge of good dispensing habits and antibiotic laws (p = 0.036, p = 0.047, and p = 0.001, respectively). Pharmacists generally agreed that antibiotics under the Food and Drug Act may have contributed to OTC dispensing in the private sector (p = 0.013) and that all antibiotics should be under the Antibiotic Act (p = 0.002). Additionally, it was found that the dispensing of antibiotics OTC in the private sector (p = 0.006) occurred: without doctors' advice and without requesting prescriptions; because it was perceived as lawful (especially by older pharmacists); and because of the perceived motivation of profit. Regulation enforcement was perceived as deficient. OTC dispensing for reasons, such as misunderstanding of laws, occurs in T&T.

Antimicrobial Consumption from 2017 to 2021 in East Trinidad and Tobago: A Study in the English-Speaking Caribbean.

An antimicrobial consumption (AMC) study was performed in Trinidad and Tobago at the Eastern Regional Health Authority (ERHA). A retrospective, cross-sectional survey was conducted from 1 November 2021 to 30 March 2022. Dosage and package types of amoxicillin, azithromycin, co-amoxiclav, cefuroxime, ciprofloxacin, levofloxacin, moxifloxacin, nitrofurantoin and co-trimoxazole were investigated. Consumption was measured using the World Health Organization's Antimicrobial Resistance and Consumption Surveillance System methodology version 1.0, as defined daily doses (DDD) per 1000 population per day (DID). They were also analyzed using the 'Access', 'Watch' and 'Reserve' classifications. In the ERHA, AMC ranged from 6.9 DID to 4.6 DID. With regards to intravenous formulations, the 'Watch' group displayed increased consumption, from 0.160 DID in 2017 to 0.238 DID in 2019, followed by a subsequent drop in consumption with the onset of the COVID-19 pandemic. Oral co-amoxiclav, oral cefuroxime, oral azithromycin and oral co-trimoxazole were the most highly consumed antibiotics. The hospital started off as the higher consumer of antibiotics, but this changed to the community. The consumption of 'Watch' group antibiotics increased from 2017 to 2021, with a drop in consumption of 'Access' antibiotics and at the onset of COVID-19. Consumption of oral azithromycin was higher in 2021 than 2020.

Acute limb ischaemia: not an uncommon complication of COVID-19 infection.

A new variant of coronavirus (2019-nCoV) causing acute respiratory distress in humans was identified for the first time in 2019, in Wuhan, China. One of the many complications of infection with this coronavirus is hypercoagulopathy, resulting in acute thrombosis; often leading to acute limb ischaemia. Herein, we report 20 cases of COVID-19 with peripheral arterial thrombosis involving either upper or lower limbs. Some patients underwent vascular procedures and most had to undergo amputation at some level. All the cases (n=20) were referred to us during the 8-month period June 2020 to March 2021. The most common age group was between 51 and 60 years, of whom 80% were males; all the patients had diabetes. The right lower limb was most affected (50%); 15 patients underwent embolectomy. Twenty-five per cent of patients presented with wet gangrene. One patient with upper limb thrombosis recovered after embolectomy and did not require any amputation. Eighty-five per cent of patients underwent some form of amputation and the mortality rate was 10%. Arterial thrombosis is one complication patients may develop during COVID-19 illness, which may affect the outcome. Patients with comorbid conditions like diabetes are at higher risk of developing arterial thrombosis during COVID-19 infection. Susceptibility to coagulopathy may continue even after patient discharge and it is important that both patients and treating physicians are aware of this limb-threatening complication and seek early medical attention.

Corrigendum: Formulation and development of transferrin targeted solid lipid nanoparticles for breast cancer therapy.

[This corrects the article DOI: 10.3389/fphar.2020.614290.].

Formulation and Development of Transferrin Targeted Solid Lipid Nanoparticles for Breast Cancer Therapy.

Breast cancer is conventionally treated by surgery, chemotherapy and radiation therapy followed by post operational hormonal therapy. Tamoxifen citrate is a best option to treat breast cancer because its selective estrogen receptor modulation activity. Owing to its antiestrogenic action on breast as well as uterine cells, Tamoxifen citrate shows uterine toxicity. The dose 20 mg per day of Tamoxifen citrate required to show therapeutic effect causes side effects and toxicity to vital organs such as liver, kidney and uterus. In the present study, transferrin-conjugated solid lipid nanoparticles (SLNs) were successfully prepared to enhance the active targeting of tamoxifen citrate in breast cancer. Developed formulations were evaluated for particle size, surface charge, surface morphology and in vitro dissolution studies. Developed formulations exhibited more cytotoxicity as compared to pure Tamoxifen citrate solution in time as well as concentration dependent manner on human breast cancer MCF-7 cells. Further, cell uptake and flow cytometry studies confirmed the qualitative uptake of developed D-SLN and SMD-SLN by human breast cancer MCF-7 cells. Overall, proposed study highlights that transferrin engineered nanocarriers could enhance the therapeutic response of nanomedicines for breast cancer treatment.

Automation and control of laser wakefield accelerators using Bayesian optimization.

Laser wakefield accelerators promise to revolutionize many areas of accelerator science. However, one of the greatest challenges to their widespread adoption is the difficulty in control and optimization of the accelerator outputs due to coupling between input parameters and the dynamic evolution of the accelerating structure. Here, we use machine learning techniques to automate a 100 MeV-scale accelerator, which optimized its outputs by simultaneously varying up to six parameters including the spectral and spatial phase of the laser and the plasma density and length. Most notably, the model built by the algorithm enabled optimization of the laser evolution that might otherwise have been missed in single-variable scans. Subtle tuning of the laser pulse shape caused an 80% increase in electron beam charge, despite the pulse length changing by just 1%.

Numerical solution of a highly nonlinear and non-integrable equation using integrated radial basis function network method.

In this paper, we investigate a wide range of dynamical regimes produced by the nonlinearly excited phase (NEP) equation (a single sixth-order nonlinear partial differential equation) using a more advanced numerical method, namely, the integrated radial basis function network method. Previously, we obtained single-step spinning solutions of the equation using the Galerkin method. First, we verify the numerical solver through an exact solution of a forced version of the equation. Doing so, we compare the numerical results obtained for different space and time steps with the exact solution. Then, we apply the method to solve the NEP equation and reproduce the previously obtained spinning regimes. In the new series of numerical experiments, we find regimes in the form of spinning trains of steps/kinks comprising one, two, or three kinks. The evolution of the distance between the kinks is analyzed. Two different kinds of boundary conditions are considered: homogeneous and periodic. The dependence of the dynamics on the size of the domain is explored showing how larger domains accommodate multiple spinning fronts. We determine the critical domain size (bifurcation size) above which non-trivial settled regimes become possible. The initial condition determines the direction of motion of the kinks but not their sizes and velocities.

Author Correction: Laser-wakefield accelerators for high-resolution X-ray imaging of complex microstructures.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

DNA DSB Repair Dynamics following Irradiation with Laser-Driven Protons at Ultra-High Dose Rates.

Protontherapy has emerged as more effective in the treatment of certain tumors than photon based therapies. However, significant capital and operational costs make protontherapy less accessible. This has stimulated interest in alternative proton delivery approaches, and in this context the use of laser-based technologies for the generation of ultra-high dose rate ion beams has been proposed as a prospective route. A better understanding of the radiobiological effects at ultra-high dose-rates is important for any future clinical adoption of this technology. In this study, we irradiated human skin fibroblasts-AG01522B cells with laser-accelerated protons at a dose rate of 109 Gy/s, generated using the Gemini laser system at the Rutherford Appleton Laboratory, UK. We studied DNA double strand break (DSB) repair kinetics using the p53 binding protein-1(53BP1) foci formation assay and observed a close similarity in the 53BP1 foci repair kinetics in the cells irradiated with 225 kVp X-rays and ultra- high dose rate protons for the initial time points. At the microdosimetric scale, foci per cell per track values showed a good correlation between the laser and cyclotron-accelerated protons indicating similarity in the DNA DSB induction and repair, independent of the time duration over which the dose was delivered.

Laser-wakefield accelerators for high-resolution X-ray imaging of complex microstructures.

Laser-wakefield accelerators (LWFAs) are high acceleration-gradient plasma-based particle accelerators capable of producing ultra-relativistic electron beams. Within the strong focusing fields of the wakefield, accelerated electrons undergo betatron oscillations, emitting a bright pulse of X-rays with a micrometer-scale source size that may be used for imaging applications. Non-destructive X-ray phase contrast imaging and tomography of heterogeneous materials can provide insight into their processing, structure, and performance. To demonstrate the imaging capability of X-rays from an LWFA we have examined an irregular eutectic in the aluminum-silicon (Al-Si) system. The lamellar spacing of the Al-Si eutectic microstructure is on the order of a few micrometers, thus requiring high spatial resolution. We present comparisons between the sharpness and spatial resolution in phase contrast images of this eutectic alloy obtained via X-ray phase contrast imaging at the Swiss Light Source (SLS) synchrotron and X-ray projection microscopy via an LWFA source. An upper bound on the resolving power of 2.7 ± 0.3 µm of the LWFA source in this experiment was measured. These results indicate that betatron X-rays from laser wakefield acceleration can provide an alternative to conventional synchrotron sources for high resolution imaging of eutectics and, more broadly, complex microstructures.

Measuring the lifetime of intense-laser generated relativistic electrons in solids via gating their Cherenkov emission.

Optical Kerr gating technique has been employed to investigate the life history of relativistic electrons in solids by temporally gating their Cherenkov emission. Mega-ampere currents of relativistic electrons are created during ultra-intense (2 × 1019 W/cm2) laser-solid interactions. In order to measure the lifetime of these relativistic electrons in solids, we temporally gate their Cherenkov emission using an optical Kerr gate (OKG). The OKG is induced in a nonlinear medium, namely, carbon-di-sulphide (CS2), with a measured gate-width (FWHM) of 2 ps. The gate femtosecond laser pulse is synchronized with the intense interaction pulse generating relativistic electrons. The arrival time of the gate laser pulse on the CS2 cell is varied with the help of a delay stage. We find that Cherenkov emission from relativistic electrons created with a ultra-short laser pulse (25 fs) lives as long as 120 ps, a few thousand times that of the incident light pulse.

Caliber-Persistent Labial Artery: A Report of a Rarely Recognized Lip Swelling.

Calibre-persistent labial artery (CPLA) is a commonly underdiagnosed vascular lesion of the lip. CPLA is an arterial branch that penetrates the submucosal tissue without loss of calibre. Clinical diagnosis is significant as misdiagnosis can lead to profuse haemorrhage following an excisional biopsy or surgical excision. Colour Doppler ultrasonography is a safe and non-invasive diagnostic tool to confirm the diagnosis. Here, we report a case of a 24-year-old man who complained of an asymptomatic pulsating non-progressive nodule on the left side of upper lip initially diagnosed as peripheral angiomatous lesion. Diagnosis was confirmed by high-resolution Colour Doppler Ultrasonography. The purpose of this case report is to highlight the clinical importance and diagnosis of a rarely reported soft tissue swelling of the lip to the attention of clinicians.

Observation of Laser Power Amplification in a Self-Injecting Laser Wakefield Accelerator.

We report on the depletion and power amplification of the driving laser pulse in a strongly driven laser wakefield accelerator. Simultaneous measurement of the transmitted pulse energy and temporal shape indicate an increase in peak power from 187±11 TW to a maximum of 318±12 TW after 13 mm of propagation in a plasma density of 0.9×10^{18} cm^{-3}. The power amplification is correlated with the injection and acceleration of electrons in the nonlinear wakefield. This process is modeled by including a localized redshift and subsequent group delay dispersion at the laser pulse front.

Mapping the Damping Dynamics of Mega-Ampere Electron Pulses Inside a Solid.

We report the lifetime of intense-laser (2×10^{19} W/cm^{2}) generated relativistic electron pulses in solids by measuring the time evolution of their Cherenkov emission. Using a picosecond resolution optical Kerr gating technique, we demonstrate that the electrons remain relativistic as long as 50 picoseconds-more than 1000 times longer than the incident light pulse. Numerical simulations of the propagation of relativistic electrons and the emitted Cherenkov radiation with Monte Carlo geant4 package reproduce the striking experimental findings.

Factors Affecting Early Treatment Goals of Sepsis Patients Presenting to the Emergency Department.

BACKGROUND AND OBJECTIVES: Sepsis is a major cause of emergency medicine admission. It is associated with high mortality and morbidity. Even though sepsis is common in the Indian subcontinent, there is a paucity of data on the management of sepsis in India. The aim was to study the factors affecting early treatment goals. METHODS: All clinically suspected sepsis patients consenting to be part of the study were included. The diagnosis of sepsis was made by the treating physician in the emergency department as per the Surviving Sepsis Guidelines criteria. All cases were managed as per institutional treatment protocol. The patients were prospectively followed up and the time taken to achieve the goal-directed sepsis bundle documented and analyzed. RESULTS AND DISCUSSION: Of the 75 patients studied, the 3-hour(h) bundles were achieved in 70.7% of cases and 6-h bundles were achieved in 84% of cases. Meantime for obtaining blood culture was 107 min and administration of first dose antibiotics was 134 min. Thirty patients failed to achieve the early treatment goals, of which six were under-triaged, seven due to physicians delay in recognizing sepsis, 11 due to logistical delay, and six were due to financial constraints. CONCLUSION: The sepsis bundle goals were not achieved because of various factors such as under triaging, delay in diagnosis, logistical delay, and financial constraints. Further studies on whether sensitization of medical fraternity about sepsis, implementation of insurance policies for patient care or better point of care diagnostics would aid in achieving the bundles may be evaluated further.

Response and recovery of fathead minnows (Pimephales promelas) following early life exposure to water and sediment found within agricultural runoff from the Elkhorn River, Nebraska, USA.

Agricultural runoff is a non-point source of chemical contaminants that are seasonally detected in surface water and sediments. Agrichemicals found within seasonal runoff can elicit endocrine disrupting effects in organisms as adults, juveniles and larvae. The objectives of this study were (1) to determine if exposure to water, sediment or the water-sediment combination collected from an agricultural runoff event was responsible for changes in endocrine-responsive gene expression and development in fathead minnow larvae, and (2) whether such early life exposure leads to adverse effects as adults. Larvae were exposed during the first month post-hatch to water and sediment collected from the Elkhorn River and then allowed to depurate in filtered water until reaching sexual maturity, exemplifying a best-case recovery scenario. Gas chromatography mass spectrometry (GC/MS) analysis of the water and sediment samples detected 12 pesticides including atrazine, acetochlor, metolachlor and dimethenamid. In minnow larvae, exposure to river water upregulated androgen receptor gene expression whereas exposure to the sediment downregulated estrogen receptor α expression. Adult males previously exposed to both water and sediment were feminized through the induction of an ovipositor structure whereas no impacts were observed in other reproductive or sex characteristic endpoints for either sex based on exposure history. Results from this study indicate that both water and sediments found in agricultural runoff elicit responses from minnow larvae, and larvae can recover following early life exposure under a best-case scenario.