High energy electron diffraction instrument with tunable camera length.

Ultrafast electron diffraction (UED) stands as a powerful technique for real-time observation of structural dynamics at the atomic level. In recent years, the use of MeV electrons from radio frequency guns has been widely adopted to take advantage of the relativistic suppression of the space charge effects that otherwise limit the temporal resolution of the technique. Nevertheless, there is not a clear choice for the optimal energy for a UED instrument. Scaling to beam energies higher than a few MeV does pose significant technical challenges, mainly related to the inherent increase in diffraction camera length associated with the smaller Bragg angles. In this study, we report a solution by using a compact post-sample magnetic optical system to magnify the diffraction pattern from a crystal Au sample illuminated by an 8.2 MeV electron beam. Our method employs, as one of the lenses of the optical system, a triplet of compact, high field gradients (>500 T/m), small-gap (3.5 mm) Halbach permanent magnet quadrupoles. Shifting the relative position of the quadrupoles, we demonstrate tuning the magnification by more than a factor of two, a 6× improvement in camera length, and reciprocal space resolution better than 0.1 Å-1 in agreement with beam transport simulations.

Revision parathyroid surgery - challenges and considerations in comparison to primary surgery.

OBJECTIVE: Revision parathyroidectomy is made necessary by recurrent or persistent parathyroid disease. This study aimed to identify challenges in revision surgery compared to primary parathyroid surgery. METHODS: All revision parathyroidectomies performed by one surgeon over a 17-year period were assessed for demographics, imaging, histology, biochemistry, cure rate, gland weight, gland location and gland ectopia, and compared to a series of 100 primary parathyroidectomies. RESULTS: Twenty-eight revision surgical procedures were identified. Sestamibi scanning for gland localisation was superior to ultrasound in both primary and revision surgery. Pre-operative calcium and gland weight were significantly higher in revision cases. There were no significant differences in post-operative calcium levels, pre- or post-operative parathyroid hormone levels, or gland location. 36 per cent of glands excised in revision surgery were ectopic, compared to 25 per cent in primary procedures. The cure rate was significantly lower in revision surgery. CONCLUSION: Revision parathyroidectomy patients present with higher pre-operative calcium and larger adenomas; the cure rate is significantly lower in these patients.

Patient outcomes following thyroid surgery for thyrotoxicosis.

OBJECTIVE: Total thyroidectomy can be used as a definitive treatment modality for thyrotoxicosis. This study assessed the outcomes of patients treated with surgery at a single secondary care site. METHOD: A retrospective cohort study was conducted analysing consecutive patients who underwent thyroid surgery for thyrotoxicosis between 24 November 2000 and 26 April 2019 (n = 595). RESULTS: Total thyroidectomy was performed in 95.4 per cent of patients. Two-thirds of patients had Graves' disease histology. Of patients, 22.8 per cent became transiently hypothyroid whilst on levothyroxine (thyroid hormone replacement therapy). Transient and persistent hypocalcaemia was present in 23.3 per cent and 2.8 per cent of patients respectively. Recurrent laryngeal nerve palsy was transient and persistent in 3.6 per cent and 0.3 per cent respectively. Of patients, 2.5 per cent developed post-operative haematomas that required surgical evacuation in the operating theatre. CONCLUSION: The overall complication rate for thyroid surgery is higher in thyrotoxic than in euthyroid patients. Compared to other treatment modalities, total thyroidectomy appears to be the most effective, definitive means of managing Graves' disease.

Comparing ultrasound assessment of thyroid nodules using BTA U classification and ACR TIRADS measured against histopathological diagnosis.

INTRODUCTION: The British Thyroid Association (BTA) recommends ultrasound assessment of thyroid nodules using the U classification. The American College of Radiologists (ACR) recommend assessment with the Thyroid Imaging Reporting and Data System (TIRADS). We conduct the first UK study to compare these two systems. METHODS: Ultrasound (US) reports of patients who underwent surgical excision of thyroid nodules over a 10-year period in one UK centre were reviewed. US findings were collected, and the classifications were retrospectively applied. The systems were compared to histopathological diagnosis. RESULTS: 308 nodules in 296 patients are included. 135 nodules (43.8%) were malignant. U classification showed sensitivity of 88.1% in recommending FNA, significantly higher than TIRADS at 73.3% (p = .0002). The U classification showed specificity of 41.6%, significantly lower than TIRADS at 64.2% (p=<0.0001). PPV between classifications at equivalent levels showed no significant difference at U3/TR-3 (p=.81), U4/TR-4 (p=.30) or U5/TR-5 (p=.90). DISCUSSION: Classification systems enable risk stratification of potentially malignant thyroid nodules. This study shows BTA U classification has a higher sensitivity but lower specificity than TIRADS.

Frequency-domain calculation of Smith-Purcell radiation for metallic and dielectric gratings.

The intensity of Smith-Purcell radiation from metallic and dielectric gratings (silicon, silica) is compared in a frequency-domain simulation. The numerical model is discussed and verified with the Frank-Tamm formula for Cherenkov radiation. For 30 keV electrons, rectangular dielectric gratings are less efficient than their metallic counterparts, by an order of magnitude for silicon, and two orders of magnitude for silica. For all gratings studied, radiation intensity oscillates with grating tooth height due to electromagnetic resonances in the grating. 3D and 2D numerical models are compared.

On-chip integrated laser-driven particle accelerator.

Particle accelerators represent an indispensable tool in science and industry. However, the size and cost of conventional radio-frequency accelerators limit the utility and reach of this technology. Dielectric laser accelerators (DLAs) provide a compact and cost-effective solution to this problem by driving accelerator nanostructures with visible or near-infrared pulsed lasers, resulting in a 104 reduction of scale. Current implementations of DLAs rely on free-space lasers directly incident on the accelerating structures, limiting the scalability and integrability of this technology. We present an experimental demonstration of a waveguide-integrated DLA that was designed using a photonic inverse-design approach. By comparing the measured electron energy spectra with particle-tracking simulations, we infer a maximum energy gain of 0.915 kilo-electron volts over 30 micrometers, corresponding to an acceleration gradient of 30.5 mega-electron volts per meter. On-chip acceleration provides the possibility for a completely integrated mega-electron volt-scale DLA.

The effect of radioiodine treatment on the diseased thyroid gland.

Purpose: Radioiodine (I131) therapy is the treatment mainstay for several benign and malignant thyroid disorders, however I131 is known to cause DNA damage and liberation of thyroidal self-antigens inducing secondary immunoreactivity. The exact mechanisms underpinning cellular death and subsequent induction of autoimmune thyroid disease following I131 treatment have not yet been fully elucidated. This manuscript aims to review the literature concerning the effects of I131 on the thyroid gland.Conclusion: The effects of I131 on malignant thyroid cells appears to depend on absorbed dose with the literature demonstrating a clear initial delay in the triggering of apoptosis in response to I131-mediated cellular damage. Some studies also observed necrotic cellular death following high-dose I131 treatment. Liberation of thyroidal self-antigen following I131 treatment helps to explain phenomena such as the subsequent induction of autoimmune thyroid disease. The clinical utility of cytokines and autoantibodies for prognostication of hypothyroidism and treatment failure following I131 remains uncertain and further appropriately-powered studies are required to clarify their role. The potential role of other cell death mechanisms activated after treatment with I131 should also be explored in order to fully delineate the thyroidal response.

Enhanced energy gain in a dielectric laser accelerator using a tilted pulse front laser.

Using an 800 nm, 45 fs pulse-front-tilted laser we demonstrate a record 315 keV energy gain in a dual grating dielectric laser accelerator (DLA) and average accelerating gradients of 560 MV/m over 0.5 mm. These results open a new regime in DLA characterized by significant evolution of the beam distribution in the longitudinal phase space, corresponding to > 1/4 of a synchrotron oscillation. By tilting the laser wavefront we control the resonant velocity of the DLA and observe a net energy gain, indicating that a tapered optical phase could be used to achieve very high energy gain.

Design of a tapered slot waveguide dielectric laser accelerator for sub-relativistic electrons.

We propose a dielectric laser accelerator design based on a tapered slot waveguide structure for sub-relativistic electron acceleration. This tapering scheme allows for straightforward tuning of the phase velocity of the accelerating field along the propagation direction, which is necessary for maintaining synchronization with electrons as their velocities increase. Furthermore, the non-resonant nature of this design allows for better tolerance to experimental errors. We also introduce a method to design this continuously tapered structure based on the eikonal approximation, and give a working example based on realistic experimental parameters.

Method for computationally efficient design of dielectric laser accelerator structures.

Dielectric microstructures have generated much interest in recent years as a means of accelerating charged particles when powered by solid state lasers. The acceleration gradient (or particle energy gain per unit length) is an important figure of merit. To design structures with high acceleration gradients, we explore the adjoint variable method, a highly efficient technique used to compute the sensitivity of an objective with respect to a large number of parameters. With this formalism, the sensitivity of the acceleration gradient of a dielectric structure with respect to its entire spatial permittivity distribution is calculated by the use of only two full-field electromagnetic simulations, the original and 'adjoint'. The adjoint simulation corresponds physically to the reciprocal situation of a point charge moving through the accelerator gap and radiating. Using this formalism, we perform numerical optimizations aimed at maximizing acceleration gradients, which generate fabricable structures of greatly improved performance in comparison to previously examined geometries.

Parathyroid surgery: from inception to the modern day.

Parathyroid surgery has undergone great changes since its inception less than a century ago. It is still the only definitive option available to cure primary or tertiary hyperparathyroidism. This review details the development of parathyroid surgery, our understanding of hyperparathyroidism and the treatment options available. It also discusses the technological advances that have enabled parathyroid localization and prediction of surgical success.

Maximizing retention in long-term clinical trials of a weight loss agent: use of a dietitian support team.

OBJECTIVE: High-attrition rates have been observed in long-term clinical trials of weight loss agents. We evaluated the impact of an innovative retention programme on 1-year retention. METHODS: Three Phase 3 global multicentre clinical trials evaluated the efficacy and safety of a CB1 receptor antagonist in subjects with BMI ≥ or = 27 kg/m2. The impact of a multifaceted retention programme including a dietitian screening interview, a comprehensive culturally adapted lifestyle modification programme, and a dietitian support system to maximize lifestyle adherence, was evaluated in 4,410 subjects from four subpopulations (non-US English-speaking, non-English-speaking, US-without dietitian screening and US-with dietitian screening) comprising 208 centres from 15 countries. RESULTS: The median proportion retained over the first year among subjects in three protocols was 82%. Non-English-speaking countries showed higher retention rates (89%) compared with the USA (73%) and non-US English-speaking (81%) countries. Within the USA, behavioural screening was associated with 29% reduction in dropout rate; for every five monthly teleconferences attended above 11, there was a 32% decrease in dropout rate. CONCLUSIONS: This novel retention programme greatly improved upon reported retention rates of studies conducted with other weight loss agents in long-term clinical trials. Its effectiveness should be confirmed in future trials.

Is pharyngeal pouch stapling superior to open pharyngeal pouch repair? An analysis of a single institution's series.

BACKGROUND: Endoscopic stapling has become the primary procedure for pharyngeal pouch surgery because it is quick, less invasive and safe, but less is known about long-term outcomes. METHOD: Medical records were reviewed to compare rates of morbidity, operative failure, symptom control and revision surgery between open and closed procedures. RESULTS: A total of 120 pharyngeal pouch procedures, carried out on 97 patients from 2000 to 2014, were studied. These included 80 endoscopic stapling and 40 open procedures. Twelve patients had complications (15 per cent) and there was one mortality (1.2 per cent) in the endoscopic stapling group. Ten patients (25 per cent) developed complications in the open procedure group, with no mortalities. Symptom recurrence was significantly greater in the endoscopic stapling group (26 per cent) than in the open procedure group (7.5 per cent). Multiple surgical procedures were required for 22 endoscopically stapled patients (32 per cent); none were required in the open procedure group. Although the male-to-female ratio for pharyngeal pouch incidence was 2:1, the ratio for multiple surgical procedures was 10:1. CONCLUSION: Endoscopic stapling outcomes are not as good as those following an open approach on long-term follow up, and the early advantages are eliminated if pouch excision is avoided.

Demonstration of acceleration of relativistic electrons at a dielectric microstructure using femtosecond laser pulses.

Acceleration of electrons using laser-driven dielectric microstructures is a promising technology for the miniaturization of particle accelerators. Achieving the desired GV m-1 accelerating gradients is possible only with laser pulse durations shorter than ∼1 ps. In this Letter, we present, to the best of our knowledge, the first demonstration of acceleration of relativistic electrons at a dielectric microstructure driven by femtosecond duration laser pulses. Using this technique, an electron accelerating gradient of 690±100 MV m-1 was measured-a record for dielectric laser accelerators.

Parathyroid ectopia: development of a surgical algorithm based on operative findings.

OBJECTIVES: To study the incidence of ectopic parathyroid adenomata from a single surgical series, and to devise a surgical algorithm from the results to follow when an adenoma cannot initially be located. METHODS: A retrospective review was conducted of prospectively collected data. The study comprised all patients who underwent parathyroidectomy between June 2001 and February 2008 under the care of the senior author. A systematic surgical protocol was developed for locating ectopic superior and inferior parathyroid adenomata based on the order of incidence identified from the database. RESULTS: Parathyroid ectopia occurs in approximately 10 per cent of hyperparathyroidism cases. It is more common in superior than inferior parathyroid glands. The most common superior location is the right retroesophageal position and the most common inferior location is within the left thymic remnant. CONCLUSION: Prospective data collection and subsequent analysis can be used to develop a systematic surgical protocol to aid the localisation of ectopic enlarged parathyroid glands in the surgical management of hyperparathyroidism.

Inferior epigastric artery pseudoaneurysms.

INTRODUCTION: Inferior epigastric artery (IEA) pseudoaneurysms are recognised complications of abdominal wall procedures, and a variety of approaches including surgical excision and ligation, percutaneous procedures and conservative management have been employed in treating this rare complication. METHODS: We describe a case of an IEA pseudoaneurysm diagnosed on computed tomography (CT) angiography, 14 days following a laparoscopic assisted low anterior resection, which was managed successfully with surgical excision and ligation. A review of the literature identified 32 reports of this complication since 1973 with 69% of cases occurring since 2000. FINDINGS: The main aetiology of IEA pseudoaneurysm was abdominal surgery (n=20); 65% of cases were attributable to abdominal wound closure or laparoscopic surgery. Two-thirds (66%) of patients presented between 11 and 63 days, and all except 1 case presented with discomfort, abdominal mass or haemodynamic instability. Colour Doppler ultrasonography was the imaging modality of choice (n=18), either alone or in combination with computed tomography and/or angiography. Surgical ligation and excision and percutaneous coil embolisation formed the mainstay of attempted treatments (69%), particularly following treatment failure using an alternative technique. CONCLUSIONS: The incidence of iatrogenic IEA pseudoaneurysms appears to be increasing. Awareness of this rare complication is of clinical importance to avoid excessive morbidity for affected individuals.

Forensic ancestry analysis with two capillary electrophoresis ancestry informative marker (AIM) panels: Results of a collaborative EDNAP exercise.

There is increasing interest in forensic ancestry tests, which are part of a growing number of DNA analyses that can enhance routine profiling by obtaining additional genetic information about unidentified DNA donors. Nearly all ancestry tests use single nucleotide polymorphisms (SNPs), but these currently rely on SNaPshot single base extension chemistry that can fail to detect mixed DNA. Insertion-deletion polymorphism (Indel) tests have been developed using dye-labeled primers that allow direct capillary electrophoresis detection of PCR products (PCR-to-CE). PCR-to-CE maintains the direct relationship between input DNA and signal strength as each marker is detected with a single dye, so mixed DNA is more reliably detected. We report the results of a collaborative inter-laboratory exercise of 19 participants (15 from the EDNAP European DNA Profiling group) that assessed a 34-plex SNP test using SNaPshot and a 46-plex Indel test using PCR-to-CE. Laboratories were asked to type five samples with different ancestries and detect an additional mixed DNA sample. Statistical inference of ancestry was made by participants using the Snipper online Bayes analysis portal plus an optional PCA module that analyzes the genotype data alongside calculation of Bayes likelihood ratios. Exercise results indicated consistent genotyping performance from both tests, reaching a particularly high level of reliability for the Indel test. SNP genotyping gave 93.5% concordance (compared to the organizing laboratory's data) that rose to 97.3% excluding one laboratory with a large number of miscalled genotypes. Indel genotyping gave a higher concordance rate of 99.8% and a reduced no-call rate compared to SNP analysis. All participants detected the mixture from their Indel peak height data and successfully assigned the correct ancestry to the other samples using Snipper, with the exception of one laboratory with SNP miscalls that incorrectly assigned ancestry of two samples and did not obtain informative likelihood ratios for a third. Therefore, successful ancestry assignments were achieved by participants in 92 of 95 Snipper analyses. This exercise demonstrates that ancestry inference tests based on binary marker sets can be readily adopted by laboratories that already have well-established CE regimes in place. The Indel test proved to be easy to use and allowed all exercise participants to detect the DNA mixture as well as achieving complete and concordant profiles in nearly all cases. Lastly, two participants successfully ran parallel next-generation sequencing analyses (each using different systems) and achieved high levels of genotyping concordance using the exercise PCR primer mixes unmodified.

High-efficiency acceleration of an electron beam in a plasma wakefield accelerator.

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.