Laboratory realization of relativistic pair-plasma beams.

Relativistic electron-positron plasmas are ubiquitous in extreme astrophysical environments such as black-hole and neutron-star magnetospheres, where accretion-powered jets and pulsar winds are expected to be enriched with electron-positron pairs. Their role in the dynamics of such environments is in many cases believed to be fundamental, but their behavior differs significantly from typical electron-ion plasmas due to the matter-antimatter symmetry of the charged components. So far, our experimental inability to produce large yields of positrons in quasi-neutral beams has restricted the understanding of electron-positron pair plasmas to simple numerical and analytical studies, which are rather limited. We present the first experimental results confirming the generation of high-density, quasi-neutral, relativistic electron-positron pair beams using the 440 GeV/c beam at CERN's Super Proton Synchrotron (SPS) accelerator. Monte Carlo simulations agree well with the experimental data and show that the characteristic scales necessary for collective plasma behavior, such as the Debye length and the collisionless skin depth, are exceeded by the measured size of the produced pair beams. Our work opens up the possibility of directly probing the microphysics of pair plasmas beyond quasi-linear evolution into regimes that are challenging to simulate or measure via astronomical observations.

Scalable radiotherapy data curation infrastructure for deep-learning based autosegmentation of organs-at-risk: A case study in head and neck cancer.

In this era of patient-centered, outcomes-driven and adaptive radiotherapy, deep learning is now being successfully applied to tackle imaging-related workflow bottlenecks such as autosegmentation and dose planning. These applications typically require supervised learning approaches enabled by relatively large, curated radiotherapy datasets which are highly reflective of the contemporary standard of care. However, little has been previously published describing technical infrastructure, recommendations, methods or standards for radiotherapy dataset curation in a holistic fashion. Our radiation oncology department has recently embarked on a large-scale project in partnership with an external partner to develop deep-learning-based tools to assist with our radiotherapy workflow, beginning with autosegmentation of organs-at-risk. This project will require thousands of carefully curated radiotherapy datasets comprising all body sites we routinely treat with radiotherapy. Given such a large project scope, we have approached the need for dataset curation rigorously, with an aim towards building infrastructure that is compatible with efficiency, automation and scalability. Focusing on our first use-case pertaining to head and neck cancer, we describe our developed infrastructure and novel methods applied to radiotherapy dataset curation, inclusive of personnel and workflow organization, dataset selection, expert organ-at-risk segmentation, quality assurance, patient de-identification, data archival and transfer. Over the course of approximately 13 months, our expert multidisciplinary team generated 490 curated head and neck radiotherapy datasets. This task required approximately 6000 human-expert hours in total (not including planning and infrastructure development time). This infrastructure continues to evolve and will support ongoing and future project efforts.

Efficacy of standard- vs reduced-dose insulin for treatment of hyperkalemia: A quasi-experiment.

PURPOSE: Hyperkalemia more commonly affects patients with a glomerular filtration rate of less than 60 mL/min. Using intravenous (IV) insulin to shift potassium intracellularly may cause hypoglycemia, requiring additional treatment or longer hospitalization. Literature on insulin dosing in this context is limited, with one previous study indicating that 5 units of IV insulin might be as effective and result in less hypoglycemia than the standard dose of 10 units of IV insulin. The hyperkalemia treatment pathway at our institution was revised in May 2018 to include a reduced-dose option (5 units of insulin) for patients with end-stage renal disease. This study aimed to compare the prevalence of hypoglycemia between patients who received standard-dose vs reduced-dose IV insulin. METHODS: This single-center, retrospective, quasi-experimental study evaluated the impact of revision of the hyperkalemia treatment pathway by assessing rates of hypoglycemia during the 6 months before and after implementation of the revised pathway. The primary endpoint was prevalence of hypoglycemia, defined as a blood glucose level of less than or equal to 70 mg/dL. RESULTS: There was no statistically significant difference in the occurrence of hypoglycemia when comparing the pre- and postimplementation groups (36 [17.7%] patients vs 34 [18.7%] patients; P = 0.7924). The postimplementation group had a statistically significant lower reduction in potassium levels after treatment than the preimplementation group (mean [interquartile range], -0.9 [-1.3, -0.5] mEq/L vs -0.6 [-1.2, -0.2] mEq/L; P = 0.0095). Baseline potassium levels were similar between the groups. CONCLUSION: Administration of reduced-dose IV insulin for treatment of hyperkalemia was significantly less effective in lowering serum potassium levels and did not decrease prevalence of hypoglycemia. When accounting for potential confounders, the only variable that was associated with hypoglycemia was pretreatment glucose level.

Observations of pressure anisotropy effects within semi-collisional magnetized plasma bubbles.

Magnetized plasma interactions are ubiquitous in astrophysical and laboratory plasmas. Various physical effects have been shown to be important within colliding plasma flows influenced by opposing magnetic fields, however, experimental verification of the mechanisms within the interaction region has remained elusive. Here we discuss a laser-plasma experiment whereby experimental results verify that Biermann battery generated magnetic fields are advected by Nernst flows and anisotropic pressure effects dominate these flows in a reconnection region. These fields are mapped using time-resolved proton probing in multiple directions. Various experimental, modelling and analytical techniques demonstrate the importance of anisotropic pressure in semi-collisional, high-ß plasmas, causing a reduction in the magnitude of the reconnecting fields when compared to resistive processes. Anisotropic pressure dynamics are crucial in collisionless plasmas, but are often neglected in collisional plasmas. We show pressure anisotropy to be essential in maintaining the interaction layer, redistributing magnetic fields even for semi-collisional, high energy density physics (HEDP) regimes.

An effective CTL peptide vaccine for Ebola Zaire Based on Survivors' CD8+ targeting of a particular nucleocapsid protein epitope with potential implications for COVID-19 vaccine design.

The 2013-2016 West Africa EBOV epidemic was the biggest EBOV outbreak to date. An analysis of virus-specific CD8+ T-cell immunity in 30 survivors showed that 26 of those individuals had a CD8+ response to at least one EBOV protein. The dominant response (25/26 subjects) was specific to the EBOV nucleocapsid protein (NP). It has been suggested that epitopes on the EBOV NP could form an important part of an effective T-cell vaccine for Ebola Zaire. We show that a 9-amino-acid peptide NP44-52 (YQVNNLEEI) located in a conserved region of EBOV NP provides protection against morbidity and mortality after mouse adapted EBOV challenge. A single vaccination in a C57BL/6 mouse using an adjuvanted microsphere peptide vaccine formulation containing NP44-52 is enough to confer immunity in mice. Our work suggests that a peptide vaccine based on CD8+ T-cell immunity in EBOV survivors is conceptually sound and feasible. Nucleocapsid proteins within SARS-CoV-2 contain multiple Class I epitopes with predicted HLA restrictions consistent with broad population coverage. A similar approach to a CTL vaccine design may be possible for that virus.

Would the introduction of the Index of Orthognathic Functional Treatment Need (IOFTN) affect referrals and acceptance of people for orthognathic treatment?

Introduction The Index of Orthognathic Functional Treatment Need (IOFTN) was developed to measure functional difficulties arising from malocclusions related to facial deformity. The IOFTN is not currently being used to determine suitability for orthognathic treatment, however, it is a useful aid for assessing and referring patients and takes into account functional and facial appearance. This paper aims to evaluate the potential impact of introduction of the IOFTN on the future provision of orthognathic services.Methods Two methods were used to consider the impact of the IOFTN on orthognathic provision. Firstly, a local retrospective audit was undertaken in Leeds Teaching Hospital NHS Trust involving thirty consecutively treated patients, for whom full records were retrieved. Data was collected using a standardised data caption form. Local standards were agreed concerning the need for treatment. Secondly, a systematic search of published studies was completed to assess evidence from across the UK.Results The audit standard, that is, 90% of patients treated with orthognathic surgery should be categorised as grade 4 (great need) or 5 (very great need) using the IOFTN, was fulfilled. The most common reason for seeking treatment related to dental and facial aesthetics and no patients were treated for speech or TMJ problems alone. The systematic review searches identified four suitable records for inclusion in the review, including two audits and two retrospective studies undertaken in secondary care settings across England and Scotland. These studies showed that at least 86% of all participants scored 4 or 5 using the IOFTN.Conclusions The findings from the audit and literature review indicate that referrals from general dentists and acceptance for orthognathic treatment in secondary care is unlikely to be significantly affected by introduction of the IOFTN. Referring dentists may find the IOFTN a useful prompt for determining whether people are suitable for orthognathic treatment.

Orthodontic therapists - has their introduction affected outcomes?

Objective To assess the effect of the introduction of orthodontic therapists (OTs) on the quality of orthodontic treatment outcomes in two specialist orthodontic practices in the UK.Study design Retrospective cross sectional observational study.Setting Multi-centre evaluation at two specialist orthodontic practices in Yorkshire. Data collection was carried out during 2014.Materials and methods The treatment undertaken by three specialist orthodontic clinicians (A, B and C) was evaluated at two time points. The first time point (T1) was before the introduction of OTs when the specialist orthodontic clinicians were solo operators. The second time point (T2) followed the introduction of OTs. Patients at T2 had their treatment planned by a specialist orthodontist and were seen for care by both the orthodontist and an OT who had been qualified for a minimum of three years. A sample size of 30 orthodontic patients per clinician at each time point was chosen. Included participants had completed a course of fixed appliance therapy. They were consecutively selected from cases that had been completed in the specified time frame for each clinician.Main outcome measures The quality of treatment was assessed objectively using the quantitative Peer Assessment Rating index (PAR index). Data extracted from the specialist practice databases also allowed conclusions to be drawn about the length of treatment time and number of appointments in each treatment group.Results and conclusions There appears to have been no change in orthodontic treatment outcomes following the introduction of supervised OTs at two specialist orthodontic practices.

Can dental registrants use the Index of Orthodontic Treatment Need accurately? Part 2. Factors influencing knowledge of IOTN among dental registrants.

Aim To understand the frequency of use and training of IOTN amongst dental registrants working in primary and secondary care. To ascertain which factors influence 'accuracy' of IOTN amongst dental registrants.Method Participants were asked to complete a short questionnaire at the same time as scoring the IOTN for 14 cases. The questionnaire was developed by the authors of this study to understand registrants' place of work, frequency of use of IOTN and training undertaken in IOTN. Multiple linear regression analysis was used to reveal which predictor factors best described a registrant's knowledge of IOTN.Results The mean kappa scores were the highest for participants working in secondary care (K = 0.68) when compared to those solely working in primary care. The SO and GDP groups were found to be the groups with the largest proportion of participants using IOTN on a daily basis. Only the participants that used the IOTN everyday achieved an acceptable mean DHC K >0.60. There is an increasing trend of mean DHC kappa scores evident with increasing frequency of use of IOTN. All participants had received training in the use of IOTN with the majority (n = 181/229) having their last episode of training within the last five years. The majority of the training received in IOTN was classified as being verifiable (n = 154/229) with the remainder classifying their training as non-verifiable. Two predictor variables were found to have a significant influence on the DHC kappa scores, which included registrant group and place of work. Only one of the predictor variables had a statistically significant influence on the AC kappa scores, which was the type of CPD, with participants who had received non-verifiable CPD having a lower kappa scores.Conclusion Place of work, frequency of use of IOTN and registrant group were the main factors which were found to influence accuracy of use of IOTN. This study has highlighted a need for greater support in terms of resources, training and tools to help dental registrants use the IOTN more accurately to an acceptable level.

Can dental registrants use the Index of Orthodontic Treatment Need accurately? Part 1: Knowledge of IOTN among dental registrants.

Aim To determine whether dental registrants can use the dental health component (DHC) and aesthetic component (AC) of the Index of Orthodontic Treatment Need (IOTN) 'accurately' to an acceptable level of agreement and diagnostic validity.Method Participants from six different registrant groups were asked to score the IOTN for 14 cases based on study models and photographs as well as completing a short questionnaire. Participants in the study were all recruited at study days and annual conferences. The main outcome measures include the different registrant groups IOTN scores compared to expert panel scores using kappa statistics. To assess for diagnostic validity, individual participants sensitivity and specificity scores were calculated.Result Overall, 229 registrants took part in the study. For the DHC the specialist orthodontist (SO), postgraduate orthodontic student (PGOS) and the qualified orthodontic therapist (QOT) groups achieved a mean kappa ≥0.60 indicating 'acceptable' agreement with the expert panel scores. The dental foundation trainee (DFT) and general dental practitioner (GDP) group achieved a mean kappa of 0.20 and 0.22 respectively indicating poor and fair agreement. The student orthodontic therapist (SOT) group achieved a mean kappa of 0.55 indicating moderate agreement. For the AC none of the registrant groups achieved an acceptable level of agreement with the mean kappa scores for the different groups ranging from kappa 0.13-0.21, indicating poor to fair agreement.Conclusion Overall agreement for the DHC was varied for the different registrant groups ranging from fair to substantial agreement. Registrants were better at applying the DHC compared to the AC with agreement ranging from poor to fair. More needs to done to help registrants use the IOTN more 'accurately'.

Effects of 0.5% Timolol Maleate Ophthalmic Solution on Heart Rate and Selected Echocardiographic Indices in Apparently Healthy Cats.

BACKGROUND: Echocardiographic assessment of diastolic function is challenging in cats, partially because of transmitral flow pattern fusion associated with high heart rates. With heart rate (HR) reduction, transmitral flow waveforms separate, allowing identification of diastolic dysfunction. Timolol, an ophthalmic, nonselective beta-blocker used in glaucoma is safe and transiently decreases HR in clinical trials. HYPOTHESIS: Administration of timolol ophthalmic solution decreases HR and facilitates echocardiographic assessment of diastolic function in cats without inducing clinically relevant adverse effects. ANIMALS: Twenty-five apparently healthy cats. METHODS: Electrocardiograms and echocardiograms including transmitral flow patterns were evaluated before and 20 minutes after ocular administration of 1 drop of timolol 0.5% solution. Twenty cats underwent treatment with timolol, and 5 different cats served as untreated controls to evaluate the effects of acclimation to the hospital environment on HR. RESULTS: Acclimation to the hospital had no effect on HR in control cats. After timolol administration, a significant median HR reduction of 25 bpm was observed (P < .0001). Timolol had no effect on E/A ratio in cats without E/A fusion (7/20, P = .44). Of the 13 cats with E and A waves that were fused before timolol application, separation of these waves was identified in 8 cats (62%) after timolol treatment. No bradyarrhythmias were noted after timolol administration, but 2 cats had first-degree atrioventricular block. Timolol resulted in resolution of dynamic outflow tract obstruction in 6 of 6 cats. CONCLUSIONS AND CLINICAL IMPORTANCE: Ocular administration of timolol safely decreases HR in cats and could facilitate assessment of diastolic function.

Who needs orthodontic treatment? Who gets it? And who wants it?

As the health and expectations of the UK population improve, demand for orthodontic treatment is increasing. This article will examine who actually needs orthodontic treatment and who is currently receiving it, while also providing an opinion on the the risks versus benefits in providing demand-led treatment.

'Who does what' in the orthodontic workforce.

The contraction of the economy in the United Kingdom and constraints on the National Health Service (NHS) together with new opportunities for the delivery of orthodontic treatment has resulted in an increasing number of dental personnel across the different registrant groups. This article focuses on the changes that have taken place in the orthodontic workforce over the past decade. Although others help deliver orthodontic services such as material suppliers, treatment coordinators and those involved in marketing, this article will restrict itself to informing the reader specifically about which dental registrants are doing what at the clinical interface. How health professionals have developed their skills to undertake the role they play within the team and possible threats arising because of these changes are also discussed.

Association of dilated cardiomyopathy with the striatin mutation genotype in boxer dogs.

BACKGROUND: Myocardial disease in the Boxer dog is characterized by 1 of 2 clinical presentations, dilated cardiomyopathy (DCM) characterized by ventricular systolic dysfunction, dilatation and tachyarrhythmias, and arrhythmogenic right ventricular cardiomyopathy (ARVC) characterized by ventricular tachyarrhythmias, syncope, and sudden death. Boxer ARVC has been associated with a deletion in the striatin gene in some families. HYPOTHESIS/OBJECTIVES: We hypothesized that both presentations represent a single disease, and the development of DCM in the Boxer is associated with the striatin deletion. ANIMALS: Thirty-three adult Boxer dogs with DCM, 29 adult Boxer dogs with the striatin deletion and ARVC, and 16 Boxers without cardiac disease. METHODS: DNA samples were evaluated for the striatin deletion. Association of the deletion with the DCM phenotype was tested by a Fisher's exact test. T-tests were used to evaluate potential differences between the positive heterozygous and positive homozygous groups with DCM with regard to age, LVIDD, LVIDS, and FS%. RESULTS: Thirty of 33 dogs with DCM were positive for the striatin deletion. The striatin mutation and the homozygous genotype were strongly associated with the DCM phenotype (P < .001 and P = .005). There was no statistical difference between the heterozygous and homozygous groups with regard to age and echocardiographic measurements. CONCLUSIONS AND CLINICAL IMPORTANCE: This study demonstrates an association between DCM in the Boxer dog and the striatin mutation, particularly with the homozygous genotype. The observation that 3/33 dogs developed DCM and lacked the striatin mutation suggests that there is at least 1 other cause of DCM in the Boxer dog.

A national study of cross infection control: 'are we clean enough?'.

OBJECTIVE: To establish what cross infection control policies and procedures are in place within UK orthodontic departments and how they compare with recommended guidelines. DESIGN: A hospital-based cross-sectional study investigating UK orthodontic departments between March 2007 and January 2008. SUBJECTS AND METHODS: The main outcome measure was a questionnaire constructed for the study, based on current cross infection control guidelines. All orthodontic departments within district general hospitals were invited to participate via email and the response rate was 48%. RESULTS: Five key areas were explored, which included a) training, education and personal protection, b) the clinical environment, c) decontamination of instruments, d) decontamination of appliances and impressions and e) disposal of waste. Ninety-eight percent of departments provided training in cross infection control and 98% also had a policy to check staff immunisation status. With respect to the clinical environment, 97% of the departments surveyed had separate 'clean' and 'dirty' zones. Half of all departments used central sterile services departments (CSSD) for instrument sterilisation. Seventy-eight percent of departments had a policy to decontaminate impressions/appliances at the chairside and all departments used 'yellow bags' for clinical waste and puncture-proof containers for sharps waste. CONCLUSIONS: UK orthodontic departments have implemented policies and procedures which would ensure a high standard of cross infection control. In particular, this related to the decontamination of surfaces and instruments, the use of personal protection and disposal of clinical waste. Most departments had policies and procedures in place for staff education and training in cross infection control and personal protection.

Are general dental practitioners effective in the management of non-apnoeic snoring using mandibular advancement appliances?

OBJECTIVE: This study assessed the effectiveness of general dental practitioners (GDPs) in the management of subjects with non-apnoeic snoring using a mandibular advancement appliance (MAA), following a one day training course. SUBJECTS AND METHODS: Sixty subjects suffering from simple, non-apnoeic snoring were treated by 15 GDPs, in three hospital centres, using a monobloc mandibular advancement appliance design. All GDPs attended a one day training course prior to the study which covered theoretical and practical training in the use of mandibular advancement appliances. Snoring and level of disturbance were assessed using a questionnaire completed by their sleeping partner before and after a three month treatment period. Daytime sleepiness was assessed by the patients using the Epworth sleepiness scale questionnaire (ESS) before and after a three month treatment period. In addition, patients completed an outcome questionnaire, to assess side-effects experienced from the MAA. RESULTS: A success rate of 48% (95% CI 0.35, 0.61) was achieved in partner-assessed snoring and disturbance levels, following a three month period of MAA treatment. The median ESS score reduced from 9 to 7.5 (95% CI 0, 3). General dental practitioners experienced problems during protrusive bite registrations, with 10% being judged inadequate. CONCLUSION: GDPs were not effective in the management of non-apnoeic snoring using a monobloc appliance after a one day training course. Further training and/or selection of a different design of appliance should be considered for GDPs to become highly competent in this area.

Providing high-quality research training for veterinary pathologists in Europe.

Despite their key role in a wide range of fields relating to animal and public health, there is currently a lack of veterinary pathologists in Europe. In 1999, to help address the problem, the European College of Veterinary Pathologists (ECVP) and the European Society of Veterinary Pathology (ESVP) established a joint Education Committee. In this Special Article, Professor Anja Kipar and colleagues, all members of the committee, describe the ECVP/ESVP Summer Schools in Veterinary Pathology programme, which aims to provide high-quality research training for veterinary pathologists from all over Europe and beyond.

American orthodontics Maurice Berman Prize 2005.

This paper describes the orthodontic treatment of two cases, which were awarded the 2005 Maurice Berman Prize.

Clinical pearl In-treatment replacement of missing incisors.

Four methods of in-treatment replacement of missing incisors are described.

A randomized clinical trial comparing the accuracy of direct versus indirect bracket placement.

OBJECTIVE: To determine the accuracy of direct or indirect bracket placement. DESIGN: A prospective, randomized comparison of 2 different methods of bracket placement. SETTING: Queens Hospital, Burton upon Trent, UK between February and May 2001. MATERIALS AND METHOD: Twenty-six consecutive patients requiring upper and lower MBT trade mark pre-adjusted Edgewise appliances had their labial segments bonded directly or indirectly according to a split mouth system of allocation. Before and after bond-up all brackets were photographed and measured from tracings to determine positional differences from the ideal. RESULTS: Using ANOVA (General Linear Model), vertical errors were found to be greater than those in the horizontal plane, which in turn were greater than angular errors (p<0.05). Errors were greater in the maxillary arch than in the mandibular arch. There was no significant difference between the mean errors produced by the two methods of bracket placement. CONCLUSIONS: Mean bracket placement errors were similar with both techniques.