Burning plasma achieved in inertial fusion.

Obtaining a burning plasma is a critical step towards self-sustaining fusion energy1. A burning plasma is one in which the fusion reactions themselves are the primary source of heating in the plasma, which is necessary to sustain and propagate the burn, enabling high energy gain. After decades of fusion research, here we achieve a burning-plasma state in the laboratory. These experiments were conducted at the US National Ignition Facility, a laser facility delivering up to 1.9 megajoules of energy in pulses with peak powers up to 500 terawatts. We use the lasers to generate X-rays in a radiation cavity to indirectly drive a fuel-containing capsule via the X-ray ablation pressure, which results in the implosion process compressing and heating the fuel via mechanical work. The burning-plasma state was created using a strategy to increase the spatial scale of the capsule2,3 through two different implosion concepts4-7. These experiments show fusion self-heating in excess of the mechanical work injected into the implosions, satisfying several burning-plasma metrics3,8. Additionally, we describe a subset of experiments that appear to have crossed the static self-heating boundary, where fusion heating surpasses the energy losses from radiation and conduction. These results provide an opportunity to study α-particle-dominated plasmas and burning-plasma physics in the laboratory.

Observation of Hydrodynamic Flows in Imploding Fusion Plasmas on the National Ignition Facility.

Inertial confinement fusion implosions designed to have minimal fluid motion at peak compression often show significant linear flows in the laboratory, attributable per simulations to percent-level imbalances in the laser drive illumination symmetry. We present experimental results which intentionally varied the mode 1 drive imbalance by up to 4% to test hydrodynamic predictions of flows and the resultant imploded core asymmetries and performance, as measured by a combination of DT neutron spectroscopy and high-resolution x-ray core imaging. Neutron yields decrease by up to 50%, and anisotropic neutron Doppler broadening increases by 20%, in agreement with simulations. Furthermore, a tracer jet from the capsule fill-tube perturbation that is entrained by the hot-spot flow confirms the average flow speeds deduced from neutron spectroscopy.

Paving the way for application of next generation risk assessment to safety decision-making for cosmetic ingredients.

Next generation risk assessment (NGRA) is an exposure-led, hypothesis-driven approach that has the potential to support animal-free safety decision-making. However, significant effort is needed to develop and test the in vitro and in silico (computational) approaches that underpin NGRA to enable confident application in a regulatory context. A workshop was held in Montreal in 2019 to discuss where effort needs to be focussed and to agree on the steps needed to ensure safety decisions made on cosmetic ingredients are robust and protective. Workshop participants explored whether NGRA for cosmetic ingredients can be protective of human health, and reviewed examples of NGRA for cosmetic ingredients. From the limited examples available, it is clear that NGRA is still in its infancy, and further case studies are needed to determine whether safety decisions are sufficiently protective and not overly conservative. Seven areas were identified to help progress application of NGRA, including further investments in case studies that elaborate on scenarios frequently encountered by industry and regulators, including those where a 'high risk' conclusion would be expected. These will provide confidence that the tools and approaches can reliably discern differing levels of risk. Furthermore, frameworks to guide performance and reporting should be developed.

Environmental barriers to sociality in an obligate eusocial sweat bee.

Understanding the ecological and environmental contexts in which eusociality can evolve is fundamental to elucidating its evolutionary origins. A sufficiently long active season is postulated to have been a key factor facilitating the transition to eusociality. Many primitively eusocial species exhibit an annual life cycle, which is thought to preclude the expression of eusociality where the active season is too short to produce successive worker and reproductive broods. However, few studies have attempted to test this idea experimentally. We investigated environmental constraints on the expression of eusociality in the obligate primitively eusocial sweat bee Lasioglossum malachurum, by transplanting nest foundresses from the south to the far north of the United Kingdom, far beyond the natural range of L. malachurum. We show that transplanted bees can exhibit eusociality, but that the short length of the season and harsher environmental conditions could preclude its successful expression. In one year, when foundresses were transplanted only after provisioning first brood (B1) offspring, workers emerged in the north and provisioned a second brood (B2) of reproductives. In another year, when foundresses were transplanted prior to B1 being provisioned, they were just as likely to initiate nesting and provisioned just as many B1 cells as foundresses in the south. However, the life cycle was delayed by approximately 7 weeks and nests suffered 100% B1 mortality. Our results suggest that short season length together with poor weather conditions represent an environmental barrier to the evolution and expression of eusociality in sweat bees.

Curriculum content and assessment of pre-clinical dental skills: A survey of undergraduate dental education in Europe.

INTRODUCTION: Since 1981, the qualifications for various healthcare professionals across the European Union have enjoyed mutual recognition in accordance with the EU Directive 81/1057/EEC. Whilst the directive includes dental practitioners, it is recognised that significant variation exists in curriculum structure, content and scope of practice across institutions. This article aimed to explore pan-European practice in relation to curriculum content, teaching and learning strategies and assessment of pre-clinical dental skills. METHOD: A request to complete an online questionnaire, in English, was sent electronically to skills leads at all Association of Dental Education in Europe member schools. The questionnaire collected information in relation to institution and country, regulatory requirements to demonstrate safety, details of specific pre-clinical skills courses, learning materials and teaching staff. RESULTS: Forty-eight institutions, from 25 European countries responded. Seven countries (n=7, 28%) reported no requirement to demonstrate student operative safety prior to patient treatment. Several core and operative clinical skills are common to the majority of institutions. The most commonly taught core skills related directly to the clinical environment such as cross-infection control and hand washing. The least common were skills that indirectly related to patient care, such as communication skills and working as a team. CONCLUSION: There are clear differences within European pre-clinical dental education, and greater efforts are needed to demonstrate that all European students are fit to practice before they start treating patients. Learning outcomes, teaching activities and assessment activities of pre-clinical skills should be shared collaboratively to further standardise curricula.

Interleukin-2 receptor-α proximal promoter hypomethylation is associated with multiple sclerosis.

Genetic studies have demonstrated association between single-nucleotide polymorphisms within the IL2RA (interleukin-2 receptor α-subunit) gene and risk of developing multiple sclerosis (MS); however, these variants do not have obvious functional consequences. DNA methylation is a source of genetic variation that could impact on autoimmune disease risk. We investigated DNA methylation of the IL2RA promoter in genomic DNA obtained from peripheral blood mononuclear cells and neural tissue using matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) mass spectrometry. A differential methylation profile of IL2RA was identified, suggesting that IL2RA expression was regulated by DNA methylation. We extended our analysis of DNA methylation to peripheral blood mononuclear cell (PBMC) of MS cases and controls using MALDI-TOF and Illumina HumanMethylation450 arrays. Analyses of CpG sites within the proximal promoter of IL2RA in PBMC showed no differences between MS cases and controls despite an increase in IL2RA expression. In contrast, we inferred significant DNA methylation differences specific to particular leukocyte subtypes in MS cases compared with controls by deconvolution of the array data. The decrease in methylation in patients correlated with an increase in IL2RA expression in T cells from MS cases in comparison with controls. Our data suggest that differential methylation of the IL2RA promoter in T cells could be an important pathogenic mechanism in MS.

Use of substitute Nonidet P-40 nonionic detergents in intracellular tubulin polymerization assays for screening of microtubule targeting agents.

Shell Chemical Company Nonidet P-40 has been used for decades in many biochemical assays as a nonionic, nondenaturing detergent; however, Shell no longer manufactures this product. Four commercially available substitutes were investigated and their activities titrated in an intracellular tubulin polymerization assay. Although claimed by the supply companies to be identical to the Shell Nonidet P-40, all four substitutes were about 10-fold more potent and needed to be diluted accordingly. As microtubule targeting drugs are a major class of anticancer agent, and many researchers use the intracellular tubulin polymerization assay, this information is important to help troubleshoot assay development with the new substitutes. As the Shell Nonidet P-40 has been used in many biochemical buffers, these results will be of general interest to the biochemical, cell, and molecular research community.

The Graduating European Dentist-Domain IV: Dentistry in Society.

This position paper outlines the areas of competence and learning outcomes of "The Graduating European Dentist" that specifically relates to Dentistry in Society. In addition to treating individual patients, a Dentist must be able to focus on promoting health, monitoring interventions and implementing effective strategies of care at community and population levels. This necessarily involves understanding population demography and health trends, engaging with health policy and promoting health. A Dentist must also understand population demography and health trends, in the context of the healthcare system within which they work.

The Graduating European Dentist-Domain II: Safe and Effective Clinical Practice.

This position paper outlines the areas of competence and learning outcomes of "The Graduating European Dentist" that specifically relate to Safe and Effective Clinical Practice. Dentists are required to ensure that they are capable of providing appropriate care for their patients, whilst also effectively managing and leading the wider clinical team. The care that is provided should align to a contemporaneous evidence base wherever possible, and the quality of care and the management systems that underpin it should be regularly audited and improved.

The Graduating European Dentist: A New Undergraduate Curriculum Framework.

With "The Graduating European Dentist", ADEE provides a new approach that reflects best academic practice for European undergraduate dental education. The new suite of documents sees increased emphasis on important curriculum components such as patient safety, working as a team and patient-centred care. There is also an increased emphasis on teaching excellence, student satisfaction and student preparedness and support. Guidance relating to methods of teaching and learning, and assessment (educational measurement), is also provided. It is anticipated that this new format will further increase accessibility and utility for educators, institutions, societies and regulators, across the sector.

The Graduating European Dentist-Domain I: Professionalism.

This position paper outlines the areas of competence and learning outcomes of "The Graduating European Dentist" that specifically relate to Professionalism. Professionalism is a commitment to a set of values, behaviours and relationships, which underpin the trust that the public hold in dental care professionals. Shortcomings within this domain are often responsible for patient dissatisfaction, concern and complaint-and emphasis is placed on the importance of embedding these values from an early stage within the curriculum.

The Graduating European Dentist-Domain III: Patient-Centred Care.

This position paper outlines the areas of competence and learning outcomes of "The Graduating European Dentist" that specifically relate to patient-centred care. This approach is becoming increasingly prominent within the literature and within policy documents. Whilst working to an evidence base is critical, dentists must also be aware of the scientific basis that underpins the treatment they provide. The evaluation process, which supports treatment planning, also requires dentists to be able to listen, collate, and record pertinent information effectively. In addition, the ability to account for a patient's social, cultural and linguistic needs (cultural competence) will result in a practitioner who is able to treatment plan for patient-centred care.

The Graduating European Dentist: Contemporaneous Methods of Teaching, Learning and Assessment in Dental Undergraduate Education.

It is often the case that good teachers just "intuitively" know how to teach. Whilst that may be true, there is now a greater need to understand the various processes that underpin both the ways in which a curriculum is delivered, and the way in which the students engage with learning; curricula need to be designed to meet the changing needs of our new graduates, providing new, and robust learning opportunities, and be communicated effectively to both staff and students. The aim of this document is to draw together robust and contemporaneous methods of teaching, learning and assessment that help to overcome some of the more traditional barriers within dental undergraduate programmes. The methods have been chosen to map specifically to The Graduating European Dentist, and should be considered in parallel with the benchmarking process that educators and institutions employ locally.

UK Lung Cancer RCT Pilot Screening Trial: baseline findings from the screening arm provide evidence for the potential implementation of lung cancer screening.

BACKGROUND: Lung cancer screening using low-dose CT (LDCT) was shown to reduce lung cancer mortality by 20% in the National Lung Screening Trial. METHODS: The pilot UK Lung Cancer Screening (UKLS) is a randomised controlled trial of LDCT screening for lung cancer versus usual care. A population-based questionnaire was used to identify high-risk individuals. CT screen-detected nodules were managed by a pre-specified protocol. Cost effectiveness was modelled with reference to the National Lung Cancer Screening Trial mortality reduction. RESULTS: 247 354 individuals aged 50-75 years were approached; 30.7% expressed an interest, 8729 (11.5%) were eligible and 4055 were randomised, 2028 into the CT arm (1994 underwent a CT). Forty-two participants (2.1%) had confirmed lung cancer, 34 (1.7%) at baseline and 8 (0.4%) at the 12-month scan. 28/42 (66.7%) had stage I disease, 36/42 (85.7%) had stage I or II disease. 35/42 (83.3%) had surgical resection. 536 subjects had nodules greater than 50 mm(3) or 5 mm diameter and 41/536 were found to have lung cancer. One further cancer was detected by follow-up of nodules between 15 and 50 mm(3) at 12 months. The baseline estimate for the incremental cost-effectiveness ratio of once-only CT screening, under the UKLS protocol, was £8466 per quality adjusted life year gained (CI £5542 to £12 569). CONCLUSIONS: The UKLS pilot trial demonstrated that it is possible to detect lung cancer at an early stage and deliver potentially curative treatment in over 80% of cases. Health economic analysis suggests that the intervention would be cost effective-this needs to be confirmed using data on observed lung cancer mortality reduction. TRIAL REGISTRATION: ISRCTN 78513845.

Attitudes of clinicians following large-scale pharmacogenomics implementation.

Clinician attitudes toward multiplexed genomic testing may be vital to the success of translational programs. We surveyed clinicians at an academic medical center about their views on a large pharmacogenomics implementation, the PREDICT (Pharmacogenomic Resource for Enhanced Decisions in Care and Treatment) program. Participants were asked about test ordering, major factors influencing use of results, expectations of efficacy and responsibility for applying results to patient care. Virtually all respondents (99%) agreed that pharmacogenomics variants influence patients' response to drug therapy. The majority (92%) favored immediate, active notification when a clinically significant drug-genome interaction was present. However, clinicians were divided on which providers were responsible for acting on a result when a prescription change was indicated and whether patients should be directly notified of a significant result. We concluded genotype results were valued for tailoring prescriptions, but clinicians do not agree on how to appropriately assign clinical responsibility for actionable results from a multiplexed panel.The Pharmacogenomics Journal advance online publication, 11 August 2015; doi:10.1038/tpj.2015.57.

Social polymorphism in the sweat bee Lasioglossum (Evylaeus) calceatum.

Temperate-zone socially polymorphic sweat bees (Hymenoptera: Halictidae) are ideal model systems for elucidating the origins of eusociality, a major evolutionary transition. Bees express either social or solitary behaviour in different parts of their range, and social phenotype typically correlates with season length. Despite their obvious utility, however, socially polymorphic sweat bees have received relatively little attention with respect to understanding the origins of eusociality. Lasioglossum (Evylaeus) calceatum is a widespread sweat bee that is thought to be socially polymorphic, with important potential as an experimental model species. We first determined the social phenotype of L. calceatum at three sites located at different latitudes within the UK. We then investigated sociality in detail across two years at the southernmost site. We found that L. calceatum exhibits latitudinal social polymorphism within the UK; bees were solitary at our two northern sites but the majority of nests were social at our southern site. Sociality in the south was characterised by a relatively small mean of two and 3.5 workers per nest in each year, respectively, and a small to medium mean caste-size dimorphism of 6.6 %. Foundresses were smaller in our more northern and high altitude populations. Sociality is clearly less specialised than in some closely related obligately social species but probably more specialied than other polymorphic sweat bees. Our research provides a starting point for future experimental work to investigate mechanisms underlying social polymorphism in L. calceatum.

Surgeons' and trainees' perceived self-efficacy in operating theatre non-technical skills.

BACKGROUND: An important factor that may influence an individual's performance is self-efficacy, a personal judgement of capability to perform a particular task successfully. This prospective study explored newly qualified surgeons' and surgical trainees' self-efficacy in non-technical skills compared with their non-technical skills performance in simulated scenarios. METHODS: Participants undertook surgical scenarios challenging non-technical skills in two simulation sessions 6 weeks apart. Some participants attended a non-technical skills workshop between sessions. Participants completed pretraining and post-training surveys about their perceived self-efficacy in non-technical skills, which were analysed and compared with their performance in surgical scenarios in two simulation sessions. Change in performance between sessions was compared with any change in participants' perceived self-efficacy. RESULTS: There were 40 participants in all, 17 of whom attended the non-technical skills workshop. There was no significant difference in participants' self-efficacy regarding non-technical skills from the pretraining to the post-training survey. However, there was a tendency for participants with the highest reported self-efficacy to adjust their score downwards after training and for participants with the lowest self-efficacy to adjust their score upwards. Although there was significant improvement in non-technical skills performance from the first to second simulation sessions, a correlation between participants' self-efficacy and performance in scenarios in any of the comparisons was not found. CONCLUSION: The results suggest that new surgeons and surgical trainees have poor insight into their non-technical skills. Although it was not possible to correlate participants' self-belief in their abilities directly with their performance in a simulation, in general they became more critical in appraisal of their abilities as a result of the intervention.

Thin shell, high velocity inertial confinement fusion implosions on the national ignition facility.

Experiments have recently been conducted at the National Ignition Facility utilizing inertial confinement fusion capsule ablators that are 175 and 165 µm in thickness, 10% and 15% thinner, respectively, than the nominal thickness capsule used throughout the high foot and most of the National Ignition Campaign. These three-shock, high-adiabat, high-foot implosions have demonstrated good performance, with higher velocity and better symmetry control at lower laser powers and energies than their nominal thickness ablator counterparts. Little to no hydrodynamic mix into the DT hot spot has been observed despite the higher velocities and reduced depth for possible instability feedthrough. Early results have shown good repeatability, with up to 1/2 the neutron yield coming from α-particle self-heating.