VUV frequency combs from below-threshold harmonics

Recent demonstrations of high-harmonic generation (HHG) at very high repetition frequencies (~100 MHz) may allow for the revolutionary transfer of frequency combs to the vacuum ultraviolet (VUV). This advance necessitates unifying optical frequency comb technology with strong-field atomic physics. While strong-field studies of HHG have often focused on above-threshold harmonic generation (photon energy above the ionization potential), for VUV frequency combs an understanding of below-threshold harmonic orders and their generation process is crucial. Here we present a new and quantitative study of the harmonics 7-13 generated below and near the ionization threshold in xenon gas. We show multiple generation pathways for these harmonics that are manifested as on-axis interference in the harmonic yield. This discovery provides a new understanding of the strong-field, below-threshold dynamics under the influence of an atomic potential and allows us to quantitatively assess the achievable coherence of a VUV frequency comb generated through below threshold harmonics. We find that under reasonable experimental conditions temporal coherence is maintained. As evidence we present the first explicit VUV frequency comb structure beyond the 3rd harmonic.Comment: 16 pages, 4 figures, 1 tabl

Analysis of dental care of children receiving comprehensive care under general anaesthesia at a teaching hospital in England

Objectives: This study aimed to analyse the characteristics of comprehensive dental care provided under general anaesthesia (CDGA) and to review the additional treatment required by children over the 6 years subsequent to CDGA. Method: Information collected from hospital records for the 6-year period following the first CDGA included the types of dental treatment performed at CDGA, the return rates for follow-up appointments, further treatment required subsequent to CDGA and the types of dental treatment performed at repeat DGA. Results: The study population consisted of 263 children, of whom 129 had a significant medical history, with mean age of 6.7 years. The results revealed that the waiting time for CDGA was significantly shorter in children who had a significant medical history, with 49 % being admitted for CDGA within 3 months of pre-GA assessment, as compared to 29 % of healthy children. 67 % of children had follow-up care recorded, with a slightly higher proportion of children with significant medical history returning for follow-up [70 % (90/129)] compared with 65 % (87/134) of healthy children. Re-treatment rates were 34 % (88/263), the majority of cases being treated under local analgesia (42/88). 34 of 263 children had repeat DGA (12.9 %). Of these 71 % (24/34) were children with significant medical history. The mean age at repeat DGA was 9 years. In 25 of 34 children (74 %), repeat DGA was due to trauma, oral pathology, supernumerary removal, hypomineralized teeth or new caries of previously sound or un-erupted teeth at CDGA. The ratio of extraction over restoration (excluding fissure sealants) performed at repeat DGA was 2.8, compared with the ratio of 1.3 in the initial CDGA. Conclusions: There was a higher ratio of extraction over restorations at the repeat DGA. This suggests that the prescribed treatments at repeat DGA were more aggressive as compared to the initial CDGA in 1997. The majority of the treatment required at repeat DGA was to treat new disease

A comparison of the cost-effectiveness of treatment of prolonged acute convulsive epileptic seizures in children across Europe

In the majority of children and adolescents with epilepsy, optimal drug therapy adequately controls their condition. However, among the remaining patients who are still uncontrolled despite mono-, bi- or tri-therapy with chronic anti-epileptic treatment, a rescue medication is required. In Western Europe, the licensed medications available for first-line treatment of prolonged acute convulsive seizures (PACS) vary widely, and so comparators for clinical and economic evaluation are not consistent. No European guidelines currently exist for the treatment of PACS in children and adolescents and limited evidence is available for the effectiveness of treatments in the community setting. The authors present cost-effectiveness data for BUCCOLAM® (midazolam oromucosal solution) for the treatment of PACS in children and adolescents in the context of the treatment pathway in seven European countries in patients from 6 months to 18 years. For each country, the health economic model consisted of a decision tree, with decision nodes informed by clinical data and expert opinion obtained via a Delphi methodology. The events modelled are those associated with a patient experiencing a seizure in the community setting. The model assessed the likelihood of medication being administered successfully and of seizure cessation. The associated resource use was also modelled, and ambulance call-outs and hospitalisations were considered. The patient's quality of life was estimated by clinicians, who completed a five-level EuroQol five dimensions questionnaire from the perspective of a child or adolescent suffering a seizure. Despite differences in current therapy, treatment patterns and healthcare costs in all countries assessed, BUCCOLAM was shown to be cost saving and offered increased health-related benefits for patients in the treatment of PACS compared with the current local standard of care

The Treatment In Morning versus Evening (TIME) study:Analysis of recruitment, follow-up and retention rates post-recruitment

Abstract Background The use of information technology (IT) is now the preferred method of capturing and storing clinical research data. The Treatment In Morning versus Evening (TIME) study predominantly uses electronic data capture and IT to compare morning dosing of hypertensive medication against evening dosing. Registration, consent, participant demographics and follow-up data are all captured via the study website. The aim of this article is to assess the success of the TIME methodology compared with similar studies. Methods To assess the TIME study, published literature on similar clinical trials was reviewed and compared against TIME recruitment, follow-up and email interaction data. Results The TIME website registered 31,695 individuals, 21,116 of whom were randomised. Recruitment cost per randomised participant varied by strategy: £17.40 by GP practice, £3.08 by UK Biobank and £58.82 for GoShare. Twelve-month follow-up retention rates were 96%. A total of 1089 participants have withdrawn from their assigned time of dosing, 2% of whom have declined follow-up by record linkage or further contact. When the TIME data are compared with similar study data, study recruitment is very successful. However, TIME suffers difficulties with participant follow-up and withdrawal rates similar to those of conventional studies. Conclusions The TIME study has been successful in recruitment. Follow-up, retention rates and withdrawal rates are all acceptable, but ongoing work is required to ensure participants remain engaged with the study. Various recruitment strategies are necessary, and all viable options should be encouraged to maintain participant engagement throughout the life of studies using IT

Validation of N-myristoyltransferase as an antimalarial drug target using an integrated chemical biology approach

Malaria is an infectious disease caused by parasites of the genus Plasmodium, which leads to approximately one million deaths per annum worldwide. Chemical validation of new antimalarial targets is urgently required in view of rising resistance to current drugs. One such putative target is the enzyme N-myristoyltransferase, which catalyses the attachment of the fatty acid myristate to protein substrates (N-myristoylation). Here, we report an integrated chemical biology approach to explore protein myristoylation in the major human parasite P. falciparum, combining chemical proteomic tools for identification of the myristoylated and glycosylphosphatidylinositol-anchored proteome with selective small-molecule N-myristoyltransferase inhibitors. We demonstrate that N-myristoyltransferase is an essential and chemically tractable target in malaria parasites both in vitro and in vivo, and show that selective inhibition of N-myristoylation leads to catastrophic and irreversible failure to assemble the inner membrane complex, a critical subcellular organelle in the parasite life cycle. Our studies provide the basis for the development of new antimalarials targeting N-myristoyltransferase

Enhancement of the high-field critical current density of superconducting MgB2 by proton irradiation

A relatively high critical temperature, Tc, approaching 40 K, places the recently-discovered superconductor magnesium diboride (MgB2) intermediate between the families of low- and copper-oxide-based high-temperature superconductors (HTS). Supercurrent flow in MgB2 is unhindered by grain boundaries, unlike the HTS materials. Thus, long polycrystalline MgB2 conductors may be easier to fabricate, and so could fill a potentially important niche of applications in the 20 to 30 K temperature range. However, one disadvantage of MgB2 is that in bulk material the critical current density, Jc, appears to drop more rapidly with increasing magnetic field than it does in the HTS phases. The magnitude and field dependence of Jc are related to the presence of structural defects that can "pin" the quantised magnetic vortices that permeate the material, and prevent them from moving under the action of the Lorentz force. Vortex studies suggest that it is the paucity of suitable defects in MgB2 that causes the rapid decay of Jc with field. Here we show that modest levels of atomic disorder, induced by proton irradiation, enhance the pinning, and so increase Jc significantly at high fields. We anticipate that chemical doping or mechanical processing should be capable of generating similar levels of disorder, and so achieve technologically-attractive performance in MgB2 by economically-viable routes.Comment: 5 pages, 4 figures, to be published in Nature (in press

Population‐based cohort study of outcomes following cholecystectomy for benign gallbladder diseases

Background The aim was to describe the management of benign gallbladder disease and identify characteristics associated with all‐cause 30‐day readmissions and complications in a prospective population‐based cohort. Methods Data were collected on consecutive patients undergoing cholecystectomy in acute UK and Irish hospitals between 1 March and 1 May 2014. Potential explanatory variables influencing all‐cause 30‐day readmissions and complications were analysed by means of multilevel, multivariable logistic regression modelling using a two‐level hierarchical structure with patients (level 1) nested within hospitals (level 2). Results Data were collected on 8909 patients undergoing cholecystectomy from 167 hospitals. Some 1451 cholecystectomies (16·3 per cent) were performed as an emergency, 4165 (46·8 per cent) as elective operations, and 3293 patients (37·0 per cent) had had at least one previous emergency admission, but had surgery on a delayed basis. The readmission and complication rates at 30 days were 7·1 per cent (633 of 8909) and 10·8 per cent (962 of 8909) respectively. Both readmissions and complications were independently associated with increasing ASA fitness grade, duration of surgery, and increasing numbers of emergency admissions with gallbladder disease before cholecystectomy. No identifiable hospital characteristics were linked to readmissions and complications. Conclusion Readmissions and complications following cholecystectomy are common and associated with patient and disease characteristics

The imperative for controlled mechanical stresses in unraveling cellular mechanisms of mechanotransduction

BACKGROUND: In vitro mechanotransduction studies are designed to elucidate cell behavior in response to a well-defined mechanical signal that is imparted to cultured cells, e.g. through fluid flow. Typically, flow rates are calculated based on a parallel plate flow assumption, to achieve a targeted cellular shear stress. This study evaluates the performance of specific flow/perfusion chambers in imparting the targeted stress at the cellular level. METHODS: To evaluate how well actual flow chambers meet their target stresses (set for 1 and 10 dyn/cm(2 )for this study) at a cellular level, computational models were developed to calculate flow velocity components and imparted shear stresses for a given pressure gradient. Computational predictions were validated with micro-particle image velocimetry (μPIV) experiments. RESULTS: Based on these computational and experimental studies, as few as 66% of cells seeded along the midplane of commonly implemented flow/perfusion chambers are subjected to stresses within ±10% of the target stress. In addition, flow velocities and shear stresses imparted through fluid drag vary as a function of location within each chamber. Hence, not only a limited number of cells are exposed to target stress levels within each chamber, but also neighboring cells may experience different flow regimes. Finally, flow regimes are highly dependent on flow chamber geometry, resulting in significant variation in magnitudes and spatial distributions of stress between chambers. CONCLUSION: The results of this study challenge the basic premise of in vitro mechanotransduction studies, i.e. that a controlled flow regime is applied to impart a defined mechanical stimulus to cells. These results also underscore the fact that data from studies in which different chambers are utilized can not be compared, even if the target stress regimes are comparable

Effect of different finishing and polishing techniques on the surface roughness of microfilled, hybrid and packable composite resins

Este estudo avaliou a rugosidade superficial (Ra, µm) de 2 resinas compostas microparticuladas (Durafill; Perfection), 1 híbrida (Filtek Z250) e 2 compactáveis (Surefil; Fill Magic), antes (baseline) e após a realização de 8 técnicas de acabamento e polimento. A rugosidade foi avaliada com rugosímetro. Dez espécimes de cada resina foram submetidos aos seguintes procedimentos: A - brocas cabide; B - pontas diamantadas fina/extrafina; C - sistema Sof-Lex; D - sistema Super-Snap; E - pontas de borracha + pastas de polimento; F - pontas diamantadas + pontas de borracha + pastas de polimento; G - pontas diamantadas + Sof-Lex; H - pontas diamantadas + Super-Snap. Os dados foram submetidos à análise de variância a dois critérios e teste de Tukey. Foi observada diferença estatisticamente significante (p<0.05) tanto entre as resinas compostas quanto entre as técnicas de acabamento/polimento. Para todas as resinas, a maior rugosidade foi produzida com o emprego das pontas diamantadas (Ra: 0.69-1.44 µm). O menor valor de rugosidade foi obtido com o sistema Sof-Lex (Ra: 0.11- 0.25 µm). A Durafill apresentou melhor lisura que a Perfection e a Z250, que apresentaram melhor lisura que as resinas compactáveis. A seqüência completa de discos Sof-Lex produziu a melhor lisura para todas as resinas. em áreas sem acesso aos discos, as pontas de borracha e pastas de polimento produziram lisura de superfície satisfatória para as resinas híbridas enquanto as brocas carbide produziram polimento adequado para as resinas compactáveis.This study examined the average surface roughness (Ra, µm) of 2 microfilled (Durafill and Perfection), 1 hybrid (Filtek Z250) and 2 packable composite resins (Surefil and Fill Magic), before (baseline) and after eight different finishing and polishing treatments. The surface roughness was assessed using a profilometer. Ten specimens of each composite resin were randomly subjected to one of the following finishing/polishing techniques: A - carbide burs; B - fine/extrafine diamond burs; C - Sof-Lex aluminum oxide discs; D - Super-Snap aluminum oxide discs; E - rubber polishing points + fine/extrafine polishing pastes; F - diamond burs + rubber polishing points + fine/extrafine polishing pastes; G - diamond burs + Sof-Lex system; H - diamond burs + Super-Snap system. Data were analyzed using two-way ANOVA and Tukey's HSD test. Significant differences (p<0.05) were detected among both the resins and the finishing/polishing techniques. For all resins, the use of diamond burs resulted in the greatest surface roughness (Ra: 0.69 to 1.44 µm). The lowest Ra means were obtained for the specimens treated with Sof-Lex discs (Ra: 0.11 to 0.25 µm). The Ra values of Durafill were lower than those of Perfection and Filtek Z250, and these in turn had lower Ra than the packable composite resins. Overall, the smoothest surfaces were obtained with the use the complete sequence of Sof-Lex discs. In areas that could not be reached by the aluminum oxide discs, the carbide burs and the association between rubber points and polishing pastes produced satisfactory surface smoothness for the packable and hybrid composite resins, respectively.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)UNESP Faculty of Dentistry of São Jose dos CamposUniversity of São Paulo Faculty of Dentistry of BauruFaculty of Dentistry of LinsUNESP Faculty of Dentistry of São Jose dos Campo