Full PIC simulation of a first ACHIP experiment @ SINBAD

In laser illuminated dielectric accelerators (DLA) high acceleration gradients can be achieved due to high damage thresholds of the materials at optical frequencies. This is a necessity for developing more compact particle accelerator technologies. The Accelerator on a CHip International Program (ACHIP) funded by the Gordon and Betty Moore Foundation is researching such devices. DESY Hamburg is part of the collaboration. The dedicated accelerator research facility SINBAD is particularly well suited for DLA experiments at relativistic electron energies. High quality beams and short bunch lengths are anticipated from the ARES linac which is currently under construction at SINBAD. The aim of the experiment is the injection of a short electron bunch from the ARES linac into a DLA. In this study the results of one of the first possible experiments at the facility are estimated via a combination of particle-in-cell (PIC) and tracking simulations. ASTRA is used to simulate an electron bunch from the ARES linac at a suitable working point. The dielectric part of the setup will be simulated using the PIC code from CST Particle Studio incorporating the retrieved bunch from the ASTRA simulation. The energy spectra of the electron bunches are calculated as would be measured from a spectrometer dipole with and without the laser fields

Longitudinal phase space synthesis with tailored 3D-printable dielectric-lined waveguides

Longitudinal phase space manipulation is a critical and necessary component for advanced acceleration concepts, radiation sources and improving performances of X-ray free electron lasers. Here we present a simple and versatile method to semi-arbitrarily shape the longitudinal phase space of a charged bunch by using wakefields generated in tailored dielectric-lined waveguides. We apply the concept in simulation and provide examples for radiation generation and bunch compression. We finally discuss the manufacturing capabilities of a modern 3D printer and investigate how printing limitations, as well as the shape of the input LPS affect the performance of the device

Simulations and plans for possible DLA experiments at SINBAD

In this work we present the outlines of possible experiments for dielectric laser acceleration (DLA) of ultra-short relativistic electron bunches produced by the ARES linac, currently under construction at the SINBAD facility (DESY Hamburg). The experiments are to be performed as part of the Accelerator on a Chip International Program (ACHIP), funded by the Gordon and Betty Moore Foundation. At SINBAD we plan to test the acceleration of already pre-accelerated relativistic electron bunches in laser-illuminated dielectric grating structures. We present outlines of both the acceleration of ultra-short single bunches, as well as the option to accelerate phase-synchronous sub-fs microbunch trains. Here the electron bunch is conditioned prior to the injection by interaction with an external laser field in an undulator. This generates a sinusoidal energy modulation that is transformed into periodic microbunches in a subsequent chicane. The phase synchronization is achieved by driving both the modulation process and the DLA with the same laser pulse. In addition to the conceptual layouts and plans of the experiments we present start-to-end simulation results for different ARES working points.Comment: EAAC'17 conference proceeding

Learning to Do or Learning While Doing: Reinforcement Learning and Bayesian Optimisation for Online Continuous Tuning

Online tuning of real-world plants is a complex optimisation problem that continues to require manual intervention by experienced human operators. Autonomous tuning is a rapidly expanding field of research, where learning-based methods, such as Reinforcement Learning-trained Optimisation (RLO) and Bayesian optimisation (BO), hold great promise for achieving outstanding plant performance and reducing tuning times. Which algorithm to choose in different scenarios, however, remains an open question. Here we present a comparative study using a routine task in a real particle accelerator as an example, showing that RLO generally outperforms BO, but is not always the best choice. Based on the study's results, we provide a clear set of criteria to guide the choice of algorithm for a given tuning task. These can ease the adoption of learning-based autonomous tuning solutions to the operation of complex real-world plants, ultimately improving the availability and pushing the limits of operability of these facilities, thereby enabling scientific and engineering advancements.Comment: 17 pages, 8 figures, 2 table

Relationship between trying an electronic cigarette and subsequent cigarette experimentation in Scottish adolescents: a cohort study.

This project was funded by the UK National Institute for Health Research (NIHR) PHR project 10/3000/07.Background This study examines whether young never smokers in Scotland, UK, who have tried an e-cigarette are more likely than those who have not, to try a cigarette during the following year. Methods Prospective cohort survey conducted in four high schools in Scotland, UK during February/March 2015 (n=3807) with follow-up 1 year later. All pupils (age 11–18) were surveyed. Response rates were high in both years (87% in 2015) and 2680/3807 (70.4%) of the original cohort completed the follow-up survey. Analysis was restricted to baseline ‘never smokers’ (n=3001/3807), 2125 of whom were available to follow-up (70.8%). Results At baseline, 183 of 2125 (8.6%) never smokers had tried an e-cigarette and 1942 had not. Of the young people who had not tried an e-cigarette at baseline, 249 (12.8%) went on to try smoking a cigarette by follow-up. This compares with 74 (40.4%) of those who had tried an e-cigarette at baseline. This effect remained significant in a logistic regression model adjusted for smoking susceptibility, having friends who smoke, family members’ smoking status, age, sex, family affluence score, ethnic group and school (adjusted OR 2.42 (95% CI 1.63 to 3.60)). There was a significant interaction between e-cigarette use and smoking susceptibility and between e-cigarette use and smoking within the friendship group. Conclusions Young never smokers are more likely to experiment with cigarettes if they have tried an e-cigarette. Causality cannot be inferred, but continued close monitoring of e-cigarette use in young people is warranted.Publisher PDFPeer reviewe

Fractional Flow Reserve and Instantaneous Wave-Free Ratio as Predictors of the Placebo-Controlled Response to Percutaneous Coronary Intervention in Stable Single-Vessel Coronary Artery Disease: Physiology-Stratified Analysis of ORBITA

BACKGROUND: There are no data on how fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR) are associated with the placebo-controlled efficacy of percutaneous coronary intervention (PCI) in stable single-vessel coronary artery disease. METHODS: We report the association between prerandomization invasive physiology within ORBITA (Objective Randomised Blinded Investigation With Optimal Medical Therapy of Angioplasty in Stable Angina), a placebo-controlled trial of patients who have stable angina with angiographically severe single-vessel coronary disease clinically eligible for PCI. Patients underwent prerandomization research FFR and iFR assessment. The operator was blinded to these values. Assessment of response variables, treadmill exercise time, stress echocardiography score, symptom frequency, and angina severity were performed at prerandomization and blinded follow-up. Effects were calculated by analysis of covariance. The ability of FFR and iFR to predict placebo-controlled changes in response variables was tested by using regression modeling. RESULTS: Invasive physiology data were available in 196 patients (103 PCI and 93 placebo). At prerandomization, the majority had Canadian Cardiovascular Society class II or III symptoms (150/196, 76.5%). Mean FFR and iFR were 0.69±0.16 and 0.76±0.22, respectively; 97% had ≥1 positive ischemia tests. The estimated effect of PCI on between-arm prerandomization-adjusted total exercise time was 20.7 s (95% confidence interval [CI], -4.0 to 45.5; P=0.100) with no interaction of FFR (Pinteraction=0.318) or iFR (Pinteraction=0.523). PCI improved stress echocardiography score more than placebo (1.07 segment units; 95% CI, 0.70-1.44; P<0.00001). The placebo-controlled effect of PCI on stress echocardiography score increased progressively with decreasing FFR (Pinteraction<0.00001) and decreasing iFR (Pinteraction<0.00001). PCI did not improve angina frequency score significantly more than placebo (odds ratio, 1.64; 95% CI, 0.96-2.80; P=0.072) with no detectable evidence of interaction with FFR (Pinteraction=0.849) or iFR (Pinteraction=0.783). However, PCI resulted in more patient-reported freedom from angina than placebo (49.5% versus 31.5%; odds ratio, 2.47; 95% CI, 1.30-4.72; P=0.006) but neither FFR (Pinteraction=0.693) nor iFR (Pinteraction=0.761) modified this effect. CONCLUSIONS: In patients with stable angina and severe single-vessel disease, the blinded effect of PCI was more clearly seen by stress echocardiography score and freedom from angina than change in treadmill exercise time. Moreover, the lower the FFR or iFR, the greater the magnitude of stress echocardiographic improvement caused by PCI

Dobutamine stress echocardiography ischemia as a predictor of the placebo-controlled efficacy of percutaneous coronary intervention in stable coronary artery disease: the stress echo-stratified analysis of ORBITA

BACKGROUND: Dobutamine stress echocardiography is widely used to test for ischemia in patients with stable coronary artery disease. In this analysis, we studied the ability of the prerandomization stress echocardiography score to predict the placebo-controlled efficacy of percutaneous coronary intervention (PCI) within the ORBITA trial (Objective Randomised Blinded Investigation With Optimal Medical Therapy of Angioplasty in Stable Angina).METHODS: One hundred eighty-three patients underwent dobutamine stress echocardiography before randomization. The stress echocardiography score is broadly the number of segments abnormal at peak stress, with akinetic segments counting double and dyskinetic segments counting triple. The ability of prerandomization stress echocardiography to predict the placebo-controlled effect of PCI on response variables was tested by using regression modeling.RESULTS: At prerandomization, the stress echocardiography score was 1.56±1.77 in the PCI arm (n=98) and 1.61±1.73 in the placebo arm (n=85). There was a detectable interaction between prerandomization stress echocardiography score and the effect of PCI on angina frequency score with a larger placebo-controlled effect in patients with the highest stress echocardiography score (Pinteraction=0.031). With our sample size, we were unable to detect an interaction between stress echocardiography score and any other patient-reported response variables: freedom from angina (Pinteraction=0.116), physical limitation (Pinteraction=0.461), quality of life (Pinteraction=0.689), EuroQOL 5 quality-of-life score (Pinteraction=0.789), or between stress echocardiography score and physician-assessed Canadian Cardiovascular Society angina class (Pinteraction=0.693), and treadmill exercise time (Pinteraction=0.426).CONCLUSIONS: The degree of ischemia assessed by dobutamine stress echocardiography predicts the placebo-controlled efficacy of PCI on patient-reported angina frequency. The greater the downstream stress echocardiography abnormality caused by a stenosis, the greater the reduction in symptoms from PCI

Ponte et stratégie de la reproduction chez les femelles du tacaud Trisopterus luscus (Gadidés) du plateau continental de la Galice, nord-ouest de l'Espagne

[EN] Pouting, Trisopterus luscus is harvested commercially on the Galician shelf by the Spanish inshore artisanal fleet. In spite of a substantial decrease in pouting catches, fishery regulations are limited to size length restrictions. This study provides biological data including length-at-maturity based on histological methods, seasonal maturation, spawning and fecundity. A collection 443 females, from 17 to 42 cm in total length, were sampled from landings (December 2003 to December 2004). Pouting length-at-maturity was estimated as 19.2 cm on average. Pouting females in spawning condition were observed throughout the year and the number of developing oocytes ranged from 20 000 to 1 327 000. Peak spawning was observed between February and April, which correlated well with trends in gonadosomatic index, and inverse to condition factor and hepatosomatic index. Histological examination of the gonads revealed that pouting ovarian development organization is asynchronous, and fecundity is probably determinate.[FR] Le tacaud, Trisopterus luscus est pêché par la flotte artisanale espagnole. En dépit d'une diminution substantielle des captures de tacaud, la pêche est réglementée uniquement à partir d'une taille minimum commerciale. Cette étude fournit des données biologiques comprenant la taille à maturité sexuelle basée sur l'histologie, la maturation saisonnière, la ponte et la fécondité. Un échantillon de 443 femelles, de 17 à 42 cm longueur totale, est examiné à partir des débarquements durant une année (de décembre 2003 à décembre 2004). La taille moyenne à maturité sexuelle est estimée à 19,2 cm. Les femelles de tacaud en condition de ponte sont observée tout au long de l'année et le nombre d'ovocytes s'étend de 20 000 to 1 327 000 par individu. Les pics de ponte sont observés entre février et avril, ce qui est bien corrélé avec l'évolution du rapport gonado-somatique et inverse de celle du facteur de condition et du rapport hépato-somatique. L'étude histologique révèle que le développement ovarien chez le tacaud est asynchrone, et que la fécondité est probablement déterminée.Peer reviewe

Large-scale genome-wide analysis identifies genetic variants associated with cardiac structure and function

BACKGROUND: Understanding the genetic architecture of cardiac structure and function may help to prevent and treat heart disease. This investigation sought to identify common genetic variations associated with inter-individual variability in cardiac structure and function. METHODS: A GWAS meta-analysis of echocardiographic traits was performed, including 46,533 individuals from 30 studies (EchoGen consortium). The analysis included 16 traits of left ventricular (LV) structure, and systolic and diastolic function. RESULTS: The discovery analysis included 21 cohorts for structural and systolic function traits (n = 32,212) and 17 cohorts for diastolic function traits (n = 21,852). Replication was performed in 5 cohorts (n = 14,321) and 6 cohorts (n = 16,308), respectively. Besides 5 previously reported loci, the combined meta-analysis identified 10 additional genome-wide significant SNPs: rs12541595 near MTSS1 and rs10774625 in ATXN2 for LV end-diastolic internal dimension; rs806322 near KCNRG, rs4765663 in CACNA1C, rs6702619 near PALMD, rs7127129 in TMEM16A, rs11207426 near FGGY, rs17608766 in GOSR2, and rs17696696 in CFDP1 for aortic root diameter; and rs12440869 in IQCH for Doppler transmitral A-wave peak velocity. Findings were in part validated in other cohorts and in GWAS of related disease traits. The genetic loci showed associations with putative signaling pathways, and with gene expression in whole blood, monocytes, and myocardial tissue. CONCLUSION: The additional genetic loci identified in this large meta-analysis of cardiac structure and function provide insights into the underlying genetic architecture of cardiac structure and warrant follow-up in future functional studies. FUNDING: For detailed information per study, see Acknowledgments.This work was supported by a grant from the US National Heart, Lung, and Blood Institute (N01-HL-25195; R01HL 093328 to RSV), a MAIFOR grant from the University Medical Center Mainz, Germany (to PSW), the Center for Translational Vascular Biology (CTVB) of the Johannes Gutenberg-University of Mainz, and the Federal Ministry of Research and Education, Germany (BMBF 01EO1003 to PSW). This work was also supported by the research project Greifswald Approach to Individualized Medicine (GANI_MED). GANI_MED was funded by the Federal Ministry of Education and Research and the Ministry of Cultural Affairs of the Federal State of Mecklenburg, West Pomerania (contract 03IS2061A). We thank all study participants, and the colleagues and coworkers from all cohorts and sites who were involved in the generation of data or in the analysis. We especially thank Andrew Johnson (FHS) for generation of the gene annotation database used for analysis. We thank the German Center for Cardiovascular Research (DZHK e.V.) for supporting the analysis and publication of this project. RSV is a member of the Scientific Advisory Board of the DZHK. Data on CAD and MI were contributed by CARDIoGRAMplusC4D investigators. See Supplemental Acknowledgments for consortium details. PSW, JFF, AS, AT, TZ, RSV, and MD had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis