Ultrafast Diagnostics for Electron Beams from Laser Plasma Accelerators

We present an overview of diagnostic techniques for measuring key parameters of electron bunches from Laser Plasma Accelerators (LPAs). The diagnostics presented here were chosen because they highlight the unique advantages (e.g., diverse forms of electromagnetic emission) and difficulties (e.g., shot-to-shot variability) associated with LPAs. Non destructiveness and high resolution (in space and time and energy) are key attributes that enable the formation of a comprehensive suite of simultaneous diagnostics which are necessary for the full characterization of the ultrashort, but highly-variable electron bunches from LPAs

Clinical data for paediatric research: the Swiss approach : Proceedings of the National Symposium in Bern, Switzerland, Dec 5-6, 2019.

Continuous improvement of health and healthcare system is hampered by inefficient processes of generating new evidence, particularly in the case of rare diseases and paediatrics. Currently, most evidence is generated through specific research projects, which typically require extra encounters with patients, are costly and entail long delays between the recognition of specific needs in healthcare and the generation of necessary evidence to address those needs. The Swiss Personalised Health Network (SPHN) aims to improve the use of data obtained during routine healthcare encounters by harmonizing data across Switzerland and facilitating accessibility for research. The project "Harmonising the collection of health-related data and biospecimens in paediatric hospitals throughout Switzerland (SwissPedData)" was an infrastructure development project funded by the SPHN, which aimed to identify and describe available data on child health in Switzerland and to agree on a standardised core dataset for electronic health records across all paediatric teaching hospitals. Here, we describe the results of a two-day symposium that aimed to summarise what had been achieved in the SwissPedData project, to put it in an international context, and to discuss the next steps for a sustainable future. The target audience included clinicians and researchers who produce and use health-related data on children in Switzerland. The symposium consisted of state-of-the-art lectures from national and international keynote speakers, workshops and plenary discussions. This manuscript summarises the talks and discussions in four sections: (I) a description of the Swiss Personalized Health Network and the results of the SwissPedData project; (II) examples of similar initiatives from other countries; (III) an overview of existing health-related datasets and projects in Switzerland; and (IV) a summary of the lessons learned and future prospective from workshops and plenary discussions. Streamlined processes linking initial collection of information during routine healthcare encounters, standardised recording of this information in electronic health records and fast accessibility for research are essential to accelerate research in child health and make it affordable. Ongoing projects prove that this is feasible in Switzerland and elsewhere. International collaboration is vital to success. The next steps include the implementation of the SwissPedData core dataset in the clinical information systems of Swiss hospitals, the use of this data to address priority research questions, and the acquisition of sustainable funding to support a slim central infrastructure and local support in each hospital. This will lay the foundation for a national paediatric learning health system in Switzerland

The Bern Birth Cohort (BeBiCo) to study the development of the infant intestinal microbiota in a high-resource setting in Switzerland: rationale, design, and methods.

BACKGROUND Microbiota composition is fundamental to human health with the intestinal microbiota undergoing critical changes within the first two years of life. The developing intestinal microbiota is shaped by maternal seeding, breast milk and its complex constituents, other nutrients, and the environment. Understanding microbiota-dependent pathologies requires a profound understanding of the early development of the healthy infant microbiota. METHODS Two hundred and fifty healthy pregnant women (≥20 weeks of gestation) from the greater Bern area will be enrolled at Bern University hospital's maternity department. Participants will be followed as mother-baby pairs at delivery, week(s) 1, 2, 6, 10, 14, 24, 36, 48, 96, and at years 5 and 10 after birth. Clinical parameters describing infant growth and development, morbidity, and allergic conditions as well as socio-economic, nutritional, and epidemiological data will be documented. Neuro-developmental outcomes and behavior will be assessed by child behavior checklists at and beyond 2 years of age. Maternal stool, milk, skin and vaginal swabs, infant stool, and skin swabs will be collected at enrolment and at follow-up visits. For the primary outcome, the trajectory of the infant intestinal microbiota will be characterized by 16S and metagenomic sequencing regarding composition, metabolic potential, and stability during the first 2 years of life. Secondary outcomes will assess the cellular and chemical composition of maternal milk, the impact of nutrition and environment on microbiota development, the maternal microbiome transfer at vaginal or caesarean birth and thereafter on the infant, and correlate parameters of microbiota and maternal milk on infant growth, development, health, and mental well-being. DISCUSSION The Bern birth cohort study will provide a detailed description and normal ranges of the trajectory of microbiota maturation in a high-resource setting. These data will be compared to data from low-resource settings such as from the Zimbabwe-College of Health-Sciences-Birth-Cohort study. Prospective bio-sampling and data collection will allow studying the association of the microbiota with common childhood conditions concerning allergies, obesity, neuro-developmental outcomes , and behaviour. Trial registration The trial has been registered at www. CLINICALTRIALS gov , Identifier: NCT04447742

Wavefront Measurement for Laser-Guiding Diagnostic

The wavefront of a short laser pulse after interaction in a laser-plasma accelerator (LPA) was measured to diagnose laser-guiding quality. Experiments were performed on a 100 TW class laser at the LOASIS facility of LBNL using a hydrogenfilled capillary discharge waveguide. Laser-guiding with a pre-formed plasma channel allows the laser pulse to propagate over many Rayleigh lengths at high intensity and is crucial to accelerate electrons to the highest possible energy. Efficient coupling of laser energy into the plasma is realized when the laser and the channel satisfy a matched guiding condition, in which the wavefront remains flat within the channel. Using a wavefront sensor, the laser-guiding quality was diagnosed based on the wavefront of the laser pulse exiting the plasma channel. This wavefront diagnostic will contribute to achieving controlled, matched guiding in future experiments

Undulator-Based Laser Wakefield Accelerator Electron Beam Energy Spread and Emittance Diagnostic

The design and current status of experiments to couple the Tapered Hybrid Undulator (THUNDER) to the Lawrence Berkeley National Laboratory (LBNL) laser plasma accelerator (LPA) to measure electron beam energy spread and emittance are presented

Systems and technologies for objective evaluation of technical skills in laparoscopic surgery

Minimally invasive surgery is a highly demanding surgical approach regarding technical requirements for the surgeon, who must be trained in order to perform a safe surgical intervention. Traditional surgical education in minimally invasive surgery is commonly based on subjective criteria to quantify and evaluate surgical abilities, which could be potentially unsafe for the patient. Authors, surgeons and associations are increasingly demanding the development of more objective assessment tools that can accredit surgeons as technically competent. This paper describes the state of the art in objective assessment methods of surgical skills. It gives an overview on assessment systems based on structured checklists and rating scales, surgical simulators, and instrument motion analysis. As a future work, an objective and automatic assessment method of surgical skills should be standardized as a means towards proficiency-based curricula for training in laparoscopic surgery and its certification

Somatic mosaicism and common genetic variation contribute to the risk of very-early-onset inflammatory bowel disease

Abstract: Very-early-onset inflammatory bowel disease (VEO-IBD) is a heterogeneous phenotype associated with a spectrum of rare Mendelian disorders. Here, we perform whole-exome-sequencing and genome-wide genotyping in 145 patients (median age-at-diagnosis of 3.5 years), in whom no Mendelian disorders were clinically suspected. In five patients we detect a primary immunodeficiency or enteropathy, with clinical consequences (XIAP, CYBA, SH2D1A, PCSK1). We also present a case study of a VEO-IBD patient with a mosaic de novo, pathogenic allele in CYBB. The mutation is present in ~70% of phagocytes and sufficient to result in defective bacterial handling but not life-threatening infections. Finally, we show that VEO-IBD patients have, on average, higher IBD polygenic risk scores than population controls (99 patients and 18,780 controls; P < 4 × 10−10), and replicate this finding in an independent cohort of VEO-IBD cases and controls (117 patients and 2,603 controls; P < 5 × 10−10). This discovery indicates that a polygenic component operates in VEO-IBD pathogenesis

Congenital portosystemic shunt: characterization of a multisystem disease

OBJECTIVES Congenital portosystemic shunts (CPSSs) are rare but increasingly recognized as a cause of important multisystem morbidity. We present new cases and a systematic literature review and propose an algorithm for the identification and care of affected patients. METHODS We reviewed the charts of consecutive patients seen in our pediatric liver clinic between 2003 and 2010 and systematically reviewed the literature of cases with CPSS. RESULTS We identified 316 published cases and 12 patients in our own clinic. Of the published cases (177 male), 185 had an extrahepatic and 131 an intrahepatic portosystemic shunt. Diagnosis was made at any age, from prenatal to late adulthood. Cardiac anomalies were found in 22% of patients. The main complications were hyperammonemia/neurological abnormalities (35%), liver tumors (26%), and pulmonary hypertension or hepatopulmonary syndrome (18%). The spectrum of neurological involvement ranged from changes in brain imaging, subtle abnormalities on neuropsychological testing, through learning disabilities to overt encephalopathy. Spontaneous shunt closure occurred mainly in infants with intrahepatic shunts. Therapeutic interventions included shunt closure by surgery or interventional radiology techniques (35%) and liver transplantation (10%) leading to an improvement of symptoms in the majority. These findings mirror the observations in our own patients. CONCLUSIONS In this largest review of the reported clinical experience, we identify that children with CPSS may present with otherwise unexplained developmental delay, encephalopathy, pulmonary hypertension, hypoxemia, or liver tumors. When CPSS is diagnosed, children should be screened for all of these complications. Spontaneous closure of intrahepatic shunts may occur in infancy. Closure of the shunt is indicated in symptomatic patients and is associated with a favorable outcome

Observation of optical transition radiation from electron beams generated by laser plasma accelerator

Laser plasma accelerators (LPAs) have made great progress, achieving electron beam with energy up to 1 GeV from a centimeter scale capillary plasma waveguide. Here, we report the measurement of optical transition radiation (OTR) from the capillary-based LPA electron beams. Transition radiation images, produced by electrons passing through two separate foils (located at 2.3 m and 3.8 m away from the exit of the LPA) were recorded with a high resolution imaging system, respectively. Two magnetic quadrupole lenses were placed right after the capillary to focus and collimate the electron beams. Significant localized spikes appeared in the OTR images when the electron beam was focused by the magnetic quadrupole lenses, indicating the coherence of the radiation and the existence of ultrashort longitudinal structures inside the electron beam. © 2013 Chinese Physical Society and the Institute of High Energy Physics of the Chinese Academy of Sciences and the Institute of Modern Physics of the Chinese Academy of Sciences and IOP Publishing Ltd

Impact of Diagnostic Delay on Disease Course in Pediatric- versus Adult-Onset Patients with Ulcerative Colitis: Data from the Swiss IBD Cohort.

Given the lack of data, we aimed to assess the impact of the length of diagnostic delay on the natural history of ulcerative colitis (UC) in pediatric (diagnosed &lt;18 years) and adult patients (diagnosed ≥18 years). Data from the Swiss Inflammatory Bowel Disease Cohort Study were analyzed. Diagnostic delay was defined as the interval between the first appearance of UC-related symptoms until diagnosis. Logistic regression modeling evaluated the appearance of the following complications in the long term according to the length of diagnostic delay: colonic dysplasia, colorectal cancer, UC-related hospitalization, colectomy, and extraintestinal manifestations (EIMs). A total of 184 pediatric and 846 adult patients were included. The median diagnostic delay was 4 [IQR 2-7.5] months for the pediatric-onset group and 3 [IQR 2-10] months for the adult-onset group (p = 0.873). In both, pediatric- and adult-onset groups, the length of diagnostic delay at UC diagnosis was not associated with colectomy, UC-related hospitalization, colon dysplasia, and colorectal cancer. EIMs were significantly more prevalent at UC diagnosis in the adult-onset group with long diagnostic delay than in the adult-onset group with short diagnostic delay (p = 0.022). In the long term, the length of diagnostic delay was associated in the adult-onset group with colorectal dysplasia (p = 0.023), EIMs (p &lt; 0.001), and more specifically arthritis/arthralgias (p &lt; 0.001) and ankylosing spondylitis/sacroiliitis (p &lt; 0.001). In the pediatric-onset UC group, the length of diagnostic delay in the long term was associated with arthritis/arthralgias (p = 0.017); however, it was not predictive for colectomy and UC-related hospitalization. As colorectal cancer and EIMs are associated with considerable morbidity and costs, every effort should be made to reduce diagnostic delay in UC patients