X-ray optics for the cavity-based X-ray free-electron laser.

A cavity-based X-ray free-electron laser (CBXFEL) is a possible future direction in the development of fully coherent X-ray sources. CBXFELs consist of a low-emittance electron source, a magnet system with several undulators and chicanes, and an X-ray cavity. The X-ray cavity stores and circulates X-ray pulses for repeated FEL interactions with electron pulses until the FEL reaches saturation. CBXFEL cavities require low-loss wavefront-preserving optical components: near-100%-reflectivity X-ray diamond Bragg-reflecting crystals, outcoupling devices such as thin diamond membranes or X-ray gratings, and aberration-free focusing elements. In the framework of the collaborative CBXFEL research and development project of Argonne National Laboratory, SLAC National Accelerator Laboratory and SPring-8, we report here the design, manufacturing and characterization of X-ray optical components for the CBXFEL cavity, which include high-reflectivity diamond crystal mirrors, a diamond drumhead crystal with thin membranes, beryllium refractive lenses and channel-cut Si monochromators. All the designed optical components have been fully characterized at the Advanced Photon Source to demonstrate their suitability for the CBXFEL cavity application.

Personalised perioperative dosing of ivabradine in noncardiac surgery: a single-centre, randomised, placebo-controlled, double-blind feasibility pilot trial.

BACKGROUND: Perioperative myocardial injury after noncardiac surgery is associated with postoperative mortality. Heart rate (HR) is an independent risk factor for perioperative myocardial injury. In this pilot trial we tested the feasibility of a randomised, placebo-controlled trial of personalised HR-targeted perioperative ivabradine. METHODS: This was a single-centre, randomised, placebo-controlled, double-blind, parallel group, feasibility pilot trial conducted at Geneva University Hospitals. We included patients ≥75 yr old or ≥45 yr old with cardiovascular risk factors planned for intermediate- or high-risk surgery. Patients were randomised to receive ivabradine (2.5, 5.0, or 7.5 mg) or placebo according to their HR, twice daily, from the morning of surgery until postoperative day 2. Primary outcomes were appropriate dosage and blinding success rates. RESULTS: Between October 2020 and January 2022, we randomised 78 patients (recruitment rate of 1.3 patients week-1). Some 439 of 444 study drug administrations were adequate (99% appropriate dosage rate). The blinding success rate was 100%. There were 137 (31%) administrations of Pill A (placebo in both groups for HR ≤70 beats min-1). Nine (11.5%) patients had a high-sensitive cardiac troponin T elevation ≥14 ng L-1 between any two measurements. The number of bradycardia episodes was eight in the placebo group and nine in the ivabradine group. CONCLUSIONS: This pilot study demonstrates the feasibility of, and provides guidance for, a future trial testing the efficacy of personalised perioperative ivabradine. Future studies should include patients at higher risk of cardiac complications. CLINICAL TRIAL REGISTRATION: NCT04436016.

High-brightness photocathodes through ultrathin surface layers on metals.

We report how ultrathin MgO films on Ag(001) surfaces can be used to control the emittance properties of photocathodes. In addition to substantially reducing the work function of the metal surface, the MgO layers also favorably influence the shape of the surface bands resulting in the generation of high-brightness electron beams. As the number of MgO surface layers varies from 0 to 3, the emitted electron beam becomes gradually brighter, reducing its transverse emittance to 0.06 mm mrad. We suggest the use of such photocathodes for the development of free-electron x-ray lasers and energy-recovery linac x-ray sources.

Teaching Adequate Prehospital Use of Personal Protective Equipment During the COVID-19 Pandemic: Development of a Gamified e-Learning Module.

BACKGROUND: The coronavirus disease (COVID-19) pandemic has led to increased use of personal protective equipment (PPE). Adequate use of this equipment is more critical than ever because the risk of shortages must be balanced against the need to effectively protect health care workers, including prehospital personnel. Specific training is therefore necessary; however, the need for social distancing has markedly disrupted the delivery of continuing education courses. Electronic learning (e-learning) may provide significant advantages because it requires neither the physical presence of learners nor the repetitive use of equipment for demonstration. OBJECTIVE: Inclusion of game mechanics, or "gamification," has been shown to increase knowledge and skill acquisition. The objective of this research was to develop a gamified e-learning module to interactively deliver concepts and information regarding the correct choice and handling of PPE. METHODS: The SERES framework was used to define and describe the development process, including scientific and design foundations. After we defined the target audience and learning objectives by interviewing the stakeholders, we searched the scientific literature to establish relevant theoretical bases. The learning contents were validated by infection control and prehospital experts. Learning mechanics were then determined according to the learning objectives, and the content that could benefit from the inclusion of game mechanics was identified. RESULTS: The literature search resulted in the selection and inclusion of 12 articles. In addition to gamification, pretesting, feedback, avoiding content skipping, and demonstrations using embedded videos were used as learning mechanics. Gamification was used to enhance the interactivity of the PPE donning and doffing sequences, which presented the greatest learning challenges. The module was developed with Articulate Storyline 3 to ensure that it would be compatible with a wide array of devices, as this software generates HTML5-compatible output that can be accessed on smartphones, tablets, and regular computers as long as a recent browser is available. CONCLUSIONS: A gamified e-learning module designed to promote better knowledge and understanding of PPE use among prehospital health care workers was created by following the SERES framework. The impact of this module should now be assessed by means of a randomized controlled trial.

Changes in Hepatic Blood Flow and Liver Function during Closed Abdominal Hyperthermic Intraperitoneal Chemotherapy following Cytoreduction Surgery.

BACKGROUND: The increase in intra-abdominal pressure (IAP) during closed abdominal hyperthermic intraperitoneal chemotherapy (HIPEC) leads to major haemodynamic changes and potential organ dysfunction. We investigated these effects on hepatic blood flow (HBF) and liver function in patients undergoing HIPEC following cytoreductive surgery and fluid management guided by dynamic preload indices. METHODS: In this prospective observational clinical study including 15 consecutive patients, we evaluated HBF by transesophageal echocardiography and liver function by determination of the indocyanine green plasma disappearance rate (ICG-PDR). Friedman's two-way analysis of variance by ranks and Wilcoxon signed-rank test were performed for statistical analysis. RESULTS: During HIPEC, HBF was markedly reduced, resulting in the loss of any pulsatile Doppler flow signal in all but one patient. The ICG-PDR, expressed as median (interquartile 25-75), decreased from 23 (20-30) %/min to 18 (12.5-19) %/min (p < 0.001). Despite a generous crystalloid infusion rate (27 (22-35) ml/kg/h), cardiac index decreased during the increased IAP period, inferior vena cava diameter decreased, stroke volume variation and pulse pressure variation increased, lung compliance dropped, and there was an augmentation in plateau pressure. All changes were significant (p < 0.001) and reversed to baseline values post HIPEC. CONCLUSION: Despite optimizing intravenous fluids during closed abdominal HIPEC, we observed a marked decrease in HBF and liver function. Both effects were transient and limited to the period of HIPEC but could influence the choice between closed or open abdominal cavity procedure for HIPEC and should be considered in similar clinical situations of increased IAP.

Seasonal palmar keratoderma in erythropoietic protoporphyria indicates autosomal recessive inheritance.

Erythropoietic protoporphyria (EPP) is an inherited disorder that results from partial deficiency of ferrochelatase (FECH). It is characterized clinically by acute photosensitivity and, in 2% of patients, liver disease. Inheritance is usually autosomal dominant with low penetrance but is recessive in about 4% of families. A cross-sectional study of 223 patients with EPP in the United Kingdom identified six individuals with palmar keratoderma. We now show that these and three additional patients, from six families, have an inherited subtype of EPP which is characterized by seasonal palmar keratoderma, relatively low erythrocyte protoporphyrin concentrations, and recessive inheritance. No patient had evidence of liver dysfunction; four patients had neurological abnormalities. Patients were hetero- or homoallelic for nine different FECH mutations; four of which were previously unreported. Prokaryotic expression predicted that FECH activities were 2.7-25% (mean 10.6%) of normal. Neither mutation type nor FECH activity provided an explanation for the unusual phenotype. Our findings show that palmar keratoderma is a clinical indicator of recessive EPP, identify a phenotype that occurs in 38% of reported families with recessive EPP that to our knowledge is previously unreported, and suggest that patients with this phenotype may carry a lower risk of liver disease than other patients with recessive EPP.