Radially polarized passively mode-locked thin-disk laser oscillator emitting sub-picosecond pulses with an average output power exceeding the 100 W level

We report on a high-power passively mode-locked radially polarized Yb:YAG thin-disk oscillator providing 125 W of average output power. To the best of our knowledge, this is the highest average power ever reported from a mode-locked radially polarized oscillator without subsequent amplification stages. Mode-locking was achieved by implementing a SESAM as the cavity end mirror and the radial polarization of the LG*01 mode was obtained by means of a circular Grating Waveguide Output Coupler. The repetition rate was 78 MHz. A pulse duration of 0.97 ps and a spectral bandwidth of 1.4 nm (FWHM) were measured at the maximum output power. This corresponds to a pulse energy of 1.6 μJ and a pulse peak power of 1.45 MW. A high degree of radial polarization of 97.3 ± 1% and an M2-value of 2.16 which is close to the theoretical value for the LG*01 doughnut mode were measured

Metabolomics as a Driver in Advancing Precision Medicine in Sepsis

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/138226/1/phar1974.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/138226/2/phar1974_am.pd

Cardiovascular Dysfunction Criteria in Critically Ill Children: The PODIUM Consensus Conference

CONTEXT Cardiovascular dysfunction is associated with poor outcomes in critically ill children. OBJECTIVE We aim to derive an evidence-informed, consensus-based definition of cardiovascular dysfunction in critically ill children. DATA SOURCES Electronic searches of PubMed and Embase were conducted from January 1992 to January 2020 using medical subject heading terms and text words to define concepts of cardiovascular dysfunction, pediatric critical illness, and outcomes of interest. STUDY SELECTION Studies were included if they evaluated critically ill children with cardiovascular dysfunction and assessment and/or scoring tools to screen for cardiovascular dysfunction and assessed mortality, functional status, organ-specific, or other patient-centered outcomes. Studies of adults, premature infants (≤36 weeks gestational age), animals, reviews and/or commentaries, case series (sample size ≤10), and non-English-language studies were excluded. Studies of children with cyanotic congenital heart disease or cardiovascular dysfunction after cardiopulmonary bypass were excluded. DATA EXTRACTION Data were abstracted from each eligible study into a standard data extraction form, along with risk-of-bias assessment by a task force member. RESULTS Cardiovascular dysfunction was defined by 9 elements, including 4 which indicate severe cardiovascular dysfunction. Cardiopulmonary arrest (>5 minutes) or mechanical circulatory support independently define severe cardiovascular dysfunction, whereas tachycardia, hypotension, vasoactive-inotropic score, lactate, troponin I, central venous oxygen saturation, and echocardiographic estimation of left ventricular ejection fraction were included in any combination. There was expert agreement (>80%) on the definition. LIMITATIONS All included studies were observational and many were retrospective. CONCLUSIONS The Pediatric Organ Dysfunction Information Update Mandate panel propose this evidence-informed definition of cardiovascular dysfunction

Inadequate intake of nutrients essential for neurodevelopment in children with fetal alcohol spectrum disorders (FASD)

This study evaluated dietary intake in children with fetal alcohol spectrum disorders (FASD). Pre-clinical research suggests that nutrient supplementation may attenuate cognitive and behavioral deficits in FASD. Currently, the dietary adequacy of essential nutrients in children with FASD is unknown. Dietary data were collected as part of a randomized, doubleblind controlled trial of choline supplementation in FASD. Participants included 31 children with FASD, ages 2.5 – 4.9 years at enrollment. Dietary intake data was collected three times during the nine month study via interview-administered 24-hour recalls with the Automated Self-Administered 24-hour Recall. Dietary intake of macronutrients and 17 vitamins/minerals from food were averaged across three data collection points. Observed nutrient intakes were compared to national dietary intake data of children ages 2 – 5 years (What we Eat in America, NHANES 2007–2008) and to the Dietary Reference Intakes. Compared to the dietary intakes of children in the NHANES sample, children with FASD had lower intakes of saturated fat, vitamin D, and calcium. The majority (>50%) of children with FASD did not meet the Recommended Dietary Allowance (RDA) or Adequate Intake (AI) for fiber, n-3 fatty acids, vitamin D, vitamin E, vitamin K, choline, and calcium. This pattern of dietary intake in children with FASD suggests that there may be opportunities to benefit from nutritional intervention. Supplementation with several nutrients including choline, vitamin D, and n-3 fatty acids, has been shown in animal models to attenuate the cognitive deficits of FASD. These results highlight the potential of nutritional clinical trials in FASD

Choline supplementation in children with fetal alcohol spectrum disorders: a randomized, double-blind, placebo-controlled trial

Background: Fetal alcohol spectrum disorders (FASDs) are conditions characterized by physical anomalies, neurodevelopmental abnormalities, and neurocognitive deficits, including intellectual, executive, and memory deficits. There are no specific biological treatments for FASDs, but rodent models have shown that prenatal or postnatal choline supplementation reduces cognitive and behavioral deficits. Potential mechanisms include phospholipid production for axonal growth and myelination, acetylcholine enhancement, and epigenetic effects

Infidelity of SARS-CoV Nsp14-Exonuclease Mutant Virus Replication Is Revealed by Complete Genome Sequencing

Most RNA viruses lack the mechanisms to recognize and correct mutations that arise during genome replication, resulting in quasispecies diversity that is required for pathogenesis and adaptation. However, it is not known how viruses encoding large viral RNA genomes such as the Coronaviridae (26 to 32 kb) balance the requirements for genome stability and quasispecies diversity. Further, the limits of replication infidelity during replication of large RNA genomes and how decreased fidelity impacts virus fitness over time are not known. Our previous work demonstrated that genetic inactivation of the coronavirus exoribonuclease (ExoN) in nonstructural protein 14 (nsp14) of murine hepatitis virus results in a 15-fold decrease in replication fidelity. However, it is not known whether nsp14-ExoN is required for replication fidelity of all coronaviruses, nor the impact of decreased fidelity on genome diversity and fitness during replication and passage. We report here the engineering and recovery of nsp14-ExoN mutant viruses of severe acute respiratory syndrome coronavirus (SARS-CoV) that have stable growth defects and demonstrate a 21-fold increase in mutation frequency during replication in culture. Analysis of complete genome sequences from SARS-ExoN mutant viral clones revealed unique mutation sets in every genome examined from the same round of replication and a total of 100 unique mutations across the genome. Using novel bioinformatic tools and deep sequencing across the full-length genome following 10 population passages in vitro, we demonstrate retention of ExoN mutations and continued increased diversity and mutational load compared to wild-type SARS-CoV. The results define a novel genetic and bioinformatics model for introduction and identification of multi-allelic mutations in replication competent viruses that will be powerful tools for testing the effects of decreased fidelity and increased quasispecies diversity on viral replication, pathogenesis, and evolution

Post–COVID-19 Conditions Among Children 90 Days After SARS-CoV-2 Infection

IMPORTANCE Little is known about the risk factors for, and the risk of, developing post-COVID-19 conditions (PCCs) among children. OBJECTIVES To estimate the proportion of SARS-CoV-2-positive children with PCCs 90 days after a positive test result, to compare this proportion with SARS-CoV-2-negative children, and to assess factors associated with PCCs. DESIGN, SETTING, AND PARTICIPANTS This prospective cohort study, conducted in 36 emergency departments (EDs) in 8 countries between March 7, 2020, and January 20, 2021, included 1884 SARS-CoV-2-positive children who completed 90-day follow-up; 1686 of these children were frequency matched by hospitalization status, country, and recruitment date with 1701 SARS-CoV-2-negative controls. EXPOSURE SARS-CoV-2 detected via nucleic acid testing. MAIN OUTCOMES AND MEASURES Post-COVID-19 conditions, defined as any persistent, new, or recurrent health problems reported in the 90-day follow-up survey. RESULTS Of 8642 enrolled children, 2368 (27.4%) were SARS-CoV-2 positive, among whom 2365 (99.9%) had index ED visit disposition data available; among the 1884 children (79.7%) who completed follow-up, the median age was 3 years (IQR, 0-10 years) and 994 (52.8%) were boys. A total of 110 SARS-CoV-2-positive children (5.8%; 95% CI, 4.8%-7.0%) reported PCCs, including 44 of 447 children (9.8%; 95% CI, 7.4%-13.0%) hospitalized during the acute illness and 66 of 1437 children (4.6%; 95% CI, 3.6%-5.8%) not hospitalized during the acute illness (difference. 5.3%; 95% CI, 2.5%-8.5%). Among SARS-CoV-2-positive children, the most common symptom was fatigue or weakness (21 [1.1%]). Characteristics associated with reporting at least 1 PCC at 90 days included being hospitalized 48 hours or more compared with no hospitalization (adjusted odds ratio [aOR], 2.67 [95% CI, 1.63-4.38]); having 4 or more symptoms reported at the index ED visit compared with 1 to 3 symptoms (4-6 symptoms: aOR, 2.35 [95% CI, 1.28-4.31]; >= 7 symptoms: aOR, 4.59 [95% CI, 2.50 8.44]); and being 14 years of age or older compared with younger than 1 year (aOR, 2.67 [95% CI, 1.43-4.99]). SARS-CoV-2-positive children were more likely to report PCCs at 90 days compared with those who tested negative, both among those who were not hospitalized (55 of 1295 [4.2%; 95% CI, 3.2%-5.5%] vs 35 of 1321[2.7%; 95% CI, 1.9%-3.7%]; difference, 1.6% [95% CI, 0.2%-3.0%]) and those who were hospitalized (40 of 391[10.2%; 95% CI, 7.4%-13.7%] vs 19 of 380 [5.0%; 95% CI, 3.0%-7.7%]; difference, 5.2% [95% CI, 1.5%-9.1%]). In addition, SARS-CoV-2 positivity was associated with reporting PCCs 90 days after the index ED visit (aOR, 1.63 [95% CI, 1.14-2.35]), specifically systemic health problems (eg, fatigue, weakness, fever; aOR, 2.44 [95% CI, 1.19-5.00]). CONCLUSIONS AND RELEVANCE In this cohort study, SARS-CoV-2 infection was associated with reporting PCCs at 90 days in children. Guidance and follow-up are particularly necessary for hospitalized children who have numerous acute symptoms and are older.This studywas supported by grants from the Canadian Institutes of Health Research (operating grant: COVID-19-clinical management); the Alberta Health Services-University of Calgary-Clinical Research Fund; the Alberta Children's Hospital Research Institute; the COVID-19 Research Accelerator Funding Track (CRAFT) Program at the University of California, Davis; and the Cincinnati Children's Hospital Medical Center Division of Emergency Medicine Small Grants Program. Dr Funk is supported by the University of Calgary Eyes-High PostDoctoral Research Fund. Dr Freedman is supported by the Alberta Children's Hospital Foundation Professorship in Child Health andWellness

Precision global health : a roadmap for augmented action

With increased complexity in various global health challenges comes a need for increased precision and the adoption of more tailored health interventions. Building on precision public health, we propose precision global health (PGH), an approach that leverages life sciences, social sciences, and data sciences, augmented with artificial intelligence (AI), in order to identify transnational problems and deliver targeted and impactful interventions through integrated and participatory approaches. With more than four billion Internet users across the globe and the accelerating power of AI, PGH taps on our current augmented capacity to collect, integrate, analyse and visualise large volumes of data, both non-specific and specific to health. With the support of governments and donors, and together with international and non-governmental organisations, universities and research institutions can generate innovative solutions to improve health and wellbeing of the most vulnerable populations around the world. In line with the Sustainable Development Goals, we propose here a road map for the development and implementation of PGH.https://jphe.amegroups.compm2021Immunolog

Actively Q-switched and mode-locked Tm³⁺-doped silicate 2 μm fiber laser for supercontinuum generation in fluoride fiber

A diode-pumped actively Q-switched and actively mode-locked Tm³⁺-doped double-clad silicate fiber laser is reported providing up to 5 W of average output power at ~60 kHz Q-switch envelope repetition rate and ~8 μJ subpulses with up to 2.4 kW peak power. Using this source as a pump laser for supercontinuum generation in a ZBLAN fiber, over 1080mWof supercontinuum from 1.9 μm to beyond 3.6 μm was obtained at an overall efficiency of 3.3% with respect to the diode pump power.3 page(s

High-average-power actively-mode-locked Tm³⁺ fiber lasers

Fiber lasers emitting in the 2 μm wavelength range doped with thulium ions can be used as highly efficient pump sources for nonlinear converters to generate mid-infrared radiation. For spectroscopic purposes, illumination and countermeasures, a broad mid-infrared emission spectrum is advantageous. This can be reached by supercontinuum generation in fibers, e.g. fluoride fibers, which up to now has, however, only been presented with either low average power, complex Raman-shifted 1.55 μm pump sources or multi-stage amplifier pump schemes. Here we present recent results of a new actively-mode-locked single-oscillator scheme that can provide the high-repetition rate sub-ns pump pulses needed for pumping supercontinuum generators. A thulium-doped silica fiber laser is presented that provides > 11 W of average power CW-mode-locked pulses at 38 MHz repetition rate at ~38 ps pulse width. Upgrading the setup to allow Q-switched mode-locked operation yields mode-locked 40 MHz pulses arranged in 60 kHz bunched Q-switch envelopes and thus increases further the available peak power. In this Q-switched mode-locked regime over 5 W of average power has been achieved.8 page(s