Ultrabroadband flying-focus using an axiparabola-echelon pair.

Flying-focus pulses promise to revolutionize laser-driven secondary sources by decoupling the trajectory of the peak intensity from the native group velocity of the medium over distances much longer than a Rayleigh range. Previous demonstrations of the flying focus have either produced an uncontrolled trajectory or a trajectory that is engineered using chromatic methods that limit the duration of the peak intensity to picosecond scales. Here we demonstrate a controllable ultrabroadband flying focus using a nearly achromatic axiparabola-echelon pair. Spectral interferometry using an ultrabroadband superluminescent diode was used to measure designed super- and subluminal flying-focus trajectories and the effective temporal pulse duration as inferred from the measured spectral phase. The measurements demonstrate that a nearly transform- and diffraction-limited moving focus can be created over a centimeter-scale-an extended focal region more than 50 Rayleigh ranges in length. This ultrabroadband flying-focus and the novel axiparabola-echelon configuration used to produce it are ideally suited for applications and scalable to >100 TW peak powers.

Modeling of a spatially resolved ion temperature diagnostic for inertial confinement fusion.

The performance of modern laser-driven inertial confinement fusion (ICF) experiments is degraded by contamination of the deuterium-tritium (DT) fuel with high-Z material during compression. Simulations suggest that this mix can be described by the ion temperature distribution of the implosion, given that such contaminants deviate in temperature from the surrounding DT plasma. However, existing neutron time-of-flight (nTOF) diagnostics only measure the spatially integrated ion temperature. This paper describes the techniques and forward modeling used to develop a novel diagnostic imaging system to measure the spatially resolved ion temperature of an ICF implosion for the first time. The technique combines methods in neutron imaging and nTOF diagnostics to measure the ion temperature along one spatial dimension at yields currently achievable on the OMEGA laser. A detailed forward model of the source and imaging system was developed to guide instrument design. The model leverages neutron imaging reconstruction algorithms, radiation hydrodynamics and Monte Carlo simulations, optical ray tracing, and more. The results of the forward model agree with the data collected on OMEGA using the completed diagnostic. The analysis of the experimental data is still ongoing and will be discussed in a separate publication.

Calibration of the sub-aperture backscatter system on OMEGA EP.

The sub-aperture backscatter (SABS) diagnostic on the OMEGA EP Laser System [Waxer et al., Opt. Photonics News 16, 30 (2005)] is a diagnostic that is used to measure the backscattered and sidescattered light during laser-plasma interaction experiments [W. L. Kruer, The Physics of Laser Plasma Interactions, Frontiers in Physics Vol. 73, edited by D. Pines (Addison-Wesley, Redwood City, CA, 1988) and Myatt et al., Phys. Plasmas 21, 055501 (2014)] that are relevant to high-energy-density physics and inertial confinement fusion. The diagnostic collects stimulated Brillouin scattering (SBS) UV light at around 351 nm and stimulated Raman scattering (SRS) in the visible-light regime in the 420-720-nm-wavelength range and provides spectrally and temporally resolved information. Five 1-in. light collectors, composed of a lens, ground glass diffuser, and coupling into a 300-µm fiber, are positioned behind the last steering mirror on one of the four beamlines to catch a portion of the beam cross section (∼1.5%) of the emission that is scattered into the beamline. The SRS light is collected in two light collectors, combined, and transported via graded index fibers to a streaked spectrometer. The SABS-SRS streak spectrometer has a temporal and spectral resolution of 100 ps and 1 nm, respectively. Three other light collectors collect, combine, and transport the SBS signal to a Hamamatsu high-voltage photodiode, where an oscilloscope digitizes the data, providing a time resolution of better than 1 ns. To obtain an absolute energy calibration of SRS measurements, light signals of known energy and wavelength were injected into the light collectors one at a time. The resulting counts on the streak camera charge-coupled device for SRS are then correlated with the incident fluence of scattered light at the light collector in order to allow a quantitative assessment of streak camera sensitivity to determine the energy of the scattered light during experiments. The measurements were performed in situ from the light collectors to the detectors. Additional offline measurements provided the transmission of the optics between the target chamber center and the light collectors.

Vulnerable newborn types: analysis of subnational, population-based birth cohorts for 541 285 live births in 23 countries, 2000-2021.

OBJECTIVE: To examine prevalence of novel newborn types among 541 285 live births in 23 countries from 2000 to 2021. DESIGN: Descriptive multi-country secondary data analysis. SETTING: Subnational, population-based birth cohort studies (n = 45) in 23 low- and middle-income countries (LMICs) spanning 2000-2021. POPULATION: Liveborn infants. METHODS: Subnational, population-based studies with high-quality birth outcome data from LMICs were invited to join the Vulnerable Newborn Measurement Collaboration. We defined distinct newborn types using gestational age (preterm [PT], term [T]), birthweight for gestational age using INTERGROWTH-21st standards (small for gestational age [SGA], appropriate for gestational age [AGA] or large for gestational age [LGA]), and birthweight (low birthweight, LBW [<2500 g], nonLBW) as ten types (using all three outcomes), six types (by excluding the birthweight categorisation), and four types (by collapsing the AGA and LGA categories). We defined small types as those with at least one classification of LBW, PT or SGA. We presented study characteristics, participant characteristics, data missingness, and prevalence of newborn types by region and study. RESULTS: Among 541 285 live births, 476 939 (88.1%) had non-missing and plausible values for gestational age, birthweight and sex required to construct the newborn types. The median prevalences of ten types across studies were T+AGA+nonLBW (58.0%), T+LGA+nonLBW (3.3%), T+AGA+LBW (0.5%), T+SGA+nonLBW (14.2%), T+SGA+LBW (7.1%), PT+LGA+nonLBW (1.6%), PT+LGA+LBW (0.2%), PT+AGA+nonLBW (3.7%), PT+AGA+LBW (3.6%) and PT+SGA+LBW (1.0%). The median prevalence of small types (six types, 37.6%) varied across studies and within regions and was higher in Southern Asia (52.4%) than in Sub-Saharan Africa (34.9%). CONCLUSIONS: Further investigation is needed to describe the mortality risks associated with newborn types and understand the implications of this framework for local targeting of interventions to prevent adverse pregnancy outcomes in LMICs.

Inverse Bremsstrahlung Absorption.

Inverse bremsstrahlung absorption was measured based on transmission through a finite-length plasma that was thoroughly characterized using spatially resolved Thomson scattering. Expected absorption was then calculated using the diagnosed plasma conditions while varying the absorption model components. To match data, it is necessary to account for (i) the Langdon effect; (ii) laser-frequency (rather than plasma-frequency) dependence in the Coulomb logarithm, as is typical of bremsstrahlung theories but not transport theories; and (iii) a correction due to ion screening. Radiation-hydrodynamic simulations of inertial confinement fusion implosions have to date used a Coulomb logarithm from the transport literature and no screening correction. We anticipate that updating the model for collisional absorption will substantially revise our understanding of laser-target coupling for such implosions.

Does gabapentin provide benefit for patients with knee OA? A benefit-harm and cost-effectiveness analysis.

OBJECTIVE: Gabapentin can treat neuropathic pain syndromes and has increasingly been prescribed to treat nociplastic pain. Some patients with knee osteoarthritis (OA) suffer from both nociceptive and nociplastic pain. We examined the cost-effectiveness of adding gabapentin to knee OA care. METHOD: We used the Osteoarthritis Policy Model, a validated Monte Carlo simulation of knee OA, to examine the value of gabapentin in treating knee OA by comparing three strategies: 1) usual care, gabapentin sparing (UC-GS); 2) targeted gabapentin (TG), which provides gabapentin plus usual care for those who screen positive for nociplastic pain on the modified PainDETECT questionnaire (mPD-Q) and usual care only for those who screen negative; and 3) universal gabapentin plus usual care (UG). Outcomes included cumulative quality-adjusted life years (QALYs), lifetime direct medical costs, and incremental cost-effectiveness ratios (ICERs), discounted at 3% annually. We derived model inputs from published literature and national databases and varied key input parameters in sensitivity analyses. RESULTS: UC-GS dominated both gabapentin-containing strategies, as it led to lower costs and more QALYs. TG resulted in a cost increase of $689 and a cumulative QALY reduction of 0.012 QALYs. UG resulted in a further $1,868 cost increase and 0.036 QALY decrease. The results were robust to plausible changes in input parameters. The lowest TG strategy ICER of $53,000/QALY was reported when mPD-Q specificity was increased to 100% and AE rate was reduced to 0%. CONCLUSION: Incorporating gabapentin into care for patients with knee OA does not appear to offer good value.

Effectiveness of remote exercise programs in reducing pain for patients with knee osteoarthritis: A systematic review of randomized trials.

Objective: Remote knee osteoarthritis (OA) management programs are becoming more popular. This systematic review examined the efficacy of remote exercise programs for relieving pain in persons with knee OA. Design: We conducted a search of studies published between January 1st, 2013 to March 31st, 2021 in PubMed, Embase, and MEDLINE. We included randomized trials of patients with knee OA or chronic knee pain, studying interventions with an element of telehealth exercise management, and evaluating knee pain as an outcome. Interventions could include fully remote or both remote and in-person components. We excluded observational cohort studies, pilot studies, and studies with poor Physiotherapy Exercise Database (PEDro) scores. Two reviewers extracted pain data, consisting of mean differences from baseline and between groups, and compared them to minimum clinically important difference (MCID) thresholds. Results: We identified 1867 reports, of which eleven trials with a total of 1861 participants met inclusion criteria. Only one trial demonstrated a clinically meaningful change from baseline between groups. Four interventions were found to result in clinically meaningful improvements in pain from baseline. Conclusion: This review was limited by variability in outcome measures, intervention content, and comparators. One trial with an inactive control demonstrated clinically meaningful between group differences in pain. All four interventions demonstrating meaningful improvements from baseline included study-initiated communications to discuss and personalize remotely delivered exercise programs. More studies comparing fully or partially remote exercise programs with both active and inactive controls could help optimize the use of remote programs for management of knee OA pain.

Instrument design for an inertial confinement fusion ion temperature imager.

A mix of contaminant mass is a known, performance-limiting factor for laser-driven inertial confinement fusion (ICF). It has also recently been shown that the contaminant mass is not necessarily in thermal equilibrium with the deuterium-tritium plasma [B. M. Haines et al., Nat. Commun. 11, 544 (2020)]. Contaminant mass temperature is one of the dominant uncertainties in contaminant mass estimates. The MixIT diagnostic is a new and potentially transformative diagnostic, capable of spatially resolving ion temperature. The approach combines principles of neutron time-of-flight and neutron imaging diagnostics. The information from the MixIT diagnostic can be used to optimize ICF target and laser drive designs as well as provide key constraints on ICF radiation-hydrodynamic simulations that are critical to contaminant mass estimates. This work details the design and optimization of the major components of the MixIT diagnostic: the neutron aperture, the neutron detector (scintillator), and the recording system.

Measurement of laser absorption in underdense plasmas using near-field imaging of the incident and transmitted beams.

Measurements of laser absorption in high-temperature, underdense plasmas produced at the Omega Laser Facility are made using two near-field imaging detectors that diagnose the spatial profile and energy of the port P9 beam before and after it transmits through the plasma. The incident beam is sampled using a partial reflection from a full-aperture, (30 cm-diam) uncoated wedge pickoff located before the target chamber vacuum window and final focus lens assembly. A concave mirror reduces the reflected beam size, allowing it to be recorded directly using a charged-coupled device (CCD) camera. The P9 transmitted beam diagnostic (P9TBD) characterizes the transmitted light by terminating the expanded beam on a semi-transparent diffuser and imaging the illuminated surface using a lens and CCD camera. The P9TBD samples a numerical aperture twice as large as the input beam, allowing the energy of transmitted beams with moderate levels of beam spray to be measured accurately. Calibration shots with no plasma provide a path to infer absorption without absolute photometric calibration of either detector. The cross-calibration between the two detectors was measured to remain stable at ±200 ppm, enabling measurements of total beam absorption below 1% with ±0.07% error.

Scattered-light uniformity imager for diagnosing laser absorption asymmetries on OMEGA.

Light scattered from a target is the most-direct measurement for diagnosing laser absorption in a direct-drive implosion. Observations from OMEGA implosions show much larger scattered-light asymmetries than predictions. A new instrument has been developed to absolutely measure the scattered-light intensity and nonuniformity for the purpose of diagnosing the asymmetry. The scattered-light uniformity imager (SLUI) diagnostic records the variation in scattered-light intensity over a transmission diffuser using a charge-coupled device (CCD)/lens assembly. At the standard operating position, an 11.3° (f/2.5) cone of light is collected. A stray light baffle, debris shield, and antireflection absorbing filter are also incorporated into the diagnostic payload inserted into the target chamber. The imaging parts of the diagnostic (light baffle, vacuum window, filters, lens, and CCD camera) are located outside the target chamber. Five SLUIs have been built and deployed in OMEGA's ten-inch manipulator diagnostic ports, covering almost 5% of the emission surface, enabling an absolute scattered-light measurement should be within a few percent of the global average. Each SLUI system is calibrated offline, providing absolute scattered-light intensity measurements. Based on the measured point spread function, each diffuser plate image contains over 20 000 independent scattered-light absolute-intensity measurements of the variation over the collection cone. SLUI provides a platform to study scattered light and absorption asymmetries, and their possible sources.

The phase-2 particle x-ray temporal diagnostic for simultaneous measurement of multiple x-ray and nuclear emission histories from OMEGA implosions (invited).

Electron-temperature (Te) measurements in implosions provide valuable diagnostic information, as Te is negligibly affected by residual flows and other non-thermal effects unlike ion-temperature inferred from a fusion product spectrum. In OMEGA cryogenic implosions, measurement of Te(t) can be used to investigate effects related to time-resolved hot-spot energy balance. The newly implemented phase-2 Particle X-ray Temporal Diagnostic (PXTD) utilizes four fast-rise (∼15 ps) scintillator-channels with distinct x-ray filtering. Titanium and stepped aluminum filtering were chosen to maximize detector sensitivity in the 10-20 keV range, as it has been shown that these x rays have similar density and temperature weighting to the emitted deuterium-tritium fusion neutrons (DTn) from OMEGA Cryo-DT implosions. High quality data have been collected from warm implosions at OMEGA. These data have been used to infer spatially integrated Te(t) with <10% uncertainty at peak emission. Nuclear and x-ray emission histories are measured with 10 ps relative timing uncertainty for x rays and DTn and 12 ps for x rays and deuterium-He3 protons (D3Hep). A future upgrade to the system will enable spatially integrated Te(t) with 40 ps time-resolution from cryogenic DT implosions.

Direct Measurement of the Return Current Instability in a Laser-Produced Plasma.

Measurements were made of the return current instability growth rate, demonstrating its concurrence with nonlocal transport. Thomson scattering was used to measure a maximum growth rate of 5.1×10^{9} Hz, which was 3 times less than classical Spitzer-Härm theory predicts. The measured plasma conditions indicate the heat flux was nonlocal, and Vlasov-Fokker-Planck simulations that account for nonlocality reproduce the measured growth rates. Furthermore, the threshold for the return current instability was measured (δ_{T}=0.017±0.002) to be in good agreement with previous theoretical models.

Treatment of the syndrome of knee pain and meniscal tear in middle-aged and older persons: A narrative review.

Objective: To summarize the literature investigating management, treatment strategies, short- and longer-term outcomes of treatment for meniscal tear in middle-aged and older adults. Design: We performed a literature search using PubMed to identify relevant articles and selected 15 for a narrative summary on the available evidence. Results: The literature suggests that middle-age and older adults with meniscal tear may benefit from initial physical therapy (PT) potentially followed by arthroscopic partial meniscectomy (APM) for those who do not experience sufficient benefit after PT and in whom other sources of pain are deemed unlikely. There is moderate evidence to suggest that some factors at baseline, such as radiographic OA, meniscal tear type, and pain at baseline may influence outcomes after APM. Over time, APM appears to increase the risk of degenerative changes in cartilage, bone, and other knee structures as evidenced by radiograph and MRI-based assessments. Conclusion: Evidence from research investigating outcomes of treatment for meniscal tear in middle-aged and older adults demonstrates that PT is a reasonable initial treatment. More research is needed to investigate the best treatment for those who do not benefit substantially from initial PT. The evidence also demonstrates that APM may be associated with greater risk of radiographic osteoarthritic changes, though more research and the addition of enhanced quantitative MRI-assessments are needed to further detail any compositional changes in the knee. Focusing on these areas of further study will clarify whether these imaging findings are clinically meaningful.

Apparatus for measuring strength in biaxial compression.

Most measurements of compressive strength of ductile materials have involved Hopkinson-Kolsky bars or Taylor anvils placing samples in uniaxial compression. In these geometries, strain is limited by the tendency of the sample to petal, in analogy to necking in uniaxial tension. Estimation of strength for any other form of the stress tensor requires assuming a shape of the yield surface; because data exist only for uniaxial compression, these assumptions are untested. In an imploding spherical shell, compression is biaxial, the plastic strain may not be small, and the material behavior may be nonlinear as a result of work hardening and heating by plastic work. We outline a method of measuring the strengths of materials in biaxial compression, both quasistatically and dynamically, using the compression of thin spherical shells. We suggest surrounding the shell with an annulus filled with a mixture of H2 and Cl2 gases whose homogeneous ignition is initiated by a flash of blue and near-ultraviolet light. Less promising approaches are described in Appendixes A-C.

Quantitative assessment of fitting errors associated with streak camera noise in Thomson scattering data analysis.

Thomson scattering measurements in high energy density experiments are often recorded using optical streak cameras. In the low-signal regime, noise introduced by the streak camera can become an important and sometimes the dominant source of measurement uncertainty. In this paper, we present a formal method of accounting for the presence of streak camera noise in our measurements. We present a phenomenological description of the noise generation mechanisms and present a statistical model that may be used to construct the covariance matrix associated with a given measurement. This model is benchmarked against simulations of streak camera images. We demonstrate how this covariance may then be used to weight fitting of the data and provide quantitative assessments of the uncertainty in the fitting parameters determined by the best fit to the data and build confidence in the ability to make statistically significant measurements in the low-signal regime, where spatial correlations in the noise become apparent. These methods will have general applicability to other measurements made using optical streak cameras.

Novel design for a polarizing DUV spectrometer using a Wollaston prism and its application as a diagnostic for measuring Thomson scattering data in the presence of strong self-emission backgrounds.

We present a novel design for an optical spectrometer for use in ultraviolet Thomson scattering measurements of plasma parameters in high energy density (HED) inertial confinement fusion experiments on large-scale high-energy laser facilities. In experiments investigating high-Z plasmas, the fidelity of measurements is commonly limited by signal/background ratios approaching or exceeding unity. An alpha barium borate Wollaston prism can provide both spectral dispersion and polarization channel separation, allowing simultaneous measurement of both the Thomson scattering signal and plasma self-emission along a single line of sight and in a single experiment, which should greatly improve data quality and reduce the opportunity cost of taking high quality measurements. We present a basic discussion of the design and a worked example of an instrument designed to take fourth harmonic electron plasma wave measurements in HED experiments at the OMEGA laser facility.

Humoral and T-cell responses to SARS-CoV-2 vaccination in multiple sclerosis patients treated with ocrelizumab.

BACKGROUND: The COVID-19 epidemic raises important questions about the efficacy of vaccines for people treated with ocrelizumab, an anti-CD20 therapy. Ocrelizumab has been shown to reduce the humoral response to SARS-CoV-2 infection and vaccination, but the T-cell response to vaccination has not been fully characterized. We sought to provide data regarding B and T-cell mediated responses to SARS-CoV-2 vaccination in ocrelizumab-treated patients, and to determine what variables correlate with vaccine immunogenicity. We hypothesized that patients without a humoral response to SARS-CoV-2 vaccination would still have intact T-cell responses. METHODS: We conducted a prospective, observational, single center cohort study of patients with MS treated with either ocrelizumab or natalizumab as a comparator between March 2, 2021, and July 1, 2021. Eligible patients were age 18 to 55 and had no known prior infection with, or vaccination against, SARS-CoV-2. Patients with prior use of immunosuppressive or chemotherapeutic agents, or treatment with any anti-CD20 therapy other than ocrelizumab within 12 months of enrollment, were excluded. The Roche Elecsys anti-SARS-CoV-2 S immunoassay was performed prior to and 3-4 weeks post vaccination to evaluate the antibody response to SARS-CoV-2 spike IgG. The Adaptive Biotechnologies T-Detect COVID Test was performed to evaluate the adaptive T-cell immune response to SARS-CoV-2 in OCR-treated patients with no detectable antibodies. Data were analyzed using descriptive statistics, Fisher's exact test, and Wilcoxon rank sum. RESULTS: Forty-eight patients were enrolled in the study, 69% treated with ocrelizumab and 31% treated with natalizumab. Eighteen percent of ocrelizumab and 100% of natalizumab patients had a positive antibody response. In ocrelizumab-treated patients, there was no correlation between age, sex, BMI, total number of infusions, immunoglobulin G, CD19, or absolute lymphocyte count and antibody response. There was a trend suggesting that a longer interval between the last infusion and vaccination increased the likelihood of producing antibodies (P = 0.062). All ocrelizumab patients with negative antibody responses had positive T-cell responses. CONCLUSIONS: Treatment with ocrelizumab substantially impaired the humoral response to SAR-CoV-2 vaccination but did not impair T-cell responses. Further research is needed to determine if the T-cell response to SARS-CoV-2 vaccination is sufficient to prevent infection or reduce severity of COVID in patients who did not produce antibodies.

Optimizing Small, Low-Risk, Unruptured Intracranial Aneurysm Treatment Using Game Theory.

The incidental diagnosis of unruptured intracranial aneurysms has been increasing in the past several decades. A significant proportion represent small, low-risk, unruptured intracranial aneurysms for which there is equipoise on whether to offer treatment or conservative management. Given this uncertainty, patients may not always be comfortable with their physicians' recommendations. Herein, we use game theory to study the interactions between physicians and patients to determine how conflict and cooperation affect the management of small, low-risk, unruptured intracranial aneurysms. We constructed a game theory model of the interaction between physicians and patients with respect to decision-making for a small, low-risk, unruptured intracranial aneurysm in an asymptomatic patient when there is perceived equipoise between whether to treat or manage conservatively. Assuming that both the physician and patient are rational and eliciting individual patient preferences is not practical, the physician should play the game based on an ex ante probability of meeting a patient with a certain type of preference. This recommendation means that the expectations of the physician regarding the patient's preferences should guide the decision to offer treatment or conservative management as a first option for a small, asymptomatic, low-risk, unruptured intracranial aneurysm for which there is clinical equipoise.

Increased odds ratio for erectile dysfunction in COVID-19 patients.

PURPOSE: Erectile dysfunction and COVID-19 share similar risk factors, including vascular disruption of integrity, cytokine release, cardiovascular disease, diabetes and obesity. The aim of this study was to investigate the association between erectile dysfunction and COVID-19 patients. METHODS: Odds ratio for erectile dysfunction in patients with a history of COVID-19 with and without comorbidities were calculated using a patients' registry platform i2b2. ICD-10 diagnoses codes were accessed for queries and data were analyzed using logistic regression. RESULTS: Patients with COVID-19 were 3.3 times more likely to have erectile dysfunction with 95% CI (2.8, 3.8). The association became stronger with odds ratio 4.8 (95% CI (4.1, 5.7)) after adjusting for age groups. The odds ratio remained the same after adjusting for smoking status with 3.5 (95% CI (3.0, 4.1)). After adjusting for race, COVID-19 patients were 2.6 (95% CI (2.2, 3.1)) times more likely to have erectile dysfunction. The odds ratio were 1.6, 1.8, 1.9 and 2.3 after adjusting for respiratory disease, obesity, circulatory disease and diabetes, respectively. CONCLUSION: COVID-19 and erectile dysfunction are strongly associated even after adjustment for known risk factors and demographics.

The burden of OA-health services and economics.

Osteoarthritis (OA) is a highly prevalent and disabling condition that affects over 7% of people globally (528 million people). Prevalence levels are even higher in countries with established market economies, which have older demographic profiles and a higher prevalence of obesity, such as the US (14%). As the 15th highest cause of years lived with disability (YLDs) worldwide, the burden OA poses to individuals is substantial, characterized by pain, activity limitations, and reduced quality of life. The economic impact of OA, which includes direct and indirect (time) costs, is also substantial, ranging from 1 to 2.5% of gross national product (GNP) in countries with established market economies. In regions around the world, the average annual cost of OA for an individual is estimated between $700-$15,600 (2019 USD). Though trends in OA prevalence vary by geography, the prevalence of OA is projected to rise in regions with established market economies such as North America and Europe, where populations are aging and the prevalence of obesity is rising.