Comparison of effect of CTG + STan with CTG alone on emergency Cesarean section rate: STan Australian Randomized controlled Trial (START).

OBJECTIVE: To investigate whether use of ST analysis of the fetal electrocardiogram (STan) as an adjunct to continuous cardiotocography (CTG) reduces the rate of emergency Cesarean section (EmCS) compared with CTG alone. METHODS: This was a randomized controlled trial of patients with a singleton fetus in cephalic presentation at ≥ 36 weeks' gestation, requiring continuous electronic fetal monitoring during labor at a tertiary maternity hospital in Adelaide, Australia, between January 2018 and July 2021. Participants were randomized to undergo CTG + STan or CTG alone. The calculated sample size was 1818 participants. The primary outcome was EmCS. Secondary outcomes included metabolic acidosis, a composite adverse perinatal outcome, and other maternal and neonatal morbidity and safety outcomes. RESULTS: The present study enrolled 970 women, of whom 967 were included in the primary analysis. EmCS occurred in 107/482 (22.2%) deliveries in the CTG + STan arm and in 107/485 (22.1%) in the CTG arm (adjusted relative risk, 1.02 (95% CI, 0.81-1.27); P = 0.89). There was no difference in the rate of adverse maternal or neonatal outcomes between arms. CONCLUSIONS: The addition of STan as an adjunct to continuous CTG did not reduce the EmCS rate. The smaller-than-anticipated sample size meant that this study was underpowered to detect absolute differences of ≤ 5% and, therefore, this negative finding could be due to a Type-2 error. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

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.

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.

3D Simulations Capture the Persistent Low-Mode Asymmetries Evident in Laser-Direct-Drive Implosions on OMEGA.

Spherical implosions in inertial confinement fusion are inherently sensitive to perturbations that may arise from experimental constraints and errors. Control and mitigation of low-mode (long wavelength) perturbations is a key milestone to improving implosion performances. We present the first 3D radiation-hydrodynamic simulations of directly driven inertial confinement fusion implosions with an inline package for polarized crossed-beam energy transfer. Simulations match bang times, yields (separately accounting for laser-induced high modes and fuel age), hot spot flow velocities and direction, for which polarized crossed-beam energy transfer contributes to the systematic flow orientation evident in the OMEGA implosion database. Current levels of beam mispointing, imbalance, target offset, and asymmetry from polarized crossed-beam energy transfer degrade yields by more than 40%. The effectiveness of two mitigation strategies for low modes is explored.

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.

Independent-hot-spot approach to multibeam laser-plasma instabilities.

The independent-hot-spot model is used to develop an analytic formulation for multibeam laser-plasma instabilities in inhomogeneous plasmas. The model is applied to the absolute two-plasmon-decay instability and shows good agreement with simulations and experiments. The success of the model indicates the emergence of single-speckle behavior for sufficiently large speckles sizes.

Nonuniform Absorption and Scattered Light in Direct-Drive Implosions Driven by Polarization Smoothing.

Laser-direct-drive symmetric implosions on OMEGA illuminate a target with 60 laser beams and are designed to produce spherical implosions. Each beam is smoothed using orthogonal polarizations obtained by passing the laser beams through distributed polarization rotators (DPRs). Observations of light scattered from OMEGA implosions do not show the expected symmetry and have much larger variation than standard predictions. For the first time, we have quantified the scattered-light nonuniformity from individual beams and identified the DPRs as the source of the enhanced nonuniformity. An instrument was invented that isolated and measured the variation in the intensity and polarization of the light scattered from each OMEGA beam. The asymmetric intensity and polarization measurements are explained when the on-target offsets between the two orthogonal polarizations produced by the DPRs are modeled using a 3D cross-beam energy transfer (CBET) code that tracks the polarizations of each beam. The time-integrated nonuniformity in laser absorption and scattered light due to CBET and the DPR polarization offsets during high-performance OMEGA implosions is predicted to be significant and dominated by low spherical harmonic mode numbers. The nonuniformity is predicted to be greatly reduced by replacing the DPRs with new optics that create smaller offsets.

Pump-depletion dynamics and saturation of stimulated Brillouin scattering in shock ignition relevant experiments.

As an alternative inertial confinement fusion scheme, shock ignition requires a strong converging shock driven by a high-intensity laser pulse to ignite a precompressed fusion capsule. Understanding nonlinear laser-plasma instabilities is crucial to assess and improve the laser-shock energy coupling. Recent experiments conducted on the OMEGA EP laser facility have demonstrated that such instabilities can ∼100% deplete the first 0.5 ns of the high-intensity laser. Analyses of the observed laser-generated blast wave suggest that this pump-depletion starts at ∼0.02 critical density and progresses to 0.1-0.2 critical density, which is also confirmed by the time-resolved stimulated Raman backscattering spectra. The pump-depletion dynamics can be explained by the breaking of ion-acoustic waves in stimulated Brillouin scattering. Such pump depletion would inhibit the collisional laser energy absorption but may benefit the generation of hot electrons with moderate temperatures for electron shock ignition [Phys. Rev. Lett. 119, 195001 (2017)PRLTAO0031-900710.1103/PhysRevLett.119.195001].

Unabsorbed light beamlets for diagnosing coronal density profiles and absorption nonuniformity in direct-drive implosions on OMEGA.

Laser light scattered from a target is the most-direct measurement for diagnosing laser absorption in a direct-drive implosion. The 3ω gated optical imager beamlets diagnostic images unabsorbed light from all 60 OMEGA beams as distinct "beamlet" spots for each beam. The implosion can be diagnosed using the position and intensity of these beamlets. The position of each beamlet in the image is determined by refraction and can be used to fit the coronal plasma density profile of the implosion. The inferred plasma density profiles are comparable to the profiles predicted by the 1D hydrodynamics code LILAC but suggest that the predictions underestimate the density farther out in the corona. The intensity of light in each spot depends on the cumulative effects of absorption and cross-beam energy transfer along the beamlet's path through the corona. The measured variation in intensity and polarization between similar spots indicates that absorption during OMEGA implosions is less uniform than previously known.

Slow and Fast Light in Plasma Using Optical Wave Mixing.

Slow and fast light, or large changes in the group velocity of light, have been observed in a range of optical media, but the fine optical control necessary to induce an observable effect has not been achieved in a plasma. Here, we describe how the ion-acoustic response in a fully ionized plasma can produce large and measurable changes in the group velocity of light. We show the first experimental demonstration of slow and fast light in a plasma, measuring group velocities between 0.12c and -0.34c.

A transmitted-beam diagnostic for the wavelength-tunable UV drive beam on OMEGA.

A transmitted-beam diagnostic (P9TBD) was developed as part of a new experimental platform used to study laser-plasma interactions on OMEGA. Located in the opposing port to the wavelength-tunable (350 nm to 353 nm) UV drive beam, the P9TBD characterizes the beam after it propagates through an undersense plasma. The instrument consists of a large-aperture window that allows light to exit the target chamber and project onto a thin sheet of semi-transparent diffuser material. Light transmitted through the diffuser is recorded using a time-integrated camera and a fiber-optically coupled streaked spectrometer, providing measurements of the energy, power, fluence, polarization, and spectrum of the transmitted beam. The diagnostic enables direct observation of a variety of cross-beam energy transfer phenomena, such as wavelength detuning, polarization effects, and gain saturation.

Cross-Beam Energy Transfer Saturation by Ion Heating.

We measure cross-beam energy transfer (CBET) saturation by ion heating in a gas-jet plasma characterized using Thomson scattering. A wavelength-tunable ultraviolet (UV) probe laser beam interacts with four intense UV pump beams to drive large-amplitude ion-acoustic waves. For the highest-intensity interactions, the power transfer to the probe laser drops, demonstrating ion-acoustic wave saturation. Over this time, the ion temperature is measured to increase by a factor of 7 during the 500-ps interaction. Particle-in-cell simulations show ion trapping and a subsequent ion heating consistent with measurements. Linear kinetic CBET models are found to agree well with the observed energy transfer when the measured plasma conditions are used.

Advanced laser development and plasma-physics studies on the multiterawatt laser.

The multiterawatt (MTW) laser, built initially as the prototype front end for a petawatt laser system, is a 1053 nm hybrid system with gain from optical parametric chirped-pulse amplification (OPCPA) and Nd:glass. Compressors and target chambers were added, making MTW a complete laser facility (output energy up to 120 J, pulse duration from 20 fs to 2.8 ns) for studying high-energy-density physics and developing short-pulse laser technologies and target diagnostics. Further extensions of the laser support ultrahigh-intensity laser development of an all-OPCPA system and a Raman plasma amplifier. A short summary of the variety of scientific experiments conducted on MTW is also presented.

Hotspot parameter scaling with velocity and yield for high-adiabat layered implosions at the National Ignition Facility.

This paper presents a study on hotspot parameters in indirect-drive, inertially confined fusion implosions as they proceed through the self-heating regime. The implosions with increasing nuclear yield reach the burning-plasma regime, hotspot ignition, and finally propagating burn and ignition. These implosions span a wide range of alpha heating from a yield amplification of 1.7-2.5. We show that the hotspot parameters are explicitly dependent on both yield and velocity and that by fitting to both of these quantities the hotspot parameters can be fit with a single power law in velocity. The yield scaling also enables the hotspot parameters extrapolation to higher yields. This is important as various degradation mechanisms can occur on a given implosion at fixed implosion velocity which can have a large impact on both yield and the hotspot parameters. The yield scaling also enables the experimental dependence of the hotspot parameters on yield amplification to be determined. The implosions reported have resulted in the highest yield (1.73×10^{16}±2.6%), yield amplification, pressure, and implosion velocity yet reported at the National Ignition Facility.

Anomalous Absorption by the Two-Plasmon Decay Instability.

Radiation-hydrodynamic simulations of directly driven fusion experiments at the Omega Laser Facility predict absorption accurately when targets are driven at low overlapped laser intensity. Discrepancies appear at increased intensity, however, with higher-than-expected laser absorption on target. Strong correlations with signatures of the two-plasmon decay (TPD) instability-including half-harmonic and hard-x-ray emission-indicate that TPD is responsible for this anomalous absorption. Scattered light data suggest that up to ≈30% of the laser power reaching quarter-critical density can be absorbed locally when the TPD threshold is exceeded. A scaling of absorption versus TPD threshold parameter was empirically determined and validated using the laser-plasma simulation environment code.

Systematic review of cognitive deficits in adult mitochondrial disease.

The profile and trajectory of cognitive impairment in mitochondrial disease are poorly defined. This systematic review sought to evaluate the current literature on cognition in mitochondrial disease, and to determine future research directions. A systematic review was conducted, employing PubMed, Medline, Psycinfo, Embase and Web of Science, and 360-degree citation methods. English language papers on adult patients were included. The literature search yielded 2421 articles, of which 167 met inclusion criteria. Case reports and reviews of medical reports of patients yielded broad diagnoses of dementia, cognitive impairment and cognitive decline. In contrast, systematic investigations of cognitive functioning using detailed cognitive batteries identified focal cognitive rather than global deficits. Results were variable, but included visuospatial functioning, memory, attention, processing speed and executive functions. Conclusions from studies have been hampered by small sample sizes, variation in genotype and the breadth and depth of assessments undertaken. Comprehensive cognitive research with concurrent functional neuroimaging and physical correlates of mitochondrial disease in larger samples of well-characterized patients may discern the aetiology and progression of cognitive deficits. These data provide insights into the pattern and trajectory of cognitive impairments, which are invaluable for clinical monitoring, health planning and clinical trial readiness.

Photon Acceleration in a Flying Focus.

A high-intensity laser pulse propagating through a medium triggers an ionization front that can accelerate and frequency upshift the photons of a second pulse. The maximum upshift is ultimately limited by the accelerated photons outpacing the ionization front or the ionizing pulse refracting from the plasma. Here, we apply the flying focus-a moving focal point resulting from a chirped laser pulse focused by a chromatic lens-to overcome these limitations. Theory and simulations demonstrate that the ionization front produced by a flying focus can frequency upshift an ultrashort optical pulse to the extreme ultraviolet over a centimeter of propagation. An analytic model of the upshift predicts that this scheme could be scaled to a novel tabletop source of spatially coherent x rays.

Comparing the effect of STan (cardiotocographic electronic fetal monitoring (CTG) plus analysis of the ST segment of the fetal electrocardiogram) with CTG alone on emergency caesarean section rates: study protocol for the STan Australian Randomised controlled Trial (START).

BACKGROUND: Cardiotocography is almost ubiquitous in its use in intrapartum care. Although it has been demonstrated that there is some benefit from continuous intrapartum fetal monitoring using cardiotocography, there is also an increased risk of caesarean section which is accompanied by short-term and long-term risks to the mother and child. There is considerable potential to reduce unnecessary operative delivery with up to a 60% false positive diagnosis of fetal distress using cardiotocography alone. ST analysis of the fetal electrocardiogram is a promising adjunct to cardiotocography alone, and permits detection of metabolic acidosis of the fetus, potentially reducing false positive diagnosis of fetal distress. METHODS: This study will be a single-centre, parallel-group, randomised controlled trial, conducted over 3 years. The primary hypothesis will be that the proportion of women with an emergency caesarean section on ST analysis will not equal that for women on cardiotocography monitoring alone. Participants will be recruited at the Women's and Children's Hospital, a high-risk specialty facility with approximately 5000 deliveries per annum. A total of 1818 women will be randomised to the treatment or conventional arm with an allocation ratio of 1:1, stratified by parity. The primary outcome is emergency caesarean section (yes/no). Statistical analysis will follow standard methods for randomised trials and will be performed on an intention-to-treat basis. Secondary maternal and neonatal outcomes will also be analysed. Additional study outcomes include psychosocial outcomes, patient preferences and cost-effectiveness. DISCUSSION: Approximately 20% of Australian babies are delivered by emergency caesarean section. This will be the first Australian trial to examine ST analysis of the fetal electrocardiogram as an adjunct to cardiotocography as a potential method for reducing this proportion. The trial will be among the first to comprehensively examine ST analysis, taking into account the impact on psychosocial well-being as well as cost-effectiveness. This research will provide Australian evidence for clinical practice and guideline development as well as for policy-makers and consumers to make informed, evidence-based choices about care in labour. TRIAL REGISTRATION: ANZCTR, ACTRN1261800006268 . Registered on 19 January 2018.

Design and baseline characteristics of the Biomarkers Of Risk In Colorectal Cancer (BORICC) Follow-Up study: A 12+ years follow-up.

BACKGROUND: Colorectal cancer (CRC) is the third most common cancer worldwide. Age is the strongest non-modifiable risk factor but it is estimated that over half of CRC cases are linked with lifestyle factors such as diet. The Biomarkers Of RIsk of Colorectal Cancer (BORICC) Study recruited 363 participants in 2005 to investigate the effects of lifestyle factors on biomarkers of CRC risk. AIM: In the present BORICC Follow-Up (BFU) Study, we are using a longitudinal study design to investigate the effects of ageing (12+ years) and lifestyle factors on biomarkers of CRC risk and on healthy ageing. METHODS: BFU Study participants attended a study visit at North Tyneside General Hospital (UK) for collection of biological samples, including blood and rectal biopsies, and information collected included anthropometric measurements, a Health & Medications Questionnaire, physical activity and sedentary behaviour, and habitual diet. Furthermore, musculoskeletal function was assessed by heel bone densitometry, timed up and go and hand grip strength as markers of healthy ageing. The BFU Study outcomes will be similar to those measured at baseline in the BORICC Study, such as DNA methylation and mitochondrial function, with additional measurements including the gut microbiome, faecal short-chain fatty acid concentrations and expression of genes associated with CRC. RESULTS: Participants' recruitment to BFU Study and all sample and data collection have been completed. Forty-seven of the original BORICC participants were re-recruited to the BFU Study (mean age 67 years, 51% female). The recruits included 37 initially healthy participants and 10 participants who had adenomatous polyps at baseline. Approximately 70% of participants were over-weight or obese. CONCLUSION: Ultimately, identifying lifestyle factors that can reduce CRC risk, and understanding the underlying mechanisms for the effects of lifestyle and ageing on CRC risk, could lead to early prevention strategies.