Analysis and mitigation of an oscillating background on hybrid complementary metal-oxide semiconductor (hCMOS) imaging sensors at the National Ignition Facility.

Nanosecond-gated hybrid complementary metal-oxide semiconductor imaging sensors are a powerful tool for temporally gated and spatially resolved measurements in high energy density science, including inertial confinement fusion, and in laser diagnostics. However, a significant oscillating background excited by photocurrent has been observed in image sequences during testing and in experiments at the National Ignition Facility (NIF). Characterization measurements and simulation results are used to explain the oscillations as the convolution of the pixel-level sensor response with a sensor-wide RLC circuit ringing. Data correction techniques are discussed for NIF diagnostics, and for diagnostics where these techniques cannot be used, a proof-of-principle image correction algorithm is presented.

Does drinking saccharin weaken an association of sweet with calories? Pre-exposure effects in flavor preference learning.

The main aim of this experiment was to examine the claim that exposure to non-nutritive sweeteners weakens the formation of a sweet-calorie association. Three groups of food-deprived rats received training in which they drank an almond-flavored maltodextrin and saccharin solution. A final test phase assessed their preference for almond. The groups differed in preexposure prior to training. One was pre-exposed to saccharin, one to saccharin plus maltodextrin, and the third, control condition, received only water at this stage. When the rats continued under food deprivation for the test phase, the group exposed to the compound (saccharin plus maltodextrin) showed a weaker preference than the other two groups, while those pre-exposed to saccharin showed as strong a preference as the controls. When the test was conducted with the rats no longer food-deprived, only the water group showed a strong preference. These results support the proposal that rats can form both flavor-flavor and flavor-nutrient associations, expression of which will depend on motivational state. They did not find support for the suggestion that prior exposure to a non-nutritive sweetener can enhance subsequent learning about the nutritive properties of a sweet food.

Reduced mixing in inertial confinement fusion with early-time interface acceleration.

In inertial confinement fusion (ICF) implosions, the interface between the cryogenic DT fuel and the ablator is unstable to shock acceleration (the Richtmyer-Meshkov instability, RM) and constant acceleration (Rayleigh-Taylor instability, RT). Instability growth at this interface can reduce the final compression, limiting fusion burnup. If the constant acceleration is in the direction of the lighter material (negative Atwood number), the RT instability produces oscillatory motion that can stabilize against RM growth. Theory and simulations suggest this scenario occurred at early times in some ICF experiments on the National Ignition Facility, possibly explaining their favorable performance compared to one-dimensional simulations. This characteristic is being included in newer, lower adiabat designs, seeking to improve compression while minimizing ablator mixing into the fuel.

Detailed analysis of in-hospital transmission of SARS-CoV-2 using whole genome sequencing.

BACKGROUND: Hospital transmission of SARS-CoV-2 has proved difficult to control, with healthcare-associated infections troublesome throughout. AIM: To understand factors contributing to hospital transmission of infections, which is necessary for containing spread. METHODS: An outbreak of 56 staff and patient cases of COVID-19 over a 31-day period in a tertiary referral unit is presented, with at least a further 29 cases identified outside of the unit and the hospital by whole genome sequencing (WGS). FINDINGS: Transmission is documented from staff to staff, staff to patients, and patients to staff, showing disruption of a tertiary referral service, despite implementation of nationally recommended control measures, superior ventilation, and use of personal protective equipment. There was extensive spread from the index case, despite this patient spending only 10 h bed bound on the ward in strict cubicle isolation and with an initial single target low level (CT = 32) polymerase chain reaction test. CONCLUSION: This investigation highlights how effectively and rapidly SARS-CoV-2 can spread in certain circumstances. It raises questions about infection control measures in place at the time and calls into question the premise that transmissibility can be reliably detected by using lower sensitivity rapid antigen lateral flow tests. We also highlight the value of early intervention in reducing impact as well as the value of WGS in understanding outbreaks.

Optimized x-ray emission from 10 ns long germanium x-ray sources at the National Ignition Facility.

This study investigates methods to optimize quasi-monochromatic, ∼10 ns long x-ray sources (XRS) for time-resolved x-ray diffraction measurements of phase transitions during dynamic laser compression measurements at the National Ignition Facility (NIF). To support this, we produce continuous and pulsed XRS by irradiating a Ge foil with NIF lasers to achieve an intensity of 2 × 1015 W/cm2, optimizing the laser-to-x-ray conversion efficiency. Our x-ray source is dominated by Ge He-α line emission. We discuss methods to optimize the source to maintain a uniform XRS for ∼10 ns, mitigating cold plasma and higher energy x-ray emission lines.

Buffer gas cooled ice chemistry. I. Buffer gas cell and mm-wave spectrometer.

A new instrument is described that will employ buffer gas cooling with mm-wave rotational spectroscopy (60-90 GHz) to probe molecules desorbed from astrochemical ices prepared in an ultrahigh vacuum environment. Here the design and performance of the buffer gas cell, mm-wave spectrometer and data acquisition system are reported, while application to molecules desorbed from ice surfaces will be described in a future publication. The effective temperature of the neon-cooled buffer gas cell is determined by monitoring a range of rotational lines of propyl cyanide introduced into the cell. Its number density is estimated from comparison to room temperature measurements and the effective collision cross section with neon is estimated by monitoring the free induction decay (FID) lifetimes. The spectrometer and data acquisition system described are capable of acquiring and time-domain averaging the FIDs at 10 Gs/s, 10 bit vertical resolution and 98% duty cycle.

The regional turnover of cartilage collagen matrix in late-stage human knee osteoarthritis.

OBJECTIVE: Cartilage collagen has very limited repair potential, though some turnover and incorporation has not been fully excluded. We aim to determine the regional turnover of human osteoarthritis cartilage. DESIGN: Patients scheduled for knee joint replacement surgery due to osteoarthritis were recruited in this prospective study of four weeks duration. Deuterium oxide (D2O) was administered orally by weekly boluses at 70% D2O, initially 150 ml followed by three boluses of 50 ml. Cartilage from the medial tibia plateau was sampled centrally, under the meniscus, and from osteophytes and treated enzymatically with hyaluronidase and trypsin. Samples were analysed for deuterium incorporation in alanine using mass spectrometry and for gene expression by real-time reverse transcriptase polymerase chain reaction. RESULTS: Twenty participants completed the study: mean (SD) age 64 ± 9.1 years, 45% female, BMI 29.5 ± 4.8 kg/m2. Enzymatically treated cartilage from central and submeniscal regions showed similar enrichments at 0.063% APE, while osteophytes showed significantly greater enrichment at 0.072% APE (95% confidence interval of difference) [0.004-0.015]). Fractional synthesis rates were similar for central 0.027%/day and submeniscal cartilage 0.022%/day but 10-fold higher in osteophytes 0.22%/day [0.098-0.363]. When compared to central cartilage, submeniscal cartilage had increased gene expression of MMP-3 and decreased lubricin expression. Untreated cartilage had higher turnover (enrichments at 0.073% APE) than enzymatically treated cartilage (0.063% APE). CONCLUSIONS: In OA, despite regional differences in gene expression, the turnover of the articular cartilage matrix across the entire joint surface is very limited, but higher turnover was observed in osteophyte cartilage.

A study of space charge induced non-linearity in the Single Line Of Sight camera.

A new generation of gated x-ray detectors at the National Ignition Facility has brought faster, enhanced imaging capabilities. Their performance is currently limited by the amount of signal they can be operated with before space charge effects in their electron tube start to compromise their temporal and spatial response. We present a technique to characterize this phenomenon and apply it to a prototype of such a system, the Single Line Of Sight camera. The results of this characterization are used to benchmark particle-in-cell simulations of the electrons drifting inside the detector, which are found to well reproduce the experimental data. These simulations are then employed to predict the optimum photon flux to the camera, with the goal to increase the quality of the images obtained on an experimental campaign while preventing the appearance of deleterious effects. They also offer some insights into some of the improvements that can be brought to the new pulse-dilation systems being built at Lawrence Livermore National Laboratory.

Turkey ovarian tissue transplantation: effects of surgical technique on graft attachment and immunological status of the grafts, 6 days post-surgery.

Biobanked poultry ovaries can be revived via transplantation into a recipient female, which upon maturity will produce donor-derived progeny. Previously, a large portion of these recipients also produced recipient-derived progeny, making them gonadal chimeras. These were potentially created when portions of the recipient's ovary were inadvertently left behind. Completely removing the recipient ovary would solve this problem; however, leaving a portion of the recipient's ovary may have inadvertently increased the transplant attachment rate by providing a damaged area for attachment. To test this hypothesis in the turkey, we removed various portions (33-100%) of recipient ovarian tissue and determined the transplant attachment rate. Furthermore, the use of the abdominal air sac membrane as an additional anchoring point was tested. The overall attachment rate of transplants was 91% (27/30), while the average size of the transplants was 4.2 ± 0.6 mm2, 6 d postsurgery. There was no difference (P > 0.05) in the attachment rates, or transplant size between groups with varying amounts of recipent tissue removed, or by using the abdominal air sac membrane as an anchor. Finally, the immunological status of the grafts were evaluated by analyzing the presences of CD3 and MUM-1 (T and B cell markers). This showed that all transplants were infiltrated by large numbers of T and B cells. Shown by a high (P ≤ 0.001) percentage of CD3-positive immunostained cytoplasmic area (49.78 ± 3.90%) in transplants compared to remnant recipient tissue (0.30 ± 0.10%), as well as a high (P ≤ 0.001) percentage of MUM-1-positive immunostained nuclear area (9.85 ± 1.95%) in transplants over remnant recipient tissues (0.39 ± 0.12%). From this study we would recommend removing the entire recipient ovary, and not covering the transplants with the abdominal air sac membrane, to prevent gonadal chimeras. The high levels of lymphocytes within the grafts indicate possible tissue rejection, which could be overcome via immunosuppression with or without histocompatibility matching between donors and recipients.

Measurement of Dark Ice-Ablator Mix in Inertial Confinement Fusion.

We present measurements of ice-ablator mix at stagnation of inertially confined, cryogenically layered capsule implosions. An ice layer thickness scan with layers significantly thinner than used in ignition experiments enables us to investigate mix near the inner ablator interface. Our experiments reveal for the first time that the majority of atomically mixed ablator material is "dark" mix. It is seeded by the ice-ablator interface instability and located in the relatively cooler, denser region of the fuel assembly surrounding the fusion hot spot. The amount of dark mix is an important quantity as it is thought to affect both fusion fuel compression and burn propagation when it turns into hot mix as the burn wave propagates through the initially colder fuel region surrounding an igniting hot spot. We demonstrate a significant reduction in ice-ablator mix in the hot-spot boundary region when we increase the initial ice layer thickness.

Improved Constraints on Primordial Gravitational Waves using Planck, WMAP, and BICEP/Keck Observations through the 2018 Observing Season.

We present results from an analysis of all data taken by the BICEP2, Keck Array, and BICEP3 CMB polarization experiments up to and including the 2018 observing season. We add additional Keck Array observations at 220 GHz and BICEP3 observations at 95 GHz to the previous 95/150/220 GHz dataset. The Q/U maps now reach depths of 2.8, 2.8, and 8.8 µK_{CMB} arcmin at 95, 150, and 220 GHz, respectively, over an effective area of ≈600 square degrees at 95 GHz and ≈400 square degrees at 150 and 220 GHz. The 220 GHz maps now achieve a signal-to-noise ratio on polarized dust emission exceeding that of Planck at 353 GHz. We take auto- and cross-spectra between these maps and publicly available WMAP and Planck maps at frequencies from 23 to 353 GHz and evaluate the joint likelihood of the spectra versus a multicomponent model of lensed ΛCDM+r+dust+synchrotron+noise. The foreground model has seven parameters, and no longer requires a prior on the frequency spectral index of the dust emission taken from measurements on other regions of the sky. This model is an adequate description of the data at the current noise levels. The likelihood analysis yields the constraint r_{0.05}<0.036 at 95% confidence. Running maximum likelihood search on simulations we obtain unbiased results and find that σ(r)=0.009. These are the strongest constraints to date on primordial gravitational waves.

Long duration x-ray source development for x-ray diffraction at the National Ignition Facility.

We present the results of experiments to produce a 10 ns-long, quasi-monochromatic x-ray source. This effort is needed to support time-resolved x-ray diffraction (XRDt) measurements of phase transitions during laser-driven dynamic compression experiments at the National Ignition Facility. To record XRDt of phase transitions as they occur, we use high-speed (∼1 ns) gated hybrid CMOS detectors, which record multiple frames of data over a timescale of a few to tens of ns. Consequently, to make effective use of these imagers, XRDt needs the x-ray source to be narrow in energy and uniform in time as long as the sensors are active. The x-ray source is produced by a laser irradiated Ge foil. Our results indicate that the x-ray source lasts during the whole duration of the main laser pulse. Both time-resolved and time-integrated spectral data indicate that the line emission is dominated by the He-α complex over higher energy emission lines. Time-integrated spectra agree well with a one-dimensional Cartesian simulation using HYDRA that predicts a conversion efficiency of 0.56% when the incident intensity is 2 × 1015 W/cm2 on a Ge backlighter.

X-ray imaging of Rayleigh-Taylor instabilities using Fresnel zone plate at the National Ignition Facility.

Being able to provide high-resolution x-ray radiography is crucial in order to study hydrodynamic instabilities in the high-energy density regime at the National Ignition Facility (NIF). Current capabilities limit us to about 20 µm resolution using pinholes, but recent studies have demonstrated the high-resolution capability of the Fresnel zone plate optics at the NIF, measuring 2.3 µm resolution. Using a zinc Heα line at 9 keV as a backlighter, we obtained a radiograph of Rayleigh-Taylor instabilities with a measured resolution of under 3 µm. Two images were taken with a time integrated detector and were time gated by a laser pulse duration of 600 ps, and a third image was taken with a framing camera with a 100 ps time gate on the same shot and on the same line of sight. The limiting factors on image quality for these two cases are the motion blur and the signal to noise ratio, respectively. We also suggest solutions to increase the image quality.

In ovo culturing of turkey (Meleagris gallopavo) ovarian tissue to assess graft viability and maturation of prefollicular germ cells and follicles.

Biobanking of turkey ovarian tissue appears to be the most cost-effective method for the long-term preservation of female genetics. However, to ensure the successful transplantation of biobanked ovarian tissue for breed or line revival, the transplantation and development of fresh ovarian tissue must be evaluated. To assess transplantability, ovaries from poults 1 to 15 days posthatch (dph) were cultured in ovo in chicken eggs for 6 d and compared with the equivalent fresh tissue. The viability of cultured ovarian tissue was evaluated visually, whereas the level of late-stage apoptosis was measured via the TUNEL assay. In addition, the diameter and density of prefollicular germ cells and follicles (primordial and primary) were measured to assess maturation. Results showed that all cultured grafts (74/74), on surviving chicken chorioallantoic membrane, were viable with low levels (0.8 ± 0.1%) of late-stage apoptosis. The diameter of prefollicular germ cells in cultured ovaries from poults at 5 and 7 dph were larger (P < 0.002) than that of their preculture counterparts but were not able to reach their in vivo size. No significant follicular growth was observed in ovaries cultured in ovo; however, prefollicular germ cell density was over 4-fold greater in ovaries cultured from 7 dph poults (81,030 ± 17,611/mm3) than in their in vivo counterpart (16,463 ± 6,805/mm3). Interestingly, cultured ovaries from all other ages displayed equal or lower (P ≤ 0.05) prefollicular germ cell densities than their in vivo counterparts. Cultured ovaries from poults at 5 and 7 dph also exhibited an increase (P ≤ 0.05) in follicle density compared with their preculture counterparts; whereas, cultured ovaries from 15 dph poults had decreased densities (P < 0.001) compared with their preculture counterparts. This study demonstrated that, although age of ovarian tissue cultured in ovo did not affect the overall viability, 7 dph ovaries appeared to have a better cellular morphology after culturing in ovo than other ages. In addition, we also demonstrated for the first time that avian follicles can form during tissue culturing in ovo.

Time-Resolved Fuel Density Profiles of the Stagnation Phase of Indirect-Drive Inertial Confinement Implosions.

The implosion efficiency in inertial confinement fusion depends on the degree of stagnated fuel compression, density uniformity, sphericity, and minimum residual kinetic energy achieved. Compton scattering-mediated 50-200 keV x-ray radiographs of indirect-drive cryogenic implosions at the National Ignition Facility capture the dynamic evolution of the fuel as it goes through peak compression, revealing low-mode 3D nonuniformities and thicker fuel with lower peak density than simulated. By differencing two radiographs taken at different times during the same implosion, we also measure the residual kinetic energy not transferred to the hot spot and quantify its impact on the implosion performance.

Germ cell dynamics during nest breakdown and formation of the primordial follicle pool in the domestic turkey (Meleagris gallopavo).

This study determined, for the first time, the different subpopulations of germ cells and stereological changes within the cortex of the functional left ovary during germ cell nest breakdown, and formation of the primordial follicle pool in the domestic turkey. This was accomplished by measuring the size, density, and count of prefollicular germ cells and primordial follicles in turkey poults between 1 and 35 days posthatch (dph). The percent volume (PV) of germ cells and follicles within the cortex was also calculated as a means of validating the counting technique. The total percent volume of germ cells and primordial follicles within the cortex ranged between 42 and 84%, suggesting that the counting technique was valid. Our findings show that before germ cell nest breakdown (5 dph), there were roughly 1,000,000 prefollicular germ cells within the cortex of the left ovary and that germ cell nest breakdown initiated between 5 and 7 dph, characterized by a decrease (P ≤ 0.001) in prefollicular germ cell density and the subsequent appearance of primordial follicles. Nest breakdown is followed on day 9 by the first increase (P ≤ 0.05) in size of prefollicular germ cells. These cells continue to grow throughout nest breakdown. The majority (>90%) of germ cell nest breakdowns concluded by 15 dph; although, the primordial follicle pool was not fully established until 35 dph, as determined by a total lack of prefollicular germ cells. At this point, the pool was comprised of an estimated 60,000 primordial follicles and shows that during nest breakdown and follicle pool formation, ∼94% of germ cells were lost. This 94% decrease in the number of germ cells during nest breakdown in the turkey is comparable to the domestic chicken but is greater than the average two-thirds which are lost in mammalian species.

Radical (chemo)radiotherapy in oropharyngeal squamous cell carcinoma: Comparison of TNM 7th and 8th staging systems.

PURPOSE: To evaluate whether the 8th staging system is a better discriminator of overall survival (OS) than the 7th edition for oropharyngeal cancer patients after definitive (chemo)radiotherapy (CRT). MATERIAL AND METHODS: Data from oropharyngeal cancer patients treated with CRT with curative intent between 2010 and 2016 at Guy's and St Thomas' Hospitals were reviewed. Human papillomavirus (HPV) status was ascertained in all cases. Patients were staged using the 7th edition and the 8th edition TNM staging system. Demographics, tumor characteristics and treatment response data were included in univariate and multivariate analysis for OS. OS and disease-free survival (DFS) were estimated using the Kaplan-Meier method. In addition, a multivariate survival Cox regression analysis of several clinical variables was performed. RESULTS: A total of 273 patients were included. The median follow-up was 4.7 years. Overall 63 patients died. In multivariate analysis, HPV status, complete response at 3 months and ≤21 units/week alcohol were prognostic for OS. For the entire cohort, the 5-year OS and DFS rates were 78.1% (95% confidence interval CI 0.719-0.831) and 73.9% (95% CI 0.677-0.792), respectively. Better stratification of OS and DFS was recorded by 8th edition for the entire cohort. In HPV-positive cases, risk stratification based on tobacco smoking and nodal stage resulted in statistically higher discrimination in OS rates (5-year OS 90.7% in low risk patients and 84.6% in intermediate risk, p = 0.05) and DFS rates (5-year DFS 91.5% in low risk and 76.1% in intermediate risk, p = 0.001). CONCLUSION: The 8th edition TNM staging system provides better OS stratification in oropharyngeal cancer after definitive CRT compared with the 7th edition. Other clinical variables, such as complete response at 3 months, alcohol and tobacco smoking, should also be considered in future classifications as they provide additional risk stratification information in both HPV-positive and HPV-negative disease.