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The Cuvette Centrale swamp forest around the Congo river has the most extensive peatland complex in the tropics, but due to its remoteness the peat was only recently discovered. The international project CongoPeat, which includes scientists from the Republic of the Congo and the Democratic Republic of the Congo and works with the local people of the Cuvette Centrale, is studying the peatlands to determine how they formed and the possible threats since it is vital that the peat is preserved. While the peatlands are at least 20,000 years old the peat is thin compared to other tropical peatlands of similar age. The JULES land surface model has been used with a reconstruction of the past annual rainfall and a simulation of other climate variables with the HadCM3 model to simulate the development of the peatlands. The model results support the hypothesis that a long period of reduced rainfall a few thousand years ago lead to a large loss of peat and recreate the age-depth profiles of the peat in measured soil cores including the feature called a “ghost interval”. This confirms that a constant high water table is needed to keep decomposition of the peat to a minimum and hence preserve the peatlands. JULES was then run with future climate projections from five global climate models to simulate how the peatlands could change up to 2100. In most projections the increased temperatures lead to increased evapotranspiration, lower water tables and increased decomposition of peat. In most cases peat is lost overall, particularly when rainfall is also reduced further lowering the water tables, in-spite of increased CO2 concentration increasing the amount of vegetation and litterfall while reducing the amount of plant transpiration. The risk to the peatland Carbon is greater at higher levels of global warming.

High-mobility group box 1 (HMGB1) is a nuclear protein that functions as a paracrine signaling molecule when released from the nucleus of stressed or injured cells into the interstitial fluid. Secreted HMGB1 can activate toll-like receptor 4 (TLR4) and we showed that activation of renal TLR4 causes autoregulatory dysfunction. In addition, microvascular function is seriously compromised in hypertension but the specific mechanisms involved are poorly defined. We tested the hypothesis that HMGB1 negatively influences renal microvascular autoregulatory capability by activating TLR4. Experiments were performed in male rats using the blood-perfused juxtamedullary nephron technique. Three groups were studied: control, HMGB1 (~1.25 μg/ml in the blood perfusate) and HMGB1+LPS-RS (TLR4 blocker; ~10 μg/ml in the blood perfusate). Afferent arteriole autoregulatory behavior was assessed in these groups by increasing perfusion pressure from 65 to 170 mmHg in 15 mmHg increments. Starting diameters of male arterioles, measured at 100 mmHg, were similar across all three groups (15.3±0.7; 15.1±0.2 and 15.3±0.1 μm, respectively). When perfusion pressure increased from 65 to 170 mmHg, control arteriole diameter decreased to 69±3% of baseline (P0.05 vs. baseline; P0.05). Increasing perfusion pressure from 65 to 170 mmHg decreased female control arteriole diameter to 78±1% (P Study supported by NIH (DK044628). This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

B.1.351 is the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant most resistant to antibody neutralization. We demonstrate how the dose and number of immunizations influence protection. Nonhuman primates received two doses of 30 or 100 µg of Moderna's mRNA-1273 vaccine, a single immunization of 30 µg, or no vaccine. Two doses of 100 µg of mRNA-1273 induced 50% inhibitory reciprocal serum dilution neutralizing antibody titers against live SARS-CoV-2 p.Asp614Gly and B.1.351 of 3,300 and 240, respectively. Higher neutralizing responses against B.1.617.2 were also observed after two doses compared to a single dose. After challenge with B.1.351, there was ~4- to 5-log10 reduction of viral subgenomic RNA and low to undetectable replication in bronchoalveolar lavages in the two-dose vaccine groups, with a 1-log10 reduction in nasal swabs in the 100-µg group. These data establish that a two-dose regimen of mRNA-1273 will be critical for providing upper and lower airway protection against major variants of concern.

IntroductionA lunar impact flash (LIF) is a rapid burst of light caused by a hypervelocity impactor hitting the moon, releasing a fraction of its energy as light. They are observable though moderately sized (0.4m) telescopes, and are therefore observable by both amateur and professional astronomers.LIF observations are typically performed in visible or NIR, and can only take place when the lunar phase is between 10-50%, during local night, and are only observable against the lunar night-side; the most commonly observed LIFs are faint, approximately MagI = 9, MagR = 10 [1], making them indistinguishable against the illuminated lunar background. This limits potential observations of LIFs to ~30h per month on average, with weather limiting this further.In order to increase the average number of observable hours that LIF observations can be made, and thereby increase the number of observed LIFs, we have developed new techniques to perform LIF observations at all local times, and all lunar illuminations. This technique theoretically only requires clear weather and a visible moon.TheoryLIFs have been shown to behave as black bodies, releasing energy according to Planck's law [2]. The temperature of LIFs observed by NELIOTA is between 1300-5800 k, with average temperature, Tavg = 2800k [3]. This average has peak wavelength of λpeak = 1.035 μm. The illuminated portion of the lunar surface is reflecting light from the sun (T = 5778 k, λpeak = 0.5 μm). In R-band and I-band, the ratio of energy radiated by the sun is greater by a factor of 57 in R-band, and 28 in I-band. My observing in wavelengths closer to the λpeak of the flash, we can improve this ratio greatly.Figure 1:The Planck curve for the sun (5778k) and the average LIF (2750k), R, I, and J-band regions are highlighted in orange, red, and grey respectively.As illustrated in Fig. 1, by observing in J-band the irradiance of the sun is lowered, being only 10 times greater than the 2800 k LIF. This effective dimming of the background leads to an increase in the signal-to-noise ratio (S/N) of the LIF against the sun-illuminated background.The S/N ratio is a measure of how detectable a signal is above the background, and can be defined as:S/N = S" / (σ × √Apix)Where S" is the total count of the signal, σB is the standard deviation of the background, and Apix is the area of the background measurement. A S/N ratio above ≈10 is generally required for a signal to be considered detectable.ObservationsObservations were performed on 2022-02-23 from the Observatoire de la Côte d'Azur, using a 0.5 m diameter, 2 m focal length telescope with Ninox 640 II camera and J-band filter attached. For the first set of observations, high gain mode was used, for the second set of observations low gain mode was used. A 30 μm exposure time was used for both sets of observations.The star HD137463 was observed, which has MagJ = 5.423, obtained by Simbad [4] Observations began during the night, and continued until after sunrise in order to measure the brightness of the sky during daytime. By performing A-B subtraction to remove the dark current and background of the observed frames, as shown in Fig. 2, a pixel count for the clean star signal, S", can be obtained. As it is constant, an average for the star signal can be used as ground truth in order to calculate the S/N ratio for the daytime sky brightness, as well as the illuminated lunar surface.Figure 2: The A-B subtraction of two observations of HD137463. The subtraction removes any dark current or background to leave only a clean positive and negative signal.ResultsThe S/N ratio for the a MagJ = 5.423 star are shown in Fig. 3. A sharp decrease in S/N ratio is observed as air-glow begins around solar altitude = -5. The S/N continues to decrease, slowly levelling off around S/N = 15 as the sun reaches solar altitude = 5. This puts the magJ = 5.423 star well above the detectable threshold, and would correspond to a MagR = 6.7 LIF. Figure 3: Left: The S/N ratio in high gain mode, of HD137463 against the sky background between solar altitudes -10 & -1. Right: The S/N ratio in low gain mode, of HD137463 against the sky background between solar altitudes -1 & -5.By taking measurements of the lunar background brightness, we can verify the S/N ratio we would expect from these LIF when observed on the lunar surface. Table 1 contains the results from count-averaged observations of the background, and the S/N of the MagJ star if observed against the background, emulating a flash. Again, even against the illuminated bright limb, the S/N ratio is above the detectable threshold, and shows that with this system, we would be able to detect LIFs of MagJ ≥ 5.423, with the possibility of even fainter magnitudes under more favourable conditions.Table 1: The S/N ratio of the reference star used against different regions on the lunar surface, from darkest to brightest.Region S/N Lunar Night Side 147 Terminator 42 Lunar Day Side 21 Lunar Bright Limb 19 References[1] Liakos et al (2019) A&A, 633, 29 pp.[2] Eichhorn (1975) P&SS, 23, 11, 1519-1525[3] Avdellidou & Vaubaillon (2019) MNRAS, 484, 5212-5222[4] Wegner et al (2000) A&A, 143, p.9-22

Spike-specific neutralizing antibodies (NAbs) are generally considered key correlates of vaccine protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Recently, robust vaccine prevention of severe disease with SARS-CoV-2 variants that largely escape NAb responses has been reported, suggesting a role for other immune parameters for virologic control. However, direct data demonstrating a role of CD8 + T cells in vaccine protection have not yet been reported. In this study, we show that vaccine-elicited CD8 + T cells contribute substantially to virologic control after SARS-CoV-2 challenge in rhesus macaques. We vaccinated 30 macaques with a single immunization of the adenovirus vector–based vaccine Ad26.COV2.S or sham and then challenged them with 5 × 10 5 median tissue culture infectious dose SARS-CoV-2 B.1.617.2 (Delta) by the intranasal and intratracheal routes. All vaccinated animals were infected by this high-dose challenge but showed rapid virologic control in nasal swabs and bronchoalveolar lavage by day 4 after challenge. However, administration of an anti-CD8α– or anti-CD8β–depleting monoclonal antibody in vaccinated animals before SARS-CoV-2 challenge resulted in higher levels of peak and day 4 virus in both the upper and lower respiratory tracts. These data demonstrate that CD8 + T cells contribute substantially to vaccine protection against SARS-CoV-2 replication in macaques.

Emergence of SARS-CoV-2 variants and waning of vaccine/infection-induced immunity pose threats to curbing the COVID-19 pandemic. Effective, safe, and convenient booster vaccines are in need. We hypothesized that a variant-modified mucosal booster vaccine might induce local immunity to prevent SARS-CoV-2 infection at the port of entry. The beta-variant is one of the hardest to cross-neutralize. Herein, we assessed the protective efficacy of an intranasal booster composed of beta variant-spike protein S1 with IL-15 and TLR agonists in previously immunized macaques. The macaques were first vaccinated with Wuhan strain S1 with the same adjuvant. A total of 1 year later, negligibly detectable SARS-CoV-2-specific antibody remained. Nevertheless, the booster induced vigorous humoral immunity including serum- and bronchoalveolar lavage (BAL)-IgG, secretory nasal- and BAL-IgA, and neutralizing antibody against the original strain and/or beta variant. Beta-variant S1-specific CD4+ and CD8+ T cell responses were also elicited in PBMC and BAL. Following SARS-CoV-2 beta variant challenge, the vaccinated group demonstrated significant protection against viral replication in the upper and lower respiratory tracts, with almost full protection in the nasal cavity. The fact that one intranasal beta-variant booster administrated 1 year after the first vaccination provoked protective immunity against beta variant infections may inform future SARS-CoV-2 booster design and administration timing.

Authorized vaccines against SARS-CoV-2 remain less available in low- and middle-income countries due to insufficient supply, high costs, and storage requirements. Global immunity could still benefit from new vaccines using widely available, safe adjuvants, such as alum and protein subunits, suited to low-cost production in existing manufacturing facilities. Here, a clinical-stage vaccine candidate comprising a SARS-CoV-2 receptor binding domain–hepatitis B surface antigen virus–like particle elicited protective immunity in cynomolgus macaques. Titers of neutralizing antibodies (>104) induced by this candidate were above the range of protection for other licensed vaccines in nonhuman primates. Including CpG 1018 did not significantly improve the immunological responses. Vaccinated animals challenged with SARS-CoV-2 showed reduced median viral loads in bronchoalveolar lavage (~3.4 log10) and nasal mucosa (~2.9 log10) versus sham controls. These data support the potential benefit of this design for a low-cost modular vaccine platform for SARS-CoV-2 and other variants of concern or betacoronaviruses.

FDA-approved and emergency use-authorized vaccines using new mRNA and viral-vector technology are highly effective in preventing moderate to severe disease; however, information on their long-term efficacy and protective breadth against severe acute respiratory syndrome coronavirus 2 variants of concern (VOCs) is currently scarce. Here, we describe the durability and broad-spectrum VOC immunity of a prefusion-stabilized spike (S) protein adjuvanted with liquid or lyophilized CoVaccine HT in cynomolgus macaques. This recombinant subunit vaccine is highly immunogenic and induces robust spike-specific and broadly neutralizing antibody responses effective against circulating VOCs (B.1.351 [Beta], P.1 [Gamma], and B.1.617 [Delta]) for at least three months after the final boost. Protective efficacy and postexposure immunity were evaluated using a heterologous P.1 challenge nearly three months after the last immunization. Our results indicate that while immunization with both high and low S doses shorten and reduce viral loads in the upper and lower respiratory tract, a higher antigen dose is required to provide durable protection against disease as vaccine immunity wanes. Histologically, P.1 infection causes similar COVID-19-like lung pathology as seen with early pandemic isolates. Postchallenge IgG concentrations were restored to peak immunity levels, and vaccine-matched and cross-variant neutralizing antibodies were significantly elevated in immunized macaques indicating an efficient anamnestic response. Only low levels of P.1-specific neutralizing antibodies with limited breadth were observed in control (nonvaccinated but challenged) macaques, suggesting that natural infection may not prevent reinfection by other VOCs. Overall, these results demonstrate that a properly dosed and adjuvanted recombinant subunit vaccine can provide protective immunity against circulating VOCs for at least three months.

BackgroundThe rapid spread of the SARS-CoV-2 Omicron (B.1.1.529) variant, including in highly vaccinated populations, has raised important questions about the efficacy of current vaccines. Immune correlates of vaccine protection against Omicron are not known.Methods30 cynomolgus macaques were immunized with homologous and heterologous prime-boost regimens with the mRNA-based BNT162b2 vaccine and the adenovirus vector-based Ad26.COV2.S vaccine. Following vaccination, animals were challenged with the SARS-CoV-2 Omicron variant by the intranasal and intratracheal routes.ResultsOmicron neutralizing antibodies were observed following the boost immunization and were higher in animals that received BNT162b2, whereas Omicron CD8+ T cell responses were higher in animals that received Ad26.COV2.S. Following Omicron challenge, sham controls showed more prolonged virus in nasal swabs than in bronchoalveolar lavage. Vaccinated macaques demonstrated rapid control of virus in bronchoalveolar lavage, and most vaccinated animals also controlled virus in nasal swabs, showing that current vaccines provide substantial protection against Omicron in this model. However, vaccinated animals that had moderate levels of Omicron neutralizing antibodies but negligible Omicron CD8+ T cell responses failed to control virus in the upper respiratory tract. Virologic control correlated with both antibody and T cell responses.ConclusionsBNT162b2 and Ad26.COV2.S provided robust protection against high-dose challenge with the SARS-CoV-2 Omicron variant in macaques. Protection against this highly mutated SARS-CoV-2 variant correlated with both humoral and cellular immune responses.

SummarySARS-CoV-2 Omicron is highly transmissible and has substantial resistance to antibody neutralization following immunization with ancestral spike-matched vaccines. It is unclear whether boosting with Omicron-specific vaccines would enhance immunity and protection. Here, nonhuman primates that received mRNA-1273 at weeks 0 and 4 were boosted at week 41 with mRNA-1273 or mRNA-Omicron. Neutralizing antibody titers against D614G were 4760 and 270 reciprocal ID50 at week 6 (peak) and week 41 (pre-boost), respectively, and 320 and 110 for Omicron. Two weeks after boost, titers against D614G and Omicron increased to 5360 and 2980, respectively, for mRNA-1273 and 2670 and 1930 for mRNA-Omicron. Following either boost, 70-80% of spike-specific B cells were cross-reactive against both WA1 and Omicron. Significant and equivalent control of virus replication in lower airways was observed following either boost. Therefore, an Omicron boost may not provide greater immunity or protection compared to a boost with the current mRNA-1273 vaccine.

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants stresses the continued need for next-generation vaccines that confer broad protection against coronavirus disease 2019. We developed and evaluated an adjuvanted SARS-CoV-2 spike ferritin nanoparticle (SpFN) vaccine in nonhuman primates. High-dose (50-μg) SpFN vaccine, given twice 28 days apart, induced a T helper cell 1 (TH1)–biased CD4 THresponse and elicited neutralizing antibodies against SARS-CoV-2 wild type and variants of concern, as well as against SARS-CoV-1. These potent humoral and cell-mediated immune responses translated into rapid elimination of replicating virus in the upper and lower airways and lung parenchyma of nonhuman primates after high-dose SARS-CoV-2 respiratory challenge. The immune response elicited by SpFN vaccination and resulting efficacy in nonhuman primates support the utility of SpFN as a vaccine candidate for SARS-causing betacoronaviruses.

Despite the rapid creation of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) vaccines, the precise correlates of immunity against severe Coronavirus Disease 2019 (COVID-19) are still unknown. Neutralizing antibodies represent a robust surrogate of protection in early Phase III studies, but vaccines provide protection prior to the evolution of neutralization, vaccines provide protection against variants that evade neutralization, and vaccines continue to provide protection against disease severity in the setting of waning neutralizing titers. Thus, in this study, using an Ad26.CoV2.S dose-down approach in nonhuman primates (NHPs), the role of neutralization, Fc effector function, and T-cell immunity were collectively probed against infection as well as against viral control. While dosing-down minimally impacted neutralizing and binding antibody titers, Fc receptor binding and functional antibody levels were induced in a highly dose-dependent manner. Neutralizing antibody and Fc receptor binding titers, but minimally T cells, were linked to the prevention of transmission. Conversely, Fc receptor binding/function and T cells were linked to antiviral control, with a minimal role for neutralization. These data point to dichotomous roles of neutralization and T-cell function in protection against transmission and disease severity and a continuous role for Fc effector function as a correlate of immunity key to halting and controlling SARS-CoV-2 and emerging variants.

A highly degraded, pre-Nectarian lunar impact basin was proposed for the region between Bailly and Newton craters in 2000. However, a publication in 2010 suggested that there was no basin there. We utilize a combination of topographic and Bouguer anomaly basin fitting tools to provide evidence that the basin exists. A revised centre and diameter of the basin is given of 77°S, 41°W and 402 km respectively. The basin is in an interesting geological context as it straddles the rim of the South Pole Aitken basin.1. IntroductionIn 2000, whilst examining a Clementine nadir stereo derived digital elevation model (DEMs) of the Moon’s south pole region[1], an impact basin was found in a stereo anaglyph visualization of the topographic dataset (Fig 1), and used to find its location in the DEM and an image mosaic. The original position and dimension were quoted as 73°S, 57°W, and 330 km in diameter.A subsequent study[2] found no evidence for a basin here. This used DEMs, hill shaded views, colour coding, perspective views, and slope maps. Using a variety of existing and new basin measuring tools, we show that there is a basin present after all. 2. MethodThree methods were used to fit a basin floor and rim to a topographic DEM (MoonTopo2600p)[3]: 1) rotational maximum height profile, 2) fitting the rotational topographic profile to three step arc tangent functions, 3) finding prominent peak maxima, ranking these and filtering the less prominent peaks out, leaving just those that should make up the basin rim. Three methods were also used to fit a basin using Bouguer anomaly data (GRGM1200B)[4] using the central mascon and surrounding low annulus: 1) finding prominent peaks maxima and ranking these and filtering out the less prominent peaks which make up the central mascon, 2) fitting the rotational Bouguer anomaly profile, similar to Baker et al.[5] but with two step arc tangent functions, 3) using an annulus method developed by Neumann et al.[6] with the annulus with inner and outer diameters set to 50% and 100% of the basin diameter, and an inner disc of 20% of the basins diameter. The difference between the annulus and the inner circle was a measure of the basin contrast.These methods were tested out on lists of published basin tables, and found to vary in diameters found by each algorithm, for each basin, if for example the basin was on a slope or was sitting on some other large scale topographic features, this could skew the results. However, a combination of topographic fit and Bouguer peak methods seemed to produce results closest to published values[6]. However, plotting out all the basin ring diameters on the DEM and then using one’s eye to judge which diameter was most appropriate, was a practical solution. 3. Analysis of the Bailly-Newton BasinThree different topographic basin measuring algorithms were applied to the DEM (Table 1) and three wildly different diameters were found. The peak method got locked onto the central topography in the basin and yielded an unrealistically small diameter for the basin – see inner blue circle in Fig 2. The rotational maxima algorithm also produced a result, the 2nd largest circle in Fig 2, that clearly does not relate to the true nature of the basin rim. The fitting to three step arc tangent functions though produced the largest diameter circle in Fig 2 and this neatly portrays the outer eroded rim of the basin. Concerning the Bouguer anomaly map of the same area, there is considerable noise, however once the Bouguer fit method is applied, a central mascon and surrounding annulus can be seen in Fig 3. The basin diameter derived by Bouguer peak algorithm is depicted by the 2nd largest circle in Fig 2. Using the topography in Fig 2 as a guide, the two outer circles appear to best fit the rim of the basin. 4. DiscussionOur analysis show that the Bailly-Newton basin is present and that it is larger than the estimate published in 2000, of 330 km namely, between 381 km and 424 km, depending upon which of the two best basin measuring method was used – with a mean 402 km. Although visual inspection of topographic data, slope maps, visualizations, can pick out obvious basins, a combination of algorithms applied to topographic and Bouguer anomaly data can identify more degraded basins. It is possible that the inclusion of evidence of other basin characteristics such as radial ejecta scour marks, and geological/geomorphological evidence[7] could help identify similar or more extensively degraded ancient basins. References[1] Cook et al., (2000) JGR (Planets), 105, p12,023-12,033. [2] Oberst et al., (2010) EPSC2010-827, [3] Wieczorek, (2015) Treratise on Geophysics (second edition), 10, p153-193. [4] Goosens et al. (2019) JGR (Planets), 125, e2019JE006086, [5] Baker et al., Icarus, 292, p54-73, [6] Neumann et al., (2015) Science Advances, 1(9), ISSN: 2375-2548. [7] Liu et al., (2020) 51st LPSC, abstract #1940.

INTRODUCTION AND OBJECTIVE:Mercaptoacetyltriglycine (MAG-3) renogram is one of the gold standard diagnostic tools of ureteropelvic junction obstruction (UPJO); however, there is no widely agreed in...

On 2017-09-27 at 18:56:12 UT a large meteoroid impacted the lunar surface, causing an impact flash with a duration of 1.12 seconds. Using Lunar Reconnaissance Orbiter Camera images, and the PyNAPLE (Python NAC Automatic Pair Lunar Evaluator) software pipeline, the resultant crater was identified. The crater is located at latitude φ= 8.0288, longitude λ = -76.546, approximately 14km east of the crater Glushko. The asymmetrical morphology of the ejecta blanket indicates the direction of impact was from the south, and impacting incidence angle was o. Introduction Lunar impacts are monitored on a regular basis, by both amateur and professional groups [1,2,3]. Since the first confirmed recording of a lunar impact flash in 1999, at least 600 confirmed impact flashes have been observed. This large volume of data has let to several studies on both the properties of the impactor, and the thermal evolution of the impact itself [4,5,6]. These studies make use of the observed brightness of the flash, and the most likely parent meteoroid stream to calculate the total energy and temperature of the impact, and estimate the resultant crater size. Very few of these impact craters have located [7] however, as finding metre scale craters and linking them to an observed impact with certainty is difficult. By identifying the resultant crater from an observed impact flash, valuable ground truth data can be obtained to help constrain the energy of the impact through use of crater scaling laws. The ejecta pattern of the impact can also tell us important information about the trajectory of the impactor. Impact Flash At 18:56:10 UT on 2017-09-27, a meteoroid impacted the lunar surface. The impact was observed by SdR UAI Luna members Bruno Cantarella and Luigi Zanatta, using a dual telescope system capturing with ZWO ASI120MM cameras, running at 25fps in one telescope, and 30fps in the other. It was also confirmed to be observed by Stefano Sposetti in Gnosca, Switzerland, ruling out the possibility the flash being a false detection. The flash lasted 29 frames in the 25fps camera, giving it a duration of 1.12s. The first 22 frames are shown in Fig. 1. Its peak luminosity is reached in the second frame after only 0.04s, with the peak quantum efficiency of the camera at 590nm. Figure 1: The first 22 frames of the 2017-09-27 impact flash. As there were no meteor streams active at the time of the impact, it is concluded that the impactor belonged to the sporadic meteor background. Crater Detection The PyNAPLE software [8] was utilised in order to search for the resultant impact crater in Lunar Reconnaissance Orbiter Narrow Angle Camera images (LRO NAC). PyNAPLE works by searching for all before-after LRO NAC image pairs for a given time and location on the lunar surface, and running them through several operations which calibrate, map project, register, and align the images in order for pixel by pixel division to occur. This produces a final image in which similarities have cancelled out, and changes between the images are highlighted. The crater, Fig. 2, was discovered in both LRO NAC images M1315871095R and M1344064055L, taken in 2019 and 2020 respectively, and and is absent from any images of the location from pre-2017. Figure 2: The crater formed during the 2017-09-27 lunar impact. Left: The ‘before’ image M1180620010R. Centre: The ‘after’ image M1315871095R. Right: The resultant image from dividing M1315871095R by M1180620010R. Crater Analysis The ejecta blanket and newly exposed regolith are higher albedo than the surrounding undisturbed material. Consequently, in the current LROC images the fresh regolith is overexposed, and no measurements as the craters diameter can be made, although the extent of the ejecta can be measured up to 600m away from the point of impact. This prevents the calculation of impact energy by employing crater scaling laws at this time. As the LRO is still collecting images, however, once new images of the site get released, these calculations will be possible. The ejecta blanket of the impact crater tells us some information on the impact. The asymmetrical morphology of the ejecta blanket, shown in Fig. 3, is formed by the meteoroid impacting with an angle below ~30o incidence, according to Shuvalov’s findings for projectiles below 100m in size [9]. The exclusion zone towards the bottom of the image containing no ejecta is indicative of the up-range direction of the impactor being towards the bottom of the image. Knowing the direction of the impact is important as incidence angle plays a large part in a number of crater scaling laws [10], but also as a way to differentiate potential parent meteoroid streams if there were multiple possible candidates. Figure 3: The cropped ratio image, with a threshold applied to highlight only the ejecta blanket. The presence of smaller exclusion zones within the ejecta blanket are likely due to effects caused by the local terrain. Future Work Once new images of the crater are collected and released by the Lunar Reconnaissance Orbiter, a size measurement for the impact crater can be obtained. This will allow for the application of crater scaling laws to calculate the impacting kinetic energy, and to solve backwards through current impact flash methodologies. Bibliography [1] Madiedo et al (2010) Advances in Astronomy, 2010:167494 [2] Xilouris et al (2018) A&A , 619, A141 [3] Suggs et al (2008) Earth Moon and Planets, 102:293298 [4] Avdellidou and Vaubaillon (2019) MNRAS, 484, 5212-5222 [5] Madiedo et al (2018) MNRAS, 480, 5010-5016 [6] Bonanos et al (2018) A&A, 612, A76 [7] Suggs et al (2014) Icarus, 10.1016 [8] Sheward et al (2019) EPSC-DPS2019, Abstract 1032-1 [9] Shuvalov (2011) Meteoritics & Planetary Science, 11, 1713-1718 [10] Horedt and Neukum (1984) Earth moon and Planets, 31, 265-269

BackgroundVaccine efficacy against the B.1.351 variant following mRNA-1273 vaccination in humans has not been determined. Nonhuman primates (NHP) are a useful model for demonstrating whether mRNA-1273 mediates protection against B.1.351.MethodsNonhuman primates received 30 or 100 µg of mRNA-1273 as a prime-boost vaccine at 0 and 4 weeks, a single immunization of 30 µg at week 0, or no vaccine. Antibody and T cell responses were assessed in blood, bronchioalveolar lavages (BAL), and nasal washes. Viral replication in BAL and nasal swabs were determined by qRT-PCR for sgRNA, and histopathology and viral antigen quantification were performed on lung tissue post-challenge.ResultsEight weeks post-boost, 100 µg x2 of mRNA-1273 induced reciprocal ID50 neutralizing geometric mean titers against live SARS-CoV-2 D614G and B.1.351 of 3300 and 240, respectively, and 430 and 84 for the 30 µg x2 group. There were no detectable neutralizing antibodies against B.1351 after the single immunization of 30 µg. On day 2 following B.1.351 challenge, sgRNA in BAL was undetectable in 6 of 8 NHP that received 100 µg x2 of mRNA-1273, and there was a ∼2-log reduction in sgRNA in NHP that received two doses of 30 µg compared to controls. In nasal swabs, there was a 1-log10 reduction observed in the 100 µg x2 group. There was limited inflammation or viral antigen in lungs of vaccinated NHP post-challenge.ConclusionsImmunization with two doses of mRNA-1273 achieves effective immunity that rapidly controls lower and upper airway viral replication against the B.1.351 variant in NHP.

Immune correlates of protection can be used as surrogate endpoints for vaccine efficacy. The nonhuman primate (NHP) model of SARS-CoV-2 infection replicates key features of human infection and may be used to define immune correlates of protection following vaccination. Here, NHP received either no vaccine or doses ranging from 0.3 – 100 μg of mRNA-1273, a mRNA vaccine encoding the prefusion-stabilized SARS-CoV-2 spike (S-2P) protein encapsulated in a lipid nanoparticle. mRNA-1273 vaccination elicited robust circulating and mucosal antibody responses in a dose-dependent manner. Viral replication was significantly reduced in bronchoalveolar lavages and nasal swabs following SARS-CoV-2 challenge in vaccinated animals and was most strongly correlated with levels of anti-S antibody binding and neutralizing activity. Consistent with antibodies being a correlate of protection, passive transfer of vaccine-induced IgG to naïve hamsters was sufficient to mediate protection. Taken together, these data show that mRNA-1273 vaccine-induced humoral immune responses are a mechanistic correlate of protection against SARS-CoV-2 infection in NHP.One-Sentence SummarymRNA-1273 vaccine-induced antibody responses are a mechanistic correlate of protection against SARS-CoV-2 infection in NHP.

SARS-CoV-2 Omicron is highly transmissible and has substantial resistance to neutralization following immunization with ancestral spike-matched vaccines. It is unclear whether boosting with Omicron-matched vaccines would enhance protection. Here, nonhuman primates that received mRNA-1273 at weeks 0 and 4 were boosted at week 41 with mRNA-1273 or mRNA-Omicron. Neutralizing titers against D614G were 4,760 and 270 reciprocal ID

Background Human monoclonal antibody (mAb) treatments are promising for COVID-19 prevention or therapy. The pre-exposure prophylactic efficacy of neutralizing antibodies that are engineered with mutations to extend their persistence in human serum and the neutralizing antibody titer in serum required for protection against SARS-CoV-2 infection remain poorly characterized. Methods The Fc-region of two neutralizing mAbs (COV2-2130 and COV2-2381) targeting non-overlapping epitopes on the receptor-binding domain of SARS-CoV-2 spike protein was engineered to extend their persistence in humans and reduce interactions with Fc gamma receptors. We assessed protection by individual antibodies or a combination of the two antibodies (designated ADM03820) given prophylactically by intravenous or intramuscular route in a non-human primate (NHP) model of SARS-CoV-2 infection. Findings Passive transfer of individual mAbs or ADM03820 conferred virological protection in the NHP respiratory tract in a dose-dependent manner, and ADM03820 potently neutralized SARS-CoV-2 variants of concern in vitro. We defined a protective serum neutralizing antibody titer and concentration in NHPs for passively transferred human antibodies that acted by direct viral neutralization. Conclusions In summary, we demonstrate that neutralizing antibodies with extended half-life and lacking Fc-mediated effector functions are efficient for pre-exposure prophylaxis of SARS-CoV-2 infection in NHPs. These results support clinical development of ADM03820 for COVID-19 prevention. Funding This research was supported by a contract from the JPEO-CBRND (W911QY-20-9-003), 20-05, the Joint Sciences and Technology Office and the Joint Program Executive Office (MCDC-16-01-002 JSTO, JPEO), DARPA grant (HR0011-18-2-0001), NIH grant (R01 AI157155), and the 2019 Future Insight Prize from Merck KGaA., Graphical Abstract, In this work, Cobb et al. described a combination of two human neutralizing antibodies, engineered with extended half-life and lacking Fc effector functions, which protected non-human primates against SARS-CoV-2 infection when given prophylactically by intravenous or intramuscular route. The serum antibody titer required for virological protection was defined.

During the 2019-01-21 lunar eclipse a lunar impact flash was observed by more than 20 observing sites, and two published estimates were made as to the location of the impact flash. In this work we present the preliminary results from the utilising PyNAPLE (Python NAC Automatic Pair Lunar Evaluator) with these coordinates in the search for the resultant impact crater. In total, 97 surface changes were detected, two of which being definite impact craters; however evidence suggests that they were formed during separate events to the 2019-01-21 impact. Introduction Lunar impact flashes been observed at least 600 times across both professional and amateur observation campaigns[1,2,3]. Despite this large amount of data, there are still unknowns when examining the relationship between the impact flash and the resultant impact crater. The most important unknown being the luminous efficiency, which determines the ratio of incoming kinetic energy converted to light, currently taken as between 10-2 and 10-4 [4]. Another unknown is to do with accuracy of crater scaling laws, which estimate the size of the formed impact crater but are derived from high energy impact tests, which become inaccurate for smaller impacts such as the most common lunar impacts [5]. In order to obtain ground truth data for refining of scaling laws, and further examination of luminous efficiency, PyNAPLE [6] is utilised to locate the resultant crater from hundreds of observed lunar impact flashes. The results discussed here are from a single search performed on the 2019-01-21 lunar impact flash, which coincided with the lunar eclipse and therefore had a number of analyses and location estimates performed [7,8]. Methods Using images from the Lunar Reconnaissance Orbiter Narrow Angle Camera (LRO NAC), a temporal pair (a pair of 'before' and 'after' images) can be divided highlighting changes between the two images. This process requires a number of constraints to be met, such as illumination angles being within 10o of each other, and being nadir pointing. This limit the number of pairs that can be formed for any location, especially as the events become more recent having less potential 'after' images. Using PyNAPLE, an exhaustive search can be performed forming each temporal pair in an area around the event location. This allows the identification of new surface features formed between the temporal pair images, which with adequate coverage locates the crater formed during the impact. The search for the 2019-01-21 crater was performed using literature values, and values calculated by AUGUR [9] (Table 1). Due to the lack of overlap between the coordinate estimates, a search area encompassing the coordinate ranges was used. Latitude Err Longitude Err AUGUR -30.03 ±0.00013 -68.20 ±0.02 Madiedo et al -29.20 ±0.30 -67.50 ±0.40 Zuluaga et al -29.43 +0.30 -0.21 -67.89 +0.07 -0.09 Table 1: Locations of the 2019-01-21 impact determined from observations of the impact flash. Results and Intepretation During PyNAPLEs ~350 computing hours search, 235 images were evaluated. After eliminating unsuitable images, this left 100 before and 30 after images. In total 108 temporal pairs were formed, and 97 confirmed surface changes identified (Fig. 1). The majority of these changes were small 'splodges' of darkened regolith due to impacts below the resolvable size for the LRO NAC, or ejecta deposits from nearby impacts. Two of the identified changes were clearly identifiable as impact craters (Fig. 2). Figure 1: The locations of identified changes for the 2019-01-21 impact flash compared to coordinates in literature. Figure 2: 400x400px 0.7m/px Top: Centred on φ=-28.276, λ=-67.073. Left: 'Before', M1165266223L Centre: 'After', M1315829707L Right: Division of 'After' by 'Before'. Bottom: Centred on φ=-28.178, λ=-67.234. Left: 'Before' , M1165266223R Centre: 'After', M1315829707R Right: Division of 'After' by 'Before'. While two confirmed impact craters were formed in the general area the impact flash was observed, it is suspected that these impacts are unconnected to the 2019-01-21 impact flash. This conclusion is drawn from a number of reasons; the main disqualifying factor is that the impacts are >6 standard deviations outside the coordinate ranges given by all three sources, and are outside the extent visual extent of the flash. For either of these to be the resultant crater, this would indicate that the impact flash originated above the lunar surface, for which there is no known mechanism that could sufficiently explain an elevated flash origin. Another factor implying no link is the fact that a large gap exists between the latest before images (2015-10-27) and earliest after images (2019-09-25), leaving a 1429 day uncertainty on when these craters were formed, the majority being before the 2019-01-21 event, indicating that they had likely already formed. The third factor is that, as seen between Figures 1 & 3, the distribution of detected impacts does not cover the entire search area. This is due to a lack of temporal pairs that could be formed, with the majority of temporal pairs overlapping one another. This led to coverage of only 30.5% of the search area, and is therefore P≈69.5 that the true primary impact resides within the unsearched area. Until further images are released from LRO NAC providing further temporal pair coverage, locating the primary crater is impossible. There are no known impact flashes, other than the 2019-01-21 event, in publicly available observations for the 2015-10-27 to 2019-09-25 period which could feasibly be the source of these craters. Figure 3: The footprints of searched temporal pairs for the 2019-01-21 impact. Future Work The method of temporal pair formation by PyNAPLE for impact flash events is being applied to both the publicly available NELIOTA impact flashes, and impact flashes detected by lunar monitoring at Aberystwyth University, UK, and Université Côte d'Azur, France. Further to this, as new images are released from LRO NAC, events such as the 2019-01-21 impact flash can be assessed for new coverage. References [1] Moser, D.E., et al (2015) NASA/TM 218213 [2] Liakos, A., et al (2019) arXiv e-prints [3] Madiedo, J.M., et al (2015) Planet. Space Sci, 111, 105-115 [4] Ortiz, J.L., et al (2015) MNRAS, 454, 1, 334-352 [5] Horedt, G.P., Neukum, G. (1984) Earth, Moon, and Planets, 31, 265-269 [6] Sheward, D., et al (2019) EPSC-DPS 2019 Abstract 1032-1 [7] Madiedo, J.M., et al (2019) MNRAS, 486(3), 3380-3387 [8] Zuluaga, J., et al (2019) MNRAS [9] Larson, R., et al (2019) EPSC-DPS 2019, Abstract 1193-3

An understanding of protective immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is critical for vaccine and public health strategies aimed at ending the global coronavirus disease 2019 (COVID-19) pandemic. A key unanswered question is whether infection with SARS-CoV-2 results in protective immunity against reexposure. We developed a rhesus macaque model of SARS-CoV-2 infection and observed that macaques had high viral loads in the upper and lower respiratory tract, humoral and cellular immune responses, and pathologic evidence of viral pneumonia. After the initial viral clearance, animals were rechallenged with SARS-CoV-2 and showed 5 log10 reductions in median viral loads in bronchoalveolar lavage and nasal mucosa compared with after the primary infection. Anamnestic immune responses after rechallenge suggested that protection was mediated by immunologic control. These data show that SARS-CoV-2 infection induced protective immunity against reexposure in nonhuman primates.

The global coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has made the development of a vaccine a top biomedical priority. In this study, we developed a series of DNA vaccine candidates expressing different forms of the SARS-CoV-2 spike (S) protein and evaluated them in 35 rhesus macaques. Vaccinated animals developed humoral and cellular immune responses, including neutralizing antibody titers at levels comparable to those found in convalescent humans and macaques infected with SARS-CoV-2. After vaccination, all animals were challenged with SARS-CoV-2, and the vaccine encoding the full-length S protein resulted in >3.1 and >3.7 log10 reductions in median viral loads in bronchoalveolar lavage and nasal mucosa, respectively, as compared with viral loads in sham controls. Vaccine-elicited neutralizing antibody titers correlated with protective efficacy, suggesting an immune correlate of protection. These data demonstrate vaccine protection against SARS-CoV-2 in nonhuman primates.

Background: Vaccines to prevent coronavirus disease 2019 (Covid-19) are urgently needed. The effect of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines on viral replication in both upper and lower airways is important to evaluate in nonhuman primates. Methods: Nonhuman primates received 10 or 100 μg of mRNA-1273, a vaccine encoding the prefusion-stabilized spike protein of SARS-CoV-2, or no vaccine. Antibody and T-cell responses were assessed before upper- and lower-airway challenge with SARS-CoV-2. Active viral replication and viral genomes in bronchoalveolar-lavage (BAL) fluid and nasal swab specimens were assessed by polymerase chain reaction, and histopathological analysis and viral quantification were performed on lung-tissue specimens. Results: The mRNA-1273 vaccine candidate induced antibody levels exceeding those in human convalescent-phase serum, with live-virus reciprocal 50% inhibitory dilution (ID50) geometric mean titers of 501 in the 10-μg dose group and 3481 in the 100-μg dose group. Vaccination induced type 1 helper T-cell (Th1)-biased CD4 T-cell responses and low or undetectable Th2 or CD8 T-cell responses. Viral replication was not detectable in BAL fluid by day 2 after challenge in seven of eight animals in both vaccinated groups. No viral replication was detectable in the nose of any of the eight animals in the 100-μg dose group by day 2 after challenge, and limited inflammation or detectable viral genome or antigen was noted in lungs of animals in either vaccine group. Conclusions: Vaccination of nonhuman primates with mRNA-1273 induced robust SARS-CoV-2 neutralizing activity, rapid protection in the upper and lower airways, and no pathologic changes in the lung. (Funded by the National Institutes of Health and others.).

Introduction: Circumcision is the most common surgical procedure performed by pediatric urologists. Ketorolac has been shown to have an efficacy similar to morphine in multimodal analgesic regimens without the commonly associated adverse effects. Concerns with perioperative bleeding limit the use of ketorolac as an adjunct for pain control in surgical patients. As such, we sought to evaluate our institutional outcomes with respect to ketorolac and postoperative bleeding.Methods: We retrospectively reviewed all pediatric patients undergoing circumcision from January 1, 2014 to December 31, 2015 at the Alberta Children’s Hospital. Demographics, perioperative analgesic regimens, and return to emergency department or clinic for bleeding were gathered through chart review.Results: A total of 475 patients undergoing circumcisions were studied, including 150 (32%) who received perioperative ketorolac and 325 (68%) who received standard analgesia. Patients receiving ketorolac were more likely to return to the emergency department or clinic for bleeding (ketorolac group 19/150 [13%], non-ketorolac group 16/325 [5.0%]; p=0.005). Patients receiving ketorolac were more likely to have postoperative sanguineous drainage (ketorolac group 96/150 [64%], non-ketorolac group 150/325 [46%]; p

Background Ureteral stents with magnetic tips (Blackstar©) were recently approved for use in Canada. To our knowledge this is the first published evidence of their use in pediatric patients. Traditionally, pediatric stent insertion and removal are performed under general anesthetic. Magnetic stents have three main benefits in pediatric patients; cost savings, decreased OR time and reduced general anesthetic exposure. Methods This study was a proof of concept pilot, ran from May 2017–May 2018 to demonstrate the safety and efficacy of magnetic stents in pediatric patients. Patients undergoing ureteroscopy, ureteric re-implantation, and pyeloplasty with simultaneous magnetic stent insertion. Forty (40) patients had regular double J stents removed under anesthesia and served as control cases, and 40 patients had a magnetic double J at initial surgery at two different sites, CHU de Quebec and Alberta Children's Hospital. Results Overall, 39 magnetic stents were successfully retrieved without general anesthetic, representing a retrieval failure rate of only 2.5%. Conclusion As demonstrated in our research, magnetic stents represent a safe and equally effective alternative to traditional stents, especially in a pediatric patient. This is because, at worst, if retrieval of the magnetic stent fails, traditional cystoscopic removal can be performed, so nothing is lost. Study Type Case–control study. Level of evidence Level III.

Electrochemical measurements and substrate analysis have been employed to study the corrosion of iron in sweet solution (pH = 6.8, T = 80 °C) over a period of 288 h. Correlated with decreasing corrosion rate, diffraction, microscopy, and spectroscopy data reveal the evolution of adhered sweet corrosion scale. Initially, it is comprised of two phases, siderite and chukanovite, with the latter affording little substrate protection. Subsequently, as the scale becomes highly protective, siderite is the sole component. Notably, siderite crystals are concluded to display a somewhat unexpected habit, which may be a trigger for local breakdown of protective sweet scales.