Global Vertical Distribution of Water Vapor on Mars: Results From 3.5 Years of ExoMars-TGO/NOMAD Science Operations.

We present water vapor vertical distributions on Mars retrieved from 3.5 years of solar occultation measurements by Nadir and Occultation for Mars Discovery onboard the ExoMars Trace Gas Orbiter, which reveal a strong contrast between aphelion and perihelion water climates. In equinox periods, most of water vapor is confined into the low-middle latitudes. In aphelion periods, water vapor sublimated from the northern polar cap is confined into very low altitudes-water vapor mixing ratios observed at the 0-5 km lower boundary of measurement decrease by an order of magnitude at the approximate altitudes of 15 and 30 km for the latitudes higher than 50°N and 30-50°N, respectively. The vertical confinement of water vapor at northern middle latitudes around aphelion is more pronounced in the morning terminators than evening, perhaps controlled by the diurnal cycle of cloud formation. Water vapor is also observed over the low latitude regions in the aphelion southern hemisphere (0-30°S) mostly below 10-20 km, which suggests north-south transport of water still occurs. In perihelion periods, water vapor sublimated from the southern polar cap directly reaches high altitudes (>80 km) over high southern latitudes, suggesting more effective transport by the meridional circulation without condensation. We show that heating during perihelion, sporadic global dust storms, and regional dust storms occurring annually around 330° of solar longitude (L S) are the main events to supply water vapor to the upper atmosphere above 70 km.

Dust, Sand, and Winds Within an Active Martian Storm in Jezero Crater.

Rovers and landers on Mars have experienced local, regional, and planetary-scale dust storms. However, in situ documentation of active lifting within storms has remained elusive. Over 5-11 January 2022 (LS 153°-156°), a dust storm passed over the Perseverance rover site. Peak visible optical depth was ∼2, and visibility across the crater was briefly reduced. Pressure amplitudes and temperatures responded to the storm. Winds up to 20 m s-1 rotated around the site before the wind sensor was damaged. The rover imaged 21 dust-lifting events-gusts and dust devils-in one 25-min period, and at least three events mobilized sediment near the rover. Rover tracks and drill cuttings were extensively modified, and debris was moved onto the rover deck. Migration of small ripples was seen, but there was no large-scale change in undisturbed areas. This work presents an overview of observations and initial results from the study of the storm.

A meta-epidemiological study of bias in randomized clinical trials of open and laparoscopic surgery.

BACKGROUND: Blinding, random sequence generation, and allocation concealment are established strategies to minimize bias in RCTs. Meta-epidemiological studies of drug trials have demonstrated exaggerated treatment effects in RCTs where such methods were not employed. As blinding is more difficult in surgical trials it is important to determine whether this applies to them. The study aimed to investigate this using systematic meta-epidemiological methods. METHOD: The Cochrane Database of Systematic Reviews was searched for systematic reviews of RCTs that compared laparoscopic and open abdominal surgical procedures. Each review was then scrutinized to determine whether at least one of the included trials was blinded. Eligible reviews were updated and individual RCTs retrieved. Extracted data included the primary outcomes of interest (length of stay and complications), secondary outcomes and a risk of bias assessment. A multistep meta-regression analysis was then performed to obtain an overall difference in the reported outcome differences between trials that employed each bias-minimization strategy, and those that did not. RESULTS: Some 316 RCTs were included, reporting on eight different procedures. Patient-blinded RCTs reported a smaller difference in length of stay between laparoscopic and open groups (difference of standardized mean differences -0·36 (95 per cent c.i. -0·73 to 0·00)) and complications (ratio of odds ratios 0·76 (95 per cent c.i. 0·61 to 0·93)). Blinding of postoperative carers and outcome assessors had similar effects. CONCLUSION: Lack of blinding significantly altered the treatment effect estimates of RCTs comparing laparoscopic and open surgery. Blinding should be implemented in surgical RCTs where possible to avoid systematic bias.

Supercomputer-Based Ensemble Docking Drug Discovery Pipeline with Application to Covid-19.

We present a supercomputer-driven pipeline for in silico drug discovery using enhanced sampling molecular dynamics (MD) and ensemble docking. Ensemble docking makes use of MD results by docking compound databases into representative protein binding-site conformations, thus taking into account the dynamic properties of the binding sites. We also describe preliminary results obtained for 24 systems involving eight proteins of the proteome of SARS-CoV-2. The MD involves temperature replica exchange enhanced sampling, making use of massively parallel supercomputing to quickly sample the configurational space of protein drug targets. Using the Summit supercomputer at the Oak Ridge National Laboratory, more than 1 ms of enhanced sampling MD can be generated per day. We have ensemble docked repurposing databases to 10 configurations of each of the 24 SARS-CoV-2 systems using AutoDock Vina. Comparison to experiment demonstrates remarkably high hit rates for the top scoring tranches of compounds identified by our ensemble approach. We also demonstrate that, using Autodock-GPU on Summit, it is possible to perform exhaustive docking of one billion compounds in under 24 h. Finally, we discuss preliminary results and planned improvements to the pipeline, including the use of quantum mechanical (QM), machine learning, and artificial intelligence (AI) methods to cluster MD trajectories and rescore docking poses.

Supercomputer-Based Ensemble Docking Drug Discovery Pipeline with Application to Covid-19.

We present a supercomputer-driven pipeline for in-silico drug discovery using enhanced sampling molecular dynamics (MD) and ensemble docking. We also describe preliminary results obtained for 23 systems involving eight protein targets of the proteome of SARS CoV-2. THe MD performed is temperature replica-exchange enhanced sampling, making use of the massively parallel supercomputing on the SUMMIT supercomputer at Oak Ridge National Laboratory, with which more than 1ms of enhanced sampling MD can be generated per day. We have ensemble docked repurposing databases to ten configurations of each of the 23 SARS CoV-2 systems using AutoDock Vina. We also demonstrate that using Autodock-GPU on SUMMIT, it is possible to perform exhaustive docking of one billion compounds in under 24 hours. Finally, we discuss preliminary results and planned improvements to the pipeline, including the use of quantum mechanical (QM), machine learning, and AI methods to cluster MD trajectories and rescore docking poses.

Quality of life, function and disability in individuals with chronic ankle symptoms: a cross-sectional online survey.

BACKGROUND: Chronic ankle conditions affect approximately 20% of Australian adults. Although there is a plethora of research on chronic hip and knee conditions, there is limited understanding of the impact of ankle problems. Thus, the significance of chronic ankle conditions is not clear. The aim of this study was to compare self-reported function, disability, instability, physical activity and quality of life (QoL) between adults with and without ankle symptoms. A secondary aim was to explore factors associated with QoL. METHOD: Individuals with symptoms of ankle pain and stiffness (symptomatic individuals) and controls with no ankle pain or stiffness (asymptomatic individuals) completed a cross-sectional online survey. The survey included the Ankle Osteoarthritis Scale (AOS), Foot and Ankle Ability Measure (FAAM), Cumberland Ankle Instability Tool (CAIT), International Physical Activity Questionnaire (IPAQ), Assessment of QoL (AQoL-6D), and questions about ankle injury history. RESULTS: A total of 394 individuals (270 symptomatic and 124 asymptomatic) with mean age of 48.8 (standard deviation (SD): 12.1) years and body mass index of 28.7 (7.7) kgm- 2 completed the survey. Standardized mean differences (SMD) were large to very large (1.45 to 3.20) for greater disability (AOS) and instability (CAIT), and poorer function (FAAM) in symptomatic compared to asymptomatic individuals. Individuals with ankle symptoms had higher body mass index and lower QoL (medium effect: SMD > 1). There were no differences in self-report physical activity between groups. Lower activities of daily living (ADL) function (FAAM-ADL) best explained QoL in a multiple regression model (R2 = 0.66, p = 0.001). CONCLUSION: Individuals with ankle symptoms reported ankle instability, greater disability, compromised function and worse QoL compared to asymptomatic individuals. There was a strong relationship between ankle function and QoL. Ankle-specific ability during ADL best explained the reduced QoL in individuals with ankle symptoms. Clinicians and researchers should consider ankle function as an antecedent to poorer QoL in patients who have ankle symptoms.

Granulysin: The attractive side of a natural born killer.

First discovered in the 1980's, granulysin has until recently been thought of solely as an effector molecule present within cytotoxic immune cell populations, and involved in the direct killing of pathogens and infected or transformed eukaryotic cells. However, recent research has suggested an additional role of granulysin, in particular the 15 kDa isoform. While 9 kDa granulysin is broadly cytotoxic and capable of the direct killing of bacteria and other pathogens, the 15 kDa isoform of this molecule has been shown to function as an immune 'alarmin', causing the maturation and migration of antigen-presenting cells and other cells of the immune system. This dual function of granulysin indirectly increases the immune response to an infection or tumour, and therefore escalates its importance in the immune system. Here we review the different roles of granulysin, both as a cytotoxic molecule, and as a modulator of the immune system, and discuss the impact this molecule may have on the response to tumour and infection.

Effects of the MY34/2018 Global Dust Storm as Measured by MSL REMS in Gale Crater.

The Rover Environmental Monitoring Station (REMS) instrument that is onboard NASA's Mars Science Laboratory (MSL) Curiosity rover. REMS has been measuring surface pressure, air and ground brightness temperature, relative humidity, and UV irradiance since MSL's landing in 2012. In Mars Year (MY) 34 (2018) a global dust storm reached Gale Crater at Ls ~190°. REMS offers a unique opportunity to better understand the impact of a global dust storm on local environmental conditions, which complements previous observations by the Viking landers and Mars Exploration Rovers. All atmospheric variables measured by REMS are strongly affected albeit at different times. During the onset phase, the daily maximum UV radiation decreased by 90% between sols 2075 (opacity ~1) and 2085 (opacity ~8.5). The diurnal range in ground and air temperatures decreased by 35K and 56K, respectively, with also a diurnal-average decrease of ~2K and 4K respectively. The maximum relative humidity, which occurs right before sunrise, decreased to below 5%, compared with pre-storm values of up to 29%, due to the warmer air temperatures at night while the inferred water vapor abundance suggests an increase during the storm. Between sols 2085 and 2130, the typical nighttime stable inversion layer was absent near the surface as ground temperatures remained warmer than near-surface air temperatures. Finally, the frequency-domain behavior of the diurnal pressure cycle shows a strong increase in the strength of the semidiurnal and terdiurnal modes peaking after the local opacity maximum, also suggesting differences in the dust abundance inside and outside Gale.

Network meta-analysis of surgical management of gastro-oesophageal reflux disease in adults.

BACKGROUND: Proton pump inhibitors are the mainstay of treatment for gastro-oesophageal reflux disease, but are associated with ongoing costs and side-effects. Antireflux surgery is cost-effective and is preferred by many patients. A total (360o or Nissen) fundoplication is the traditional procedure, but other variations including partial fundoplications are also commonly performed, with the aim of achieving durable reflux control with minimal dysphagia. Many RCTs and some pairwise meta-analyses have compared some of these procedures but there is still uncertainty about which, if any, is superior. Network meta-analysis allows multiple simultaneous comparisons and robust synthesis of the available evidence in these situations. A network meta-analysis comparing all antireflux procedures was performed to identify which has the most favourable outcomes at short-term (3-12 months), medium-term (1-5 years) and long-term (10 years and more than 10 years) follow-up. METHODS: Article databases were searched systematically for all eligible RCTs. Primary outcomes were quality-of-life measures and dysphagia. Secondary outcomes included reflux symptoms, pH studies and complications. RESULTS: Fifty-one RCTs were included, involving 5357 patients and 14 different treatments. Posterior partial fundoplication ranked best in terms of reflux symptoms, and caused less dysphagia than most other interventions including Nissen fundoplication. This was consistent across all time points and outcome measures. CONCLUSION: Posterior partial fundoplication provides the best balance of long-term, durable reflux control with less dysphagia, compared with other treatments.

Composite infrared spectrometer (CIRS) on Cassini.

The Cassini spacecraft orbiting Saturn carries the composite infrared spectrometer (CIRS) designed to study thermal emission from Saturn and its rings and moons. CIRS, a Fourier transform spectrometer, is an indispensable part of the payload providing unique measurements and important synergies with the other instruments. It takes full advantage of Cassini's 13-year-long mission and surpasses the capabilities of previous spectrometers on Voyager 1 and 2. The instrument, consisting of two interferometers sharing a telescope and a scan mechanism, covers over a factor of 100 in wavelength in the mid and far infrared. It is used to study temperature, composition, structure, and dynamics of the atmospheres of Jupiter, Saturn, and Titan, the rings of Saturn, and surfaces of the icy moons. CIRS has returned a large volume of scientific results, the culmination of over 30 years of instrument development, operation, data calibration, and analysis. As Cassini and CIRS reach the end of their mission in 2017, we expect that archived spectra will be used by scientists for many years to come.

Composite infrared spectrometer (CIRS) on Cassini: publisher's note.

This publisher's note renumbers the reference list in Appl. Opt.56, 5274 (2017)APOPAI0003-693510.1364/AO.56.005274.

The Vertical Dust Profile over Gale Crater, Mars.

We create a vertically coarse, but complete, vertical profile of dust mixing ratio from the surface to the upper atmosphere over Gale Crater, Mars, using the frequent joint atmospheric observations of the orbiting Mars Climate Sounder (MCS) and the Mars Science Laboratory (MSL) Curiosity rover. Using these data and an estimate of planetary boundary layer (PBL) depth from the MarsWRF general circulation model, we divide the vertical column into three regions. The first region is the Gale Crater PBL, the second is the MCS-sampled region, and the third is between these first two. We solve for a well-mixed dust mixing ratio within this third (middle) layer of atmosphere to complete the profile. We identify a unique seasonal cycle of dust within each atmospheric layer. Within the Gale PBL, dust mixing ratio maximizes near southern hemisphere summer solstice (Ls = 270°) and minimizes near winter solstice (Ls = 90-100°) with a smooth sinusoidal transition between them. However, the layer above Gale Crater and below the MCS-sampled region more closely follows the global opacity cycle and has a maximum in opacity near Ls = 240° and exhibits a local minimum (associated with the "solsticial pause" in dust storm activity) near Ls = 270°. With knowledge of the complete vertical dust profile, we can also assess the frequency of high-altitude dust layers over Gale. We determine that 36% of MCS profiles near Gale Crater contain an "absolute" high-altitude dust layer wherein the dust mixing ratio is the maximum in the entire vertical column.

Network meta-analysis of the effect of preoperative carbohydrate loading on recovery after elective surgery.

BACKGROUND: Three meta-analyses have summarized the effects of preoperative carbohydrate administration on postoperative outcomes in adult patients undergoing elective surgery. However, these studies could not account for the different doses of carbohydrate administered and the different controls used. Multiple-treatments meta-analysis allows robust synthesis of all available evidence in these situations. METHODS: Article databases were searched systematically for RCTs comparing preoperative carbohydrate administration with water, a placebo drink, or fasting. A four-treatment multiple-treatments meta-analysis was performed comparing two carbohydrate dose groups (low, 10-44 g; high, 45 g or more) with two control groups (fasting; water or placebo). Primary outcomes were length of hospital stay and postoperative complication rate. Secondary outcomes included postoperative insulin resistance, vomiting and fatigue. RESULTS: Some 43 trials involving 3110 participants were included. Compared with fasting, preoperative low-dose and high-dose carbohydrate administration decreased postoperative length of stay by 0·4 (95 per cent c.i. 0·03 to 0·7) and 0·2 (0·04 to 0·4) days respectively. There was no significant decrease in length of stay compared with water or placebo. There was no statistically significant difference in the postoperative complication rate, or in most of the secondary outcomes, between carbohydrate and control groups. CONCLUSION: Carbohydrate loading before elective surgery conferred a small reduction in length of postoperative hospital stay compared with fasting, and no benefit in comparison with water or placebo.

Photosynthetic responses of a dominant C4 grass to an experimental heat wave are mediated by soil moisture.

Extreme heat waves and drought are predicted to increase in frequency and magnitude with climate change. These extreme events often co-occur, making it difficult to separate their direct and indirect effects on important ecophysiological and carbon cycling processes such as photosynthesis. Here, we assessed the independent and interactive effects of experimental heat waves and drought on photosynthesis in Andropogon gerardii, a dominant C4 grass in a native mesic grassland. We experimentally imposed a two-week heat wave at four intensity levels under two contrasting soil moisture regimes: a well-watered control and an extreme drought. There were three main findings from this study. First, the soil moisture regimes had large effects on canopy temperature, leading to extremely high temperatures under drought and low temperatures under well-watered conditions. Second, soil moisture mediated the photosynthetic response to heat; heat reduced photosynthesis under the well-watered control, but not under the extreme drought treatment. Third, the effects of heat on photosynthesis appeared to be driven by a direct thermal effect, not indirectly through other environmental or ecophysiological variables. These results suggest that while photosynthesis in this dominant C4 grass is sensitive to heat stress, this sensitivity can be overwhelmed by extreme drought stress.

Photophysics of GFP-related chromophores imposed by a scaffold design.

In this paper, a rigid scaffold imposes the photophysics of chromophores with a benzylidene imidazolidinone core by mimicking the ß-barrel structure of the green fluorescent protein (GFP) and its analogs. The designed artificial frameworks maintain fluorescence responses and, therefore, conformational rigidity of typically non-emissive GFP-related chromophores. To replicate a small weight percent of the chromophore inside the natural GFP, two synthetic approaches were utilized: coordinative immobilization and non-coordinative inclusion. Despite low chromophore loading in the rigid matrix, both approaches resulted in formation of photoluminescent hybrid materials. Furthermore, the rigid scaffold dictates chromophore fluorescence by replicating its behavior in solution or the solid state. The presented results open an avenue for utilization of rigid scaffolds in the engineering of materials with tunable photoluminescence profiles for a variety of practical applications.

Liberal transfusion strategies still the trend in burn surgery.

OBJECTIVE: Blood is a limited resource in middle-income countries such as South Africa. Transfusion is associated with complications and expense. We aimed to understand our transfusion practices in burn surgery as well as ascertain the opinion of a broader group of surgeons and anaesthetists regarding transfusion triggers in order to understand the rationale and bias that drives current transfusion practice in our setting. METHOD: Firstly, we investigated the current blood practices at our regional burn service through an audit of perioperative notes for all patients receiving packed cell transfusions in a 24-month period. Secondly, we formulated a questionnaire asking for opinion on acceptable preoperative and postoperative haemoglobin targets for a list of elective, emergency and burn operations that was distributed at a number of meetings. RESULTS: Seventy-two patients received a total of 103 perioperative transfusions. The median preoperative haemoglobin was 9.8 g/dL in both children and adults and the median postoperative haemoglobin was 10.1 and 9.1 g/dL in children and adults respectively. The cohort was divided into two groups: the first surgery and the subsequent surgeries. In the adult group the mean time to first surgery post burn was 11.5 days with a median volume of 0.73 mls/kg/% operated surface area (range 0.16-1.54) of packed cells transfused per operation. In the paediatric group the mean time to first surgery post burn was 9 days (range 2-54) with a median volume of 1.1 mls/kg/% operated surface area (range 0.56-2.14) of packed cells transfused per operation. One hundred and fifty questionnaires were handed out and 103 (69%) were completed. The average proposed preoperative and postoperative haemoglobin was 9.3 g/dL and 8.4g/dL respectively. The majority of respondents (60% in elective surgery, 43% in emergency surgery and 60% in burn surgery) would like preoperative haemoglobin to be 10 g/dL and above. CONCLUSION: Research suggests that a restrictive blood transfusion approach is being increasingly implemented as best practice. However, our surgical community does not seem to accept a restrictive strategy as part of blood management principles. A shift in this practice could result in clinical benefit by reducing complications and increasing cost saving in our resource constrained setting. We plan to protocolise earlier surgery and blood conservation strategies intraoperatively in addition to a restrictive strategy in our burn service.

Chronic pancreatitis, depression and substance use disorders: A not uncommon combination.

Chronic pancreatitis (CP) is a progressive and debilitating disease. A potentially important consideration is the relationship between CP, depression and substance use disorders, which seems to be circular and multiplicative. Pain management is a critical component of intervention, and it would seem that in the context of chronic illness this requires a biopsychosocial approach aiming for a tailored intervention that strikes an appropriate therapeutic balance.

The effect of flexor digitorum profundus tendon shortening on jersey finger surgical repair: a cadaveric biomechanical study.

Delayed diagnosis of jersey finger injuries often results in retraction of the flexor digitorum profundus tendon. Current practice recommends limiting tendon advancement to 1 cm in delayed repairs. The purpose of this study was to investigate the biomechanical consequences of tendon shortening on the force required to form a fist. The flexor digitorum profundus muscle was isolated in ten cadaveric forearms and the force required to form a fist was recorded. Simulated jersey finger injuries to the ring finger were then created and repaired. The forces required to pull the fingertips to the palm after serial tendon advancements were measured. There was a near linear increase in the force required for making a fist with shortening up to 2.5 cm. The force required to make a fist should be taken into account when considering the limit of 'safe' tendon shortening in delayed repair of jersey finger injuries.

Strong water isotopic anomalies in the martian atmosphere: probing current and ancient reservoirs.

We measured maps of atmospheric water (H2O) and its deuterated form (HDO) across the martian globe, showing strong isotopic anomalies and a significant high deuterium/hydrogen (D/H) enrichment indicative of great water loss. The maps sample the evolution of sublimation from the north polar cap, revealing that the released water has a representative D/H value enriched by a factor of about 7 relative to Earth's ocean [Vienna standard mean ocean water (VSMOW)]. Certain basins and orographic depressions show even higher enrichment, whereas high-altitude regions show much lower values (1 to 3 VSMOW). Our atmospheric maps indicate that water ice in the polar reservoirs is enriched in deuterium to at least 8 VSMOW, which would mean that early Mars (4.5 billion years ago) had a global equivalent water layer at least 137 meters deep.