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Human DUX4 and its mouse ortholog Dux are normally expressed in the early embryo—the 4-cell or 2-cell cleavage stage embryo, respectively—and activate a portion of the first wave of zygotic gene expression. DUX4 is epigenetically suppressed in nearly all somatic tissue, whereas facioscapulohumeral dystrophy (FSHD)-causing mutations result in its aberrant expression in skeletal muscle, transcriptional activation of the early embryonic program and subsequent muscle pathology. Although DUX4 and Dux both activate an early totipotent transcriptional program, divergence of their DNA binding domains limits the use of DUX4 expressed in mice as a preclinical model for FSHD. In this study, we identify the porcine DUXC messenger ribonucleic acid expressed in early development and show that both pig DUXC and human DUX4 robustly activate a highly similar early embryonic program in pig muscle cells. These results support further investigation of pig preclinical models for FSHD.

Headcut erosion is a very common process occurring at the head of rills, crop furrows and ephemeral gullies. A numerical model of the headcut flow was built to study the wall shear stress characteristics downstream of the scour hole, which is very important in headcut erosion prediction models. The calculated nappe parameters are very close to experimental data and/or equation results. The calculated flow field, velocity centreline of the free jet part and the locations of the maximum velocity in the scour hole are also close to the experimental data. It was found that the upstream flow rate and downstream water level can affect both the maximum value and the distribution of the wall shear stress. Taking into account the affecting factors and referencing the form of the existing relations on the maximum wall shear stress caused by the impinging jet, the relation of the maximum wall shear stress occurring downstream of the headcut is obtained. The wall shear stress distribution can be described by exponential functions. The new prediction equation of the maximum wall shear stress can be used in existing headcut erosion prediction models for calculating equilibrium scour hole depth or scour hole deepening rate.

Background Cerebral oximetry using near-infrared spectroscopy (NIRS) has been shown to reduce neurological dysfunction and hospital length-of-stay after adult cardiac surgery in some but not all studies. We audited maintaining cerebral saturations at or above baseline and showed improved neurological and length-of-stay outcomes. Our hypothesis for this study was that our NIRS protocol would improve neurological and length-of-stay outcomes. Methods This prospective, single centre, double-blinded controlled study randomized 182 consecutive patients, scheduled for cardiac surgery using cardiopulmonary bypass. Participants were randomized by concealed envelope prior to anaesthesia. NIRS study group were managed perioperatively using our NIRS protocol of 8 interventions, increase cardiac output, normocapnia, increase mean arterial pressure, increase inspired oxygen, depth of anaesthesia, blood transfusion, correction of bypass cannula, change of surgical plan to restore levels equal to or above baseline. The control group had standard management without NIRS. Primary outcomes were neurological impairment (early and late) and hospital length-of-stay. Secondary outcomes were ventilation times, intensive care length-of-stay, major organ dysfunction and mortality. Results 91 patients entered each group. There was a significant improvement in self-reported six-month general functionality in the NIRS group ( p = 0.016). Early neurological dysfunction and hospital length-of-stay was the same in both groups. Of the secondary outcomes only Intensive Care length-of-stay was statistically significant, being shorter in the NIRS group ( p = 0.026). Conclusion Maintaining cerebral saturations above baseline reduces time spent in Intensive Care and may improve long term functional recovery but not stroke, major organ dysfunction and mortality.

Chikungunya virus (CHIKV) disease is an ongoing public health threat. We aimed to evaluate the safety and immunogenicity of PXVX0317, an aluminium hydroxide-adjuvanted formulation of a CHIKV virus-like particle (VLP) vaccine.This randomised, double-blind, parallel-group, phase 2 trial was conducted at three clinical trial centres in the USA. Eligible participants were healthy CHIKV-naïve adults aged 18-45 years. Participants were stratified by site and randomly assigned (1:1:1:1:1:1:1:1) to one of the eight vaccination groups using a block size of 16. Group 1 received two doses of unadjuvanted PXVX0317 28 days apart (2 × 20 μg; standard); all other groups received adjuvanted PXVX0317: groups 2-4 received two doses 28 days apart (2 × 6 μg [group 2], 2 × 10 μg [group 3], or 2 × 20 μg [group 4]; standard); group 4 also received a booster dose 18 months after the first active injection (40 μg; standard plus booster); groups 5-7 received two doses 14 days apart (2 × 6 μg [group 5], 2 × 10 μg [group 6], or 2 × 20 μg [group 7]; accelerated); and group 8 received one dose (1 × 40 μg; single). The primary endpoint was the geometric mean titre of anti-CHIKV neutralising antibody on day 57 (28 days after the last vaccination), assessed in the immunogenicity-evaluable population. Additionally, we assessed safety. This trial is registered at ClinicalTrials.gov, NCT03483961.This trial was conducted from April 18, 2018, to Sept 21, 2020; 468 participants were assessed for eligibility. Of these, 415 participants were randomly assigned to eight groups (n=53 in groups 1, 5, and 6; n=52 in groups 2 and 8; n=51 in groups 3 and 7; and n=50 in group 4) and 373 were evaluable for immunogenicity. On day 57, serum neutralising antibody geometric mean titres were 2057·0 (95% CI 1584·8-2670·0) in group 1, 1116·2 (852·5-1461·4; p=0·0015 vs group 1 used as a reference) in group 2, 1465·3 (1119·1-1918·4; p=0·076) in group 3, 2023·8 (1550·5-2641·7; p=0·93) in group 4, 920·1 (710·9-1190·9; p0·0001) in group 5, 1206·9 (932·4-1562·2; p=0·0045) in group 6, 1562·8 (1204·1-2028·3; p=0·14) in group 7, and 1712·5 (1330·0-2205·0; p=0·32) in group 8. In group 4, a booster dose increased serum neutralising antibody geometric mean titres from 215·7 (95% CI 160·9-289·1) on day 547 to 10 941·1 (7378·0-16 225·1) on day 575. Durability of the immune response (evaluated in groups 1, 4, and 8) was shown up to 2 years. The most common solicited adverse event was pain at the injection site, reported in 12 (23%) of 53 participants who received the unadjuvanted vaccine (group 1) and 111 (31%) of 356 who received the adjuvanted vaccine. No vaccine-related serious adverse events were reported.PXVX0317 was well tolerated and induced a robust and durable serum neutralising antibody immune response against CHIKV up to 2 years. A single 40 μg injection of adjuvanted PXVX0317 is being further investigated in phase 3 clinical trials (NCT05072080 and NCT05349617).Emergent BioSolutions.

Both red blood cell (RBC) transfusion and anaemia or low haematocrit increase morbidity and mortality associated with surgery. Chronic anaemia in the elective patient carries a small risk in non-haemorrhagic surgery. Where bleeding is anticipated anaemia should be treated medically to avoid (RBC) transfusion which will increase the risk to the patient. Major bleeding (MB) has the biggest impact on adverse outcomes. Acute anaemia is caused by surgical bleeding and requires RBC transfusion to keep the haematocrit (Hct) above 21% and haemoglobin (Hb) above 7 g/dl in patients without coronary artery disease (CAD) and between Hct 24–27% or Hb >8 g/dl in patients with CAD. Having a patient blood management programme can mitigate the problem. Medical, surgical and anaesthetic planning are paramount to avoid bleeding and transfusion which together have a significant impact on adverse outcomes for the patient.

Topographic effects on Cs-137 concentrations in a forested area were quantitatively examined using 58 soil core samples collected in a village in Fukushima, Japan, which was directly impacted by the radioactive plume emitted during the 2011 Fukushima Daiichi Nuclear Power Plant (FDNPP) accident. In this study, five topographic parameters and two soil properties were evaluated as controls on the soil Cs-137 concentration using generalized additive models (GAMs), a flexible statistical method for evaluating the functional dependencies of multiple parameters. GAMs employing soil dry bulk density, mass water content, and elevation explained 54 % of the observed concentrations of Cs-137 within this landscape, whereas GAMs employing elevation, slope, and upslope distance explained 47 % of the observed concentrations, which provide strong evidence of topographic effects on Cs-137 concentrations in soils. The model fit analysis confirmed that the topographic effects are strongest when multiple topographic parameters and soil properties are included. The ability of each topographic feature to predict Cs-137 concentrations was influenced by the resolution of the digital elevation models. The movement of Cs-137 into the subsurface in this area near Fukushima was faster in comparison to regions affected by the Chernobyl Nuclear Power Plant accident. These results suggest that the effects of topographic parameters should be considered carefully in the use of anthropogenic radionuclides as environmental tracers and in the assessment of current and future environmental risks due to nuclear power plant accidents.

Introduction: Cardiac surgery is associated with significant morbidity and longer length-of-stay (LOS) than most other surgeries. Regional cerebral oximetry (rSO2) using near-infrared spectroscopy (NIRS) on the patient’s forehead monitors cerebral oxygenation during surgery and cardiopulmonary bypass (CPB). Its purpose is to detect and manage periods of cerebral hypoxia which may otherwise go undetected, thereby reducing morbidity. But outcomes have been inconsistent, and not all cardiac departments have adopted this non-invasive, simple-to-use technology. We aimed to study the efficacy of our use of rSO2 by recording seven outcomes for each patient according to their preoperative rSO2, the mean intraoperative rSO2, and four ischemic thresholds during surgery. Method: This is a retrospective audit of cardiac surgical patients in whom a protocol was used to maintain rSO2 above the preoperative value and studied seven major morbidity outcomes. Cerebral oximetry data were recorded for each patient and analyzed for six variables: preoperative baseline rSO2, mean intraoperative rSO2, and four ischemic thresholds defined as an area under the curve (AUC) in minutes% below the baseline rSO2,minus 10% below the baseline, minus 20% the below baselineand minus 50% below baseline. Outcomes examined were: delirium, stroke, postoperative rise in creatinine of 50 mmol, absolute creatinine of 200 mmol, need for new renal replacement therapy (RRT), hospital LOS and inpatient mortality. Results: Complete data were available for 166 patients. Lower mean preoperative rSO2 was associated with stroke (p=0.031), mild and severe renal dysfunction (p=0.045 and p=0.036), death-in-hospital (p=0.027) and prolonged hospital LOS (p=0.005). Lower mean intraoperative rSO2 during surgery was associated with the outcomes of renal dysfunction, mild (p=0.027), moderate (p=0.003) or severe (p=0.002), death-in-hospital (p=0.003) and prolonged hospital LOS (p=0.015). Of the four ischemic thresholds defined, only new RRT occurring at minus 20% and minus 50% below baseline was significant. Conclusion: Lower preoperative rSO2 and mean intraoperative rSO2 were associated with poor outcomes, notably leading to a significant increase in hospital LOS. Mild degrees of cerebral ischemia below the baseline and minus 10% of the baseline during surgery were well tolerated.

This research collected forest soil samples from Fukushima, Japan, where the 2011 Fukushima Daiichi Nuclear Power Plant (FDNPP) accident contaminated the land. The purpose of this study was to examine how the local topography influenced the radiocesium (Cs-137) accumulation patterns in soils over the years since the accident. As an analytical method, the general additive model (GAM) was used to determine at what percentages the topographic parameters explain Cs-137 contamination levels down to a depth of 30 cm. For comparison, topographic parameters were extracted from both 1 m and 10 m digital evaluation models (DEMs). The effects of topography were compared with the effects of the soil water content and dry soil bulk density. An additional Tukey’s honestly significant difference (HSD) test was conducted to determine the significance of the hillslope aspect and vegetation cover differences on concentration predictions. The results showed that, at this study site, topographic parameters extracted from the 10 m DEM better predicted Cs-137 levels. The models with a single topographic parameter did not explain Cs-137 levels higher than 30 %. However, combining the parameters improved the explanation percentages. The relative influences of topographic parameters and soil properties were similar throughout the soil depth, showing their subsurface co-functionalities for Cs-137 concentration levels. Tukey’s HSD test results showed the inter-effects of topography and vegetation cover differences. The results of this study indicate that the selection of topographic parameters, as well as the chosen methods of their extractions, have implications for physical models assessing radionuclide contamination levels.

An experimental study was conducted to examine the formation of secondary circulation in a grid-mixing box and to determine its effect on turbulence. This apparatus has been used extensively to study turbulence and mixing in a variety of geophysical contexts, and it is commonly assumed that turbulence is nearly isotropic and horizontally homogenous and that it is a zero-mean shear flow. Exceptions to these assumptions, however, have been reported, where a secondary flow pattern has been observed consisting of two roughly symmetric large-scale circulations with upward flow in the center of the box and downward return flow along the sides. These secondary flows appear to be associated with different grid oscillation conditions and box and grid geometries, and criteria have been proposed to describe conditions when secondary flow may be expected. Experiments were conducted for three different combinations of the grid oscillation stroke and frequency, while maintaining a near constant grid Reynolds number, to examine the formation and strength of the secondary flow and its effect on the magnitude and distribution of turbulence within the box. Velocity characteristics were obtained by particle image velocimetry (PIV). Results show that (1) secondary circulations were present for all combinations of the grid oscillation conditions; (2) as stroke length increased, the intensity of the secondary circulation and the contribution of these motions to total kinetic energy increased; and (3) the presence of secondary circulation results in greater overall mixing and turbulent transport in the region close to the grid. These insights are expected to be relevant to a wide range of mixing box applications.

The following fictional case is intended as a learning tool within the Pathology Competencies for Medical Education (PCME), a set of national standards for teaching pathology. These are divided into three basic competencies: Disease Mechanisms and Processes, Organ System Pathology, and Diagnostic Medicine and Therapeutic Pathology. For additional information, and a full list of learning objectives for all three competencies, see http://journals.sagepub.com/doi/10.1177/2374289517715040 . 1

Introduction The extravascular lung water content is determined by the use of lung ultrasound (LUS) which is represented as B-lines. The aim of this study was to investigate whether the LUS measurement of extravascular lung water was correlated to changes in oxygenation. Methods This prospective cohort study was comprised of 73 patients with an average age of 56 (range: 18 to 87 years) who underwent elective cardiac surgery using cardiopulmonary bypass. The LUS score was performed preoperatively, time zero (T0), at one hour (T1), and at 24 hours (T2) post-surgery. Additionally, arterial oxygen partial pressure and fraction of inspired oxygen (PaO2/FiO2) ratio were measured at each time and the time-to-extubation. Results A negative correlation was found between the LUS score and PaO2/FiO2 at T1 (p < 0.004). Extubation time and changes in the lung ultrasound score at T0 - T2 were positively correlated (p < 0.03). Plus, there was a positive correlation between fluid balance and lung ultrasound score at T2 (p < 0.03). Conclusion We found three significant correlations that support the use of LUS in cardiac surgery: 1) the more B-lines, the lower the oxygenation; 2) the more B-lines, the longer the period of ventilation; 3) the more B-lines, the more positive the fluid balance. LUS is a non-invasive bedside investigation that can be used to judge extravascular lung water, providing useful information in the management of patient oxygenation, fluid balance, and extubation.

Introduction Renal dysfunction is a significant variable in determining the outcome of surgery, such as cardiopulmonary bypass graft and valvular replacement, used to treat cardiovascular diseases. In Saudi Arabia, the incidence of renal failure and diabetes is higher than in most western populations. Our aim is to determine the renal outcome of patients who underwent cardiac surgery at King Faisal Cardiac Center from 2014 to 2017. Methods This a retrospective cohort study using a non-probability consecutive sampling technique for selection of the study population to assess the renal outcome in cardiac surgery patients using cardiopulmonary bypass from May 2014 to June 2017 in King Faisal Cardiac Center, Jeddah. Patients older than 18 years of age undergoing cardiac surgery, with available data, were included. Categorical variables were summarized by percentages and frequencies, and continuous variables by means and standard deviations, or medians and interquartile ranges if their distributions were skewed. Logistic regression was done with post-op renal impairment as the dependent variable and pre-op renal dysfunction, age, gender, smoking status, diabetes, hypertension, dyslipidemia, and cardiopulmonary bypass time as independent variables. Results Our sample size included 244 patients who underwent cardiac surgery in this study period; their mean age was 60.5 (SD =7.5) with a mean body mass index (BMI) of 28.62 (SD=5.19). Among our population, 73% (n = 179) were males and 27% (n =66) were females. Two percent (2%) of patients (n = 5) died within 30 days, 4% of patients (n = 10) with temporary dialysis, 8% of patients (n = 19) with postoperative renal dysfunction, and no patients with permanent dialysis. The data showed a significant relationship between levels of creatinine preoperatively and postoperative renal dysfunction (p-value = 0.0001, OR=1.05, 95% CI of 1.031 to 1.064). Conclusion The main predictor of poor renal outcomes for cardiac surgery is preoperative creatinine. While other factors, such as age, gender, body mass index, cardiopulmonary bypass time, diabetes, hypertension, and dyslipidemia, did not show any risk to the postoperative renal outcome.

Background Blood transfusion is a commonly used therapy in cardiac surgery, whether it is given during the surgery or in the intensive care unit. It is important to evaluate the risks and benefits of exposure to blood transfusion. The use of blood transfusions can influence patient outcome. Previous studies have implicated blood transfusion as a causative factor in post-operative infection. Objectives We aim to determine the effect of blood transfusion on post-operative infection in cardiac surgery patients at the King Faisal Cardiac Center, Jeddah, Saudia Arabia, from January 2017 to January 2019. Methods The regular six-week follow-up of cardiac surgery patients allowed us to maintain a six-week infection span. The main variables included patient characteristics, operative characteristics, pre-operative hemoglobin, six-week infection, blood transfusion, and clinical outcomes. A logistic regression model was developed to identify patient and procedure variables that were associated with blood transfusion and infection. The baseline variables were entered into the model. Variables with p-value less than 0.05 were considered significant. Results The incidence of transfusion out of 197 patients was 93.4% (n = 184). The occurrence of infection was 31.82% (n = 63). There was no difference in post-operative infection for patients who received blood transfusions compared with those who did not receive blood transfusions (p = 0.902). In comparing patients receiving 1-2 units of red blood cells (RBCs) (48%) and those receiving >2 units of RBCs (52%), there was no significance (p = 0.549). Conclusions There was no association between the incidence of infection and blood transfusion. While there are other reasons for withholding blood, it would not be recommended to do so based on the concern of infection.

Soil erosion due to rainfall and overland flow can be detrimental to agricultural management and long-term agricultural sustainability. Although numerous conservation measures and planning strategies have greatly reduced the amount of sediment moving within the landscape, there are still unresolved questions concerning initiation of particle motion, susceptibility to erosion, total soil loss, sediment transport and general measurement theory. Within agricultural fields, ephemeral erosion is particularly harmful because these sources can accelerate sediment transport, often yield more sediment than interrill sources and are more challenging to mitigate. In this study, terrain data were collected by aerial photogrammetry using an unmanned aerial system (UAS) following planting and approximately one month later, while climate variables during the period were collected using NexRad radar. Imagery was captured within seven agricultural fields (six in Iowa and one in Minnesota), ranging in size from 0.6 to 3.6 hectare (1.6 to 8.8 acre). Considering the small scale in topographic variation between two surveys, extreme efforts were applied to image processing and geospatial registration. Advanced models for camera calibration utilizing Micmac open-source photogrammetry software package were used to account for complex distortion patterns in the raw image data set. The undistorted images were then processed using Agisoft Photoscan for camera alignment, model georeferencing and dense point cloud generation (millions to billions of points per survey), from which digital elevation models (DEMs; 10 to 57 million cells) were produced. A physically-based finite element hydrodynamic and sediment transport model (CCHE2D, developed at the National Center for Computational Hydroscience and Engineering) was applied to simulate hydrological (runoff), sediment detachment (raindrop splash, sheet flow, and concentrated flow erosion) and sediment transport/deposition landscape evolution processes. Simulated geomorphological and sediment budget results over time were compared to field observations for model input parameter adjustment and consequently quantification of estimates. Integration of high-resolution spatial and temporal topographic measurements with physically-based numerical models support the development and validation of dynamic landscape evolution models needed for accurate prediction and quantification of gully initiation, evolution and impact on total soil loss and effective conservation management planning.

The past 4 years has seen an expansion of end-of-life-care (EoLC) in the intensive care unit (ICU), especially in Western countries. ICUs are increasingly becoming the preferred place for the complex dying patient whether intentionally or not. For the majority of patients who die on ICU, it is a planned event with the numbers requiring cardiopulmonary resuscitation reducing. With general ICU mortality being between 20 and 30 %, ‘dying’ is one of the most common ICU diagnoses, making EoLC a daily responsibility for the ICU doctor at all levels of training. Acquiring the knowledge, practical skills, compassion and communication to manage the needs of the diverse population admitted to ICU takes time, but when it is done well this can be a rewarding area of practice. Once it is recognized that a patient is dying, a structured approach and shift in emphasis of patient care has been shown to improve family satisfaction and reduce complaints. This article talks through four real-life cases to bring attention to clinical skills, a structured approach for communication and a decision-making process with reference to the relevant paragraphs of the General Medical Council (GMC) guidelines: Treatment and Care Towards the End-of-Life.

Freshwater mussels are among the world’s most imperilled species, and much effort has been expended to understand their precipitous decline. The current paradigm is that relative river bed stability over decades is critical to maintaining mussel beds at a given river reach. Such information, however, is in stark contrast to the fundamental understanding of self‐formed rivers. Here, we examine the relationship between long‐term occurrence of aggregated freshwater mussel communities (mussel beds) and the dynamic rivers in which they live. We surveyed mussel assemblages in two streams with historical records to document their long‐term persistence, and we simulated bed mobility with a two‐dimensional flow and sediment transport model to estimate bedload transport during channel‐forming discharges. We found evidence of long‐term mussel bed persistence, in time and in kind, within these two streams and that significant bed mobility within mussel beds occurs every 1–2 years, as to be expected for self‐formed rivers with labile beds. Flow refugia, or bed immobility, thus cannot completely explain the persistence of these mussel beds. Our results suggest that mussels have adapted to proliferate in river channels that often experience significant bed mobility, but further studies are needed to understand the biophysical mechanisms enabling the long‐term persistence of mussel communities.

Major incidents during the past 30 years have caused the NHS and other agencies to respond in a coordinated fashion and create the comprehensive Emergency Preparedness, Resilience and Response framework 2013. This along with supporting documents gives a detailed structure of the role of the NHS in any type of major incident from man-made disaster to pandemic flu. This has required preparation of communication, transport, security, military and healthcare systems. Included is also how the response is handled at a more local level and for different levels of response. The Royal Colleges have responded by including specialist training at the higher and advanced level for trainees so that victims are triaged at the scene and received by consultants with appropriate training in such work. Hospitals, ambulance services and intensive care units across the country are able to use networks to ensure not only logical and rapid access to major trauma centres but also to network highly sophisticated skills when advanced life support is required. The NHS is better able to cope with major incidents than ever before.

Background Saponin adjuvants reliably enhance immune response to a variety of antigens, but their use is hindered by dose-limiting toxicities and supply constraints. TQL1055 is a semi-synthetic analog of the natural saponin adjuvant QS-21, rationally modified to improve tolerability and enable large-scale manufacturing. We previously showed that the combination of acellular pertussis vaccine (aP) and TQL1055 was well-tolerated and increased anti-pertussis toxin (PT) antibody responses in mice and rabbits, with a no observed adverse effect level (NOAEL) > 2000 mcg/dose. Methods Here we report interim results from a Phase 1 first-in-humans dose-escalation study of TQL1055. Healthy adults 18 to 50 years of age were sequentially enrolled into 6 groups (n=12/group) and randomized 10:2 to receive one intramuscular dose of aP + TQL1055 or aP alone on Day 1. TQL1055 dose increased by group from 25 to 800 mcg (Figure 1). Local adverse events (AEs) (injection site pain, redness, swelling) and systemic AEs (fever, chills, headache, fatigue, myalgia, arthralgia, nausea, vomiting, diarrhea) were solicited through Day 8. Clinical laboratory panels (chemistry, hematology, coagulation) were performed on Days 1 (pre-dose), 8, and 29. Serious AEs were collected through Day 365. Antibodies to PT were assessed at all visits. Figure 1. Study Design Results Blinded safety data from the first four groups (n=48) through Day 8 were analyzed, including 2 subjects/group receiving aP alone. All solicited AEs were mild or moderate (Figure 2). Local AEs, mainly injection site pain, occurred in 75% of subjects (mild 65%, moderate 10%). The incidence of total local AEs increased with TQL1055 dose, from 50% at 25 mcg to 92% at 200 mcg. The mean duration of local AEs was 1.8 days and also increased with TQL1055 dose, from 1.3 days at 25 mcg to 2.1 days at 200 mcg. Systemic AEs, mostly fatigue, headache, and nausea, occurred in 63% of subjects (mild 40%, moderate 23%), with no fevers. The mean duration of systemic AEs was 1.4 days, with no association with TQL1055 dose. No severe or serious adverse events were reported. Figure 2. Solicited Adverse Events by Severity and TQL1055 Dose Conclusion In this early analysis, the safety profile of aP + TQL1055 appears similar to that of licensed aP vaccines, without severe or prolonged injection site pain. These data support further dose escalation and assessment of immunogenicity. Disclosures Sean R. Bennett, MD PhD, Adjuvance Technologies (Employee) Tyler Martin, MD, Adjuvance Technologies (Employee, Shareholder)

Soil-mantled landscapes subjected to rainfall, runoff events, and downstream base level adjustments will erode and evolve in time and space. Yet the precise mechanisms for soil erosion also will vary, and such variations may not be adequately captured by soil erosion prediction technology. This study sought to monitor erosion processes within an experimental landscape filled with packed homogenous soil, which was exogenically forced by rainfall and base level adjustments, and to define the temporal and spatial variation of the erosion regimes. Close-range photogrammetry and terrain analysis were employed as the primary methods to discriminate these erosion regimes. Results show that (1) four distinct erosion regimes can be identified (raindrop impact, sheetflow, rill, and gully), and these regimes conformed to an expected trajectory of landscape evolution; (2) as the landscape evolved, the erosion regimes varied in areal coverage and in relative contribution to total sediment efflux measured at the outlet of the catchment; and (3) the sheetflow and rill erosion regimes dominated the contributions to total soil loss. Disaggregating the soil erosion processes greatly facilitated identifying and mapping each regime in time and space. Such information has important implications for improving soil erosion prediction technology, for assessing landscape degradation by soil erosion, for mapping regions vulnerable to future erosion, and for mitigating soil losses and managing soil resources.

The submerged Jet Erosion Test (JET) is a commonly used technique to assess the erodibility of cohesive soil. Employing a linear excess shear stress equation and impinging jet theory, simple numerical methods have been developed to analyze data collected using a JET to determine the critical shear stress and erodibility coefficient of soil. These include the Blaisdell, Iterative, and Scour Depth Methods, and all have been organized into easy to use spreadsheet routines. The analytical framework of the JET and its associated methods, however, are based on many assumptions that may not be satisfied in field and laboratory settings. The main objective of this study is to critically assess this analytical framework and these methodologies. Part of this assessment is to include the effect of flow confinement on the JET. The possible relationship between the derived erodibility coefficient and critical shear stress, a practical tool in soil erosion assessment, is examined, and a review of the deficiencies in the JET methodology also is presented. Using a large database of JET results from the United States and data from literature, it is shown that each method can generate an acceptable curve fit through the scour depth measurements as a function of time. The analysis shows, however, that the Scour Depth and Iterative Methods may result in physically unrealistic values for the erosion parameters. The effect of flow confinement of the impinging jet increases the derived critical shear stress and decreases the erodibility coefficient by a factor of 2.4 relative to unconfined flow assumption. For a given critical shear stress, the length of time over which scour depth data are collected also affects the calculation of erosion parameters. In general, there is a lack of consensus relating the derived soil erodibility coefficient to the derived critical shear stress. Although empirical relationships are statistically significant, the calculated erodibility coefficient for a given critical shear stress has an uncertainty of several orders of magnitude. This study shows that JET results should be used with caution and the magnitude of the uncertainty in the derived erodibility parameters should be carefully considered.

Freshwater mussels are important ecosystem engineers, and recent studies have illustrated their many ecological contributions, but little is known about the interaction between mussels and their surrounding flow environment at the organism scale. In the present experimental campaign, we examine the hydraulic interactions between mussels and open-channel flow. We quantify how a mussel-covered bed alters bed roughness and near-bed turbulent flow, determine the filter behavior and capacity of live Lampsilis siliquoidea, and design a model mussel to simulate live mussel filtering to examine the impact of the biologically mediated activity of filter feeding on near-bed turbulent flow. In comparison to a gravel bed, a mussel-covered bed increased shear velocity by 28% and bed roughness by nearly 300%, and significantly reduced near-bed flow velocity. The filter velocity in L. siliquoidea varied within and between individuals, and ranged from 0.4 to 20 cm/s. The excurrent flow of the model mussel accurately simulated excurrent flow observed in live mussels and, when subjected to various boundary conditions, altered water velocity and turbulent kinetic energy downstream. The ability to describe and quantify these hydrodynamic interactions provides new insight into how mussels modulate near-bed flow and mixing processes, which can contribute to future conservation efforts.

Background Vaccination against both seasonal and pandemic influenza requires effective adjuvants to maximize the utility of limited antigen and to enhance immunogenicity in hyporesponsive at-risk populations. First-generation natural saponins are potent immuno-enhancers but are reactogenic and have supply constraints. As part of a NIH-funded project, the novel semisynthetic saponin TQL1055 was evaluated for its potential to augment the immunogenicity of influenza antigens. Figure 1: TQL1055 Enhances the Antibody Response to a Recombinant Antigen Influenza Vaccine (Flublok®) and Exhibits Antigen Dose-Sparing Effects Figure 2: TQL1055 Exhibits Improved Systemic Tolerability Over QS-21. Methods Groups of 10 C57BL/6J mice were immunized subcutaneously (SC) with Flublok® (H3N2 antigen) alone at either a 4.5 mcg or 1.1 mcg dose, or at a 1.1 mcg dose in combination with 10, 30 or 100 mcg TQL1055 on Days 0 and 21. Sera were analyzed at days 0, 21 and 42 by ELISA for H3N2-specific IgG. Body weights were measured serially. Results A 2-dose series of 1.1 mcg Flublok with TQL1055 elicited anti-H3N2 antibodies in all mice. This effect was TQL1055 dose-dependent, with GMTs of 2178 in the 10 mcg group, 13674 in the 30 mcg group and 48959 in the 100 mcg group. The GMT in all TQL1055 groups was higher than the GMT of 176 in the group receiving 4.5 mcg of Flublok alone. Mice receiving TQL1055 gained weight steadily after immunization, compared with a maximum weight loss of >10% in mice receiving 20 mcg of QS-21. Conclusion TQL1055 exhibits robust adjuvant activity for influenza antigens, demonstrating a dose-sparing effect and improved systemic tolerability compared with QS-21. Taken together, these finding support further evaluation of its potential as an adjuvant for influenza vaccines. Disclosures Chloe Buzz, BS, Adjuvance Technologies (Employee) Eric Farris, PhD, Adjuvance Technologies (Employee) Sean R. Bennett, MD PhD, Adjuvance Technologies (Employee) Pat Frenchick, PhD, Adjuvance Technologies (Consultant) Tyler Martin, MD, Adjuvance Technologies (Employee, Shareholder)

Forests provide valuable water and nutrient resources to farming activities as well as places for various leisure activities. However, decontaminating forests in the aftermath of a massive radionuclide contamination event presents challenges because of the topography and the difficulty of collecting a large number of field samples. Achieving accurate remote measurements also can be hindered by the canopy cover. In Fukushima, Japan, where elevated radioactive fallout occurred following the Fukushima Daiichi Nuclear Power Plant (FDNPP) accident in March 2011, about 70 percent of the land is covered with forests. Soil samples collected in a forest in Iitate Village, Fukushima, beginning in 2016 through 2018 still contained an average 98200 Bq/kg of Cs-137 in the top 4 cm depth (std. dev. 114100 Bq/kg). Thus, decontamination and identification of Cs-137 distribution patterns in those forests is still a pressing issue. However, soil types in that region, 1000 mm annual precipitation with intense rain during typhoons, and microtopography have presented challenges to understanding how Cs-137 behaves in those forests. In this study, six topographic parameters were computed from 1-m and 10-m resolution DEMs and the relationships between those parameters and soil water content and bulk density were systematically analyzed for their effects on Cs-137 concentration levels. As the first analytical step, correlation indices and the generalized additive models (GAM) analysis were conducted on those parameters. The results show that not all topographic effects are apparent in the correlation analysis, yet the results can be improved when mixed with other parameters in GAM models. Overall the effect of topographic parameters on Cs-137 levels is DEM resolution-dependent while individual soil properties indicate a strong relationship. Also, it was found that depending on the analysis depth, correlation levels and significance of those parameters in GAM models fluctuate. As the second step, Cs-137 levels were extrapolated to a larger area in the study site to understand further the connections between topography and soil properties. The results, including the limitations and proposals for future forest decontamination, will be presented in the session. Understanding how Cs-137 moves and accumulates in forests, especially immediately after contamination, is critical to avoiding the negative impacts on the environment by decontamination measures and to protecting lowlands from harmful radioactivity levels. This study contributes to the radionuclide research field by presenting an example of data analysis processes using field sampled data.

The DUX4 transcription factor is normally expressed in the cleavage-stage embryo and regulates genes involved in embryonic genome activation. Misexpression of DUX4 in skeletal muscle, however, is toxic and causes facioscapulohumeral muscular dystrophy (FSHD). We recently showed DUX4-induced toxicity is due, in part, to the activation of the double-stranded RNA (dsRNA) response pathway and the accumulation of intranuclear dsRNA foci. Here, we determined the composition of DUX4-induced dsRNAs. We found that a subset of DUX4-induced dsRNAs originate from inverted Alu repeats embedded within the introns of DUX4-induced transcripts and from DUX4-induced dsRNA-forming intergenic transcripts enriched for endogenous retroviruses, Alu and LINE-1 elements. However, these repeat classes were also represented in dsRNAs from cells not expressing DUX4. In contrast, pericentric human satellite II (HSATII) repeats formed a class of dsRNA specific to the DUX4 expressing cells. Further investigation revealed that DUX4 can initiate the bidirectional transcription of normally heterochromatin-silenced HSATII repeats. DUX4-induced HSATII RNAs co-localized with DUX4-induced nuclear dsRNA foci and with intranuclear aggregation of EIF4A3 and ADAR1. Finally, gapmer-mediated knockdown of HSATII transcripts depleted DUX4-induced intranuclear ribonucleoprotein aggregates and decreased DUX4-induced cell death, suggesting that HSATII-formed dsRNAs contribute to DUX4 toxicity.

Experiments are conducted to study the effects of suspended sediment on flow dynamics in a mixing box. Results from particle image velocimetry, providing the velocity of the sediment and fluid phases separately, demonstrate the formation of a stratified layer where turbulent modulation increases.

Background Renal dysfunction is a significant variable in determining the outcome of the surgeries used to treat cardiovascular diseases - the most common being cardiopulmonary bypass graft (CABG) and valvular replacement (VR). In Saudi Arabia, the incidence of renal failure and diabetes is higher than that in most western populations. Our aim is to determine the renal outcome of patients who underwent cardiac surgery at King Faisal Cardiac Center (KFCC) over the past 3 years and explore the risk of preoperative renal function on the outcome. Methods We conducted a retrospective cohort study of all patients older than 18 years who underwent cardiac surgery at KFCC from May 2014 to June 2017. Data were analyzed using the statistical package IBM SPSS 22. Results The 244 patients who underwent cardiac surgery in this study period had a mean age of 60.5±7.5 years and mean body- mass index (BMI) of 28.62±5.19. The patients in this sample had median postoperative creatinine of 77 (IQR 66–99.75) and median bypass time of 117 (IQR 84–143). There were five (2%) patients who died within 30 days, ten (4%) patients with temporary dialysis, 19 (7.8%) patients with postoperative renal dysfunction, and no patients with permanent dialysis. The data showed a significant relationship between levels of preoperative creatinine and postoperative renal dysfunction (p=0.0001, odds ratio 1.05, 95% CI 1.031–1.064). Time on bypass (p=0.998), hypertension (p=1.969), and diabetes (p=1.061) were all not significant. CABG was done in 180 (72%) of the patients. Conclusion The main predictor for poor renal outcomes for cardiac surgery is preoperative creatinine, while other variables such as age, sex, BMI, cardiopulmonary bypass time, diabetes, hypertension, and dyslipidemia did not show any risk to the renal outcome.

Background Blood transfusion is a commonly used therapy in cardiac surgery, whether it is given during the surgery or in the intensive care unit. Because of this alarming number, it is necessary to evaluate the risk and complications that patients are exposed to once transfusion therapy is applied. Postoperative infection in cardiac surgery patients has been linked to patient outcome. Nosocomial pneumonia, surgical site infection, mediastinitis, bacteremia, and sepsis are common infectious processes affecting the outcome. In the King Faisal Cardiac Center (KFCC), the liberal use of blood transfusions has been raising questions on the outcomes of patients. In an attempt to decrease the use of transfusions, it is essential to understand the risk and complications associated with them. Postoperative infection is the main complication that causes most concern. We aimed to determine the effects of blood transfusion on postoperative infection in cardiac surgery patients and to assess the benefits or negatives of our large transfusion rate at the KFCC from January 2017 to January 2019. Methods We did a retrospective cohort study of all patients aged older than 18 years who underwent cardiac surgery at KFCC from January 2017 to January 2019. Data were analyzed using the statistical package IBM SPSS 22. Categorical variables were reported as percentages, while numerical variables were reported as means and medians. P values less than 0.05 were considered significant. Results 197 was the sample size. Mean age was 57.64 years and body-mass index (BMI) was 28.91. 93.4% of patients had blood transfused and 31.98% had postoperative infection. Comparing transfused and non-transfused patients, hemoglobin (Hb) on discharge values and postoperative infection were similar; only preoperative Hb was significantly different (p Conclusion Blood transfusion was not significantly linked to postoperative infection and discharge hemoglobin. The findings show us that giving blood has not increased or decreased the risk of infection. Therefore, it is safe to say that, regarding postoperative infection and discharge Hb, we are transfusing too much blood and using up resources for outcomes that could have been achieved otherwise. Although our curiosity for the high infection rate has still not been answered completely, we assume HbA1c plays a major role because of the high prevalence of diabetes, and especially uncontrolled diabetes, in our population.

Background Acellular pertussis vaccines are better tolerated but less immunogenic than older whole cell vaccines. Novel adjuvants may be useful to enhance their immunogenicity. First-generation natural saponins are potent immuno-enhancers but are highly reactogenic. The novel semisynthetic saponin TQL1055 was evaluated for its potential to enhance the immunogenicity of a commercially available acellular pertussis vaccine as part of a National Institute of Allergy and Infectious Disease (NIAID) funded project. Methods Groups of 10 female C57BL/6J mice were immunized subcutaneously (SC) with Adacel® (containing 0.5 mcg pertussis toxin antigen) alone or in combination with QS-21 at 20 mcg/dose or TQL1055 at 50 mcg/dose on Days 0 and 28. Serum antibody titer to pertussis antigen was determined by ELISA (Alpha Diagnostics) at Days 0, 28, and 42 and geometric mean titers (GMT) in IU/mL were determined. Body weights were measured serially for 7 days after dose 1. Results At 28 days following dose 1, mice receiving TQL1055 had an anti-pertussis toxin IgG GMT of 8492, compared with 2263 in mice receiving QS-21 (p = 0.005). At Day 42, 14 days after dose 2, the GMTs increased to 18719 in the TQL1055 group and 10851 in the QS-21 group (p = 0.0653 vs TQL1055 dose 2; p = 0.6038 vs TQL1055 dose 1). Mice in the Adacel and TQL1055 groups gained weight steadily after dose 1, while mice in the QS-21 group had an average weight loss of 10% from baseline at 3 days after dose 1 (p < 0.0001). Figure 1: TQL1055 Enhances the Antibody Response to Adacel® (Commercial Acellular Pertussis Vaccine) in C57BL/6J Female Mice Figure 2: TQL1055 Shows Enhanced Tolerability (measured by decreased weight loss) Compared to QS-21 Following Subcutaneous Injection in C57BL/6J Female Mice Conclusion TQL1055 enhanced the antibody response to a commercial acellular pertussis vaccine to a greater degree than QS-21. Additionally, TQL1055 was better tolerated than QS-21, with no weight loss after vaccination. These findings suggested that TQL1055 may improve the performance of acellular pertussis vaccines without an increase in reactogenicity. Disclosures Chloe Buzz, BS, Adjuvance Technologies (Employee) Sean R. Bennett, MD PhD, Adjuvance Technologies (Employee) Phil Livingston, MD, Adjuvance Technologies (Consultant, Shareholder) Eric Farris, PhD, Adjuvance Technologies (Employee) Tyler Martin, MD, Adjuvance Technologies (Employee, Shareholder)

SUMMARY The DUX4 transcription factor is briefly expressed in the early cleavage-stage embryo, where it induces an early wave of zygotic gene transcription, whereas its mis-expression in skeletal muscle causes the muscular dystrophy facioscapulohumeral dystrophy (FSHD). Here, we show that DUX4 induces the expression of the histone variants H3.X and H3.Y. We have used a myoblast cell line with doxycycline-inducible DUX4 to show that these histone variants are incorporated throughout the body of DUX4-induced genes. Following a brief pulse of DUX4, these histones contribute to greater perdurance and to enhanced re-activation of DUX4 target gene expression. These findings provide a model for H3.X/Y as a chromatin mechanism that facilitates the expression of DUX4 target genes subsequent to a brief pulse of DUX4 expression., Graphical Abstract, In Brief Resnick et al. show that the DUX4-induced histone variants, H3.X and H3.Y, incorporate into the chromatin of DUX4-induced genes, making them more sensitive to subsequent expression. This suggests a mechanism for how the brief expression of DUX4 can establish a memory of its transcriptional network.