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We present ultraviolet/optical/near-infrared observations and modeling of Type II supernovae (SNe II) whose early time ( δ t < 2 days) spectra show transient, narrow emission lines from shock ionization of confined ( r < 10 ^15 cm) circumstellar material (CSM). The observed electron-scattering broadened line profiles (i.e., IIn-like) of H i , He i/ii , C iv , and N iii/iv/v from the CSM persist on a characteristic timescale ( t _IIn ) that marks a transition to a lower-density CSM and the emergence of Doppler-broadened features from the fast-moving SN ejecta. Our sample, the largest to date, consists of 39 SNe with early time IIn-like features in addition to 35 “comparison” SNe with no evidence of early time IIn-like features, all with ultraviolet observations. The total sample includes 50 unpublished objects with a total of 474 previously unpublished spectra and 50 multiband light curves, collected primarily through the Young Supernova Experiment and Global Supernova Project collaborations. For all sample objects, we find a significant correlation between peak ultraviolet brightness and both t _IIn and the rise time, as well as evidence for enhanced peak luminosities in SNe II with IIn-like features. We quantify mass-loss rates and CSM density for the sample through the matching of peak multiband absolute magnitudes, rise times, t _IIn , and optical SN spectra with a grid of radiation hydrodynamics and non-local thermodynamic equilibrium radiative-transfer simulations. For our grid of models, all with the same underlying explosion, there is a trend between the duration of the electron-scattering broadened line profiles and inferred mass-loss rate: ${t}_{\mathrm{IIn}}\approx 3.8[\dot{M}/$ (0.01 M _⊙ yr ^−1 )] days.

We present the second and final release of optical spectroscopy of Type Ia supernovae (SNe Ia) obtained during the first and second phases of the Carnegie Supernova Project (CSP-I and CSP-II). The newly released data consist of 148 spectra of 30 SNe Ia observed in the course of CSP-I and 234 spectra of 127 SNe Ia obtained during CSP-II. We also present 216 optical spectra of 46 historical SNe Ia, including 53 spectra of 30 SNe Ia observed by the Calán/Tololo Supernova Survey. We combine these observations with previously published CSP data and publicly available spectra to compile a large sample of measurements of spectroscopic parameters at maximum light, consisting of pseudo-equivalent widths and expansion velocities of selected features for 232 CSP and historical SNe Ia (including more than 1000 spectra). Finally, we review some of the strongest correlations between spectroscopic and photometric properties of SNe Ia. Specifically, we define two samples: one consisting of SNe Ia discovered by targeted searches (most of them CSP-I objects) and the other composed of SNe Ia discovered by untargeted searches, which includes most of the CSP-II objects. The analyzed correlations are similar for both samples. We find a larger incidence of SNe Ia belonging to the cool and broad-line Branch subtypes among the events discovered by targeted searches, shallow-silicon SNe Ia are present with similar frequencies in both samples, while core normal SNe Ia are more frequent in untargeted searches.

SN 2023emq is a fast-evolving transient initially classified as a rare Type Icn supernova (SN), interacting with a H- and He-free circumstellar medium (CSM) around maximum light. Subsequent spectroscopy revealed the unambiguous emergence of narrow He lines, confidently placing SN 2023emq in the more common Type Ibn class. Photometrically, SN 2023emq has several uncommon properties regardless of its class, including its extreme initial decay (faster than >90% of Type Ibn/Icn SNe) and sharp transition in the decline rate from 0.20 to 0.07 mag day ^−1 at +20 days. The bolometric light curve can be modeled as CSM interaction with 0.32 M _⊙ of ejecta and 0.12 M _⊙ of CSM, with 0.006 M _⊙ of nickel, as expected of fast, interacting SNe. Furthermore, broadband polarimetry at +8.7 days ( P = 0.55% ± 0.30%) is consistent with spherical symmetry. A discovery of a transitional Type Icn/Ibn SN would be unprecedented and would give valuable insights into the nature of mass loss suffered by the progenitor just before death, but we favor an interpretation that SN 2023emq is a Type Ibn SN that exhibited flash-ionized features in the earliest spectrum, as the features are not an exact match with other Type Icn SNe to date. However, the feature at 5700 Å, in the region of C iii and N ii emission, is significantly stronger in SN 2023emq than in the few other flash-ionized Type Ibn SNe, and if it is related to C iii , it possibly implies a continuum of properties between the two classes.

We present optical photometric and spectroscopic observations of the 02es-like type Ia supernova (SN) 2022ywc. The transient occurred in the outskirts of an elliptical host galaxy and showed a striking double-peaked light curve with an early excess feature detected in the ATLAS orange and cyan bands. The early excess is remarkably luminous with an absolute magnitude ∼ − 19, comparable in luminosity to the subsequent radioactively driven second peak. The spectra resemble the hybrid 02es-like SN 2016jhr, which is considered to be a helium shell detonation candidate. We investigate different physical mechanisms that could power such a prominent early excess and rule out massive helium shell detonation, surface ^56 Ni distribution, and ejecta–companion interaction. We conclude that SN ejecta interacting with circumstellar material (CSM) is the most viable scenario. Semianalytical modeling with MOSFiT indicates that SN ejecta interacting with ∼0.05 M _⊙ of CSM at a distance of ∼10 ^14 cm can explain the extraordinary light curve. A double-degenerate scenario may explain the origin of the CSM, by tidally stripped material from either the secondary white dwarf or disk-originated matter launched along polar axes following the disruption and accretion of the secondary white dwarf. A nonspherical CSM configuration could suggest that a small fraction of 02es-like events viewed along a favorable line of sight may be expected to display a very conspicuous early excess like SN 2022ywc.

We present multiwavelength photometry and spectroscopy of SN 2022jli, an unprecedented Type Ic supernova discovered in the galaxy NGC 157 at a distance of ≈ 23 Mpc. The multiband light curves reveal many remarkable characteristics. Peaking at a magnitude of g = 15.11 ± 0.02, the high-cadence photometry reveals periodic undulations of 12.5 ± 0.2 days superimposed on the 200-day supernova decline. This periodicity is observed in the light curves from nine separate filter and instrument configurations with peak-to-peak amplitudes of ≃ 0.1 mag. This is the first time that repeated periodic oscillations, over many cycles, have been detected in a supernova light curve. SN 2022jli also displays an extreme early excess that fades over ≈25 days, followed by a rise to a peak luminosity of L _opt = 10 ^42.1 erg s ^−1 . Although the exact explosion epoch is not constrained by data, the time from explosion to maximum light is ≳ 59 days. The luminosity can be explained by a large ejecta mass ( M _ej ≈ 12 ± 6 M _⊙ ) powered by ^56 Ni, but we find it difficult to quantitatively model the early excess with circumstellar interaction and cooling. Collision between the supernova ejecta and a binary companion is a possible source of this emission. We discuss the origin of the periodic variability in the light curve, including interaction of the SN ejecta with nested shells of circumstellar matter and neutron stars colliding with binary companions.

We present the discovery and extensive follow-up of a remarkable fast-evolving optical transient, AT 2022aedm, detected by the Asteroid Terrestrial impact Last Alert Survey (ATLAS). In the ATLAS o band, AT 2022aedm exhibited a rise time of 9 ± 1 days, reaching a luminous peak with M _g ≈ −22 mag. It faded by 2 mag in the g band during the next 15 days. These timescales are consistent with other rapidly evolving transients, though the luminosity is extreme. Most surprisingly, the host galaxy is a massive elliptical with negligible current star formation. Radio and X-ray observations rule out a relativistic AT 2018cow–like explosion. A spectrum in the first few days after explosion showed short-lived He ii emission resembling young core-collapse supernovae, but obvious broad supernova features never developed; later spectra showed only a fast-cooling continuum and narrow, blueshifted absorption lines, possibly arising in a wind with v ≈ 2700 km s ^−1 . We identify two further transients in the literature (Dougie in particular, as well as AT 2020bot) that share similarities in their luminosities, timescales, color evolution, and largely featureless spectra and propose that these may constitute a new class of transients: luminous fast coolers. All three events occurred in passive galaxies at offsets of ∼4–10 kpc from the nucleus, posing a challenge for progenitor models involving massive stars or black holes. The light curves and spectra appear to be consistent with shock breakout emission, though this mechanism is usually associated with core-collapse supernovae. The encounter of a star with a stellar-mass black hole may provide a promising alternative explanation.

We present observations and analysis of the hostless and luminous Type Ia supernova 2022ilv, illustrating it is part of the 2003fg-like family, often referred to as super-Chandrasekhar (Ia-SC) explosions. The Asteroid Terrestrial-impact Last Alert System light curve shows evidence of a short-lived, pulse-like early excess, similar to that detected in another luminous Type Ia supernova (SN 2020hvf). The light curve is broad, and the early spectra are remarkably similar to those of SN 2009dc. Adopting a redshift of z = 0.026 ± 0.005 for SN 2022ilv based on spectral matching, our model light curve requires a large ^56 Ni mass in the range 0.7–1.5 M _⊙ and a large ejecta mass in the range 1.6–2.3 M _⊙ . The early excess can be explained by fast-moving SN ejecta interacting with a thin, dense shell of circumstellar material close to the progenitor (∼10 ^13 cm) a few hours after the explosion. This may be realized in a double-degenerate scenario, wherein a white dwarf merger is preceded by the ejection of a small amount (∼10 ^−3 –10 ^−2 M _⊙ ) of hydrogen and helium-poor tidally stripped material. A deep pre-explosion Pan-STARRS1 stack indicates no host galaxy to a limiting magnitude of r ∼ 24.5. This implies a surprisingly faint limit for any host of M _r ≳ −11, providing further evidence that these types of explosions occur predominantly in low-metallicity environments.

A rigorous exploration of the sea ice data assimilation (DA) problem using a framework specifically developed for rapid, interpretable hypothesis testing is presented. In many applications, DA is implemented to constrain a modeled estimate of a state with observations. The sea ice DA application is complicated by the wide range of spatiotemporal scales over which key sea ice variables evolve, a variety of physical bounds on those variables, and the particular construction of modern complex sea ice models. By coupling a single-column sea ice model (Icepack) to the Data Assimilation Research Testbed (DART) in a series of observing system simulation experiments (OSSEs), the grid-cell-level response of a complex sea ice model to a range of ensemble Kalman DA methods designed to address the aforementioned complications is explored. The impact on the modeled ice thickness distribution and the bounded nature of both state and prognostic variables in the sea ice model are of particular interest, as these problems are under-examined. Explicitly respecting boundedness has little effect in the winter months, but it correctly accounts for the bounded nature of the observations, particularly in the summer months when the prescribed sea ice concentration (SIC) error is large. Assimilating observations representing each of the individual modeled sea ice thickness categories consistently improves the analyses across multiple diagnostic variables and sea ice mean states. These results elucidate many of the positive and negative results of previous sea ice DA studies, highlight the many counterintuitive aspects of this particular DA application, and motivate better future sea ice analysis products.

This activity provides students with a way of understanding expectancy violations theory (EVT) by examining incidents that occurred during televised award shows. In this activity, in small groups, students will delve into well-known award-show incidents, such as Will Smith's slapping of Chris Rock at the 2022 Academy Awards, to understand the events leading up to the incident, what happened at the time of the event, and the repercussions occurring after. Using this information, students will work through the components of EVT to enhance their understanding of the theory and its lens through which to view relationships. This activity allows students to use their familiarity with pop culture to gain a greater understanding of EVT in order to better utilize the theory when examining their own interpersonal relationships. Courses: Introduction to Mass Media Communication, Interpersonal Communication, Mass Media Theory and Criticism, Organizational Communication. Objectives: Students will understand the principles of EVT; be able to explain EVTs components (expectancy, communicator reward valance, and violation valence); and be able to apply EVT to examples of interpersonal interactions.

One promising practice for increasing active learning in undergraduate science education is the use of a mentoring network. The Promoting Active Learning and Mentoring (PALM) Network was launched with practitioners from several professional societies and disciplines to make changes in their teaching based on evidence-based practices and to encourage the members to reflect deeply on their teaching experiences. Members of the Network interviewed seven previous Fellows, 1 to 6 years after completing their fellowship, to better understand the value of the Network and how these interactions impacted their ability to sustain change toward more active teaching practices. The interviews resulted in the creation of three personas that reflect the kinds of educators who engaged with the Network: Neil the Novice, Issa the Isolated, and Etta the Expert. Key themes emerged from the interviews about how interactions with the PALM Network sustained change toward evidence-based teaching practices allowing the members to readily adapt to the online learning environment during the COVID-19 pandemic. Understanding how the personas intersect with the ADKAR model contributes to a better understanding of how mentoring networks facilitate transformative change toward active learning and can inform additional professional development programs.

Abstract Background Rural children are at greater obesity risk than their urban peers. The NU-HOME study is an innovative collaborative effort to prevent childhood obesity in rural communities. Weight outcomes of the NU-HOME study, a family-meal focused randomized controlled trial (RCT) are described. We hypothesized that compared to control group children, intervention group children would have significantly lower weight-related post-intervention (PI) outcomes. Methods Participants were 114 dyads (7–10 year-old rural children and a parent). In 2017–2018 and 2018–2019, research staff measured height, weight and body fat at baseline (BL) and PI. Families were randomized to intervention (n = 58) or control (n = 56) groups without blinding. Designed with Social Cognitive Theory and community engagement, the NU-HOME program included seven monthly sessions delivered in community settings and four goal-setting calls. The program engaged entire families to improve healthy eating, physical activity, family meals and the home food environment. Multiple linear and logistic regression models tested PI outcomes of child BMIz-score, percent body fat, percent over 50th percentile BMI, and overweight/obesity status by treatment group, adjusted for BL values and demographics (n = 102). Results No statistically significant intervention effects were seen for child BMIz or overweight/obesity status. However, a promising reduction in boys’ percent body fat (− 2.1, 95% CI [− 4.84, 0.63]) was associated with the intervention. Conclusions Although our findings were in the hypothesized direction, making significant impacts on weight-related outcomes remains challenging in community trials. Comprehensive family-focused programming may require intensive multi-pronged interventions to mitigate complex factors associated with excess weight gain. Clinical trial registration This study is registered with NIH ClinicalTrials.gov: NCT02973815 .

Physical activity (PA) built environments may support PA among rural youth and families. In the United States (U.S.), differences between rural and urban PA built environments are assessed using coarse scale, county-level methods. However, this method insufficiently examines environmental differences within rural counties. The present study uses rural-specific geospatial mapping techniques and a fine scale, within-rural grouping strategy to identify differing levels of access to the PA built environment among a rural sample. First, PA infrastructure variables (parks, sidewalks) within a rural region of the Midwest U.S. were mapped. Then, households (N = 112) of participants in the NU-HOME study, a childhood obesity prevention trial, were categorized to community-level and neighborhood-level PA built environment groups using two access indicators; Rural-Urban Commuting Area (RUCA) codes and Walk Scores®, respectively. Finally, households were categorized to new groups that combined community-level RUCA codes and neighborhood-level Walk Scores® to indicate the diverse ways in which rural families might access PA built environments, including by vehicle travel and pedestrian commuting. Household access to PA infrastructure (per geospatial proximity and density analyses), parent perceptions of the PA environment, and child PA were examined across the new combined access groups. All measures of household access to PA infrastructure significantly differed by group (p

Abstract Background During the early part of the COVID-19 pandemic, the Canadian Society of Otolaryngology - Head & Neck Surgery (CSO-HNS) task force published recommendations on performance of tracheotomy. Since then, our understanding of the virus has evolved with ongoing intensive research efforts. New literature has helped us better understand various aspects including patient outcomes and health care worker (HCW) risks associated with tracheotomy during the COVID-19 pandemic. Accordingly, the task force has re-evaluated and revised some of the previous recommendations. Main body Based on recent evidence, a negative reverse transcription polymerase chain reaction (RT-PCR) COVID-19 swab status is no longer the main deciding factor in the timing of tracheotomy. Instead, tracheotomy may be considered as soon as COVID-19 swab positive patients are greater than 20 days beyond initial symptoms and 2 weeks of mechanical ventilation. Furthermore, both open and percutaneous surgical techniques may be considered with both techniques showing similar safety and outcome profiles. Additional recommendations with discussion of current evidence are presented. Conclusion These revised recommendations apply new evidence in optimizing patient and health care system outcomes as well as minimizing risks of COVID-19 transmission during aerosol-generating tracheotomy procedures. As previously noted, additional evidence may lead to further evolution of these and other similar recommendations. Graphical abstract

Background. Laparoscopic donor nephrectomy (LDN) offers advantages to the donor. The reported incidence of testicular pain after LDN varies in the literature ranging from 3% to 55%. Methods. A survey was sent to 322 male LDN patients who donated from February 5, 2009, to February 5, 2019. The survey assessed if the donor had testicular pain or saw an additional medical professional after donation. Results. Of the 322 surveyed, 147 (46%) responses were received. Of those who had a left nephrectomy, 39% had testicular pain; 23.8% of those patients had testicular swelling in addition. Of those who had pain, laterality of kidney donated did not impact if the patient had pain, pain onset, pain level, or pain duration. Of those who donated their right kidney, 35% had testicular pain, and 16.7% of those patients reported testicular swelling in addition. Twenty-seven symptomatic patients sought additional medical care for the testicular symptoms postdonation. Seven (25%) had hydroceles, 2 (7%) had testicular cysts, 1 had a urinary tract infection, and 16 (59%) had reassurance or no additional procedures provided. Conclusions. Our results suggest that orchialgia is not as uncommon as previously thought and may be one of the most common minor complications experienced by male donors.

Permafrost underlies one-quarter of the Northern Hemisphere but is at increasing risk of thaw from climate warming. Recent studies across the Arctic have identified areas of rapid permafrost degradation from both top-down and lateral thaw. Of particular concern is thawing syngenetic “yedoma” permafrost which is ice-rich and has a high carbon content. This type of permafrost is common in the region around Fairbanks, Alaska, and across central Alaska expanding westward to the Seward Peninsula. A major knowledge gap is relating belowground measurements of seasonal thaw, permafrost characteristics, and residual thaw layer development with aboveground ecotype properties and thermokarst expansion that can readily quantify vegetation cover and track surface elevation changes over time. This study was conducted from 2013 to 2020 along four 400 to 500 m long transects near Fairbanks, Alaska. Repeat active layer depths, near-surface permafrost temperature measurements, electrical resistivity tomography (ERT), deep (> 5 m) boreholes, and repeat airborne light detection and ranging (lidar) were used to measure top-down permafrost thaw and map thermokarst development at the sites. Our study confirms previous work using ERT to map surface thawed zones; however, our deep boreholes confirm the boundaries between frozen and thawed zones that are needed to model top-down, lateral, and bottom-up thaw. At disturbed sites seasonal thaw increased up to 25 % between mid-August and early October and suggests measurements to evaluate active layer depth must be made as late in the fall season as possible because the projected increase in the summer season of just a few weeks could lead to significant additional thaw. At our sites, tussock tundra and spruce forest are associated with the lowest mean annual near-surface permafrost temperatures while mixed-forest ecotypes are the warmest and exhibit the highest degree of recent temperature warming and thaw degradation. Thermokarst features, residual thaw layers, and taliks have been identified at all sites. Our measurements, when combined with longer-term records from yedoma across the 500 000 km2 area of central Alaska, show widespread near-surface permafrost thaw since 2010. Projecting our thaw depth increases, by ecotype, across the yedoma domain, we calculate a first-order estimate that 0.44 Pg of organic carbon in permafrost soil has thawed over the past 7 years, which, for perspective, is an amount of carbon nearly equal to the yearly CO2 emissions of Australia. Since the yedoma permafrost and the variety of ecotypes at our sites represent much of the Arctic and subarctic land cover, this study shows remote sensing measurements, top-down and bottom-up thermal modeling, and ground-based surveys can be used predictively to identify areas of the highest risk for permafrost thaw from projected future climate warming.

Microphysical processes are important for the development of clouds and thus Earth's climate. For example, turbulent fluctuations in the water vapor mixing ratio, r, and temperature, T, cause fluctuations in the saturation ratio, S. Because S is the driving factor in the condensational growth of droplets, fluctuations may broaden the cloud droplet size distribution due to individual droplets experiencing different growth rates. The small-scale turbulent fluctuations in the atmosphere that are relevant to cloud droplets are difficult to quantify through field measurements. We investigate these processes in the laboratory using Michigan Tech's Π Chamber. The Π Chamber utilizes Rayleigh–Bénard convection (RBC) to create the turbulent conditions inherent in clouds. In RBC it is common for a large-scale circulation (LSC) to form. As a consequence of the LSC, the temperature field of the chamber is not spatially uniform. In this paper, we characterize the LSC in the Π Chamber and show how it affects the shape of the distributions of r, T, and S. The LSC was found to follow a single roll with an updraft and downdraft along opposing walls of the chamber. Near the updraft (downdraft), the distributions of T and r were positively (negatively) skewed. At each measuring position, S consistently had a negatively skewed distribution, with the downdraft being the most negative.

Observations of winds in the planetary boundary layer remain sparse making it challenging to simulate and predict atmospheric conditions that are most important for describing and predicting urban air quality. Short-lived chemicals are observed as plumes whose location is affected by boundary layer winds and whose lifetime is affected by boundary layer height and mixing. Here we investigate the application of data assimilation of NO2 columns as will be observed from geostationary orbit to improve predictions and retrospective analysis of wind fields in the boundary layer.

Button-Simons et al. report on two different genetic crosses of Plasmodium falciparum derived from Asian and African origin parasites, and generate large numbers of recombinant progeny. These crosses are characterized and have the potential to map biologically important traits across parasite genomes.

Stratospheric HCl observations are an important diagnostic for the evaluation of catalytic processes that impact the ozone layer. We report here in situ balloon-borne observations of HCl employing an off-axis integrated cavity output spectrometer (OA-ICOS) fitted with a reinjection mirror. Laboratory assessments demonstrated that the spectrometer has a 90 % response time of 10 s to changes in HCl and a 30 s precision of 26 pptv. The instrument was deployed alongside an ozone instrument in August 2018 on a balloon-borne descent between 20–80 hPa (29–18 km altitude). The observations agreed with nearby satellite measurements made by the Earth Observing System Microwave Limb Sounder within 10 % on average. This is the first time that stratospheric measurements of HCl have been made with ICOS and the first time any cavity-enhanced HCl instrument has been tested in flight.

Uncertain or inaccurate parameters in sea ice models influence seasonal predictions and climate change projections in terms of both mean and trend. We explore the feasibility and benefits of applying an ensemble Kalman filter (EnKF) to estimate parameters in the Los Alamos sea ice model (CICE). Parameter estimation (PE) is applied to the highly influential dry snow grain radius and combined with state estimation in a series of perfect model observing system simulation experiments (OSSEs). Allowing the parameter to vary in space improves performance along the sea ice edge but degrades in the central Arctic compared to requiring the parameter to be uniform everywhere, suggesting that spatially varying parameters will likely improve PE performance at local scales and should be considered with caution. We compare experiments with both PE and state estimation to experiments with only the latter and have found that the benefits of PE mostly occur after the data assimilation period, when no observations are available to assimilate (i.e., the forecast period), which suggests PE's relevance for improving seasonal predictions of Arctic sea ice.

Lidar backscatter and wind retrievals of the planetary boundary layer height (PBLH) are assimilated into 22-hourly forecasts from the NASA Unified – Weather and Research Forecast (NU-WRF) model during the Plains Elevated Convection at Night (PECAN) campaign on 11 July 2015 in Greensburg, Kansas, using error statistics collected from the model profiles to compute the necessary covariance matrices. Two separate forecast runs using different PBL physics schemes were employed, and comparisons with six independent radiosonde profiles were made for each run. Both of the forecast runs accurately predicted the PBLH and the state variable profiles within the planetary boundary layer during the early morning, and the assimilation had a small impact during this time. In the late afternoon, the forecast runs showed decreased accuracy as the convective boundary layer developed. However, assimilation of the Doppler lidar PBLH observations was found to improve the temperature and V-velocity profiles relative to independent radiosonde profiles. Water vapor was overcorrected, leading to increased differences with independent data. Errors in the U velocity were made slightly larger. The computed forecast error covariances between the PBLH and state variables were found to rise in the late afternoon, leading to the larger improvements in the afternoon. This work represents the first effort to assimilate PBLH into forecast states using ensemble methods.

Global coupled chemistry–climate models underestimate carbon monoxide (CO) in the Northern Hemisphere, exhibiting a pervasive negative bias against measurements peaking in late winter and early spring. While this bias has been commonly attributed to underestimation of direct anthropogenic and biomass burning emissions, chemical production and loss via OH reaction from emissions of anthropogenic and biogenic volatile organic compounds (VOCs) play an important role. Here we investigate the reasons for this underestimation using aircraft measurements taken in May and June 2016 from the Korea–United States Air Quality (KORUS-AQ) experiment in South Korea and the Air Chemistry Research in Asia (ARIAs) in the North China Plain (NCP). For reference, multispectral CO retrievals (V8J) from the Measurements of Pollution in the Troposphere (MOPITT) are jointly assimilated with meteorological observations using an ensemble adjustment Kalman filter (EAKF) within the global Community Atmosphere Model with Chemistry (CAM-Chem) and the Data Assimilation Research Testbed (DART). With regard to KORUS-AQ data, CO is underestimated by 42 % in the control run and by 12 % with the MOPITT assimilation run. The inversion suggests an underestimation of anthropogenic CO sources in many regions, by up to 80 % for northern China, with large increments over the Liaoning Province and the North China Plain (NCP). Yet, an often-overlooked aspect of these inversions is that correcting the underestimation in anthropogenic CO emissions also improves the comparison with observational O3 datasets and observationally constrained box model simulations of OH and HO2. Running a CAM-Chem simulation with the updated emissions of anthropogenic CO reduces the bias by 29 % for CO, 18 % for ozone, 11 % for HO2, and 27 % for OH. Longer-lived anthropogenic VOCs whose model errors are correlated with CO are also improved, while short-lived VOCs, including formaldehyde, are difficult to constrain solely by assimilating satellite retrievals of CO. During an anticyclonic episode, better simulation of O3, with an average underestimation of 5.5 ppbv, and a reduction in the bias of surface formaldehyde and oxygenated VOCs can be achieved by separately increasing by a factor of 2 the modeled biogenic emissions for the plant functional types found in Korea. Results also suggest that controlling VOC and CO emissions, in addition to widespread NOx controls, can improve ozone pollution over East Asia.

What genes determine in vitro growth and nutrient utilization in asexual blood-stage malaria parasites? Competition experiments between NF54, clone 3D7, a lab-adapted African parasite, and a recently isolated Asian parasite (NHP4026) reveal contrasting outcomes in different media: 3D7 outcompetes NHP4026 in media containing human serum, while NHP4026 outcompetes 3D7 in media containing AlbuMAX, a commercial lipid-rich bovine serum formulation. To determine the basis for this polymorphism, we conducted parasite genetic crosses using humanized mice and compared genome-wide allele frequency changes in three independent progeny populations cultured in media containing human serum or AlbuMAX. This bulk segregant analysis detected three quantitative trait loci (QTL) regions [on chromosome (chr) 2 containing aspartate transaminase AST; chr 13 containing EBA-140; and chr 14 containing cysteine protease ATG4] linked with differential growth in serum or AlbuMAX in each of the three independent progeny pools. Selection driving differential growth was strong (s = 0.10 – 0.23 per 48-hour lifecycle). We conducted validation experiments for the strongest QTL on chr 13: competition experiments between ΔEBA-140 and 3D7 wildtype parasites showed fitness reversals in the two medium types as seen in the parental parasites, validating this locus as the causative gene. These results (i) demonstrate the effectiveness of bulk segregant analysis for dissecting fitness traits in P. falciparum genetic crosses, and (ii) reveal intimate links between red blood cell invasion and nutrient composition of growth media. Use of parasite crosses combined with bulk segregant analysis will allow systematic dissection of key nutrient acquisition/metabolism and red blood cell invasion pathways in P. falciparum.

# Background We surveyed addiction journal editorial board members to better understand their opinions towards data-sharing. # Methods Survey items consisted of Likert-type (e.g., one to five scale), multiple-choice, and free-response questions. Journal websites were searched for names and email addresses. Emails were distributed using SurveyMonkey. Descriptive statistics were used to characterize the responses. # Results We received 178 responses (of 1039; 17.1%). Of these, 174 individuals agreed to participate in our study (97.8%). Most respondents did not know whether their journal had a data-sharing policy. Board members "somewhat agree" that addiction journals should recommend but not require data-sharing for submitted manuscripts \[M=4.09 (SD=0.06); 95% CI: 3.97-4.22\]. Items with the highest perceived benefit ratings were "secondary data use (e.g., meta-analysis)" \[M=3.44 (SD=0.06); 95% CI: 3.31-3.56\] and "increased transparency" \[M=3.29 (SD=0.07); 95% CI: 3.14-3.43\]. Items perceived to be the greatest barrier to data-sharing included "lack of metadata standards" \[M=3.21 (SD=0.08); 95% CI: 3.06-3.36\], "no incentive" \[M=3.43 (SD=0.07); 95% CI: 3.30-3.57\], "inadequate resources" \[M=3.53 (SD=0.05); 95% CI: 3.42-3.63\], and "protection of privacy"\[M=3.22 (SD=0.07); 95% CI: 3.07-3.36\]. # Conclusion Our results suggest addiction journal editorial board members believe data-sharing has a level of importance within the research community. However, most board members are unaware of their journals' data-sharing policies, and most data-sharing should be recommended but not required. Future efforts aimed at better understanding common reservations and benefits towards data-sharing, as well as avenues to optimize data-sharing while minimizing potential risks, are warranted.

Subglacial meltwater drainage can enhance localized melting along grounding zones and beneath the ice shelves of marine-terminating glaciers. Efforts to constrain the evolution of subglacial hydrology and the resulting influence on ice stability in space and on decadal to millennial timescales are lacking. Here, we apply sedimentological, geochemical, and statistical methods to analyze sediment cores recovered offshore Thwaites Glacier, West Antarctica to reconstruct meltwater drainage activity through the pre-satellite era. We find evidence for a long-lived subglacial hydrologic system beneath Thwaites Glacier and indications that meltwater plumes are the primary mechanism of sedimentation seaward of the glacier today. Detailed core stratigraphy revealed through computed tomography scanning captures variability in drainage styles and suggests greater magnitudes of sediment-laden meltwater have been delivered to the ocean in recent centuries compared to the past several thousand years. Fundamental similarities between meltwater plume deposits offshore Thwaites Glacier and those described in association with other Antarctic glacial systems imply widespread and similar subglacial hydrologic processes that occur independently of subglacial geology. In the context of Holocene changes to the Thwaites Glacier margin, it is likely that subglacial drainage enhanced submarine melt along the grounding zone and amplified ice-shelf melt driven by oceanic processes, consistent with observations of other West Antarctic glaciers today. This study highlights the necessity of accounting for the influence of subglacial hydrology on grounding-zone and ice-shelf melt in projections of future behavior of the Thwaites Glacier ice margin and marine-based glaciers around the Antarctic continent.

Abstract Infrasound monitoring is used in the forensic analysis of events, studying the physical processes of sources of interest, and probing the atmosphere. The dynamical nature of the atmosphere and the use of infrasound as a forensic tool lead to the following questions; (1) what is the timescale of atmospheric variability that affects infrasonic signals? (2) how do infrasound signals vary as a function of time? This study addresses these questions by monitoring a repetitive infrasound source and its corresponding tropospheric returns 54 km away. Source‐receiver empirical Green's functions are obtained every 20 s and used to demonstrate the effect of atmospheric temporal variability on infrasound propagation. In addition, observations are compared to predicted simulated signals based on realistic atmospheric conditions. Based on 127 events over 3 days, it is shown that infrasound properties change within tens of seconds. Particularly, phases can appear and disappear, the propagation time varies, and the signals' energy fluctuates. Such variations are attributed to changes in temperatures and winds. Furthermore, atmospheric models can partly explain the observed changes. Therefore, this study highlights the potential of high temporal infrasound‐based atmospheric sounding.

Here, the authors characterize tissue-level SARS-CoV-2 infection and pathogenesis in transgenic mice expressing human angiotensin converting enzyme 2 (hACE2) by the human cytokeratin 18 promoter (K18-hACE2) and show that infection induces lethality, making the K18-hACE2 model suitable for vaccine and therapeutic evaluation.

The geometry of the sea floor immediately beyond Antarctica's marine-terminating glaciers is a fundamental control on warm-water routing, but it also describes former topographic pinning points that have been important for ice-shelf buttressing. Unfortunately, this information is often lacking due to the inaccessibility of these areas for survey, leading to modelled or interpolated bathymetries being used as boundary conditions in numerical modelling simulations. At Thwaites Glacier (TG) this critical data gap was addressed in 2019 during the first cruise of the International Thwaites Glacier Collaboration (ITGC) project. We present more than 2000 km2 of new multibeam echo-sounder (MBES) data acquired in exceptional sea-ice conditions immediately offshore TG, and we update existing bathymetric compilations. The cross-sectional areas of sea-floor troughs are under-predicted by up to 40 % or are not resolved at all where MBES data are missing, suggesting that calculations of trough capacity, and thus oceanic heat flux, may be significantly underestimated. Spatial variations in the morphology of topographic highs, known to be former pinning points for the floating ice shelf of TG, indicate differences in bed composition that are supported by landform evidence. We discuss links to ice dynamics for an overriding ice mass including a potential positive feedback mechanism where erosion of soft erodible highs may lead to ice-shelf ungrounding even with little or no ice thinning. Analyses of bed roughnesses and basal drag contributions show that the sea-floor bathymetry in front of TG is an analogue for extant bed areas. Ice flow over the sea-floor troughs and ridges would have been affected by similarly high basal drag to that acting at the grounding zone today. We conclude that more can certainly be gleaned from these 3D bathymetric datasets regarding the likely spatial variability of bed roughness and bed composition types underneath TG. This work also addresses the requirements of recent numerical ice-sheet and ocean modelling studies that have recognised the need for accurate and high-resolution bathymetry to determine warm-water routing to the grounding zone and, ultimately, for predicting glacier retreat behaviour.

Abstract Background Tracking and understanding artemisinin resistance is key for preventing global setbacks in malaria eradication efforts. The ring-stage survival assay (RSA) is the current gold standard for in vitro artemisinin resistance phenotyping. However, the RSA has several drawbacks: it is relatively low throughput, has high variance due to microscopy readout, and correlates poorly with the current benchmark for in vivo resistance, patient clearance half-life post-artemisinin treatment. Here a modified RSA is presented, the extended Recovery Ring-stage Survival Assay (eRRSA), using 15 cloned patient isolates from Southeast Asia with a range of patient clearance half-lives, including parasite isolates with and without kelch13 mutations. Methods Plasmodium falciparum cultures were synchronized with single layer Percoll during the schizont stage of the intraerythrocytic development cycle. Cultures were left to reinvade to early ring-stage and parasitaemia was quantified using flow cytometry. Cultures were diluted to 2% haematocrit and 0.5% parasitaemia in a 96-well plate to start the assay, allowing for increased throughput and decreased variability between biological replicates. Parasites were treated with 700 nM of dihydroartemisinin or 0.02% dimethyl sulfoxide (DMSO) for 6 h, washed three times in drug-free media, and incubated for 66 or 114 h, when samples were collected and frozen for PCR amplification. A SYBR Green-based quantitative PCR method was used to quantify the fold-change between treated and untreated samples. Results 15 cloned patient isolates from Southeast Asia with a range of patient clearance half-lives were assayed using the eRRSA. Due to the large number of pyknotic and dying parasites at 66 h post-exposure (72 h sample), parasites were grown for an additional cell cycle (114 h post-exposure, 120 h sample), which drastically improved correlation with patient clearance half-life compared to the 66 h post-exposure sample. A Spearman correlation of − 0.8393 between fold change and patient clearance half-life was identified in these 15 isolates from Southeast Asia, which is the strongest correlation reported to date. Conclusions eRRSA drastically increases the efficiency and accuracy of in vitro artemisinin resistance phenotyping compared to the traditional RSA, which paves the way for extensive in vitro phenotyping of hundreds of artemisinin resistant parasites.

Background Primary hyperparathyroidism (PHPT), caused by an ectopic mediastinal parathyroid adenoma, is uncommon. In the past, when the adenoma was not accessible from the neck, median sternotomy was advocated for safe and successful parathyroidectomy. Video‐assisted thoracoscopic surgical (VATS) parathyroidectomy represents a modern alternative approach to this problem. Methods Information on patients undergoing VATS was obtained from a specific database, including clinical presentation, biochemistry, preoperative imaging, surgical approach and patient outcomes. A comprehensive literature review was undertaken to draw comparisons with other publications. Results Over a 2‐year period, nine patients underwent VATS parathyroidectomy for sporadic PHPT. Five patients had persistent PHPT following previous unsuccessful parathyroidectomy via cervicotomy, and four had had no previous parathyroid surgery. The median duration of surgery was 90 (range 60–160) min. Eight patients were cured biochemically, with no major complications. One patient required conversion to a median sternotomy for removal of a thymoma that had resulted in false‐positive preoperative imaging. Conclusion With appropriate preoperative imaging, multidisciplinary input and expertise, VATS parathyroidectomy is an effective, safe and well tolerated approach to ectopic mediastinal parathyroid adenoma.

Slope failures in roadway embankments are common occurrences and can lead to traffic disruptions and large costs to repair damage. In areas with high-plasticity clays, special attention must be paid to characterizing both the stratigraphy and the potential for strength loss. This study demonstrates the use of an integrated site characterization approach, which seeks to utilize results from geotechnical and geophysical tests to understand the behavior of a landslide in west Alabama. The timing and mechanism of the initial failure causing the preexisting shear plane at this site are not known. Results from electrical resistivity and seismic geophysical tests are integrated with information from borings and index tests to develop a representative cross-section for the landslide, and torsional ring shear results are used to measure the drained fully softened and residual strengths. Both the limit equilibrium (LEM) and strength reduction method (SRM) analyses are used to examine possible failure mechanisms. The results show good agreement between noncircular LEM and SRM analyses and indicate that the initial failure was likely due to undrained loading of the clay. Analyses utilizing the residual drained strength envelopes produce FS values significantly lower than 1 indicating the slope to be unstable when soil on the failure plane exists at the residual state. Sensitivity analyses suggest that the combined effect of lowering the water table and strength recovery may explain the intermittent nature of movements.

MalariaGEN is a data-sharing network that enables groups around the world to work together on the genomic epidemiology of malaria. Here we describe a new release of curated genome variation data on 7,000 Plasmodium falciparum samples from MalariaGEN partner studies in 28 malaria-endemic countries. High-quality genotype calls on 3 million single nucleotide polymorphisms (SNPs) and short indels were produced using a standardised analysis pipeline. Copy number variants associated with drug resistance and structural variants that cause failure of rapid diagnostic tests were also analysed. Almost all samples showed genetic evidence of resistance to at least one antimalarial drug, and some samples from Southeast Asia carried markers of resistance to six commonly-used drugs. Genes expressed during the mosquito stage of the parasite life-cycle are prominent among loci that show strong geographic differentiation. By continuing to enlarge this open data resource we aim to facilitate research into the evolutionary processes affecting malaria control and to accelerate development of the surveillance toolkit required for malaria elimination.

Background: The primary aim of our study was to evaluate the effects of undisclosed financial conflicts of interest in Achilles tendon rupture repair–focused systematic reviews. Methods: Following a cross-sectional study design, we searched MEDLINE and Embase for Achilles tendon rupture repair systematic reviews. We performed screening and data extraction in a blind, triplicate fashion. Each systematic review was evaluated on the individual characteristics of the study, presence of undisclosed and disclosed conflicts of interest, favorability of results and conclusions, and the relationship between conflicts of interest and the favorability of results and conclusions. Results: Our search produced 172 total systematic reviews pertaining to Achilles tendon rupture repair; of those, only 12 were included in our study. Undisclosed conflicts of interest were found in half (6/12) of the included reviews. However, no significant association was found between conflict of interest and the favorability of results and conclusions. Conclusion: Undisclosed conflicts of interests were discovered in a large percentage of our sample. This lack of disclosure did not appear to increase the likelihood of the systematic review results or conclusions reporting favorability of the intervention being investigated. Level of Evidence: Level II.

Two excavations were instrumented at the Auburn National Geotechnical Experimentation Site (NGES) in Opelika, AL. The excavations were constructed approximately 6 m deep × 30 m long with a vertical face. The primary goal of this experiment was to determine the boundary conditions that resulted in failure of the excavation. In doing so, conclusions were drawn regarding the accuracy of common laboratory test methods for estimating the strength properties of residual soil. The instrumentation plan was designed to monitor real-time pore water pressures (positive and negative) surrounding the excavation throughout the course of each 1-year test period. Time-lapse cameras were used to identify when failures occurred, and the approximate geometry of the failure planes. Undisturbed soil samples were taken during the subsurface exploration and used in conjunction with previous soil test results to accurately define the material properties and layering based on common laboratory test methods. In addition to common laboratory tests, unsaturated triaxial tests were also conducted, and soil-water characteristic curves were measured to further define the unsaturated properties of the soil. In both excavations, failure was observed along a similar plane, which began at the bottom of the excavation, and propagated to the surface (approximately 2 m behind the face of the excavation) along existing tension cracks that developed during the construction of the excavation. Based on these results, recommendations are provided as related to the most appropriate test methods for determining the strength properties of residual soil for use in geotechnical design.

Abstract Background Parasite traits associated with transmission success, such as the number of infective stages released from the host, are expected to be optimized by natural selection. However, in the trematode parasite Schistosoma mansoni, a key transmission trait, i.e. the number of cercariae larvae shed from infected Biomphalaria spp. snails, varies significantly within and between different parasite populations and selection experiments demonstrate that this variation has a strong genetic basis. In this study, we compared the transmission strategies of two laboratory schistosome population and their consequences for their snail host. Methods We infected inbred Biomphalaria glabrata snails using two S. mansoni parasite populations (SmBRE and SmLE), both isolated from Brazil and maintained in the laboratory for decades. We compared life history traits of these two parasite populations by quantifying sporocyst growth within infected snails (assayed using qPCR), output of cercaria larvae and impact on snail host physiological response (i.e. hemoglobin rate, laccase-like activity) and survival. Results We identified striking differences in virulence and transmission between the two studied parasite populations. SmBRE (low shedder (LS) parasite population) sheds very low numbers of cercariae and causes minimal impact on the snail physiological response (i.e. laccase-like activity, hemoglobin rate and snail survival). In contrast, SmLE (high shedder (HS) parasite population) sheds 8-fold more cercariae (mean ± SE cercariae per shedding: 284 ± 19 vs 2352 ± 113), causes high snail mortality and has strong impact on snail physiology. We found that HS sporocysts grow more rapidly inside the snail host, comprising up to 60% of cells within infected snails, compared to LS sporocysts, which comprised up to 31%. Cercarial production is strongly correlated to the number of S. mansoni sporocyst cells present within the snail host tissue, although the proportion of sporocyst cells alone does not explain the low cercarial shedding of SmBRE. Conclusions We demonstrated the existence of alternative transmission strategies in the S. mansoni parasite consistent with trade-offs between parasite transmission and host survival: a “boom-bust” strategy characterized by high virulence, high transmission and short duration infections and a “slow and steady” strategy with low virulence, low transmission but long duration of snail host infections.

Abstract Background Competitive outcomes between co-infecting malaria parasite lines can reveal fitness disparities in blood stage growth. Blood stage fitness costs often accompany the evolution of drug resistance, with the expectation that relatively fitter parasites will be more likely to spread in populations. With the recent emergence of artemisinin resistance, it is important to understand the relative competitive fitness of the metabolically active asexual blood stage parasites. Genetically distinct drug resistant parasite clones with independently evolved sets of mutations are likely to vary in asexual proliferation rate, contributing to their chance of transmission to the mosquito vector. Methods An optimized in vitro 96-well plate-based protocol was used to quantitatively measure-head-to-head competitive fitness during blood stage development between seven genetically distinct field isolates from a hotspot of emerging artemisinin resistance and the laboratory strain, NF54. These field isolates were isolated from patients in Southeast Asia carrying different alleles of kelch13 and included both artemisinin-sensitive and artemisinin-resistant isolates. Fluorescent labeled microsatellite markers were used to track the relative densities of each parasite throughout the co-growth period of 14–60 days. All-on-all competitions were conducted for the panel of eight parasite lines (28 pairwise competitions) to determine their quantitative competitive fitness relationships. Results Twenty-eight pairwise competitive growth outcomes allowed for an unambiguous ranking among a set of seven genetically distinct parasite lines isolated from patients in Southeast Asia displaying a range of both kelch13 alleles and clinical clearance times and a laboratory strain, NF54. This comprehensive series of assays established the growth relationships among the eight parasite lines. Interestingly, a clinically artemisinin resistant parasite line that carries the wild-type form of kelch13 outcompeted all other parasites in this study. Furthermore, a kelch13 mutant line (E252Q) was competitively more fit without drug than lines with other resistance-associated kelch13 alleles, including the C580Y allele that has expanded to high frequencies under drug pressure in Southeast Asian resistant populations. Conclusions This optimized competitive growth assay can be employed for assessment of relative growth as an index of fitness during the asexual blood stage growth between natural lines carrying different genetic variants associated with artemisinin resistance. Improved understanding of the fitness costs of different parasites proliferating in human blood and the role different resistance mutations play in the context of specific genetic backgrounds will contribute to an understanding of the potential for specific mutations to spread in populations, with the potential to inform targeted strategies for malaria therapy.

In 1995, a geotechnical experimentation site was established in rural Lee County, Alabama near the area often referred to as Spring Villa. The Auburn University National Geotechnical Experimentation Site (AUNGES) site is situated near the southern terminus of the Appalachian Piedmont Physiographic province. The site consists of two sub sites, one that is a thick profile of residual soil and the other is an outcrop of fractured weathered quartzite. Extensive site investigation has been conducted at the site by many agencies and researchers using a wide array of in-situ soil tests. Foundations, excavations, and retaining structures have been constructed and load tested at the AUNGES. This paper summarizes all the work conducted at the site since its inception. Maps that detail the location of all in-situ tests and structures tested were generated. Representative profiles are included that relate early site investigation, between 1995 and 2005, and contemporary work done after 2010 are generated based on the results of piezocone, dilatometer, standard penetration, and shear wave velocity tests.

The microbial by-product nitrous oxide (N2O), a potent greenhouse gas and ozone depleting substance, has conventionally been assumed to have minimal emissions in permafrost regions. This assumption has been questioned by recent in situ studies which have demonstrated that some geologic features in permafrost may, in fact, have elevated emissions comparable to those of tropical soils. However, these recent studies, along with every known in situ study focused on permafrost N2O fluxes, have used chambers to examine small areas ( m2). In late August 2013, we used the airborne eddy-covariance technique to make in situ N2O flux measurements over the North Slope of Alaska from a low-flying aircraft spanning a much larger area: around 310 km2. We observed large variability of N2O fluxes with many areas exhibiting negligible emissions. Still, the daily mean averaged over our flight campaign was 3.8 (2.2–4.7) mg N2O m−2 d−1 with the 90 % confidence interval shown in parentheses. If these measurements are representative of the whole month, then the permafrost areas we observed emitted a total of around 0.04–0.09 g m−2 for August, which is comparable to what is typically assumed to be the upper limit of yearly emissions for these regions.

Oxamniquine (OXA) is a prodrug activated by a sulfotransferase (SULT) that was only active against Schistosoma mansoni. We have reengineered OXA to be effective against S. haematobium and S. japonicum. Three derivatives stand out, CIDD-0066790, CIDD-0072229, and CIDD-0149830 as they kill all three major human schistosome species. However, questions remain. Is the OXA mode of action conserved in derivatives? RNA-interference experiments demonstrate that knockdown of the SmSULT, ShSULT, and SjSULT results in resistance to CIDD-0066790. Confirming that the OXA-derivative mode of action is conserved. Next is the level of expression of the schistosome SULTs in each species, as well as changes in SULT expression throughout development in S. mansoni. Using multiple tools, our data show that SmSULT has higher expression compared to ShSULT and SjSULT. Third, is the localization of SULT in the adult, multicellular eucaryotic schistosome species. We utilized fluorescence in situ hybridization and uptake of radiolabeled OXA to determine that multiple cell types throughout the adult schistosome worm express SULT. Thus, we hypothesize the ability of many cells to express the sulfotransferase accounts for the ability of the OXA derivatives to kill adult worms. Our studies demonstrate that the OXA derivatives are able to kill all three human schistosome species and thus will be a useful complement to PZQ.

Objective: To assess the influence of industry sponsorship and authors’ conflicts of interest on the favorability of results and conclusions of systematic reviews regarding osteoarthritis of the knee. Design: We searched MEDLINE, Embase, and the Cochrane Database of Systematic Reviews on June 26, 2020 for systematic reviews with or without meta-analyses focusing on treatment of osteoarthritis of the knee. Author COI were collected from the systematic review’s COI disclosure statement, the CMS Open Payments Database, Dollars for Profs, Google Patents, the United States Patent and Trademark Office (USPTO), as well as previously published COI disclosure statements. Study sponsorship was determined using information provided in each systematic review’s funding statement. Results: Our study included 53 systematic reviews conducted by a total of 279 authors. Thirty-one authors (of 279; 11.1%) had one or more COI. Fourteen systematic reviews (of 53; 26.4%) had one or more conflicted authors. Of these reviews, only two (of 14; 14.3%) reported narrative results favoring the treatment group, whereas five (of 14; 35.7%) reported conclusions favoring the treatment group. Our results showed no statistically significant association between the presence of COI and the favorability of results (P= 0.11) and conclusions (P= 0.73). Because our sample only included one industry-sponsored systematic review, we were unable to adequately assess for a relationship between industry-sponsorship and favorability of results and conclusions. Conclusion: We found no association between the favorability of systematic review results and conclusions with either the presence of author’s conflicts of interest or industry-sponsorship.

MalariaGEN is a data-sharing network that enables groups around the world to work together on the genomic epidemiology of malaria. Here we describe a new release of curated genome variation data on 7,000 Plasmodium falciparum samples from MalariaGEN partner studies in 28 malaria-endemic countries. High-quality genotype calls on 3 million single nucleotide polymorphisms (SNPs) and short indels were produced using a standardised analysis pipeline. Copy number variants associated with drug resistance and structural variants that cause failure of rapid diagnostic tests were also analysed. Almost all samples showed genetic evidence of resistance to at least one antimalarial drug, and some samples from Southeast Asia carried markers of resistance to six commonly-used drugs. Genes expressed during the mosquito stage of the parasite life-cycle are prominent among loci that show strong geographic differentiation. By continuing to enlarge this open data resource we aim to facilitate research into the evolutionary processes affecting malaria control and to accelerate development of the surveillance toolkit required for malaria elimination.

Characterising connectivity between geographically separated biological populations is a common goal in many fields. Recent approaches to understanding connectivity between malaria parasite populations, with implications for disease control efforts, have used estimates of relatedness based on identity-by-descent (IBD). However, uncertainty around estimated relatedness has not been accounted for. IBD-based relatedness estimates with uncertainty were computed for pairs of monoclonal Plasmodium falciparum samples collected from five cities on the Colombian-Pacific coast where long-term clonal propagation of P. falciparum is frequent. The cities include two official ports, Buenaventura and Tumaco, that are separated geographically but connected by frequent marine traffic. Fractions of highly-related sample pairs (whose classification using a threshold accounts for uncertainty) were greater within cities versus between. However, based on both highly-related fractions and on a threshold-free approach (Wasserstein distances between parasite populations) connectivity between Buenaventura and Tumaco was disproportionally high. Buenaventura-Tumaco connectivity was consistent with transmission events involving parasites from five clonal components (groups of statistically indistinguishable parasites identified under a graph theoretic framework). To conclude, P. falciparum population connectivity on the Colombian-Pacific coast abides by accessibility not isolation-by-distance, potentially implicating marine traffic in malaria transmission with opportunities for targeted intervention. Further investigations are required to test this hypothesis. For the first time in malaria epidemiology (and to our knowledge in ecological and epidemiological studies more generally), we account for uncertainty around estimated relatedness (an important consideration for studies that plan to use genotype versus whole genome sequence data to estimate IBD-based relatedness); we also use threshold-free methods to compare parasite populations and identify clonal components. Threshold-free methods are especially important in analyses of malaria parasites and other recombining organisms with mixed mating systems where thresholds do not have clear interpretation (e.g. due to clonal propagation) and thus undermine the cross-comparison of studies.

Currently there is only one method of treatment for human schistosomiasis, the drug praziquantel. Strong selective pressure has caused a serious concern for a rise in resistance to praziquantel leading to the necessity for additional pharmaceuticals, with a distinctly different mechanism of action, to be used in combination therapy with praziquantel. Previous treatment of Schistosoma mansoni included the use of oxamniquine (OXA), a prodrug that is enzymatically activated in S. mansoni but is ineffective against S. haematobium and S. japonicum. The oxamniquine activating enzyme was identified as a S. mansoni sulfotransferase (SmSULT-OR). Structural data have allowed for directed drug development in reengineering oxamniquine to be effective against S. haematobium and S. japonicum. Guided by data from X-ray crystallographic studies and Schistosoma worm killing assays on oxamniquine, our structure-based drug design approach produced a robust SAR program that tested over 300 derivatives and identified several new lead compounds with effective worm killing in vitro. Previous studies resulted in the discovery of compound CIDD-0066790, which demonstrated broad-species activity in killing of schistosome species. As these compounds are racemic mixtures, we tested and demonstrate that the R enantiomer CIDD-007229 kills S. mansoni, S. haematobium and S. japonicum better than the parent drug (CIDD-0066790). The search for derivatives that kill better than CIDD-0066790 has resulted in a derivative (CIDD- 149830) that kills 100% of S. mansoni, S. haematobium and S. japonicum adult worms within 7 days. We hypothesize that the difference in activation and thus killing by the derivatives is due to the ability of the derivative to fit in the binding pocket of each sulfotransferase (SmSULT-OR, ShSULT-OR, SjSULT-OR) and to be efficiently sulfated. The purpose of this research is to develop a second drug to be used in conjunction with praziquantel to treat the major human species of Schistosoma. Collectively, our findings show that CIDD-00149830 and CIDD-0072229 are promising novel drugs for the treatment of human schistosomiasis and strongly support further development and in vivo testing.

Canine Chronic Ulcerative Stomatitis is a spontaneously occurring inflammatory disease of the oral mucosa. An immune-mediated pathogenesis is suspected though not yet proven. We have recently reported on the clinical and histologic features, and identification of select leukocyte cell populations within the lesion. A clinical and histologic similarity to oral lichen planus of people was proposed. In the present study, these initial observations are extended by examining lesions from 24 dogs with clinical evidence of chronic ulcerative stomatitis. Because dogs with chronic ulcerative stomatitis often have concurrent periodontal disease, we wondered if dental plaque/biofilm may be a common instigator of inflammation in both lesions. We hypothesized that dogs with chronic ulcerative stomatitis would exhibit a spectrum of pathologic changes and phenotype of infiltrating leukocytes that would inform lesion pathogenesis and that these changes would differ from inflammatory phenotypes in periodontitis. Previously we identified chronic ulcerative stomatitis lesions to be rich in FoxP3+ and IL17+ cells. As such, we suspect that these leukocytes play an important role in lesion pathogenesis. The current study confirms the presence of moderate to large numbers of FoxP3+ T cells and IL17+ cells in all ulcerative stomatitis lesions using confocal immunofluorescence. Interestingly, the majority of IL17+ cells were determined to be non-T cells and IL17+ cell frequencies were negatively correlated with severity on the clinical scoring system. Three histologic subtypes of ulcerative stomatitis were determined; lichenoid, deep stomatitis and granulomatous. Periodontitis lesions, like stomatitis lesions, were B cell and plasma cell rich, but otherwise differed from the stomatitis lesions. Direct immunofluorescence results did not support an autoantibody-mediated autoimmune disease process. This investigation contributes to the body of literature regarding leukocyte involvement in canine idiopathic inflammatory disease pathogenesis.

Assimilation of atmospheric composition retrievals presents computational challenges due to their high data volume and often sparse information density. Assimilation of compact phase space retrievals (CPSRs) meets those challenges and offers a promising alternative to assimilation of raw retrievals at reduced computational cost (Mizzi et al., 2016). This paper compares analysis and forecast results from assimilation of Terra/Measurement of Pollution in the Troposphere (MOPITT) carbon monoxide (CO) CPSRs with independent observations. We use MetOp-A/Infrared Atmospheric Sounding Interferometer (IASI) CO retrievals and Measurement of OZone, water vapor, carbon monoxide, and nitrogen oxides by in-service AIrbus airCraft (MOZAIC) in situ CO profiles for our independent observation comparisons. Generally, the results confirm that assimilation of MOPITT CPSRs improves the Weather Research and Forecasting model with chemistry coupled to the ensemble Kalman filter data assimilation from the Data Assimilation Research Testbed (WRF-Chem/DART) analysis fit and forecast skill at a reduced computational cost compared to assimilation of raw retrievals. Comparison with the independent observations shows that assimilation of MOPITT CO generally improved the analysis fit and forecast skill in the lower troposphere but degraded it in the upper troposphere. We attribute that degradation to assimilation of MOPITT CO retrievals with a possible bias of ∼ 14 % above 300 hPa. To discard the biased retrievals, in this paper, we also extend CPSRs to assimilation of truncated retrieval profiles (as opposed to assimilation of full retrieval profiles). Those results show that not assimilating the biased retrievals (i) resolves the upper tropospheric analysis fit degradation issue and (ii) reduces the impact of assimilating the remaining unbiased retrievals because the total information content and vertical sensitivities are changed.