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We present a parallel combination of existing, well-known and robust software used in modelling the neotectonics of planetary lithosphere, which we call ShellSet. An added parallel framework allows multiple models to be run at the same time with varied input parameters. Additionally, we have included a grid search option to automatically generate models within a given parameter space. ShellSet offers significant advantages over the original programs through its simplicity, efficiency and speed. We demonstrate the performance improvement obtained by ShellSet's parallel framework by presenting timing and speedup information for a parallel grid search, varying the number of processes and models, on both a typical computer and a high-performance computing cluster node. A possible use case for ShellSet is shown using two examples in which we improve on an existing global model. In the first example we improve the model using the same data, and in the second example we further improve the model through the addition of a new scoring dataset. The necessary ShellSet program version along with all the required input and post-processing files needed to recreate the results presented in this article are available at https://doi.org/10.5281/zenodo.7986808 (May et al., 2023).

Spaceborne lidar provides a unique opportunity to supplement the field plot measurements of national forest inventories (NFIs) by providing dense measurements of vertical canopy structure. For full waveform instruments such as the Global Ecosystem Dynamics Investigation (GEDI), measurements take the form of reflected energy as a function of height within an observed footprint. Many forest attributes cannot be directly computed from the waveforms, and thus statistical models relating the measurements to target attributes must be trained using field plot data. Because the discrete footprint samples produced by spaceborne lidar instruments have little chance of collocation with pre-existing field plots, model calibration remains a primary challenge. We leveraged the density and spatial correlation of GEDI observations to make predictions of the cumulative waveform over 326,787 NFI plots distributed across the contiguous United States. The predictions yield probability distributions, giving not only a predicted waveform but quantification of prediction uncertainty. The product of this work is a data set comprised of the NFI plots paired with the predictive waveform distributions. The predicted waveforms and their uncertainties can be used to train models with “error-in-variables” techniques that account for and filter the uncertainty in the predicted waveforms. This data set and the corresponding techniques allow statistically rigorous model training without requirements of collocation, yielding downstream forest attribute predictions that are consistent with NFI measurements and estimates. We demonstrate the data set by training a model for forest above ground biomass density (AGBD) and then use the model to produce a spatially complete 1 km map of AGBD for the contiguous United States. We further compare our AGBD predictions to US NFI estimates at a 64,000 hectare scale, showing the increase in precision to be proportional to the collection of almost 500,000 additional NFI plots across forested regions of CONUS.

Dopamine has multiple physiological functions including feed intake control in which it can act as an anorectic or orexigenic agent. This study had the objective to evaluate intra-abomasal administration of L-DOPA (levodopa; L-3,4-dihydroxyphenylalanine) from -Mucuna pruriens on circulating catecholamines, indicators of energy metabolism and feed intake in cattle. Eight Holstein steers (340 ± 20 kg) fitted with ruminal cannula were used in a replicated 4 x 4 Latin Square design experiment. Intra-abomasal infusion of L-DOPA at 0, 0.5, 1 and 2 mg/kg BW was carried out for seven days and blood samples were collected at 0, 30, 60, 120, 240 and 480 min from L-DOPA infusion on day 7. The area under the curve (AUC) of plasma L-DOPA and free dopamine increased quadratically with the administration of L-DOPA. However, the AUC of plasma total dopamine had a positive linear response with the increase of L-DOPA. Conversely, the serum 5-hydroxytriptophan (5-HTP), plasma serotonin, serum serotonin, serum tyrosine, plasma glucose and plasma free fatty acids were not affected by the intra-abomasal infusion of L-DOPA. The circulating concentration of the epinephrine, norepinephrine, serotonin, glucose and free fatty acids did not change with L-DOPA infusion. It can be concluded that intra-abomasal L-DOPA administration produced a strong increase in circulating dopamine with no change in energy metabolites and feed intake in cattle.

Background: Studies have shown conflicting results on the efficacy of tocilizumab (TCZ) for patients with COVID-19, with many confounders of clinical status and limited duration of the observation. Here, we evaluate the real-world long-term efficacy of TCZ in COVID-19 patients. Methods: We conducted a retrospective study of hospitalized adult patients with COVID-19 using a large US-based multicenter COVID-19 database (Cerner Real-World Data; updated in September, 2020). The TCZ group was defined as patients who received at least one dose of the drug. Matching weight (MW) and a propensity score weighting method were used to balance confounding factors. Results: A total of 20,399 patients were identified. 1,510 and 18,899 were in the TCZ and control groups, respectively. After MW adjustment, no statistically significant differences in all-cause mortality were found for the TCZ vs. control group (Hazard Ratio [HR]:0.76, p=0.06). Survival curves suggested a better trend in short-term observation, driven from a subgroup of patients requiring oxygen masks, BIPAP or CPAP. Conclusion: We observed a temporal (early) benefit of TCZ, especially in patients on non-invasive high-flow supplemental oxygen. However, the benefit effects faded with longer observation. The long-term benefits and risks of TCZ should be carefully evaluated with follow-up studies.

Abstract Background Endoscopic submucosal dissection (ESD) is a novel endoscopic treatment for early esophageal adenocarcinoma (EAC). The western pathologists’ experience with ESD specimens remains limited. This study aimed to correlate histopathologic features of Barrett’s esophagus (BE)-associated adenocarcinoma in ESD resections with clinical outcomes to determine whether they aid future management decisions. Methods We retrospectively evaluated 49 consecutive ESD resection specimens from 42 patients with BE-associated adenocarcinoma (24 intramucosal and 18 submucosal EAC) at a single tertiary referral center. Pathologic evaluation included presence of dysplasia, invasive adenocarcinoma, peritumoral inflammation, desmoplasia, lymphovascular and perineural invasion; tumor differentiation, depth of invasion, morphology, and budding; and margin status for dysplasia or carcinoma. Follow up data included endoscopic biopsies in 35 patients and pathology reports of esophagectomies in 11 patients. Poor outcomes were defined as recurrence or residual invasive adenocarcinoma at esophagectomy, metastasis on imaging, or R1 resection in patients undergoing ESD for tumor debulking. Results Two patients (8%) with intramucosal adenocarcinoma and 9 patients (50%) with submucosal adenocarcinoma had poor outcomes. Histopathologic features associated with poor outcomes included poor differentiation, lymphovascular invasion, submucosal invasion > 500 μm, tumor budding, and tubuloinfiltrative histologic pattern. Four patients had positive deep margin away from the deepest tumor invasion and did not show residual tumor on follow up. Conclusions Our results validated European Society of Gastroenterology (ESGE) guidelines of high-risk pathologic features for additional therapy in esophageal adenocarcinoma and identified tumor budding frequently in association with other high-risk features. Positive deep margin distant from deepest tumor invasion could be procedural and warrants endoscopic correlation for management.

Historically, ecological monitoring of marine habitats has primarily relied on labour-intensive, non-automated survey methods. The field of passive acoustic monitoring (PAM) has demonstrated the potential of this practice to automate surveying in marine habitats. This has primarily been through the use of ‘ecoacoustic indices’ to quantify attributes from natural soundscapes. However, investigations using individual indices have had mixed success. Using PAM recordings collected at one of the world’s largest coral reef restoration programmes, we instead apply a machine-learning approach across a suite of ecoacoustic indices to improve predictive power of ecosystem health. Healthy and degraded reef sites were identified through live coral cover surveys, with 90–95% and 0–20% cover respectively. A library of one-minute recordings were extracted from each. Twelve ecoacoustic indices were calculated for each recording, in up to three different frequency bandwidths (low: 0.05–0.8 kHz, medium: 2–7 kHz and broad: 0.05–20 kHz). Twelve of these 33 index-frequency combinations differed significantly between healthy and degraded habitats. However, the best performing single index could only correctly classify 47% of recordings, requiring extensive sampling from each site to be useful. We therefore trained a regularised discriminant analysis machine-learning algorithm to discriminate between healthy and degraded sites using an optimised combination of ecoacoustic indices. This multi-index approach discriminated between these two habitat classes with improved accuracy compared to any single index in isolation. The pooled classification rate of 1000 cross-validated iterations of the model had a 91.7% 0.8, mean SE) success rate at correctly classifying individual recordings. The model was subsequently used to classify recordings from two actively restored sites, established >24 months prior to recordings, with coral cover values of 79.1% (±3.9) and 66.5% (±3.8). Of these recordings, 37/38 and 33/39 received a classification as healthy respectively. The model was also used to classify recordings from a newly restored site established

Summary: Volatile short-chain fatty acids such as butyric and acetic acid have been supplemented in poultry rations as a feed ingredient and nutritive supplement. A novel Clostridium fermentation solubles broth (MiruTyton), containing short-chain fatty acids, minerals, and amino acids, was supplemented in a standard corn/soybean meal–based ration at a rate of 750, 1,500, 3,000, and 6,000 mg/kg to achieve approximately 277, 554, 1,108, and 2,216 mg/kg of ammonium butyrate in the diet. After 6 wk, supplementation at all levels did not cause significant changes in the blood parameters or any live performance metric of mixed-sex Cobb-500 broilers (N = 1,920). In addition, administering 6,000 mg/kg of MiruTyton caused no significant lesions in any of the tissue examined except for an increase (P

Earth Observation data are uniquely positioned to estimate forest aboveground biomass density (AGBD) in accordance with the United Nations Framework Convention on Climate Change (UNFCCC) principles of ‘transparency, accuracy, completeness, consistency and comparability’. However, the use of space-based AGBD maps for national-level reporting to the UNFCCC is nearly non-existent as of 2023, the end of the first global stocktake (GST). We conduct an evidence-based comparison of AGBD estimates from the NASA Global Ecosystem Dynamics Investigation and ESA Climate Change Initiative, describing differences between the products and National Forest Inventories (NFIs), and suggesting how science teams must align efforts to inform the next GST. Between the products, in the tropics, the largest differences in estimated AGBD are primarily in the Congolese lowlands and east/southeast Asia. Where NFI data were acquired (Peru, Mexico, Lao PDR and 30 regions of Spain), both products show strong correlation to NFI-estimated AGBD, with no systematic deviations. The AGBD-richest stratum of these, the Peruvian Amazon, is accurately estimated in both. These results are remarkably promising, and to support the operational use of AGB map products for policy reporting, we describe targeted ways to align products with Intergovernmental Panel on Climate Change (IPCC) guidelines. We recommend moving towards consistent statistical terminology, and aligning on a rigorous framework for uncertainty estimation, supported by the provision of open-science codes for large-area assessments that comprehensively report uncertainty. Further, we suggest the provision of objective and open-source guidance to integrate NFIs with multiple AGBD products, aiming to enhance the precision of national estimates. Finally, we describe and encourage the release of user-friendly product documentation, with tools that produce AGBD estimates directly applicable to the IPCC guideline methodologies. With these steps, space agencies can convey a comparable, reliable and consistent message on global biomass estimates to have actionable policy impact.

BackgroundIdentification of people with HIV from electronic health record (EHR) data is an essential first step in the study of important HIV outcomes, such as risk assessment. This task has been historically performed via manual chart review, but the increased availability of large clinical data sets has led to the emergence of phenotyping algorithms to automate this process. Existing algorithms for identifying people with HIV rely on a combination of International Classification of Disease codes and laboratory tests or closely mimic clinical testing guidelines for HIV diagnosis. However, we found that existing algorithms in the literature missed a significant proportion of people with HIV in our data. ObjectiveThe aim of this study is to develop and evaluate HIV-Phen, an updated criteria-based HIV phenotyping algorithm. MethodsWe developed an algorithm using HIV-specific laboratory tests and medications and compared it with previously published algorithms in national and local data sets to identify cohorts of people with HIV. Cohort demographics were compared with those reported in the national and local surveillance data. Chart reviews were performed on a subsample of patients from the local database to calculate the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of the algorithm. ResultsOur new algorithm identified substantially more people with HIV in both national (up to an 85.75% increase) and local (up to an 83.20% increase) EHR databases than the previously published algorithms. The demographic characteristics of people with HIV identified using our algorithm were similar to those reported in national and local HIV surveillance data. Our algorithm demonstrated improved sensitivity over existing algorithms (98% vs 56%-92%) while maintaining a similar overall accuracy (96% vs 80%-96%). ConclusionsWe developed and evaluated an updated criteria-based phenotyping algorithm for identifying people with HIV in EHR data that demonstrates improved sensitivity over existing algorithms.

ABSTRACT Irrigation water sources have been shown to harbor foodborne pathogens and could contribute to the outbreak of foodborne illness related to consumption of contaminated produce. Determining the probability of and the degree to which these irrigation water sources contain these pathogens is paramount. The purpose of this study was to determine the prevalence of Salmonella enterica and Listeria monocytogenes in alternative irrigation water sources. Water samples (n = 188) were collected over 2 years (2016 to 2018) from 2 reclaimed water plants, 3 nontidal freshwater rivers, and 1 tidal brackish river on Maryland’s Eastern Shore (ESM). Samples were collected by filtration using modified Moore swabs (MMS) and analyzed by culture methods. Pathogen levels were quantified using a modified most probable number (MPN) procedure with three different volumes (10 liters, 1 liter, and 0.1 liter). Overall, 65% (122/188) and 40% (76/188) of water samples were positive for S. enterica and L. monocytogenes, respectively. For both pathogens, MPN values ranged from 0.015 to 11 MPN/liter. Pathogen levels (MPN/liter) were significantly (P

Agricultural drainage ditches represent a major source of nutrient pollution. Shifts in nitrogen source and use of animal manures have changed the bacterial composition both in species of bacteria and their abundance in agricultural ditches. This change affects how nitrogen is being cycled and potentially the final forms of available nutrients. In particular, animal manures often have bacteria such as Escherichia coli present, increasing the abundance of a bacterial species in ditches. Research has shown that the effect of different nitrogen sources is to change bacterial community composition (class, family). How this influences the role of an individual bacterial species is poorly understood. Thus, our question was how individual species would respond to different sources of nitrogen. We used Aeromonas hydrophila, Bacillus thuringiensis, Escherichia coli and Pseudomonas aeruginosa that are common in agricultural ditches and exposed them to different concentrations of nitrogen in cultures of 1 × 100 and 1 × 10−1 dilutions from a stock solution of bacteria. Nitrogen sources were ammonium chloride, sodium nitrate and urea. The results showed A. hydrophila and E. coli have strong similarities particularly with nitrate-N and urea-N utilization and the response was often correlated with the amount of nutrient added. P. aeruginosa while similar did not show any strong correlation with amount of nutrient added. B. thuringiensis was different from the other three bacteria in utilization or production. Research has provided insight into the role of some bacteria in nitrogen cycling and may be valuable in the future to developing management strategies to reduce nutrients.

Few interventions have been shown to improve retention in HIV care. We recently completed a randomized, controlled trial of a peer mentoring intervention, which failed to increase retention in care or HIV suppression. We sought to gain insight into this negative result and elicit suggestions for future interventions. We conducted semi-structured one-on-one interviews with a sub-sample of participants and all available interventionists after completion of the primary study. Interviews were coded by two researchers and thematically analyzed. Participants in the intervention arm (N = 16) reported good rapport with and benefit from peer mentoring and found the mentors helpful in facilitating the transition from hospital to out-patient clinic. Control arm participants (N = 9) reported similar emotional and social support benefits from the health educators. In both arms, ongoing challenges including completing paperwork, securing transportation, and rescheduling missed appointments were cited, along with internalized stigma and lack of will to seek care, despite the mentors' best efforts. Suggested improvements to the intervention included: more frequent contact with interventionists; additional support for mental health problems; and targeting overall health rather than a more selective focus on HIV. Mentors and health educators agreed with the participant-reported barriers and added that some participants were too sick to meaningfully participate in the intervention, while others appeared unwilling to engage with the interventionists in a meaningful way. Mentoring was highly acceptable and felt to be impactful, however it was not sufficient to overcome structural barriers or stigma and low motivation in some participants. The attention control intervention may have had an unintended positive impact. Future interventions should focus on broad aspects of health and well-being.

This paper will show a comparison between the Kepler, Maxwell and Pascal GPU architectures using CUDA-Fortran, with and without dynamic calls, to efficiently solve partial differential equations. The target is to show the possibility of using affordable hardware, such as the GTX670, GTX970 and GTX1080 NVIDIA GPUs, which are commonly found in personal and portable computers, for scientific applications. For simplicity we consider a standard wave equation where we use a second order finite difference method for the spatial and time discretizations to obtain the numerical solution. We found that, as we increase the spatial resolution of the domain we also increase the performance difference between the GPU and the Central Processing Unit (CPU).

There is strong interest in adapting denitrifying bioreactors to mid-Atlantic drainage systems to help address Chesapeake Bay water quality goals. Three ditch drainage-oriented bioreactors were constructed in 2015 in Maryland to evaluate site-specific design and installation concerns and nitrate (NO–N) removal. All three bioreactor types removed NO–N, as measured by load and/or concentration reduction, showing promise for denitrifying bioreactors in the mid-Atlantic’s low gradient Coastal Plain landscape. The ditch diversion bioreactor (25% NO–N load reduction; 0.97 g NO–N removed m d) and the sawdust denitrification wall adjacent to a ditch (>90% NO–N concentration reduction; 1.9–2.9 g NO–N removed m d) had removal rates within range of the literature. The in-ditch bioreactor averaged 65% NO–N concentration reduction, but sedimentation is expected to be one of the biggest challenges. A robust water balance is critical for future assessment of bioreactors’ contribution to water quality improvement in low gradient mid-Atlantic landscapes.

Helicobacter pylori colonises the human stomach and has tropism for the gastric mucin, MUC5AC. The majority of organisms live in the adherent mucus layer within their preferred location, close to the epithelial surface where the pH is near neutral. Trefoil factor 1 (TFF1) is a small trefoil protein co-expressed with the gastric mucin MUC5AC in surface foveolar cells and co-secreted with MUC5AC into gastric mucus. Helicobacter pylori binds with greater avidity to TFF1 dimer, which is present in gastric mucus, than to TFF1 monomer. Binding of H. pylori to TFF1 is mediated by the core oligosaccharide subunit of H. pylori lipopolysaccharide at pH 5.0−6.0. Treatment of H. pylori lipopolysaccharide with mannosidase or glucosidase inhibits its interaction with TFF1. Both TFF1 and H. pylori have a propensity for binding to mucins with terminal non-reducing α- or β-linked N-acetyl-d-glucosamine or α-(2,3) linked sialic acid or Gal-3-SO42−. These findings are strong evidence that TFF1 has carbohydrate-binding properties that may involve a conserved patch of aromatic hydrophobic residues on the surface of its trefoil domain. The pH-dependent lectin properties of TFF1 may serve to locate H. pylori deep in the gastric mucus layer close to the epithelium rather than at the epithelial surface. This restricted localisation could limit the interaction of H. pylori with epithelial cells and the subsequent host signalling events that promote inflammation.

Investigations into the genesis and dynamical properties of cave ice are essential for assessing the climate significance of these underground glaciers. We drilled an ice core through a 7.1 m-thick ice body filling a large cavern of the dynamic ice cave Eisenriesenwelt (Austria). In addition to visual core inspections, quasi-continuous measurements at 2 cm resolution comprised particulate matter, stable water isotope (δ18O, δD) and electrolytic conductivity profiles supplemented by specifically selected samples analyzed for tritium and radiocarbon. We found that recent ablation led to an almost complete loss of bomb-derived tritium removing any ice accumulated since, at least, the early fifties leaving the actual ice surface even below the natural tritium level. The small particulate organic masses rendered radiocarbon dating inconclusive, though a crude estimate gave a basal ice age in the order of several thousand years. The visual stratigraphy and all investigated parameters showed a clear dichotomy between the upper 2 m and the bottom 3 m of the core, which points to a substantial change in the ice formation process. Main features of the core comprise the changing appearance and composition of distinct cryocalcite layers, extremely low total ion content and a surprisingly high variability of the isotope signature. Co-isotope evaluation (δD versus δ18O) of the core in comparison with data from precipitation and karst spring water clearly indicate that ice formation is governed by (slow) freezing of dripping water.

The aim of this case series was to describe the clinical, laboratory and epidemiological characteristics and the presentation of bacillary angiomatosis cases (and/or parenchymal bacillary peliosis) that were identified in five public hospitals of Rio de Janeiro state between 1990 and 1997; these cases were compared with those previously described in the medical literature. Thirteen case-patients were enrolled in the study; the median age was 39 years and all patients were male. All patients were human immunodeficiency virus type 1 (HIV-1) infected and they had previous or concomitant HIV-associated opportunistic infections or malignancies diagnosed at the time bacillary angiomatosis was diagnosed. Median T4 helper lymphocyte counts of patients was 96 cells per mm³. Cutaneous involvement was the most common clinical manifestation of bacillary angiomatosis in this study. Clinical remission following appropriate treatment was more common in our case series than that reported in the medical literature, while the incidence of relapse was similar. The frequency of bacillary angiomatosis in HIV patients calculated from two of the hospitals included in our study was 1.42 cases per 1000 patients, similar to the frequencies reported in the medical literature. Bacillary angiomatosis is an unusual opportunistic pathogen in our setting.

Obesity has reached epidemic proportions in the developed world. The progression from obesity to diabetes mellitus type 2, via metabolic syndrome, is recognised, and the significant associated increase in the risk of major human cancers acknowledged. We review the molecular basis of the involvement of morbidly high concentrations of endogenous or therapeutic insulin and of insulin-like growth factors in the progression from obesity to diabetes and finally to cancer. Epidemiological and biochemical studies establish the role of insulin and hyperinsulinaemia in cancer risk and progression. Insulin-like growth factors, IGF-1 and IGF-2, secreted by visceral or mammary adipose tissue have significant paracrine and endocrine effects. These effects can be exacerbated by increased steroid hormone production. Structural studies elucidate how each of the three ligands, insulin, IGF-1, and IGF-2, interacts differently with isoforms A and B of the insulin receptor and with type I IGF receptor and explain how these protagonists contribute to diabetes-associated cancer. The above should inform appropriate treatment of cancers that arise in obese individuals and in those with diabetes mellitus type 2. Novel drugs that target the insulin and insulin-like growth factor signal transduction pathways are in clinical trial and should be effective if appropriate biomarker-informed patient stratification is implemented.

Helicobacter pylori colonises the gastric mucosa of humans. The majority of organisms live in mucus. These organisms are an important reservoir for infection of the underlying epithelium. Cell culture models for H. pylori infection do not normally possess a mucus layer. The interaction of H. pylori with TFF1, a member of the trefoil factor family found in gastric mucin, is mediated by lipopolysaccharide. To test the hypothesis that the interaction of H. pylori with TFF1 promotes mucus colonization we characterised the interaction of H. pylori with a mucus secreting cell line, HT29-MTX-E12. An isogenic mutant of H. pylori with truncated core oligosaccharides was produced and binding to TFF1 and ability to colonise HT29-MTX-E12 cells determined. The adherent mucus layer of HT29-MTX-E12 cells contained the gastric mucin MUC5AC and trefoil factors, TFF1 and TFF3. H. pylori was found within the mucus layer in discrete clusters and in close association with TFF1. It also interacted with the membrane bound mucin MUC1 and replicated when co-cultured with the cells. An isogenic mutant of H. pylori with a truncated LPS core did not interact with TFF1, and colonization of HT29-MTX-E12 cells was reduced compared to the wild-type strain (p