Search

The disruption of antimicrobial stewardship programmes (ASPs) caused by coronavirus disease 2019 (COVID-19) has been recognized but not explored in depth. This study used a theoretical, qualitative approach to understand the impact of COVID-19 on ASP implementation in hospitals.Semi-structured online interviews, informed by the Consolidated Framework for Implementation Research (CFIR), were conducted with ASP team members and non-members in hospitals. Participants were recruited via purposeful and snowball sampling with interviews video recorded, transcribed and analysed independently by two researchers based on mapping against CFIR constructs.Thirty-one interviews were conducted across 11 hospitals. The following themes were identified: (i) increased complexity of ASP implementation and changes in prescribing behaviour influenced by COVID-19; (ii) adaptations, networking and cosmopolitanism to enhance integration of COVID-19 management into ASP services; and (iii) adaptations and networking to support continuity of the ASP implementation process. A disruption to pre-pandemic ASP activities was reported, with complexity of COVID-19 overwhelming the healthcare system. ASP team members and services showed an ability to adapt and repurpose roles to respond to the pandemic. Interventions included developing national guidelines for treatment of patients with COVID-19 and contributing to guideline management and monitoring. A gradual restoration of ASP activities was perceived. Technological adaptations and enhancements in networking were reported as positive impacts of the pandemic.Despite the initial disruption of ASP implementation caused by the pandemic, successful adaptation and evolution of ASP services reflects the high value and adaptability of ASP implementation in hospitals in the United Arab Emirates.

In the present study, a facile, eco-friendly, and controlled synthesis of gold nanoparticles (Au NPs) using Prunus nepalensis fruit extract is reported. The biogenically synthesized Au NPs possess ultra-active intrinsic peroxidase-like activity for the oxidation of 3,3′,5,5′-tetramethylbenzidine (TMB) in the presence of H2O2. Chemical analysis of the fruit extract demonstrated the presence of various bioactive molecules such as amino acids (l-alanine and aspartic acids), organic acids (benzoic acid and citric acid), sugars (arabinose and glucose), phenolic acid, and bioflavonoids (niacin and myo-inositol), which likely attributed to the formation of stable biogenic Au NPs with excellent peroxidase-mimicking activity. In comparison with the natural horseradish peroxidase (HRP) enzyme, the biogenic Au NPs displayed a 9.64 times higher activity with regard to the reaction velocity at 6% (v/v) H2O2, presenting a higher affinity toward the TMB substrate. The Michaelis-Menten constant (KM) values for the biogenic Au NPs and HRP were found to be 6.9 × 10-2 and 7.9 × 10-2 mM, respectively, at the same concentration of 100 pM. To investigate its applicability for biosensing, a monoclonal antibody specific for Mycobacterium bovis (QUBMA-Bov) was directly conjugated to the surface of the biogenic Au NPs. The obtained results indicate that the biogenic Au NPs-QUBMA-Bov conjugates are capable of detecting M. bovis based on a colorimetric immunosensing method within a lower range of 100 to 102 cfu mL-1 with limits of detection of 53 and 71 cfu mL-1 in an artificial buffer solution and in a soft cheese spiked sample, respectively. This strategy demonstrates decent specificity in comparison with those of other bacterial and mycobacterial species. Considering these findings together, this study indicates the potential for the development of a cost-effective biosensing platform with high sensitivity and specificity for the detection of M. bovis using antibody-conjugated Au nanozymes.

Greenhouse gas (GHG) emissions from crop residue management have been studied extensively, yet the effects of harvesting more than one crop residue in a rotation have not been reported. Here, we measured the short-term changes in methane (CH4), nitrous oxide (N2O), and carbon dioxide (CO2) emissions in response to residue removal from continuous corn (Zea mays L.) (CC) and corn–wheat (Triticum aestivum L.)–soybean (Glycine max L. Merr.) (CWS) rotations in the Mid-Atlantic USA. A first experiment retained five corn stover rates (0, 3.33, 6.66, 10, and 20 Mg ha−1) in a continuous corn (CC) in Blacksburg, VA, in 2016 and 2017. Two other experiments, initiated during the wheat and corn phases of the CWS rotation in New Kent, VA, utilized a factorial combination of retained corn (0, 3.33, 6.66, and 10.0 Mg ha−1) and wheat residue (0, 1, 2, and 3 Mg ha−1). Soybean residue was not varied. Different crop retention rates did not affect CO2 fluxes in any of the field studies. In Blacksburg, retaining 5 Mg ha−1 stover or more increased CH4 and N2O emissions by ~25%. Maximum CH4 and N2O fluxes (4.16 and 5.94 mg m−2 day−1) occurred with 200% (20 Mg ha−1) retention. Two cycles of stover management in Blacksburg, and one cycle of corn or wheat residue management in New Kent did not affect GHG fluxes. This study is the first to investigate the effects of crop residue on GHG emissions in a multi-crop system in humid temperate zones. Longer-term studies are warranted to understand crop residue management effects on GHG emissions in these systems. Published version

Conservation management practices - including agroforestry, cover cropping, no-till, reduced tillage, and residue return - have been applied for decades to control surface runoff and soil erosion, yet results have not been integrated and evaluated across cropping systems. In this study we collected data comparing agricultural production with and without conservation management strategies. We used a bootstrap resampling analysis to explore interactions between practice type, soil texture, surface runoff, and soil erosion. We then used a correlation analysis to relate changes in surface runoff and soil erosion to 13 other soil health and agronomic indicators, including soil organic carbon, soil aggregation, infiltration, porosity, subsurface leaching, and cash crop yield. Across all conservation management practices, surface runoff and erosion had respective mean decreases of 67% and 80% compared with controls. Use of cover cropping provided the largest decreases in erosion and surface runoff, thus emphasizing the importance of maintaining continuous vegetative cover on soils. Coarse- and medium-textured soils had greater decreases in both erosion and runoff than fine-textured soils. Changes in surface runoff and soil erosion under conservation management were highly correlated with soil organic carbon, aggregation, porosity, infiltration, leaching, and yield, showing that conservation practices help drive important interactions between these different facets of soil health. This study offers the first large-scale comparison of how different conservation agriculture practices reduce surface runoff and soil erosion, and at the same time provides new insight into how these interactions influence the improvement or loss of soil health. (C) 2021 International Research and Training Center on Erosion and Sedimentation, China Water and Power Press, and China Institute of Water Resources and Hydropower Research. Publishing services by Elsevier B.V. on behalf of KeAi Communications Co. Ltd. Research, Terrestrial Ecosystem Sciences Program [DE-AC05-76RL01830]; Yangling Vocational & Technical College 2019 Natural Science Research Fund Project [A2019048]; U.S. Department of Agriculture NRCS Conservation Innovation Grant [69-3A75-14-260]; Virginia Agricultural Experiment Station; Hatch Program of the National Institute of Food and Agriculture, U.S. Department of Agriculture Published version Research as part of the Terrestrial Ecosystem Sciences Program, under contract DE-AC05-76RL01830. Can Du was supported by the Yangling Vocational & Technical College 2019 Natural Science Research Fund Project, under grant number: A2019048. Ryan Stewart was supported by the U.S. Department of Agriculture NRCS Conservation Innovation Grant (No. 69-3A75-14-260) and the Vir-ginia Agricultural Experiment Station and the Hatch Program of the National Institute of Food and Agriculture, U.S. Department of Agriculture.

Adenosine is an immunosuppressive factor that limits anti-tumor immunity through the suppression of multiple immune subsets including T cells via activation of the adenosine A2A receptor (A2AR). Using both murine and human chimeric antigen receptor (CAR) T cells, here we show that targeting A2AR with a clinically relevant CRISPR/Cas9 strategy significantly enhances their in vivo efficacy, leading to improved survival of mice. Effects evoked by CRISPR/Cas9 mediated gene deletion of A2AR are superior to shRNA mediated knockdown or pharmacological blockade of A2AR. Mechanistically, human A2AR-edited CAR T cells are significantly resistant to adenosine-mediated transcriptional changes, resulting in enhanced production of cytokines including IFNγ and TNF, and increased expression of JAK-STAT signaling pathway associated genes. A2AR deficient CAR T cells are well tolerated and do not induce overt pathologies in mice, supporting the use of CRISPR/Cas9 to target A2AR for the improvement of CAR T cell function in the clinic., Activation of the adenosine receptor A2AR is associated with suppression of T cell function in the tumor microenvironment. To overcome immunosuppression, here the authors show that CRISPR/Cas9 mediated deletion of A2AR enhances CAR T cell effector functions without altering memory or persistence properties, improving CAR-T mediated tumor control in pre-clinical models.

Objective: To investigate whether pT1 renal cell carcinoma (RCC) should be followed differently after partial (PN) or radical nephrectomy (RN) based on a retrospective analysis of a multicentre database (RECUR). Subjects: A retrospective study was conducted in 3380 patients treated for nonmetastatic RCC between January 2006 and December 2011 across 15 centres from 10 countries, as part of the RECUR database project. For patients with pT1 clear-cell RCC, patterns of recurrence were compared between RN and PN according to recurrence site. Univariate and multivariate models were used to evaluate the association between surgical approach and recurrence-free survival (RFS) and cancer-specific mortality (CSM). Results: From the database 1995 patients were identified as low-risk patients (pT1, pN0, pNx), of whom 1055 (52.9%) underwent PN. On multivariate analysis, features associated with worse RFS included tumour size (hazard ratio [HR] 1.32, 95% confidence interval [CI] 1.14–1.39; P < 0.001), nuclear grade (HR 2.31, 95% CI 1.73–3.08; P < 0.001), tumour necrosis (HR 1.5, 95% CI 1.03–2.3; P = 0.037), vascular invasion (HR 2.4, 95% CI 1.3–4.4; P = 0.005) and positive surgical margins (HR 4.4, 95% CI 2.3–8.5; P < 0.001). Kaplan–Meier analysis of CSM revealed that the survival of patients with recurrence after PN was significantly better than those with recurrence after RN (P = 0.02). While the above-mentioned risk factors were associated with prognosis, type of surgery alone was not an independent prognostic variable for RFS nor CSM. Limitations include the retrospective nature of the study. Conclusion: Our results showed that follow-up protocols should not rely solely on stage and type of primary surgery. An optimized regimen should also include validated risk factors rather than type of surgery alone to select the best imaging method and to avoid unnecessary imaging. A follow-up of more than 3 years should be considered in patients with pT1 tumours after RN. A novel follow-up strategy is proposed. (Less)

Purpose Previous research suggests that treatment process can have an influence on patient preference and health state utilities. This study examined preferences and estimated utilities for treatment processes of two daily oral treatment regimens and two weekly injectable regimens for treatment of type 2 diabetes (T2D). Methods Participants with T2D in the UK reported preferences and valued four health state vignettes in time trade-off utility interviews. The vignettes had identical descriptions of T2D but differed in treatment process: (1) daily simple oral treatment (tablets without administration requirements), (2) daily oral semaglutide (with administration requirements per product label), (3) weekly dulaglutide injection, (4) weekly semaglutide injection. Results Interviews were completed by 201 participants (52.7% male; mean age = 58.7). Preferences between treatment processes varied widely. Mean utilities were 0.890 for simple oral, 0.880 for oral semaglutide, 0.878 for dulaglutide injection, and 0.859 for semaglutide injection (with higher scores indicating greater preference). All pairwise comparisons found statistically significant differences between utilities (p Conclusions Results suggest that routes of administration cannot be compared using only the simplest descriptions (e.g., oral versus injectable). Dose frequency and specific details of the treatment process administration had an impact on patient preference and health state utilities. The utilities estimated in this study may be useful in cost-utility models comparing these treatments for T2D. Results also suggest that it may be helpful to consider patient preferences for treatment process when selecting medications for patients in clinical settings.

Arsenic in private drinking water wells is a significant problem across much of eastern Wisconsin, USA. The release mechanism and stratigraphic distribution of sulfide and iron (hydr)oxide sources of arsenic in bedrock aquifers are well understood for northeastern Wisconsin. However, recent geologic mapping has identified numerous small bedrock folds to the south, and the impact of these geologic structures on local groundwater flow and well contamination has been little studied. This paper examines the hydrologic and structural effects of the Beaver Dam anticline, southeast Wisconsin, on arsenic in groundwater in the region. Multivariate logistic regression shows wells near the Beaver Dam anticline are statistically more likely to detect arsenic in groundwater compared to wells farther away. Structural and hydrologic changes related to folding are interpreted to be the cause. Core drilled near the fold axis is heavily fractured, and many fractures are filled with sulfides. Elevated hydraulic conductivity estimates are also recorded near the fold axis, which may reflect a higher concentration of vertical fractures. These structural and hydrologic changes may have led to systematic changes in the distribution and concentration of arsenic-bearing mineral hosts, resulting in the observed detection pattern. For areas with similar underlying geology, this approach may improve prediction of arsenic risk down to the local level.

Currently there are no specific guidelines for the post-operative follow-up of chromophobe renal cell carcinoma (chRCC). We aimed to evaluate the pattern, location and timing of recurrence after surgery for non-metastatic chRCC and establish predictors of recurrence and cancer-specific death. Retrospective analysis of consecutive surgically treated non-metastatic chRCC cases from the Royal Free London NHS Foundation Trust (UK, 2015–2019) and the international collaborative database RECUR (15 institutes, 2006–2011). Kaplan–Meier curves were plotted. The association between variables of interest and outcomes were analysed using univariate and multivariate Cox proportional hazards regression models with shared frailty for data source. 295 patients were identified. Median follow-up was 58 months. The five and ten-year recurrence-free survival rates were 94.3% and 89.2%. Seventeen patients (5.7%) developed recurrent disease, 13 (76.5%) with distant metastases. 54% of metastatic disease diagnoses involved a single organ, most commonly the bone. Early recurrence (

Sclerosing polycystic adenoma (SPA) is an uncommon entity with fewer than 100 reported cases in the literature. Predominately affecting the major salivary glands, SPA typically presents as a painless, slow-growing mass in a middle-aged woman. The lesion’s histopathologic features are reminiscent of fibrocystic changes of the breast, but recent genetic studies provide evidence for a neoplastic process. We present a case of a sclerosing polycystic adenoma in a 69-year-old female with no significant medical history who was found to have a left parotid mass. This led to a fine needle aspiration (FNA) which was non-diagnostic. Superficial parotidectomy yielded a well-circumscribed unencapsulated mass with histologic and immunohistochemical features consistent with the diagnosis of SPA. We present this case to further characterize SPA, adding to the body of literature regarding the tumor’s presentation and histopathologic and immunohistochemical features.

As critical educational policy scholarship continues to move toward transformational knowledge production, critical and contextualized quantitative methods are central to justice and equity. In this study, the authors used Structural Equation Modeling (SEM), guided by quantitative critical race methodology, to examine teachers’ beliefs about their ability to instantiate critical pedagogy— critical pedagogical efficacy. We parametrized a latent path model to examine the additive influence teacher solidarity for justice has on the relationship between teacher justice collaboration frequency and critical pedagogical efficacy. The model estimate indicated the cruciality of teacher solidarity in improving critical pedagogical efficacy beliefs. Our study’s discussion section offers implications for teachers, leaders, policy actors, and critical quantitative researchers contributing to, or planning to join educational justice movements.

Lung cancer detection and monitoring are hampered by a lack of sensitive biomarkers, which results in diagnosis at late stages and difficulty in tracking response to treatment. Recent developments have established liquid biopsies as promising non-invasive methods for detecting biomarkers in lung cancer patients. With concurrent advances in high-throughput sequencing technologies and bioinformatics tools, new approaches for biomarker discovery have emerged. In this article, we survey established and emerging biomarker discovery methods using nucleic acid materials derived from bodily fluids in the context of lung cancer. We introduce nucleic acid biomarkers extracted from liquid biopsies and outline biological sources and methods of isolation. We discuss next-generation sequencing (NGS) platforms commonly used to identify novel biomarkers and describe how these have been applied to liquid biopsy. We highlight emerging biomarker discovery methods, including applications of long-read sequencing, fragmentomics, whole-genome amplification methods for single-cell analysis, and whole-genome methylation assays. Finally, we discuss advanced bioinformatics tools, describing methods for processing NGS data, as well as recently developed software tailored for liquid biopsy biomarker detection, which holds promise for early diagnosis of lung cancer.

Autoimmune diseases are thought to develop as a consequence of various environmental and genetic factors, each of which contributes to dysfunctional immune responses and/or a breakdown in immunological tolerance towards native structures. Molecular mimicry by microbial components is among the environmental factors thought to promote a breakdown in immune tolerance, particularly through the presence of cross-reactive epitopes shared with the human host. While resident members of the microbiota are essential promoters of human health through immunomodulation, defence against pathogenic colonisation and conversion of dietary fibre into nutritional resources for host tissues, there may be an underappreciated role of these microbes in the aetiology and/or progression of autoimmune disease. An increasing number of molecular mimics are being identified amongst the anaerobic microbiota which structurally resemble endogenous components and, in some cases, for example the human ubiquitin mimic of Bacteroides fragilis and DNA methyltransferase of Roseburia intestinalis, have been associated with promoting antibody profiles characteristic of autoimmune diseases. The persistent exposure of molecular mimics from the microbiota to the human immune system is likely to be involved in autoantibody production that contributes to the pathologies associated with immune-mediated inflammatory disorders. Here-in, examples of molecular mimics that have been identified among resident members of the human microbiota and their ability to induce autoimmune disease through cross-reactive autoantibody production are discussed. Improved awareness of the molecular mimics that exist among human colonisers will help elucidate the mechanisms involved in the breakdown of immune tolerance that ultimately lead to chronic inflammation and downstream disease.

Tarnished plant bug, Lygus lineolaris Palisot de Beauvois (Hemiptera: Miridae), has become a primary pest of cotton in the Midsouthern United States. Insect growth regulators such as novaluron are an important part of L. lineolaris management. While novaluron is lethal to nymphs, it does not kill adults, so it has been used when nymphs are the primary stage present. However, cotton yield protection was observed from an application of novaluron when adults were the predominant stage present. To explain this, a series of studies were conducted to examine sublethal impacts of novaluron to L. lineolaris adults. Novaluron ingestion by adults reduced hatch rate and sometimes reduced oviposition rate. Ingestion by either males or females reduced hatch rates, but the reduction was greater from female exposure. Contact exposure of adults with novaluron residues within 1 d of application reduced hatch rate by about 50%, but the impact on oviposition was inconsistent. A field study showed reduced hatch rate from contact exposure to mixed-age natural populations, but the overall net reproductive rate was not reduced. Surface exposure of eggs to novaluron did not reduce hatch rate. Overall, exposure of tarnished plant bug adults to novaluron, regardless of adult age or exposure route, reduced egg viability. However, the impact on oviposition rate and net reproductive rate varied with adult age and exposure route. This understanding of sublethal impacts of novaluron, in addition to lethal impacts on nymphs, should be considered when choosing application times to maximize effects on L. lineolaris populations.

Static bending tests to measure modulus of elasticity (MOEST) or wood stiffness provide an indicator of the structural performance of a finished product. These tests are however, slow and expensive...

Whale sharks collect in predictable seasonal aggregations across the tropics. South Ari Atoll in the Maldives is one of a few aggregation sites where whale sharks can be encountered year‐round. Here, areas with high levels of tourism‐related boating traffic overlap with the whale shark hotspot, increasing the probability of anthropogenic injury. Whale sharks have been reported to remain faithful to this aggregation site following injury, despite the costs of injury and the risk of re‐injury. However, the impacts of injury on site fidelity and residency behaviour are not fully understood. Encounter data on individual sharks from the Maldives Whale Shark Research Programme database (2006–2018) were analysed to assess the relationship between injury and site fidelity in whale sharks. There was no difference in geographic site use, with injured and non‐injured individuals being encountered in the same areas. However, there were differences in residency timings: injured resident whale sharks (individuals repeatedly encountered over 6 months or longer) spent significantly more time at the atoll and less time absent, and were seen more consistently than non‐injured residents. Increased residency duration, return rate and number of residency periods correlated with increasing injury number. These differences in behaviour imply a cost to injury, with whale sharks potentially remaining at this site to recover. With boat traffic being concentrated at the aggregation site, injured sharks may be more vulnerable to further injury. Alternatively, these individuals may remain at the atoll despite injury because the benefits gained from this area outweigh the potential costs, with more resident individuals facing greater exposure to anthropogenic threats. These findings highlight the importance of this location and emphasize the need for improved management of anthropogenic activities, particularly boating traffic, at aggregation hotspots to reduce injury rates and any subsequent impacts on behaviour and fitness.

Patients with complex systemic and pulmonary venous anatomy, common atrioventricular canal defects and conotruncal anomalies have traditionally been routed to univentricular palliation and labeled as "unseptatable." This report describes our initial experience in septation/biventricular conversion ("ventricular switch"), utilizing the left ventricle (LV) as the subpulmonary ventricle, essentially recapitulating the physiology of congenitally corrected transposition of the great arteries. Five consecutive patients with challenging anatomic configuration underwent septation. All patients were severely cyanotic and had important functional limitations. All patients required complex atrial septation. Ventricular septation was precluded by fixed pulmonary vascular resistance in 2 patients. Systemic venous return was diverted to the morphologic LV as part of physiological 2V (n = 4) or 1.5 V repair (n = 1). Median conversion age was 9 years (range 11 months-46 years). Four patients had 12 previous cardiac surgical procedures in preparation for univentricular repair elsewhere. Three dimensional-printed heart models evaluated feasibility of septation. All patients are alive at a median follow-up of 0.6 years (range 0.08-2.7 years). Median hospital stay was 13 (range 10-60) days. LV recruitment improved functional status and significantly increased systemic oxygen saturation in all patients (79 ± 7% vs 95 ± 5%, P = 0.003). We report a novel paradigm for successfully utilizing both ventricles with the morphologic LV as the subpulmonary ventricle, in a complex population thought to be unseptatable. This approach is versatile and can likely be extrapolated to other complex anatomic configurations. Although we utilized this strategy in patients of variable age, earlier ventricular switch may yield the best results.

HighlightsNatural sediments labeled with rare earth elements can effectively be used as tracers for quantifying fine sediment transport and deposition.Two artificial floods in a small stream (100 ha watershed, 1.5 year return flow of 515 L s-1) transported fine sediment 0 m to >850 m at a maximum flow rate of 55 L s-1.Sediment deposition per unit area was greater in the channel than in the near-channel floodplain.Use of two distinct tracers demonstrated resuspension extent during sequential high-flow events.Presence of large wood in the channel was associated with reduced streamflow rate, decreased suspended sediment transport velocity, increased channel sediment deposition, and reduced near-floodplain sediment deposition.Abstract. Effective sediment management requires an understanding of the lag time between best management practice implementation and observable changes in the target water body. To improve our understanding of sediment lag times, we tested a method to label locally sourced sediments with rare earth elements to quantify fine sediment flow-through and storage in fluvial systems. We injected sediments labeled with lanthanum and ytterbium into a small stream during two artificial flood events. During the floods, we collected and quantified suspended sediments and sediment deposition in the stream channel and floodplain at four cross-sections within our study reach. Two down-gradient (90 m and 850 m) time-integrated suspended sediment samplers evaluated total travel distance. Sediment tracer observations of particle transport distances ranged from 0 m to at least 850 m at a maximum flow rate of 55 L s-1 (stream 1.5 year flow was 515 L s-1). Sediment deposition per unit area was greater in the channel than in the floodplain. The majority of sediment tracer mass injected into the stream entered storage within the first 69 m of the reach. Some particles that deposited following the first flood were resuspended and either transported downstream or redeposited within the study reach. Our results support the further use of rare earth elements as sediment tracers to inform water quality and sediment transport models, and to provide estimates of lag times between management actions and downstream improvements. Keywords: Fine sediment, Flood, Fluvial geomorphology, Lag time, Large wood, Rare earth elements, Sediment deposition, Sediment transport, Tracer.

In cross-platform analyses of 174 metabolites, we identify 499 associations (P

Up to 2 km of siliciclastic and chemical sedimentary rocks, metamorphosed to greenschist facies, are preserved in the Baraboo Hills of southern Wisconsin. The strata compose two sedimentary...

Subsurface injection of liquid manure is a no-till compatible application method that may fundamentally change nutrient cycling dynamics. This study investigated subsurface injection and surface broadcast application methods on soil nitrate-nitrogen (NO3–-N) at 0, 1, 2, 4, 6, 8, 10, 14, 18, and 22 weeks after first-year applications of liquid dairy slurry in 0 to 15 cm and 15 to 30 cm sampling depths. The effect on corn (Zea mays L.) grain yield and quality parameters was considered. Soil health was assessed by proxy on weeks 0, 2, 8, 14, and 22 by two microbial indicators sensitive to change: carbon (C) mineralization and microbial biomass C. Soil NO3–-N and the microbial indicators were also measured at distances from an injected band of manure: In-band, 10 cm, 20 cm, and 36 cm. The injection application resulted in significantly (p 0.05) different between treatments. Carbon mineralization was significantly (p 0.05) different from the no-manure control. Microbial biomass C was significantly (p

Upstream identification of wood properties using non-destructive testing methods such as acoustic velocity (AV) measurements is important for optimizing allocation of wood to mills or products. We evaluated the effectiveness of field AV measurement tools in predicting lodgepole pine wood stiffness (modulus of elasticity, MOE) as measured by Silviscan on wood samples. AV was measured on trees and logs from six sites in Alberta and British Columbia. We evaluated the effect on MOE estimation of calculating averages of the adjustment factor k and of green density (GD) at different spatial scales from individual tree to population. The effect of using forest inventory variables on MOE prediction were also examined. Prediction of tree-level MOE from tree-level measurements of AV, k and GD resulted in R2 values of 0.59. Using estimates of k and GD averaged at plot, site or population scales significantly diminished the R2 of the MOE predictions at tree level. Predicting MOE at plot or stand level from corresponding averages of AV, k and GD gave R2 values >0.8. Including inventory variables in tree-level MOE predictions increased the R2 to 0.62. AV measurements can give operationally useful estimates of MOE in lodgepole pine trees at the stand level.

In the present study, a facile, eco-friendly, and controlled synthesis of gold nanoparticles (Au NPs) using

From micro to planetary scales, spatial heterogeneity—patchiness—is ubiquitous in ecological systems, defining the environments in which organisms move and interact. While this fact has been recognized for decades, most large-scale ecosystem models still use spatially averaged “mean fields” to represent natural populations, while fine-scale, spatially explicit models are mostly restricted to particular organisms or systems. In a conceptual paper, Grünbaum (2012,Interface Focus2: 150-155) introduced a heuristic framework, based on three dimensionless ratios quantifying movement, reproduction, and resource consumption, to characterize patchy ecological interactions and identify when mean-field assumptions are justifiable. In this paper, we calculated Grünbaum’s dimensionless numbers for 33 real interactions between consumers and their resource patches in terrestrial, aquatic, and aerial environments. Consumers ranged in size from bacteria to blue whales, and patches lasted from minutes to millennia, spanning spatial scales of mm to hundreds of km. We found that none of the interactions could be accurately represented by a purely mean-field model, though 26 of them (79%) could be partially simplified by averaging out movement, reproductive, or consumption dynamics. Clustering consumer-resource pairs by their non-dimensional ratios revealed several unexpected dynamic similarities between disparate interactions. For example, bacterialPseudoalteromonasexploit nutrient plumes in a similar manner to Mongolian gazelles grazing on ephemeral patches of steppe vegetation. Our findings suggest that dimensional analysis is a valuable tool for characterizing ecological patchiness, and can link the dynamics of widely different systems into a single quantitative framework.

Background: We recently introduced the myocardial-ischemic-injury-index (MI3), a machine learning algorithm that predicts the likelihood of myocardial infarction in patients with suspected acute coronary syndrome. Whether this algorithm performs well in routine clinical practice or predicts subsequent events is unknown.Methods: MI3 was validated in a prespecified exploratory analysis from a multi-centre randomised trial that included consecutive patients with suspected acute coronary syndrome undergoing serial high-sensitivity cardiac troponin I measurement. Patients with ST-segment elevation myocardial infarction were excluded. MI3 incorporates age, sex, and two troponin measurements to compute a value (0-100) reflecting an individual’s likelihood of myocardial infarction during the index visit and estimates diagnostic performance metrics at the computed score. Model performance for an index diagnosis of myocardial infarction, and for subsequent myocardial infarction or cardiovascular death at one year was determined using previously defined low- and high-probability MI3 thresholds (1·6 and 49·7, respectively). Findings: In total, 20,761 patients (64±16 years, 46% women) were included of whom 3,272 (15·8%) had myocardial infarction. MI3 had an area under the receiver-operating-characteristic curve of 0·949 (95% confidence interval 0·946-0·952) identifying 12,983 (62·5%) patients as low-probability (sensitivity 99·3% [99·0-99·6%], negative predictive value 99·8% [99·8-99·9%]), and 2,961 (14·3%) as high-probability (specificity 95·0% [94·6-95·3%], positive predictive value 70·4% [68·7-72·0%]). At one year, subsequent myocardial infarction or cardiovascular death occurred more often in high-probability compared to low-probability patients (17·6% [520/2,961] versus 1·5% [197/12,983], PInterpretation: In consecutive patients undergoing serial cardiac troponin measurement for suspected acute coronary syndrome, the MI3 algorithm accurately estimates the likelihood of myocardial infarction and predicts subsequent adverse cardiovascular events.

Intervertebral disc-associated epidural hemorrhage (EH) in dogs is a poorly understood neurological condition.To compare the clinical presentation, magnetic resonance imaging (MRI) changes, and clinical outcome of dogs with acute thoracolumbar intervertebral disc herniation (TL-IVDH) with and without EH.One hundred sixty client-owned dogs that underwent MRI and hemilaminectomy for acute TL-IVDH at a private practice in Colorado, including 63 dogs with EH and 97 dogs without EH.Retrospective review of medical record data from 160 dogs presenting sequentially to a single practice with acute TL-IVDH that underwent MRI and hemilaminectomy surgery.Sixty-three of 160 (39%) dogs had confirmed EH. French Bulldogs were significantly overrepresented (23/63; odds ratio [OR]: 4.1; 95% confidence interval [CI]: 1.8-9.0; P .001) of the EH cases. Dogs with EH were more likely to present with clinical signs less than 48 hours than were dogs without EH (24-48 vs 48-72 hours; OR: 2.4; 95% CI: 1.2-4.6; P = .02) and were more likely to be nonambulatory on presentation (OR: 2.1; 95% CI: 1.0-4.1; P = .04). Dogs with EH were more likely to have50% cross-sectional spinal cord compression than dogs without EH (OR: 2.3 vs. 0.4; 95% CI: 1.2-4.4 and 0.2-0.9, respectively), longer longitudinal spinal cord compression (3 spaces vs 1 space, P .001), and greater intrinsic spinal cord change (grade 3/severe vs grade 1/mild; P .001) based on MRI. The location of the intervertebral disc herniation in French Bulldogs with EH was more likely to be thoracolumbar (OR: 10.8; 95% CI: 2.1-55.7; P = .03).French Bulldogs have a high prevalence of intervertebral disc-associated EH. Dogs with EH have a shorter clinical course and are more likely to be nonambulatory on initial presentation.

Soil organic matter (SOM) retains and attenuates many contaminants; however, its interactions with neonicotinoid insecticides under field conditions remain poorly understood. The goal of this study was to determine if SOM influences the persistence or leaching of two neonicotinoid insecticides: thiamethoxam (TMX) and its transformation-product clothianidin (CLO). Thiamethoxam-coated soybean [Glycine max (L.) Merr.] was planted into a clay soil containing different soil organic carbon (SOC) concentrations. Leachate and soil samples were collected for 10 wk after planting and were analyzed for insecticide concentrations using liquid chromatography–tandem mass spectrometry. Single and multiple linear regressions were performed between SOC, leaching volumes, and measured insecticide concentrations, focusing on rainfall events near the beginning, middle, and end of the study. Correlations were also tested between SOC and cumulative mass of leached insecticides. Neither SOC nor per-event leachate volumes explained variability in TMX leaching or residual CLO concentrations in soils; however, by the conclusion of the study residual thiamethoxam concentrations in soil were negatively correlated with cumulative volume of leached water. Initially, the concentration and total mass of leached CLO were significantly and negatively correlated with SOC content; however, this effect faded with time. Leachate dynamics also affected CLO transport, with positive correlations between leachate volume and CLO concentration during the latter events. This analysis demonstrates that SOM can reduce peak loading of neonicotinoids but may not alter cumulative leaching over the entire growing season. Funding for this work was provided by the USDA National Institute of Food and Agriculture (Grant 2018-67019-27851) and by the Virginia Agricultural Experiment Station and the Hatch Program of the USDA National Institute of Food and Agriculture (1026126). Published version

Amino acids are key to protein synthesis, energy metabolism, cell signaling and gene expression; however, the contribution of specific maternal amino acids to fetal growth is unclear. We explored the effect of maternal circulating amino acids on fetal growth, proxied by birthweight, using two-sample Mendelian randomization and summary data from a genome-wide association study (GWAS) of serum amino acids levels (sample 1, n = 86,507) and a maternal GWAS of offspring birthweight, adjusting for fetal genotype effects (sample 2, n = 406,063 with maternal and/or fetal genotype effect estimates). A total of 106 independent single nucleotide polymorphisms (SNPs) robustly associated with 19 amino acids (p < 4.9 × 10−10) were used as genetic instrumental variables. Our results provide evidence that maternal circulating glutamine (59 g offspring birthweight increase per SD increase in maternal amino acid level, 95% CI: 7, 110) and serine (27 g, 95% CI: 9, 46) raise, while leucine (−59 g, 95% CI: -106, -11) and phenylalanine (−25 g, 95% CI: -47, -4) lower offspring birthweight. Our findings strengthen evidence for key roles of maternal circulating amino acids in healthy fetal growth.

Despite 50+ years of drug discovery, current antipsychotics have limited efficacy against negative and cognitive symptoms of schizophrenia, and are ineffective—with the exception of clozapine—against any symptom domain for patients who are treatment resistant. Novel therapeutics with diverse non-dopamine D2 receptor targets have been explored extensively in clinical trials, yet often fail due to a lack of efficacy despite showing promise in preclinical development. This lack of translation between preclinical and clinical efficacy suggests a systematic failure in current methods that determine efficacy in preclinical rodent models. In this review, we critically evaluate rodent models and behavioural tests used to determine preclinical efficacy, and look to clinical research to provide a roadmap for developing improved translational measures. We highlight the dependence of preclinical models and tests on dopamine-centric theories of dysfunction and how this has contributed towards a self-reinforcing loop away from clinically meaningful predictions of efficacy. We review recent clinical findings of distinct dopamine-mediated dysfunction of corticostriatal circuits in patients with treatment-resistant vs. non-treatment-resistant schizophrenia and suggest criteria for establishing rodent models to reflect such differences, with a focus on objective, translational measures. Finally, we review current schizophrenia drug discovery and propose a framework where preclinical models are validated against objective, clinically informed measures and preclinical tests of efficacy map onto those used clinically.

Aim: To evaluate a digital intervention to improve physical activity in people in the UK with a musculoskeletal condition delivered during movement restrictions brought about because of the COVID-19 pandemic. Method: Service evaluation data collected from 26,041 participants over 5 months was assessed against national datasets to understand the reach and representativeness of the digital physical activity intervention. Measures to restrict the movement and interaction of people were in place during these 5 months. Cross-sectional data from 2752 participants across different stages of the 12-week programme assessed levels of physical activity and the components of behaviour as defined by the COM-B model (Capability, Opportunity, Motivation = Behaviour). Regression analysis investigated the relationship between programme stage and physical activity and the components of behaviour. Results: In comparison to the UK population of people with a musculoskeletal condition, the intervention participants were over-represented by females, White, and inactive people. A cross-sectional analysis suggested that the number of participants regularly active increased by programme stage. Scores for the behavioural components of automatic and reflective motivation, physical and psychological capability, and physical opportunity were also improved by programme stage. Conclusion: The service evaluation suggests that the digital intervention, designed to improve physical activity in people with a musculoskeletal condition, could be beneficial during measures to restrict movement to slow the spread of infectious disease in those who are already motivated to become or stay active.

The application of large-scale metabolomic profiling provides new opportunities for realizing the potential of omics-based precision medicine for asthma. By leveraging data from over 14,000 individuals in four distinct cohorts, this study identifies and independently replicates 17 steroid metabolites whose levels were significantly reduced in individuals with prevalent asthma. Although steroid levels were reduced among all asthma cases regardless of medication use, the largest reductions were associated with inhaled corticosteroid (ICS) treatment, as confirmed in a 4-year low-dose ICS clinical trial. Effects of ICS treatment on steroid levels were dose dependent; however, significant reductions also occurred with low-dose ICS treatment. Using information from electronic medical records, we found that cortisol levels were substantially reduced throughout the entire 24-hour daily period in patients with asthma who were treated with ICS compared to those who were untreated and to patients without asthma. Moreover, patients with asthma who were treated with ICS showed significant increases in fatigue and anemia as compared to those without ICS treatment. Adrenal suppression in patients with asthma treated with ICS might, therefore, represent a larger public health problem than previously recognized. Regular cortisol monitoring of patients with asthma treated with ICS is needed to provide the optimal balance between minimizing adverse effects of adrenal suppression while capitalizing on the established benefits of ICS treatment.