Evaluating expert-based habitat suitability information of terrestrial mammals with GPS-tracking data.

Aim: Macroecological studies that require habitat suitability data for many species often derive this information from expert opinion. However, expert-based information is inherently subjective and thus prone to errors. The increasing availability of GPS tracking data offers opportunities to evaluate and supplement expert-based information with detailed empirical evidence. Here, we compared expert-based habitat suitability information from the International Union for Conservation of Nature (IUCN) with habitat suitability information derived from GPS-tracking data of 1,498 individuals from 49 mammal species. Location: Worldwide. Time period: 1998-2021. Major taxa studied: Forty-nine terrestrial mammal species. Methods: Using GPS data, we estimated two measures of habitat suitability for each individual animal: proportional habitat use (proportion of GPS locations within a habitat type), and selection ratio (habitat use relative to its availability). For each individual we then evaluated whether the GPS-based habitat suitability measures were in agreement with the IUCN data. To that end, we calculated the probability that the ranking of empirical habitat suitability measures was in agreement with IUCN's classification into suitable, marginal and unsuitable habitat types. Results: IUCN habitat suitability data were in accordance with the GPS data (> 95% probability of agreement) for 33 out of 49 species based on proportional habitat use estimates and for 25 out of 49 species based on selection ratios. In addition, 37 and 34 species had a > 50% probability of agreement based on proportional habitat use and selection ratios, respectively. Main conclusions: We show how GPS-tracking data can be used to evaluate IUCN habitat suitability data. Our findings indicate that for the majority of species included in this study, it is appropriate to use IUCN habitat suitability data in macroecological studies. Furthermore, we show that GPS-tracking data can be used to identify and prioritize species and habitat types for re-evaluation of IUCN habitat suitability data.

Seasonal and temporal patterns of rainfall shape arthropod community composition and multi-trophic interactions in an arid environment.

In arid and semi-arid ecosystems, rainfall and rainfall temporal distribution shape species communities and multi-trophic interactions. Whereas the relationship between climate change-induced decline of precipitation and plants is well know, there is little knowledge of these relationships with consumers, such as arthropods of different trophic levels. In a 6-year period we studied precipitation effects and microhabitat conditions on multi-trophic interactions of ground-dwelling arthropods in an arid savannah. We analysed the effects of seasonal rainfall, plant cover and soil texture on community composition and activity density of arthropods of different trophic levels and investigated the critical window of vegetation and occurrence arthropods in relation to rainfall. Our result show, that arthropod community composition was determined by seasonal rainfall and plant cover. Soil texture did not explain arthropod response sufficiently. Especially detritivorous arthropods were strongly affected by precipitation and can therefore serve as indicators of droughts. Further, multi-trophic interactions can better be explained by short-term rainfall pulses, rather than by seasonal patterns, with a window of seven days being most suitable to explain the influence of rainfall. Plant cover responded immediately after the rainfall, followed by herbivorous and predatory arthropods, and with a lag of 23 days omnivorous arthropods. This highlights the importance of short-term rain pulses for multi-trophic interactions among arthropods and emphasized the relevance of studying detailed precipitation effects for the arthropod diversity and ecosystem stability in arid ecosystems.

The contribution of roadsides to connect grassland habitat patches for butterflies in landscapes of contrasting permeability.

Roadsides, in particular those being species-rich and of conservation value, are considered to improve landscape permeability by providing corridors among habitat patches and by facilitating species' dispersal. However, little is known about the potential connectivity offered by such high-value roadsides. Using circuit theory, we modelled connectivity provided by high-value roadsides in landscapes with low or high permeability in south-central Sweden, with 'permeability' being measured by the area of semi-natural grasslands. We modelled structural connectivity and, for habitat generalists and specialists, potential functional connectivity focusing on butterflies. We further assessed in which landscapes grassland connectivity is best enhanced through measures for expanding the area of high-value roadsides. Structural connectivity provided by high-value roadsides resulted in similar patterns to those of a functional approach, in which we modelled habitat generalists. In landscapes with low permeability, all target species showed higher movements within compared to between grasslands using high-value roadsides. In landscapes with high permeability, grassland generalists and specialists showed the same patterns, whereas for habitat generalists, connectivity provided by high-value roadsides and grasslands was similar. Increasing the ratio of high-value roadsides can thus enhance structural and functional connectivity in landscapes with low permeability. In contrast, in landscapes with high permeability, roadsides only supported movement of specialised species. Continuous segments of high-value roadsides are most efficient to increase connectivity for specialists, whereas generalists can utilize also short segments of high-value roadsides acting as stepping-stones. Thus, land management should focus on the preservation and restoration of existing semi-natural grasslands. Management for enhancing grassland connectivity through high-value roadsides should aim at maintaining and creating high-value roadside vegetation, preferably in long continuous segments, especially in landscapes with low permeability.

Propionate induces cross-tolerance to TLR1/2 and TLR4 agonists in an IFIT-dependent manner.

In this study, we have identified Interferon-stimulated genes (ISGs), especially IFIT1, 2 and 3, as target genes of propionate-induced signalling in the human epithelial cell line A549, the monocytic cell line THP-1 as well as in primary, human peripheral blood-derived macrophages (PBMs). Induction of the IFIT gene family by propionate negatively regulates TLR-induced signalling. Propionate stimulation results in downregulation of pro-inflammatory cytokine and chemokine expression as well as MHC class II expression upon TLR1/2 and TLR4 re-stimulation in A549 and THP-1 cells as well as in PBMs, demonstrating that propionate-induced signalling is involved in the induction of TLR cross-tolerance. Signalling pathway analysis clearly demonstrates that propionate-induced IFIT expression is mediated by FFAR2 in a Gαq/11 signalling pathway-dependent manner. Furthermore, propionate-induced IFIT expression is dependent on IFN type I and/or type III-mediated signalling since pre-treatment of A549 cells with Ruxolitinib, a specific JAK1/2 tyrosine kinase inhibitor, prior to stimulation with propionate, inhibited the upregulation of IFIT1 expression. The hypo-responsiveness towards TLR1/2 and TLR4 agonists seems to be mediated by different members of the IFIT gene family in a cell type-specific manner. Collectively, our data indicate that propionate-induced signalling controls pro-inflammatory responses by activation of IFN type I and/or type III-induced and IFIT-mediated counter-regulatory mechanisms in order to protect against exacerbating inflammatory reactions.

Evaluation of the Usage and Dosing of Guideline-Directed Medical Therapy for Heart Failure With Reduced Ejection Fraction Patients in Clinical Practice.

BACKGROUND: Although strategies for optimization of pharmacologic therapy in patients with heart failure with reduced ejection fraction (HFrEF) are scripted by guidelines, data from HF registries suggests that guideline-directed medical therapies (GDMT) are underutilized among eligible patients. Whether this discrepancy reflects medication intolerance, contraindications, or a quality of care issue remains unclear. OBJECTIVE: The objective of this initiative was to identify reasons for underutilization and under-dosing of HFrEF therapy in patients at a large, academic medical center. METHODS: Among 500 patients with HFrEF enrolled in a quality improvement project at a tertiary center, we evaluated usage and dosing of 4 categories of GDMT: ACE inhibitors/Angiotensin Receptor Blockers (ACE-i/ARB), Angiotensin Receptor-Neprilysin Inhibitors (ARNi), beta blockers, and Mineralocorticoid Receptor Antagonists (MRA). Reasons for nonprescription and usage of suboptimal doses were abstracted from notes in the chart and from telephone review of previous medication trials with the patient. RESULTS: Of 500 patients identified, 472 subjects had complete data for analysis. Among eligible patients, ACE-i/ARB were prescribed in 81.4% (293 of 360) and beta blockers in 94.4% (442 of 468). Of these patients, 10.6% were prescribed target doses of ACE-i/ARB and 12.4% were prescribed target doses of beta blockers. Utilization of other categories of GDMT was lower, with 54% of eligible patients prescribed MRAs and 27% prescribed an ARNi. In most cases, the reasons for nonprescription or under-dosing of GDMT were not apparent on review of the health record or discussion with the patient. CONCLUSION: Clear rationale for nonprescription and under-dosing of GDMT often cannot be ascertained from detailed review and is only rarely related to documented medication intolerance or contraindications, suggesting an opportunity for quality improvement.

The VitMin Lab Sandwich-ELISA Assays for Iron and Inflammation Markers Compared Well with Clinical Analyzer Reference-Type Assays in Subsamples of the Nepal National Micronutrient Status Survey.

BACKGROUND: The low cost and small specimen volume of the VitMin Lab ELISA assays for serum ferritin (Fer), soluble transferrin receptor (sTfR), C-reactive protein (CRP), and α-1-acid glycoprotein (AGP) have allowed their application to micronutrient surveys conducted in low-resource countries for ∼2 decades. OBJECTIVES: We conducted a comparison between the ELISA and reference-type assays used in the US NHANES. METHODS: Using the Roche clinical analyzer as a reference, we measured random subsets of the 2016 Nepal National Micronutrient Status Survey (200 serum samples from children aged 6-59 mo; 100 serum samples from nonpregnant women) for Fer, sTfR, CRP, and AGP. We compared the combined data sets with the ELISA survey results using descriptive analyses. RESULTS: The Lin's concordance coefficients between the 2 assays were ≥0.89 except for sTfR (Lin's ρ = 0.58). The median relative difference to the reference was as follows: Fer, -8.5%; sTfR, 71.2%; CRP, -19.5%; and AGP, -8.2%. The percentage of VitMin samples agreeing within ±30% of the reference was as follows: Fer, 88.5%; sTfR, 1.70%; CRP, 74.9%; and AGP, 92.9%. The prevalence of abnormal results was comparable between the 2 assays for Fer, CRP, and AGP, and for sTfR after adjusting to the Roche assay. Continued biannual performance (2007-2019) of the VitMin assays in CDC's external quality assessment program (6 samples/y) demonstrated generally acceptable performance. CONCLUSIONS: Using samples from the Nepal survey, the VitMin ELISA assays produced mostly comparable results to the Roche reference-type assays for Fer, CRP, and AGP. The lack of sTfR assay standardization to a common reference material explains the large systematic difference observed for sTfR, which could be corrected by an adjustment equation pending further validation. This snapshot comparison together with the long-term external quality assessment links the survey data generated by the VitMin Lab to the Roche assays used in NHANES.

Impacts of roads on bird species richness: A meta-analysis considering road types, habitats and feeding guilds.

Roadsides can harbour remarkable biodiversity; thus, they are increasingly considered as habitats with potential for conservation value. To improve construction and management of roadside habitats with positive effects on biodiversity, we require a quantitative understanding of important influential factors that drive both positive and negative effects of roads. We conducted meta-analyses to assess road effects on bird communities. We specifically tested how the relationship between roads and bird richness varies when considering road type, habitat characteristics and feeding guild association. Overall, bird richness was similar in road habitats compared to non-road habitats, however, the two apparently differ in species composition. Bird richness was lowered by road presence in areas with denser tree cover but did not differ according to road type. Richness differences between habitats with and without roads further depended on primary diet of species, and richness of omnivores was positively affected by road presence. We conclude that impacts of roads on bird richness are highly context-dependent, and planners should carefully evaluate road habitats on a case by case basis. This emphasizes the need for further studies that explicitly test for differences in species composition and abundance, to disentangle contexts where a road will negatively affect bird communities, and where it will not.

Nanoparticular Inhibitors of Flavivirus Proteases from Zika, West Nile and Dengue Virus Are Cell-Permeable Antivirals.

Viral proteases have been established as drug targets in several viral diseases including human immunodeficiency virus and hepatitis C virus infections due to the essential role of these enzymes in virus replication. In contrast, no antiviral therapy is available to date against flaviviral infections including those by Zika virus (ZIKV), West Nile virus (WNV), or dengue virus (DENV). Numerous potent inhibitors of flaviviral proteases have been reported; however, a huge gap remains between the in vitro and intracellular activities, possibly due to low cellular uptake of the charged compounds. Here, we present an alternative, nanoparticular approach to antivirals. Conjugation of peptidomimetic inhibitors and cell-penetrating peptides to dextran yielded chemically defined nanoparticles that were potent inhibitors of flaviviral proteases. Peptide-dextran conjugates inhibited viral replication and infection in cells at nontoxic, low micromolar or even nanomolar concentrations. Thus, nanoparticular antivirals might be alternative starting points for the development of broad-spectrum antiflaviviral drugs.

A multicenter analytical performance evaluation of a multiplexed immunoarray for the simultaneous measurement of biomarkers of micronutrient deficiency, inflammation and malarial antigenemia.

A lack of comparative data across laboratories is often a barrier to the uptake and adoption of new technologies. Furthermore, data generated by different immunoassay methods may be incomparable due to a lack of harmonization. In this multicenter study, we describe validation experiments conducted in a single lab and cross-lab comparisons of assay results to assess the performance characteristics of the Q-plex™ 7-plex Human Micronutrient Array (7-plex), an immunoassay that simultaneously quantifies seven biomarkers associated with micronutrient (MN) deficiencies, inflammation and malarial antigenemia using plasma or serum; alpha-1-acid glycoprotein, C-reactive protein, ferritin, histidine-rich protein 2, retinol binding protein 4, soluble transferrin receptor, and thyroglobulin. Validations included repeated testing (n = 20 separately prepared experiments on 10 assay plates) in a single lab to assess precision and linearity. Seven independent laboratories tested 76 identical heparin plasma samples collected from a cohort of pregnant women in Niger using the same 7-plex assay to assess differences in results across laboratories. In the analytical validation experiments, intra- and inter-assay coefficients of variation were acceptable at <6% and <15% respectively and assay linearity was 96% to 99% with the exception of ferritin, which had marginal performance in some tests. Cross-laboratory comparisons showed generally good agreement between laboratories in all analyte results for the panel of 76 plasma specimens, with Lin's concordance correlation coefficient values averaging ≥0.8 for all analytes. Excluding plates that would fail routine quality control (QC) standards, the inter-assay variation was acceptable for all analytes except sTfR, which had an average inter-assay coefficient of variation of ≥20%. This initial cross-laboratory study demonstrates that the 7-plex test protocol can be implemented by users with some experience in immunoassay methods, but familiarity with the multiplexed protocol was not essential.

Rolling pits of Hartmann's mountain zebra (Zebra equus hartmannae) increase vegetation diversity and landscape heterogeneity in the Pre-Namib.

Microsites created by soil-disturbing animals are important landscape elements in arid environments. In the Pre-Namib, dust-bathing behavior of the near-endemic Hartmann's mountain zebra creates unique rolling pits that persist in the landscape. However, the ecohydrological characteristics and the effects of those microsites on the vegetation and on organisms of higher trophic levels are still unknown. In our study, we characterized the soil grain size composition and infiltration properties of rolling pits and reference sites and recorded vegetation and arthropod assemblages during the rainy season of five consecutive years with different amounts of seasonal rainfall. We further used the excess green vegetation index derived from drone imagery to demonstrate the different green up and wilting of pits and references after a rainfall event. In contrast to the surrounding grassland, rolling pits had finer soil with higher nutrient content, collected runoff, showed a higher infiltration, and kept soil moisture longer. Vegetation in the rolling pits was denser, dominated by annual forbs and remained green for longer periods. The denser vegetation resulted in a slightly higher activity density of herbivorous arthropods, which in turn increased the activity density of omnivorous and predatory arthropods. In times of drought, the rolling pits could act as safe sites and refuges for forbs and arthropods. With their rolling pits, Hartmann's mountain zebras act as ecosystem engineers, contributing to the diversity of forb communities and heterogeneity of the landscape in the Pre-Namib.

Seed traits matter-Endozoochoric dispersal through a pervasive mobile linker.

Although many plants are dispersed by wind and seeds can travel long distances across unsuitable matrix areas, a large proportion relies on co-evolved zoochorous seed dispersal to connect populations in isolated habitat islands. Particularly in agricultural landscapes, where remaining habitat patches are often very small and highly isolated, mobile linkers as zoochorous seed dispersers are critical for the population dynamics of numerous plant species. However, knowledge about the quali- or quantification of such mobile link processes, especially in agricultural landscapes, is still limited. In a controlled feeding experiment, we recorded the seed intake and germination success after complete digestion by the European brown hare (Lepus europaeus) and explored its mobile link potential as an endozoochoric seed disperser. Utilizing a suite of common, rare, and potentially invasive plant species, we disentangled the effects of seed morphological traits on germination success while controlling for phylogenetic relatedness. Further, we measured the landscape connectivity via hares in two contrasting agricultural landscapes (simple: few natural and semi-natural structures, large fields; complex: high amount of natural and semi-natural structures, small fields) using GPS-based movement data. With 34,710 seeds of 44 plant species fed, one of 200 seeds (0.51%) with seedlings of 33 species germinated from feces. Germination after complete digestion was positively related to denser seeds with comparatively small surface area and a relatively slender and elongated shape, suggesting that, for hares, the most critical seed characteristics for successful endozoochorous seed dispersal minimize exposure of the seed to the stomach and the associated digestive system. Furthermore, we could show that a hare's retention time is long enough to interconnect different habitats, especially grasslands and fields. Thus, besides other seed dispersal mechanisms, this most likely allows hares to act as effective mobile linkers contributing to ecosystem stability in times of agricultural intensification, not only in complex but also in simple landscapes.

Remote Optimization of Guideline-Directed Medical Therapy in Patients With Heart Failure With Reduced Ejection Fraction.

Importance: Optimal treatment of heart failure with reduced ejection fraction (HFrEF) is scripted by treatment guidelines, but many eligible patients do not receive guideline-directed medical therapy (GDMT) in clinical practice. Objective: To determine whether a remote, algorithm-driven, navigator-administered medication optimization program could enhance implementation of GDMT in HFrEF. Design, Setting, and Participants: In this case-control study, a population-based sample of patients with HFrEF was offered participation in a quality improvement program directed at GDMT optimization. Treating clinicians in a tertiary academic medical center who were caring for patients with heart failure and an ejection fraction of 40% or less (identified through an electronic health record-based search) were approached for permission to adjust medical therapy according to a sequential titration algorithm modeled on the current American College of Cardiology/American Heart Association heart failure guidelines. Navigators contacted participants by telephone to direct medication adjustment and conduct longitudinal surveillance of laboratory tests, blood pressure, and symptoms under supervision of a pharmacist, nurse practitioner, and heart failure cardiologist. Patients and clinicians declining to participate served as a control group. Exposures: Navigator-led remote optimization of GDMT compared with usual care. Main Outcomes and Measures: Proportion of patients receiving GDMT in the intervention and control groups at 3 months. Results: Of 1028 eligible patients (mean [SD] values: age, 68 [14] years; ejection fraction, 32% [8%]; and systolic blood pressure, 122 [18] mm Hg; 305 women (30.0%); 892 individuals [86.8%] in New York Heart Association class I and II), 197 (19.2%) participated in the medication optimization program, and 831 (80.8%) continued with usual care as directed by their treating clinicians (585 [56.9%] general cardiologists; 443 [43.1%] heart failure specialists). At 3 months, patients participating in the remote intervention experienced significant increases from baseline in use of renin-angiotensin system antagonists (138 [70.1%] to 170 [86.3%]; P < .001) and ß-blockers (152 [77.2%] to 181 [91.9%]; P < .001) but not mineralocorticoid receptor antagonists (51 [25.9%] to 60 [30.5%]; P = .14). Doses for each category of GDMT also increased from baseline in the intervention group. Among the usual-care group, there were no changes from baseline in the proportion of patients receiving GDMT or the dose of GDMT in any category. Conclusions and Relevance: Remote titration of GDMT by navigators using encoded algorithms may represent an efficient, population-level strategy for rapidly closing the gap between guidelines and clinical practice in patients with HFrEF.

Effects of body size on estimation of mammalian area requirements.

Accurately quantifying species' area requirements is a prerequisite for effective area-based conservation. This typically involves collecting tracking data on species of interest and then conducting home-range analyses. Problematically, autocorrelation in tracking data can result in space needs being severely underestimated. Based on the previous work, we hypothesized the magnitude of underestimation varies with body mass, a relationship that could have serious conservation implications. To evaluate this hypothesis for terrestrial mammals, we estimated home-range areas with global positioning system (GPS) locations from 757 individuals across 61 globally distributed mammalian species with body masses ranging from 0.4 to 4000 kg. We then applied block cross-validation to quantify bias in empirical home-range estimates. Area requirements of mammals <10 kg were underestimated by a mean approximately15%, and species weighing approximately100 kg were underestimated by approximately50% on average. Thus, we found area estimation was subject to autocorrelation-induced bias that was worse for large species. Combined with the fact that extinction risk increases as body mass increases, the allometric scaling of bias we observed suggests the most threatened species are also likely to be those with the least accurate home-range estimates. As a correction, we tested whether data thinning or autocorrelation-informed home-range estimation minimized the scaling effect of autocorrelation on area estimates. Data thinning required an approximately93% data loss to achieve statistical independence with 95% confidence and was, therefore, not a viable solution. In contrast, autocorrelation-informed home-range estimation resulted in consistently accurate estimates irrespective of mass. When relating body mass to home range size, we detected that correcting for autocorrelation resulted in a scaling exponent significantly >1, meaning the scaling of the relationship changed substantially at the upper end of the mass spectrum.

Efectos del Tamaño Corporal sobre la Estimación de los Requerimientos de Área de Mamíferos Resumen La cuantificación precisa de los requerimientos de área de una especie es un prerrequisito para que la conservación basada en áreas sea efectiva. Esto comúnmente implica la recolección de datos de rastreo de la especie de interés para después realizar análisis de la distribución local. De manera problemática, la autocorrelación en los datos de rastreo puede resultar en una subestimación grave de las necesidades de espacio. Con base en trabajos previos, formulamos una hipótesis en la que supusimos que la magnitud de la subestimación varía con la masa corporal, una relación que podría tener implicaciones serias para la conservación. Para probar esta hipótesis en mamíferos terrestres, estimamos las áreas de distribución local con las ubicaciones en GPS de 757 individuos de 61 especies de mamíferos distribuidas mundialmente con una masa corporal entre 0.4 y 4,000 kg. Después aplicamos una validación cruzada en bloque para cuantificar el sesgo en estimaciones empíricas de la distribución local. Los requerimientos de área de los mamíferos <10 kg fueron subestimados por una media ∼15% y las especies con una masa ∼100 kg fueron subestimadas en ∼50% en promedio. Por lo tanto, encontramos que la estimación del área estaba sujeta al sesgo inducido por la autocorrelación, el cual era peor para las especies de talla grande. En combinación con el hecho de que el riesgo de extinción incrementa conforme aumenta la masa corporal, el escalamiento alométrico del sesgo que observamos sugiere que la mayoría de las especies amenazadas también tienen la probabilidad de ser aquellas especies con las estimaciones de distribución local menos acertadas. Como corrección, probamos si la reducción de datos o la estimación de la distribución local informada por la autocorrelación minimizan el efecto de escalamiento que tiene la autocorrelación sobre las estimaciones de área. La reducción de datos requirió una pérdida de datos del ∼93% para lograr la independencia estadística con un 95% de confianza y por lo tanto no fue una solución viable. Al contrario, la estimación de la distribución local informada por la autocorrelación resultó en estimaciones constantemente precisas sin importar la masa corporal. Cuando relacionamos la masa corporal con el tamaño de la distribución local, detectamos que la corrección de la autocorrelación resultó en un exponente de escalamiento significativamente >1, lo que significa que el escalamiento de la relación cambió sustancialmente en el extremo superior del espectro de la masa corporal.

Rationale and design of a navigator-driven remote optimization of guideline-directed medical therapy in patients with heart failure with reduced ejection fraction.

Although optimal pharmacological therapy for heart failure with reduced ejection fraction (HFrEF) is carefully scripted by treatment guidelines, many eligible patients are not treated with guideline-directed medical therapy (GDMT) in clinical practice. We designed a strategy for remote optimization of GDMT on a population scale in patients with HFrEF leveraging nonphysician providers. An electronic health record-based algorithm was used to identify a cohort of patients with a diagnosis of heart failure (HF) and ejection fraction (EF) ≤ 40% receiving longitudinal follow-up at our center. Those with end-stage HF requiring inotropic support, mechanical circulatory support, or transplantation and those enrolled in hospice or palliative care were excluded. Treating providers were approached for consent to adjust medical therapy according to a sequential, stepped titration algorithm modeled on the current American College of Cardiology (ACC)/American Heart Association (AHA) HF Guidelines within a collaborative care agreement. The program was approved by the institutional review board at Brigham and Women's Hospital with a waiver of written informed consent. All patients provided verbal consent to participate. A navigator then facilitated medication adjustments by telephone and conducted longitudinal surveillance of laboratories, blood pressure, and symptoms. Each titration step was reviewed by a pharmacist with supervision as needed from a nurse practitioner and HF cardiologist. Patients were discharged from the program to their primary cardiologist after achievement of an optimal or maximally tolerated regimen. A navigator-led remote management strategy for optimization of GDMT may represent a scalable population-level strategy for closing the gap between guidelines and clinical practice in patients with HFrEF.

Phenotyping to Facilitate Accrual for a Cardiovascular Intervention.

BACKGROUND: The conventional approach for clinical studies is to identify a cohort of potentially eligible patients and then screen for enrollment. In an effort to reduce the cost and manual effort involved in the screening process, several studies have leveraged electronic health records (EHR) to refine cohorts to better match the eligibility criteria, which is referred to as phenotyping. We extend this approach to dynamically identify a cohort by repeating phenotyping in alternation with manual screening. METHODS: Our approach consists of multiple screen cycles. At the start of each cycle, the phenotyping algorithm is used to identify eligible patients from the EHR, creating an ordered list such that patients that are most likely eligible are listed first. This list is then manually screened, and the results are analyzed to improve the phenotyping for the next cycle. We describe the preliminary results and challenges in the implementation of this approach for an intervention study on heart failure. RESULTS: A total of 1,022 patients were screened, with 223 (23%) of patients being found eligible for enrollment into the intervention study. The iterative approach improved the phenotyping in each screening cycle. Without an iterative approach, the positive screening rate (PSR) was expected to dip below the 20% measured in the first cycle; however, the cyclical approach increased the PSR to 23%. CONCLUSIONS: Our study demonstrates that dynamic phenotyping can facilitate recruitment for prospective clinical study. Future directions include improved informatics infrastructure and governance policies to enable real-time updates to research repositories, tooling for EHR annotation, and methodologies to reduce human annotation.

The interplay of landscape composition and configuration: new pathways to manage functional biodiversity and agroecosystem services across Europe.

Managing agricultural landscapes to support biodiversity and ecosystem services is a key aim of a sustainable agriculture. However, how the spatial arrangement of crop fields and other habitats in landscapes impacts arthropods and their functions is poorly known. Synthesising data from 49 studies (1515 landscapes) across Europe, we examined effects of landscape composition (% habitats) and configuration (edge density) on arthropods in fields and their margins, pest control, pollination and yields. Configuration effects interacted with the proportions of crop and non-crop habitats, and species' dietary, dispersal and overwintering traits led to contrasting responses to landscape variables. Overall, however, in landscapes with high edge density, 70% of pollinator and 44% of natural enemy species reached highest abundances and pollination and pest control improved 1.7- and 1.4-fold respectively. Arable-dominated landscapes with high edge densities achieved high yields. This suggests that enhancing edge density in European agroecosystems can promote functional biodiversity and yield-enhancing ecosystem services.

Extraction of Ejection Fraction from Echocardiography Notes for Constructing a Cohort of Patients having Heart Failure with reduced Ejection Fraction (HFrEF).

Left ventricular ejection fraction (LVEF) is an important prognostic indicator of cardiovascular outcomes. It is used clinically to determine the indication for several therapeutic interventions. LVEF is most commonly derived using in-line tools and some manual assessment by cardiologists from standardized echocardiographic views. LVEF is typically documented in free-text reports, and variation in LVEF documentation pose a challenge for the extraction and utilization of LVEF in computer-based clinical workflows. To address this problem, we developed a computerized algorithm to extract LVEF from echocardiography reports for the identification of patients having heart failure with reduced ejection fraction (HFrEF) for therapeutic intervention at a large healthcare system. We processed echocardiogram reports for 57,158 patients with coded diagnosis of Heart Failure that visited the healthcare system over a two-year period. Our algorithm identified a total of 3910 patients with reduced ejection fraction. Of the 46,634 echocardiography reports processed, 97% included a mention of LVEF. Of these reports, 85% contained numerical ejection fraction values, 9% contained ranges, and the remaining 6% contained qualitative descriptions. Overall, 18% of extracted numerical LVEFs were ≤ 40%. Furthermore, manual validation for a sample of 339 reports yielded an accuracy of 1.0. Our study demonstrates that a regular expression-based approach can accurately extract LVEF from echocardiograms, and is useful for delineating heart-failure patients with reduced ejection fraction.

A dominance shift in arid savanna: An herbaceous legume outcompetes local C4 grasses.

The characteristic vegetation structure of arid savannas with a dominant layer of perennial grass is maintained by the putative competitive superiority of the C4 grasses. When this competitive balance is disturbed by weakening the grasses or favoring the recruitment of other species, trees, shrubs, single grass, or forb species can increase and initiate sudden dominance shifts. Such shifts involving woody species, often termed "shrub encroachment", or the mass spreading of so-called increaser species have been extensively researched, but studies on similar processes without obvious preceding disturbance are rare. In Namibia, the native herbaceous legume Crotalaria podocarpa has recently encroached parts of the escarpment region, seriously affecting the productivity of local fodder grasses. Here, we studied the interaction between seedlings of the legume and the dominant local fodder grass (Stipagrostis ciliata). We used a pot experiment to test seedling survival and to investigate the growth of Crotalaria in competition with Stipagrostis. Additional field observations were conducted to quantify the interactive effect. We found germination and growth of the legume seedlings to be facilitated by inactive (dead or dormant) grass tussocks and unhindered by active ones. Seedling survival was three times higher in inactive tussocks and Crotalaria grew taller. In the field, high densities of the legume had a clear negative effect on productivity of the grass. The C4 grass was unable to limit the recruitment and spread of the legume, and Crotalaria did outcompete the putative more competitive grass. Hence, the legume is able to spread and establish itself in large numbers and initiate a dominance shift in savannas, similar to shrub encroachment.

A Preclinical Study of Casein Glycomacropeptide as a Dietary Intervention for Acute Mania.

Background: Casein glycomacropeptide is a peptide that lacks phenylalanine, tyrosine, and tryptophan. This profile may enable it to deplete phenylalanine, tyrosine, and tryptophan, and subsequently the synthesis of dopamine and serotonin in the brain. Dopamine- and serotonin-depleting amino acid mixtures have shown promise as acute antimanic treatments. In this study, we explore the depleting effects on amino acids, dopamine and serotonin as well as its actions on manic-like and other behavior in rats. Methods: Casein glycomacropeptide and a selection of amino acid mixtures were administered orally at 2, 4, or 8 h or for 1 week chronically. Amino acid and monoamine levels were measured in plasma and brain and behavior was assessed in the amphetamine-hyperlocomotion, forced swim, prepulse inhibition, and elevated plus maze tests. Results: Casein glycomacropeptide induced a time-dependent reduction in tyrosine, tryptophan, and phenylalanine in brain and plasma which was augmented by supplementing with leucine. Casein glycomacropeptide +leucine reduced dopamine in the frontal cortex and serotonin in the hippocampus, frontal cortex, and striatum after 2 and 4 h. Casein glycomacropeptide+leucine also had antimanic activity in the amphetamine-induced hyperlocomotion test at 2 h after a single acute treatment and after 1 week of chronic treatment. Conclusions: Casein glycomacropeptide-based treatments and a branched-chain amino acid mixture affected total tissue levels of dopamine in the frontal cortex and striatum and serotonin in the frontal cortex, striatum, and hippocampus of rats in a time-dependent fashion and displayed antimanic efficacy in a behavioral assay of mania.

Moving in the Anthropocene: Global reductions in terrestrial mammalian movements.

Animal movement is fundamental for ecosystem functioning and species survival, yet the effects of the anthropogenic footprint on animal movements have not been estimated across species. Using a unique GPS-tracking database of 803 individuals across 57 species, we found that movements of mammals in areas with a comparatively high human footprint were on average one-half to one-third the extent of their movements in areas with a low human footprint. We attribute this reduction to behavioral changes of individual animals and to the exclusion of species with long-range movements from areas with higher human impact. Global loss of vagility alters a key ecological trait of animals that affects not only population persistence but also ecosystem processes such as predator-prey interactions, nutrient cycling, and disease transmission.