Urban hedges: a review of plant species and cultivars for ecosystem service delivery in north-west Europe

Urban hedges provide a number of important ecosystem services (ESs) including microclimate alteration, flood and pollution mitigation, and biodiversity provision, along with some disservices (DSs, e.g. invasiveness, allergenicity). However, hedge plant species differ in their capacity to promote different services, so it is important that the decision to plant hedges is evidence-based. The objectives of this study were thus to (i) to review the role of urban hedges within NW Europe; (ii) review the available literature detailing the ESs and DSs provided by different plant species and cultivars when used as hedge plants; (iii) identify where there is a lack of evidence for certain species or ESs/DSs; and (iv) develop a starting point for a discussion about appropriate species/cultivar selection to deliver multiple ESs, and avoid DSs. Many studies consider biodiversity and air quality ESs. There are significant gaps in the literature relating to rainfall mitigation/flood protection, but also CO2 sequestration, allergenicity and human psychological well-being impact of different species. Additionally, for noise and pollution mitigation studies, a range of methodologies and units are used, making comparisons between hedge species difficult/impossible. A number of common hedge species demonstrated high levels of ESs delivery, including Fagus sylvatica, Crataegus monogyna, Ilex aquifolium and Rosa rugosa. No species surveyed had an entirely negative association with ESs, and most provide at least some benefits in supporting ESs provision (e.g. Viburnum tinus, Laurus nobilis). We created a matrix, in a table form, linking plant species, key plant traits and ESs/DSs, which should make it easier for professionals to choose species best suited to provide multiple benefits, whilst minimising the drawbacks. Our review suggests that the relative contribution of urban hedges to ESs delivery may be under-valued currently, and calls for more research

AI is a viable alternative to high throughput screening: a 318-target study

: High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery

Genetic mechanisms of critical illness in COVID-19.

Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 ×  10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2–4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Adapting roughages varying in quality and curing processes to the nutrition of beef cattle. A comparison of alfalfa silage and alfalfa hay; prairie hay and corn cobs; a special supplement vs. corn and soybean oilmeal.

The Hereford heifers used in this test were of good to choice quality from the Brite Ranch at Marfa, Texas. They were delivered to Manhattan, Kansas, November 3, 1952, at a cost of 23 cents per pound. From that date until started on test December 22, 1952, they were fed prairie hay and 1 pound of soybean pellets per head daily. The first cutting alfalfa fed to Lots 1, 2, and 3 came from the same field. No preservative was used in making the silage. The wilted alfalfa was left in the field from 30 minutes to 3 hours. The non-wilted was cut, raked, picked up with H silage cutter, and hauled to the silo as rapidly as possible. The special supplement fed to Lot 5 at the rate of 3 pounds per head daily was of the following; composition: soybean oilmeal, 2.25 pounds; molasses, 0.50 pound; steamed bonemeal, 0.18 pound; salt, 0.06 pound; vitamin supplement, 0.01 pound (2,250 A and 400 D per gram)

A comparison of alfalfa silage and alfalfa hay for wintering heifer calves.

Forty Texas Hereford heifer calves averaging 360 pounds each were divided into four lots of 10 head each. The feeding test was conducted from December 17, 1953, to April 8. 1954, or 113 days. The alfalfa silage and hay were made from first-cutting feed in the same field, when it was approaching one-half bloom. One lot of silage was preserved with cornmeal at the rate of 150 pounds per ton of green forage. The other silage was made without preservative. Both silages were field-chopped and hauled immediately to the silos. The first feeding plan was to add concentrates to the roughages at the same rate as the corn in the alfalfa-cornmeal silage. However since consumption and gains of all the calves were so unsatisfactory at the end of 29 days of feeding, the plan was altered so that all groups were fed concentrates at the rate of 4 pounds per head daily, allowance being made in Lot 3 for the corn contained in the silage

Adapting roughages varying in quality and curing processes to the nutrition of beef cattle: A comparison of prairie hay and corn cobs; a special supplement vs. milo grain and cottonseed meal.

Forty good quality Hereford heifer calves were divided as equally as possible into four lots of 10 animals each. The heifers originated in the vicinity of Snyder. Texas. They were dehorned, vaccinated, and branded before starting the experiment. The rations used in this experiment are shown in Table 11. An attempt was made to keep the protein and total digestible nutrients on an equal basis between the prairie hay and corn cob lots. The animals receiving corn cobs as their roughage were given 50,000 International Units of vitamin A per head daily. The 3 pounds of special supplement fed daily to Lot 12 was composed of 2.25 pounds cottonseed meal, .50 pound molasses, .18 pound steamed bonemeal, .06 pound salt, and .01 pound vitamin supplement (2250 international units of vitamin A and 400 international units of vitamin D per gram). All lots were fed once daily during the morning