System properties determine food security and biodiversity outcomes at landscape scale: a case study from West Flores, Indonesia

The food-biodiversity nexus is a concept that defines and characterizes the complex interactions between agricultural systems and biodiversity conservation. Here we use a social-ecological systems approach that combines fuzzy cognitive mapping and graph theoretic analyses to uncover system properties that determine food security and biodiversity outcomes at a landscape scale. We studied a rice-based agricultural landscape system situated in Mbeliling district of West Flores, Indonesia. A graphical representation of the Mbeliling district food-biodiversity nexus was created by local experts. The representation revealed system properties that help reconcile the trade-offs between food security and biodiversity conservation. The graph represented a diverse set of food security and biodiversity nodes, and showed that there is not a simple dichotomy between 'production and protection'. The analysis captured greater complexity than popular academic concepts such as land sparing-land sharing or sustainable intensification. Three major themes emerged from the graph. We found distinct clusters of factors influencing biodiversity and food security. We named these sources of influence (1) Modernisation and sustainable farming; (2) Knowledge and management; and (3) Governance and processes. Component 2 was the most representative of emergent system properties that contribute positively to managing a sustainable food-biodiversity nexus in the Mbeliling landscape. The key determinants of outcomes were: improving agronomic practices, diversifying production, maintaining forest cover and connectivity, and using knowledge and natural resource management processes to mitigate the main drivers of change. Our approach highlights the complexities in the food-biodiversity nexus, and could have wide application in other locations

Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.

Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Background: Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Methods: We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515. Findings: Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p<0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (<1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (<1%) deaths in the albiglutide group. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes. Funding: GlaxoSmithKline

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

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

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Non-metric multidimensional performance indicator scaling reveals seasonal and team dissimilarity within the National Rugby League

Objectives: Analysing the dissimilarity of seasonal and team profiles within elite sport may reveal the evolutionary dynamics of game-play, while highlighting the similarity of individual team profiles. This study analysed seasonal and team dissimilarity within the National Rugby League (NRL) between the 2005 to 2016 seasons. Methods: Total seasonal values for 15 performance indicators were collected for every NRL team over the analysed period (n = 190 observations). Non-metric multidimensional scaling was used to reveal seasonal and team dissimilarity. Results: Compared to the 2005 to 2011 seasons, the 2012 to 2016 seasons were in a state of flux, with a relative dissimilarity in the positioning of team profiles on the ordination surface. There was an abrupt change in performance indicator characteristics following the 2012 season, with the 2014 season reflecting a large increase in the total count of ‘all run metres’ (d = 1.21; 90% CI = 0.56 – 1.83), ‘kick return metres’ (d = 2.99; 90% CI = 2.12 – 3.84) and decrease in ‘missed tackles’ (d = -2.43; 90% CI = -3.19 – -1.64) and ‘tackle breaks’ (d = -2.41; 90% CI = -3.17 – -1.62). Interpretation of team ordination plots showed that certain teams evolved in (dis)similar ways over the analysed period. Conclusions: It appears that NRL match-types evolved following the 2012 season and are in a current state of flux. The modification of coaching tactics and rule changes may have contributed to these observations. Coaches could use these results when designing prospective game strategies in the NRL

Classification of playing position in elite junior Australian football using technical skill indicators

In team sport, classifying playing position based on a players' expressed skill sets can provide a guide to talent identification by enabling the recognition of performance attributes relative to playing position. Here, elite junior Australian football players were a priori classified into 1 of 4 common playing positions; forward, midfield, defence, and ruck. Three analysis approaches were used to assess the extent to which 12 in-game skill performance indicators could classify playing position. These were a linear discriminant analysis (LDA), random forest, and a PART decision list. The LDA produced classification accuracy of 56.8%, with class errors ranging from 19.6% (midfielders) to 75.0% (ruck). The random forest model performed at a slightly worse level (51.62%), with class errors ranging from 27.8% (midfielders) to 100% (ruck). The decision list revealed 6 rules capable of classifying playing position at accuracy of 70.1%, with class errors ranging from 14.4% (midfielders) to 100% (ruck). Although the PART decision list produced the greatest relative classification accuracy, the technical skill indicators reported were generally unable to accurately classify players according to their position using the 3 analysis approaches. This player homogeneity may complicate recruitment by constraining talent recruiter's ability to objectively recognise distinctive positional attributes

Interactions between species richness, herbivory and precipitation affect standing biomass in Mongolian rangelands

Questions: Livestock management in rangelands depends on the production of plant biomass. Biomass production is driven by the temporal and spatial variability in precipitation, but our understanding of how precipitation variability mediates grazing effects on biomass production is still fragmented. Along a 600-km precipitation gradient we extracted biomass data to ask the questions: (a) what are the effects of grazing intensity on biomass production; (b) does grazing intensity interact with plant species richness to affect biomass production; and (c) how do plant functional groups respond to grazing and precipitation?. Location: Mongolia. Methods: Biomass was sampled along 15 grazing intensity transects within the precipitation gradient over two consecutive years. We modeled spatial variability in above-ground plant biomass using mixed-effects models. Normalized difference vegetation index (NDVI) data were combined with field-sampled biomass data to correct for inter-annual precipitation variation. The effects of species richness were modeled with respect to possible interactions with grazing intensity, and the composition of plant functional groups was modeled with respect to possible interactions between grazing intensity and precipitation. Results: Biomass was negatively correlated with grazing intensity and this effect increased as precipitation increased. Biomass was positively correlated with species richness in both years, but the strength of this effect and the interaction between species richness and grazing intensity differed between 2014 and 2015 in line with highly variable precipitation between both years. The plant functional groups grasses, sedges, legumes, wormwood and forbs had contrasting responses to grazing and precipitation. Conclusion: Biomass production in drylands is more vulnerable to changes in precipitation variability and grazing intensities in relatively moist and productive rangelands than in dry and unproductive ones. Future rangeland management needs to address potentially increasing precipitation variability in order to promote desired forage plants, and to preserve the positive effects of biodiversity for biomass production