Cessation of grazing causes biodiversity loss and homogenization of soil food webs.

There is widespread concern that cessation of grazing in historically grazed ecosystems is causing biotic homogenization and biodiversity loss. We used 12 montane grassland sites along an 800 km north-south gradient across the UK, to test whether cessation of grazing affects local α- and ß-diversity of below-ground food webs. We show cessation of grazing leads to strongly decreased α-diversity of most groups of soil microbes and fauna, particularly of relatively rare taxa. By contrast, the ß-diversity varied between groups of soil organisms. While most soil microbial communities exhibited increased homogenization after cessation of grazing, we observed decreased homogenization for soil fauna after cessation of grazing. Overall, our results indicate that exclusion of domesticated herbivores from historically grazed montane grasslands has far-ranging negative consequences for diversity of below-ground food webs. This underscores the importance of grazers for maintaining the diversity of below-ground communities, which play a central role in ecosystem functioning.

Loss of Independent Living in Patients Undergoing Transcatheter or Surgical Aortic Valve Replacement: A Retrospective Cohort Study.

BACKGROUND: The recommendation for transcatheter aortic valve replacement (TAVR) or surgical aortic valve replacement (SAVR) in patients 65 to 80 years of age is equivocal, leaving patients with a difficult decision. We evaluated whether TAVR compared to SAVR is associated with reduced odds for loss of independent living in patients ≤65, 66 to 79, and ≥80 years of age. Further, we explored mechanisms of the association of TAVR and adverse discharge. METHODS: Adult patients undergoing TAVR or SAVR within a large academic medical system who lived independently before the procedure were included. A multivariable logistic regression model, adjusting for a priori defined confounders including patient demographics, preoperative comorbidities, and a risk score for adverse discharge after cardiac surgery, was used to assess the primary association. We tested the interaction of patient age with the association between aortic valve replacement (AVR) procedure and loss of independent living. We further assessed whether the primary association was mediated (ie, percentage of the association that can be attributed to the mediator) by the procedural duration as prespecified mediator. RESULTS: A total of 1751 patients (age median [quartiles; min-max], 76 [67, 84; 23-100]; sex, 56% female) were included. A total of 27% (222/812) of these patients undergoing SAVR and 20% (188/939) undergoing TAVR lost the ability to live independently. In our cohort, TAVR was associated with reduced odds for loss of independent living compared to SAVR (adjusted odds ratio [OR adj ] 0.19 [95% confidence interval {CI}, 0.14-0.26]; P < .001). This association was attenuated in patients ≤65 years of age (OR adj 0.63 [0.26-1.56]; P = .32) and between 66 and 79 years of age (OR adj 0.23 [0.15-0.35]; P < .001), and magnified in patients ≥80 years of age (OR adj 0.16 [0.10-0.25]; P < .001; P -for-interaction = .004). Among those >65 years of age, a shorter procedural duration mediated 50% (95% CI, 28-76; P < .001) of the beneficial association of TAVR and independent living. CONCLUSIONS: Patients >65 years of age undergoing TAVR compared to SAVR had reduced odds for loss of independent living. This association was partly mediated by shorter procedural duration. No association between AVR approach and the primary end point was found in patients ≤65 years of age.

A prospective observational study evaluating the use of remote patient monitoring in ED discharged COVID-19 patients in NYC.

OBJECTIVES: We investigated whether continuous remote patient monitoring (RPM) could significantly reduce return Emergency Department (ED) revisits among coronavirus disease 2019 (COVID-19) patients discharged from the emergency Department. MATERIALS AND METHODS: A prospective observational study was conducted from a total of 2833 COVID-19 diagnosed patients who presented to the Montefiore Medical Center ED between September 2020-March 2021. Study patients were remotely monitored through a digital platform that was supervised 24/7 by licensed healthcare professionals. Age and time-period matched controls were randomly sampled through retrospective review. The primary outcome was ED revisit rates among the two groups. RESULTS: In our study, 150 patients enrolled in the RPM program and 150 controls were sampled for a total of 300 patients. Overall, 59.1% of the patients identified as Hispanic/Latino. The RPM group had higher body mass index (BMI) (29 (25-35) vs. 27 (25-31) p-value 0.020) and rates of hypertension (50.7% (76) vs. 35.8% (54) p-value 0.009). There were no statistically significant differences in rates of ED revisit between the RPM group (8% (12)) and control group (9.3% (14)) (OR: 0.863; 95% CI:0.413-1. 803; p- 0.695). DISCUSSION AND CONCLUSION: Our study explored the impact of continuous monitoring versus intermittent monitoring for reducing ED revisits in a largely underrepresented population of the Bronx. Our study demonstrated that continuous remote patient monitoring showed no significant difference in preventing ED revisits compared to non-standardized intermittent monitoring. However, potential other acute care settings where RPM may be useful for identifying high-risk patients for early interventions warrant further study.

On-admission anemia predicts mortality in COVID-19 patients: A single center, retrospective cohort study.

OBJECTIVES: We investigated the impact of anemia based on admission hemoglobin (Hb) level as a prognostic risk factor for severe outcomes in hospitalized patients with coronavirus disease 2019 (COVID-19). METHODS: A single-center, retrospective cohort study was conducted from a random sample of 733 adult patients (age ≥ 18 years) obtained from a total of 4356 laboratory confirmed SARS-CoV-2 cases who presented to the Emergency Department of Montefiore Medical Center between March-June 2020. The primary outcome was a composite endpoint of in-hospital severe outcomes of COVID-19. A secondary outcome was in-hospital all-cause mortality. RESULTS: Among the 733 patients included in our final analysis, 438 patients (59.8%) presented with anemia. 105 patients (14.3%) had mild, and 333 patients (45.5%) had moderate-severe anemia. Overall, 437 patients (59.6%) had a composite endpoint of severe outcomes. On-admission anemia was an independent risk factor for all-cause mortality, (Odds Ratio 1.52, 95% CI [1.01-2.30], p = 0.046) but not for composite severe outcomes. However, moderate-severe anemia (Hb < 11 g/dL) on admission was independently associated with both severe outcomes (OR1.53, 95% CI [1.05-2.23], p = 0.028) and mortality (OR 1.67, 95% CI [1.09-2.56], p = 0.019) during hospitalization. CONCLUSION: Anemia on admission was independently associated with increased odds of all-cause mortality in patients hospitalized with COVID-19. Furthermore, moderate-severe anemia (Hb <11 g/dL) was an independent risk factor for severe COVID-19 outcomes. Moving forward, COVID-19 patient management and risk stratification may benefit from addressing anemia on admission.

Reasons for article retraction in anesthesiology: a comprehensive analysis.

BACKGROUND: Increasing awareness of scientific misconduct has prompted various fields of medicine, including orthopedic surgery, neurosurgery, and dentistry to characterize the reasons for article retraction. The purpose of this review was to evaluate the reasons for and the rate of article retraction in the field of anesthesia within the last 30 years. METHODS: Based on a reproducible search strategy, two independent reviewers searched MEDLINE, EMBASE, and the Retraction Watch website to identify retracted anesthesiology articles. Extracted data included: author names, year of publication, year of the retracted article, journal name, journal five-year impact factor, research type (clinical, basic science, or review), reason for article retraction, number of citations, and presence of a watermark indicating article retraction. RESULTS: Three hundred and fifty articles were included for data extraction. Reasons for article retraction could be grouped into six broad categories. The most common reason for retraction was fraud (data fabrication or manipulation), which accounted for nearly half (49.4%) of all retractions, followed by lack of appropriate ethical approval (28%). Other reasons for retraction included publication issues (e.g., duplicate publications), plagiarism, and studies with methodologic or other non-fraud data issues. Four authors were associated with most of the retracted articles (59%). The majority (69%) of publications utilized a watermark on the original article to indicate that the article was retracted. Journal Citation Reports journal impact factors ranged from 0.9 to 48.1 (median [interquartile range (IQR)], 3.6 [2.5-4.0]), and the most cited article was referenced 197 times (median [IQR], 13 [5-26]). Most retracted articles (66%) were cited at least once by other journal articles after having been withdrawn. CONCLUSIONS: Most retracted articles in anesthesiology literature were retracted because of research misconduct. Limited information is available in the retraction notices, unless explicitly stated, so it is challenging to distinguish between an honest error and research misconduct. Therefore, a standardized reporting process with structured retraction notices is desired.

Comprehensive characterization of ureagenesis in the spfash mouse, a model of human ornithine transcarbamylase deficiency, reveals age-dependency of ammonia detoxification.

The most common ureagenesis defect is X-linked ornithine transcarbamylase (OTC) deficiency which is a main target for novel therapeutic interventions. The spf ash mouse model carries a variant (c.386G>A, p.Arg129His) that is also found in patients. Male spf ash mice have a mild biochemical phenotype with low OTC activity (5%-10% of wild-type), resulting in elevated urinary orotic acid but no hyperammonemia. We recently established a dried blood spot method for in vivo quantification of ureagenesis by Gas chromatography-mass spectrometry (GC-MS) using stable isotopes. Here, we applied this assay to wild-type and spf ash mice to assess ureagenesis at different ages. Unexpectedly, we found an age-dependency with a higher capacity for ammonia detoxification in young mice after weaning. A parallel pattern was observed for carbamoylphosphate synthetase 1 and OTC enzyme expression and activities, which may act as pacemaker of this ammonia detoxification pathway. Moreover, high ureagenesis in younger mice was accompanied by elevated periportal expression of hepatic glutamine synthetase, another main enzyme required for ammonia detoxification. These observations led us to perform a more extensive analysis of the spf ash mouse in comparison to the wild-type, including characterization of the corresponding metabolites, enzyme activities in the liver and plasma and the gut microbiota. In conclusion, the comprehensive enzymatic and metabolic analysis of ureagenesis performed in the presented depth was only possible in animals. Our findings suggest such analyses being essential when using the mouse as a model and revealed age-dependent activity of ammonia detoxification.

Preparing for a Fellowship in Adult Cardiothoracic Anesthesiology: Resources and Approaches for the Anesthesiology Trainee.

Adult cardiothoracic anesthesiology (ACTA) is a competitive fellowship. Despite increases in both the number of programs offering cardiothoracic fellowships and the number of residents applying each year, there is little direction or advice for prospective candidates. This review aims to educate anesthesiology residents who are hoping to pursue cardiothoracic anesthesiology, by examining a brief history of the advanced perioperative echocardiography qualification, the credentialing goals of ACTA fellowships, and the current status of ACTA fellowships. The second part of the review covers the ACTA fellowship application and aims to assist the candidate in navigating this process. The review examines the qualifications that fellowship programs look for in a candidate, including a discussion on professional behavior, and what an applicant can look for in a program. Finally, there is a brief discussion on post-match preparation.

Hybrid Coronary Revascularization - Current State of the Art.

Hybrid coronary revascularization (HCR) seeks to combine the benefit of surgical and nonsurgical techniques for optimum management for selective patients with multivessel obstructive coronary artery disease. The goal of HCR is to combine the benefit of surgical anastomosis of the left internal mammary artery to the left anterior descending coronary artery (LAD) graft along with stenting of non-LAD lesions with percutaneous coronary intervention (PCI). HCR usually involves the use of minimally invasive surgical techniques like robotically assisted coronary artery bypass graft (CABG), with the objective to produce a rapid recovery in the postoperative period, lower complications, and decreased length of stay in the hospital. In this review the authors seek to define the role of HCR in current practice including patient selection, techniques, logistics, outcome data and the challenges it faces in comparison to conventional CABG and PCI.

Validation Study of the Transfusion Risk and Clinical Knowledge (TRACK) Tool in Cardiac Surgery Patients: A Retrospective Analysis.

OBJECTIVE: The Transfusion Risk and Clinical Knowledge (TRACK) scoring system has been developed for predicting perioperative blood transfusions. However, the TRACK score needs to be validated externally in the US population. The primary objective of this study is to validate TRACK at the authors' institution. DESIGN: This study was a single-center retrospective analysis. SETTING: Operating room and intensive care units of academic medical center. PARTICIPANTS: Adult cardiac surgery patients. INTERVENTIONS: The authors retrospectively queried all cardiac surgeries at the authors' institution between 2010 and 2015 from the Society of Thoracic Surgeons database. The TRACK scores were determined for all patients. The authors used receiver operating characteristic (ROC) curves to assess the discriminatory power of TRACK in predicting any perioperative, intraoperative, and postoperative transfusions. The maximum Youden's index was used to determine optimal cutoff scores for predicting perioperative transfusions. MEASUREMENTS AND MAIN RESULTS: The authors analyzed 2,776 cardiac surgery patients with 51.8% transfused perioperatively. The average TRACK score (mean ± standard deviation) in transfused versus non-transfused patients was 12.4 ± 7.2 versus 6.1 ± 5.4, respectively (p < 0.001). The area under the ROC curve was 0.768 (95% confidence interval 0.800-0.835, p < 0.001) for any perioperative transfusion. Optimal sensitivity (67%) and specificity (73%) for predicting any perioperative transfusions was achieved with a TRACK score cutoff of greater than or equal to 22 of 32. CONCLUSION: This study demonstrates the validity of the TRACK score in predicting blood perioperative transfusions in cardiac surgery patients at the authors' institution. This study supports the external validity of TRACK and adds to its clinical utility by establishing cutoff scores for identifying patients at high risk of transfusion.

Patient Demographics and Extracorporeal Membranous Oxygenation (ECMO)-Related Complications Associated With Survival to Discharge or 30-Day Survival in Adult Patients Receiving Venoarterial (VA) and Venovenous (VV) ECMO in a Quaternary Care Urban Center.

OBJECTIVE: Investigate how a multitude of patient demographics and extracorporeal membranous oxygenation (ECMO)-related complications affect 30-day survival or survival to discharge. DESIGN: Retrospective observational study. SETTING: Urban university hospital, quaternary care center. PARTICIPANTS: Patients who underwent ECMO circulatory support from January 2012 to May 2016. INTERVENTIONS: Date-based data extraction, univariate and multivariate regression analysis. MEASUREMENTS AND MAIN RESULTS: The hospital database contained complete data for 235 adult patients who received venoarterial ECMO (74.04 %) and venovenous ECMO (25.96 %); 106 patients (45.11%) survived. The independent predictors significant in the odds of in-hospital mortality in a multiregression model were age (odds ratio [OR] = 1.028, p = 0.008), extracorporeal cardiopulmonary resuscitation (ECPR) after unsuccessful high-quality CPR (OR = 7.93, p =0.002), cardiogenic shock as the primary indication for circulatory support (OR = 2.58, p = 0.02), acute kidney injury (AKI) before ECMO initiation (OR = 7.53, p < 0.001), time spent on ECMO in days (OR = 1.08, p = 0.03), and limb ischemia (OR = 3.18, p = 0.047). CONCLUSION: The most significant findings of advancing age, time spent on ECMO, AKI, ECMO use in the setting of cardiogenic shock, ECPR, and limb ischemia as a complication of ECMO all independently increase the odds of in-hospital and 30-day mortality. To the best of the authors' knowledge, this study is the first to demonstrate a significant relationship between limb ischemia and mortality.

Microbes follow Humboldt: temperature drives plant and soil microbial diversity patterns from the Amazon to the Andes.

More than 200 years ago, Alexander von Humboldt reported that tropical plant species richness decreased with increasing elevation and decreasing temperature. Surprisingly, coordinated patterns in plant, bacterial, and fungal diversity on tropical mountains have not yet been observed, despite the central role of soil microorganisms in terrestrial biogeochemistry and ecology. We studied an Andean transect traversing 3.5 km in elevation to test whether the species diversity and composition of tropical forest plants, soil bacteria, and fungi follow similar biogeographical patterns with shared environmental drivers. We found coordinated changes with elevation in all three groups: species richness declined as elevation increased, and the compositional dissimilarity among communities increased with increased separation in elevation, although changes in plant diversity were larger than in bacteria and fungi. Temperature was the dominant driver of these diversity gradients, with weak influences of edaphic properties, including soil pH. The gradients in microbial diversity were strongly correlated with the activities of enzymes involved in organic matter cycling, and were accompanied by a transition in microbial traits towards slower-growing, oligotrophic taxa at higher elevations. We provide the first evidence of coordinated temperature-driven patterns in the diversity and distribution of three major biotic groups in tropical ecosystems: soil bacteria, fungi, and plants. These findings suggest that interrelated and fundamental patterns of plant and microbial communities with shared environmental drivers occur across landscape scales. These patterns are revealed where soil pH is relatively constant, and have implications for tropical forest communities under future climate change.

A Comparison of Inflammatory Responses Between Robotically Enhanced Coronary Artery Bypass Grafting and Conventional Coronary Artery Bypass Grafting: Implications for Hybrid Revascularization.

OBJECTIVE: The inflammatory response elicited by robotically enhanced coronary artery bypass grafting (r-CABG) has not been well described. When r-CABG is performed as part of hybrid coronary revascularization, the inflammatory milieu and the timing of percutaneous coronary intervention may affect the stent patency negatively in the short and long term. The goal of this study was to describe the extent and time course of cytokine release after r-CABG compared with conventional CABG (c-CABG) and to elucidate the optimal timing for r-CABG in the setting of hybrid coronary revascularization for a future study. DESIGN: Prospective, observational study. SETTING: Tertiary-care center in a university hospital. PARTICIPANTS: The study comprised patients scheduled to undergo r-CABG or c-CABG from October 2012 to November 2014. INTERVENTIONS: Cytokine levels of interleukin (IL)-6, IL-8, IL-10; tumor necrosis factor-α; and C-reactive protein (CRP) were measured at the following time points: preprocedure; at the end of the procedure; and at 4, 8, 12, 24, and 48 hours after the procedure. MEASUREMENTS AND MAIN RESULTS: Twenty-eight patients undergoing r-CABG and 10 patients undergoing c-CABG were enrolled. The levels of cytokines after r-CABG and c-CABG were compared using the mixed-effect linear regression model for longitudinal data. Cytokine release in the r-CABG group was comparatively less for IL-6, IL-10, tumor necrosis factor, and CRP levels. They all trended toward the baseline by the 48th hour in both groups, except CRP levels, which reached their peak at 48 hours in both groups. CONCLUSIONS: The inflammatory response to r-CABG was blunted compared with that of c-CABG. The high CRP levels on the second postoperative day after r-CABG were a cause for concern in regard to percutaneous coronary intervention performed at that time period, but additional studies are necessary.

Continental-scale distributions of dust-associated bacteria and fungi.

It has been known for centuries that microorganisms are ubiquitous in the atmosphere, where they are capable of long-distance dispersal. Likewise, it is well-established that these airborne bacteria and fungi can have myriad effects on human health, as well as the health of plants and livestock. However, we have a limited understanding of how these airborne communities vary across different geographic regions or the factors that structure the geographic patterns of near-surface microbes across large spatial scales. We collected dust samples from the external surfaces of ∼1,200 households located across the United States to understand the continental-scale distributions of bacteria and fungi in the near-surface atmosphere. The microbial communities were highly variable in composition across the United States, but the geographic patterns could be explained by climatic and soil variables, with coastal regions of the United States sharing similar airborne microbial communities. Although people living in more urbanized areas were not found to be exposed to distinct outdoor air microbial communities compared with those living in more rural areas, our results do suggest that urbanization leads to homogenization of the airborne microbiota, with more urban communities exhibiting less continental-scale geographic variability than more rural areas. These results provide our first insight into the continental-scale distributions of airborne microbes, which is information that could be used to identify likely associations between microbial exposures in outdoor air and incidences of disease in crops, livestock, and humans.

Consistent responses of soil microbial communities to elevated nutrient inputs in grasslands across the globe.

Soil microorganisms are critical to ecosystem functioning and the maintenance of soil fertility. However, despite global increases in the inputs of nitrogen (N) and phosphorus (P) to ecosystems due to human activities, we lack a predictive understanding of how microbial communities respond to elevated nutrient inputs across environmental gradients. Here we used high-throughput sequencing of marker genes to elucidate the responses of soil fungal, archaeal, and bacterial communities using an N and P addition experiment replicated at 25 globally distributed grassland sites. We also sequenced metagenomes from a subset of the sites to determine how the functional attributes of bacterial communities change in response to elevated nutrients. Despite strong compositional differences across sites, microbial communities shifted in a consistent manner with N or P additions, and the magnitude of these shifts was related to the magnitude of plant community responses to nutrient inputs. Mycorrhizal fungi and methanogenic archaea decreased in relative abundance with nutrient additions, as did the relative abundances of oligotrophic bacterial taxa. The metagenomic data provided additional evidence for this shift in bacterial life history strategies because nutrient additions decreased the average genome sizes of the bacterial community members and elicited changes in the relative abundances of representative functional genes. Our results suggest that elevated N and P inputs lead to predictable shifts in the taxonomic and functional traits of soil microbial communities, including increases in the relative abundances of faster-growing, copiotrophic bacterial taxa, with these shifts likely to impact belowground ecosystems worldwide.

Following Rapoport's Rule: the geographic range and genome size of bacterial taxa decline at warmer latitudes.

We sought to test whether stream bacterial communities conform to Rapoport's Rule, a pattern commonly observed for plants and animals whereby taxa exhibit decreased latitudinal range sizes closer to the equator. Using a DNA sequencing approach, we explored the biogeography of biofilm bacterial communities in 204 streams across a ∼1000 km latitudinal gradient. The range sizes of bacterial taxa were strongly correlated with latitude, decreasing closer to the equator, which coincided with a greater than fivefold increase in bacterial taxonomic richness. The relative richness and range size of bacteria were associated with spatially correlated variation in temperature and rainfall. These patterns were observed despite enormous variability in catchment environmental characteristics. Similar results were obtained when restricting the same analyses to native forest catchments, thereby controlling for spatial biases in land use. We analysed genomic data from ∼500 taxa detected in this study, for which data were available and found that bacterial communities at cooler latitudes also tended to possess greater potential metabolic potential. Collectively, these data provide the first evidence of latitudinal variation in the range size distributions of freshwater bacteria, a trend which may be determined, in part, by a trade-off between bacterial genome size and local variation in climatic conditions.

Plant domestication and the assembly of bacterial and fungal communities associated with strains of the common sunflower, Helianthus annuus.

Root and rhizosphere microbial communities can affect plant health, but it remains undetermined how plant domestication may influence these bacterial and fungal communities. We grew 33 sunflower (Helianthus annuus) strains (n = 5) that varied in their extent of domestication and assessed rhizosphere and root endosphere bacterial and fungal communities. We also assessed fungal communities in the sunflower seeds to investigate the degree to which root and rhizosphere communities were influenced by vertical transmission of the microbiome through seeds. Neither root nor rhizosphere bacterial communities were affected by the extent of sunflower domestication, but domestication did affect the composition of rhizosphere fungal communities. In particular, more modern sunflower strains had lower relative abundances of putative fungal pathogens. Seed-associated fungal communities strongly differed across strains, but several lines of evidence suggest that there is minimal vertical transmission of fungi from seeds to the adult plants. Our results indicate that plant-associated fungal communities are more strongly influenced by host genetic factors and plant breeding than bacterial communities, a finding that could influence strategies for optimizing microbial communities to improve crop yields.

Building a drug development database: challenges in reliable data availability.

CONTEXT: Policy and legislative efforts to improve the biomedical innovation process must rely on a detailed and thorough analysis of drug development and industry output. OBJECTIVE: As part of our efforts to build a publicly-available database on the characteristics of drug development, we present work undertaken to test methods for compiling data from public sources. These initial steps are designed to explore challenges in data extraction, completeness and reliability. Specifically, filing dates for Investigational New Drugs (IND) applications with the U.S. Food and Drug Administration (FDA) were chosen as the initial objective data element to be collected. MATERIALS AND METHODS: FDA's Drugs@FDA database and the Federal Register (FR) were used to collect IND dates for the 587 New Molecular Entities (NMEs) approved between 1994 and 2014. When available, the following data were captured: approval date, IND number, IND date and source of information. RESULTS: At least one IND date was available for 445 (75.8%) of the 587 NMEs. The Drugs@FDA database provided IND dates for 303 (51.6%) NMEs and the FR contributed with 297 (50.6%) IND dates. Out of the 445 NMEs for which an IND date was obtained, 274 (61.6%) had more than one date reported. DISCUSSION: Key finding of this paper is a considerable inconsistency in reliably available or reported data elements, in this particular case, IND application filing dates as assembled from publicly-available sources. CONCLUSION: Our team will continue to focus on finding ways to collect relevant information to measure impact of drug innovation.

Pirfenidone for idiopathic pulmonary fibrosis: analysis of pooled data from three multinational phase 3 trials.

Pirfenidone is an antifibrotic agent that has been evaluated in three multinational phase 3 trials in patients with idiopathic pulmonary fibrosis (IPF). We analysed pooled data from the multinational trials to obtain the most precise estimates of the magnitude of treatment effect on measures of disease progression.All patients randomised to pirfenidone 2403 mg·day(-1) or placebo in the CAPACITY or ASCEND studies were included in the analysis. Pooled analyses of outcomes at 1 year were based on the pre-specified end-points and analytic methods described in the ASCEND study protocol.A total of 1247 patients were included in the analysis. At 1 year, pirfenidone reduced the proportion of patients with a ≥10% decline in per cent predicted forced vital capacity or death by 43.8% (95% CI 29.3-55.4%) and increased the proportion of patients with no decline by 59.3% (95% CI 29.0-96.8%). A treatment benefit was also observed for progression-free survival, 6-min walk distance and dyspnoea. Gastrointestinal and skin-related adverse events were more common in the pirfenidone group, but rarely led to discontinuation.Analysis of data from three phase 3 trials demonstrated that treatment with pirfenidone for 1 year resulted in clinically meaningful reductions in disease progression in patients with IPF.

Long-lasting effects of land use history on soil fungal communities in second-growth tropical rain forests.

Our understanding of the long-lasting effects of human land use on soil fungal communities in tropical forests is limited. Yet, over 70% of all remaining tropical forests are growing in former agricultural or logged areas. We investigated the relationship among land use history, biotic and abiotic factors, and soil fungal community composition and diversity in a second-growth tropical forest in Puerto Rico. We coupled high-throughput DNA sequencing with tree community and environmental data to determine whether land use history had an effect on soil fungal community descriptors. We also investigated the biotic and abiotic factors that underlie such differences and asked whether the relative importance of biotic (tree diversity, basal tree area, and litterfall biomass) and abiotic (soil type, pH, iron, and total carbon, water flow, and canopy openness) factors in structuring soil fungal communities differed according to land use history. We demonstrated long-lasting effects of land use history on soil fungal communities. At our research site, most of the explained variation in soil fungal composition (R2  = 18.6%), richness (R2  = 11.4%), and evenness (R2  = 10%) was associated with edaphic factors. Areas previously subject to both logging and farming had a soil fungal community with lower beta diversity and greater evenness of fungal operational taxonomic units (OTUs) than areas subject to light logging. Yet, fungal richness was similar between the two areas of historical land use. Together, these results suggest that fungal communities in disturbed areas are more homogeneous and diverse than in areas subject to light logging. Edaphic factors were the most strongly correlated with soil fungal composition, especially in areas subject to light logging, where soils are more heterogenous. High functional tree diversity in areas subject to both logging and farming led to stronger correlations between biotic factors and fungal composition than in areas subject to light logging. In contrast, fungal richness and evenness were more strongly correlated with biotic factors in areas of light logging, suggesting that these metrics might reflect long-term associations in old-growth forests. The large amount of unexplained variance in fungal composition suggests that these communities are structured by both stochastic and niche assemblage processes.

Infection with a Shoot-Specific Fungal Endophyte (Epichloë) Alters Tall Fescue Soil Microbial Communities.

Tall fescue (Schedonorus arundinaceus) is a widespread grass that can form a symbiotic relationship with a shoot-specific fungal endophyte (Epichloë coenophiala). While the effects of fungal endophyte infection on fescue physiology and ecology have been relatively well studied, less attention has been given to how this relationship may impact the soil microbial community. We used high-throughput DNA sequencing and phospholipid fatty acid analysis to determine the structure and biomass of microbial communities in both bulk and rhizosphere soils from tall fescue stands that were either uninfected with E. coenophiala or were infected with the common toxic strain or one of several novel strains of the endophyte. We found that rhizosphere and bulk soils harbored distinct microbial communities. Endophyte presence, regardless of strain, significantly influenced soil fungal communities, but endophyte effects were less pronounced in prokaryotic communities. E. coenophiala presence did not change total fungal biomass but caused a shift in soil and rhizosphere fungal community composition, increasing the relative abundance of taxa within the Glomeromycota phylum and decreasing the relative abundance of genera in the Ascomycota phylum, including Lecanicillium, Volutella, Lipomyces, Pochonia, and Rhizoctonia. Our data suggests that tripartite interactions exist between the shoot endophyte E. coenophiala, tall fescue, and soil fungi that may have important implications for the functioning of soils, such as carbon storage, in fescue-dominated grasslands.