Organic matter composition and the protist and nematode communities around anecic earthworm burrows

By living in permanent burrows and incorporating organic detritus from the soil surface, anecic earthworms contribute to soil heterogeneity, but their impact is still under-studied in natural field conditions. We investigated the effects of the anecic earthworm Lumbricus centralis on fresh carbon (C) incorporation, soil organic matter composition, protists, and nematodes of a Cambisol under grassland. We used plant material labelled with stable isotope tracers to detect fresh C input around earthworm-occupied burrows or around burrows from which the earthworm had been removed. After 50 days, we sampled soil (0–10 cm depth) in concentric layers around the burrows, distinguishing between drilosphere (0–8 mm) and bulk soil (50–75 mm). L. centralis effectively incorporated fresh C into the drilosphere, and this shifted soil organic matter amount and chemistry: total soil sugar content was increased compared to unoccupied drilosphere and bulk soil, and the contribution of plant-derived sugars to soil organic matter was enhanced. Earthworms also shifted the spatial distribution of soil C towards the drilosphere. The total abundance of protists and nematodes was only slightly higher in earthworm-occupied drilosphere, but strong positive effects were found for some protist clades (e.g. Stenamoeba spp.). Additional data for the co-occurring anecic earthworm species Aporrectodea longa showed that it incorporated fresh C less than L. centralis, suggesting that the two species may have different effects on soil C distribution and organic matter quality

IL-17 producing innate lymphoid cells and the NLRP3 inflammasome facilitate obesity-associated airway hyperreactivity

Obesity is associated with the development of asthma and considerable asthma-related healthcare utilization. To understand the immunological pathways that lead to obesity-associated asthma, we fed mice a high fat diet for 12 weeks, which resulted in obesity and the development of airway hyperreactivity (AHR), a cardinal feature of asthma. This AHR depended on innate immunity, since it occurred in obese Rag−/− mice, and on IL-17A and the NLRP3 inflammasome, since it did not develop in obese Il17−/− or Nlrp3−/− mice. The AHR was also associated with the presence in the lungs of CCR6+ innate lymphoid cells producing IL-17A (ILC3 cells), which could by themselves mediate AHR when adoptively transferred into Rag2−/− Il2rγ−/− mice. IL-1β played an important role by expanding the ILC3 cells, and treatment to block the function of IL-1β abolished obesity-induced AHR. Since we found ILC3-like cells in the bronchoalveolar lavage fluid of human patients with asthma, we suggest that obesity-associated asthma is facilitated by inflammation mediated by NLRP3, IL-1β and ILC3 cells

Indoor robot gardening: design and implementation

This paper describes the architecture and implementation of a distributed autonomous gardening system with applications in urban/indoor precision agriculture. The garden is a mesh network of robots and plants. The gardening robots are mobile manipulators with an eye-in-hand camera. They are capable of locating plants in the garden, watering them, and locating and grasping fruit. The plants are potted cherry tomatoes enhanced with sensors and computation to monitor their well-being (e.g. soil humidity, state of fruits) and with networking to communicate servicing requests to the robots. By embedding sensing, computation, and communication into the pots, task allocation in the system is de-centrally coordinated, which makes the system scalable and robust against the failure of a centralized agent. We describe the architecture of this system and present experimental results for navigation, object recognition, and manipulation as well as challenges that lie ahead toward autonomous precision agriculture with multi-robot teams.Swiss National Science Foundation (contract number PBEL2118737)United States. Army Research Office. Multidisciplinary University Research Initiative (MURI SWARMS project W911NF-05-1-0219)National Science Foundation (U.S.) (NSF IIS-0426838)Intel Corporation (EFRI 0735953 Intel)Massachusetts Institute of Technology (UROP program)Massachusetts Institute of Technology (MSRP program

Rationale and design of Ferinject® Assessment in patients with IRon deficiency and chronic Heart Failure (FAIR-HF) study: a randomized, placebo-controlled study of intravenous iron supplementation in patients with and without anaemia

Iron deficiency (ID) and anaemia are common in patients with chronic heart failure (CHF). The presence of anaemia is associated with increased morbidity and mortality in CHF, and ID is a major reason for the development of anaemia. Preliminary studies using intravenous (i.v.) iron supplementation alone in patients with CHF and ID have shown improvements in symptom status. FAIR-HF (Clinical Trials.gov NCT00520780) was designed to determine the effect of i.v. iron repletion therapy using ferric carboxymaltose on self-reported patient global assessment (PGA) and New York Heart Association (NYHA) in patients with CHF and ID. This is a multi-centre, randomized, double-blind, placebo-controlled study recruiting ambulatory patients with symptomatic CHF with LVEF < 40% (NYHA II) or < 45% (NYHA III), ID [ferritin < 100 ng/mL or ferritin 100-300 ng/mL when transferrin saturation (TSAT) < 20%], and haemoglobin 9.5-13.5 g/dL. Patients were randomized in a 2:1 ratio to receive ferric carboxymaltose (Ferinject((R))) 200 mg iron i.v. or saline i.v. weekly until iron repletion (correction phase), then monthly until Week 24 (maintenance phase). Primary endpoints are (i) self-reported PGA at Week 24 and (ii) NYHA class at Week 24, adjusted for baseline NYHA class. This study will provide evidence on the efficacy and safety of iron repletion with ferric carboxymaltose in CHF patients with ID with and without anaemia

Enhancing Discovery of Genetic Variants for Posttraumatic Stress Disorder Through Integration of Quantitative Phenotypes and Trauma Exposure Information

Funding Information: This work was supported by the National Institute of Mental Health / U.S. Army Medical Research and Development Command (Grant No. R01MH106595 [to CMN, IL, MBS, KJRe, and KCK], National Institutes of Health (Grant No. 5U01MH109539 to the Psychiatric Genomics Consortium ), and Brain & Behavior Research Foundation (Young Investigator Grant [to KWC]). Genotyping of samples was provided in part through the Stanley Center for Psychiatric Genetics at the Broad Institute supported by Cohen Veterans Bioscience . Statistical analyses were carried out on the LISA/Genetic Cluster Computer ( https://userinfo.surfsara.nl/systems/lisa ) hosted by SURFsara. This research has been conducted using the UK Biobank resource (Application No. 41209). This work would have not been possible without the financial support provided by Cohen Veterans Bioscience, the Stanley Center for Psychiatric Genetics at the Broad Institute, and One Mind. Funding Information: MBS has in the past 3 years received consulting income from Actelion, Acadia Pharmaceuticals, Aptinyx, Bionomics, BioXcel Therapeutics, Clexio, EmpowerPharm, GW Pharmaceuticals, Janssen, Jazz Pharmaceuticals, and Roche/Genentech and has stock options in Oxeia Biopharmaceuticals and Epivario. In the past 3 years, NPD has held a part-time paid position at Cohen Veterans Bioscience, has been a consultant for Sunovion Pharmaceuticals, and is on the scientific advisory board for Sentio Solutions for unrelated work. In the past 3 years, KJRe has been a consultant for Datastat, Inc., RallyPoint Networks, Inc., Sage Pharmaceuticals, and Takeda. JLM-K has received funding and a speaking fee from COMPASS Pathways. MU has been a consultant for System Analytic. HRK is a member of the Dicerna scientific advisory board and a member of the American Society of Clinical Psychopharmacology Alcohol Clinical Trials Initiative, which during the past 3 years was supported by Alkermes, Amygdala Neurosciences, Arbor Pharmaceuticals, Dicerna, Ethypharm, Indivior, Lundbeck, Mitsubishi, and Otsuka. HRK and JG are named as inventors on Patent Cooperative Treaty patent application number 15/878,640, entitled “Genotype-guided dosing of opioid agonists,” filed January 24, 2018. RP and JG are paid for their editorial work on the journal Complex Psychiatry. OAA is a consultant to HealthLytix. All other authors report no biomedical financial interests or potential conflicts of interest. Funding Information: This work was supported by the National Institute of Mental Health/ U.S. Army Medical Research and Development Command (Grant No. R01MH106595 [to CMN, IL, MBS, KJRe, and KCK], National Institutes of Health (Grant No. 5U01MH109539 to the Psychiatric Genomics Consortium), and Brain & Behavior Research Foundation (Young Investigator Grant [to KWC]). Genotyping of samples was provided in part through the Stanley Center for Psychiatric Genetics at the Broad Institute supported by Cohen Veterans Bioscience. Statistical analyses were carried out on the LISA/Genetic Cluster Computer (https://userinfo.surfsara.nl/systems/lisa) hosted by SURFsara. This research has been conducted using the UK Biobank resource (Application No. 41209). This work would have not been possible without the financial support provided by Cohen Veterans Bioscience, the Stanley Center for Psychiatric Genetics at the Broad Institute, and One Mind. This material has been reviewed by the Walter Reed Army Institute of Research. There is no objection to its presentation and/or publication. The opinions or assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting true views of the U.S. Department of the Army or the Department of Defense. We thank the investigators who comprise the PGC-PTSD working group and especially the more than 206,000 research participants worldwide who shared their life experiences and biological samples with PGC-PTSD investigators. We thank Mark Zervas for his critical input. Full acknowledgments are in Supplement 1. MBS has in the past 3 years received consulting income from Actelion, Acadia Pharmaceuticals, Aptinyx, Bionomics, BioXcel Therapeutics, Clexio, EmpowerPharm, GW Pharmaceuticals, Janssen, Jazz Pharmaceuticals, and Roche/Genentech and has stock options in Oxeia Biopharmaceuticals and Epivario. In the past 3 years, NPD has held a part-time paid position at Cohen Veterans Bioscience, has been a consultant for Sunovion Pharmaceuticals, and is on the scientific advisory board for Sentio Solutions for unrelated work. In the past 3 years, KJRe has been a consultant for Datastat, Inc. RallyPoint Networks, Inc. Sage Pharmaceuticals, and Takeda. JLM-K has received funding and a speaking fee from COMPASS Pathways. MU has been a consultant for System Analytic. HRK is a member of the Dicerna scientific advisory board and a member of the American Society of Clinical Psychopharmacology Alcohol Clinical Trials Initiative, which during the past 3 years was supported by Alkermes, Amygdala Neurosciences, Arbor Pharmaceuticals, Dicerna, Ethypharm, Indivior, Lundbeck, Mitsubishi, and Otsuka. HRK and JG are named as inventors on Patent Cooperative Treaty patent application number 15/878,640, entitled ?Genotype-guided dosing of opioid agonists,? filed January 24, 2018. RP and JG are paid for their editorial work on the journal Complex Psychiatry. OAA is a consultant to HealthLytix. All other authors report no biomedical financial interests or potential conflicts of interest. Publisher Copyright: © 2021 Society of Biological PsychiatryBackground: Posttraumatic stress disorder (PTSD) is heritable and a potential consequence of exposure to traumatic stress. Evidence suggests that a quantitative approach to PTSD phenotype measurement and incorporation of lifetime trauma exposure (LTE) information could enhance the discovery power of PTSD genome-wide association studies (GWASs). Methods: A GWAS on PTSD symptoms was performed in 51 cohorts followed by a fixed-effects meta-analysis (N = 182,199 European ancestry participants). A GWAS of LTE burden was performed in the UK Biobank cohort (N = 132,988). Genetic correlations were evaluated with linkage disequilibrium score regression. Multivariate analysis was performed using Multi-Trait Analysis of GWAS. Functional mapping and annotation of leading loci was performed with FUMA. Replication was evaluated using the Million Veteran Program GWAS of PTSD total symptoms. Results: GWASs of PTSD symptoms and LTE burden identified 5 and 6 independent genome-wide significant loci, respectively. There was a 72% genetic correlation between PTSD and LTE. PTSD and LTE showed largely similar patterns of genetic correlation with other traits, albeit with some distinctions. Adjusting PTSD for LTE reduced PTSD heritability by 31%. Multivariate analysis of PTSD and LTE increased the effective sample size of the PTSD GWAS by 20% and identified 4 additional loci. Four of these 9 PTSD loci were independently replicated in the Million Veteran Program. Conclusions: Through using a quantitative trait measure of PTSD, we identified novel risk loci not previously identified using prior case-control analyses. PTSD and LTE have a high genetic overlap that can be leveraged to increase discovery power through multivariate methods.publishersversionpublishe

A novel formulation of inhaled sodium cromoglicate (PA101) in idiopathic pulmonary fibrosis and chronic cough: a randomised, double-blind, proof-of-concept, phase 2 trial

Background Cough can be a debilitating symptom of idiopathic pulmonary fibrosis (IPF) and is difficult to treat. PA101 is a novel formulation of sodium cromoglicate delivered via a high-efficiency eFlow nebuliser that achieves significantly higher drug deposition in the lung compared with the existing formulations. We aimed to test the efficacy and safety of inhaled PA101 in patients with IPF and chronic cough and, to explore the antitussive mechanism of PA101, patients with chronic idiopathic cough (CIC) were also studied. Methods This pilot, proof-of-concept study consisted of a randomised, double-blind, placebo-controlled trial in patients with IPF and chronic cough and a parallel study of similar design in patients with CIC. Participants with IPF and chronic cough recruited from seven centres in the UK and the Netherlands were randomly assigned (1:1, using a computer-generated randomisation schedule) by site staff to receive PA101 (40 mg) or matching placebo three times a day via oral inhalation for 2 weeks, followed by a 2 week washout, and then crossed over to the other arm. Study participants, investigators, study staff, and the sponsor were masked to group assignment until all participants had completed the study. The primary efficacy endpoint was change from baseline in objective daytime cough frequency (from 24 h acoustic recording, Leicester Cough Monitor). The primary efficacy analysis included all participants who received at least one dose of study drug and had at least one post-baseline efficacy measurement. Safety analysis included all those who took at least one dose of study drug. In the second cohort, participants with CIC were randomly assigned in a study across four centres with similar design and endpoints. The study was registered with ClinicalTrials.gov (NCT02412020) and the EU Clinical Trials Register (EudraCT Number 2014-004025-40) and both cohorts are closed to new participants. Findings Between Feb 13, 2015, and Feb 2, 2016, 24 participants with IPF were randomly assigned to treatment groups. 28 participants with CIC were enrolled during the same period and 27 received study treatment. In patients with IPF, PA101 reduced daytime cough frequency by 31·1% at day 14 compared with placebo; daytime cough frequency decreased from a mean 55 (SD 55) coughs per h at baseline to 39 (29) coughs per h at day 14 following treatment with PA101, versus 51 (37) coughs per h at baseline to 52 (40) cough per h following placebo treatment (ratio of least-squares [LS] means 0·67, 95% CI 0·48–0·94, p=0·0241). By contrast, no treatment benefit for PA101 was observed in the CIC cohort; mean reduction of daytime cough frequency at day 14 for PA101 adjusted for placebo was 6·2% (ratio of LS means 1·27, 0·78–2·06, p=0·31). PA101 was well tolerated in both cohorts. The incidence of adverse events was similar between PA101 and placebo treatments, most adverse events were mild in severity, and no severe adverse events or serious adverse events were reported. Interpretation This study suggests that the mechanism of cough in IPF might be disease specific. Inhaled PA101 could be a treatment option for chronic cough in patients with IPF and warrants further investigation

Rare copy number variation in posttraumatic stress disorder

Posttraumatic stress disorder (PTSD) is a heritable (h2 = 24-71%) psychiatric illness. Copy number variation (CNV) is a form of rare genetic variation that has been implicated in the etiology of psychiatric disorders, but no large-scale investigation of CNV in PTSD has been performed. We present an association study of CNV burden and PTSD symptoms in a sample of 114,383 participants (13,036 cases and 101,347 controls) of European ancestry. CNVs were called using two calling algorithms and intersected to a consensus set. Quality control was performed to remove strong outlier samples. CNVs were examined for association with PTSD within each cohort using linear or logistic regression analysis adjusted for population structure and CNV quality metrics, then inverse variance weighted meta-analyzed across cohorts. We examined the genome-wide total span of CNVs, enrichment of CNVs within specified gene-sets, and CNVs overlapping individual genes and implicated neurodevelopmental regions. The total distance covered by deletions crossing over known neurodevelopmental CNV regions was significant (beta = 0.029, SE = 0.005, P = 6.3 × 10-8). The genome-wide neurodevelopmental CNV burden identified explains 0.034% of the variation in PTSD symptoms. The 15q11.2 BP1-BP2 microdeletion region was significantly associated with PTSD (beta = 0.0206, SE = 0.0056, P = 0.0002). No individual significant genes interrupted by CNV were identified. 22 gene pathways related to the function of the nervous system and brain were significant in pathway analysis (FDR q < 0.05), but these associations were not significant once NDD regions were removed. A larger sample size, better detection methods, and annotated resources of CNV are needed to explore this relationship further

Physical, cognitive, and mental health impacts of COVID-19 after hospitalisation (PHOSP-COVID): a UK multicentre, prospective cohort study

Background The impact of COVID-19 on physical and mental health and employment after hospitalisation with acute disease is not well understood. The aim of this study was to determine the effects of COVID-19-related hospitalisation on health and employment, to identify factors associated with recovery, and to describe recovery phenotypes. Methods The Post-hospitalisation COVID-19 study (PHOSP-COVID) is a multicentre, long-term follow-up study of adults (aged ≥18 years) discharged from hospital in the UK with a clinical diagnosis of COVID-19, involving an assessment between 2 and 7 months after discharge, including detailed recording of symptoms, and physiological and biochemical testing. Multivariable logistic regression was done for the primary outcome of patient-perceived recovery, with age, sex, ethnicity, body-mass index, comorbidities, and severity of acute illness as covariates. A post-hoc cluster analysis of outcomes for breathlessness, fatigue, mental health, cognitive impairment, and physical performance was done using the clustering large applications k-medoids approach. The study is registered on the ISRCTN Registry (ISRCTN10980107). Findings We report findings for 1077 patients discharged from hospital between March 5 and Nov 30, 2020, who underwent assessment at a median of 5·9 months (IQR 4·9–6·5) after discharge. Participants had a mean age of 58 years (SD 13); 384 (36%) were female, 710 (69%) were of white ethnicity, 288 (27%) had received mechanical ventilation, and 540 (50%) had at least two comorbidities. At follow-up, only 239 (29%) of 830 participants felt fully recovered, 158 (20%) of 806 had a new disability (assessed by the Washington Group Short Set on Functioning), and 124 (19%) of 641 experienced a health-related change in occupation. Factors associated with not recovering were female sex, middle age (40–59 years), two or more comorbidities, and more severe acute illness. The magnitude of the persistent health burden was substantial but only weakly associated with the severity of acute illness. Four clusters were identified with different severities of mental and physical health impairment (n=767): very severe (131 patients, 17%), severe (159, 21%), moderate along with cognitive impairment (127, 17%), and mild (350, 46%). Of the outcomes used in the cluster analysis, all were closely related except for cognitive impairment. Three (3%) of 113 patients in the very severe cluster, nine (7%) of 129 in the severe cluster, 36 (36%) of 99 in the moderate cluster, and 114 (43%) of 267 in the mild cluster reported feeling fully recovered. Persistently elevated serum C-reactive protein was positively associated with cluster severity. Interpretation We identified factors related to not recovering after hospital admission with COVID-19 at 6 months after discharge (eg, female sex, middle age, two or more comorbidities, and more acute severe illness), and four different recovery phenotypes. The severity of physical and mental health impairments were closely related, whereas cognitive health impairments were independent. In clinical care, a proactive approach is needed across the acute severity spectrum, with interdisciplinary working, wide access to COVID-19 holistic clinical services, and the potential to stratify care. Funding UK Research and Innovation and National Institute for Health Research

Serum vitamin d is significantly inversely associated with disease severity in caucasian adults with obstructive sleep apnea syndrome

Study Objectives: To evaluate vitamin D (25(OH)D) levels in obstructive sleep apnea syndrome (OSAS) and possible relationships to OSAS severity, sleepiness, lung function, nocturnal heart rate (HR), and body composition. We also aimed to compare the 25(OH)D status of a subset of OSAS patients compared to controls matched for important determinants of both OSAS and vitamin D deficiency (VDD). Methods: This was a cross-sectional study conducted at an urban, clinical sleep medicine outpatient center. We recruited newly diagnosed, Caucasian adults who had recently undergone nocturnal polysomnography. We compared body mass index (BMI), body composition (bioelectrical impedance analysis), neck circumference, sleepiness (Epworth Sleepiness Scale), lung function, and vitamin D status (serum 25-hydrpoxyvitamin D (25(OH)D) across OSAS severity categories and non-OSAS subjects. Next, using a case-control design, we compared measures of serum 25(OH)D from OSAS cases to non-OSAS controls who were matched for age, gender, skin pigmentation, sleepiness, season, and BMI. Results: 106 adults (77 male; median age = 54.5; median BMI = 34.3 kg/m(2)) resident in Dublin, Ireland (latitude 53 degrees N) were recruited and categorized as non-OSAS or mild/moderate/severe OSAS. 98% of OSAS cases had insufficient 25(OH) D (&amp;lt; 75 nmol/L), including 72% with VDD (&amp;lt; 50 nmol/L). 25(OH)D levels decreased with OSAS severity (P = 0.003). 25(OH) D was inversely correlated with BMI, percent body fat, AHI, and nocturnal HR. Subsequent multivariate regression analysis revealed that 25(OH) D was independently associated with both AHI (P = 0.016) and nocturnal HR (P = 0.0419). Our separate case-control study revealed that 25(OH) D was significantly lower in OSAS cases than matched, non-OSAS subjects (P = 0.001). Conclusions: We observed widespread vitamin D deficiency and insufficiency in a Caucasian, OSAS population. There were significant, independent, inverse relationships between 25(OH)D and AHI as well as nocturnal HR, a known cardiovascular risk factor. Further, 25(OH)D was significantly lower in OSAS cases compared to matched, non-OSAS subjects. We provide evidence that 25(OH)D and OSAS are related, but the role, if any, of replenishment has not been investigated