Artificial intelligence-based software (AID-FOREST) for tree detection: A new framework for fast and accurate forest inventorying using LiDAR point clouds

Forest inventories are essential to accurately estimate different dendrometric and forest stand parameters. However, classical forest inventories are time consuming, slow to conduct, sometimes inaccurate and costly. To address this problem, an efficient alternative approach has been sought and designed that will make this type of field work cheaper, faster, more accurate, and easier to complete. The implementation of this concept has required the development of a specifically designed software called "Artificial Intelligence for Digital Forest (AID-FOREST)", which is able to process point clouds obtained via mobile terrestrial laser scanning (MTLS) and then, to provide an array of multiple useful and accurate dendrometric and forest stand parameters. Singular characteristics of this approach are: No data pre-processing is required either pre-treatment of forest stand; fully automatic process once launched; no limitations by the size of the point cloud file and fast computations.To validate AID-FOREST, results provided by this software were compared against the obtained from in-situ classical forest inventories. To guaranty the soundness and generality of the comparison, different tree spe-cies, plot sizes, and tree densities were measured and analysed. A total of 76 plots (10,887 trees) were selected to conduct both a classic forest inventory reference method and a MTLS (ZEB-HORIZON, Geoslam, ltd.) scanning to obtain point clouds for AID-FOREST processing, known as the MTLS-AIDFOREST method. Thus, we compared the data collected by both methods estimating the average number of trees and diameter at breast height (DBH) for each plot. Moreover, 71 additional individual trees were scanned with MTLS and processed by AID-FOREST and were then felled and divided into logs measuring 1 m in length. This allowed us to accurately measure the DBH, total height, and total volume of the stems.When we compared the results obtained with each methodology, the mean detectability was 97% and ranged from 81.3 to 100%, with a bias (underestimation by MTLS-AIDFOREST method) in the number of trees per plot of 2.8% and a relative root-mean-square error (RMSE) of 9.2%. Species, plot size, and tree density did not significantly affect detectability. However, this parameter was significantly affected by the ecosystem visual complexity index (EVCI). The average DBH per plot was underestimated (but was not significantly different from 0) by the MTLS-AIDFOREST, with the average bias for pooled data being 1.8% with a RMSE of 7.5%. Similarly, there was no statistically significant differences between the two distribution functions of the DBH at the 95.0% confidence level.Regarding the individual tree parameters, MTLS-AIDFOREST underestimated DBH by 0.16 % (RMSE = 5.2 %) and overestimated the stem volume (Vt) by 1.37 % (RMSE = 14.3 %, although the BIAS was not statistically significantly different from 0). However, the MTLS-AIDFOREST method overestimated the total height (Ht) of the trees by a mean 1.33 m (5.1 %; relative RMSE = 11.5 %), because of the different height concepts measured by both methodological approaches. Finally, AID-FOREST required 30 to 66 min per ha-1 to fully automatically process the point cloud data from the *.las file corresponding to a given hectare plot. Thus, applying our MTLS-AIDFOREST methodology to make full forest inventories, required a 57.3 % of the time required to perform classical plot forest inventories (excluding the data postprocessing time in the latter case). A free trial of AID -FOREST can be requested at [email protected]

Assigning protein function from domain-function associations using DomFun

Background: Protein function prediction remains a key challenge. Domain composition affects protein function. Here we present DomFun, a Ruby gem that uses associations between protein domains and functions, calculated using multiple indices based on tripartite network analysis. These domain-function associations are combined at the protein level, to generate protein-function predictions. Results: We analysed 16 tripartite networks connecting homologous superfamily and FunFam domains from CATH-Gene3D with functional annotations from the three Gene Ontology (GO) sub-ontologies, KEGG, and Reactome. We validated the results using the CAFA 3 benchmark platform for GO annotation, finding that out of the multiple association metrics and domain datasets tested, Simpson index for FunFam domain-function associations combined with Stouffer’s method leads to the best performance in almost all scenarios. We also found that using FunFams led to better performance than superfamilies, and better results were found for GO molecular function compared to GO biological process terms. DomFun performed as well as the highest-performing method in certain CAFA 3 evaluation procedures in terms of Fmax and Smin We also implemented our own benchmark procedure, Pathway Prediction Performance (PPP), which can be used to validate function prediction for additional annotations sources, such as KEGG and Reactome. Using PPP, we found similar results to those found with CAFA 3 for GO, moreover we found good performance for the other annotation sources. As with CAFA 3, Simpson index with Stouffer’s method led to the top performance in almost all scenarios. Conclusions: DomFun shows competitive performance with other methods evaluated in CAFA 3 when predicting proteins function with GO, although results vary depending on the evaluation procedure. Through our own benchmark procedure, PPP, we have shown it can also make accurate predictions for KEGG and Reactome. It performs best when using FunFams, combining Simpson index derived domain-function associations using Stouffer’s method. The tool has been implemented so that it can be easily adapted to incorporate other protein features, such as domain data from other sources, amino acid k-mers and motifs. The DomFun Ruby gem is available from https://rubygems.org/gems/DomFun. Code maintained at https://github.com/ElenaRojano/DomFun. Validation procedure scripts can be found at https://github.com/ElenaRojano/DomFun_project

Prevalence and clinical outcomes of dystrophin-associated dilated cardiomyopathy without severe skeletal myopathy

Aims: Dilated cardiomyopathy (DCM) associated with dystrophin gene (DMD) mutations in individuals with mild or absent skeletal myopathy is often indistinguishable from other DCM forms. We sought to describe the phenotype and prognosis of DMD associated DCM in DMD mutation carriers without severe skeletal myopathy. Methods and results: At 26 European centres, we retrospectively collected clinical characteristics and outcomes of 223 DMD mutation carriers (83% male, 33 ± 15 years). A total of 112 individuals (52%) had DCM at first evaluation [n = 85; left ventricular ejection fraction (LVEF) 34 ± 11.2%] or developed DCM (n = 27; LVEF 41.3 ± 7.5%) after a median follow-up of 96 months (interquartile range 5–311 months). DCM penetrance was 45% in carriers older than 40 years. DCM appeared earlier in males and was independent of the type of mutation, presence of skeletal myopathy, or elevated serum creatine kinase levels. Major adverse cardiac events (MACE) occurred in 22% individuals with DCM, 18% developed end-stage heart failure and 9% sudden cardiac death or equivalent. Skeletal myopathy was not associated with survival free of MACE in patients with DCM. Decreased LVEF and increased left ventricular end-diastolic diameter at baseline were associated with MACE. Individuals without DCM had favourable prognosis without MACE or death during follow-up. Conclusions: DMD-associated DCM without severe skeletal myopathy is characterized by incomplete penetrance but high risk of MACE, including progression to end-stage heart failure and ventricular arrhythmias. DCM onset is the major determinant of prognosis with similar survival regardless of the presence of skeletal myopathy

Immunosuppression in acutely decompensated cirrhosis is mediated by prostaglandin E-2

Liver disease is one of the leading causes of death worldwide1. Patients with cirrhosis display an increased predisposition to and mortality from infection due to multimodal defects in the innate immune system2,3,4; however, the causative mechanism has remained elusive. We present evidence that the cyclooxygenase (COX)-derived eicosanoid prostaglandin E2 (PGE2) drives cirrhosis-associated immunosuppression. We observed elevated circulating concentrations (more than seven times as high as in healthy volunteers) of PGE2 in patients with acute decompensation of cirrhosis. Plasma from these and patients with end-stage liver disease (ESLD) suppressed macrophage proinflammatory cytokine secretion and bacterial killing in vitro in a PGE2-dependent manner via the prostanoid type E receptor-2 (EP2), effects not seen with plasma from patients with stable cirrhosis (Child-Pugh score grade A). Albumin, which reduces PGE2 bioavailability, was decreased in the serum of patients with acute decompensation or ESLD (<30 mg/dl) and appears to have a role in modulating PGE2-mediated immune dysfunction. In vivo administration of human albumin solution to these patients significantly improved the plasma-induced impairment of macrophage proinflammatory cytokine production in vitro. Two mouse models of liver injury (bile duct ligation and carbon tetrachloride) also exhibited elevated PGE2, reduced circulating albumin concentrations and EP2-mediated immunosuppression. Treatment with COX inhibitors or albumin restored immune competence and survival following infection with group B Streptococcus. Taken together, human albumin solution infusions may be used to reduce circulating PGE2 levels, attenuating immune suppression and reducing the risk of infection in patients with acutely decompensated cirrhosis or ESLD

Clinical Phenotypes and Prognosis of Dilated Cardiomyopathy Caused by Truncating Variants in the TTN Gene

BACKGROUND: Truncating variants in the TTN gene (TTNtv) are the commonest cause of heritable dilated cardiomyopathy. This study aimed to study the phenotypes and outcomes of TTNtv carriers. METHODS: Five hundred thirty-seven individuals (61% men; 317 probands) with TTNtv were recruited in 14 centers (372 [69%] with baseline left ventricular systolic dysfunction [LVSD]). Baseline and longitudinal clinical data were obtained. The primary end point was a composite of malignant ventricular arrhythmia and end-stage heart failure. The secondary end point was left ventricular reverse remodeling (left ventricular ejection fraction increase by ≥10% or normalization to ≥50%). RESULTS: Median follow-up was 49 (18-105) months. Men developed LVSD more frequently and earlier than women (45±14 versus 49±16 years, respectively; P=0.04). By final evaluation, 31%, 45%, and 56% had atrial fibrillation, frequent ventricular ectopy, and nonsustained ventricular tachycardia, respectively. Seventy-six (14.2%) individuals reached the primary end point (52 [68%] end-stage heart failure events, 24 [32%] malignant ventricular arrhythmia events). Malignant ventricular arrhythmia end points most commonly occurred in patients with severe LVSD. Male sex (hazard ratio, 1.89 [95% CI, 1.04-3.44]; P=0.04) and left ventricular ejection fraction (per 10% decrement from left ventricular ejection fraction, 50%; hazard ratio, 1.63 [95% CI, 1.30-2.04]; P<0.001) were independent predictors of the primary end point. Two hundred seven of 300 (69%) patients with LVSD had evidence of left ventricular reverse remodeling. In a subgroup of 29 of 74 (39%) patients with initial left ventricular reverse remodeling, there was a subsequent left ventricular ejection fraction decrement. TTNtv location was not associated with statistically significant differences in baseline clinical characteristics, left ventricular reverse remodeling, or outcomes on multivariable analysis (P=0.07). CONCLUSIONS: TTNtv is characterized by frequent arrhythmia, but malignant ventricular arrhythmias are most commonly associated with severe LVSD. Male sex and LVSD are independent predictors of outcomes. Mutation location does not impact clinical phenotype or outcomes

A search for very young Planetary Nebulae

Despite numerous efforts, the transition from Asymptotic Giant Branch (AGB) stars to Planetary Nebulae (PN) is a poorly understood phase of stellar evolution. We have therefore carried out interferometric (VLA) radio observations of a sample of hot post-AGB stars, selected on the basis of their optical and infrared properties. Ten sources out of the 16 observed were detected. This indicates that most of our targets are surrounded by a nebula where the ionization has already started. This definitively determines the evolutionary status of the selected sources and provides us with a unique sample of very young Planetary Nebulae (yPNe). A comparison with another sample of yPNe confirms our working hypothesis that our targets are indeed very young, probably just in the transition toward PN. Finding transition objects is extremely important as they can provide unique clues for a better understanding of this important phase of stellar evolution.Comment: 10 pages, 6 figure

Genetic Variants Associated With Cancer Therapy-Induced Cardiomyopathy

BACKGROUND: Cancer therapy-induced cardiomyopathy (CCM) is associated with cumulative drug exposures and preexisting cardiovascular disorders. These parameters incompletely account for substantial interindividual susceptibility to CCM. We hypothesized that rare variants in cardiomyopathy genes contribute to CCM. METHODS: We studied 213 patients with CCM from 3 cohorts: retrospectively recruited adults with diverse cancers (n=99), prospectively phenotyped adults with breast cancer (n=73), and prospectively phenotyped children with acute myeloid leukemia (n=41). Cardiomyopathy genes, including 9 prespecified genes, were sequenced. The prevalence of rare variants was compared between CCM cohorts and The Cancer Genome Atlas participants (n=2053), healthy volunteers (n=445), and an ancestry-matched reference population. Clinical characteristics and outcomes were assessed and stratified by genotypes. A prevalent CCM genotype was modeled in anthracycline-treated mice. RESULTS: CCM was diagnosed 0.4 to 9 years after chemotherapy; 90% of these patients received anthracyclines. Adult patients with CCM had cardiovascular risk factors similar to the US population. Among 9 prioritized genes, patients with CCM had more rare protein-altering variants than comparative cohorts ( P≤1.98e-04). Titin-truncating variants (TTNtvs) predominated, occurring in 7.5% of patients with CCM versus 1.1% of The Cancer Genome Atlas participants ( P=7.36e-08), 0.7% of healthy volunteers ( P=3.42e-06), and 0.6% of the reference population ( P=5.87e-14). Adult patients who had CCM with TTNtvs experienced more heart failure and atrial fibrillation ( P=0.003) and impaired myocardial recovery ( P=0.03) than those without. Consistent with human data, anthracycline-treated TTNtv mice and isolated TTNtv cardiomyocytes showed sustained contractile dysfunction unlike wild-type ( P=0.0004 and P<0.002, respectively). CONCLUSIONS: Unrecognized rare variants in cardiomyopathy-associated genes, particularly TTNtvs, increased the risk for CCM in children and adults, and adverse cardiac events in adults. Genotype, along with cumulative chemotherapy dosage and traditional cardiovascular risk factors, improves the identification of patients who have cancer at highest risk for CCM. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifiers: NCT01173341; AAML1031; NCT01371981.This work was supported in part by grants from the Instituto de Salud Carlos III (ISCIII) (PI15/01551, PI17/01941 and CB16/11/00432 to P.G-P. and L.A-P.), the Spanish Ministry of Economy and Competitiveness (SAF2015-71863-REDT to P.G-P.), the John S. LaDue Memorial Fellowship at Harvard Medical School (Y.K.), Wellcome Trust (107469/Z/15/Z to J.S.W.), Medical Research Council (intramural awards to S.A.C. and J.S.W; MR/M003191/1 to U.T), National Institute for Health Research Biomedical Research Unit at the Royal Brompton and Harefield National Health Service Foundation Trust and Imperial College London (P.J.B., S.A.C., J.S.W.), National Institute for Health Research Biomedical Research Centre at Imperial College London Healthcare National Health Service Trust and Imperial College London (D.O.R., S.A.C., S.P., J.S.W.), Sir Henry Wellcome Postdoctoral Fellowship (C.N.T.), Rosetrees and Stoneygate Imperial College Research Fellowship (N.W.), Fondation Leducq (S.A.C., C.E.S., J.G.S.), Health Innovation Challenge Fund award from the Wellcome Trust and Department of Health (UK; HICF-R6-373; S.A.C., P.J.B., J.S. W.), the British Heart Foundation (NH/17/1/32725 to D.O.R.; SP/10/10/28431 to S.A.C), Alex’s Lemonade Stand Foundation (K.G.), National Institutes of Health (R.A.: U01CA097452, R01CA133881, and U01CA097452; Z.A.: R01 HL126797; B.K.: R01 HL118018 and K23-HL095661; J.G.S. and C.E.S.: 5R01HL080494, R01HL084553), and the Howard Hughes Medical Institute (C.E.S.). The Universitario Puerta de Hierro and Virgen de la Arrixaca Hospitals are members of the European Reference Network on Rare and Complex Diseases of the Heart (Guard-Heart; http://guard-heart.ern-net.eu). This publication includes independent research commissioned by the Health Innovation Challenge Fund (HICF), a parallel funding partnership between the Department of Health and Wellcome Trust. The Centro Nacional de Investigaciones Cardiovasculares (CNIC) is supported by the Ministry of Economy, Industry and Competitiveness and the Pro CNIC Foundation, and is a Severo Ochoa Center of Excellence (SEV-2015-0505). Grants from ISCIII and the Spanish Ministry of Economy and Competitiveness are supported by the Plan Estatal de I+D+I 2013-2016 – European Regional Development Fund (FEDER) “A way of making Europe”.S

Surgical treatment for colorectal cancer: Analysis of the influence of an enhanced recovery programme on long-term oncological outcomes-a study protocol for a prospective, multicentre, observational cohort study

Introduction The evidence currently available from enhanced recovery after surgery (ERAS) programmes concerns their benefits in the immediate postoperative period, but there is still very little evidence as to whether their correct implementation benefits patients in the long term. The working hypothesis here is that, due to the lower response to surgical aggression and lower rates of postoperative complications, ERAS protocols can reduce colorectal cancer-related mortality. The main objective of this study is to analyse the impact of an ERAS programme for colorectal cancer on 5-year survival. As secondary objectives, we propose to analyse the weight of each of the predefined items in the oncological results as well as the quality of life. Methods and analysis A multicentre prospective cohort study was conducted in patients older than 18 years of age who are scheduled to undergo surgery for colorectal cancer. The study involved 12 hospitals with an implemented enhanced recovery protocol according to the guidelines published by the Spanish National Health Service. The intervention group includes patients with a minimum implementation level of 70%, and the control group includes those who fail to reach this level. Compliance will be studied using 18 key performance indicators, and the results will be analysed using cancer survival indicators, including overall survival, cancer-specific survival and relapse-free survival. The time to recurrence, perioperative morbidity and mortality, hospital stay and quality of life will also be studied, the latter using the validated EuroQol Five questionnaire. The propensity index method will be used to create comparable treatment and control groups, and a multivariate regression will be used to study each variable. The Kaplan-Meier estimator will be used to estimate survival and the log-rank test to make comparisons. A p value of less than 0.05 (two-tailed) will be considered to be significant. Ethics and dissemination Ethical approval for this study was obtained from the Aragon Ethical Committee (C.P.-C.I. PI20/086) on 4 March 2020. The findings of this study will be submitted to peer-reviewed journals (BMJ Open, JAMA Surgery, Annals of Surgery, British Journal of Surgery). Abstracts will be submitted to relevant national and international meetings.The present research study was awarded a Ministerio de Ciencia e Innovación health research project grant (PI19/00291) from the Carlos III Institute of the Spanish National Health Service as part of the 2019 call for Strategic Action in Health