Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Genome Size Evolution and Dynamics in Iris, with Special Focus on the Section Oncocyclus

Insights into genome size dynamics and its evolutionary impact remain limited by the lack of data for many plant groups. One of these is the genus Iris, of which only 53 out of c. 260 species have available genome sizes. In this study, we estimated the C-values for 41 species and subspecies of Iris mainly from the Eastern Mediterranean region. We constructed a phylogenetic framework to shed light on the distribution of genome sizes across subgenera and sections of Iris. Finally, we tested evolutionary models to explore the mode and tempo of genome size evolution during the radiation of section Oncocyclus. Iris as a whole displayed a great variety of C-values; however, they were unequally distributed across the subgenera and sections, suggesting that lineage-specific patterns of genome size diversification have taken place within the genus. The evolutionary model that best fitted our data was the speciational model, as changes in genome size appeared to be mainly associated with speciation events. These results suggest that genome size dynamics may have contributed to the radiation of Oncocyclus irises. In addition, our phylogenetic analysis provided evidence that supports the segregation of the Lebanese population currently attributed to Iris persica as a distinct species

Caractérisation génétique du genre Iris évoluant dans la méditerranée orientale

The Iris genus belonging to the Iridaceae family includes over 220 species distributed throughout the Northern Hemisphere. The Oncocyclus section (Siems.) Baker is confined to the Southwest Asia and includes more than 65 species with a discussed taxonomic status.This study focuses on the Iris species complex evolving in the countries of the Eastern Mediterranean Region: Lebanon, Syria, Jordan, Palestine / Israel, Armenia, Turkey and Iran.The rate of endemism within this genus is relatively high. The overharvesting and the destruction of their habitats threaten many of its species.To clarify the taxonomic status of the species and to elucidate the phylogenetic relationships that connect them, several methods are used: the analysis of the genome size, the study of the karyotype, genome organization based on the ribosomal genes location and the study of genetic diversity and phylogeny based on nuclear and chloroplast molecular markers.Laboratory studies are complemented by field work to monitor the dynamics of Lebanon's endemic taxa for their preservation.In our study, the ITS regions, trnL-F and matK of all Lebanese irises and 20 Oncocylus irises of the East Mediterranean region were sequenced to construct phylogenetic trees. Both techniques FISH and Feulgen were applied to several Lebanese Oncocyclus species. Extensive cytogenetic studies have been conducted on all species of collected Iris taxa.Le genre Iris appartenant à la famille des Iridacées comprend plus de 220 espèces distribuées à travers l’hémisphère Nord. La section Oncocyclus (Siems.) Baker de ce genre est confinée au Sud-ouest de l’Asie et comprend plus de 65 espèces au statut taxonomique souvent discuté.La présente étude porte sur le complexe d’espèces d’Iris évoluant dans les pays de la Méditerranée orientale : Liban, Syrie, Jordanie, Palestine/Israël, Arménie, Turquie et Iran.Le taux d’endémisme au sein de ce genre est relativement élevé et la cueillette excessive ainsi que la destruction de leurs habitats menace un grand nombre de ces espèces.En vue de préciser le statut taxonomique des espèces et d’élucider les relations phylogénétiques qui les relient plusieurs méthodes sont employées : l’analyse de la taille du génome, l’étude du caryotype, l’organisation du génome basée sur la localisation des gènes ribosomiques et l’étude de la structuration de la diversité génétique et la phylogénie basée sur des marqueurs moléculaires nucléaires et chloroplastiques.Les études de laboratoires sont complétées par des travaux de terrain afin de suivre l’évolution de la dynamique des taxons endémiques du Liban en vue de leur préservation.Au cours de notre étude, les régions ITS, TrnL-F et matk de tous les iris du Liban et 20 Oncocylus de la région Est-Méditerranéenne ont été séquencées pour construire les arbres phylogénétiques. Les deux techniques FISH et Feulgen ont été appliquées sur plusieurs espèces Oncocyclus du Liban. Des études cytogénétiques approfondies ont été menées sur toutes les espèces d’Iris collectées

Genetic characterization of Iris genus evovlving in the East Mediterranean region

Le genre Iris appartenant à la famille des Iridacées comprend plus de 220 espèces distribuées à travers l’hémisphère Nord. La section Oncocyclus (Siems.) Baker de ce genre est confinée au Sud-ouest de l’Asie et comprend plus de 65 espèces au statut taxonomique souvent discuté.La présente étude porte sur le complexe d’espèces d’Iris évoluant dans les pays de la Méditerranée orientale : Liban, Syrie, Jordanie, Palestine/Israël, Arménie, Turquie et Iran.Le taux d’endémisme au sein de ce genre est relativement élevé et la cueillette excessive ainsi que la destruction de leurs habitats menace un grand nombre de ces espèces.En vue de préciser le statut taxonomique des espèces et d’élucider les relations phylogénétiques qui les relient plusieurs méthodes sont employées : l’analyse de la taille du génome, l’étude du caryotype, l’organisation du génome basée sur la localisation des gènes ribosomiques et l’étude de la structuration de la diversité génétique et la phylogénie basée sur des marqueurs moléculaires nucléaires et chloroplastiques.Les études de laboratoires sont complétées par des travaux de terrain afin de suivre l’évolution de la dynamique des taxons endémiques du Liban en vue de leur préservation.Au cours de notre étude, les régions ITS, TrnL-F et matk de tous les iris du Liban et 20 Oncocylus de la région Est-Méditerranéenne ont été séquencées pour construire les arbres phylogénétiques. Les deux techniques FISH et Feulgen ont été appliquées sur plusieurs espèces Oncocyclus du Liban. Des études cytogénétiques approfondies ont été menées sur toutes les espèces d’Iris collectées.The Iris genus belonging to the Iridaceae family includes over 220 species distributed throughout the Northern Hemisphere. The Oncocyclus section (Siems.) Baker is confined to the Southwest Asia and includes more than 65 species with a discussed taxonomic status.This study focuses on the Iris species complex evolving in the countries of the Eastern Mediterranean Region: Lebanon, Syria, Jordan, Palestine / Israel, Armenia, Turkey and Iran.The rate of endemism within this genus is relatively high. The overharvesting and the destruction of their habitats threaten many of its species.To clarify the taxonomic status of the species and to elucidate the phylogenetic relationships that connect them, several methods are used: the analysis of the genome size, the study of the karyotype, genome organization based on the ribosomal genes location and the study of genetic diversity and phylogeny based on nuclear and chloroplast molecular markers.Laboratory studies are complemented by field work to monitor the dynamics of Lebanon's endemic taxa for their preservation.In our study, the ITS regions, trnL-F and matK of all Lebanese irises and 20 Oncocylus irises of the East Mediterranean region were sequenced to construct phylogenetic trees. Both techniques FISH and Feulgen were applied to several Lebanese Oncocyclus species. Extensive cytogenetic studies have been conducted on all species of collected Iris taxa

Genome Size Evolution and Dynamics in Iris, with Special Focus on the Section Oncocyclus

Insights into genome size dynamics and its evolutionary impact remain limited by the lack of data for many plant groups. One of these is the genus Iris, of which only 53 out of c. 260 species have available genome sizes. In this study, we estimated the C-values for 41 species and subspecies of Iris mainly from the Eastern Mediterranean region. We constructed a phylogenetic framework to shed light on the distribution of genome sizes across subgenera and sections of Iris. Finally, we tested evolutionary models to explore the mode and tempo of genome size evolution during the radiation of section Oncocyclus. Iris as a whole displayed a great variety of C-values; however, they were unequally distributed across the subgenera and sections, suggesting that lineage-specific patterns of genome size diversification have taken place within the genus. The evolutionary model that best fitted our data was the speciational model, as changes in genome size appeared to be mainly associated with speciation events. These results suggest that genome size dynamics may have contributed to the radiation of Oncocyclus irises. In addition, our phylogenetic analysis provided evidence that supports the segregation of the Lebanese population currently attributed to Iris persica as a distinct species.This work was subsidised by the National Council for Scientific Research Lebanon under Grant [01-06-08] and the Research Council of Saint Joseph University under Grant FS 56. O.H. was supported by a Marie Skłodowska-Curie Action Individual Fellowship (grant agreement n°657918) and a Ramón y Cajal Fellowship (RYC-2016-21176).Peer reviewe

Unlocking the Karyological and Cytogenetic Diversity of Iris from Lebanon: Oncocyclus Section Shows a Distinctive Profile and Relative Stasis during Its Continental Radiation.

Despite being an important target of conservation concern and horticultural interest, Lebanese irises yet have a confusing taxonomic history and species' delimitation is often considered problematic, more especially among royal irises (Iris section Oncocyclus). Indeed, these irises of exceptionally large and spectacular flowers have radiated across Caucasus and eastern Mediterranean giving rise to a number of strict endemic taxa, many of them being considered under threat. Whilst efforts have mostly focused on clarifying the evolutionary relationships in the group based on morphological and molecular data, karyological and cytogenetic characters have been comparatively overlooked. In this study, we established for the first time the physical mapping of 35S rDNA loci and heterochromatin, and obtained karyo-morphological data for ten Lebanese Iris species belonging to four sections (Iris, Limniris, Oncocyclus and Scorpiris). Our results evidenced distinctive genomic profiles for each one of the sections, where Oncocyclus irises, while having the lowest chromosome numbers, exhibit both the highest number of 35S loci and CMA3+ sites. The continental radiation of royal irises has been accompanied by a relative karyological and cytogenetic stasis, even though some changes were observed regarding karyotype formula and asymmetry indexes. In addition to that, our results enabled taxonomic differentiation between I. germanica and I. mesopotamica-two taxa currently considered as synonyms-and highlighted the need for further studies on populations of I. persica and I. wallasiae in the Eastern Mediterranean Region

Diversity of Lebanese royal irises, illustrated by some of the studied taxa.

<p>A: <i>Iris sofarana</i> subsp. <i>sofarana</i>, B: <i>I</i>. <i>sofarana</i> subsp. <i>kasruwana</i>, C: <i>I</i>. <i>cedreti</i>, D: <i>I</i>. <i>westii</i>, E: <i>I</i>. <i>bismarckiana</i>, F: <i>I</i>. <i>lortetii</i>, G: <i>I</i>. <i>antilibanotica</i>. Photographs from M. Bou Dagher-Kharrat</p

Unlocking the Karyological and Cytogenetic Diversity of <i>Iris</i> from Lebanon: <i>Oncocyclus</i> Section Shows a Distinctive Profile and Relative Stasis during Its Continental Radiation - Fig 2

<p><b>Metaphase chromosome plates and Idiograms of <i>Iris</i> taxa A</b>–<b>K</b>: Metaphase chromosome plates of <i>Iris</i> taxa after double target FISH with 5S (green signals) and 18-26S rDNA (red signals) probes. C1 represents CMA staining (yellow signals). <b>A’</b>–<b>K’</b>: Idiograms with location of 5S (green) and 18-26S rDNA (red) rRNA genes. <b>A’</b>: <i>I</i>. <i>sofarana</i> subsp. <i>sofarana</i> (Falougha), <b>B’</b>: <i>I</i>. <i>sofarana</i> subsp. <i>sofarana</i> (Hazzerta) <b>C’</b>: <i>I</i>. <i>sofarana</i> subsp. <i>kasruwana</i>, <b>D’</b>: <i>I</i>. <i>cedreti</i>, <b>E’</b>: <i>I</i>. <i>westii</i>, <b>F’</b>: <i>I</i>. <i>bismarckiana</i>, <b>G’</b>: <i>I</i>. <i>lortetii</i>, <b>H’</b>: <i>I</i>. <i>antilibanotica</i>, <b>I’</b>: <i>I</i>. <i>persica</i>, <b>J’</b>: <i>I</i>. <i>unguicularis</i> var. <i>cretensis</i>, <b>K’</b>: <i>I</i>. <i>mesopotamica</i>. Scale bar 10 <i>μ</i>m.</p

Main data on karyotype features of investigated <i>Iris</i> taxa.

<p>Main data on karyotype features of investigated <i>Iris</i> taxa.</p

Synthesis of results concerning molecular cytogenetic approach of investigated <i>Iris</i> taxa.

<p>Synthesis of results concerning molecular cytogenetic approach of investigated <i>Iris</i> taxa.</p