24 research outputs found

    Determinants of penetrance and variable expressivity in monogenic metabolic conditions across 77,184 exomes

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    Penetrance of variants in monogenic disease and clinical utility of common polygenic variation has not been well explored on a large-scale. Here, the authors use exome sequencing data from 77,184 individuals to generate penetrance estimates and assess the utility of polygenic variation in risk prediction of monogenic variants

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

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    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

    Root biomass and production of mangroves surrounding a karstic oligotrophic coastal lagoon

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    Root production influences a range of belowground processes, such as soil accretion, carbon sequestration and nutrient acquisition. Here, we measured biomass and root production of mangroves surrounding a karstic oligotrophic lagoon that spans a nutrient and salinity gradient. We also measured forest structure and soil physicochemical conditions (salinity, bulk density, carbon, nitrogen (N) and phosphorus (P)) in order to determine factors associated with root production. We tested the following hypotheses: 1) root biomass and production increase at low soil P and N in order to maximize resource utilization, and 2) root biomass and production increase with high interstitial salinity. Root biomass (947- 3,040 g m) and production (0.46-1.85 g m day-1) increased where soil P and interstitial salinity were relatively high. Thus, we rejected the first hypothesis and confirmed the second. The larger root fraction (5-20 mm) was the major contributor to root biomass and production. Our findings suggest that root production and thus capacity for belowground carbon storage in karstic regions, where P is often limiting, is greater where interstitial salinity and P are higher. This contrasts with past assessments indicating that Pdeficiency stimulates root growth, suggesting wide variation in belowground responses in mangroves

    Carbon stocks of tropical coastal wetlands within the karstic landscape of the Mexican Caribbean.

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    Coastal wetlands can have exceptionally large carbon (C) stocks and their protection and restoration would constitute an effective mitigation strategy to climate change. Inclusion of coastal ecosystems in mitigation strategies requires quantification of carbon stocks in order to calculate emissions or sequestration through time. In this study, we quantified the ecosystem C stocks of coastal wetlands of the Sian Ka'an Biosphere Reserve (SKBR) in the Yucatan Peninsula, Mexico. We stratified the SKBR into different vegetation types (tall, medium and dwarf mangroves, and marshes), and examined relationships of environmental variables with C stocks. At nine sites within SKBR, we quantified ecosystem C stocks through measurement of above and belowground biomass, downed wood, and soil C. Additionally, we measured nitrogen (N) and phosphorus (P) from the soil and interstitial salinity. Tall mangroves had the highest C stocks (987±338 Mg ha(-1)) followed by medium mangroves (623±41 Mg ha(-1)), dwarf mangroves (381±52 Mg ha(-1)) and marshes (177±73 Mg ha(-1)). At all sites, soil C comprised the majority of the ecosystem C stocks (78-99%). Highest C stocks were measured in soils that were relatively low in salinity, high in P and low in N∶P, suggesting that P limits C sequestration and accumulation potential. In this karstic area, coastal wetlands, especially mangroves, are important C stocks. At the landscape scale, the coastal wetlands of Sian Ka'an covering ≈172,176 ha may store 43.2 to 58.0 million Mg of C

    Ecosystem C stocks of coastal wetlands of Sian Ka'an Biosphere Reserve.

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    <p>The stocks are partitioned by A) aboveground (trees and down wood) and B) belowground (roots and soil) components. Lower case letters represent significant differences among sites and vegetation types (<i>n</i> = 6 per site, <i>p</i>≀0.0001). Note different scales between panel A and B.</p

    Relationship among mangrove C stocks, interstitial salinity and surface soil phosphorus.

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    <p>Seven mangrove sites were sampled within Sian Ka'an Biosphere Reserve, Mexico; three dwarf, two medium, and two tall mangroves, one of the latter associated to a fresh water spring. Soil phosphorus (P) was measured in the 0–15 cm soil horizon. The correlations are significant with <i>R</i><sup>2</sup> = 0.54, <i>F</i> = 31.3, <i>p</i><0.0001 and <i>R</i><sup>2</sup> = 0.58, <i>F</i> = 26.3, <i>p</i><0.001 for C stocks against salinity and soil P, respectively. Collectively, salinity and soil P explained 86% of the variance in mangrove C stocks (<i>F</i> = 45.6, <i>p</i><0.001; VIF = 2.2).</p

    Aboveground biomass, belowground biomass and total C stocks in vegetation (Mg ha<sup>−1</sup>).

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    <p>Data are mean (standard error).</p><p>Nine sites were sampled (<i>n</i> = 6 plots per site) within coastal wetlands of Sian Ka'an Biosphere Reserve, Mexico. Values are shown as mean (standard error); n.a. = not available.</p>*<p>aboveground biomass of marsh.</p>**<p>aboveground biomass of marsh plus mangrove trees.</p>***<p>belowground biomass of mangrove trees.</p

    Biomass (Mg ha<sup>−1</sup>) and C stocks (Mg ha<sup>−1</sup>) of downed wood for tall and medium mangroves.

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    <p>Sites were sampled within Sian Ka'an Biosphere Reserve, Mexico. Wood debris was calculated separately for small wood (diameter >2.5 and <7.5 cm), and large sound and large rotten wood (diameter >7.5 cm). Values are shown as mean (standard error).</p
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