Trace-elemental and multi-isotopic (Sr-Nd-Pb) discrimination of jade in the circum-Caribbean: Implications for pre-colonial inter-island exchange networks

Dense and strong, hydrothermal-metasomatic jadeitite and jadeite-omphacite rocks were used as tools and adornments throughout the wider Caribbean since initial inhabitation. Regionally, rich sources of jadeitite and jadeite-omphacite jade are known only in Guatemala (north and south of the Motagua Fault Zone), eastern Cuba and the northern Dominican Republic, establishing that humans transported jadeitic material over vast distances. This study validates that geochemical fingerprinting is a viable provenance method for Caribbean pre-colonial jadeitic lithologies. An assemblage of 101 source rocks has been characterised for trace element and combined Sr-Nd-Pb isotope compositions. Four statistical approaches (Principal Component Analysis, t-Distributed Stochastic Neighbour Embedding, Decision Tree, and Multiclass Regression) were assessed, employing source-distinct trace element ratios. A multiclass regression technique based on trace element ratios of immobile high field strength, light to medium rare earth and fluid-mobile, large-ion-lithophile elements is shown to be most effective in discriminating the four source regions. Ninety-one % of the Guatemalan samples can be discriminated from the Dominican and Cuban sources using La/Th, Zr/Hf and Y/Th ratios. Jadeitic rocks cropping out in the Dominican Republic can be distinguished from Cuban jades employing Er/Yb, Nb/Ta and Ba/Rb ratios with 71% certainty. Furthermore, the two Guatemala sources, north and south of the Motagua Fault Zone, can be discriminated by using (among others) Zr/Hf, Ta/Th, La/Sm and Dy/Y ratios with an 89% success rate. This raises the possibility of determining, in detail, former trading and mobility networks between different islands and the Meso- and Central American mainland within the Greater Caribbean. The provenance technique was applied to 19 pre-colonial jade celts excavated from the Late Ceramic Age Playa Grande archaeological site in the northern Dominican Republic. Three artefacts are discriminated as derived from the Guatemalan source, indicating that, despite a source of jade within 25 km, material was traded from Guatemala. The presence of Guatemalan jade in the Playa Grande lithic assemblage provides further evidence of large scale (>3000 km), regional trading and indigenous knowledge transfer networks.This research received funding from the European Research Council under the European Union’s Seventh Framework Programme (FP7/2007–2013)/ERC grant agreement No 319209 (ERC-Synergy NEXUS 1492) and the European Union’s Horizon 2020 research and innovation programme under grant agreement No 654208 (Europlanet 2020 RI). We are grateful to the Museo del Hombre Dominicano for providing the Playa Grande samples. Thanks to Richard Smeets, Bas van der Wagt, Kirsten van Zuilen, Bouke Lacet, Eva Kelderman and Quinty Boosten for analytical assistance

Variants in the fetal genome near FLT1 are associated with risk of preeclampsia.

: Preeclampsia, which affects approximately 5% of pregnancies, is a leading cause of maternal and perinatal death. The causes of preeclampsia remain unclear, but there is evidence for inherited susceptibility. Genome-wide association studies (GWAS) have not identified maternal sequence variants of genome-wide significance that replicate in independent data sets. We report the first GWAS of offspring from preeclamptic pregnancies and discovery of the first genome-wide significant susceptibility locus (rs4769613; P = 5.4 × 10(-11)) in 4,380 cases and 310,238 controls. This locus is near the FLT1 gene encoding Fms-like tyrosine kinase 1, providing biological support, as a placental isoform of this protein (sFlt-1) is implicated in the pathology of preeclampsia. The association was strongest in offspring from pregnancies in which preeclampsia developed during late gestation and offspring birth weights exceeded the tenth centile. An additional nearby variant, rs12050029, associated with preeclampsia independently of rs4769613. The newly discovered locus may enhance understanding of the pathophysiology of preeclampsia and its subtypes.<br/

Utilization of antenatal ultrasound scan and implications for caesarean section: a cross-sectional study in rural Eastern China

<p>Abstract</p> <p>Background</p> <p>Antenatal ultrasound scan is a widely accepted component of antenatal care. Studies have looked at the relationship between ultrasound scanning and caesarean section (CS) in certain groups of women in China. However, there are limited data on the utilization of antenatal ultrasound scanning in the general population, including its association with CS. The purpose of this study is to describe the utilization of antenatal ultrasound screening in rural Eastern China and to explore the association between antenatal ultrasound scan and uptake of CS.</p> <p>Methods</p> <p>Based on a cluster randomized sample, a total of 2326 women with childbirth participated in the study. A household survey was conducted to collect socio-economic information, obstetric history and utilization of maternal health services.</p> <p>Results</p> <p>Coverage of antenatal care was 96.8% (2251/2326). During antenatal care, 96.1% (2164/2251) women received ultrasound screening and the reported average number was 2.55. 46.8% women received at least 3 ultrasound scans and the maximum number reached 11. The CS rate was found to be 54.8% (1275/2326). After adjusting for socio-demographic and clinical variables, it showed a statistically significant association between antenatal ultrasound scans and uptake of CS by multivariate logistic regression model. High husband education level, high maternal age, having previous adverse pregnant outcome and pregnancy complications during the index pregnancy were also found to be risk factors of choosing a CS.</p> <p>Conclusions</p> <p>A high use of antenatal ultrasound scan in rural Eastern China is found and is influenced by socio-demographic and clinical factors. Evidence-based guidelines for antenatal ultrasound scans need to be developed and disseminated to clinicians including physicians, nurses and sonographers. Guidance about the appropriate use of ultrasound scans should also be shared with women in order to discourage unreasonable expectations and demands. It is important to monitor the use of antenatal ultrasound scan as well as the indications for caesarean section in rural China.</p

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

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 middle-income 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 low-income 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 low-income, 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

Effects of antibiotic resistance, drug target attainment, bacterial pathogenicity and virulence, and antibiotic access and affordability on outcomes in neonatal sepsis: an international microbiology and drug evaluation prospective substudy (BARNARDS)

Background Sepsis is a major contributor to neonatal mortality, particularly in low-income and middle-income countries (LMICs). WHO advocates ampicillin–gentamicin as first-line therapy for the management of neonatal sepsis. In the BARNARDS observational cohort study of neonatal sepsis and antimicrobial resistance in LMICs, common sepsis pathogens were characterised via whole genome sequencing (WGS) and antimicrobial resistance profiles. In this substudy of BARNARDS, we aimed to assess the use and efficacy of empirical antibiotic therapies commonly used in LMICs for neonatal sepsis. Methods In BARNARDS, consenting mother–neonates aged 0–60 days dyads were enrolled on delivery or neonatal presentation with suspected sepsis at 12 BARNARDS clinical sites in Bangladesh, Ethiopia, India, Pakistan, Nigeria, Rwanda, and South Africa. Stillborn babies were excluded from the study. Blood samples were collected from neonates presenting with clinical signs of sepsis, and WGS and minimum inhibitory concentrations for antibiotic treatment were determined for bacterial isolates from culture-confirmed sepsis. Neonatal outcome data were collected following enrolment until 60 days of life. Antibiotic usage and neonatal outcome data were assessed. Survival analyses were adjusted to take into account potential clinical confounding variables related to the birth and pathogen. Additionally, resistance profiles, pharmacokinetic–pharmacodynamic probability of target attainment, and frequency of resistance (ie, resistance defined by in-vitro growth of isolates when challenged by antibiotics) were assessed. Questionnaires on health structures and antibiotic costs evaluated accessibility and affordability. Findings Between Nov 12, 2015, and Feb 1, 2018, 36 285 neonates were enrolled into the main BARNARDS study, of whom 9874 had clinically diagnosed sepsis and 5749 had available antibiotic data. The four most commonly prescribed antibiotic combinations given to 4451 neonates (77·42%) of 5749 were ampicillin–gentamicin, ceftazidime–amikacin, piperacillin–tazobactam–amikacin, and amoxicillin clavulanate–amikacin. This dataset assessed 476 prescriptions for 442 neonates treated with one of these antibiotic combinations with WGS data (all BARNARDS countries were represented in this subset except India). Multiple pathogens were isolated, totalling 457 isolates. Reported mortality was lower for neonates treated with ceftazidime–amikacin than for neonates treated with ampicillin–gentamicin (hazard ratio [adjusted for clinical variables considered potential confounders to outcomes] 0·32, 95% CI 0·14–0·72; p=0·0060). Of 390 Gram-negative isolates, 379 (97·2%) were resistant to ampicillin and 274 (70·3%) were resistant to gentamicin. Susceptibility of Gram-negative isolates to at least one antibiotic in a treatment combination was noted in 111 (28·5%) to ampicillin–gentamicin; 286 (73·3%) to amoxicillin clavulanate–amikacin; 301 (77·2%) to ceftazidime–amikacin; and 312 (80·0%) to piperacillin–tazobactam–amikacin. A probability of target attainment of 80% or more was noted in 26 neonates (33·7% [SD 0·59]) of 78 with ampicillin–gentamicin; 15 (68·0% [3·84]) of 27 with amoxicillin clavulanate–amikacin; 93 (92·7% [0·24]) of 109 with ceftazidime–amikacin; and 70 (85·3% [0·47]) of 76 with piperacillin–tazobactam–amikacin. However, antibiotic and country effects could not be distinguished. Frequency of resistance was recorded most frequently with fosfomycin (in 78 isolates [68·4%] of 114), followed by colistin (55 isolates [57·3%] of 96), and gentamicin (62 isolates [53·0%] of 117). Sites in six of the seven countries (excluding South Africa) stated that the cost of antibiotics would influence treatment of neonatal sepsis

26th Annual Computational Neuroscience Meeting (CNS*2017): Part 3 - Meeting Abstracts - Antwerp, Belgium. 15–20 July 2017

This work was produced as part of the activities of FAPESP Research,\ud Disseminations and Innovation Center for Neuromathematics (grant\ud 2013/07699-0, S. Paulo Research Foundation). NLK is supported by a\ud FAPESP postdoctoral fellowship (grant 2016/03855-5). ACR is partially\ud supported by a CNPq fellowship (grant 306251/2014-0)