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

Culture of Oral Mucosal Epithelial Cells for the Purpose of Treating Limbal Stem Cell Deficiency

The cornea is critical for normal vision as it allows allowing light transmission to the retina. The corneal epithelium is renewed by limbal epithelial cells (LEC), which are located in the periphery of the cornea, the limbus. Damage or disease involving LEC may lead to various clinical presentations of limbal stem cell deficiency (LSCD). Both severe pain and blindness may result. Transplantation of cultured autologous oral mucosal epithelial cell sheet (CAOMECS) represents the first use of a cultured non-limbal autologous cell type to treat this disease. Among non-limbal cell types, CAOMECS and conjunctival epithelial cells are the only laboratory cultured cell sources that have been explored in humans. Thus far, the expression of p63 is the only predictor of clinical outcome following transplantation to correct LSCD. The optimal culture method and substrate for CAOMECS is not established. The present review focuses on cell culture methods, with particular emphasis on substrates. Most culture protocols for CAOMECS used amniotic membrane as a substrate and included the xenogeneic components fetal bovine serum and murine 3T3 fibroblasts. However, it has been demonstrated that tissue-engineered epithelial cell sheet grafts can be successfully fabricated using temperature-responsive culture surfaces and autologous serum. In the studies using different substrates for culture of CAOMECS, the quantitative expression of p63 was generally poorly reported; thus, more research is warranted with quantification of phenotypic data. Further research is required to develop a culture system for CAOMECS that mimics the natural environment of oral/limbal/corneal epithelial cells without the need for undefined foreign materials such as serum and feeder cells

Assessing gaming simulation validity for training traffic controllers.

Background. The Dutch railway company ProRail is performing large-scale capacity upgrades to their infrastructure network. As part of these upgrades, ProRail uses gaming simulations to help prepare train traffic controllers for new infrastructure situations. Researching the validity of these gaming simulations is essential, since the conclusions drawn from gaming simulation use may result in decisions with large financial and social impact for ProRail and Dutch train passengers. Aim. In this article, we aim to investigate the validity of the gaming simulations for training traffic controllers for new situations in rail infrastructure. We also aim to contribute to the discussion on the minimum level of fidelity required to develop and conduct gaming simulations in a valid way. Method. We investigate the validity by using training sessions in conjunction with questionnaires. We based the approach and questionnaires on the earlier work of Raser. Results. Our results show that the validity of the gaming simulation ranges from medium to good. They also show that while the fidelity of the gaming simulation is not like the real-world operating conditions, this does not reduce validity to low levels. Conclusions. We conclude that the gaming simulation used in this study was of medium to good validity. We also conclude that maximum fidelity is not required in order to run a valid gaming simulation session.Organisation and Governanc

Hybrid Ground Station Technology for RF and Optical Communication Links

To support future enhancements of NASA's deep space and planetary communications and tracking services, the Jet Propulsion Laboratory is developing a hybrid ground station that will be capable of simultaneously supporting RF and optical communications. The main reason for adding optical links to the existing RF links is to significantly increase the capacity of deep space communications in support of future solar system exploration. It is envisioned that a mission employing an optical link will also use an RF link for telemetry and emergency purposes, hence the need for a hybrid ground station. A hybrid station may also reduce operations cost by requiring fewer staff than would be required to operate two stations. A number of approaches and techniques have been examined. The most promising ones have been prototyped for field examination and validation

Hypothalamic prostaglandin E2 during lipopolysaccharide-induced fever in guinea pigs

Prostaglandin E2 (PGE2) is postulated to be a central mediator of fever. It is generally believed that it is produced in the preoptic area of the anterior hypothalamus (POA) because, among other evidence, its level increases both in the third ventricle and in the POA in response to pyrogens. However, lately, the question has arisen whether PGE2 might, in fact, be formed outside of the brain substance and then penetrate it, in particular through the organum vasculosum laminae terminalis. If produced outside the brain substance, the peripheral blockade of its synthesis should prevent lipopolysaccharides (LPS)-induced fever, whereas the intracarotid infusion of PGE2 should produce an increase in core temperature (Tc) as well as in preoptic PGE2. To verify this hypothesis, continuous measurements of Tc and preoptic PGE2 levels were made in conscious guinea pigs administered the PGE2 synthase inhibitor, indomethacin (10 or 50 mg/kg, im) 30 min before S. enteritidis LPS (2 μg/kg, iv) or before PGE2 microdialyzed into the POA (1 μg/μl at 2μl/min for 2.5 h) and during PGE2 infused into a carotid artery (1 μg and 10 μg/μl at 2 μl/min for 1 h). LPS induced a biphasic 1.4°C fever that was consistently associated with an increase in the level of PGE2 in the POA. Indomethacin at 10 mg/kg attenuated the course of the LPS-induced fever and prevented the associated increase in preoptic PGE2 for 90 min after fover onset; thereafter, PGE2 was significantly reduced by comparison with controls. Indomethacin at 50 mg/kg completely abolished both the fever and the increased levels of PGE2 in the POA; the fever induced by PGE2 microdialyzed into the POA was not affected by indomethacin pretreatment. The intracarotid infusion of PGE2 produced Tc falls and no increase in preoptic PGE2 levels. The indomethacin-induced blockade of fever and inhibition of the associated increase in preoptic PGE2 levels further substaintiates the presumptive link between PGE2 in the POA and fever caused by LPS. The failure of exogenous PGE2 infusion to induce increases in Tc and preoptic PGE2 levels excludes the possibility that PGE2 formed outside of the brain penetrates the POA and induces fever. Thus, in guinea pigs, the PGE2 associated with LPS-induced fever may be synthesized in the POA

Accumulation and removal of Streptococcus mutans biofilm on enamel and root surfaces in vitro

Objective: This study aimed to quantitatively investigate the accumulation of Streptococcus mutans biofilm on enamel and root surfaces and assess the amount of biofilm removal using (1) experimental toothpaste and (2) water, in a closed system of flow chamber. <p<Methods: Eight sound premolars were embedded in epoxy resin and polished with silicon carbide grinding papers to display enamel and root surfaces. To mimic biofilm, cultures of Streptococcus mutans were prepared and grown on the tooth surfaces over night before they were exposed to either 2 liters of Milli Q water or 2 liters of 40% experimental toothpaste in the flow chamber. The amount of biofilm was measured and quantified in Fluorescence microscopy. Mean fluorescence values were recorded and analysed using Microsoft® Excel® (MS Excel 2016). Results: The ability to grow biofilm was equally present at both the enamel and root surfaces. The use of water and 40% experimental toothpaste showed a significant reduction of areas covered with biofilm on both enamel and root dentin in comparison to untreated surfaces (p < 0.01). Significantly more biofilm was removed from enamel compared to root surfaces when treated with either water and toothpaste (p < 0.01). Slightly less biofilm was removed by the use of water compared to toothpaste on both enamel and root dentin surfaces, although the differences were not statistically significant. Conclusion: The results indicate that less biofilm is removed from the root surfaces than enamel by the use of water and 40% experimental toothpaste in flow chamber. Assessing oral biofilm accumulation and monitoring biofilm formation on enamel and root dentin surfaces give oral health professionals important directions that could strenghten the significance of dental caries prevention. Improving older individuals’ oral hygiene practices should therefore be considered an important measure to prevent root caries