Growth kinetics of nuclei formed from different binders and powders in vertical cylindrical mixing devices

peer-reviewedGranulation is the process of forming large aggregates from fine particles using a high shear mixer. This method is used in several industries from pharmaceuticals to chemical and fertilizer production. This research will study the effect of four process variables: speed of mixer rotation in the range 100–200 rpm, powder bed mass (25–40 g), mass of the initial nucleus (0.6–2 g), and binder viscosity (water, carboxymethyl cellulose (CMC) solutions with concentrations in the range 0.5–20 g/L) on single nuclei growth kinetics in low mixing devices. The powders under study were: lactose, tea, sugar, starch, and limestone. The results show the initial size of nuclei, the initial mass of the powder bed and binder viscosity and speed of rotation all influence the rate of nuclei growth. Analysis of the stokes deformation number of the nuclei show that growth rate of the nuclei decreases as the deformation number increases whilst the percentage gain in mass of the nuclei increases with increasing deformation number. The binder viscosity was shown to have the biggest influence of the growth rate of the nuclei. Results show that difference in powder density also has an effect on the growth kinetics of nuclei. The initial position of nuclei was also shown to influence the nuclei growth rate; the closer the starting position of the nuclei to the wall of the vessel the slower the growth rate

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

Growth kinetics of nuclei formed from different binders and powders in vertical cylindrical mixing devices

Granulation is the process of forming large aggregates from fine particles using a high shear mixer. This method is used in several industries from pharmaceuticals to chemical and fertilizer production. This research will study the effect of four process variables: speed of mixer rotation in the range 100–200 rpm, powder bed mass (25–40 g), mass of the initial nucleus (0.6–2 g), and binder viscosity (water, carboxymethyl cellulose (CMC) solutions with concentrations in the range 0.5–20 g/L) on single nuclei growth kinetics in low mixing devices. The powders under study were: lactose, tea, sugar, starch, and limestone. The results show the initial size of nuclei, the initial mass of the powder bed and binder viscosity and speed of rotation all influence the rate of nuclei growth. Analysis of the stokes deformation number of the nuclei show that growth rate of the nuclei decreases as the deformation number increases whilst the percentage gain in mass of the nuclei increases with increasing deformation number. The binder viscosity was shown to have the biggest influence of the growth rate of the nuclei. Results show that difference in powder density also has an effect on the growth kinetics of nuclei. The initial position of nuclei was also shown to influence the nuclei growth rate; the closer the starting position of the nuclei to the wall of the vessel the slower the growth rate

Thermal and mechanical properties of epoxy resin reinforced with modified iron oxide nanoparticles

Epoxy polymers, having good mechanical properties and thermal stability, are often used for engineering applications. Their properties can be further enhanced by the addition of iron oxide (Fe3O4) nanoparticles (NPs) as fillers to the resin. In this study, pristine Fe3O4 NPs were functionalized with polydopamine (PDA), (3-glycidoxypropyl)trimethoxysilane (GPTMS), and (3-aminopropyl)trimethoxysilane (APTES). X-ray diffraction and scanning electron microscopy (SEM) were used to study any changes in the crystal structure and size of the NPs while Fourier-Transform Infrared Spectroscopy (FTIR) and Thermogravimetric Analysis (TGA) were used to ensure the presence of functional groups on the surface. The mechanical properties of the Fe3O4-based nanocomposites generally improved except when reinforced with Fe3O4/PDA. The maximum improvement in tensile strength (∼34%) and fracture toughness (∼13%) were observed for pristine Fe3O4-based nanocomposites. Dynamic mechanical analysis (DMA) showed that the use of any of the treated NPs improved the material's initial storage modulus and had a substantial impact on its dissipation potential. Also, it was observed that the glass transition temperature measurements by DMA and differential scanning calorimetry were below that of pure epoxy. SEM of the cracked surfaces shows that the incorporation of any NPs leads to an enhancement in its thermal and mechanical properties.Peer reviewe

Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19

BackgroundWe previously reported that impaired type I IFN activity, due to inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity or to autoantibodies against type I IFN, account for 15-20% of cases of life-threatening COVID-19 in unvaccinated patients. Therefore, the determinants of life-threatening COVID-19 remain to be identified in similar to 80% of cases.MethodsWe report here a genome-wide rare variant burden association analysis in 3269 unvaccinated patients with life-threatening COVID-19, and 1373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. Among the 928 patients tested for autoantibodies against type I IFN, a quarter (234) were positive and were excluded.ResultsNo gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants was TLR7, with an OR of 27.68 (95%CI 1.5-528.7, P=1.1x10(-4)) for biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR=3.70[95%CI 1.3-8.2], P=2.1x10(-4)). This enrichment was further strengthened by (1) adding the recently reported TYK2 and TLR7 COVID-19 loci, particularly under a recessive model (OR=19.65[95%CI 2.1-2635.4], P=3.4x10(-3)), and (2) considering as pLOF branchpoint variants with potentially strong impacts on splicing among the 15 loci (OR=4.40[9%CI 2.3-8.4], P=7.7x10(-8)). Finally, the patients with pLOF/bLOF variants at these 15 loci were significantly younger (mean age [SD]=43.3 [20.3] years) than the other patients (56.0 [17.3] years; P=1.68x10(-5)).ConclusionsRare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60 years old