Association of single nucleotide polymorphisms in the CFH, ARMS2 and HTRA1 genes with risk of developing age related macular degeneration in Egyptian patients

Age related macular degeneration (AMD) is one of the leading causes of blindness in the elderly worldwide. Due to earlier clinical observations that AMD concentrates in families, a genetic component to the disease has been suggested. Several genetic studies have identified areas of association with AMD on chromosomes 1q31 and 10q26. On chromosome 1q31 the most famous single nucleotide polymorphism (SNP) to be linked to AMD was rs1061170 on the complement factor H gene (CFH). This SNP was studied in several populations and was found to be highly associated with AMD in most Caucasian populations with odds Ratio (OR) reaching 9.79 for CC homozygous and 4.36 for CT heterozygous in some cases. However in Japan, China, Korea and South Africa no or weak association was found. Other SNPs on chromosome 10q26 were also associated with AMD. SNP rs10490924 (Ala69Ser) on the age related maculopathy susceptibility 2 gene (ARMS2) was associated with AMD in the USA, Germany, China, Turkey and India with OR values reaching 8.61 for homozygotes. On the HTRA1 (HtrA serine peptidase 1) gene rs11200638 was associated with AMD in China, India and the USA with OR reaching up to 7.9 for individuals homozygous for the risk allele. Due to varying results of association in different populations we aimed to examine the association between AMD and SNPs on CFH, ARMS2 and HTRA1 in Egyptian patients, a previously unstudied population. We recruited 26 individuals diagnosed with AMD and twenty unrelated age matched controls. Genotyping was carried out through polymerase chain reaction (PCR) followed by allele-specific restriction digestion and direct sequencing for some cases. We found all three SNPs to be significantly associated with AMD. For rs1061170 the OR for heterozygous TC genotype was 5.5 (95% CI: 1.145-26.412). While for the combined TC+CC genotypes the OR was 8 (95% CI: 1.726-37.090). Similarly, for rs10490924 the OR for heterozygous TG genotype was 4.667 (95% CI: 1.187-18.352) and for the combined TG+TT genotypes it was 7 (95% CI: 1.852-26.461). In HTRA1 rs11200638 OR for GA genotype was 5 (95% CI: 1.195-20.922) and for combined GA+AA genotypes it was 6 (95% CI: 1.456-24.733). We conclude that our study results indicate a trend of association between the three polymorphisms studied and AMD in agreement with findings in Caucasian populations

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements

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