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BACKGROUND The role of primary immunodeficiencies (PID) in susceptibility to sepsis remains unknown. It is unclear whether children with sepsis benefit from genetic investigations. We hypothesized that sepsis may represent the first manifestation of underlying PID. We applied whole-exome sequencing (WES) to a national cohort of children with sepsis to identify rare, predicted pathogenic variants in PID genes. METHODS Multicenter population-based prospective study including previously healthy children ≥28 days and less then 17 years admitted with blood culture-proven sepsis. Using a stringent variant filtering procedure, analysis of WES data was restricted to rare, predicted pathogenic variants in 240 PID genes for which increased susceptibility to bacterial infection has been reported. RESULTS 176 children presenting with 185 sepsis episodes underwent WES (median age 52 months, IQR 15.4-126.4). 41 unique predicted pathogenic PID variants (1 homozygous, 5 hemizygous, and 35 heterozygous) were found in 35/176 (20%) patients, including 3/176 (2%) patients carrying variants which were previously reported to lead to PID. The variants occurred in PID genes across all 8 PID categories as defined by the International Union of Immunological Societies. We did not observe a significant correlation between clinical or laboratory characteristics of patients and the presence or absence of PID variants. CONCLUSIONS Applying WES to a population-based cohort of previously healthy children with bacterial sepsis detected Variants of Uncertain Significance in PID genes in one out of five children. Future studies need to investigate the functional relevance of these variants to determine whether variants in PID genes contribute to pediatric sepsis susceptibility. © The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America.We applied whole genome sequencing to identify putative transmission clusters among clinical multidrug-resistant Escherichia coli sequence type 131-H30 isolates from 4 United States children's hospitals. Of 126 isolates, 17 were involved in 8 putative transmission clusters; 4 clusters showed evidence of healthcare-associated epidemiologic linkages. Geographic clustering analyses showed weak geographic clustering. © The Author(s) 2020. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.Few studies have examined how parasite impact is affected by host size. In a glasshouse experiment, we investigated the impact of the Australian native hemiparasitic vine, Cassytha pubescens, on a major invasive shrub, Ulex europaeus, of different sizes. Infected plants had significantly lower total, shoot and root biomass, but the parasite's impact was more severe on small than large hosts. When infected small but not large hosts had significantly lower nodule biomass. Irrespective of size, infection significantly decreased host shoot/root ratio, predawn and midday quantum yields, maximum electron transport rates and carbon isotope composition, and host nodule biomass g-1 root biomass significantly increased in response to infection. Infection did not affect host foliar nitrogen concentration or midday shoot water potential. Parasite biomass was significantly lower on small relative to large hosts, but was similar g-1 host total biomass. Parasite stem nitrogen, phosphorous and potassium concentration were significantly greater when C. pubescens was growing on small than large hosts. Our results clearly show that C. pubescens strongly decreases performance of this major invasive shrub, especially when hosts are small. This suggests that C. pubescens could be used most effectively as a native biocontrol when deployed on smaller hosts. © The Author(s) 2020. Published by Oxford University Press on behalf of the Society for Experimental Biology.CONTEXT Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is an autoimmune endocrinopathy with severe and unpredictable course. The impact of APECED on mortality has not been determined. OBJECTIVE To assess overall and cause-specific mortality of patients with APECED. DESIGN and Setting A follow-up study of Finnish patients with APECED in 1971-2018. Causes and dates of death were collected from Finnish registries. PATIENTS Ninety-one patients with APECED. MAIN OUTCOME MEASURE Overall and cause-specific standardized mortality ratios (SMRs) determined by comparing the observed numbers of death and those expected on the basis of respective population death rates in Finland. https://www.selleckchem.com/products/FK-506-(Tacrolimus).html RESULTS The overall disease mortality was significantly increased [29 deaths, SMR 11; 95% confidence interval (CI) 7.2-16; p less then 0.001]. The relative risk (SMR) was highest in the youngest age groups but the absolute excess risk was similar (about 10 per 10,000 person-years) in all age categories. The highest SMRs were seen for endocrine and metabolic diseases (SMR 570; 95% CI 270-1000; p less then 0.001) and for oral and esophageal malignancies (SMR 170; 95% CI 68-360; p less then 0.001). Mortality was also increased for infections, diseases of digestive system, alcohol-related deaths, and for accidents. Due to small number of cases we were unable to evaluate whether mortality was affected by disease severity. CONCLUSIONS Patients with APECED have significantly increased mortality in all age groups. Highest SMRs are found for causes that are directly related to APECED but also for infections. Increased alcohol- and accident-related deaths may be influenced by psychosocial factors. & Endocrine Society 2020. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.BACKGROUND Due to delays in vaccinations, diphtheria-tetanus-whole-cell-pertussis (DTP) is often given with or after measles vaccine (MV) - out of sequence. We reanalysed data from Matlab, Bangladesh, to examine how administration of MV and DTP out-of-sequence was associated with child survival. METHODS 36,650 children born between 1986 and 1999 were followed with registration of vaccinations and survival. Controlling for background factors using Cox proportional hazards models, survival was analysed between 9 and 24 months of age. We measured the mortality rate ratio (MRR) to compare vaccination groups. Oral polio vaccine (OPV) campaigns, which started in 1995, reduced the mortality rate and reduced the difference between vaccination groups. In the main analysis, we therefore censored for OPV campaigns; there were 151 non-accidents deaths before the OPV campaigns. RESULTS Compared with MV administered alone (MV-only), DTP administered with or after MV had MRR 2.20 (1.31-3.70), and DTP-only had MRR 1.78 (1.01-3.
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