Survival, by birth weight and gestational age, in individuals with congenital heart disease: a population-based study

BACKGROUND: Congenital heart disease (CHD) survival estimates are important to understand prognosis and evaluate health and social care needs. Few studies have reported CHD survival estimates according to maternal and fetal characteristics. This study aimed to identify predictors of CHD survival and report conditional survival estimates. METHODS AND RESULTS: Cases of CHD (n=5070) born during 1985–2003 and notified to the Northern Congenital Abnormality Survey (NorCAS) were matched to national mortality information in 2008. Royston–Parmar regression was performed to identify predictors of survival. Five‐year survival estimates conditional on gestational age at delivery, birth weight, and year of birth were produced for isolated CHD (ie, CHD without extracardiac anomalies). Year of birth, gestational age, birth weight, and extracardiac anomalies were independently associated with mortality (all P≤0.001). Five‐year survival for children born at term (37–41 weeks) in 2003 with average birth weight (within 1 SD of the mean) was 96.3% (95% CI, 95.6–97.0). Survival was most optimistic for high‐birth‐weight children (>1 SD from the mean) born post‐term (≥42 weeks; 97.9%; 95% CI, 96.8–99.1%) and least optimistic for very preterm (<32 weeks) low‐birth‐weight (<1 SD from mean) children (78.8%; 95% CI, 72.8–99.1). CONCLUSIONS: Five‐year CHD survival is highly influenced by gestational age and birth weight. For prenatal counseling, conditional survival estimates provide best‐ and worst‐case scenarios, depending on final gestational age and birth weight. For postnatal diagnoses, they can provide parents with more‐accurate predictions based on their baby's birth weight and gestational age

Long-term survival of children born with congenital anomalies: A systematic review and meta-analysis of population-based studies.

BACKGROUND: Following a reduction in global child mortality due to communicable diseases, the relative contribution of congenital anomalies to child mortality is increasing. Although infant survival of children born with congenital anomalies has improved for many anomaly types in recent decades, there is less evidence on survival beyond infancy. We aimed to systematically review, summarise, and quantify the existing population-based data on long-term survival of individuals born with specific major congenital anomalies and examine the factors associated with survival. METHODS AND FINDINGS: Seven electronic databases (Medline, Embase, Scopus, PsycINFO, CINAHL, ProQuest Natural, and Biological Science Collections), reference lists, and citations of the included articles for studies published 1 January 1995 to 30 April 2020 were searched. Screening for eligibility, data extraction, and quality appraisal were performed in duplicate. We included original population-based studies that reported long-term survival (beyond 1 year of life) of children born with a major congenital anomaly with the follow-up starting from birth that were published in the English language as peer-reviewed papers. Studies on congenital heart defects (CHDs) were excluded because of a recent systematic review of population-based studies of CHD survival. Meta-analysis was performed to pool survival estimates, accounting for trends over time. Of 10,888 identified articles, 55 (n = 367,801 live births) met the inclusion criteria and were summarised narratively, 41 studies (n = 54,676) investigating eight congenital anomaly types (spina bifida [n = 7,422], encephalocele [n = 1,562], oesophageal atresia [n = 6,303], biliary atresia [n = 3,877], diaphragmatic hernia [n = 6,176], gastroschisis [n = 4,845], Down syndrome by presence of CHD [n = 22,317], and trisomy 18 [n = 2,174]) were included in the meta-analysis. These studies covered birth years from 1970 to 2015. Survival for children with spina bifida, oesophageal atresia, biliary atresia, diaphragmatic hernia, gastroschisis, and Down syndrome with an associated CHD has significantly improved over time, with the pooled odds ratios (ORs) of surviving per 10-year increase in birth year being OR = 1.34 (95% confidence interval [95% CI] 1.24-1.46), OR = 1.50 (95% CI 1.38-1.62), OR = 1.62 (95% CI 1.28-2.05), OR = 1.57 (95% CI 1.37-1.81), OR = 1.24 (95% CI 1.02-1.5), and OR = 1.99 (95% CI 1.67-2.37), respectively (p < 0.001 for all, except for gastroschisis [p = 0.029]). There was no observed improvement for children with encephalocele (OR = 0.98, 95% CI 0.95-1.01, p = 0.19) and children with biliary atresia surviving with native liver (OR = 0.96, 95% CI 0.88-1.03, p = 0.26). The presence of additional structural anomalies, low birth weight, and earlier year of birth were the most commonly reported predictors of reduced survival for any congenital anomaly type. The main limitation of the meta-analysis was the small number of studies and the small size of the cohorts, which limited the predictive capabilities of the models resulting in wide confidence intervals. CONCLUSIONS: This systematic review and meta-analysis summarises estimates of long-term survival associated with major congenital anomalies. We report a significant improvement in survival of children with specific congenital anomalies over the last few decades and predict survival estimates up to 20 years of age for those born in 2020. This information is important for the planning and delivery of specialised medical, social, and education services and for counselling affected families. This trial was registered on the PROSPERO database (CRD42017074675)

Nondestructive 3D Imaging and Quantification of Hydrated Biofilm-Sediment Aggregates Using X-ray Microcomputed Tomography.

Biofilm-sediment aggregate (BSA) contains a high water content, either within internal pores and channels or bound by extracellular polymeric substances (EPS) forming a highly hydrated biofilm matrix. Desiccation of BSAs alters the biofilm morphology and thus the physical characteristics of porous media, such as the binding matrix within BSA and internal pore geometry. Observing BSAs in their naturally hydrated form is essential but hampered due to the lack of techniques for imaging and discerning hydrated materials. Generally, imagery techniques (scanning electron microscopy (SEM), transmission electron microscopy (TEM), and focused ion beam nanotomography (FIB-nt)) involve the desiccation of BSAs (freeze-drying or acetone dehydration) or prevent differentiation between BSA components such as inorganic particles and pore water (confocal laser scanning microscopic (CLSM)). Here, we propose a novel methodology that simultaneously achieves the 3D visualization and quantification of BSAs and their components in their hydrated form at a submicron resolution using X-ray microcomputed tomography (μ-CT). It enables the high-resolution detection of comparable morphology of multiphase components within a hydrated aggregate: each single inorganic particle and the hydrated biofilm matrix. This allows the estimation of aggregate density and the illustration of biofilm-sediment binding matrix. This information provides valuable insights into investigations of the transport of BSAs and aggregate-associated sediment particles, contaminants (such as microplastics), organic carbon, and their impacts on aquatic biogeochemical cycling

Cooperative secretions facilitate host range expansion in bacteria

The majority of emergent human pathogens are zoonotic in origin, that is, they can transmit to humans from other animals. Understanding the factors underlying the evolution of pathogen host range is therefore of critical importance in protecting human health. There are two main evolutionary routes to generalism: organisms can tolerate multiple environments or they can modify their environments to forms to which they are adapted. Here we use a combination of theory and a phylogenetic comparative analysis of 191 pathogenic bacterial species to show that bacteria use cooperative secretions that modify their environment to extend their host range and infect multiple host species. Our results suggest that cooperative secretions are key determinants of host range in bacteria, and that monitoring for the acquisition of secreted proteins by horizontal gene transfer can help predict emerging zoonoses

Temporal changes in key maternal and fetal factors affecting birth outcomes: A 32-year population-based study in an industrial city

<p>Abstract</p> <p>Background</p> <p>The link between maternal factors and birth outcomes is well established. Substantial changes in society and medical care over time have influenced women's reproductive choices and health, subsequently affecting birth outcomes. The objective of this study was to describe temporal changes in key maternal and fetal factors affecting birth outcomes in Newcastle upon Tyne over three decades, 1961–1992.</p> <p>Methods</p> <p>For these descriptive analyses we used data from a population-based birth record database constructed for the historical cohort <b>Pa</b>rticulate <b>M</b>atter and <b>P</b>erinatal <b>E</b>vents <b>R</b>esearch (PAMPER) study. The PAMPER database was created using details from paper-based hospital delivery and neonatal records for all births during 1961–1992 to mothers resident in Newcastle (out of a total of 109,086 singleton births, 97,809 hospital births with relevant information). In addition to hospital records, we used other sources for data collection on births not included in the delivery and neonatal records, for death and stillbirth registrations and for validation.</p> <p>Results</p> <p>The average family size decreased mainly due to a decline in the proportion of families with 3 or more children. The distribution of mean maternal ages in all and in primiparous women was lowest in the mid 1970s, corresponding to a peak in the proportion of teenage mothers. The proportion of older mothers declined until the late 1970s (from 16.5% to 3.4%) followed by a steady increase. Mean birthweight in all and term babies gradually increased from the mid 1970s. The increase in the percentage of preterm birth paralleled a two-fold increase in the percentage of caesarean section among preterm births during the last two decades. The gap between the most affluent and the most deprived groups of the population widened over the three decades.</p> <p>Conclusion</p> <p>Key maternal and fetal factors affecting birth outcomes, such as maternal age, parity, socioeconomic status, birthweight and gestational age, changed substantially during the 32-year period, from 1961 to 1992. The availability of accurate gestational age is extremely important for correct interpretation of trends in birthweight.</p

The dynamics of neural fields on bounded domains: an interface approach for Dirichlet boundary conditions

Continuum neural field equations model the large scale spatio-temporal dynamics of interacting neurons on a cortical surface. They have been extensively studied, both analytically and numerically, on bounded as well as unbounded domains. Neural field models do not require the specification of boundary conditions. Relatively little attention has been paid to the imposition of neural activity on the boundary, or to its role in inducing patterned states. Here we redress this imbalance by studying neural field models of Amari type (posed on one- and two-dimensional bounded domains) with Dirichlet boundary conditions. The Amari model has a Heaviside nonlinearity that allows for a description of localised solutions of the neural field with an interface dynamics. We show how to generalise this reduced but exact description by deriving a normal velocity rule for an interface that encapsulates boundary effects. The linear stability analysis of localised states in the interface dynamics is used to understand how spatially extended patterns may develop in the absence and presence of boundary conditions. Theoretical results for pattern formation are shown to be in excellent agreement with simulations of the full neural field model. Furthermore, a numerical scheme for the interface dynamics is introduced and used to probe the way in which a Dirichlet boundary condition can limit the growth of labyrinthine structures

Protocol for population testing of an Internet-based Personalised Decision Support system for colorectal cancer screening

Extent: 8p.Background: Australia has a comparatively high incidence of colorectal (bowel) cancer; however, population screening uptake using faecal occult blood test (FOBT) remains low. This study will determine the impact on screening participation of a novel, Internet-based Personalised Decision Support (PDS) package. The PDS is designed to measure attitudes and cognitive concerns and provide people with individually tailored information, in real time, that will assist them with making a decision to screen. The hypothesis is that exposure to (tailored) PDS will result in greater participation in screening than participation following exposure to non-tailored PDS or resulting from the current non-tailored, paper-based approach. Methods/design: A randomised parallel trial comprising three arms will be conducted. Men and women aged 50-74 years (N = 3240) will be recruited. They must have access to the Internet; have not had an FOBT within the previous 12 months, or sigmoidoscopy or colonoscopy within the previous 5 years; have had no clinical diagnosis of bowel cancer. Groups 1 and 2 (PDS arms) will access a website and complete a baseline survey measuring decision-to-screen stage, attitudes and cognitive concerns and will receive immediate feedback; Group 1 will receive information 'tailored' to their responses in the baseline survey and group 2 will received 'non-tailored' bowel cancer information. Respondents in both groups will subsequently receive an FOBT kit. Group 3 (usual practice arm) will complete a paper-based version of the baseline survey and respondents will subsequently receive 'non-tailored' paper-based bowel cancer information with accompanying FOBT kit. Following despatch of FOBTs, all respondents will be requested to complete an endpoint survey. Main outcome measures are (1) completion of FOBT and (2) change in decision-to-screen stage. Secondary outcomes include satisfaction with decision and change in attitudinal scores from baseline to endpoint. Analyses will be performed using Chi-square tests, analysis of variance and log binomial generalized linear models as appropriate. Discussion: It is necessary to restrict participants to Internet users to provide an appropriately controlled evaluation of PDS. Once efficacy of the approach has been established, it will be important to evaluate effectiveness in the wider at-risk population, and to identify barriers to its implementation in those settings.Carlene J Wilson, Ingrid HK Flight, Ian T Zajac, Deborah Turnbull, Graeme P Young, Stephen R Cole, Tess Gregor

LRCH Proteins: A Novel Family of Cytoskeletal Regulators

Background: Comparative genomics has revealed an unexpected level of conservation for gene products across the evolution of animal species. However, the molecular function of only a few proteins has been investigated experimentally, and the role of many animal proteins still remains unknown. Here we report the characterization of a novel family of evolutionary conserved proteins, which display specific features of cytoskeletal scaffolding proteins, referred to as LRCHs. Principal Findings: Taking advantage of the existence of a single LRCH gene in flies, dLRCH, we explored its function in cultured cells, and show that dLRCH act to stabilize the cell cortex during cell division. dLRCH depletion leads to ectopic cortical blebs and alters positioning of the mitotic spindle. We further examined the consequences of dLRCH deletion throughout development and adult life. Although dLRCH is not essential for cell division in vivo, flies lacking dLRCH display a reduced fertility and fitness, particularly when raised at extreme temperatures. Conclusion/Significance: These results support the idea that some cytoskeletal regulators are important to buffer environmental variations and ensure the proper execution of basic cellular processes, such as the control of cell shape