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Aberrant DNA methylation within circadian entrainment and clock genes two years after pediatric critical illness is associated with impaired physical and neurocognitive development
No full textBACKGROUND: Pediatric critical illness can disrupt circadian rhythms, potentially leading to long-term deficits in growth, neurocognition, and behavior. Disturbances in circadian rhythms have been associated with altered gene expression and DNA methylation. We investigated long-term DNA methylation alterations in circadian entrainment and clock genes in children previously admitted to the pediatric intensive care unit (PICU), the influence of parenteral nutrition (PN) timing hereon and their associations with long-term health outcomes.METHODS: This study is a secondary analysis of the PEPaNIC randomized controlled trial (RCT) and its two-year follow-up. The PEPaNIC-RCT randomized critically ill children to early initiation of supplemental PN within the first 24 h or its omission in the first week of PICU admission. DNA methylation of 127 circadian entrainment and clock genes was studied in buccal mucosa DNA of former PICU patients (n = 818) and matched healthy children (n = 392) at the two-year follow-up using Infinium® HumanMethylation EPIC BeadChips. Multivariable linear models were used to identify differential methylation between former patients and controls and their association with randomization group and outcomes at two-year follow-up.RESULTS: Former PICU patients showed 61 differentially methylated CpG sites (DMPs) within 34 of the genes, with 60 (98.4%) showing hypomethylation as compared with healthy children. Omitting early PN during PICU stay did not affect CpG site methylation. 702 associations (34.9%) were observed between abnormal DNA methylation and adverse long-term health and developmental outcomes, most notably visual-motor integration (47 DMPs, 77%), height (46 DMPs, 75%) and total IQ (46 DMPs, 75%).CONCLUSION: Former PICU patients exhibited altered DNA methylation in circadian entrainment and clock genes compared to healthy children, and this was associated with impaired growth, neurocognition and behavioral problems at two-year follow-up. Disruptions in circadian entrainment and clock gene methylation may contribute to the adverse long-term health consequences that children experience after critical illness.</p
Effect of Systemic Hydrocortisone in Ventilated Infants Born Preterm:Mortality and 5.5-Year Neurodevelopmental Outcomes of a Randomized Clinical Trial
No full textObjective:To examine neurodevelopmental outcomes at 5.5 years of corrected age in children included in the Systemic hydrocortisone (HC) To Prevent Bronchopulmonary Dysplasia in preterm infants (SToP-BPD) study, and to investigate the neurodevelopmental outcomes and mortality with HC treatment started between 7 and 14 days after birth compared with placebo in infants born preterm who required mechanical ventilation. Study design Data at 5.5 years of corrected age on cognitive, motor and neurosensory functioning, behavior, schooling, and general health outcomes were derived from regular follow-up visits. The primary outcome was death or moderate-severe neurodevelopmental impairment (NDI, complete case analysis), with NDI defined as a disability in at least 1 of the domains of cognition, motor development, vision, or hearing. Other outcomes included neurologic and behavioral assessments as well as parent reports of service use and school function.Results:NDI was assessed in 213 of the 277 (77%) surviving children. Children attending follow-up were more likely to have highly educated or nonsmoking parents and had better neurodevelopmental outcomes at 2 years of corrected age than nonattending children. Baseline characteristics of assessed children were comparable between treatment arms. No significant difference was found on the primary outcome (OR 0.75; 95% CI 0.49-1.14; P = .18). All developmental outcomes were comparable between the HC and placebo group. Conclusions:Treatment with HC started between 7 and 14 days after birth in infants born preterm at risk of BPD did not affect death or moderate-severe NDI nor any of the separate developmental outcome measures at 5.5 years of corrected age. Trial registration:2010-023777-19; https://www.clinicaltrialsregister.eu</p
Academia Europaea’s guidelines for the visualization of clinical outcomes
No full textA working group of Academia Europaea proposes the addition of a ‘ring diagram’ in clinical publications for the quick evaluation of translational implications.</p
Unmasking cardiopulmonary consequences of neonatal lung injury:translational studies in two species
No full textThis thesis aims to investigate the effect of neonatal oxidative injury of the lungs during adolescence/early adulthood when overt cardiopulmonary disease is absent. Part I of this thesis presents a review that provides an overview of cardiac consequences of BPD during infanthood and challenges and recommendations in studying the pathophysiology in this population
Urban Creativity:An Efficiency Evaluation Combining DEA With SFA Models
No full textTechnical efficiency analysis is widely applied in the cultural and creative sectors. However, little research uses this notion to understand how these economic activities perform at the urban level. In this paper, conceptually, we operationalize urban creativity (UC) as the joint realm of cultural heritage and creative economy; empirically, we measure UC by combining their respective technical-efficiency scores via entropy-weighted aggregation. Our research focuses on 107 Italian cities at NUTS-3 levels and tests the diverse contributions made by the activities mentioned above in the period from 2014 to 2019. Data envelopment analysis and stochastic frontier analysis, both considered in two-stages approach and output-oriented, were combined through weighted entropy. The first results show that cultural heritage is the most efficient and decisive contributor to the UC index. In the entropy‑weighted composite, a high CH efficiency score carries greater weight and thus contributes more strongly to overall UC. Conversely, where CH efficiency is weaker, a high CE score can partially compensate, reflecting a synergy mechanism in the composite index. Moreover, we found that small cities tend to make careful and efficient use of resources, while most of the large cities, even when well-endowed, struggle to govern their CCIs efficiently. This work also examines the contribution of external factors to UC, finding that the influence of GDP, crime, unemployment, educational level, and geographical location (South-North or West-East) on UC is limited to specific clusters or peripheral cities. Political faith, understood as local political action, has a generally positive effect and can result in up to +14% improvement, with less equipped cities more likely to benefit from it.</p
Young Spanish Women Migrants as Au Pairs in the UK:Cleaning and Childcare During the COVID-19 Pandemic
No full textSince the 2008 financial crisis, the UK has emerged as a popular destination for young Spanish women navigating labour precariousness through (formerly intra-European Union) migration. Many adopt the au pair pathway as a strategic means to improve their English language skills and enhance future employability. However, while framed as a “cultural exchange”, the au pair scheme has faced sustained critique for masking a reality often characterised by precarious work, exploitation, and even abuse due to the great dependency of au pairs on host families and the various forms of worker control au pairs are exposed to. These dynamics were only exacerbated during the COVID-19 pandemic. Drawing on seven qualitative interviews with au pairs with a Spanish migration background and direct experience as an au pair by one of this article’s authors, this article applies the labour process theory (LPT) to interrogate the deterioration of living and working conditions for au pairs in the UK. The analysis demonstrates how the interplay of three distinct worker control mechanisms, intersecting with gendered vulnerabilities, intensified the subjugation of this specific group of domestic and care workers during the global health crisis.</p
Goldilocks:American Precious Metals and the Rise of the West
No full textWe estimate the contribution of the American precious metal windfall to Western Europe's growth performance in the early modern period. The exogenous nature of American precious metal extraction allows for the identification of monetary effects. We find that American precious metals fostered Western Europe's growth by stimulating trade and capital accumulation. Our findings place Western Europe's second-stage receivers in a particularly fortunate goldilocks zone that enjoyed monetary stimulus, while being insulated against the transport-loss induced financial crises that caused persistent damage to first-stage receiver Spain.</p
A Method for Comparing Health Inequality Impact Magnitudes, with an Illustration for Hypothetical Treatments of 1336 Diseases
No full textObjective: We aimed to facilitate the comparison and communication of magnitudes of health inequality impact across interventions for different diseases, and to indicate the potential range of such impacts. Methods: We propose rescaling the slope index of inequality to measure the health inequality impact as the change in the gap in total predicted quality-adjusted life-years between the least and most socially disadvantaged groups, with linear regression predictions used to account for effects on intermediate groups. We suggest reporting the inequality impact relative to the total health opportunity cost to facilitate comparison across interventions varying in scale and unit costs. We illustrated the approach with aggregate distributional cost-effectiveness analyses of hypothetical treatments for 1336 diseases in England. We approximated benefit shares for neighbourhood deprivation quintile groups using disease-specific hospital admissions. We tested between-group equality using generalised linear regression and constructed uncertainty intervals using Monte Carlo simulation. We assumed an equal total health opportunity cost and benefit-cost ratio of one, with alternative scenarios in a sensitivity analysis. Results: Health inequality impacts of hypothetical treatments ranged from − 33.1% of the total health opportunity cost (inequality increasing) to + 45.3% (inequality decreasing), and were ≤ − 5% for 1.6% of diseases, ≥ + 5% for 41.8% and ≥ + 20% for 1.6%. The impact was positively associated with the benefit-cost ratio and decreased when more deprived groups were assumed to incur proportionately more total health opportunity costs. Conclusions: Health inequality impacts can be compared using the change in the total predicted quality-adjusted life-year gap between the least and most socially disadvantaged groups as a proportion of the total health opportunity cost.</p
Dental care in the cleft team
No full textOral health is one of the main problems in Cleft Lip and/or Palate (CL/P) patients. Dental caries is a major contributor to compromised oral health. As dental caries is the consequence of persistent dental plaque and a frequent intake of free sugars, it can be prevented or arrested by changing oral health behaviour in the form of tooth brushing with fluoride containing toothpaste and reducing the intake of sugary foods and drinks. However, caries prevention in children with CL/P poses unique challenges, and their risk of developing dental caries is significantly elevated.The overall aim of the thesis is to improve dentistry related care for CL/P patients within the multidisciplinary cleft team setting. The thesis had two major objectives. Firstly, to optimize the use of the orodental related outcome measures of the value based cleft set. Secondly, to identify strategies for improving the dental care during cleft team consultation hours.<br/
Tuberculosis incidence in solid organ transplant recipients in Europe:A multicenter TBnet cohort study
No full textBackground: Solid organ transplant (SOT) recipients face elevated tuberculosis risk, yet optimal prevention strategies in low- to medium-incidence regions remain unclear. Methods: We conducted a multicenter retrospective cohort study of adult SOT recipients transplanted between 2007 and 2012 at 15 European centers, with follow-up through 2018. The primary outcome was microbiologically confirmed post-transplant tuberculosis. Incidence rates were calculated per 100,000 person-years; standardized incidence ratios (SIRs) used World Health Organization country-specific background rates. Cox models assessed risk factors.Results: Among 5805 patients (median age 51; 62.7% male; 73.9% renal transplants), 33.8% were tested for tuberculosis infection and 10.3% received tuberculosis preventive therapy (TPT). Over 33,785 person-years, 23 patients (0.4%) developed tuberculosis (68.0/100,000 person-years). Highest incidence occurred in patients with positive screening but no TPT (233.8/100,000). Incidence was higher in Southern vs. Central Europe (251.9 vs. 28.7/100,000), with pooled SIRs of 12.8 and 3.1, respectively. Tuberculosis risk was elevated among Southern European recipients (HR 22.9) and those with migration history (HR 2.7). Conclusion: Tuberculosis risk is increased in European SOT recipients. Regionally adapted prevention strategies, including targeted screening in low-incidence areas and universal screening in higher-incidence regions, are warranted.</p