Genome sequencing provides insight into the reproductive biology, nutritional mode and ploidy of the fern pathogen M ixia osmundae

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/106716/1/nph12653.pd

A statistical analysis protocol for the time-differentiated target temperature management after out-of-hospital cardiac arrest (TTH48) clinical trial

Background: The TTH48 trial aims to determine whether prolonged duration (48 hours) of targeted temperature management (TTM) at 33 (+/- 1) degrees C results in better neurological outcomes compared to standard duration (24 hours) after six months in comatose out-of-hospital cardiac arrest (OHCA) patients.Methods: TTH48 is an investigator-initiated, multicentre, assessor-blinded, randomised, controlled superiority trial of 24 and 48 hours of TTM at 33 (+/- 1) degrees C performed in 355 comatose OHCA patients aged 18 to 80 years who were admitted to ten intensive care units (ICUs) in six Northern European countries.The primary outcome of the study is the Cerebral Performance Category (CPC) score observed at six months after cardiac arrest. CPC scores of 1 and 2 are defined as good neurological outcomes, and CPC scores of 3, 4 and 5 are defined as poor neurological outcomes. The secondary outcomes are as follows: mortality within six months after cardiac arrest, CPC at hospital discharge, Glasgow Coma Scale (GCS) score on day 4, length of stay in ICU and at hospital and the presence of any adverse events such as cerebral, circulatory, respiratory, gastrointestinal, renal, metabolic measures, infection or bleeding.With the planned sample size, we have 80% power to detect a 15% improvement in good neurological outcomes at a two-sided statistical significance level of 5%.Discussion: We present a detailed statistical analysis protocol (SAP) that specifies how primary and secondary outcomes should be evaluated. We also predetermine covariates for adjusted analyses and pre-specify sub-groups for sensitivity analyses. This pre-planned SAP will reduce analysis bias and add validity to the findings of this trial on the effect of length of TTM on important clinical outcomes after cardiac arrest

Health-related quality of life at 5 years of age for children born very preterm with congenital anomalies: a multi-national cohort study

Background: This study aimed to investigate the health-related quality of life (HRQoL) at 5 years of age of European children born very preterm across multi-dimensional outcomes by presence and severity of congenital anomalies. Methods: The study used data from a European cohort of children born very preterm (<32 weeks of gestation) and followed up to 5 years of age (N = 3493). Multilevel Ordinary Least Squares (OLS) regression were used to explore the associations between the presence and severity of congenital anomalies. Results: The mean total PedsQL™ GCS score for children with a mild congenital anomaly was lower than the respective value for children without a congenital anomaly by 3.7 points (p < 0.05), controlling for socioeconomic variables only; this effect was attenuated when accumulatively adjusting for perinatal characteristics (3.3 points (p < 0.05)) and neonatal morbidities (3.1 (p < 0.05)). The mean total PedsQL™ GCS scores for children who had a severe congenital anomaly were lower by 7.1 points (p < 0.001), 6.6 points (p < 0.001) and 6.0 points (p < 0.001) when accumulatively adjusting for socioeconomic, perinatal and neonatal variables, respectively. Conclusion: This study revealed that the presence and severity of congenital anomalies are significant predictors of HRQoL outcomes in children born very preterm. Impact: Children born very preterm with congenital anomalies experience poorer health-related quality of life (HRQoL) than their very preterm counterparts born without congenital anomalies. Increased severity of these anomalies compounds the negative impacts on HRQoL. Our findings can be used by stakeholders for clinical and planning purposes. © The Author(s) 2024.We appreciate all the participants that completed the parental questionnaires. The entire SHIPS study team reviewed and approved the final version for publication. Funding/Support This study was supported by a grant from the European Union’s Horizon 2020 Research and Innovation Programme under grant agreement No 633724. Prof Petrou receives support as a UK National Insitute for Health and Care Research (NIHR) Senior Investigator (NF-SI-0616-10103) and from the NIHR Applied Research Collaboration Oxford and Thames Valley at the Oxford Health NHS Foundation Trust. The European Union’s Horizon 2020 Research and Innovation Programme and the NIHR Applied Research Collaboration Oxford and Thames Valley at the Oxford Health NHS Foundation Trust had no role in the design and conduct of the study

Health-related quality of life at 5 years of age for children born very preterm with congenital anomalies: a multi-national cohort study

\ua9 The Author(s) 2024.Background: This study aimed to investigate the health-related quality of life (HRQoL) at 5 years of age of European children born very preterm across multi-dimensional outcomes by presence and severity of congenital anomalies. Methods: The study used data from a European cohort of children born very preterm (&lt;32 weeks of gestation) and followed up to 5 years of age (N = 3493). Multilevel Ordinary Least Squares (OLS) regression were used to explore the associations between the presence and severity of congenital anomalies. Results: The mean total PedsQL™ GCS score for children with a mild congenital anomaly was lower than the respective value for children without a congenital anomaly by 3.7 points (p &lt; 0.05), controlling for socioeconomic variables only; this effect was attenuated when accumulatively adjusting for perinatal characteristics (3.3 points (p &lt; 0.05)) and neonatal morbidities (3.1 (p &lt; 0.05)). The mean total PedsQL™ GCS scores for children who had a severe congenital anomaly were lower by 7.1 points (p &lt; 0.001), 6.6 points (p &lt; 0.001) and 6.0 points (p &lt; 0.001) when accumulatively adjusting for socioeconomic, perinatal and neonatal variables, respectively. Conclusion: This study revealed that the presence and severity of congenital anomalies are significant predictors of HRQoL outcomes in children born very preterm. Impact: Children born very preterm with congenital anomalies experience poorer health-related quality of life (HRQoL) than their very preterm counterparts born without congenital anomalies. Increased severity of these anomalies compounds the negative impacts on HRQoL. Our findings can be used by stakeholders for clinical and planning purposes

Associations of language barriers with very preterm children’s behavioural and socio-emotional problems across Europe

\ua9 The Author(s) 2024. Background: Very preterm birth (&lt;32 weeks gestation, VP), immigrant background, and language barriers are all independently associated with a high risk for mental health problems in childhood, but research has neglected the long-term development of immigrant children born VP. We assessed whether behavioural and socio-emotional problems of 5-year-old children born VP growing up across different language contexts in the European Union are associated with an immigrant background and linguistic distance of families’ mother tongue (L1) to the host countries’ official languages. Methods: Data are from a population-based cohort including all VP births in 2011/12 in 11 European countries; a total of 3,067 children were followed up at 2 and 5 years of age. Behavioural and socio-emotional difficulties were assessed using the parent-reported Strengths and Difficulties Questionnaire (SDQ). Results: Mixed-effects models showed that a larger linguistic distance of children’s L1 to the host countries’ official language was associated with higher SDQ total scores (0.02 [0.01, 0.03]), after adjusting for a wide range of social risks, biological, and perinatal clinical factors. Conclusion: Language barriers in the form of linguistic distance between VP children’s L1 and countries’ official languages play a critically important role for the behavioural and socio-emotional development of immigrant children born VP. Impact: Immigrant children born very preterm across Europe face systemic inequalities such as language barriers. Language barriers can be operationalised as a continuous linguistic distance score between children’s mother tongues and countries’ official languages. Linguistic distance plays an important role for the behavioural and socio-emotional development of immigrant children born VP. Research, policy, and practice need to better account for language barriers to increase equity in health and education

Variation in follow-up for children born very preterm in Europe

Background: Children born very preterm (<32 weeks of gestation) face high risks of neurodevelopmental and health difficulties compared with children born at term. Follow-up after discharge from the neonatal intensive care unit is essential to ensure early detection and intervention, but data on policy approaches are sparse. Methods: We investigated the characteristics of follow-up policy and programmes in 11 European countries from 2011 to 2022 using healthcare informant questionnaires and the published/grey literature. We further explored how one aspect of follow-up, its recommended duration, may be reflected in the percent of parents reporting that their children are receiving follow-up services at 5 years of age in these countries using data from an area-based cohort of very preterm births in 2011/12 (N = 3635). Results: Between 2011/12 and 22, the number of countries with follow-up policies or programmes increased from 6 to 11. The policies and programmes were heterogeneous in eligibility criteria, duration and content. In countries that recommended longer follow-up, parent-reported follow-up rates at 5 years of age were higher, especially among the highest risk children, born <28 weeks’ gestation or with birthweight <1000 g: between 42.1% and 70.1%, vs. <20% in most countries without recommendations. Conclusions: Large variations exist in follow-up policies and programmes for children born very preterm in Europe; differences in recommended duration translate into cross-country disparities in reported follow-up at 5 years of age

Genome sequencing provides insight into the reproductive biology, nutritional mode and ploidy of the fern pathogen Mixia osmundae

Mixia osmundae (Basidiomycota, Pucciniomycotina) represents a monotypic class containing an unusual fern pathogen with incompletely understood biology. We sequenced and analyzed the genome of M. osmundae, focusing on genes that may provide some insight into its mode of pathogenicity and reproductive biology. Mixia osmundae has the smallest plant pathogenic basidiomycete genome sequenced to date, at 13.6 Mb, with very few repeats, high gene density, and relatively few significant gene family gains. The genome shows that the yeast state of M. osmundae is haploid and the lack of segregation of mating genes suggests that the spores produced on Osmunda spp. fronds are probably asexual. However, our finding of a complete complement of mating and meiosis genes suggests the capacity to undergo sexual reproduction. Analyses of carbohydrate active enzymes suggest that this fungus is a biotroph with the ability to break down several plant cell wall components. Analyses of publicly available sequence data show that other Mixia members may exist on other plant hosts and with a broader distribution than previously known.Keywords: Fungal genomics, Myxomycetes, CAZy, Osmunda spp., Biotrophic fungi, Sporogenesi

Fluid challenges in intensive care: the FENICE study A global inception cohort study

Fluid challenges (FCs) are one of the most commonly used therapies in critically ill patients and represent the cornerstone of hemodynamic management in intensive care units. There are clear benefits and harms from fluid therapy. Limited data on the indication, type, amount and rate of an FC in critically ill patients exist in the literature. The primary aim was to evaluate how physicians conduct FCs in terms of type, volume, and rate of given fluid; the secondary aim was to evaluate variables used to trigger an FC and to compare the proportion of patients receiving further fluid administration based on the response to the FC.This was an observational study conducted in ICUs around the world. Each participating unit entered a maximum of 20 patients with one FC.2213 patients were enrolled and analyzed in the study. The median [interquartile range] amount of fluid given during an FC was 500 ml (500-1000). The median time was 24 min (40-60 min), and the median rate of FC was 1000 [500-1333] ml/h. The main indication for FC was hypotension in 1211 (59 %, CI 57-61 %). In 43 % (CI 41-45 %) of the cases no hemodynamic variable was used. Static markers of preload were used in 785 of 2213 cases (36 %, CI 34-37 %). Dynamic indices of preload responsiveness were used in 483 of 2213 cases (22 %, CI 20-24 %). No safety variable for the FC was used in 72 % (CI 70-74 %) of the cases. There was no statistically significant difference in the proportion of patients who received further fluids after the FC between those with a positive, with an uncertain or with a negatively judged response.The current practice and evaluation of FC in critically ill patients are highly variable. Prediction of fluid responsiveness is not used routinely, safety limits are rarely used, and information from previous failed FCs is not always taken into account