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Aim: Organisation of care, perinatal and neonatal management of very preterm infants in the Nordic regions were hypothesised to vary significantly. The aim of this observational study was to test this hypothesis.Methods: Information on preterm infants in the 21 greater healthcare regions of Denmark, Finland, Iceland, Norway and Sweden was gathered from national registers in 2021. Preterm birth rates, case-mix, perinatal interventions, neonatal morbidity and survival to hospital discharge in very (Results: Out of 287 642 infants born alive, 16 567 (5.8%) were preterm, 2389 (0.83%) very preterm and 800 (0.28%) were extremely preterm. In very preterm infants, exposure to antenatal corticosteroids varied from 85% to 98%, live births occurring at regional centres from 48% to 100%, surfactant treatment from 28% to 69% and use of mechanical ventilation varied from 13% to 77% (p < 0.05 for all comparisons). Significant regional variations within and between countries were also seen in capacity in neonatal care, case-mix and number of admissions, whereas there were no statistically significant differences in survival or major neonatal morbidities.Conclusion: Management of very preterm infants exhibited significant regional variations in the Nordic countries. Aim: Organisation of care, perinatal and neonatal management of very preterm infants in the Nordic regions were hypothesised to vary significantly. The aim of this observational study was to test this hypothesis. Methods: Information on preterm infants in the 21 greater healthcare regions of Denmark, Finland, Iceland, Norway and Sweden was gathered from national registers in 2021. Preterm birth rates, case-mix, perinatal interventions, neonatal morbidity and survival to hospital discharge in very (

A method for estimation of rubber bushing stiffness parameters is presented. Four individual rubber bushings, mounted in a car rear subframe are considered. A traditional model of the bushing elements using a generalised spring model, known as a CBUSH element in Nastran, is compared to a geometrically more realistic approach where the bushing is modelled with solid elements and a linear elastic material model. Each bushing is mass loaded to better reveal the bushing’s dynamic behaviour in a lower frequency range of interest. In an initial step, the overall subframe model is updated towards test data. In a second step, the bushing parameters are updated. Three nominally identical components are used to investigate the spread between the identified parameters. The model updating procedure is based on frequency responses and equalised damping. The undamped behaviour at frequencies below 300 Hz are considered. To quantify the parameter uncertainty, with respect to measurement noise for each individual, an uncertainty quantification procedure is proposed, using a linear-in-parameters surrogate model with bootstrapping.

As part of the development of an automated virtual design classification approach for nonlinear structural dynamics, alternative excitation functions are evaluated with respect to their overall performance and efficiency in feature-based response analysis. Robust design of nonlinear structures requires analysis of extensive parameter variations. Both the character of the stimulus and feature metrics used are central to the performance of a response classification approach. The main purpose of this study is to compare stimulus candidates with respect to their efficiency in response classification. A deterministic multilevel, multifrequency stepped-sine periodic test function is used as a baseline. Order-wise differences between generalized and linearized system frequency response functions are evaluated by a selected feature metric to allow categorization into primary, sub and super harmonic responses, as well as odd and even order response distortions. An alternative excitation function type is the pseudorandom phase multi-sine. Its robust variant estimates the best linear approximation of the generalized frequency response function and related nonlinear and noise variances, which can be used for response classification. The fast variant of this method further detects and classifies occurring even and odd order nonlinear responses using a hypothesis test. This article describes the application of these three methods to a virtually running two-piece rotor shaft model. Time response signals from simulated test parameter variations are used to calculate selected nonlinear feature metric values. The total simulation and measurement time, as well as the predictive performance in a few typical nonlinear response cases are evaluated.

The probability of an instant rail break, initiated at a single pre-existing rail foot crack due to a severe wheel impact loading, is predicted using statistical methods and a time-domain model for the simulation of dynamic vehicle–track interaction. A linear elastic fracture mechanics approach is employed to calculate the stress intensity at the crack in a continuously welded rail subjected to combined bending and temperature loading. Based on long-term field measurements in a wayside wheel load detector, a three-parameter probability distribution of the dynamic wheel load is determined. For a faster numerical assessment of the probability of failure, a thin plate spline regression is implemented to develop a meta-model of the performance function quantifying the stress intensity at the crack. The methodology is demonstrated by investigating the influence of initial crack length, fracture toughness and rail temperature difference on the risk for an instant rail break.

Aim To explore mothers experiences of the EArly Collaborative Intervention. Background Preterm birth puts a considerable emotional and psychological burden on parents and families. Parents to moderate and late premature infants have shorter stays at the neonatal intensive care unit and have described a need for support. The EArly Collaborative Intervention was developed to support parents with preterm infants born between gestational Weeks 30 to 36. In this study, mothers experiences of the new intervention were explored. Design A qualitative design guided by a reflexive thematic analysis according to Braun and Clarke. Interviews were individually performed with 23 mothers experienced with the EArly Collaborative Intervention. Data were identified, analysed and reported using reflexive thematic analysis. The COREQ checklist was used preparing the manuscript. Results Two main overarching themes were constructed. The first theme, mothers feelings evoked from the EArly Collaborative Intervention describes the emotions raised by the intervention and how the intervention affected their parental role. Their awareness of the preterm babys behaviour increased, and the intervention helped the parents to communicate around their babys needs. The second theme, based on the preterm babys behavior, describes experiences of the provision and the learning process about their preterm babys needs and communication. The intervention was experienced as helpful both immediately and for future interaction with the baby. Conclusions Mothers found the intervention to be supportive and encouraging. They came to look upon their baby as an individual, and the new knowledge on how to care and interact with their baby affected both their own and their babys well-being. Furthermore, the intervention felt strengthening for their relationship with the other parent. Relevance to Clinical Practice The EArly Collaborative Intervention can support parents abilities as well as their relation to their baby and may thereby contribute to infant development, cognition and well-being. Funding Agencies|Region Ostergotland; Stiftelsen Sven Jerrings Fond

Summary 16S rRNA gene sequencing enables microbial community profiling, but recovering fecal DNA from extremely premature infants is challenging. Here, we describe an optimized protocol for fecal DNA isolation, library preparation for 16S rRNA gene sequencing, taxonomy assignation, and statistical analyses. The protocol is complemented with a quantitative PCR for probiotic L. reuteri identification. This protocol describes how to characterize preterm infant gut microbiota and relate it to probiotic supplementation and clinical outcomes. It is customizable for other clinical trials. For complete details on the use and execution of this protocol, please refer to Martí et al. (2021) and Spreckels et al. (2021)., Graphical abstract, Highlights • Customizable protocol for characterization of infant gut microbiota in clinical trials • Optimized sample preparation for 16S rRNA gene sequencing for infant fecal samples • Quantitative PCR for probiotic Lactobacillus reuteri quantification in infant feces • Easy-to-use bioinformatic and statistical analysis pipeline, 16S rRNA gene sequencing enables microbial community profiling, but recovering fecal DNA from extremely premature infants is challenging. Here, we describe an optimized protocol for fecal DNA isolation, library preparation for 16S rRNA gene sequencing, taxonomy assignation, and statistical analyses. The protocol is complemented with a quantitative PCR for probiotic L. reuteri identification. This protocol describes how to characterize preterm infant gut microbiota and relate it to probiotic supplementation and clinical outcomes. It is customizable for other clinical trials.

Objectives Extremely low gestational age neonates with extremely low birthweight (ELGAN/ELBW) are highly susceptible to infection. This is linked to their relatively immature immune system which is not yet fully compatible with an extra‐uterine environment. Here, we performed a longitudinal characterisation of unconventional T and natural killer (NK) cells in ELGAN/ELBW during their first months of life. Methods Peripheral blood mononuclear cells were collected from 97 ELGAN/ELBW at 14 and 28 days of life and at a time point corresponding to postmenstrual week 36 + 0. γδ T‐cell, NKT‐cell, mucosa‐associated invariant T‐cell and NK cell frequencies and characteristics were analysed by flow cytometry. As control, cells from 14‐day‐old full‐term (FT) infants were included. Results Extreme prematurity had significant bearing on γδ T‐cell and NK cell frequencies and characteristics. ELGAN/ELBW had significantly higher proportions of γδ T cells that were skewed towards effector and effector memory phenotypes, characteristics that were maintained throughout the study period. Expression of the gut homing receptor CCR9 was also more common in γδ T cells from ELGAN/ELBW. Conversely, NK cell frequencies were markedly lower and skewed towards a cytotoxic phenotype in the ELGAN/ELBW group at 14 days of age. Culture‐proven sepsis with an onset during the first 14 days after birth further manifested these differences in the γδ T‐ and NK cell populations at 14 days of age. Conclusion Prematurity strongly influences the levels of γδ T and NK cells, in particular in cases where sepsis debuts during the first 2 weeks of life., Extreme prematurity impacts frequencies and characteristics of γδ T and NK cells, in particular in cases where sepsis debuts during the first 2 weeks of life. Probiotic supplementation with Lactobacillus reuteri did not influence these parameters.

Extremely low birth weight (ELBW) infants often develop an altered gut microbiota composition, which is related to clinical complications, such as necrotizing enterocolitis and sepsis. Probiotic supplementation may reduce these complications, and modulation of the gut microbiome is a potential mechanism underlying the probiotic effectiveness. In a randomized, double-blind, placebo-controlled trial, we assessed the effect of Lactobacillus reuteri supplementation, from birth to post-menstrual week (PMW)36, on infant gut microbiota. We performed 16S amplicon sequencing in 558 stool samples from 132 ELBW preterm infants at 1 week, 2 weeks, 3 weeks, 4 weeks, PMW36, and 2 years. Probiotic supplementation results in increased bacterial diversity and increased L. reuteri abundance during the 1st month. At 1 week, probiotic supplementation also results in a lower abundance of Enterobacteriaceae and Staphylococcaceae. No effects were found at 2 years. In conclusion, probiotics may exert benefits by modulating the gut microbiota composition during the 1st month in ELBW infants. Funding Agencies|Lions Forskningsfond mot folksjukdomar [Lions LiU-2019-03041]; Swedish Research CouncilSwedish Research CouncilEuropean Commission [921.2014-7060, 2016-01715_3]; Swedish Society for Medical Research; Swedish Society of Medicine; Research Council for South-East Sweden; Region Ostergotland; BioGaia AB, Stockholm, Sweden; Swedish National Infrastructure for Computing (SNIC) through Uppsala Multidisciplinary Center for Advanced Computational Science (UPPMAX) [SNIC 2020/5-336]; The Ekhaga Foundation; ALF

Objective To compare length of stay (LOS) in neonatal care for babies born extremely preterm admitted to networks participating in the International Network for Evaluating Outcomes of Neonates (iNeo). Study design Data were extracted for babies admitted from 2014 to 2016 and born at 24 to 28 weeks of gestational age (n = 28 204). Median LOS was calculated for each network for babies who survived and those who died while in neonatal care. A linear regression model was used to investigate differences in LOS between networks after adjusting for gestational age, birth weight z score, sex, and multiplicity. A sensitivity analysis was conducted for babies who were discharged home directly. Results Observed median LOS for babies who survived was longest in Japan (107 days); this result persisted after adjustment (20.7 days more than reference, 95% CI 19.3-22.1). Finland had the shortest adjusted LOS (−4.8 days less than reference, 95% CI –7.3 to −2.3). For each week's increase in gestational age at birth, LOS decreased by 12.1 days (95% CI –12.3 to −11.9). Multiplicity and male sex predicted mean increases in LOS of 2.6 (95% CI 2.0-3.2) and 2.1 (95% CI 1.6-2.6) days, respectively. Conclusions We identified between-network differences in LOS of up to 3 weeks for babies born extremely preterm. Some of these may be partly explained by differences in mortality, but unexplained variations also may be related to differences in clinical care practices and healthcare systems between countries.

When developing alpine skis, new design is often built upon experience from what has been done in the past. This allows for stable but incremental improvements that limit the possibilities of ground-breaking design changes. To allow such major changes, without risking spending a fortune on trial and error studies, simulation-based design is a must. This paper presents a method for such a simulation-based design approach, focusing on the effect of the internal ski structure and its effect on bending and vibration characteristics. As a prototype ski, we have studied Faction Skis’ Candide 3.0, for which a finite element model was developed and validated. In the next step, the effect of a design ski variation was analysed to demonstrate how simulation-based screening of design options can be easily implemented.

Scope Necrotizing enterocolitis (NEC) is a devastating gastrointestinal emergency and currently the leading cause of mortality in preterm infants. Recent studies show that human milk oligosaccharides (HMOs) reduce the frequency and incidence of NEC; however, the molecular mechanisms for their protection are largely unexplored. Methods and results To address this gap, a genome-wide profiling of the intestinal epithelial transcriptome in response to HMOs using RNA-sequencing is performed. It is found that HMOs alter the host transcriptome in 225 unique target genes pertaining to cell proliferation and differentiation, including upregulation of stem cell differentiation marker HMGCS2. To validate these results, differentiation in Caco-2Bbe1 (Caco-2) intestinal cells is verified by Alcian Blue staining and transepithelial electrical resistance (TER) recordings. Furthermore, an in vivo model of NEC is also employed whereby neonatal pups are gavage fed HMOs. Interestingly, HMOs-fed pups show enhanced cell MUC2 differentiation and HMGCS2 expression. Conclusions These findings demonstrate HMOs protect against NEC in part by altering the differentiation of the crypt-villus axis. In addition, this study suggests that pooled HMOs directly induce a series of biological processes, which provide mechanistic insights to how HMOs protect the host intestine.

Extremely low birth weight (ELBW) infants often develop an altered gut microbiota composition, which is related to clinical complications, such as necrotizing enterocolitis and sepsis. Probiotic supplementation may reduce these complications, and modulation of the gut microbiome is a potential mechanism underlying the probiotic effectiveness. In a randomized, double-blind, placebo-controlled trial, we assessed the effect of

Allergic diseases have become a major health problem, partly due to reduced microbial stimulation and a decreased dietary omega-3/omega-6 long-chain polyunsaturated fatty acid ratio. Prenatal exposures have been reported to influence allergy development, possibly induced via changes in maternal immune regulation. In a randomized double-blind placebo-controlled multicenter allergy prevention trial (PROOM-3), pregnant women were recruited at gestational week 20, and randomized to four study groups, one receiving both L. reuteri oil drops and omega-3 PUFA capsules (n=22), the second receiving omega-3 PUFA supplementation and placebo regarding L. reuteri (n=21), the third receiving L. reuteri and placebo regarding omega-3 PUFA (n=22) and the fourth group receiving placebo capsules and placebo oil drops (n=23). In this substudy, supplemental and pregnancy-related effects on maternal peripheral immune cell populations during pregnancy were assessed by flow cytometry immune phenotyping at gestational week 20, 32 and 4 days after delivery. The numbers of activated and regulatory T (Treg) cells (CD45RA(-) Foxp3(++)/CD45RA(+)Foxp3(+)) were reduced after delivery, with the lowest count in the L. reuteri supplemented group compared with the placebo group 4 days after delivery, while the omega-3 PUFA group did not differ from the placebo group. Several treatment-independent changes were observed during and after pregnancy in lymphocytes (CD4(+)/8(+)/19(+)/56(+)/45RA(+/-)), CD14(+)16(+/-) monocytes, and in subpopulations of T helper cells (Th) CD4(+)CD45RA(-)Tbet(+) (Th1) and CD4(+)CD45RA(-)RORC(+) (Th17) cells. In conclusion, probiotic supplementation to the mother during the second half of pregnancy resulted in immunomodulatory effects among activated and resting Treg cells. Furthermore, several systemic immune modifying effects of pregnancy were observed. Funding Agencies|Linkoping University Library; Swedish Research CouncilSwedish Research Council [2016-01698]; Swedish Heart and Lung FoundationSwedish Heart-Lung Foundation [20140321, 20170365]; Cancer and Allergy Foundation; Medical Research Council of Southeast Sweden [FORSS-666771, FORSS-758981]; Hesselman Foundation [IKE-2014-00434]; Samariten Foundation; Ostergotlands Research-and Scholarship Foundations [LIO-470781]; Mayflower Foundation [IKE-2015-00054]; Lions [IKE-2016-00417]; BioGaia AB

Background Very preterm infants are at high risk of death or severe morbidity. The objective was to determine the significance of severe congenital heart defects ( CHDs ) for these risks. Methods and Results This cohort study included infants from 10 countries born from 2007–2015 at 24 to 31 weeks’ gestation with birth weights CHDs were defined by International Classification of Diseases, Ninth Revision ( ICD‐9 ) and Tenth ( ICD‐10 ) codes and categorized as those compromising systemic output, causing sustained cyanosis, or resulting in congestive heart failure. The primary outcome was in‐hospital mortality. Secondary outcomes were neonatal brain injury, necrotizing enterocolitis, bronchopulmonary dysplasia, and retinopathy of prematurity. Adjusted and propensity score–matched odds ratios ( ORs ) were calculated. Analyses were stratified by type of CHD , gestational age, and network. A total of 609 (0.77%) infants had severe CHD and 76 371 without any malformation served as controls. The mean gestational age and birth weight were 27.8 weeks and 1018 g, respectively. The mortality rate was 18.6% in infants with CHD and 8.9% in controls (propensity score–matched OR , 2.30; 95% CI , 1.61–3.27). Severe CHD was not associated with neonatal brain injury, necrotizing enterocolitis, or retinopathy of prematurity, whereas the OR for bronchopulmonary dysplasia increased. Mortality was higher in all types, with the highest propensity score–matched OR (4.96; 95% CI, 2.11–11.7) for CHD causing congestive heart failure. While mortality did not differ between groups at OR for mortality in infants with CHD increased to 10.9 (95% CI, 5.76–20.70) at 31 weeks’ gestational age. Rates of CHD and mortality differed significantly between networks. Conclusions Severe CHD is associated with significantly increased mortality in very preterm infants.

Aim This study evaluated if oral supplementation with the probiotic bacterium Lactobacillus reuteri DSM 17938 improved enteral feeding tolerance and growth rates in extremely low birthweight (ELBW) infants. Method A randomised, double‐blind, placebo‐controlled trial comprising 134 ELBW (Funding Agencies|Swedish Research Council [921.2014-7060]; Swedish Society for Medical Research; Swedish Society of Medicine; Research Council for the South-East Sweden; ALF Grants, Region Ostergotland; Ekhaga Foundation; BioGaia AB

An applied system design analysis approach for automated processing and classification of simulated structural responses is presented. Deterministic and nonlinear dynamics are studied under ideal loading and low noise conditions to determine fundamental system properties, how they vary and possibly interact. Using powerful computer resources, large amounts of simulated raw data can be produced in a short period of time. Efficient tools for data processing and interpretation are then needed, but existing ones often require much manual preparation and direct human judgement. Thus, there is a need to develop techniques that help to treat more virtual prototype variants and efficiently extract useful information from them. For this, time signals are evaluated by methods commonly used within structural dynamics and statistical learning. A multi-level multi-frequency stimulus function is constructed and simulated response signals are combined into frequency domain functions. These are associated with qualitative system features, such as being periodic or aperiodic, linear or nonlinear and further into subcategories of nonlinear systems, such as fundamental, sub or super harmonic and even or odd order types. Appropriate classes are then determined from selected feature metrics and rules-of-thumb criteria. To automate the classification of large data sets, a support vector machine is trained on categorised responses to determine whether a single feature, or combinations of features, applies or not. The trained classifier can then efficiently process new sets of data and pick out cases that are associated with possible vibrational problems, which subsequently can be further analysed and understood. This article describes elements of the analysis, discuss the effectiveness of evaluated feature metrics, reports practical considerations and results from two separate training study examples.

To make better use of simulations in the automotive driveline design process there is a need for both improved predictive capabilities of typical system models and increased number of variant evaluations carried out during system concept design phase. A previously developed large-scale multibody rotor dynamical powertrain model that combines detailed linear-elastic finite element components and nonlinear joints is used to more accurately simulate system response modes and their variations across the operating-range. However, the total simulation time is too long to include extensive parameter evaluations during the rapid design iterations, which will have a negative influence on the total understanding of the designed system's behaviour. Therefore this paper is about reducing such a large-scale model to one that runs faster, but without losing the ability to predict the most fundamental system characteristics. Reduction methods considering defined stimuli-response relations are well established and used within the field of control systems, to balance prediction accuracy and evaluation effort, but are not yet commonly applied to large-scaled structural models and analysis of vibrations in continuous and lightly damped structures. Here, an implementation of two such state-space reduction methods into a common computational software workflow is described and their overall efficiency is compared to standard methods. Reductions are applied to two major structural components of the powertrain model. Steady-state simulations are performed for multiple engine speeds and responses related to vehicle noise and vibrations are compared using a quantitative error metric. The prediction accuracy, reduction and response simulation times of different model orders are evaluated, as well as the corresponding mode frequency spectra.

The estimation of modal parameters from a set of noisy measured data is a highly judgmental task, with user expertise playing a significant role in distinguishing between estimated physical and noise modes of a test-piece. Various methods have been developed to automate this procedure. The common approach is to identify models with different orders and cluster similar modes together. However, most proposed methods based on this approach suffer from high-dimensional optimization problems in either the estimation or clustering step. To overcome this problem, this study presents an algorithm for autonomous modal parameter estimation in which the only required optimization is performed in a three-dimensional space. To this end, a subspace-based identification method is employed for the estimation and a non-iterative correlation-based method is used for the clustering. This clustering is at the heart of the paper. The keys to success are correlation metrics that are able to treat the problems of spatial eigenvector aliasing and nonunique eigenvectors of coalescent modes simultaneously. The algorithm commences by the identification of an excessively high-order model from frequency response function test data. The high number of modes of this model provides bases for two subspaces: one for likely physical modes of the tested system and one for its complement dubbed the subspace of noise modes. By employing the bootstrap resampling technique, several subsets are generated from the same basic dataset and for each of them a model is identified to form a set of models. Then, by correlation analysis with the two aforementioned subspaces, highly correlated modes of these models which appear repeatedly are clustered together and the noise modes are collected in a so-called Trashbox cluster. Stray noise modes attracted to the mode clusters are trimmed away in a second step by correlation analysis. The final step of the algorithm is a fuzzy c-means clustering procedure applied to a three-dimensional feature space to assign a degree of physicalness to each cluster. The proposed algorithm is applied to two case studies: one with synthetic data and one with real test data obtained from a hammer impact test. The results indicate that the algorithm successfully clusters similar modes and gives a reasonable quantification of the extent to which each cluster is physical.

In frequency range vibration testing a few outside band eigenmodes are often included in the system identification to compensate for residual mass and stiffness influences. It has been observed that, in particular, energy conjugate input-output pair transfer functions with strong outside band modes tend to render models with poor fit even after inclusion of mass and stiffness residuals. For such problems the inclusion of another complementary residual term has been found to improve the fit to data. In this paper, modal models identified from acceleration data with a subspace state-space method are considered. The residual mass influence is modelled with a state-space direct throughput while the stiffness and complementary residuals are modelled with extra states. Furthermore, for state-space models on accelerance form it is shown that the direct throughput matrix can be partitioned into a flexible and rigid motion partition. For systems with more inputs and outputs than rigid body modes it is shown that the rigid body motion partition has a bounded rank. The upper bound is equal to the number of rigid body modes. Therefore, for identified models on accelerance form this constraint must be enforced for physical consistency. The proposed method is applied on simulated finite element test data from an automotive component.

IMPORTANCE: Since 2004-2007, national guidelines and recommendations have been developed for the management of extremely preterm births in Sweden. If and how more uniform management has affected in ...

A method is developed for propagation of model parameter uncertainties into frequency response functions based on a modal representation of the equations of motion. Individual local surrogate models of the eigenfrequencies and residue matrix elements for each mode are trained to build a global surrogate model. The computational cost of the global surrogate model is reduced in three steps. First, modes outside the range of interest, necessary to describe the in-band frequency response, are approximated with few residual modes. Secondly, the dimension of the residue matrices for each mode is reduced using principal component analysis. Lastly, multiple surrogate model structures are employed in a mixture. Cheap second-order multivariate polynomial models and more expensive Gaussian process models with different kernels are used to model the modal data. Leave-one-out cross-validation is used for model selection of the local surrogate models. The approximations introduced allow the method to be used for modally dense models at a small computational cost, without sacrificing the global surrogate model’s ability to capture mode veering and crossing phenomena. The method is compared to a Monte Carlo based approach and verified on one industrial-sized component and on one assembly of two car components.

A new multi-level Markov Chain Monte Carlo algorithm for Approximate Bayesian Computation, ABC-SubSim, has recently appeared that exploits the Subset Simulation method for efficient rare-event simulation. ABC-SubSim adaptively creates a nested decreasing sequence of data-approximating regions in the output space that correspond to increasingly closer approximations of the observed output vector in this output space. At each level, multiple samples of the model parameter vector are generated by a component-wise Metropolis algorithm so that the predicted output corresponding to each parameter value falls in the current data-approximating region. Theoretically, if continued to the limit, the sequence of data-approximating regions would converge on to the observed output vector and the approximate posterior distributions, which are conditional on the data-approximation region, would become exact, but this is not practically feasible. In this paper we study the performance of the ABC-SubSim algorithm for Bayesian updating of the parameters of dynamical systems using a general hierarchical state-space model. We note that the ABC methodology gives an approximate posterior distribution that actually corresponds to an exact posterior where a uniformly distributed combined measurement and modeling error is added. We also note that ABC algorithms have a problem with learning the uncertain error variances in a stochastic state-space model and so we treat them as nuisance parameters and analytically integrate them out of the posterior distribution. In addition, the statistical efficiency of the original ABC-SubSim algorithm is improved by developing a novel strategy to regulate the proposal variance for the component-wise Metropolis algorithm at each level. We demonstrate that Self-regulated ABC-SubSim is well suited for Bayesian system identification by first applying it successfully to model updating of a two degree-of-freedom linear structure for three cases: globally, locally and un-identifiable model classes, and then to model updating of a two degree-of-freedom nonlinear structure with Duffing nonlinearities in its interstory force-deflection relationship.

Since 2004-2007, national guidelines and recommendations have been developed for the management of extremely preterm births in Sweden. If and how more uniform management has affected infant survival is unknown.To compare survival of extremely preterm infants born during 2004-2007 with survival of infants born during 2014-2016.All births at 22-26 weeks' gestational age (n = 2205) between April 1, 2004, and March 31, 2007, and between January 1, 2014, and December 31, 2016, in Sweden were studied. Prospective data collection was used during 2004-2007. Data were obtained from the Swedish pregnancy, medical birth, and neonatal quality registries during 2014-2016.Delivery at 22-26 weeks' gestational age.The primary outcome was infant survival to the age of 1 year. The secondary outcome was 1-year survival among live-born infants who did not have any major neonatal morbidity (specifically, without intraventricular hemorrhage grade 3-4, cystic periventricular leukomalacia, necrotizing enterocolitis, retinopathy of prematurity stage 3-5, or severe bronchopulmonary dysplasia).During 2004-2007, 1009 births (3.3/1000 of all births) occurred at 22-26 weeks' gestational age compared with 1196 births (3.4/1000 of all births) during 2014-2016 (P = .61). One-year survival among live-born infants at 22-26 weeks' gestational age was significantly lower during 2004-2007 (497 of 705 infants [70%]) than during 2014-2016 (711 of 923 infants [77%]) (difference, -7% [95% CI, -11% to -2.2%], P = .003). One-year survival among live-born infants at 22-26 weeks' gestational age and without any major neonatal morbidity was significantly lower during 2004-2007 (226 of 705 infants [32%]) than during 2014-2016 (355 of 923 infants [38%]) (difference, -6% [95% CI, -11% to -1.7%], P = .008).Among live births at 22-26 weeks' gestational age in Sweden, 1-year survival improved between 2004-2007 and 2014-2016.

Simulating the nonlinear behavior of complex systems requires significant computational effort. Despite the rapid progress in computing technology, the demand is still strong for more efficient simulation methods in diverse structural dynamics fields such as nonlinear system identification and nonlinear system reliability. In addition to efficiency, algorithmic stability and accuracy must be addressed in the development of new simulation procedures. In this paper, a method to treat localized nonlinearities in a structure efficiently and accurately is proposed. The method is conditionally stable. The system equations are separated into a state-invariant linear part and a state-dependent nonlinear part that is considered to be external pseudo-forces that act on the linear system. The response of the system is obtained by fixed point iterations in which the pseudo-forces are updated until convergence. In addition to the one time-step-ahead prediction form, the novel idea of multiple time-step-ahead prediction is proposed. The effect of this approach is investigated and shown to increase algorithm efficiency and stability. To perform the numerical integration, time-stepping schemes like the exponential first-order hold method can be used to the advantage of efficiency and accuracy. To increase the accuracy and stability of the method, a novel second-order hold equivalent is derived and implemented. The efficiency, stability, and accuracy of the method are demonstrated in numerical examples. Finally, the method is applied to the earthquake-induced motion of a 20-story building with local nonlinearities.

Preterm delivery in Sweden constitutes 5.7 % of all deliveries, which is among the lowest rates in the world. There has not been any increase in the proportion of iatrogenic preterm deliveries during the last decades.The main hypothesis concerning the causality of preterm delivery is still that of the ascending infection from the vagina to the uterus and inflammation resulting in contractions, rupture of membranes and delivery. The mechanisms behind parturition at term are still elusive and this is also true for preterm delivery. The genetic contribution to preterm delivery is about 25-30 %. The first genes that are associated with preterm delivery and gestational duration have recently been published. Huge progress has been made in care of preterm born infants. Sweden has among the lowest rates of mortality and morbidity in the world, especially in the lowest gestational weeks. New modes of care, family-centered care and hospital-assisted home care, have empowered the parents and reduced the cost for care.

The recently documented high survival of extremely preterm infants in Sweden is related to a high degree of centralization of pre- and postnatal care and to recently issued national consensus guidelines providing recommendations for perinatal care at 22-24 gestational weeks. The prevalence of major neonatal morbidity remains high and exceeded 60 % in a recent study of extremely preterm infants born at27 gestational weeks delivered in Sweden in 2014-2016 and surviving to 1 year of age. Damage to immature organ systems inflicted during the neonatal period causes varying degrees of functional impairment with lasting effects in the growing child. There is an urgent need for evidence-based novel interventions aiming to prevent neonatal morbidity with a subsequent improvement of long-term outcome.

γδ T cells are unconventional T cells that function on the border of innate and adaptive immunity. They are suggested to play important roles in neonatal and infant immunity, although their phenotype and function are not fully characterized in early childhood. We aimed to investigate γδ T cells in relation to age, prematurity and cytomegalovirus (CMV) infection. Therefore, we used flow cytometry to characterize the γδ T‐cell compartment in cord blood and peripheral blood cells from 14‐day‐, 2‐year‐ and 5‐year‐old children, as well as in peripheral blood samples collected at several time points during the first months of life from extremely premature neonates. γδ T cells were phenotypically similar at 2 and 5 years of age, whereas cord blood was divergent and showed close proximity to γδ T cells from 14‐day‐old neonates. Interestingly, 2‐year‐old children and adults showed comparable Vδ2+ γδ T‐cell functionality toward both microbial and polyclonal stimulations. Importantly, extreme preterm birth compromised the frequencies of Vδ1+ cells and affected the functionality of Vδ2+ γδ T cells shortly after birth. In addition, CMV infection was associated with terminal differentiation of the Vδ1+ compartment at 2 years of age. Our results show an adult‐like functionality of the γδ T‐cell compartment already at 2 years of age. In addition, we demonstrate an altered γδ T‐cell phenotype early after birth in extremely premature neonates, something which could possible contribute to the enhanced risk for infections in this vulnerable group of children., This research provides important insights into the γδ T‐cell phenotype and function during early infancy, by highlighting a mature γδ T‐cell compartment at 2 years of age and clear short‐term implications of extreme preterm birth.

Background Perinatal childhood exposures, including probiotic supplementation, may affect epigenetic modifications and impact on immune maturation and allergy development. The aim of this study was to assess the effects of pre- and postnatal Lactobacillus reuteri supplementation on DNA methylation in relation to immune maturation and allergy development. Methods DNA methylation patterns were investigated for allergy-related T helper subsets using a locus-specific method and at a genome-wide scale using the Illumina 450K array. From a randomised, double-blind, placebo-controlled allergy prevention trial with pre- and postnatal probiotic supplementation, CD4+ T helper cells were obtained at birth (from cord blood), and 12 and 24 months of age (total (placebo/probiotics); locus-specific method: CB = 32 (17/15), 12 months = 24 (9/15), 24 months = 35 (15/20); Illumina: CB = 19 (10/9), 12 months = 10 (6/4), 24 months = 19(11/8)). Results Comparing probiotics to placebo, the greatest genome-wide differential DNA methylation was observed at birth, where the majority of sites were hypomethylated, indicating transcriptional accessibility in the probiotic group. Bioinformatic analyses, including network analyses, revealed a module containing 91 genes, enriched for immune-related pathways such as chemotaxis, PI3K-Akt, MAPK and TGF-beta signalling. A majority of the module genes were associated with atopic manifestations (OR = 1.43, P = 2.4 x 10(-6)), and a classifier built on this model could predict allergy development (AUC = 0.78, P = 3.0 x 10(e-3)). Pathways such as IFN-gamma signalling and T-cell activation were more hypermethylated at birth compared with later in life in both intervention groups over time, in line with DNA methylation patterns in the IFNG locus obtained by the locus-specific methodology. Conclusion Maternal L. reuteri supplementation during pregnancy alters DNA methylation patterns in CD4+ T cells towards enhanced immune activation at birth, which may affect immune maturation and allergy development. Funding Agencies|Swedish Research CouncilSwedish Research Council [K201156X-21854-01-06, 2015-03807, 201601698]; Heart and Lung FoundationSwedish Heart-Lung Foundation [20140321, 20170365]; Ekhaga Foundation; Ake Viberg Foundation; Olle Engkvist Foundation; Research Council for South-East Sweden; Swedish Asthma and Allergy Association; Cancer and Allergy Association; Foundation Samariten; Konsul Th C Berghs Foundation for Scientific Research; University Hospital of Linkoping, Sweden; Research and Scholarship Foundation in Ostergotland, Sweden

Extremely preterm neonates are particularly susceptible to infections, likely because of severely impaired immune function. However, little is known on the composition of the T cell compartment in early life in this vulnerable population. We conducted a comprehensive phenotypic flow cytometry–based longitudinal analysis of the peripheral conventional T cell compartment of human extremely low gestational age neonates (ELGAN) with extremely low birth weight (ELBW

There are several ways to formulate the dynamics of a substructure. The different domains in which the dynamics can be described will be reviewed since the manner in which substructures are characterized will later determine the substructuring methodology that can be applied. In addition to how the substructures are formulated, the way in which the coupling/decoupling problem is expressed will allow us in the subsequent chapters to develop different numerical and experimental techniques. Two conditions must be satisfied on the interface between substructures: a condition on the displacement field (compatibility) and on the interface stresses (force equilibrium). Those conditions can be accounted for following several different formulations, all mathematically equivalent, but each leading to different numerical methods, experimental approaches, and approximation techniques, as will be explained in the following chapters. In this chapter, we outline the basic concepts of the so-called three-field formulation, dual and primal assembly.—Chapter Author: Daniel Rixen

This chapter reviews common nonlinearities that are encountered in engineering structures, with a particular emphasis on geometric nonlinearity. Popular ways to construct reduced order models for geometrically nonlinear problems are discussed. The concept of nonlinear normal modes is presented to help understand the dynamics of these structures, and some recently presented substructuring methods are reviewed. —Chapter Authors: Matt Allen & Paolo Tiso.

The prior chapter presented rigorous theory and methods for nonlinear systems, which is necessary in general because many nonlinear systems exhibit strong modal coupling due to the nonlinearity; this is commonly the case for the geometrically nonlinear structures that were the focus of that chapter. However, one of the most common sources of nonlinearity in built-up structures is the joints, and in many cases, these introduce only a weak stiffness nonlinearity together with a significant damping nonlinearity. In this case, and in many others that are relevant to industry, one can obtain good estimates of the response of the structure using a weakly nonlinear model in which the linear modes of the structure are presumed to be preserved and coupling between modes is neglected. This chapter provides a brief introduction to these concepts.—Chapter Authors: Randall Mayes and Matt Allen

This section highlights some specialized substructuring methods, such as methods for estimating the fixed-interface modes of a substructure from measurements of the free–free structure with a fixture attached at the interface, and also highlights some industrial examples. Transfer path analysis is reviewed, elaborating some of the similarities in the theoretical foundations. Most information about TPA has been obtained from van der Seijs et al. (2016), please refer to the original paper for a more elaborate discussion. — Chapter Authors: Maarten van der Seijs, Randall Mayes and Matt Allen.

Background: Early colonization with a diverse microbiota seems to play a crucial role for appropriate immune maturation during childhood. Breastmilk microbiota is one important source of microbes for the infant, transferred together with maternal IgA antibodies. We previously observed that allergy development during childhood was associated with aberrant IgA responses to the gut microbiota already at 1 month of age, when the IgA antibodies are predominantly maternally derived in breastfed infants.Objective: To determine the microbial composition and IgA‐coated bacteria in breastmilk in relation to allergy development in children participating in an intervention trial with pre‐ and post‐natal Lactobacillus reuteri supplementation. Methods: A combination of flow cytometric cell sorting and 16S rRNA gene sequencing was used to characterize the bacterial recognition patterns by IgA in breastmilk samples collected one month post‐partum from 40 mothers whose children did or did not develop allergic and asthmatic symptoms during the first 7 years of age. Results: The milk fed to children developing allergic manifestations had significantly lower bacterial richness, when compared to the milk given to children that remained healthy. Probiotic treatment influenced the breastmilk microbiota composition. However, the proportions of IgA‐coated bacteria, the total bacterial load and the patterns of IgA‐coating were similar in breastmilk between mothers of healthy children and those developing allergies. Conclusion: Consumption of breastmilk with a reduced microbial richness in the first month of life may play an important role in allergy development during childhood., This study was supported by the Spanish Ministry of Economy and Competitiveness (Grant No. BIO2015‐68711‐R) to Alex Mira. This study was supported by the Swedish Research Council (2016‐01698), the Swedish Heart and Lung Foundation (20140321 and 20170365) and the Cancer and Allergy Foundation to Maria C. Jenmalm. This study was supported by European Research Council (ERC‐starting grant 639226) to M. Carmen Collado.