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Background and Aims A better understanding of distinct subgroups in atopic dermatitis (AD) is warranted. The aim was to identify and determine characteristics of clusters based on anatomical location of AD. Methods In this 8‐week, observational, decentralized study, patients with AD completed a baseline questionnaire about anatomical location and severity of AD, and a principal component analysis (PCA) was applied to identify clusters. The Patient‐Oriented Eczema Measure (POEM) was completed weekly and photographs of affected body areas were captured by the participants' own smartphones. From the weekly photographs, the AD severity was evaluated using the intensity part of the SCORing Atopic Dermatitis. Results Fifty‐five participants were recruited, of which 53 completed the baseline questionnaire with a mean POEM of 14.5 (SD: 5.6). The PCA analysis revealed three clusters, with AD predominantly on the shins, knees, and genitals (Cluster 1), with involvement of the upper body (Cluster 2), and with AD on the hands and feet (Cluster 3). Cluster 1 had a lower mean POEM score (11.12, SD: 5.3) compared with Clusters 2 (12.64, SD: 4.5) and 3 (15.98, SD: 4.7), respectively (p = 0.007). Further, Cluster 1 had the highest age of AD onset (mean 9.5 vs. 2.5 and 4.7 years, p = 0.02) and the lowest proportion of asthma/allergy (47% vs. 82% and 90%, p = 0.01). Conclusion Three clusters of patients with AD based on affected body areas were identified. The cluster with involvement of legs and genitals was characterized by the oldest age of AD onset and the lowest prevalence of asthma/allergy.

Infectious diarrhoea is a worldwide problem in newborns. Optimal bacterial colonisation may enhance gut maturation and protect against pathogenic bacteria after birth. We hypothesised that lactic acid bacteria (LAB) administration prevents pathogen-induced diarrhoea in formula-fed newborns. Newborn caesarean-delivered, colostrum-deprived term piglets on parenteral nutrition for the first 15 h, were used as models for sensitive newborn infants. A commercially available probiotic strain, Lactobacillus paracasei F19 (LAP, 2·6×108 colony-forming units (CFU)/kg per d) and a novel LAB isolate, Pediococcus pentosaceus (PEP, 1·3×1010 CFU/kg per d), were administered for 5 d with or without inoculation of the porcine pathogen, Escherichia coli F18 (F18, 1010 CFU/d). This resulted in six treatment groups: Controls (n 9), LAP (n 10), PEP (n 10), F18 (n 10), F18–LAP (n 10) and F18–PEP (n 10). The pathogen challenge increased diarrhoea and density of F18 in the intestinal mucosa (P<0·05). LAB supplementation further increased the diarrhoea score, relative to F18 alone (P<0·01). Intestinal structure and permeability were similar among groups, whereas brush border enzymes were affected in variable intestinal regions with decreased activities in most cases after F18 and LAB inoculation. Bacterial density in colon mucosa increased after F18 inoculation (P<0·05) but was unaffected by LAB supplementation. In colon contents, acetic and butyric acids were increased by PEP (P<0·05). The LAB used in this study failed to reduce E. coli-induced diarrhoea in sensitive newborn pigs. In vulnerable newborns there may be a delicate balance among bacterial composition and load, diet and the host. Caution may be required when administering LAB to compromised newborns suffering from enteric infections.

Several studies have investigated the effects of fish oil (FO) on infant growth, but little is known about the effects of FO and sex on insulin-like growth factor-1 (IGF-1), the main regulator of growth in childhood. We explored whether FO v. sunflower oil (SO) supplementation from 9 to 18 months of age affected IGF-1 and its binding protein-3 (IGFBP-3) and whether the potential effects were sex specific. Danish infants (n 115) were randomly allocated to 5 ml/d FO (1·2 g/d n-3 long-chain PUFA (n-3 LCPUFA)) or SO. We measured growth, IGF-1, IGFBP-3 and erythrocyte EPA, a biomarker of n-3 LCPUFA intake and status, at 9 and 18 months. Erythrocyte EPA increased strongly with FO compared with SO (P<0·001). There were no effects of FO compared with SO on IGF-1 in the total population, but a sex×group interaction (P=0·02). Baseline-adjusted IGF-1 at 18 months was 11·1 µg/l (95 % CI 0·4, 21·8; P=0·04) higher after FO compared with SO supplementation among boys only. The sex×group interaction was borderline significant in the model of IGFBP-3 (P=0·09), with lower IGFBP-3 with FO compared with SO among girls only (P=0·03). The results were supported by sex-specific dose–response associations between changes in erythrocyte EPA and changes in IGF-1 and IGFBP-3 (both P<0·03). Moreover, IGF-1 was sex specifically associated with BMI and length. In conclusion, FO compared with SO resulted in higher IGF-1 among boys and lower IGFBP-3 among girls. The potential long-term implications for growth and body composition should be investigated further.

Preterm pigs show many signs of immaturity that are characteristic of preterm infants. In preterm infants, the cerebellum grows particularly rapid and hypoplasia and cellular lesions are associated with motor dysfunction and cognitive deficits. We hypothesized that functional brain delays observed in preterm pigs would be paralleled by both structural and molecular differences in the cerebellum relative to term born piglets. Cerebella were collected from term (n = 56) and preterm (90% gestation, n = 112) pigs at 0, 5, and 26 days after birth for stereological volume estimations, large‐scale qPCR gene expression analyses (selected neurodevelopmental genes) and western blot protein expression analysis (Sonic Hedgehog pathway). Memory and learning was tested using a T‐maze, documenting that preterm pigs showed delayed learning. Preterm pigs also showed reduced volume of both white and gray matter at all three ages but the proportion of white matter increased postnatally, relative to term pigs. Early initiation of enteral nutrition had limited structural or molecular effects. The Sonic Hedgehog pathway was unaffected by preterm birth. Few differences in expression of the selected genes were found, except consistently higher mRNA levels of Midkine, p75, and Neurotrophic factor 3 in the preterm cerebellum postnatally, probably reflecting an adaptive response to preterm birth. Pig cerebellar development appears more affected by postconceptional age than by environmental factors at birth or postnatally. Compensatory mechanisms following preterm birth may include faster white matter growth and increased expression of selected genes for neurotrophic factors and regulation of angiogenesis. While the pig cerebellum is immature in 90% gestation preterm pigs, it appears relatively mature and resilient toward environmental factors. We recently demonstrated impaired motor skills and cognitive capacity in our well established pig model of premature birth (Andersen et al., Am. J. Physiol. Regul. Integr. Comp. Physiol., 310(6): R481‐R492, 2016) and hypothesized that moderate preterm birth would be associated with impaired cerebellar growth and altered gene expression postnatally. Cerebella were collected from term (n = 56) and preterm (90% gestation, n = 112) pigs at 0, 5 and 26 days after birth for stereological volume estimations, large‐scale qPCR neurodevelopmental gene expression analyses and Western blot (Sonic Hedgehog pathway). Although minor differences with regards to cerebellar gray and white matter volumes and gene expression difference for a few specific angiogenesis and neurotrophic factors was observed between the preterm and term cerebella, development of this pig brain region seemed more affected by postconceptional age than by environmental factors at birth or postnatally, indicating an advanced level of maturation.

Cyber-physical systems (CPSs) for real-time advanced process control (RT-APC) are a class of control systems using network communication to control industrial processes. In this paper, we use simple examples to describe the software principles and concepts used in the implementation of such systems. The key software principles are 1) shared data in the form of a database, files, or shared memory, 2) timers and threads for concurrent periodic execution of tasks, and 3) network communication between the control system and the process, and communication between the control system and the internet, e.g., the cloud to enable remote monitoring and commands. We show how to implement such systems for Linux operating systems applying the C programming language and we also comment on the implementation using the Python programming language. Finally, we present a complete simulation experiment using a real-time simulator.

We compare the performance of proportional-integral-derivative (PID) control, linear model predictive control (LMPC), and nonlinear model predictive control (NMPC) for a physical setup of the quadruple tank system (QTS). We estimate the parameters in a continuous-discrete time stochastic nonlinear model for the QTS using a prediction-error-method based on the measured process data and a maximum likelihood (ML) criterion. In the NMPC algorithm, we use this identified continuous-discrete time stochastic nonlinear model. The LMPC algorithm is based on a linearization of this nonlinear model. We tune the PID controller using Skogestad's IMC tuning rules using a transfer function representation of the linearized model. Norms of the observed tracking errors and the rate of change of the manipulated variables are used to compare the performance of the control algorithms. The LMPC and NMPC perform better than the PID controller for a predefined time-varying setpoint trajectory. The LMPC and NMPC algorithms have similar performance.

Ribosomes are complex ribozymes that interpret genetic information by translating messenger RNA (mRNA) into proteins. Natural variation in ribosome composition has been documented in several organisms and can arise from several different sources. A key question is whether specific control over ribosome heterogeneity represents a mechanism by which translation can be regulated. We used RiboMeth-seq to demonstrate that differential 2′-O-methylation of ribosomal RNA (rRNA) represents a considerable source of ribosome heterogeneity in human cells, and that modification levels at distinct sites can change dynamically in response to upstream signaling pathways, such as MYC oncogene expression. Ablation of one prominent methylation resulted in altered translation of select mRNAs and corresponding changes in cellular phenotypes. Thus, differential rRNA 2′-O-methylation can give rise to ribosomes with specialized function. This suggests a broader mechanism where the specific regulation of rRNA modification patterns fine tunes translation. Dynamic changes in 2′-O-methylation of rRNA in human cells lead to ribosome heterogeneity and result in altered translation of select mRNAs, correlating with changes in cellular phenotypes.

Previous studies have linked activity in the upper trapezius muscle with neck pain. However, no studies have examined whether asymmetric activation of these muscles during the working day is associated with neck pain. This study aimed to investigate this relationship. Seven research institutes provided data on bilateral upper trapezius muscle activity on one working day, along with corresponding questionnaire data on cross-sectional (n = 530) and longitudinal (n = 256) neck pain intensity. The asymmetry, defined as the activity difference between the two upper trapezius muscles, was calculated as an average across the entire workday and within various intensity levels in relation to maximum voluntary isometric contraction (MVIC). Unadjusted and adjusted linear regression analyses were executed to examine the association between asymmetric muscle activation and neck pain intensity. In cross-sectional analyses, asymmetry in the levels 0-0.05 and 0.05-2%MVIC was significantly positively associated with neck pain intensity in both unadjusted and adjusted analyses. Asymmetry in the levels of 4-6, 6-8 and 8-10%MVIC was significantly negatively associated with neck pain in unadjusted analyses. In longitudinal analyses, significant positive associations were found for asymmetry in level 0-0.05%MVIC and negative associations for asymmetry in levels > 20%MVIC. While asymmetry in the very low levels of muscle activity may be associated with higher neck pain intensity, asymmetry in the higher levels of muscle activity was negatively associated with neck pain intensity. However, the explained variance of the models was small, and the results should therefore be interpreted with caution. The findings suggest that work conditions facilitating simultaneous relaxation during breaks and balanced activation of both muscles during static activities may be relevant for neck pain prevention, though further research is needed to establish causality.

Objectives:To determine the role of physical activity intensity and bout-duration in modulating associations between physical activity and cardiometabolic risk markers.Methods:A cross-sectional study using the International Children’s Accelerometry Database (ICAD) including 38,306 observations (in 29,734 individuals aged 4–18 years). Accelerometry data was summarized as time accumulated in 16 combinations of intensity thresholds (≥500 to ≥3000 counts/min) and bout-durations (≥1 to ≥10 min). Outcomes were body mass index (BMI, kg/m2), waist circumference, biochemical markers, blood pressure, and a composite score of these metabolic markers. A second composite score excluded the adiposity component. Linear mixed models were applied to elucidate the associations and expressed per 10 min difference in daily activity above the intensity/bout-duration combination. Estimates (and variance) from each of the 16 combinations of intensity and bout-duration examined in the linear mixed models were analyzed in meta-regression to investigate trends in the association.Results:Each 10 min positive difference in physical activity was significantly and inversely associated with the risk factors irrespective of the combination of intensity and bout-duration. In meta-regression, each 1000 counts/min increase in intensity threshold was associated with a −0.027 (95% CI: −0.039 to −0.014) standard deviations lower composite risk score, and a −0.064 (95% CI: −0.09 to −0.038) kg/m2 lower BMI. Conversely, meta-regression suggested bout-duration was not significantly associated with effect-sizes (per 1 min increase in bout-duration: −0.002 (95% CI: −0.005 to 0.0005) standard deviations for the composite risk score, and −0.005 (95% CI: −0.012 to 0.002) kg/m2 for BMI).Conclusions:Time spent at higher intensity physical activity was the main determinant of variation in cardiometabolic risk factors, not bout-duration. Greater magnitude of associations was consistently observed with higher intensities. These results suggest that, in children and adolescents, physical activity, preferably at higher intensities, of any bout-duration should be promoted.

A large Scandinavian randomized trial showed no important outcome differences between hemoglobin levels of 7 g per deciliter and 9 g per deciliter as transfusion thresholds in patients with septic shock. Blood transfusions are frequently given to patients with septic shock. 1 – 4 Some of these transfusions are given to patients who are bleeding, but many nonbleeding patients also undergo transfusion. 5 The recommendations of the Surviving Sepsis Campaign regarding blood transfusion in patients with septic shock are complex and include a recommendation for transfusion to maintain a hematocrit of more than 30% in the presence of hypoperfusion in the first 6 hours. 6 After that, the transfusion threshold should be a hemoglobin level of less than 7 g per deciliter, aiming at levels between 7 g and 9 g per deciliter in patients . . .