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Recently, a regional MPC approach has been proposed that exploits the piecewise affine structure of the optimal solution (without computing the entire explicit solution before). Here, regional refers to the idea of using the affine feedback law that is optimal in a vicinity of the current state of operation, and therefore provides the optimal input signal without requiring to solve a QP. In the present paper, we apply the idea of regional MPC to min-max MPC problems. We show that the new robust approach can significantly reduce the number of QPs to be solved within min-max MPC resulting in a reduced overall computational effort. Moreover, we compare the performance of the new approach to an existing robust regional MPC approach using a numerical example with varying horizon. Finally, we provide a rule for choosing a suitable robust regional MPC approach based on the horizon., Comment: 9 pages, 1 figure

Postnatal maturation of the immune system is poorly understood, as is its impact on illnesses afflicting term or preterm infants, such as bronchopulmonary dysplasia (BPD) and BPD-associated pulmonary hypertension. These are both cardiopulmonary inflammatory diseases that cause substantial mortality and morbidity with high treatment costs. Here, we characterized blood samples collected from 51 preterm infants longitudinally at five time points, 20 healthy term infants at birth and age 3 to 16 weeks, and 5 healthy adults. We observed strong associations between type 2 immune polarization in circulating CD3 + CD4 + T cells and cardiopulmonary illness, with odds ratios up to 24. Maternal magnesium sulfate therapy, delayed hepatitis B vaccination, and increasing fetal, but not maternal, chorioamnionitis severity were associated with attenuated type 2 polarization. Blocking type 2 mediators such as interleukin-4 (IL-4), IL-5, IL-13, or signal transducer and activator of transcription 6 (STAT6) in murine neonatal cardiopulmonary disease in vivo prevented changes in cell type composition, increases in IL-1β and IL-13, and losses of pulmonary capillaries, but not gains in larger vessels. Thereby, type 2 blockade ameliorated lung inflammation, protected alveolar and vascular integrity, and confirmed the pathological impact of type 2 cytokines and STAT6. In-depth flow cytometry and single-cell transcriptomics of mouse lungs further revealed complex associations between immune polarization and cardiopulmonary disease. Thus, this work advances knowledge on developmental immunology and its impact on early life disease and identifies multiple therapeutic approaches that may relieve inflammation-driven suffering in the youngest patients.

In model predictive control (MPC), an optimal control problem (OCP) is solved for the current state and the first input of the solution, the optimal feedback law, is applied to the system. This procedure requires to solve the OCP in every time step. Recently, a new approach was suggested for linear MPC. The parametric solution of a linear quadratic OCP is a piecewise-affine feedback law. The solution at a point in state space provides an optimal feedback law and a domain on which this law is the optimal solution. As long as the system remains in the domain, the law can be reused and the calculation of an OCP is avoided. In some domains the optimal feedback laws are identical. By uniting the corresponding domains, bigger domains are achieved and the optimal feedback law can be reused more often. In the present paper, we investigate in how far this approach can be extended from linear to nonlinear MPC, we propose an algorithm and we illustrate the achieved savings with an example., Comment: 7 pages, 3 figures

Zusammenfassung Prädiktive Regler basieren üblicherweise auf dem numerischen Lösen von Optimalsteuerungsaufgaben (OSA). Dieses Vorgehen kann als punktweises Auswerten eines nur implizit definierten Regelgesetzes aufgefasst werden. Bei der linearen modellprädiktiven Regelung (MPC) definiert die Lösung der OSA nicht nur die optimale Rückführung an einem Punkt, sondern auf einem Polytop im Zustandsraum. Indem dieses Gesetz so lange verwendet wird, wie das System im aktuellen Polytop bleibt, entsteht eine regionale MPC, und die OSA muss nur bei Verlassen des Polytops gelöst werden. Es werden zwei Ansätze vorgeschlagen, die die Zahl der zu lösenden OSA weiter reduzieren. Der erste basiert auf der Aktualisierung des Regelgesetzes mit Hilfe einer Analyse benachbarter Polytope. Der zweite lässt eine suboptimale Verwendung der Rückführung zu, die zu vergrößerten Gültigkeitsregionen führt.

The solution to a linear MPC problem for a fixed state x is usually interpreted as the optimal feedback signal u(x) for that particular state variable value. The solution to the MPC problem at a point in state space contains more information, however. It does not only determine the optimal feedback signal u(x) at the particular point x, but it determines an affine control law u(•) that provides the optimal feedback on an entire state-space polytope. It is an obvious idea to use this affine control law as long as the closed-loop system stays in the current polytope, and to solve a QP only to determine a new affine law and polytope of validity whenever the current polytope is left. The present paper extends this idea by a method that avoids solving QPs (or optimality conditions) when a new polytope is entered. This is accomplished by triggering active set updates instead of solving QPs or optimality conditions whenever possible. We state conditions under which these active set updates are possible and demonstrate the usefulness of the idea with several examples.

We extend a recently proposed robust event-triggered MPC approach that exploits the piecewise affine structure of the solution. Robust optimal feedback laws and their regions of validity are calculated on a central compute node on demand. These regional laws are used by one or more local nodes in local feedback loops. Whenever one of the local systems detects that the region of validity of the current optimal control law has been left, it requests a new law from the central node. The present paper uses a particular variant of updating the control laws in a way that reduces the number of requests to the central node.

We show how to exploit the piecewise affine structure of the optimal control law in networked linear-quadratic MPC. The complete explicit solution is not required in this approach, but the current piece, i.e., the feedback law and its polytope of validity, is computed on demand instead. Assuming such a piece has been determined for the current state, a lean local computational node suffices to check whether future states are still in the current polytope and to evaluate the optimal affine feedback law if that is the case. Whenever the system leaves the current polytope, the local node requests a central, powerful node to determine a new control law and polytope by solving a MPC problem, and to send the resulting law and polytope over the network. In this contribution we extend the approach by not sending the information for a single control law, but for multiple control laws for the predicted system behavior. We show that the number of requests and the amount of transmitted data can be reduced by using active set updates on the local node.

Summary Objective B-type natriuretic peptide (BNP) has been shown to correlate with pulmonary hypertension (PH) in term neonates with persistent pulmonary hypertension of the newborn or congenital diaphragmatic hernia, and in very preterm infants with bronchopulmonary dysplasia. This study investigated the potential association of BNP and N-terminal-pro-BNP (NTproBNP) and PH within the first 72 hr of life in very preterm infants. Methods Preterm infants

Necrotizing enterocolitis (NEC) is a severe, currently untreatable intestinal disease that predominantly affects preterm infants and is driven by poorly characterized inflammatory pathways. Here, human and murine NEC intestines exhibit an unexpected predominance of type 3/TH17 polarization. In murine NEC, pro-inflammatory type 3 NKp46−RORγt+Tbet+ innate lymphoid cells (ILC3) are 5-fold increased, whereas ILC1 and protective NKp46+RORγt+ ILC3 are obliterated. Both species exhibit dysregulation of intestinal TLR repertoires, with TLR4 and TLR8 increased, but TLR5-7 and TLR9-12 reduced. Transgenic IL-37 effectively protects mice from intestinal injury and mortality, whilst exogenous IL-37 is only modestly efficacious. Mechanistically, IL-37 favorably modulates immune homeostasis, TLR repertoires and microbial diversity. Moreover, IL-37 and its receptor IL-1R8 are reduced in human NEC epithelia, and IL-37 is lower in blood monocytes from infants with NEC and/or lower birthweight. Our results on NEC pathomechanisms thus implicate type 3 cytokines, TLRs and IL-37 as potential targets for novel NEC therapies., Necrotizing Enterocolitis (NEC) is an untreatable intestinal disease in infants. Here the authors show that human and experimental mouse NEC is associated with altered toll-like receptor expression in the intestine, enhanced Th17/type 3 polarization in adaptive immune and innate lymphoid cells, dysregulated microbiota, and reduced interleukin-37 signaling.

The piecewise affine structure of an MPC law can be efficiently used in event-triggered control (without computing the whole law explicitly). We extend the original approach for linear deterministic systems to systems with additive disturbances. Surprisingly, the resulting event-triggered RMPC performs better than its deterministic counterpart in that the reduction of the computational effort during runtime is higher.

Objective Unplanned extubation (UE) occurs as an infrequent complication of mechanical ventilation in the neonatal intensive care unit (NICU). Following UE, a trial of noninvasive ventilation (NIV) may be considered if a neonate is showing adequate respiratory effort. This study investigated the success and failure rate of NIV management of neonates experiencing UE. Study Design Retrospective single-center study of neonates experiencing UE in the NICU over a 9-year period. Reintubation within 12 hours of a trial of NIV following UE was defined as treatment failure. Short-term respiratory outcomes were analyzed for all infants plus the incidence of bronchopulmonary dysplasia for preterm infants born less than 32 weeks' gestation. Results A total of 43 patients were included. Of those, 30 infants were trialed on NIV following UE. Baseline demographics were similar between both the groups except for the oxygen requirement before UE. The NIV was successful in 20 and failed in 10 infants. Infants who failed a trial of the NIV were reintubated between 0.45 and 5.25 hours following UE. Respiratory outcomes in very preterm infants did not differ between groups. Conclusion A trial of NIV may be considered as a treatment option in preterm and term newborns experiencing UE in the NICU.

Aim B-type natriuretic peptide (BNP) and N-terminal pro-BNP (NTproBNP) have been shown to correlate with the size of the patent ductus arteriosus (PDA) in preterm infants. We investigated whether BNP or NTproBNP was more closely correlated with PDA size. Methods This prospective observational study included preterm infants born

Language barriers hinder the interaction with patients and relatives. The use of language services increases knowledge, satisfaction and the use of medical care and thus improves patient's clinical outcome. The recommended use of professional interpreters (PI) is not always feasible. We tested an online translation tool as an alternative for PI for the transla-tion of standardized sentences from a neonatal doctor-/nurse-relative-interview.Translation of 20 sentences from a German neonatal intensive care unit parent information brochure to English, Portuguese and Arabic, using Google Translate (GT). Assessment of accuracy concerning grammar and content, in a second step simplification of all incorrect sentences, translation by GT and critical re-assessment and evaluation.An average of 42% of the sentences was correctly translated concerning grammar and content. The proportion of incorrectly translated sentences varied between 45-70%. By simpli-fication another 23% were translated correctly.Translations by GT were often incorrect in content and grammar. We suppose that the design of GT, which is a statistical translation engine, might be an explanation for this phenomenon. Presently, GT cannot guarantee unambiguous translations and cannot substitute PIs, only in particular circumstances, the use of GT or similar engines may be justified. For future use of electronic translation services, we suggest to compile a catalogue of sentences containing central information, which can be translated into defined foreign languages without misinterpretation or loss of information.

Sildenafil has been shown to preserve alveolar growth and lung angiogenesis in a rat model of bronchopulmonary dysplasia. We conducted a proof-of-concept randomised controlled pilot study to assess the feasibility of oral sildenafil treatment in extremely preterm infants with evolving bronchopulmonary dysplasia.Preterm infants28 weeks gestational age were eligible if they were mechanically ventilated on day 7 of life. Infants were randomised to a 4-weeks course of either oral sildenafil (3 mg/kg/day) or placebo solution. Pre-discharge cardiorespiratory outcomes and medication side effects were collected.Twenty infants were randomised, 10 received sildenafil (mean gestational age 24 + 5 weeks (SD 4.9 days), mean weight 692 g (SD 98)) and 10 received placebo (mean gestational age 24 + 5 weeks (SD 6.5 days), mean weight 668 g (SD 147)). One infant in the sildenafil group did not receive treatment because of an early pneumoperitoneum. Two infants did not complete the study (transferred out). Of the remaining seven treated infants, three died (two from respiratory-related causes). One infant in the control group died from a non-respiratory cause. Sildenafil did not reduce length of invasive (median 688 versus 227 h) or non-invasive ventilation (median 1609 versus 1416 h). More infants in the sildenafil group required postnatal steroid treatment. One infant developed hypotension following sildenafil administration and was excluded after three doses.In this pilot study, oral sildenafil treatment did not improve any short-term respiratory outcomes in extremely preterm infants.

Non-invasive ventilation (NIV) is increasingly used as first-line management of respiratory distress syndrome in preterm infants to avoid the lung-damaging effects of mechanical ventilation (MV). We hypothesised that even a short period of MV following surfactant treatment would increase the rate of bronchopulmonary dysplasia (BPD).Retrospective study including preterm infants30 weeks gestational age over a six-year period if they required surfactant followed by MV not longer than 24 h (SURFMV group) or if managed exclusively with NIV (NIV group). Baseline and morbidity variables such as gestation, birth weight, sex, place of birth, antenatal steroids, sepsis, pneumothorax, intraventricular haemorrhage, necrotising enterocolitis, and patent ductus arteriosus were analysed in a multivariate model for potential confounding.289 infants were included: 150 in the NIV group and 139 in the SURFMV group. Seventeen infants in the NIV group and 23 in the SURFMV group developed BPD (odds ratio: 1.55; 95% confidence interval (CI): 0.79-3.05; p = 0.202). After adjusting for potential confounders, the odds ratio was 1.09 for the SURFMV group to develop BPD (95% CI: 0.52-2.28; p = 0.812).The rate of BPD did not differ between infants managed with NIV or with surfactant administration followed by ≤24 h of MV after adjusting for confounding factors.

Background: Excessive ambient noise levels have been identified as a potential risk factor for adverse outcome in very preterm infants. Noise level measurements for continuous positive airway pressure (CPAP) devices demonstrated that these constantly exceed current recommendations. The use of high-flow nasal cannula (HFNC) as an alternative non-invasive ventilation modality has become more popular in recent years in neonatal care. Objective: To study noise levels of two HFNC devices commonly used in newborns. As a comparison, noise levels of a continuous flow CPAP device were also studied. Methods: In-vitro study. The noise levels of two contemporary HFNC devices (Fisher & Paykel NHF™ and Vapotherm Precision Flow®) and one CPAP device (Dräger Babylog® 8000 plus) were measured in the oral cavity of a newborn manikin in an incubator in a quiet environment. HFNC flows of 4-8 l/min and CPAP pressures of 4-8 cm H2O were applied. The CPAP flow was set at 8 l/min as per unit practice. Results: Vapotherm HFNC generated the highest noise levels, measuring 81.2-91.4 dB(A) with increasing flow. Fisher & Paykel HFNC noise levels were between 78.8 and 81.2 dB(A). The CPAP device generated the lowest noise levels between 73.9 and 77.4 dB(A). Conclusions: Both HFNC devices generated higher noise levels than the CPAP device. All noise levels were far above current recommendations of the American Academy of Pediatrics. In light of the long duration of non-invasive respiratory support of very preterm infants, less noisy devices are required to prevent the potentially adverse effects of continuing excessive noise exposure in the neonatal intensive care unit.

We investigated dwell times and risk of non-elective removal of 975 single-lumen 1-French peripherally inserted central catheters (1FR-PICC) according to tip position in a cohort of very preterm infants with a mean (SD) gestational age of 27+6 (2+1) weeks and a mean (SD) birth weight of 988 (294) g over an eight-year period. Infants with a 1FR-PICC inserted for continuous infusion of intravenous fluids within the first 30 days of life were eligible. Dwell times of PICC with elective versus non-elective removal, risk of non-elective removal of PICC according to tip position, and differences between upper versus lower limb catheter insertion were analysed. 33.8% PICC were removed non-electively. Median (IQR) dwell time was 193 (142–287) versus 154 (102–260) h for elective versus non-elective removal (p < 0.001). Non-elective removal was more common for lower limb insertion sites: 41 versus 31% (p = 0.002). PICC were significantly more likely to be removed non-electively when located in the axillary (odds ratio (OR) 2.08), cephalic (OR 8.93), external iliac (OR 4.99), and femoral (OR 10.31) vein.

The behavior of charged bio polymer micro particles when deposited onto a CMOS chip can be analytically modeled in form of the incompressible Navier-Stokes equation and the electrostatic Poisson equation, as we describe in this article. Based on these models, numerical simulations of depositions can be implemented in COMSOL that lead to improvements in the experimental setup, optimizing the size and charge distribution of the micro particles. Adapting the experiments according to the simulation results, we will show the powerful gain in deposition precision, which is essential for a contamination-free deposition and hence high quality combinatorial deposition.

We built high voltage complementary metal oxide semiconductor (CMOS) chips that generate electrical fields on their surface, such that electrically charged microparticles (diameter 10–20 μm on average) can be addressed on distinct pixel electrodes according to arbitrary field patterns. Each pixel contains a memory cell in canonical low-voltage CMOS-technology controlling a high voltage (30–100 V) potential area on the top metal layer. Particle transfer with minimal contaminations in less than 10 s for a complete chip was observed for pixels of 100 μm × 100 μm down to 65 μm × 65 μm. This allows a new way to create surface modifications on top of CMOS chips without need for additional masks or stamps. Using suitable particles, a chemically modified chip surface, and compatible chemistry, this method can be utilized for self-aligned high-density biopolymer arrays, e.g., peptide arrays. Transfer of microparticles loaded with amino acids for combinatorial peptide synthesis is demonstrated. Successful synthesis of different peptides (octamers) was proven by immunostaining. Based on results obtained by a chip containing pixel areas of different characteristics, a chip for biological applications with 16,384 pixels (10,000 pixel/cm 2 ) was built. Good homogeneity of peptide synthesis over the chip area was verified by immunostaining.

however, thedecodingofpeptidebindersislaborintensive.Furthermore,problematicpeptides,forexample,hydrophobicpeptidesthatbind nonspecifically to any protein, are also synthesizedduringlibrarypreparationbythesemethods.Arrays do not have these drawbacks. The position of agivenpeptideonanarraycorrespondsdirectlytoitssequence,and problematic peptides can be omitted in subsequentarrays. Peptide arrays were first described by Frank, whosespotsynthesisdominatesthefieldbecauseofitsreliabilityandwideapplicability.

We report the uncommon clinical course of tetanus in a completely immunized 14-year-old boy. His initial symptoms, which included a flaccid paralysis, supported a diagnosis of botulism. Preliminary mouse-test results with combined botulinum antitoxins A, B, and E, obtained from tetanus-immunized horses, backed this diagnosis. The change in his clinical course from paralysis to rigor and the negative, more specific, botulinum mouse test with isolated botulinum antitoxins A, B, and E, obtained from nonvaccinated rabbits, disproved the diagnosis of botulism. Tetanus was suspected despite complete vaccination. The final results of a positive mouse test performed with isolated tetanus antitoxin confirmed the diagnosis. Adequate treatment was begun, and the boy recovered completely.

We present a method based on induced currents in a cylindrical probe which allows analysis of the micro-particle charging processes in an aerosol. The micro particles were triboelectrically charged by passing through a dielectric tube coaxially mounted into the probe. The cylindrical probe enabled the quantification of particle charging without prior calibration of the probe. An analytic model was developed for the description of the measured induced currents and implemented into a computer simulation program. The combination of model simulations and an appropriate experimental setup revealed comprehensive data for the determination of the particles' electric charge against time of flight through the tube. In methodological proof of principle experiments, the formations of particle clouds with charges of different signs were observed using magnetite micro particles.

B-type natriuretic peptide (BNP) has been shown to correlate with pulmonary hypertension (PH) in term neonates with persistent pulmonary hypertension of the newborn or congenital diaphragmatic hernia, and in very preterm infants with bronchopulmonary dysplasia. This study investigated the potential association of BNP and N-terminal-pro-BNP (NTproBNP) and PH within the first 72 hr of life in very preterm infants.Preterm infants32 weeks gestational age who received an echocardiogram within the first 72 hr of life were eligible. BNP and NTproBNP were sampled at the time of the echocardiogram. Right ventricular systolic pressure (RVSP) was calculated as a surrogate marker of PH. Simple and multiple linear regression analysis was performed to examine associations and potential confounding factors.Sixty-one infants were included with a median (IQR) birth weight of 983 g (826-1,167) and a median (IQR) gestational age of 27(2) weeks (26(2) -28(6) ). There was no difference between BNP or NTproBNP levels for infants with or without measurable RVSP. There was no significant correlation of BNP and RVSP in multiple linear regression analysis (regression coefficient -0.0035 (95%CI: -0.020 to 0.013), P = 0.67). Also, NTproBNP and RVSP were not significantly correlated in multiple linear regression analysis (regression coefficient 0.0071 (95%CI: -0.019 to 0.033), P = 0.58).B-type natriuretic peptides did not correlate with RVSP in the early postnatal period of very preterm infants. Pediatr Pulmonol. 2016;51:820-824. © 2016 Wiley Periodicals, Inc.

Summary Background Molybdenum cofactor deficiency (MoCD) is characterised by early, rapidly progressive postnatal encephalopathy and intractable seizures, leading to severe disability and early death. Previous treatment attempts have been unsuccessful. After a pioneering single treatment we now report the outcome of the complete first cohort of patients receiving substitution treatment with cyclic pyranopterin monophosphate (cPMP), a biosynthetic precursor of the cofactor. Methods In this observational prospective cohort study, newborn babies with clinical and biochemical evidence of MoCD were admitted to a compassionate-use programme at the request of their treating physicians. Intravenous cPMP (80–320 μg/kg per day) was started in neonates diagnosed with MoCD (type A and type B) following a standardised protocol. We prospectively monitored safety and efficacy in all patients exposed to cPMP. Findings Between June 6, 2008, and Jan 9, 2013, intravenous cPMP was started in 16 neonates diagnosed with MoCD (11 type A and five type B) and continued in eight type A patients for up to 5 years. We observed no drug-related serious adverse events after more than 6000 doses. The disease biomarkers urinary S-sulphocysteine, xanthine, and urate returned to almost normal concentrations in all type A patients within 2 days, and remained normal for up to 5 years on continued cPMP substitution. Eight patients with type A disease rapidly improved under treatment and convulsions were either completely suppressed or substantially reduced. Three patients treated early remain seizure free and show near-normal long-term development. We detected no biochemical or clinical response in patients with type B disease. Interpretation cPMP substitution is the first effective therapy for patients with MoCD type A and has a favourable safety profile. Restoration of molybdenum cofactor-dependent enzyme activities results in a greatly improved neurodevelopmental outcome when started sufficiently early. The possibility of MoCD type A needs to be urgently explored in every encephalopathic neonate to avoid any delay in appropriate cPMP substitution, and to maximise treatment benefit. Funding German Ministry of Education and Research; Orphatec/Colbourne Pharmaceuticals.

D. Woodrow Benson Cincinnati Children’s Hospital Medical Center Cincinnati, OH, USA Sirs: Congenital heart disease has the highest incidence of all birth defects affecting about 6–8/1000 live births. These heart malformations are believed to arise during cardiac development, but there is little known about the underlying mechanisms of disease [12]. Cardiac development is a complex process, and in recent years, the role of transcription factors as possible navigators of development has been frequently investigated [7, 10, 19]. The cardiac transcription factor NKX2.5 was identified as the first genetic cause of nonsyndromic congenital heart disease [22]. A total of 33 heterozygous mutations in NKX2.5 have been reported in individuals with a variety of congenital heart malformations, including atrial septal defect, ventricular septal defect, tetralogy of Fallot and abnormalities of the tricuspid valve [2, 6, 8, 9, 11, 13, 14, 16, 18, 21–23]. Specific types of mutations result in progressive atrioventricular (AV) conduction disturbance, requiring pacemaker implantation. These studies have provided important insight into the genetic origins of cardiac malformations and, by providing tools for the developmental biologist, have contributed to improved insights into the pathogenesis of congenital heart disease [3, 5]. As such, these results are important to pediatricians, cardiologists and surgeons who diagnose, treat and provide longterm follow-up to these patients. Here we report a novel NKX2.5 mutation in a small family where progressive AV block and congenital heart disease was identified in two generations.

Aims This study aims to determine if there is a difference in the pharyngeal pressure, measured as a surrogate for continuous positive distending airway pressure, delivered to premature infants between two commonly used heated, humidified high-flow nasal cannulae (HHHFNC) devices: Fisher & Paykel Healthcare HHHFNC and Vapotherm 2000i. Methods Pharyngeal pressure measurements were taken from stable premature infants receiving HHHFNC for respiratory support. Flow rates of 2–8 L/min were studied. Results Nine infants had pharyngeal pressure measurements recorded with both HHHFNC devices at flow rates of 2–8 L/min. There was no difference in pharyngeal pressures recorded between devices at flow rates of 2–6 L/min; measured pressure was linearly associated with flow (R2 = 0.9). At flow rates of 7 L/min, Vapotherm delivered a mean (standard deviation) pharyngeal pressure of 4.7 (2.2) cmH2O compared with 4.23 (2.2) cmH2O by the Fisher & Paykel device (P = 0.04). At a flow of 8 L/min, the mean pharyngeal pressure via Vapotherm was 4.9 (2.2) cmH2O compared with 4.1 (2.3) cmH2O with the Fisher & Paykel device (P = 0.05). Conclusions Both HHHFNC delivered similar pharyngeal pressures at flow rates of 2–6 L/min. The pressure limiter valve of the Fisher & Paykel device attenuated the pharyngeal pressures at flows of 7 and 8 L/min. Vapotherm trended towards higher delivered pharyngeal pressure at flow rates 7 and 8 L/min, but the clinical significance of the difference remains unclear.

To evaluate a simplified gentamicin extended-interval dosing regimen in a large cohort of preterm and term newborns, we conducted a retrospective cohort study over a 4-year period. All inborn newborns who received gentamicin for the first episode of suspected or proven sepsis were eligible. Newborns received 4 mg/kg gentamicin intravenously 24-hourly, except for those at28 weeks of gestation who received gentamicin 36-hourly. Trough levels were taken before the third dose and considered non-toxic if ≤2 μg/mL. Infants were analysed in gestational age subgroups:28 weeks, 28-31 weeks, 32-35 weeks, 36-39 weeks and ≥40 weeks. Newborns who received indomethacin co-medication were analysed separately. Nine hundred ninety-three newborns, gestational age range 23(+2)-42(+1) weeks, birth weight range 397-5936 g, were included. The median (interquartile range (IQR)) gentamicin trough level for all newborns was 1.3 μg/mL (0.8-1.7). Ninety per cent of newborns had non-toxic trough levels. The incidence of trough levels2 μg/mL was between 2.2 and 9.7 % in all subgroups except for infants born at 28-31 weeks of gestation, where 21.7 % of trough levels were2 μg/mL. Indomethacin co-medication significantly increased the median gentamicin trough level in preterm infants at32 weeks of gestation.This study demonstrates that simplified gentamicin dosage regimens are feasible. Prospective evaluations are required to establish safety profiles.

Herpes simplex virus hepatitis is a rare but potentially fatal condition that usually affects the immunocompromised, including pregnant women. This case report details the course of fulminant hepatic failure in a woman at 31 weeks gestation resulting in emergent delivery of the fetus and liver transplant in the mother.

To study the impact on newborn behavioural states and accuracy of three infrared thermometers compared with digital axillary thermometer measurements in very low birth weight infants.Single-centre prospective observational study. Preterm infants born1500-g birth weight were eligible. Infants were observed for pre-measurement behaviour state using a five-point neonatal behaviour observation tool. One infrared temperature was taken from each of the devices, followed by an axillary measurement. Further behaviour-state observations were recorded following infrared and axillary measurements.One hundred measurements were collected from each infrared device among a cohort of 42 very low birth weight infants. Only one infrared device showed satisfactory agreement with bias -0.071 (95% limits of agreement -0.68 to 0.54). The other two devices demonstrated poor agreement: bias -1.34; 95% limits of agreement -2.62 to -0.5 and bias -0.56; 95% limits of agreement -1.38 to 0.25. Neonatal behavioural scores showed only minimal changes when infrared measurements were performed but increased significantly following axillary measurements. The difference between the two modalities was statistically significant with a mean increase of 1.44 points following axillary measurements (95% confidence interval 1.21 to 1.67, P0.001).Temperature measurements taken with infrared thermometers demonstrated less disruption to preterm infants' behavioural state, however accuracy of devices varied.

Low superior vena cava (SVC) flow has been associated with intraventricular haemorrhage (IVH) in very preterm infants. We studied the diagnostic value of a single measurement of SVC flow within the first 24 h of life in very preterm infants and its association with occurrence or extension of IVH in a setting of limited availability of neonatal echocardiography. Preterm infants who were born at less than 30 weeks gestation and who had an echocardiogram within 24 h after birth were eligible. Baseline, clinical and ultrasound data were collected. A total of 165 preterm infants were included. Low SVC flow (

Blood pressure (BP) monitoring is an essential procedure in intensive care. There is controversy about the reliability of non-invasive BP measurements in very preterm infants. This prospective trial compared non-invasive BP monitoring with BP monitoring via an umbilical arterial catheter (UAC) in this population.Preterm infants born at less than 32 weeks gestation requiring a UAC for clinical management were eligible. Enrolled infants had up to three BP measurements on the right arm (RA) and right leg (RL) when in a resting state. UAC-BP measurements were noted immediately after the non-invasive BP was displayed on the monitor. Measurements were analysed in subgroups according to birth weight: no greater than 750 g, 751-1,000 g, above 1,000 g. Statistical analysis reports median, range, and Bland-Altman analysis.Sixty infants were included. Median (range) gestational age was 26.4 weeks (23.6, 31.2); birth weight 924 g (581, 1,518). A total of 1,865 measurements were performed (RA: 935, RL: 930). Mean difference (95% limits of agreement) for infants no greater than 750 g: RA 2.53 mmHg (-11.18, 16.24), RL -0.804 mmHg (-12.65, 11.04); for infants 751-1,000 g: RA 3.535 mmHg (-9.6, 16.7), RL -1.239 mmHg (-13.14, 10.66); for infants above 1,000 g: RA -1.65 mmHg (-13.47, 10.17), RL -4.101 mmHg (-14.17, 5.96).Although the average differences between invasive and non-invasive BP measurements are acceptable, the range of under- and overestimation of non-invasive BP measurements is large and not consistent, making reliance on non-invasive modalities to guide circulatory management problematic. If arterial BP monitoring is not available, our results suggest measuring non-invasive BP on the leg in preterm infants with a birth weight no greater than 1,000 g.

To investigate the applicability, efficacy, and safety of single-pass albumin dialysis in children.Retrospective data review of uncontrolled clinical data.University-based pediatric intensive care unit collaborating with a local center for liver transplantation.Nine children, aged 2 to 15 yrs, who were treated with single-pass albumin dialysis for acute liver failure of various origins under a compassionate-use protocol between 2000 and 2006. All patients met high-urgency liver transplantation criteria.Single-pass albumin dialysis was performed as rescue therapy for children with acute liver failure.The decrease in hepatic encephalopathy (grades 1-4) and the serum levels of bilirubin, bile acids, and ammonium were measured to assess the efficacy of detoxification. As a measure of liver synthesis function, thromboplastin time and fibrinogen were analyzed. The safety of the procedure was assessed by documenting adverse effects on mean arterial blood pressure, platelet count, and clinical course. Seven out of nine patients were bridged successfully to either native organ recovery (n = 1) or liver transplantation (n = 6), one of them twice. Six out of nine patients undergoing single-pass albumin dialysis (ten treatments) survived. In six patients, hepatic encephalopathy could be reduced at least by one degree. Ammonium, bilirubin, and bile acid levels decreased in all patients. One patient had an allergic reaction to albumin.In childhood acute liver failure, treatment with single-pass albumin dialysis was generally well tolerated and seems to be effective in detoxification and in improving blood pressure, thus stabilizing the critical condition of children before liver transplantation and facilitating bridging to liver transplantation. It may be beneficial in avoiding severe neurologic sequelae after acute liver failure and thereby improve survival. Single-pass albumin dialysis is an inexpensive albumin-based detoxification system that is easy to set up and requires little training. Whether and to what extent single-pass albumin dialysis can support children with acute liver failure until native liver recovery remains unclear.

Today, lithographic methods enable combinatorial synthesis of50,000 oligonucleotides per cm(2), an advance that has revolutionized the whole field of genomics. A similar development is expected for the field of proteomics, provided that affordable, very high-density peptide arrays are available. However, peptide arrays lag behind oligonucleotide arrays. This is mainly due to the monomer-by-monomer repeated consecutive coupling of 20 different amino acids associated with lithography, which adds up to an excessive number of coupling cycles. A combinatorial synthesis based on electrically charged solid amino acid particles resolves this problem. A computer chip consecutively addresses the different charged particles to a solid support, where, when completed, the whole layer of solid amino acid particles is melted at once. This frees hitherto immobilized amino acids to couple all 20 different amino acids in one single coupling reaction to the support. The method should allow for the translation of entire genomes into a set of overlapping peptides to be used in proteome research.