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Surfactant improves lung mechanics and the success of non-invasive respiratory support in preterm infants. The lack of non-invasive bedside tools for monitoring lung mechanics makes current guidelines for surfactant therapy based on O2 requirements, which may be not specific for this application. Objective: To assess feasibility and role of early, non-invasive evaluation of respiratory mechanics by FOT in non-intubated preterm infants for stratifying the severity of respiratory disease. Eligibility: 28-34wk gestation, no need of early intubation after birth. FOT at 10Hz was applied by a modified ventilator (Fabian, Acutronic) and a face-mask during CPAP=5cmH2O. Measurements were performed at 2 and 24h of life. FiO2 was titrated and surfactant given as in Sweet (2016). 4 groups (n=45) were considered: Patients not requiring respiratory support (SB); receiving CPAP for less than (CPAP-S) or more than 28d (CPAP-L) but who never received surfactant and patients who received surfactant (Surf). Xrs in Surf and CPAP-L was significantly lower at 2h compared to SB and CPAP-S (fig 1). After receiving surfactant patients improved, leaving CPAP-L only showing significantly lower Xrs at 24h. Xrs stratifies patients according to the degree of respiratory disease. CPAP-L infants presented poor Xrs at 2h, did not match clinical criteria for surfactant but had a long respiratory support dependence.

OBJECTIVE: To provide a non-invasive approach to monitoring lung function in spontaneously breathing lambs, from birth to five months of life, by the forced oscillation technique (FOT). This report describes the experimental set-up, data processing, and identification of normal predicted values of resistance (Rrs) and reactance (Xrs) of the respiratory system, along with normal bronchodilator response for bronchial reversibility testing. APPROACH: Rrs and Xrs at 5, 11, and 19 Hz were measured monthly for five months in 20 normal term lambs that breathed spontaneously. In seven lambs, repeated measurements also were made within the first month of life (at 3, 7, 14, and 21 d of life). We determined the repeatability and reproducibility of the measurements and characterized the relationship between lung mechanics and age, sex, and body dimensions, using regression analysis, and measured changes in lung mechanics in response to inhaled bronchodilator. MAIN RESULTS: The measurements provided repeatable and reproducible data. Rrs decreased, whereas Xrs increased, with growth from birth through the first two months of life, after which no statistically significant differences were detected. We identified normal value equations for Rrs and Xrs and for each of the measured anthropometric variables. Respiratory system mechanics were not affected by the bronchodilator. SIGNIFICANCE: The FOT provides reliable non-invasive measurement of respiratory system mechanics in spontaneously breathing term lambs from birth to five months of age. The methods and normal reference values defined in this study will facilitate testing of the pathophysiological consequences of preterm birth and prolonged respiratory support on respiratory system mechanics.

Between 2013 and 2016, a broad range of Catholic groups following pro-life and pro-family agendas has conducted a large anti-gender campaign, whose main result was the definition of a Catholic anti...

Une reflexion autour du modele d’un groupe psycho-educatif pour adolescents qui a debute il y a dix ans au sein du Service medico-psychologique de Lugano. Le groupe peut devenir un agent potentiel de transformation pour les jeunes qui ne se pretent pas au jeu symbolique de la psychotherapie, mais qui peuvent beneficier de la relation psycho-educative qui se propose comme territoire intermediaire, transitionnel entre le concret et la pensee.

CMOS image sensors can suffer from background noise in absence of any light. In order to suppress this it is important to keep this noise, referred to as dark-current low. This implies that the internal generation current should be very low. Trace metal impurities have been reported to increase the generation current. In this study the trap-assisted generation current contributions due to 7 different metal impurities have been calculated. It was concluded that Cu and Mn impurities yield the highest generation current contribution.

To describe the interrelationship between antenatal steroids, exogenous surfactant, and two approaches to lung recruitment at birth on oxygenation and respiratory system compliance (Cdyn) in preterm lambs.Lambs (n = 63; gestational age 127 ± 1 d) received either surfactant at 10-min life (Surfactant), antenatal corticosteroids (Steroid), or neither (Control). Within each epoch lambs were randomly assigned to a 30-s 40 cmH2O sustained inflation (SI) or an initial stepwise positive end-expiratory pressure (PEEP) open lung ventilation (OLV) maneuver at birth. All lambs then received the same management for 60-min with alveolar-arterial oxygen difference (AaDO2) and Cdyn measured at regular time points.Overall, the OLV strategy improved Cdyn and AaDO2 (all epochs except Surfactant) compared to SI (all P0.05; two-way ANOVA). Irrespective of strategy, Cdyn was better in the Steroid group in the first 10 min (all P0.05). Thereafter, Cdyn was similar to Steroid epoch in the OLV + Surfactant, but not SI + Surfactant group. OLV influenced the effect of steroid and surfactant (P = 0.005) on AaDO2 more than SI (P = 0.235).The antenatal state of the lung influences the type and impact of a recruitment maneuver at birth. The effectiveness of surfactant maybe enhanced using PEEP-based time-dependent recruitment strategies rather than approaches solely aimed at initial lung liquid clearance.

Ineffective aeration during the first inflations at birth creates regional aeration and ventilation defects, initiating injurious pathways. This study aimed to compare a sustained first inflation at birth or dynamic end-expiratory supported recruitment during tidal inflations against ventilation without intentional recruitment on gas exchange, lung mechanics, spatiotemporal regional aeration and tidal ventilation, and regional lung injury in preterm lambs. Lambs (127 ± 2 d gestation), instrumented at birth, were ventilated for 60 minutes from birth with either lung-protective positive pressure ventilation (control) or as per control after either an initial 30 seconds of 40 cm H2O sustained inflation (SI) or an initial stepwise end-expiratory pressure recruitment maneuver during tidal inflations (duration 180 s; open lung ventilation [OLV]). At study completion, molecular markers of lung injury were analyzed. The initial use of an OLV maneuver, but not SI, at birth resulted in improved lung compliance, oxygenation, end-expiratory lung volume, and reduced ventilatory needs compared with control, persisting throughout the study. These changes were due to more uniform inter- and intrasubject gravity-dependent spatiotemporal patterns of aeration (measured using electrical impedance tomography). Spatial distribution of tidal ventilation was more stable after either recruitment maneuver. All strategies caused regional lung injury patterns that mirrored associated regional volume states. Irrespective of strategy, spatiotemporal volume loss was consistently associated with up-regulation of early growth response-1 expression. Our results show that mechanical and molecular consequences of lung aeration at birth are not simply related to rapidity of fluid clearance; they are also related to spatiotemporal pressure-volume interactions within the lung during inflation and deflation.

A vertical ferroelectric HfO 2 field effect transistor based on 3-D macaroni NAND architecture is reported for the first time. Up to 2 V memory window was obtained after the application of 100 ns program/erase pulses. Flash-like endurance of 104 cycles is reported and first reliability assessments were performed.

Respiratory management during extracorporeal membrane oxygenation (ECMO) is complex. Assessment of lung mechanics might support a patient-tailored ventilatory strategy. We report, for the first time, the use of the forced oscillation technique (FOT) to evaluate lung function during neonatal ECMO to improve the individualization of respiratory support. The patient was a formerly preterm infant at a corrected age of 40 weeks (gestational age 32 weeks) undergoing veno-arterial ECMO for refractory respiratory failure secondary to influenza A (H1N1) pneumonia. We used the FOT as a bedside non-invasive tool for daily monitoring of lung mechanics, from ECMO day 6 (E6) until decannulation. A small-amplitude, 5-Hz oscillatory pressure was overimposed on the ventilation waveform at the airway opening during positive end-expiratory pressure (PEEP) trials. From E6 to E9, lung mechanics changes with PEEP indicated a largely de-recruited and easily over-distendable lung that was not recruitable by applying lung-protective PEEP values. After surfactant and steroid administration, oscillatory reactance (Xrs) values began improving, suggesting a more recruited and pressure-recruitable lung. On E11, despite the lack of improvement in the radiographic appearance of the thorax, the FOT measurements showed a more recruited lung. Weaning from ECMO was started, and the patient was extubated within 48 h. The decannulation was successful, and the patient was extubated within 48 h after ECMO weaning. First-year respiratory and neurodevelopmental follow-up evaluation was unremarkable. This report suggests the potential usefulness of the FOT for monitoring the lung mechanics of ventilated newborns during ECMO to achieve individualized respiratory management. Such tailoring might improve neonatal outcomes and support clinicians with the establishment of a timely and safer weaning approach. These findings need to be verified on a larger population.

Background: Ventilated preterm infants may have respiratory morbidities early in life and later at school age and adulthood (Clemm HH, 2014). Modeling with large animals is needed to identify mechanisms Aim: Use a new former preterm (FPT) lamb model to evaluate lung mechanics, airway reactivity, and airway smooth muscle (ASM) thickness. Methods: 6 preterm lambs (128d; term ~150d; ~28w gestation in humans) were resuscitated and supported by mechanical ventilation for 3-6d before weaning from respiratory support (FPT lambs). They lived for ~6m (~5m corrected postnatal age; ≈6y in humans). Control lambs (n=20), born at term, lived 5m. We measured respiratory mechanics monthly by forced oscillation technique (FOT; 11Hz) and airway reactivity by changes in FOT variables after increased doses of nebulized methacholine (MCh; 0.06-4.00 mg; ATS guideline, 1999). We used quantitative histology to measure ASM thickness in terminal bronchioles. Results: FPT lambs had increased airway reactivity during the first 2m of life (figure). ASM thickness was significantly greater in FPT lambs (6.7±1.1vs 3.1±0.5 mm control lambs). Conclusions: The new FPT lamb model recapitulates altered lung mechanics and airway reactivity in FPT humans. Interestingly, airway muscularization persists at 5m when lung mechanics and airway reactivity are no longer impaired. This model provides opportunity to identify pathogenic mechanisms.

Background: SLI at birth has been shown to promote lung aeration in intubated preterm lambs (Tingay et al PedRes 2014). The effectiveness of applying SLI by full-face mask might be impaired by leaks, glottis closure, and accumulation of air in the stomach. Aim: To compare timing and magnitude of lung aeration at birth in preterm lambs receiving non-invasive resuscitation with and without the application of SLI. Methods: Preterm lambs (128d; ~28w in humans) were randomly assigned to receive SLI at birth (SLI group, n=7) or not (noSLI group, n=6). SLI group received two SLIs of 35s at 30cmH2O separated by 55s of nIPPV. All lambs received surfactant and were maintained with nIPPV (PEEP=8cmH2O, RR=60). PIP and FiO2 were adjusted to maintain PaCO2 at 35-55 mmHg and PaO2 at 60-80 mmHg up to 3h of life in both groups. Lung aeration was assessed as changes in lung reactance (Xrs) at 5Hz (Dellaca’ et al, ICM2011) measured by the forced oscillation technique. Data reported as median (IQR). Results: In both groups, Xrs increased with time (Figure). Xrs was significantly greater in SLI group at the end of each SLI and more variable in noSLI group. At 3h, Xrs stabilized at similar values for both groups. Conclusions: SLI applied non-invasively improved lung aeration and a more homogenous response in preterm lambs at birth. However, the improvements compared to CPAP disappear within few minutes.

After the successful introduction as a replacement for the SiO2 gate dielectric in metal–oxide–semiconductor field-effect transistors, HfO2 is currently one of the most studied binary oxide systems with ubiquitous applications in nanoelectronics. For years, the interest of microelectronic downscaling has focused on tuning the dielectric constant of HfO2, particularly for monoclinic and tetragonal phases. Recently, Muller et al. showed the occurrence of ferroelectricity in orthorhombic HfO2 obtained by doping with Si, Y or Al which can alter the centrosymmetric atomic structure of the elemental binary oxide. Ferroelectric HfO2 is characterized by a permanent electric dipole that can be reversed through the application of an external voltage. As all ferroelectrics, a strong coupling between the polarization and the deformation exists, a property which has allowed the development of piezoelectric sensors and actuators. However, ferroelectrics also show a coupling between the electrical polarization and the deformation gradient, defined as flexoelectricity. In essence, the free charge inside the material redistributes in response to strain gradients, inducing a net non-zero dipole moment, eventually reaching polarization reversal by the sole application of a mechanical stress. Here we show the flexoelectric effect in Al-doped hafnium oxide, using the tip of an atomic force microscope (AFM) to maximize the strain gradient at the nanometre scale. Our analysis indicates that pure mechanical force can be used for the local polarization control of sub-100 nm domains. Due to the full compatibility of HfO2 in the modern CMOS process, the discovery of flexoelectricity in hafnia paves the way for (1) nanoscopic memory bits that can be written mechanically and read electrically, (2) tip-induced reprogrammable ferroelectric-based logic and (3) electromechanical transducers.

Ferroelectric HfO 2 devices are potential candidates for non-volatile memory applications. However, they often exhibit a pinched hysteresis, which requires the application of cycles to “wake-up” the device. In this paper, endurance of FE-Al: HfO 2 MIM is investigated using TDDB measurements. An improvement in TDDB lifetime is observed with cycling. A hypothesis involving rearrangement of defects is proposed to explain this behavior.

BackgroundDespite the theoretical benefits of high-frequency oscillatory ventilation (HFOV) in preterm infants, systematic reviews of randomized clinical trials do not confirm improved outcomes. The authors hypothesized that oscillating a premature lung with multiple frequencies simultaneously would improve gas exchange compared with traditional single-frequency oscillatory ventilation (SFOV). The goal of this study was to develop a novel method for HFOV, termed “multifrequency oscillatory ventilation” (MFOV), which relies on a broadband flow waveform more suitable for the heterogeneous mechanics of the immature lung.MethodsThirteen intubated preterm lambs were randomly assigned to either SFOV or MFOV for 1 h, followed by crossover to the alternative regimen for 1 h. The SFOV waveform consisted of a pure sinusoidal flow at 5 Hz, whereas the customized MFOV waveform consisted of a 5-Hz fundamental with additional energy at 10 and 15 Hz. Per standardized protocol, mean pressure at airway opening () and inspired oxygen fraction were adjusted as needed, and root mean square of the delivered oscillatory volume waveform (Vrms) was adjusted at 15-min intervals. A ventilatory cost function for SFOV and MFOV was defined as , where Wt denotes body weight.ResultsAveraged over all time points, MFOV resulted in significantly lower VC (246.9 ± 6.0 vs. 363.5 ± 15.9 ml2 mmHg kg−1) and (12.8 ± 0.3 vs. 14.1 ± 0.5 cm H2O) compared with SFOV, suggesting more efficient gas exchange and enhanced lung recruitment at lower mean airway pressures.ConclusionOscillation with simultaneous multiple frequencies may be a more efficient ventilator modality in premature lungs compared with traditional single-frequency HFOV.

A sustained first inflation (SI) at birth may aid lung liquid clearance and aeration, but the impact of SI duration relative to the volume-response of the lung is poorly understood. We compared three SI strategies: 1) variable duration defined by attaining volume equilibrium using real-time electrical impedance tomography (EIT; SIplat); 2) 30 s beyond equilibrium (SIlong); 3) short 30-s SI (SI30); and 4) positive pressure ventilation without SI (no-SI) on spatiotemporal aeration and ventilation (EIT), gas exchange, lung mechanics, and regional early markers of injury in preterm lambs. Fifty-nine fetal-instrumented lambs were ventilated for 60 min after applying the allocated first inflation strategy. At study completion molecular and histological markers of lung injury were analyzed. The time to SI volume equilibrium, and resultant volume, were highly variable; mean (SD) 55 (34) s, coefficient of variability 59%. SIplatand SIlongresulted in better lung mechanics, gas exchange and lower ventilator settings than both no-SI and SI30. At 60 min, alveolar-arterial difference in oxygen was a mean (95% confidence interval) 130 (13, 249) higher in SI30vs. SIlonggroup (two-way ANOVA). These differences were due to better spatiotemporal aeration and tidal ventilation, although all groups showed redistribution of aeration towards the nondependent lung by 60 min. Histological lung injury scores mirrored spatiotemporal change in aeration and were greatest in SI30group ( P < 0.01, Kruskal-Wallis test). An individualized volume-response approach to SI was effective in optimizing aeration, homogeneous tidal ventilation, and respiratory outcomes, while an inadequate SI duration had no benefit over positive pressure ventilation alone.

Even if the accuracy of mechanical ventilators (MV) stated by manufacturers are largely within clinically relevant ranges, Govoni et al. (2012) found large deviations from original specifications in adult MV during real life usage, especially on volume-related parameters. This loss of accuracy can be extremely critical in neonatal MV, where the recent spreading of the volume guarantee (VG) modality made flow measurements more critical. The aim of this study was to evaluate the real life performances of MV used in neonatal intensive care unit (NICU). A test lung (TL) equipped with pressure and flow sensors mimicking a mild RDS (R=50cmH2O*s/l, C=0.35ml/cmH2O) baby was connected to the MVs ready to be used on patients (n=20) available in 3 NICUs. MVs were tested in both pressure controlled (PC, peak inspiratory pressure PIP=22cmH2O) and PC with VG (tidal volume VT=6ml) modalities in random order. In all tests, positive end-expiratory pressure (PEEP) was 6cmH2O, respiratory rate 45breaths/min, inspiratory time 0.33s, oxygen fraction 30%. The values of PEEP, PIP (during PC) and VT (during VG) delivered by MVs are reported in Figure. In several MVs, the ventilation delivered was considerably different from the set one with actual VT ranging from 5.3 to 8.0ml, urging the need of improving quality control procedures for preserving the performances of MVs with usage.

Ferroelectric hafnium oxide (HfO 2 )attracted a lot of interests since its discovery in 2007. Its scalability and CMOS compatibility are two advantages over conventional ferroelectric materials, favoring new device integration. Doped ferroelectric HfO 2 Metal/Insulator/Metal capacitors have been widely studied for DRAM and FeFET applications. Silicon electrodes have not been discussed in much detail so far, though it provides an input for vertical ferroelectric FET (V-FeFET), based on Flash NAND architecture. In this work, planar and vertical capacitors are presented using silicon as electrodes and aluminum doped HfO 2 as ferroelectric material. The process of the vertical integration is described. Polarization-Voltage measurements show a steep ferroelectric hysteresis loop for the planar as well as vertical capacitors. This demonstrates the conservation of the ferroelectric properties of the dielectric after deposition on an etched vertical wall and lays the first stone toward V-FeFET integration.

A 3D ferroelectric Al doped HfO 2 device for NAND applications was fabricated for the first time. The polysilicon (poly-Si) channel, whose diameter ranges from 60 to 200 nm, was highly doped for a better understanding of the ferroelectric properties. Electrical results confirmed the presence of the ferroelectric phase with a coercive voltage (2Vc) of 6 V extracted from the hysteresis loop. The drain anneal was found to have a significant impact on HfO 2 properties and needs to be reduced to preserve the ferroelectricity. Finally, reliability investigations showed an estimated time to failure of more than 10 years at 85 °C. This study lays the foundation for the fabrication of 3D ferroelectric field effect transistors (FeFET).

An in-depth analysis of gate stack enhancements that enable multi-Gb 3D NAND products is performed. Alternative charge trapping layer, enhanced tunnel oxide based on the VariOT concept and metal gate with Al2O3 high-k liner have been proposed and evaluated. The most promising solutions were successfully integrated in 3D devices. Integration challenges of the replacement gate approach, required to have metal gate in 3D NAND, are also analyzed and discussed in detail.