Reproducibility of Air Displacement Plethysmography in Term and Preterm Infants-A Study to Enhance Body Composition Analysis in Clinical Routine.

The quality-initiative analysis of weekly duplicate PEAPOD® body composition measurements was conducted from clinical practice (January to September 2021) on preterm and term infants without respiratory support. Statistical analysis, including regression analysis, Bland-Altman plots and cv-root-mean-square tests, was performed. A total of 188 duplicate (376 individual) measurements were collected from 119 infants (88 preterm, 31 term). The median absolute difference between duplicates was 31.5 g for fat-free mass (FFM). Linear correlation analysis showed R2 = 0.97 for FFM. The absolute differences in FFM and fat mass did not significantly correlate with increasing age. The %FFM differed (p = 0.02) across body weight groups of 1 kg < BW ≤ 2 kg (1.8%; IQR: 0.8, 3.6) and BW > 3 kg (0.9%; IQR: 0.3, 2.1). The median absolute differences were 1 g (IQR: 0.4, 3.1) for body weight and 5.6 mL (IQR: 2.1, 11.8) for body volume. Body volume estimation is charged with a constant absolute error, which is the main factor for differences between repeated body composition assessments. This error becomes more prominent in infants with lower body weights. Nevertheless, reproducibility of weekly PEAPOD testing is sufficient to monitor body compartment changes, offering a foundation for nutritional decisions in both preterm and term infants.

Governing beyond the project: Refocusing innovation governance in emerging science and technology funding.

This article analyses how a recent idiom of innovation governance, 'responsible innovation', is enacted in practice, how this shapes innovation processes, and what aspects of innovation are left untouched. Within this idiom, funders typically focus on one point in an innovation system: researchers in projects. However, the more transformational aspirations of responsible innovation are circumscribed by this context. Adopting a mode of critique that assembles, this article considers some alternative approaches to governing the shared trajectories of science, technology, and society. Using the idea of institutional invention to focus innovation governance on four inflection points-agendas, calls, spaces, evaluation-would allow funding organizations and researchers to look 'beyond the project', developing new methods to unpack and reflect on assumed purposes of science, technology, and innovation, and to potentially reconfigure the institutions that condition scientific practice.

Crosstalk between regulatory elements in disordered TRPV4 N-terminus modulates lipid-dependent channel activity.

Intrinsically disordered regions (IDRs) are essential for membrane receptor regulation but often remain unresolved in structural studies. TRPV4, a member of the TRP vanilloid channel family involved in thermo- and osmosensation, has a large N-terminal IDR of approximately 150 amino acids. With an integrated structural biology approach, we analyze the structural ensemble of the TRPV4 IDR and the network of antagonistic regulatory elements it encodes. These modulate channel activity in a hierarchical lipid-dependent manner through transient long-range interactions. A highly conserved autoinhibitory patch acts as a master regulator by competing with PIP2 binding to attenuate channel activity. Molecular dynamics simulations show that loss of the interaction between the PIP2-binding site and the membrane reduces the force exerted by the IDR on the structured core of TRPV4. This work demonstrates that IDR structural dynamics are coupled to TRPV4 activity and highlights the importance of IDRs for TRP channel function and regulation.

Towards European automatic bioaerosol monitoring: Comparison of 9 automatic pollen observational instruments with classic Hirst-type traps.

To benefit allergy patients and the medical practitioners, pollen information should be available in both a reliable and timely manner; the latter is only recently possible due to automatic monitoring. To evaluate the performance of all currently available automatic instruments, an international intercomparison campaign was jointly organised by the EUMETNET AutoPollen Programme and the ADOPT COST Action in Munich, Germany (March-July 2021). The automatic systems (hardware plus identification algorithms) were compared with manual Hirst-type traps. Measurements were aggregated into 3-hourly or daily values to allow comparison across all devices. We report results for total pollen as well as for Betula, Fraxinus, Poaceae, and Quercus, for all instruments that provided these data. The results for daily averages compared better with Hirst observations than the 3-hourly values. For total pollen, there was a considerable spread among systems, with some reaching R2 > 0.6 (3 h) and R2 > 0.75 (daily) compared with Hirst-type traps, whilst other systems were not suitable to sample total pollen efficiently (R2 < 0.3). For individual pollen types, results similar to the Hirst were frequently shown by a small group of systems. For Betula, almost all systems performed well (R2 > 0.75 for 9 systems for 3-hourly data). Results for Fraxinus and Quercus were not as good for most systems, while for Poaceae (with some exceptions), the performance was weakest. For all pollen types and for most measurement systems, false positive classifications were observed outside of the main pollen season. Different algorithms applied to the same device also showed different results, highlighting the importance of this aspect of the measurement system. Overall, given the 30 % error on daily concentrations that is currently accepted for Hirst-type traps, several automatic systems are currently capable of being used operationally to provide real-time observations at high temporal resolutions. They provide distinct advantages compared to the manual Hirst-type measurements.

Mathematical Modeling and Simulation Provides Evidence for New Strategies of Ovarian Stimulation.

New approaches to ovarian stimulation protocols, such as luteal start, random start or double stimulation, allow for flexibility in ovarian stimulation at different phases of the menstrual cycle. It has been proposed that the success of these methods is based on the continuous growth of multiple cohorts ("waves") of follicles throughout the menstrual cycle which leads to the availability of ovarian follicles for ovarian controlled stimulation at several time points. Though several preliminary studies have been published, their scientific evidence has not been considered as being strong enough to integrate these results into routine clinical practice. This work aims at adding further scientific evidence about the efficiency of variable-start protocols and underpinning the theory of follicular waves by using mathematical modeling and numerical simulations. For this purpose, we have modified and coupled two previously published models, one describing the time course of hormones and one describing competitive follicular growth in a normal menstrual cycle. The coupled model is used to test ovarian stimulation protocols in silico. Simulation results show the occurrence of follicles in a wave-like manner during a normal menstrual cycle and qualitatively predict the outcome of ovarian stimulation initiated at different time points of the menstrual cycle.

[The new radiation protection legislation-part 2 : Modifications in radiology regarding approval procedure and special fields including teleradiology]. / Die neue Strahlenschutzgesetzgebung ­ Teil 2 : Änderungen in der Radiologie bezüglich Vorabkontrolle und Sonderbereiche, einschließlich Teleradiologie.

BACKGROUND: The entry of the new Radiation Protection Act and new Radiation Protection Regulation into force in Germany created many changes for radiology with regard to the old Radiation Protection Regulation and X­ray Regulation. OBJECTIVES: The substantial modifications in radiology regarding the areas of approval and notification procedures, teleradiology, screening, research and radon in the workplace are summarized. METHOD: Changes in the new Radiation Protection Act and Regulation compared to the old Radiation Protection Regulation and X­ray Regulation were evaluated. Thereby, the focus was on areas beyond the workflow in clinical routine. RESULTS AND CONCLUSION: The requirements for the approval and notification procedure have increased. For example, proof must be provided that a medical physics expert can be consulted. The establishment of deadlines for the process by the responsible authorities may accelerate the procedure and create planning certainty.

[The new radiation protection legislation-part 1 : Modifications in radiology for the workflow in clinical routine]. / Die neue Strahlenschutzgesetzgebung ­ Teil 1 : Änderungen für die arbeitstägliche Routine in der Radiologie.

BACKGROUND: On 31 December 2018, the new Radiation Protection Regulation came into effect in Germany and made the new Radiation Protection Act more concrete. The old Radiation Protection Regulation and X­ray Regulation have thereby been replaced. OBJECTIVES: The substantial modifications regarding the practical daily routine in radiology are summarized. METHODS: Modifications and innovations of the New Radiation Protection Act and Regulation compared to the old Radiation Protection Regulation and X­ray Regulation and accordances were evaluated. Thereby the main focus was in the relevance for workflow in clinical routine. RESULTS AND CONCLUSION: The new legislation contains a number of regulations that provide crucial tools for implementation of radiation protection, quality assurance, and dose optimization. However, this also requires additional time and personnel.

Active perinatal care of preterm infants in the German Neonatal Network.

OBJECTIVE: To determine if survival rates of preterm infants receiving active perinatal care improve over time. DESIGN: The German Neonatal Network is a cohort study of preterm infants with birth weight <1500 g. All eligible infants receiving active perinatal care are registered. We analysed data of patients discharged between 2011 and 2016. SETTING: 43 German level III neonatal intensive care units (NICUs). PATIENTS: 8222 preterm infants with a gestational age between 22/0 and 28/6 weeks who received active perinatal care. INTERVENTIONS: Participating NICUs were grouped according to their specific survival rate from 2011 to 2013 to high (percentile >P75), intermediate (P25-P75) and low (

Modification of chest radiography exposure parameters using a neonatal chest phantom.

BACKGROUND: The acquisition of chest radiographs in neonates is of critical importance in diagnostics because of the risk of respiratory distress syndrome and pneumothorax in preterm infants. OBJECTIVE: To achieve a dose reduction while preserving a diagnostic image quality for chest radiographs of neonates. MATERIALS AND METHODS: All radiographs, generated on a fully digital X-ray unit by using a neonatal chest phantom, were evaluated under variation of the tube voltage (40-70 kV) and mAs levels (1-10.2 mAs) with and without an additional 0.1-mm copper (Cu) filtration. Noise, contrast and contrast-to-noise ratio for bronchus, heart, lungs and vessels were determined. Visual assessment of the image quality was carried out by three radiologists using a Likert scale. To evaluate a maximally possible dose reduction, the dose of the radiographs with still acceptable image quality at a minimal dose was compared to the dose of the radiographs with the standard settings used in clinical routine. RESULTS: The noise showed decreasing values with increasing dose, while the contrast values were increased. For the contrast-to-noise ratio, a digressive course of the values as a function of the tube voltage was found. The visual evaluation of image quality showed the best evaluation of the structures at the lowest possible dose in the settings (44 kV, 3.36 mAs) with copper filtration and in the settings (44 kV, 1.56 mAs) without copper filtration. A maximum dose reduction from 8.29 µSv to 2.21 µSv (about 73%) was obtained. CONCLUSION: A dose reduction while preserving diagnostic image quality in a digital X-ray system is generally possible by reducing the tube voltage and simultaneous adaptation of the mAs settings.

Optimization of Whole-Body CT Examinations of Polytrauma Patients in Comparison with the Current Diagnostic Reference Levels. / Optimierung von Ganzkörper-CT-Untersuchungen an Polytraumatisierten anhand des Vergleichs mit den aktuellen diagnostischen Referenzwerten.

PURPOSE: Evaluation of the dose values of a polytrauma whole-body CT examination used in clinical practice with regard to the 2016 updated diagnostic reference levels and reduction of the mean exposure levels using simple optimization steps. MATERIALS AND METHODS: In each case, 100 exposure values before and after dose optimization were compared with the old and new diagnostic reference levels. The grayscale values and the signal-to-noise ratio (SNR) were determined for the lung, the aortic arch and the liver. A visual assessment of the image quality was performed by two radiologists on the basis of a Likert scale (0 - non-diagnostic, 1 - poor visualization, 2 - moderate visualization, 3 - good visualization, 4 - excellent visualization) for CT examinations both before and after optimization. RESULTS: The acquired exposure values after dose optimization were below the old and new diagnostic reference levels (1319.98 ±â€Š463.16 mGy ·â€Šcm) while the mean value of the exposure values before optimization (1774.96 ±â€Š608.78 mGy ·â€Šcm) exceeded the current diagnostic reference levels. The measured grayscale values (HU) were (before versus after optimization): lung - 833 HU vs. - 827 HU (p = 0.43), aortic arch 341 HU vs. 343 HU (p = 0.70) and liver 68 HU vs. 67 HU (p = 0.35). After dose optimization the SNR in the lung was minimally higher, while it was minimally lower in the two other regions than before the optimization. Visual assessment of the image quality showed almost identical values with 3.85 evaluation points before and 3.82 evaluation points after dose optimization (p = 0.57). CONCLUSION: Due to the updating of the diagnostic reference levels, an analysis of the own exposure values is necessary in order to be able to detect high values promptly and to initiate appropriate measures for dose reduction. Appropriate adaptation of the examination parameters with consideration of the necessary image quality allows a significant reduction of the radiation exposure in most cases, also on CT devices of older generations. KEY POINTS: · In many cases a dose reduction below the DRLs is already possible by optimizing the examination technique.. · In order to ensure a diagnostic image quality, the control of the image quality is unavoidable in a dose reduction.. · Through suitable parameter adjustments a compliance with the DRLs is also possible, using CT devices of older generation without iterative image reconstruction.. CITATION FORMAT: · Schäfer SB, Rudolph C, Kolodziej M et al. Optimization of Whole-Body CT Examinations of Polytrauma Patients in Comparison with the Current Diagnostic Reference Levels. Fortschr Röntgenstr 2019; 191: 1015 - 1025.

Development and Validation of a Life-Sized Mock Circulatory Loop of the Human Circulation for Fluid-Mechanical Studies.

Mock circulatory loops (MCLs) are usually developed for assessment of ventricular assist devices and consist of abstracted anatomical structures represented by connecting tubing pipes and controllable actuators which could mimic oscillating flow processes. However, with increasing use of short-term peripheral mechanical support (extracorporeal life support [ECLS]) and the upcoming evidence of even counteracting flow processes between the failing native circulation and ECLS, MCLs incorporating the peripheral vascular system and preserved anatomical structures are becoming more important for systematic assessment of these processes. For reproducible and standardized fluid-mechanical studies using magnetic resonance imaging, Doppler ultrasound, and computational fluid dynamics measurements, we developed a MCL of the human circulation. Silicon-based life-sized dummies of the human aorta and vena cava (vascular module) were driven by paracorporeal pneumatic assist devices. The vascular module is placed in a housing with all arterial branches merging into peripheral resistance and compliances modules, and blood-mimicking fluid returns to the heart module through the venous dummy. Compliance and resistance chambers provide for an adequate simulation of the capillary system. Extracorporeal life support cannulation can be performed in the femoral and subclavian arteries and in the femoral and jugular veins. After adjusting vessel diameters using variable Hoffmann clamps, physiologic flow rates were achieved in the supraaortic branches, the renal and mesenteric arteries, and the limb arteries with physiologic blood pressure and cardiac output (4 L/min). This MCL provides a virtually physiologic platform beyond conventional abstracted MCLs for simulation of flow interactions between the human circulation and external circulation generated by ECLS.

Follicular competition in cows: the selection of dominant follicles as a synergistic effect.

The reproductive cycle of mono-ovulatory species such as cows or humans is known to show two or more waves of follicular growth and decline between two successive ovulations. Within each wave, there is one dominant follicle escorted by subordinate follicles of varying number. Under the surge of the luteinizing hormone a growing dominant follicle ovulates. Rarely the number of ovulating follicles exceeds one. In the biological literature, the change of hormonal concentrations and individually varying numbers of follicular receptors are made responsible for the selection of exactly one dominant follicle, yet a clear cause has not been identified. In this paper, we suggest a synergistic explanation based on competition, formulated by a parsimoniously defined system of ordinary differential equations (ODEs) that quantifies the time evolution of multiple follicles and their competitive interaction during one wave. Not discriminating between follicles, growth and decline are given by fixed rates. Competition is introduced via a growth-suppressing term, equally supported by all follicles. We prove that the number of dominant follicles is determined exclusively by the ratio of follicular growth and competition. This number turns out to be independent of the number of subordinate follicles. The asymptotic behavior of the corresponding dynamical system is investigated rigorously, where we demonstrate that the [Formula: see text]-limit set only contains fixed points. When also including follicular decline, our ODEs perfectly resemble ultrasound data of bovine follicles. Implications for the involved but not explicitly modeled hormones are discussed.

Evaluating climate geoengineering proposals in the context of the Paris Agreement temperature goals.

Current mitigation efforts and existing future commitments are inadequate to accomplish the Paris Agreement temperature goals. In light of this, research and debate are intensifying on the possibilities of additionally employing proposed climate geoengineering technologies, either through atmospheric carbon dioxide removal or farther-reaching interventions altering the Earth's radiative energy budget. Although research indicates that several techniques may eventually have the physical potential to contribute to limiting climate change, all are in early stages of development, involve substantial uncertainties and risks, and raise ethical and governance dilemmas. Based on present knowledge, climate geoengineering techniques cannot be relied on to significantly contribute to meeting the Paris Agreement temperature goals.

Optimizing radiation exposure for CT localizer radiographs.

INTRODUCTION: The trend towards submillisievert CT scans leads to a higher dose fraction of localizer radiographs in CT examinations. The already existing technical capabilities make dose optimization of localizer radiographs worthwhile. Modern CT scanners apply automatic exposure control (AEC) based on attenuation data in such a localizer. Therefore not only this aspect but also the detectability of anatomical landmarks in the localizer for the desired CT scan range adjustment needs to be considered. MATERIALS AND METHODS: The effective dose of a head, chest, and abdomen-pelvis localizer radiograph with standard factory settings and user-optimized settings was determined using Monte Carlo simulations. CT examinations of an anthropomorphic phantom were performed using multiple sets of acquisition parameters for the localizer radiograph and the AEC for the subsequent helical CT scan. Anatomical landmarks were defined to assess the image quality of the localizer. CTDIvol and effective mAs per slice of the helical CT scan were recorded to examine the impact of localizer settings on a helical CT scan. RESULTS: The dose of the localizer radiograph could be decreased by more than 90% while the image quality remained sufficient when selecting the lowest available settings (80kVp, 20mA, pa tube position). The tube position during localizer acquisition had a greater impact on the AEC than the reduction of tube voltage and tube current. Except for the use of a pa tube position, all changes of acquisition parameters for the localizer resulted in a decreased total radiation exposure. CONCLUSION: A dose reduction of CT localizer radiograph is necessary and possible. In the examined CT system there was no negative impact on the modulated helical CT scan when the lowest tube voltage and tube current were used for the localizer.

Potent and Selective Human Neutrophil Elastase Inhibitors with Novel Equatorial Ring Topology: in vivo Efficacy of the Polar Pyrimidopyridazine BAY-8040 in a Pulmonary Arterial Hypertension Rat Model.

Human neutrophil elastase (HNE) is a key driver of inflammation in many cardiopulmonary and systemic inflammatory and autoimmune conditions. Overshooting high HNE activity is the consequence of a disrupted protease-antiprotease balance. Accordingly, there has been an intensive search for potent and selective HNE inhibitors with suitable pharmacokinetics that would allowing oral administration in patients. Based on the chemical probe BAY-678 and the clinical candidate BAY 85-8501 we explored further ring topologies along the equator of the parent pyrimidinone lead series. Novel ring systems were annulated in the east, yielding imidazolo-, triazolo-, and tetrazolopyrimidines in order to ensure additional inhibitor-HNE contacts beyond the S1 and the S2 pocket of HNE. The western annulation of pyridazines led to the polar pyrimidopyridazine BAY-8040, which combines excellent potency and selectivity with a promising pharmacokinetic profile. In vivo efficacy with regard to decreasing cardiac remodeling and amelioration of cardiac function was shown in a monocrotaline-induced rat model for pulmonary arterial hypertension. This demonstrated in vivo proof of concept in animals.