Translational design for limited resource settings as demonstrated by Vent-Lock, a 3D-printed ventilator multiplexer

BACKGROUND: Mechanical ventilators are essential to patients who become critically ill with acute respiratory distress syndrome (ARDS), and shortages have been reported due to the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: We utilized 3D printing (3DP) technology to rapidly prototype and test critical components for a novel ventilator multiplexer system, Vent-Lock, to split one ventilator or anesthesia gas machine between two patients. FloRest, a novel 3DP flow restrictor, provides clinicians control of tidal volumes and positive end expiratory pressure (PEEP), using the 3DP manometer adaptor to monitor pressures. We tested the ventilator splitter circuit in simulation centers between artificial lungs and used an anesthesia gas machine to successfully ventilate two swine. RESULTS: As one of the first studies to demonstrate splitting one anesthesia gas machine between two swine, we present proof-of-concept of a de novo, closed, multiplexing system, with flow restriction for potential individualized patient therapy. CONCLUSIONS: While possible, due to the complexity, need for experienced operators, and associated risks, ventilator multiplexing should only be reserved for urgent situations with no other alternatives. Our report underscores the initial design and engineering considerations required for rapid medical device prototyping via 3D printing in limited resource environments, including considerations for design, material selection, production, and distribution. We note that optimization of engineering may minimize 3D printing production risks but may not address the inherent risks of the device or change its indications. Thus, our case report provides insights to inform future rapid prototyping of medical devices

The PROVENT-C19 registry: A study protocol for international multicenter SIAARTI registry on the use of prone positioning in mechanically ventilated patients with COVID-19 ARDS

Background The worldwide use of prone position (PP) for invasively ventilated patients with COVID-19 is progressively increasing from the first pandemic wave in everyday clinical practice. Among the suggested treatments for the management of ARDS patients, PP was recommended in the Surviving Sepsis Campaign COVID-19 guidelines as an adjuvant therapy for improving ventilation. In patients with severe classical ARDS, some authors reported that early application of prolonged PP sessions significantly decreases 28-day and 90-day mortality. Methods and analysis Since January 2021, the COVID19 Veneto ICU Network research group has developed and implemented nationally and internationally the "PROVENT-C19 Registry", endorsed by the Italian Society of Anesthesia Analgesia Resuscitation and Intensive Care. . .'(SIAARTI). The PROVENT-C19 Registry wishes to describe 1. The real clinical practice on the use of PP in COVID-19 patients during the pandemic at a National and International level; and 2. Potential baseline and clinical characteristics that identify subpopulations of invasively ventilated patients with COVID-19 that may improve daily from PP therapy. This web-based registry will provide relevant information on how the database research tools may improve our daily clinical practice. Conclusions This multicenter, prospective registry is the first to identify and characterize the role of PP on clinical outcome in COVID-19 patients. In recent years, data emerging from large registries have been increasingly used to provide real-world evidence on the effectiveness, quality, and safety of a clinical intervention. Indeed observation-based registries could be effective tools aimed at identifying specific clusters of patients within a large study population with widely heterogeneous clinical characteristics. Copyright

Formate dehydrogenase takes part in molybdenum and iron homeostasis and affects dark-induced senescence in plants

Formate is produced, in plants, by various biochemical pathways and it is degraded by Formate Dehydrogenase FDH, in presence of NAD+, into CO2 and NADH. FDH has been proposed as one of the enzymes regulating molybdenum (Mo) and iron (Fe) homeostasis. Here we explored the impact of FDH perturbation on Mo and Fe plant nutritional status and FDH relevance on the plant responses against abiotic stresses, by using in silico and experimental approaches. The characterization of different Arabidopsis thaliana and Nicotiana tabacum FDH transgenic lines suggests that FDH promoter activity is dependent on both Mo and Fe nutritional supply and that FDH overexpression alters Mo concentrations in seeds and Fe concentration in seeds, leaves and stems. Also, FDH overexpression delays the dark-induced senescence whereas the lack of FDH accelerates its progression. FDH is therefore a multifaceted enzyme with impact on Mo and Fe homeostasis and regulation of dark-induced senescence

Strongly curved super-conducting magnets: beam optics modeling and field quality

Superconducting (SC) dipoles with a strong curvature (radius smaller than 2 meters, for an aperture of about 100 mm and a length of 1-3 meters) are required for applications where compactness is key, such as the synchrotron and gantry for Carbon-ion therapy developed within the European program HITRIplus. Such magnets challenge several assumptions in the field description and put to the test the range of validity of beam optics codes. In particular, the equivalence that holds for the straight magnets between the transverse multipoles description obtained from the Fourier analysis (used for magnet design and measurements) and the Taylor expansion of the vertical field component along the horizontal axis (used in beam optics) is not valid any longer. Proper fringe field modelling also becomes important due to the curved geometry and the aperture being large compared to the magnetic length. We explore the feasibility and the limits of modelling such magnets with optics elements (such as sector bends and multipoles), which allows parametric optics studies for optimization, field quality definition and fast long-term multi-pass tracking.Superconducting dipoles with a strong curvature (radius smaller than 2 meters, for an aperture of about 100 mm and a length of 1-3 meters) are required for applications where compactness is key, such as the synchrotron and gantry for Carbon-ion therapy developed within the European program HITRIplus.Such magnets challenge several assumptions in the field description and put to the test the range of validity of beam optics codes. In particular, the equivalence that holds for the straight magnets between the transverse multipoles description obtained from the Fourier analysis (used for magnet design and measurements) and the Taylor expansion of the vertical field component along the horizontal axis (used in beam optics) is not valid any longer. A proper fringe field modelling also becomes important, due to the curved geometry and the aperture being large compared to the magnetic length.We explore the feasibility and the limits of modeling such magnets with optics elements (such as sector bends and multipoles), which allows parametric optics studies for optimization, field quality definition and fast long-term multi-pass tracking