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Background Inhaled treprostinil (iTre) is the only treatment approved for pulmonary hypertension due to interstitial lung disease (PH-ILD) to improve exercise capacity. This post hoc analysis evaluated clinical worsening and PH-ILD exacerbations from the 16-week INCREASE study and change in 6-minute walking distance (6MWD) in the INCREASE open-label extension (OLE) in patients with less severe haemodynamics.Methods Patients were stratified by baseline pulmonary vascular resistance (PVR) of 5 WU. Exacerbations of underlying lung disease, clinical worsening and change in N-terminal prohormone of brain natriuretic peptide (NT-proBNP) in INCREASE were evaluated. For the OLE, patients previously assigned to placebo were considered to have a 16-week treatment delay. 6MWD and clinical events in the OLE were evaluated by PVR subgroup.Results Of the 326 patients enrolled in INCREASE, patients with less severe haemodynamics receiving iTre had fewer exacerbations of underlying lung disease and clinical worsening events. This was supported by the Bayesian analysis of the risk of disease progression (HR

Abstract Pulmonary hypertension (PH) due to interstitial lung disease (ILD), a commonly encountered complication of fibrotic ILDs, is associated with significant morbidity and mortality. Until recently, the studies of pulmonary vasodilator therapy in PH‐ILD have been largely disappointing, with some even demonstrating the potential for harm. This paper is part of a series of Consensus Statements from the Pulmonary Vascular Research Institute's Innovative Drug Development Initiative for Group 3 Pulmonary Hypertension, with prior publications covering pathogenesis, prevalence, clinical features, phenotyping, clinical trials, and impact of PH‐ILD. It offers a comprehensive review of and a holistic approach to treatment of PH‐ILD, including the management of underlying interstitial lung diseases, importance of treating the comorbidities, emphasis on importance of exercise and palliation of dyspnea, and review of the most up‐to‐date guidelines for referral for potential lung transplant work up. It also summarizes the prior, ongoing, and possibly future studies in treatment of the vascular derangement of this morbid condition.

Treprostinil is a prostacyclin approved for the treatment of pulmonary arterial hypertension. Commercial data sets indicate that approximately 20–25% of patients are prescribed a higher dose than the maximum recommended dosage of nine breaths per treatment session (bps) (54 μg), four times a day (QID) and numerous studies have demonstrated the safety of doses >9 bps QID. This phase 4, retrospective analysis of specialty pharmacy records assessed the effects of inhaled treprostinil at doses >9 bps QID. Patients receiving inhaled treprostinil between September 2009 and June 2018 were included, and a random sampling of 5000 patients was selected for further analysis. Subjects were grouped based on the highest dose reached for ≥2 months within a rolling six‐month window and were followed for up to three years. Of the total of 5000 patients analyzed, 28.5% received >9 bps QID. Survival rates were significantly higher in the >9 bps QID dosing group for years one, two, and three (P 9 bps (17.5 months) compared to doses ≤9 bps (9.5 moths; P 9 bps at years 1, 2, and 3 (P 9 bps QID had a higher rate of survival and drug persistence over a three‐year period, suggesting that higher doses may provide clinically relevant benefits while remaining tolerable.

A method where particulates are transferred via a cosmetic brush onto liquid drops created on a highly non-wetting substrate with a hole to generate talc and graphite liquid marbles (LMs) and talc-graphite Janus liquid marbles is described. van der Waals forces facilitated the attachment of particulates to the dry brush bristles. Subsequently, the surface tension forces that developed from particle interaction with water (which were O(102) higher than the van der Waals forces) could then engender transfer of the particulates to the liquid-gas interface of the drop. Forces below 1 mN applied by a dangling foil on the LM ensured preservation of the drop shape when the force was removed. During the application of this force, the contact angles at the contact lines behaved differently from sessile drops that are inclined on surfaces. This preparation method portends the ability to automate the creation of LMs and Janus LMs for various applications.

Abstract Pulmonary hypertension (PH) has been linked to worse outcomes in chronic lung diseases. The presence of PH in the setting of underlying Interstitial Lung Disease (ILD) is strongly associated with decreased exercise and functional capacity, an increased risk of hospitalizations and death. Examining the scope of this issue and its impact on patients is the first step in trying to define a roadmap to facilitate and encourage future research in this area. The aim of our working group is to strengthen the communities understanding of PH due to lung diseases and to improve the care and quality of life of affected patients. This introductory statement provides a broad overview and lays the foundation for further in‐depth papers on specific topics pertaining to PH‐ILD.

Digital microfluidics, which relies on the movement of drops, is relatively immune to clogging problems, making it suited for micro-reactor applications. Here, graphene oxide paper of 100 μm thickness, fabricated by blade coating sedimented dispersions onto roughened substrates, followed by drying and mechanical exfoliation, was found to be relatively free of cracks and curling. It also exhibited high wettability and elasto-capillary characteristics. Possessing low enough stiffness, it could rapidly and totally self-wrap water drops of 20 μL volume placed 2 mm from its edge when oriented between 0 and 60° to the horizontal. This complete wrapping behavior allowed drops to be translated via movement of the paper over long distances without dislodgement notwithstanding accelerations and decelerations. An amount of 2 drops that were wrapped with separate papers, when collided with each other at speeds up to 0.64 m/s, were found to eschew coalescence. This portends the development of robust digital microfluidic approaches for micro-reactors.

A facile one-step method of roughened copper foils of 0.0076 ​mm thickness heated on the open flame for 15 ​s produced superhydrophilic surfaces that exhibited superwetting at average radial growths of 10.8 ​mm/s following drop dispensation. Superhydrophilicity was found to deteriorate over time and XRD analysis ruled out compositional change as the cause of this behaviour. Instead, SEM imaging revealed wrinkled 20–30 ​nm-thick nanoflakes that were predominantly stretched out initially to engender superwetting properties via Wenzel wetting. These extended microstructures folded up with time due to relaxation of the residual stresses from the thermal oxidation process, resulting in temporal reduction in superhydrophilicity, which can be restored by reapplying thermal oxidation. The impingement of air with 80 psi pressure on the substrate also caused similar deterioration. The superwetting characteristic also endowed these substrates with anti-bacterial properties where a 56% reduction in bacteria count with Staphylococcus epidermidis was found.

A two-component liquid drop is generated over a hole on a superhydrophobic substrate. When a 6 V electrolysis voltage was applied to the overhanging component of the liquid drop, bubbles of oxygen and hydrogen at rates of 0.0025 and 0.045 mm3/s respectively were produced. Positioning the electrode beneath the hole allowed the gas bubbles to travel upwards by buoyancy into the overhead liquid component for aeration. The bubbles broke-up into smaller sizes, which would facilitate gas diffusion to the liquid phase, and populated the apex of the overhead component.

Treprostinil is a prostacyclin analogue approved for the treatment of pulmonary arterial hypertension. Apart from the inhaled formulation, there is neither a target dose nor a ceiling dose to guide clinicians using treprostinil; doses are individualized for each patient based upon tolerability and clinical improvement. Using combined data from the pivotal subcutaneous and oral treprostinil studies, we evaluated the effect of treprostinil dose on hospitalization and exercise capacity to better define the treprostinil dose–response relationship. Data from the pivotal subcutaneous and oral treprostinil studies were combined by converting oral doses to weight-based continuous doses (ng/kg/min) accounting for patient weight and bioavailability. Patients were divided into dose tertiles (lowest, middle, highest 33%) and retrospectively analyzed. Analysis 1 assessed the effect of dose on pulmonary arterial hypertension-related and all-cause hospitalizations. Analysis 2 evaluated the effects of dose on six-minute walk distance, Borg dyspnea score, and World Health Organization functional class. Results showed that, in Analysis 1, higher doses of treprostinil were associated with significantly longer times to first pulmonary arterial hypertension-related and all-cause hospitalization. In Analysis 2, there was a trend toward improvements in six-minute walk distance with higher doses. In patients with pulmonary arterial hypertension on systemic treprostinil therapy, higher doses were associated with significantly longer time to first pulmonary arterial hypertension-related and all-cause hospitalization. There was a trend toward improvements in six-minute walk distance. Collectively, these results underscore the importance of managing prostacyclin adverse events in order to achieve appropriate dose titration. Further studies are required to confirm these findings and to better characterize the dose–response relationship of treprostinil.

In building retrofit projects, dynamic simulations are performed to simulate building performance. Uncertainty may negatively affect model calibration and predicted lighting energy savings, which increases the chance of default on performance-based contracts. Therefore, the aim of this paper is to develop a simulation-based method that can analyze lighting performance risk in lighting retrofit decisions. The model uses a surrogate model, which is constructed by adaptively selecting sample points and generating approximation surfaces with fast computing time. The surrogate model is a replacement of the computation intensive process. A statistical method is developed to generate extreme weather profile based on the 20-year historical weather data. A stochastic occupancy model was created using actual occupancy data to generate realistic occupancy patterns. Energy usage of lighting, and heating, ventilation, and air conditioning (HVAC) is simulated using EnergyPlus. The method can evaluate the influence of different risk factors (e.g., variation of luminaire input wattage, varying weather conditions) on lighting and HVAC energy consumption and lighting electricity demand. Probability distributions are generated to quantify the risk values. A case study was conducted to demonstrate and validate the methods. The surrogate model is a good solution for quantifying the risk factors and probability distribution of the building performance.

Digital microfluidics, which relies on the movement of drops, is relatively immune to clogging problems, making it suited for micro-reactor applications. Here, graphene oxide paper of 100 μm thickness, fabricated by blade coating sedimented dispersions onto roughened substrates, followed by drying and mechanical exfoliation, was found to be relatively free of cracks and curling. It also exhibited high wettability and elasto-capillary characteristics. Possessing low enough stiffness, it could rapidly and totally self-wrap water drops of 20 μL volume placed 2 mm from its edge when oriented between 0 and 60° to the horizontal. This complete wrapping behavior allowed drops to be translated via movement of the paper over long distances without dislodgement notwithstanding accelerations and decelerations. An amount of 2 drops that were wrapped with separate papers, when collided with each other at speeds up to 0.64 m/s, were found to eschew coalescence. This portends the development of robust digital microfluidic approaches for micro-reactors. [ABSTRACT FROM AUTHOR]

A better understanding of the mechanics of condensation is needed to devise active bioaerosol samplers. Here, dropwise water condensation produced by directing humid air flow perpendicularly on ambient (25 °C) and cooled (4 °C) copper plate substrates was studied. Numerical data obtained from solving the two-dimensional incompressible Navier–Stokes equations with low Reynolds numbers (=40) showed significant vorticity strength developing at the edges of the copper plate. This resulted in a higher degree of aerosol deposition and an increased likelihood of drop nucleation at the impaction zone. When a drop is already present at the edge, simulations predicted that the high vorticity region shifted to the apexes of drops with concomitant increase in the magnitude of vorticity strength. These results explained the experimentally observed dropwise condensation of larger drops at the edges of the ambient substrate. Analyses of drop size distributions at the center and edges of ambient and cooled substrates showed that drop growth was enhanced by improved condensation on the cooled substrate surface in addition to the flow vorticity effect. Preliminary findings indicate that the recovery of viable aerosolized Escherichia coli from ambient and cooled substrate was found to be invariant, portending its utility for sampling when the electrical power available for cooling is limited. Copyright © 2023 American Association for Aerosol Research [ABSTRACT FROM AUTHOR]

A thermal cycling method, whereby capillary tubes holding polymerase chain reactions are subjected to programmed tilt displacements so that they are moved using gravity over three spatial regions (I, II, and III) kept at different constant temperatures to facilitate deoxyribonucleic acid (DNA) denaturation, annealing, and extension, is described. At tilt speeds in excess of 0.2 rad/s, the standard deviation of static coefficient of friction values was below 0.03, indicating in sync movement of multiple capillary tubes over the holding platform. The travel time during the acceleration phase and under constant velocity between adjacent regions (I to II and II to III) and distant regions (III to I) was 0.03 s and 0.31 s, respectively. The deviations in temperature did not exceed 0.05 °C from the average at the prescribed denaturing, annealing, and extension temperatures applied. DNA amplification was determined by optical readings, the fluorescence signal was found to increase twofold after 30 thermal cycles, and 1.16 × 106 DNA copies/μl could be detected. The approach also overcomes problems associated with thermal inertia, sample adhesion, sample blockage, and handling of the reaction vessels encountered in the other thermal cycling schemes used. [ABSTRACT FROM AUTHOR]

Single-cell proteomics is an emerging approach to characterize cell-to-cell differences. Here, the authors develop chips that enable complete proteomic sample processing down to the single-cell level and integrate them with DIA-MS into a streamlined single-cell proteomics workflow.

Transparent wood composites, with their high strength and toughness, thermal insulation, and excellent transmissivity, offer a route to replace glass for diffusely transmitting windows. Here, conjugated‐polymer‐based electrochromic devices (ECDs) that switch on‐demand are demonstrated using transparent wood coated with poly(3,4‐ethylenedioxythiophene):poly(styrene sulfonate) (PEDOT:PSS) as a transparent conducting electrode. These ECDs exhibit a vibrant magenta‐to‐clear color change that results from a remarkably colorless bleached state. Furthermore, they require low energy and power inputs of 3 mWh m−2 at 2 W m−2 to switch due to a high coloration efficiency (590 cm2 C−1) and low driving voltage (0.8 V). Each device component is processed with high‐throughput methods, which highlights the opportunity to apply this approach to fabricate mechanically robust, energy‐efficient smart windows on a large scale. [ABSTRACT FROM AUTHOR]

A vast majority of syringe pumps operate on stepper motors, which limits their effectiveness for precision fluid delivery using estimation algorithms. Such a system also hampers the ability to ascertain if the infusion or aspiration instruction has been correctly carried out in the event of power interruptions. To address this issue, a linear servo based actuator system is described to provide absolute indications of the plunger position. System performance in terms of linearity and reliability of plunger translation were verified using a camera tracking system with syringe capacities ranging from 3 to 50 ml and at syringe plunger speeds ranging from 1 to 6.6 mm/s when distilled water was used as the medium. In investigations involving more viscous liquids, the system revealed similarly linear characteristics with 50% glycerol-water (v/v), but cyclical stick-slip behavior with Freund's adjuvant. [ABSTRACT FROM AUTHOR]

Throughout the literature, a variety of counter electrode materials have been used in conjugated polymer-based electrochromic devices (ECDs) without a comparative understanding of their effects on the electrochromic properties of the device. In this study, we show that poor ECD performance, often attributed to electrochromic polymer (ECP) stability, is in fact largely due to an inappropriate choice of counter electrode. We have compared a set of counter electrode materials used in the ECD literature in magenta-to-clear and black-to-clear devices and evaluated how they affect the device parameters including contrast, switching time, stability, and voltage requirements. We demonstrate that through the appropriate choice of counter electrode material (i) the operating voltage can be lowered, (ii) no additional equilibration/break-in time is required, and (iii) the contrast and switching times of the ECP is maintained when incorporated into a device. Furthermore, we show that even unencapsulated ECDs with ECP-Magenta as the vibrantly colored material assembled and operated under ambient conditions can withstand over 10 000 switches without compromising contrast or switching time. [ABSTRACT FROM AUTHOR]

This work describes the manufacture and performance of an electrochromic display with solution-based processing. The presented process yields devices with very high life times of more than 100,000 cycles even when switched asymmetrically (with respect to time). [ABSTRACT FROM AUTHOR]

Nowadays, hospitals are ubiquitous and integral to modern society. Patients flow in and out of a veritable whirlwind of paperwork, consultations, and potential inpatient admissions, through an abstracted system that is not without flaws. One of the biggest flaws in the medical system is perhaps an unexpected one: the patient alarm system. One longitudinal study reported an 88.8% rate of false alarms, with other studies reporting numbers of similar magnitudes. These false alarm rates lead to deleterious effects that manifest in a lower standard of care across clinics. This paper discusses a model-based probabilistic inference approach to estimate physiological variables at a detection level. We design a generative model that complies with a layman’s understanding of human physiology and perform approximate Bayesian inference. One primary goal of this paper is to justify a Bayesian modeling approach to increasing robustness in a physiological domain. In order to evaluate our algorithm we look at the application of heart beat detection using four datasets provided by PhysioNet, a research resource for complex physiological signals, in the form of the PhysioNet 2014 Challenge set-p1 and set-p2, the MIT-BIH Polysomnographic Database, and the MGH/MF Waveform Database. On these data sets our algorithm performs on par with the other top six submissions to the PhysioNet 2014 challenge. The overall evaluation scores in terms of sensitivity and positive predictivity values obtained were as follows: set-p1 (99.72%), set-p2 (93.51%), MIT-BIH (99.66%), and MGH/MF (95.53%). These scores are based on the averaging of gross sensitivity, gross positive predictivity, average sensitivity, and average positive predictivity. [ABSTRACT FROM AUTHOR]

Cryopreservation is a widely used long-term preservation method to ensure the quality and vitality of microbes in laboratories and biological resource facilities. However, freeze-thaw damage and osmotic pressure changes during cryopreservation adversely impacts microbial survival. Significant expenditure of resources and expertise are required to select the right cryoprotectant and optimize its concentration for maximum survival of diverse microorganisms. This work describes a cryopreservation method that obviates the need for cryoprotectants by exploiting the unique thermal characteristics of semi-spherical drops. Here, a plurality of these drops, each 10 μl in volume, created on a highly non-wetting flat-sheet substrate with holes and frozen at −70 °C. Deriving an f (x) metric as a measure of relative viability, storage in drops in the absence of cryoprotectants was found to improve the survivability of Staphylococcus epidermidis by 1.91 times compared with the same sample stored in larger 50-μl volumes in standard 1.5-ml tubes. This also compares well with a value of 2.33 obtained with standard preservation with cryoprotectant. The drop method allows high throughput aliquoting of the bacterial culture into multiple discrete drops using multichannel pipettes or automated liquid handlers and the edges of the holes provides a pinning action that holds the drop stably against gravitational roll-offs. It also allows samples to be removed in discrete small volumes, thus, reducing the number of freeze thaw cycles and associated cell damage. The flat-sheet architecture of the substrate reduces the amount of plastic waste generated and augments green laboratory practices. • Semi-spherical drops of bacteria samples, each 10 μl in volume, were formed on non-wetting substrates with holes. • When frozen to −70 °C, the Staphylococcus epidermidis in these drops had 2 times higher survivability than in vials. • This approach portends to be a viable long-term storage of microorganisms in biobanks for studies over time. [ABSTRACT FROM AUTHOR]

Dry ice (solid CO 2) remains highly useful when temperature-sensitive biological samples need to be cryogenically transported. CO 2 released during the sublimation of dry ice can diffuse through gas permeable receptacle material or any defective seals resulting in potential sample acidification and compromised integrity. In addition, the quality of cryopreservation can be undermined once the dry ice is exhausted. The dry ice carrier design described here has been demonstrated to prevent sublimated CO 2 from reaching the samples while maintaining storage temperature below −60 °C for 19 h. It is also equipped with microcontroller-based temperature monitoring for traceability and CO 2 gas monitoring for safety. Image 1 • The dry ice carrier design here prevents sublimated CO2 from reaching samples to cause acidification. • It also maintains the storage temperature below −60 °C for 19 h using 1.35 kg of dry ice during transport. • It is equipped with microcontroller-based temperature monitoring for traceability and CO2 gas monitoring for safety. [ABSTRACT FROM AUTHOR]

The use of an inverted burette arrangement that allowed volume and time-course tracking of bubble movement via camera imaging is shown here to improve on the classical inverted jar (or beaker) method for measuring gases generated in small volumes and at slow rates (below 1 mL/s). In tests involving discrete gas volume measurements delivered at 0.57 mL/s, comparison with pre-set air volume delivered by a syringe pump showed high correspondence, linearity, and repeatability. Tests with continuous gas flows at 0.2, 0.32 and 0.57 mL/s revealed average bubble count versus volume trends that displayed high linearity to indicate that the bubble volumes (at any flowrate) were constant. The average bubble count versus time also showed linear trends and repeatability indicating that the time intervals between the appearance of any two bubbles (at a particular flowrate) were uniform. The analytical and simulated results helped to explain why bubble size determination by high speed camera recording for measuring gas volume and flowrate is fraught with inherent problems. An analysis using light ray tracing showed that flowrate determination using such an approach would necessitate complicated image correction when two cameras are used for simultaneous recording due to distortion effects resulting from refraction. A virtual gate approach involving the binarization of images recorded with a standard camera is shown to be more feasible in establishing the flowrate using bubble counting or finding the time interval between bubbles. Image 1 • The inverted burette arrangement here improves on the classical inverted jar in volume and rate gas measurement. • Good measurement correspondence, linearity and repeatability of volume was confirmed with absolute syringe pump. • Bubbles formed have constant volumes and regular periods between their creation to aid flowrate measurement. • Optical analytical and simulations reveal problems with flowrate determination using bubble size measurement. • A virtual gate approach that involves the binarization of images allows use of standard cameras. [ABSTRACT FROM AUTHOR]

• Thermal analysis of immersion PCR with capillary tubes more effectively done numerically than experimentally. • The temperature field could be coupled with the fluid-structure interaction using a moving mesh physics module in COMSOL. • In PCR using the tilt method, uniform temperature distributions could be obtained with 5s of settling time. • In PCR using the classical method, translation speeds over 150 mm/min are needed to limit temperature drop to 10 °C. • The tilt method offers a more effective way to implement extreme PCR with low volume reagents. Polymerase Chain Reaction (PCR) amplifies specific deoxyribonucleic acid (DNA) targets whereby the reaction vessels are placed in high thermal inertia media and subjected to multiple cycles of discrete temperatures to effect denaturation, annealing and extension events. Precise temperature control and efficient heat transfer are crucial factors in achieving amplification reproducibility and reliability as well as in reducing the time required for PCR. Understanding the temperature distribution and transfer characteristics during PCR will facilitate system optimization to enhance the efficiency of DNA amplification. We describe a numerical thermal study investigating temperature profiles achieved using the classical method of manual transfer of PCR reaction vessels through a series of temperature-controlled media compared with that of a more recently reported method that displaces reaction vessels spatially by tilting through different temperature zones. It was found that while the classical method allows the reagent to achieve uniform temperature distribution, natural convection effects would necessitate translation speeds in excess of 150 mm/min in order to limit the reagent temperature drop to within 10 °C. With the tilt method, uniform temperature distributions as well as temperature settling times within 5 s could be attained. The simulation results demonstrated here indicate that the tilt method can be developed further to augment extreme PCR requiring less than 2s for each cycle. [Display omitted] [ABSTRACT FROM AUTHOR]

A system devised to conduct Polymerase Chain Reaction (PCR) in-flight on drones that uses the spatial displacement of capillary tubes on thermal blocks kept at 94 °C, 58 °C and 72 °C corresponding to cycling temperatures for denaturation, annealing and extension is demonstrated here. The use of acetal as the thermal block material reduced heat loss and the input power (within 18.5 W) needed to maintain the required temperatures. Tests showed that concentrations of samples down to 1.16 × 106 DNA copies/μL could be significantly and consistently detected above the background emission of the fluorescence signal intensity. Image 1 • PCR done in-flight on drones using spatial displacement of capillary tubes on thermal blocks is demonstrated. • Thermal blocks with acetal reduced heat loss and input power needed to maintain the required temperatures. • Samples down to 1.16 x 106 DNA copies/μL could be significantly and consistently detected. [ABSTRACT FROM AUTHOR]

Highly wetting and nonwetting substrates have been widely used in fogwater collection systems for enhanced water harvesting. In this work, fog harvesting substrates comprising PVC strips of different wetting properties and widths ranging from 1-5 mm were vertically aligned and spaced apart at regular intervals to give the same solid area fraction of 0.8. Evaluation of the water collection efficiencies of the tested configurations revealed that 1 mm wide superhydrophilic strips was the most efficient, achieving double the amount of water harvested compared with 2.8 mm wide strips. This finding was attributed to the low Stokes numbers of the aerosol particle distribution of the fog which tended to result in them being brought by the flow streamlines toward the air gaps between the strips. Stagnant flow regions at the edges of each strip, revealed through potential flow calculations, then caused higher liquid imbibition and impaction there for water harvesting. It was also found that the Cassie nonwetting substrates that originally exhibited contact angles of 161° transformed to Wenzel wetting with zero contact angle within 60 min of fog interception. Optical profilometry revealed no obvious difference in surface roughness between the central region and edges of the strips, indicating that surface morphology was unlikely to be a contributing factor for enhanced water collection at the edges. The findings here indicated that highly wetting vertical strip architectures with narrow widths (1 mm) were favorable over wider strips for water harvesting provided that clogging and re-entrainment were not significant factors.