Aerial additive manufacturing with multiple autonomous robots.

Additive manufacturing methods1-4 using static and mobile robots are being developed for both on-site construction5-8 and off-site prefabrication9,10. Here we introduce a method of additive manufacturing, referred to as aerial additive manufacturing (Aerial-AM), that utilizes a team of aerial robots inspired by natural builders11 such as wasps who use collective building methods12,13. We present a scalable multi-robot three-dimensional (3D) printing and path-planning framework that enables robot tasks and population size to be adapted to variations in print geometry throughout a building mission. The multi-robot manufacturing framework allows for autonomous three-dimensional printing under human supervision, real-time assessment of printed geometry and robot behavioural adaptation. To validate autonomous Aerial-AM based on the framework, we develop BuilDrones for depositing materials during flight and ScanDrones for measuring the print quality, and integrate a generic real-time model-predictive-control scheme with the Aerial-AM robots. In addition, we integrate a dynamically self-aligning delta manipulator with the BuilDrone to further improve the manufacturing accuracy to five millimetres for printing geometry with precise trajectory requirements, and develop four cementitious-polymeric composite mixtures suitable for continuous material deposition. We demonstrate proof-of-concept prints including a cylinder 2.05 metres high consisting of 72 layers of a rapid-curing insulation foam material and a cylinder 0.18 metres high consisting of 28 layers of structural pseudoplastic cementitious material, a light-trail virtual print of a dome-like geometry, and multi-robot simulations. Aerial-AM allows manufacturing in-flight and offers future possibilities for building in unbounded, at-height or hard-to-access locations.

Plasma Adsorption with the MTx.100 Column in Critically Ill COVID-19 Patients: A Prospective Study and Propensity Score Analysis.

BACKGROUND: Early in the COVID-19 pandemic, patients with severe disease admitted to the intensive care unit (ICU) had a high incidence of mortality. We aimed to investigate whether plasma adsorption with the MTx.100 Column could improve survival. METHODS: We performed a prospective, single-arm, multicenter, Emergency Use Authorization (EUA) trial in patients admitted to the ICU with severe COVID-19 who were worsening despite standard therapy. The primary outcome was all-cause mortality on day 28. Outcomes were analyzed using both a pre-specified performance goal (PG), and a propensity score-matched (PSM) analysis from the highest enrolling center, in which patients treated with the standard of care (SOC) plus the MTx.100 Column (n = 70) were compared to a contemporaneous cohort treated at the same center with SOC only (n = 244). FINDINGS: Between May 21, 2020, and November 2, 2021, 107 patients with severe COVID-19 (mean age 58.1) at 7 US centers were enrolled and had at least one plasma adsorption treatment initiated. All-cause mortality on day 28 was 37.4% (40/107), an improvement over the prespecified PG (88.1%, p < 0.0001). There were no serious adverse events attributable to the MTx.100 Column or plasmapheresis. Improvements in most metabolic and inflammatory markers were also noted. The PSM analysis showed that survival odds were three times higher for MTx.100 Column-treated patients (95% CI: 1.56-5.88) than for those treated with SOC only. INTERPRETATION: The MTx.100 Column treatment in severe COVID-19 resulted in a lower mortality than SOC by both pre-specified PG and PSM analysis. TRIAL REGISTRATION: clinicaltrials.gov (NCT04358003).

Longitudinal analysis of anti-SARS-CoV-2 neutralizing antibody (NAb) titers in vaccinees using a novel giant magnetoresistive (GMR) assay.

The COVID-19 pandemic has highlighted the need to monitor important correlates of immunity on a population-wide level. To this end, we have developed a competitive assay to assess neutralizing antibody (NAb) titer on the giant magnetoresistive (GMR) biosensor platform. We compared the clinical performance of our biosensor with established techniques such as Ortho's VITROS Anti-SARS-CoV-2 IgG Quantitative Antibody test. Results obtained between the VITROS test and the GMR assay showed correlation (r = -0.93). We then validated the assay with patient plasma samples that had been tested using focus reduction neutralization testing (FRNT). The results obtained from our GMR assay exhibit a previously identified trend of increased NAb titers 2 weeks post-vaccination. We further evaluated NAb titers 6 months post-vaccination and observed waning neutralizing antibody titers over that time in vaccinated patients. In addition, we calibrated our assay to an arbitrary unit (IU/mL) using World Health Organization (WHO) reference plasma provided by the National Institute of Biological Standards and Control (NIBSC). Our biosensor provides highly specific and sensitive results in serum and plasma with analytical, clinical, and point-of-care (POC) applications due to quick turnaround times on samples and the cost-effectiveness of the platform.

The BlueScreen HC assay to predict the genotoxic potential of fragrance materials.

BlueScreen HC is a mammalian cell-based assay for measuring the genotoxicity and cytotoxicity of chemical compounds and mixtures. The BlueScreen HC assay has been utilized at the Research Institute for Fragrance Materials in a safety assessment program as a screening tool to prioritize fragrance materials for higher-tier testing, as supporting evidence when using a read-across approach, and as evidence to adjust the threshold of toxicological concern. Predictive values for the BlueScreen HC assay were evaluated based on the ability of the assay to predict the outcome of in vitro and in vivo mutagenicity and chromosomal damage genotoxicity assays. A set of 371 fragrance materials was assessed in the BlueScreen HC assay along with existing or newly generated in vitro and in vivo genotoxicity data. Based on a weight-of-evidence approach, the majority of materials in the data set were deemed negative and concluded not to have the potential to be genotoxic, while only a small proportion of materials were determined to show genotoxic effects in these assays. Analysis of the data set showed a combination of high positive agreement but low negative agreement between BlueScreen HC results, in vitro regulatory genotoxicity assays, and higher-tier test results. The BlueScreen HC assay did not generate any false negatives, thereby providing robustness when utilizing it as a high-throughput screening tool to evaluate the large inventory of fragrance materials. From the perspective of protecting public health, it is desirable to have no or minimal false negatives, as a false-negative result may incorrectly indicate the lack of a genotoxicity hazard. However, the assay did have a high percentage of false-positive results, resulting in poor positive predictivity of the in vitro genotoxicity test battery outcome. Overall, the assay generated 100% negative predictivity and 3.9% positive predictivity. In addition to the data set of 371 fragrance materials, 30 natural complex substances were evaluated for BlueScreen HC, Ames, and in vitro micronucleus assay, and a good correlation in all three assays was observed. Overall, while a positive result may have to be further investigated, these findings suggest that the BlueScreen HC assay can be a valuable screening tool to detect the genotoxic potential of fragrance materials and mixtures.

Cardiopulmonary Resuscitation in Intensive Care Unit Patients With Coronavirus Disease 2019.

Cardiopulmonary resuscitation (CPR) in patients with severe acute respiratory syndrome coronavirus-2-associated disease (coronavirus disease 2019) poses a unique challenge to health- care providers due to the risk of viral aerosolization and disease transmission. This has caused some centers to modify existing CPR procedures, limit the duration of CPR, or consider avoiding CPR altogether. In this review, the authors propose a procedure for CPR in the intensive care unit that minimizes the number of personnel in the immediate vicinity of the patient and conserves the use of scarce personal protective equipment. Highlighting the low likelihood of successful resuscitation in high-risk patients may prompt patients to decline CPR. The authors recommend the preemptive placement of central venous lines in high-risk patients with intravenous tubing extensions that allow for medication delivery from outside the patients' rooms. During CPR, this practice can be used to deliver critical medications without delay. The use of a mechanical compression system for CPR further reduces the risk of infectious exposure to health- care providers. Extracorporeal membrane oxygenation should be reserved for patients with few comorbidities and a single failing organ system. Reliable teleconferencing tools are essential to facilitate communication between providers inside and outside the patients' rooms. General principles regarding the ethics and peri-resuscitative management of coronavirus 2019 patients also are discussed.

Tuning Molecular Interactions for Highly Reproducible and Efficient Formamidinium Perovskite Solar Cells via Adduct Approach.

The Lewis acid-base adduct approach has been widely used to form uniform perovskite films, which has provided a methodological base for the development of high-performance perovskite solar cells. However, its incompatibility with formamidinium (FA)-based perovskites has impeded further enhancement of photovoltaic performance and stability. Here, we report an efficient and reproducible method to fabricate highly uniform FAPbI3 films via the adduct approach. Replacement of the typical Lewis base dimethyl sulfoxide (DMSO) with N-methyl-2-pyrrolidone (NMP) enabled the formation of a stable intermediate adduct phase, which can be converted into a uniform and pinhole-free FAPbI3 film. Infrared and computational analyses revealed a stronger interaction between NMP with the FA cation than DMSO, which facilitates the formation of a stable FAI·PbI2·NMP adduct. On the basis of the molecular interactions with different Lewis bases, we proposed criteria for selecting the Lewis bases. Owed to the high film quality, perovskite solar cells with the highest PCE over 20% (stabilized PCE of 19.34%) and average PCE of 18.83 ± 0.73% were demonstrated.

A review and quantitative assessment of cattle-related thermal indices.

Many thermal indices have been developed to assess the levels of heat stress imposed on cattle during hot weather. In this paper, the 16 cattle-related thermal indices are critically reviewed. The primary emphasis is to evaluate each index's coherence to the typical heat transfer characteristics of a cow. Other perspectives including incorporated environmental parameters in the equation(s), experimental data, correlated physiological responses, heat-stress thresholds, scope of application, specific cattle breed involved, and experiment location(s) are also well categorised and discussed. The coherence evaluation indicates that the main effects of environmental parameters on heat stress have been properly reflected, while some interactions between the parameters have been treated differently. Given the variety of the equations used to define the 16 indices and the wide range of information used to develop each index, we conclude that each thermal index is distinct to an extent that it should be selected and employed carefully.

Assessment using CFD of the wind direction on the air discharges caused by natural ventilation of a poultry house.

Air inside poultry houses must be removed on a regular basis to prevent excess of heat, particles and noxious gases that can imperil animals. To cope with this issue, natural ventilation could be an effective method when assisted by accurate predictions. This study investigates air discharges caused by natural ventilation of a poultry house by means of a three-dimensional computational fluid dynamics (CFD) model. It solves the governing equations of momentum, heat and mass transport, radiative transfers and animal-generated heat. Wind directions of 0°, 36° and 56° (0° corresponds to a wind blowing perpendicular to the ridgeline) were investigated; the CFD model predictions achieved a RMSE of 1.2 °C and 0.6 g[H2O] kg-1 [dry air] for internal temperature and absolute humidity, respectively, when air blew with an angle of 36°. Air renewal rates (ARR) were 39.5 (± 1.9), 34.9 (± 2.2) and 33.6 (± 1.7) volumes of the building per hour, when air blew at 0°, 36° and 56°, respectively. Such ARR predictions served to know how the gases contained in air would likely spread downstream from the building in order to define regions of potentially high gas concentration that could endanger neighbouring habitable facilities.

Color Fine-Tuning of Optical Materials Through Rational Design.

We report on the feasibility for color fine-tuning of optical materials using rational design principles based on chemical reasoning. For this purpose, a modular framework for the construction of symmetrical cap-linker-cap compounds, using triarylamine caps and oligothiophene linkers, is applied. The chosen structural scaffolds are heavily used in recent industrial applications and provide five possibilities for altering their electronic and steric properties: electron donor/acceptor groups, planarization/deplanarization, and modulation of the π-conjugation length. Permutation of the used building blocks leads to a set of 54 different molecules, out of which 32 are synthesized and characterized in solution as well as in example fabricated OLED devices. This setup allows for color fine-tuning in the range of 412 nm to 540 nm with typical steps of 4 nm. In addition, to further benefit from the large experimental data set the spectroscopic results are used to benchmark quantum chemical computations, which show excellent agreement thus highlighting the potential of these calculations to guide future syntheses.

Acetone promoted 1,4-migration of an alkoxycarbonyl group on a syn-1,2-diamine.

A 2-protected cis-amino mitosene undergoes an irreversible acetone promoted isomerization and converts to the 1-isomer. Kinetic studies and DFT calculations of the reaction are reported. An organocatalytic mechanism is proposed, involving a covalent intermediate formed by reaction of the mitosene and acetone.

Gene therapy for adenosine deaminase-deficient severe combined immune deficiency: clinical comparison of retroviral vectors and treatment plans.

We conducted a gene therapy trial in 10 patients with adenosine deaminase (ADA)-deficient severe combined immunodeficiency using 2 slightly different retroviral vectors for the transduction of patients' bone marrow CD34(+) cells. Four subjects were treated without pretransplantation cytoreduction and remained on ADA enzyme-replacement therapy (ERT) throughout the procedure. Only transient (months), low-level (< 0.01%) gene marking was observed in PBMCs of 2 older subjects (15 and 20 years of age), whereas some gene marking of PBMC has persisted for the past 9 years in 2 younger subjects (4 and 6 years). Six additional subjects were treated using the same gene transfer protocol, but after withdrawal of ERT and administration of low-dose busulfan (65-90 mg/m(2)). Three of these remain well, off ERT (5, 4, and 3 years postprocedure), with gene marking in PBMC of 1%-10%, and ADA enzyme expression in PBMC near or in the normal range. Two subjects were restarted on ERT because of poor gene marking and immune recovery, and one had a subsequent allogeneic hematopoietic stem cell transplantation. These studies directly demonstrate the importance of providing nonmyeloablative pretransplantation conditioning to achieve therapeutic benefits with gene therapy for ADA-deficient severe combined immunodeficiency.

Impact of tilling on biosolids drying and indicator microorganisms survival during solar drying process.

As biosolids application to croplands becomes a common practice, potential harm from pathogenic microbes needs to be mitigated for its safe reuse. The objective of this study was to investigate the impacts of tilling treatment on biosolids drying and microbial inactivation during the solar drying process in a semi-arid and temperate region. Solar drying experiments were conducted in sand and gravel dying beds open-to-the-air and under covering structures with biosolids to 20 cm depth from 2004 to 2006. Anaerobically- and Aerobically-digested biosolids received different tilling treatments throughout the drying process, while a series of biosolids samples were collected to determine the impact on total solids and microbial concentrations (Salmonella spp and heminth ova). Tilling treatments appeared to enhance the biosolids drying and microbial inactivation. Tilling was more effective during the cold season compared with the summer season and tilling treatments were also helpful in elevating biosolids temperature by expediting biosolids drying. The combined effect of temperature increase and moisture decrease by tilling may have resulted in faster microbial inactivation, particularly for persistent helminth ova. It was concluded that incorporation of tilling into biosolids solar drying can expedite biosolids drying as well as microbial inactivation, and thus can be an effective measure for shortening the biosolids conversion to Class A biosolids in which pathogens are reduced to below detectable levels.

Impacts of tilling and covering treatments on the biosolids solar drying conversion from class B to class A.

The objective of this study was to evaluate the effects of tillage and cover treatments of solar drying on the conversion of class B treated sewage sludge to a class A product. The experiments were performed over two years at Green Valley, Arizona in steel-constructed sand-filled drying beds of 1.0 m (width) x 3.0 m (length) x 0.6 m (depth). Freshly produced aerobically and anaerobically digested biosolids from nearby wastewater treatment plants received tillage and cover treatments for expediting solar drying and microbial inactivation. During the summer drying, covered drying bed increased faecal inactivation rate by 26% over other treatments and automated rain shield abated faecal coliform regrowth from summer rains. Tilling accelerated evaporation of moisture from the biosolids and increased the inactivation rate of faecal coliforms during the summer season. An automated retractable roof to protect the biosolids from rain aided in maintaining class A criteria by preventing dried biosolids from re-wetting by rainfall. However, results from tilling and passive solar heating during the cold winter seasons did not improve the faecal coliform inactivation rate due mainly to lower ambient temperatures. Thus, tilling and cover treatments can be effective in accelerating biosolids solar drying and thus enhancing pathogen inactivation during the summer season. Investigation on the effects of tillage depth and frequency is recommended to determine optimal tilling practice.

The Use of Flap Techniques to Preserve Limb Length in Patients with Transmetatarsal Amputations.

BACKGROUND: Chronic lower extremity wounds affect up to 13% of the US population. Transmetatarsal amputation (TMA) is frequently performed in patients with chronic forefoot wounds. TMA allows limb salvage and preserves functional gait, without need for prosthesis. Traditionally, when tension-free primary closure is not possible, a higher-level amputation is performed. This is the first series to evaluate the outcomes of local and free flap coverage of TMA stumps in patients with chronic foot wounds. METHODS: A retrospective cohort of patients who underwent TMA with flap coverage from 2015 through 2021 was reviewed. Primary outcomes included flap success, early postoperative complications, and long-term outcomes (limb salvage and ambulatory status). Patient-reported outcome measures using the Lower Extremity Functional Scale (LEFS) were also collected. RESULTS: Fifty patients underwent 51 flap reconstructions (26 local, 25 free flap) after TMA. Average age and body mass index were 58.5 years and 29.8 kg/m 2 , respectively. Comorbidities included diabetes [ n = 43 (86%)] and peripheral vascular disease [ n = 37 (74%)]. Flap success rate was 100%. At a mean follow-up of 24.8 months (range, 0.7 to 95.7 months), the limb salvage rate was 86.3% ( n = 44). Forty-four patients (88%) were ambulatory. The LEFS survey was completed by 24 surviving patients (54.5%). Mean LEFS score was 46.6 ± 13.9, correlating with 58.2% ± 17.4% of maximal function. CONCLUSIONS: Local and free flap reconstruction after TMA are viable methods of soft-tissue coverage for limb salvage. Applying plastic surgery flap techniques for TMA stump coverage allows for preservation of increased foot length and ambulation without a prosthesis. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Distal ureter morphogenesis depends on epithelial cell remodeling mediated by vitamin A and Ret.

Almost 1% of human infants are born with urogenital abnormalities, many of which are linked to irregular connections between the distal ureters and the bladder. During development, ureters migrate by an unknown mechanism from their initial integration site in the Wolffian ducts up to the base of the bladder in a process that we call ureter maturation. Rara(-/-) Rarb2(-/-) mice display impaired vitamin A signaling and develop syndromic urogenital malformations similar to those that occur in humans, including renal hypoplasia, hydronephrosis and mega-ureter, abnormalities also seen in mice with mutations in the proto-oncogene Ret. Here we show that ureter maturation depends on formation of the 'trigonal wedge', a newly identified epithelial outgrowth from the base of the Wolffian ducts, and that the distal ureter abnormalities seen in Rara(-/-) Rarb2(-/-) and Ret(-/-) mutant mice are probably caused by a failure of this process. Our studies indicate that formation of the trigonal wedge may be essential for correct insertion of the distal ureters into the bladder, and that these events are mediated by the vitamin A and Ret signaling pathways.

Postoperative Respiratory Failure and Advanced Ventilator Settings.

Postoperative respiratory failure has a multifactorial etiology, of which atelectasis is the most common mechanism. Its injurious effects are magnified by surgical inflammation, high driving pressures, and postoperative pain. Chest physiotherapy and noninvasive ventilation are good options to prevent progression of respiratory failure. Acute respiratory disease syndrome is a late and severe finding, which is associated with high morbidity and mortality. If present, proning is a safe, effective, and underutilized therapy. Extracorporeal membrane oxygenation is an option only when traditional supportive measures have failed.

Photopatternable Porous Separators for Micro-Electrochemical Energy Storage Systems.

The miniaturization of electrochemical energy storage (EES) systems, one of the key challenges facing the rapid expansion of the Internet-of-Things, has been limited by poor performance of the various energy-storage components at the micrometer scale. Here, the development of a unique photopatternable porous separator that overcomes the electrolyte difficulties involving resistive losses at small dimensions is reported. The separator is based on modifying the chemistry of SU-8, an epoxy-derived photoresist, through the addition of a miscible ionic liquid. The ionic liquid serves as a templating agent, which is selectively removed by solution methods, leaving the SU-8 scaffold whose interconnected porosity provides ion transport from the confined liquid electrolyte. The photopatternable separator exhibits good electrochemical, chemical, thermal, and mechanical stability during the operation of electrochemical devices in both 2D and 3D formats. For the latter, the separator demonstrates the ability to form conformal coatings over 3D structures. The development of the photopatternable separator overcomes the electrolyte issues, which have limited progress in the field of micro-EES.