Increasing Supportive Care for Patients With COVID-19-Related Respiratory Deterioration in Non-ICU Settings.

BACKGROUND: Prepandemic hospital guidelines were unable to support an acute influx of patients with respiratory deterioration. New processes for general care practice were needed to facilitate patient care. PURPOSE: To develop and evaluate guidelines to safely treat patients with COVID-19 respiratory deterioration in the general care setting. METHODS: A quality improvement project with 2 PDSA (Plan-Do-Study-Act) cycles was used to develop guidelines for high-flow oxygen and prone positioning, along with frequent monitoring and collaboration with virtual critical care support. RESULTS: Over 6 months, 126 patients with COVID-19 were cared for on general care units. Zero intubations occurred on the general care units, with 211 patient hospital days spent in general care that previously would have required an intensive care unit bed. CONCLUSIONS: Patients in the general care setting with respiratory decline can safely be managed with appropriate monitoring criteria, oxygen device settings, and nursing support unitizing technology.

The Effect of Ocean Salinity on Climate and Its Implications for Earth's Habitability.

The influence of atmospheric composition on the climates of present-day and early Earth has been studied extensively, but the role of ocean composition has received less attention. We use the ROCKE-3D ocean-atmosphere general circulation model to investigate the response of Earth's present-day and Archean climate system to low versus high ocean salinity. We find that saltier oceans yield warmer climates in large part due to changes in ocean dynamics. Increasing ocean salinity from 20 to 50 g/kg results in a 71% reduction in sea ice cover in our present-day Earth scenario. This same salinity change also halves the pCO2 threshold at which Snowball glaciation occurs in our Archean scenarios. In combination with higher levels of greenhouse gases such as CO2 and CH4, a saltier ocean may allow for a warm Archean Earth with only seasonal ice at the poles despite receiving ∼20% less energy from the Sun.

Human-Inspired Robotic Eye-Hand Coordination Enables New Communication Channels Between Humans and Robots.

This paper concerns human-inspired robotic eye-hand coordination algorithms using custom built robotic eyes that were interfaced with a Baxter robot. Eye movement was programmed anthropomorphically based on previously reported research on human eye-hand coordination during grasped object transportation. Robotic eye tests were first performed on a component level where accurate position and temporal control were achieved. Next, 11 human subjects were recruited to observe the novel robotic system to quantify the ability of robotic eye-hand coordination algorithms to convey two kinds of information to people during object transportation tasks: first, the transported object's delivery location and second, the level of care exerted by the robot to transport the object. Most subjects correlated decreased frequency in gaze fixations on an object's target location with increased care of transporting an object, although these results were somewhat mixed among the 11 human subjects. Additionally, the human subjects were able to reliably infer the delivery location of the transported object purely by the robotic eye-hand coordination algorithm with an overall success rate of 91.4%. These results suggest that anthropomorphic eye-hand coordination of robotic entities could be useful in pedagogical or industrial settings.

Improved Ipsilateral Breast and Chest Wall Sparing With MR-Guided 3-fraction Accelerated Partial Breast Irradiation: A Dosimetric Study Comparing MR-Linac and CT-Linac Plans.

PURPOSE: External beam accelerated partial breast irradiation (APBI) is subject to treatment uncertainties that must be accounted for through planning target volume (PTV) margin. We hypothesize that magnetic resonance-guided radiation therapy with reduced PTV margins enabled by real-time cine magnetic resonance image (MRI) target monitoring results in better normal tissue sparing compared with computed tomography (CT)-guided radiation therapy with commonly used clinical PTV margins. In this study, we compare the plan quality of ViewRay MRIdian Linac forward planned intensity modulated radiation therapy and TrueBeam volumetric modulated arc therapy for a novel 3-fraction APBI schedule. METHODS AND MATERIALS: Targets and organs at risk (OARs) were segmented for 10 patients with breast cancer according to NSABP B39/RTOG 0413 protocol. A 3 mm margin was used to generate MR PTV3mm and CT PTV3mm plans, and a 10 mm margin was used for CT PTV10mm. An APBI schedule delivering 24.6 Gy to the clinical target volume and 23.4 Gy to the PTV in 3 fractions was used. OAR dose constraints were scaled down from existing 5-fraction APBI protocols. Target and OAR dose-volume metrics for the following data sets were analyzed using Wilcoxon matched-pairs signed-rank test: (1) MR PTV3mm versus CT PTV3mm plans and (2) MR PTV3mm versus CT PTV10mm. RESULTS: Average PTVs were 84.3 ± 51.9 cm3 and 82.6 ± 55 cm3 (P = .5) for MR PTV3mm and CT PTV3mm plans, respectively. PTV V23.4Gy, dose homogeneity index, conformity index (CI), and R50 were similar. There was no meaningful difference in OAR metrics, despite MR PTV3mm being larger than the CT PTV3mm in 70% of the patients. Average PTVs for MR PTV3mm and CT PTV10mm plans were 84.3 ± 51.9 cm3 and 131.7 ± 74.4 cm3, respectively (P = .002). PTV V23.4Gy was 99% ± 0.9% versus 97.6% ± 1.4% (P = .03) for MR PTV3mm and CT PTV10mm, respectively. Dose homogeneity index, CI, and R50 were similar. MR PTV3mm plans had better ipsilateral breast (V12.3Gy, 34.8% ± 12.7% vs 44.4% ± 10.9%, P = .002) and chest wall sparing (V24Gy, 8.5 ± 5.5 cm3 vs 21.8 ± 14.9 cm3, P = .004). CONCLUSIONS: MR- and CT-based planning systems produced comparable plans when a 3 mm PTV margin was used for both plans. As expected, MR PTV3mm plans produced better ipsilateral breast and chest wall sparing compared with CT PTV10mm. The clinical relevance of these differences in dosimetric parameters is not known.

Reduction of cardiac dose using respiratory-gated MR-linac plans for gastro-esophageal junction cancer.

Treatment of locally advanced adenocarcinoma of the gastroesophageal junction (GEJ) with chemoradiation may be associated with high rates of symptomatic cardiac toxicity. Large margins are typically required to ensure coverage of GEJ tumors with free-breathing volumetric modulated arc therapy (VMAT) radiotherapy. The purpose of this study is to determine whether treatment with tighter margins enabled by maximum-inhalation breath hold (MIBH)-gated intensity modulated radiation therapy (IMRT) on an integrated MRI-linear accelerator system (MR-linac) can decrease radiation doses to the heart and cardiac substructures. Ten patients with locally advanced GEJ adenocarcinoma underwent both free breathing 4-dimensional computed tomography (4DCT) and MIBH MRI simulation scans. MR-linac IMRT plans were created with a 3 mm clinical target volume (CTV) to planning target volume (PTV) isotropic margin and 4DCT VMAT plans were created with a 11, 13, and 9 mm CTV to PTV anisotropic margins in the left-right, cranial-caudal, and anterior-posterior directions according to GEJ-specific PTV expansion recommendations by Voncken et al. Prescription dose to PTV was 50.4 Gy in 28 fractions. Dosimetry to the heart and cardiac substructures was compared with paired t test; p < 0.05 was considered significant. Mean PTV on the MR-linac IMRT plans was significantly smaller compared to the 4DCT VMAT plans (689 cm3vs 1275 cm3, p < 0.01). Mean dose to the heart and all cardiac substructures was significantly lower in the MR-linac IMRT plans compared to the 4DCT VMAT plans: heart 20.9 Gy vs 27.8 Gy, left atrium 29.6 Gy vs 39.4 Gy, right atrium 20.5 Gy vs 25.6 Gy, left ventricle 21.6 Gy vs 29.6 Gy, and right ventricle 18.7 Gy vs 25.2 Gy (all p values <0.05). MIBH-gated MR-linac IMRT treatment of locally advanced GEJ adenocarcinoma can significantly decrease doses to the heart and cardiac substructures and this may translate to reduced rates of cardiac toxicity.

A bacterial biosynthetic pathway for methylated furan fatty acids.

Fatty acids play many important roles in cells and also in industrial processes. Furan fatty acids (FuFAs) are present in the lipids of some plant, fish, and microbial species and appear to function as second messengers in pathways that protect cells from membrane-damaging agents. We report here the results of chemical, genetic, and synthetic biology experiments to decipher the biosynthesis of the monomethylated FuFA, methyl 9-(3-methyl-5-pentylfuran-2-yl) nonanoate (9M5-FuFA), and its dimethyl counterpart, methyl 9-(3,4-dimethyl-5-pentylfuran-2-yl) nonanoate (9D5-FuFA), in two α-proteobacteria. Each of the steps in FuFA biosynthesis occurs on pre-existing phospholipid fatty acid chains, and we identified pathway intermediates and the gene products that catalyze 9M5-FuFA and 9D5-FuFA synthesis in Rhodobacter sphaeroides 2.4.1 and Rhodopseudomonas palustris CGA009. One previously unknown pathway intermediate was a methylated diunsaturated fatty acid, (10E,12E)-11-methyloctadeca-10,12-dienoic acid (11Me-10t,12t-18:2), produced from (11E)-methyloctadeca-11-enoic acid (11Me-12t-18:1) by a newly identified fatty acid desaturase, UfaD. We also show that molecular oxygen (O2) is the source of the oxygen atom in the furan ring of 9M5-FuFA, and our findings predict that an O2-derived oxygen atom is incorporated into 9M5-FuFA via a protein, UfaO, that uses the 11Me-10t,12t-18:2 fatty acid phospholipid chain as a substrate. We discovered that R. palustris also contains a SAM-dependent methylase, FufM, that produces 9D5-FuFA from 9M5-FuFA. These results uncover the biochemical sequence of intermediates in a bacterial pathway for 9M5-FuFA and 9D5-FuFA biosynthesis and suggest the existence of homologs of the enzymes identified here that could function in FuFA biosynthesis in other organisms.

Exoplanet Biosignatures: A Review of Remotely Detectable Signs of Life.

In the coming years and decades, advanced space- and ground-based observatories will allow an unprecedented opportunity to probe the atmospheres and surfaces of potentially habitable exoplanets for signatures of life. Life on Earth, through its gaseous products and reflectance and scattering properties, has left its fingerprint on the spectrum of our planet. Aided by the universality of the laws of physics and chemistry, we turn to Earth's biosphere, both in the present and through geologic time, for analog signatures that will aid in the search for life elsewhere. Considering the insights gained from modern and ancient Earth, and the broader array of hypothetical exoplanet possibilities, we have compiled a comprehensive overview of our current understanding of potential exoplanet biosignatures, including gaseous, surface, and temporal biosignatures. We additionally survey biogenic spectral features that are well known in the specialist literature but have not yet been robustly vetted in the context of exoplanet biosignatures. We briefly review advances in assessing biosignature plausibility, including novel methods for determining chemical disequilibrium from remotely obtainable data and assessment tools for determining the minimum biomass required to maintain short-lived biogenic gases as atmospheric signatures. We focus particularly on advances made since the seminal review by Des Marais et al. The purpose of this work is not to propose new biosignature strategies, a goal left to companion articles in this series, but to review the current literature, draw meaningful connections between seemingly disparate areas, and clear the way for a path forward. Key Words: Exoplanets-Biosignatures-Habitability markers-Photosynthesis-Planetary surfaces-Atmospheres-Spectroscopy-Cryptic biospheres-False positives. Astrobiology 18, 663-708.

Perceptions and performance using computer-based testing: One institution's experience.

BACKGROUND AND PURPOSE: The purpose of this study was to evaluate student and faculty perceptions of the transition to a required computer-based testing format and to identify any impact of this transition on student exam performance. EDUCATIONAL ACTIVITY AND SETTING: Separate questionnaires sent to students and faculty asked about perceptions of and problems with computer-based testing. Exam results from program-required courses for two years prior to and two years following the adoption of computer-based testing were compared to determine if this testing format impacted student performance. FINDINGS: Responses to Likert-type questions about perceived ease of use showed no difference between students with one and three semesters experience with computer-based testing. Of 223 student-reported problems, 23% related to faculty training with the testing software. Students most commonly reported improved feedback (46% of responses) and ease of exam-taking (17% of responses) as benefits to computer-based testing. Faculty-reported difficulties were most commonly related to problems with student computers during an exam (38% of responses) while the most commonly identified benefit was collecting assessment data (32% of responses). Neither faculty nor students perceived an impact on exam performance due to computer-based testing. An analysis of exam grades confirmed there was no consistent performance difference between the paper and computer-based formats. DISCUSSION AND SUMMARY: Both faculty and students rapidly adapted to using computer-based testing. There was no evidence that switching to computer-based testing had any impact on student exam performance.

Bone marrow suppression as a complication of total skin helical tomotherapy in the treatment of mycosis fungoides.

BACKGROUND: Total skin electron beam therapy (TSEBT) is an effective treatment in mycosis fungoides. Total skin helical tomotherapy (TSHT) may be an alternative to TSEBT and may offer several dosimetric and treatment advantages. There are currently very few published treatment results using TSHT in place of TSEBT for treatment of mycosis fungoides. CASE PRESENTATION: Two patients with mycosis fungoides were treated at our institution using TSHT. The first patient was a 69-year-old Caucasian female with stage IVA2 (T2 N3 M0 B2) disease who was treated to a dose of 12 Gy in 8 fractions, with a bone marrow mean dose of 1.66 Gy and V10 = 0.41%. Two weeks after ending treatment the patient developed myelosuppression including grade 4 thrombocytopenia and required blood and platelet transfusions. The second patient was a 29-year-old Caucasian female with stage I (T2 N0 M0 B0) disease. This patient previously had been treated for mycosis fungoides using helical tomotherapy (HT) at a dose of 20 Gy to a localized region and experienced mild thrombocytopenia at that time. The patient then underwent retreatment 17 months later with TSHT to a dose of 12 Gy in 6 fractions with a mean bone marrow dose of 2.3 Gy and V10 = 4.28%. This patient once again experienced myelosuppression that included grade 4 thrombocytopenia. She also required blood and platelet transfusions. CONCLUSIONS: Both patients treated with TSHT experienced severe bone marrow suppression including grade 4 thrombocytopenia. This was more severe than expected considering the relatively low overall prescription dose and despite a planning constraint placed on the bone marrow of a mean dose of < 2 Gy. These outcomes suggest that patients treated using TSHT should be closely monitored for myelosuppression and caution used even when treating to a dose of 12 Gy.

Disequilibrium biosignatures over Earth history and implications for detecting exoplanet life.

Chemical disequilibrium in planetary atmospheres has been proposed as a generalized method for detecting life on exoplanets through remote spectroscopy. Among solar system planets with substantial atmospheres, the modern Earth has the largest thermodynamic chemical disequilibrium due to the presence of life. However, how this disequilibrium changed over time and, in particular, the biogenic disequilibria maintained in the anoxic Archean or less oxic Proterozoic eons are unknown. We calculate the atmosphere-ocean disequilibrium in the Precambrian using conservative proxy- and model-based estimates of early atmospheric and oceanic compositions. We omit crustal solids because subsurface composition is not detectable on exoplanets, unlike above-surface volatiles. We find that (i) disequilibrium increased through time in step with the rise of oxygen; (ii) both the Proterozoic and Phanerozoic may have had remotely detectable biogenic disequilibria due to the coexistence of O2, N2, and liquid water; and (iii) the Archean had a biogenic disequilibrium caused by the coexistence of N2, CH4, CO2, and liquid water, which, for an exoplanet twin, may be remotely detectable. On the basis of this disequilibrium, we argue that the simultaneous detection of abundant CH4 and CO2 in a habitable exoplanet's atmosphere is a potential biosignature. Specifically, we show that methane mixing ratios greater than 10-3 are potentially biogenic, whereas those exceeding 10-2 are likely biogenic due to the difficulty in maintaining large abiotic methane fluxes to support high methane levels in anoxic atmospheres. Biogenicity would be strengthened by the absence of abundant CO, which should not coexist in a biological scenario.

False Negatives for Remote Life Detection on Ocean-Bearing Planets: Lessons from the Early Earth.

Ocean-atmosphere chemistry on Earth has undergone dramatic evolutionary changes throughout its long history, with potentially significant ramifications for the emergence and long-term stability of atmospheric biosignatures. Though a great deal of work has centered on refining our understanding of false positives for remote life detection, much less attention has been paid to the possibility of false negatives, that is, cryptic biospheres that are widespread and active on a planet's surface but are ultimately undetectable or difficult to detect in the composition of a planet's atmosphere. Here, we summarize recent developments from geochemical proxy records and Earth system models that provide insight into the long-term evolution of the most readily detectable potential biosignature gases on Earth-oxygen (O2), ozone (O3), and methane (CH4). We suggest that the canonical O2-CH4 disequilibrium biosignature would perhaps have been challenging to detect remotely during Earth's ∼4.5-billion-year history and that in general atmospheric O2/O3 levels have been a poor proxy for the presence of Earth's biosphere for all but the last ∼500 million years. We further suggest that detecting atmospheric CH4 would have been problematic for most of the last ∼2.5 billion years of Earth's history. More broadly, we stress that internal oceanic recycling of biosignature gases will often render surface biospheres on ocean-bearing silicate worlds cryptic, with the implication that the planets most conducive to the development and maintenance of a pervasive biosphere will often be challenging to characterize via conventional atmospheric biosignatures. Key Words: Biosignatures-Oxygen-Methane-Ozone-Exoplanets-Planetary habitability. Astrobiology 17, 287-297.

Cyanobacterial Diazotrophy and Earth's Delayed Oxygenation.

The redox landscape of Earth's ocean-atmosphere system has changed dramatically throughout Earth history. Although Earth's protracted oxygenation is undoubtedly the consequence of cyanobacterial oxygenic photosynthesis, the relationship between biological O2 production and Earth's redox evolution remains poorly understood. Existing models for Earth's oxygenation cannot adequately explain the nearly 2.5 billion years delay between the origin of oxygenic photosynthesis and the oxygenation of the deep ocean, in large part owing to major deficiencies in our understanding of the coevolution of O2 and Earth's key biogeochemical cycles (e.g., the N cycle). For example, although possible links between O2 and N scarcity have been previously explored, the consequences of N2 limitation for net biological O2 production have not been examined thoroughly. Here, we revisit the prevailing view that N2 fixation has always been able to keep pace with P supply and discuss the possibility that bioavailable N, rather than P, limited export production for extended periods of Earth's history. Based on the observation that diazotrophy occurs at the expense of oxygenesis in the modern ocean, we suggest that an N-limited biosphere may be inherently less oxygenic than a P-limited biosphere-and that cyanobacterial diazotrophy was a primary control on the timing and tempo of Earth's oxygenation by modulating net biogenic O2 fluxes. We further hypothesize that negative feedbacks inhibit the transition between N and P limitation, with the implication that the pervasive accumulation of O2 in Earth's ocean-atmosphere system may not have been an inevitable consequence of oxygenic photosynthesis by marine cyanobacteria.

Limited role for methane in the mid-Proterozoic greenhouse.

Pervasive anoxia in the subsurface ocean during the Proterozoic may have allowed large fluxes of biogenic CH4 to the atmosphere, enhancing the climatic significance of CH4 early in Earth's history. Indeed, the assumption of elevated pCH4 during the Proterozoic underlies most models for both anomalous climatic stasis during the mid-Proterozoic and extreme climate perturbation during the Neoproterozoic; however, the geologic record cannot directly constrain atmospheric CH4 levels and attendant radiative forcing. Here, we revisit the role of CH4 in Earth's climate system during Proterozoic time. We use an Earth system model to quantify CH4 fluxes from the marine biosphere and to examine the capacity of biogenic CH4 to compensate for the faint young Sun during the "boring billion" years before the emergence of metazoan life. Our calculations demonstrate that anaerobic oxidation of CH4 coupled to SO42- reduction is a highly effective obstacle to CH4 accumulation in the atmosphere, possibly limiting atmospheric pCH4 to less than 10 ppm by volume for the second half of Earth history regardless of atmospheric pO2 If recent pO2 constraints from Cr isotopes are correct, we predict that reduced UV shielding by O3 should further limit pCH4 to very low levels similar to those seen today. Thus, our model results likely limit the potential climate warming by CH4 for the majority of Earth history-possibly reviving the faint young Sun paradox during Proterozoic time and challenging existing models for the initiation of low-latitude glaciation that depend on the oxidative collapse of a steady-state CH4 greenhouse.

Earth's oxygen cycle and the evolution of animal life.

The emergence and expansion of complex eukaryotic life on Earth is linked at a basic level to the secular evolution of surface oxygen levels. However, the role that planetary redox evolution has played in controlling the timing of metazoan (animal) emergence and diversification, if any, has been intensely debated. Discussion has gravitated toward threshold levels of environmental free oxygen (O2) necessary for early evolving animals to survive under controlled conditions. However, defining such thresholds in practice is not straightforward, and environmental O2 levels can potentially constrain animal life in ways distinct from threshold O2 tolerance. Herein, we quantitatively explore one aspect of the evolutionary coupling between animal life and Earth's oxygen cycle-the influence of spatial and temporal variability in surface ocean O2 levels on the ecology of early metazoan organisms. Through the application of a series of quantitative biogeochemical models, we find that large spatiotemporal variations in surface ocean O2 levels and pervasive benthic anoxia are expected in a world with much lower atmospheric pO2 than at present, resulting in severe ecological constraints and a challenging evolutionary landscape for early metazoan life. We argue that these effects, when considered in the light of synergistic interactions with other environmental parameters and variable O2 demand throughout an organism's life history, would have resulted in long-term evolutionary and ecological inhibition of animal life on Earth for much of Middle Proterozoic time (∼1.8-0.8 billion years ago).