A US perspective on closing the carbon cycle to defossilize difficult-to-electrify segments of our economy.

Electrification to reduce or eliminate greenhouse gas emissions is essential to mitigate climate change. However, a substantial portion of our manufacturing and transportation infrastructure will be difficult to electrify and/or will continue to use carbon as a key component, including areas in aviation, heavy-duty and marine transportation, and the chemical industry. In this Roadmap, we explore how multidisciplinary approaches will enable us to close the carbon cycle and create a circular economy by defossilizing these difficult-to-electrify areas and those that will continue to need carbon. We discuss two approaches for this: developing carbon alternatives and improving our ability to reuse carbon, enabled by separations. Furthermore, we posit that co-design and use-driven fundamental science are essential to reach aggressive greenhouse gas reduction targets.

Total Capital Investment of plastic recycling plants correlates with energy losses and capacity.

Plastic pollution is a generational problem, and stakeholders are turning to chemical recycling as a potential solution. However, decision-makers necessitate quick and reliable capital investment estimations to evaluate innovative technologies, especially in the early project stage, when limited historical data are available. To address this need, we built a database of 160+ chemical recycling plants, querying for nominal capacity, year and place of construction, total capital investment (TCI), number of long-term jobs and opportunity of subsidies. Then, we compared conventional association of the advancement of cost engineering AACE class 5 estimation methods, with literature estimates, and commercial capital expenditure confidence intervals for pyrolysis, gasification, solvolysis, and selective dissolution. We demonstrate the unreliability of classic methods, and we propose ballpark correlations based on the plant capacity, or the energy loss. Chemical recycling plants suffer from poor economy of scale (with current technologies), and capacity is not always the best indicator for TCI estimation. Pyrolysis and gasification are energy-driven technologies, and their TCI correlates very well (R2 =0.91-0.92) with the total energy losses. Solvolysis and selective dissolution, instead, are at an earlier development stage, so cost engineers or researchers will have to accept less certain TCI vs capacity (R2 =0.60).

Augmented Reality Microsurgery: Proof of Concept for a Novel Approach to Microsurgical Field Visualization in Plastic Surgery.

BACKGROUND: Microsurgery is conducted on tiny anatomical structures such as blood vessels and nerves. Over the past few decades, little has changed in the way plastic surgeons visualize and interact with the microsurgical field. New advances in augmented reality (AR) technology present a novel method for microsurgical field visualization. Voice- and gesture-based commands can be used in real time to adjust the size and position of a digital screen. Surgical decision support and/or navigation may also be used. The authors assess the use of AR in microsurgery. METHODS: The video feed from a Leica Microsystems OHX surgical microscope was streamed to a Microsoft HoloLens2 AR headset. A fellowship-trained microsurgeon and three plastic surgery residents then performed a series of four arterial anastomoses on a chicken thigh model using the AR headset, a surgical microscope, a video microscope (or "exoscope"), and surgical loupes. RESULTS: The AR headset provided an unhindered view of the microsurgical field and peripheral environment. The subjects remarked on the benefits of having the virtual screen track with head movements. The ability of participants to place the microsurgical field in a tailored comfortable, ergonomic position was also noted. Points of improvement were the low image quality compared with current monitors, image latency, and the lack of depth perception. CONCLUSIONS: AR is a useful tool that has the potential to improve microsurgical field visualization and the way surgeons interact with surgical monitors. Improvements in screen resolution, latency, and depth of field are needed.

Chemical Signatures of Seasonally Unique Anthropogenic Influences on Organic Aerosol Composition in the Central Amazon.

Urbanization and fires perturb the quantities and composition of fine organic aerosol in the central Amazon, with ramifications for radiative forcing and public health. These disturbances include not only direct emissions of particulates and secondary organic aerosol (SOA) precursors but also changes in the pathways through which biogenic precursors form SOA. The composition of ambient organic aerosol is complex and incompletely characterized, encompassing millions of potential structures relatively few of which have been synthesized and characterized. Through analysis of submicron aerosol samples from the Green Ocean Amazon (GoAmazon2014/5) field campaign by two-dimensional gas chromatography coupled with machine learning, ∼1300 unique compounds were traced and characterized over two seasons. Fires and urban emissions produced chemically and interseasonally distinct impacts on product signatures, with only ∼50% of compounds observed in both seasons. Seasonally unique populations point to the importance of aqueous processing in Amazonian aerosol aging, but further mechanistic insights are impeded by limited product identity knowledge. Less than 10% of compounds were identifiable at an isomer-specific level. Overall, the findings (i) provide compositional characterization of anthropogenic influence on submicron organic aerosol in the Amazon, (ii) identify key season-to-season differences in chemical signatures, and (iii) highlight high-priority knowledge gaps in current speciated knowledge.

Impact of ACAPS Coordinated Interview Release Policy: Applicant and Program Attitudes, Adherence, and Interview Trends.

BACKGROUND: The authors studied the impact of a new, coordinated interview release date for integrated plastic surgery residencies. METHODS: A cross-sectional study of all 2020 integrated plastic surgery residencies and applicants was performed. Voluntary, anonymous surveys were administered following implementation of the interview policy. RESULTS: Program response rates were 55.6% for the initial survey and 57.1% for the follow-up survey. Programs released an average of 2.1 (95% CI, 1.8 to 2.4) rounds of interview invitations and invited 39.0 (95% CI, 35.3 to 42.6) applicants to interview. Policy adherence was high (91.1%). Most programs believed the interview policy was an improvement for applicants (46.5% yes; 9.1% no) and programs (41.9% yes; 27.0% no). Median rank of matched candidates was 13, and 55.1% of programs matched candidates within the top quartile of their rank list. The average candidate applied to 72 programs, attended 11 interviews, and ranked 12 programs. Interview distribution was bimodal, with peaks at six and 15 total interview invitations. Applicants within the top fifth, tenth, and fifteenth percentile for total interview invites disproportionately accounted for 15.3%, 26.6%, and 36.5%, respectively, of all invitations received. Survey data suggested applicant satisfaction with travel planning, improved scheduling, and cost savings following implementation of the interview policy. Applicants were somewhat dissatisfied with interview distribution. CONCLUSIONS: A coordinated interview release date is facile to adopt and does not adversely impact program interview trends or match rates. Applicants benefit from improved scheduling, travel planning, and cost savings; however, interview distribution continues to favor top-tier candidates.

Chip for dielectrophoretic microbial capture, separation and detection II: experimental study.

In our previous paper we have modelled a dielectrophoretic force (DEP) and cell particle behavior in a microfluidic channel (Weber MUet al2023 Chip for dielectrophoretic microbial capture, separation and detection I: theoretical basis of electrode designNanotechnologythis issue). Here we test and confirm the results of our modeling work by experimentally validating the theoretical design constraints of the ring electrode architecture. We have compared and tested the geometry and particle capture and separation performance of the two separate electrode designs (the ring and dot electrode structures) by investigating bacterial motion in response to the applied electric field. We have quantitatively evaluated the electroosmosis (EO) to positive DEP (PDEP) transition in both electrode designs and explained the differences in capture efficiency of the ring and dot electrode systems. The ring structure shows 99% efficiency of bacterial capture both for PDEP and for EO. Moreover, the ring structure shows an over 200 faster bacterial response to the electric field. We have also established that the ring electrode architecture, with appropriate structure periodicity and spacing, results in efficient capture and separation of microbial cells. We have identified several critical design constraints that are required to achieve high efficiency bacterial capture. We have established that the spacing between consecutive DEP traps smaller than the length of the depletion zone will ensure that the DEP force dominates bacterial motion over motility and Brownian motion.

Chip for dielectrophoretic microbial capture, separation and detection I: theoretical basis of electrode design.

We model the dielectrophoretic response ofE. colibacterial cells and red blood cells, upon exposure to an electric field. We model the separation, capture, and release mechanisms under flow conditions in a microfluidic channel and show under which conditions efficient separation of different cell types occurs. The modelling work is aimed to guide the separation electrode architecture and design for experimental validation of the model. The dielectrophoretic force is affected both by the geometry of the electrodes (the gradient of the electric field), the Re{CM(ω)} factor, and the permittivity of the medium ϵm. Our modelling makes testable predictions and shows that designing the electrode structure to ensure structure periodicity with spacing between consecutive traps smaller than the length of the depletion zone ensures efficient capture and separation. Such electrode system has higher capture and separation efficiency than systems with the established circular electrode architecture. The simulated, modelled microfluidic design allows for the separated bacteria, concentrated by dedicated dielectrophoretic regions, to be subsequently detected using label-free functionalized nanowire sensors. The experimental validation of the modelling work presented here and the validation of the theoretical design constraints of the chip electrode architecture is presented in the companion paper in the same issue (Weber MUet al2022 Chip for dielectrophoretic Microbial Capture, Separation and Detection II: Experimental Study).

Anthropogenic and Biogenic Contributions to the Organic Composition of Coastal Submicron Sea Spray Aerosol.

The organic composition of coastal sea spray aerosol is important for both atmospheric chemistry and public health but remains poorly characterized. Coastal waters contain an organic material derived from both anthropogenic processes, such as wastewater discharge, and biological processes, including biological blooms. Here, we probe the chemical composition of the organic fraction of sea spray aerosol over the course of the 2019 SeaSCAPE mesocosm experiment, in which a phytoplankton bloom was facilitated in natural coastal water from La Jolla, California. We apply untargeted two-dimensional gas chromatography to characterize submicron nascent sea spray aerosol samples, reporting ∼750 unique organic species traced over a 19 day phytoplankton bloom experiment. Categorization and quantitative compositional analysis reveal three major findings. First, anthropogenic species made up 30% of total submicron nascent sea spray aerosol organic mass under the pre-bloom condition. Second, biological activity drove large changes within the aerosolized carbon pool, decreasing the anthropogenic mass fraction by 89% and increasing the biogenic and biologically transformed fraction by a factor of 5.6. Third, biogenic marine organics are underrepresented in mass spectral databases in comparison to marine organic pollutants, with more than twice as much biogenic aerosol mass attributable to unlisted compounds.

Mapping hormone-regulated cell-cell interaction networks in the human breast at single-cell resolution.

The rise and fall of estrogen and progesterone across menstrual cycles and during pregnancy regulates breast development and modifies cancer risk. How these hormones impact each cell type in the breast remains poorly understood because they act indirectly through paracrine networks. Using single-cell analysis of premenopausal breast tissue, we reveal a network of coordinated transcriptional programs representing the tissue-level response to changing hormone levels. Our computational approach, DECIPHER-seq, leverages person-to-person variability in breast composition and cell state to uncover programs that co-vary across individuals. We use differences in cell-type proportions to infer a subset of programs that arise from direct cell-cell interactions regulated by hormones. Further, we demonstrate that prior pregnancy and obesity modify hormone responsiveness through distinct mechanisms: obesity reduces the proportion of hormone-responsive cells, whereas pregnancy dampens the direct response of these cells to hormones. Together, these results provide a comprehensive map of the cycling human breast.

Colonization of Dogs and Their Owners with Staphylococcus aureus and Staphylococcus pseudintermedius in Households, Veterinary Practices, and Healthcare Facilities.

There are uncertainties with respect to the transmission of methicillin-susceptible and methicillin-resistant Staphylococcus aureus (MSSA and MRSA) and Staphylococcus pseudintermedius between dogs and humans. In this study, we investigated concomitant nasal colonization of dogs and humans in three cohorts. Cohort I, households owning dogs: In 42 of 84 households, 66 humans (36.9%) and 10 dogs (8.9%) carried S. aureus. MRSA, attributed to sequence type (ST) 22 and ST130, were detected in two (1.1%) of the humans but in none of the dogs. Typing by means of spa-typing and whole-genome sequencing (WGS) indicated eight transmissions of S. aureus between humans and dogs in 8 of 42 (19.0%) households with human S. aureus carriers, whereas in 11 of 38 (29.0%) households with ≥two persons and S. aureus colonization of humans, 15 human-to-human transmissions were observed (p = 0.43). S. pseudintermedius was isolated from 42 dogs (37.5%), but from only one human (0.6%). In this case, WGS-based typing indicated strong relatedness of this isolate with a canine isolate from the same household. Cohort II, dogs and their owners visiting a veterinary practice: Among 17 humans and 17 dogs attending a veterinary practice, MSSA was detected in three humans and two dogs, and S. pseudintermedius in only six dogs. Cohort III, dogs used for animal-assisted interventions in human healthcare facilities and their owners: MSSA was obtained in 1 of 59 dogs (1.7%) and in 17 of 60 (28.3%) of the dog owners, while S. pseudintermedius was isolated from seven (12%) dogs and one (1.7%) human owner. We conclude that the risk of exchanging S. aureus/MRSA between humans and dogs is higher than that for S. pseudintermedius.

Epidemiological and genetic characteristics of vancomycin-resistant Enterococcus faecium isolates in a University Children's Hospital in Germany: 2019 to 2020.

BACKGROUND: Vancomycin-resistant Enterococcus faecium (VREfm) strains are one of the most important pathogens causing nosocomial infections in Germany. Due to limited treatment options and an increased risk for acquisition in immunocompromised children, surveillance to monitor occurrence of VREfm in paediatric clinical facilities is of critical importance. Following an unusual accumulation of VREfm positive patients between April 2019 and August 2020 at Dr. von Hauner Children's Hospital in Munich, Germany, our study aimed to identify dynamics and routes of transmission, and analyse the affected population in view of previously described host risk factors for VREfm colonisation or infection. METHODS: The hospital database was used to collect epidemiological and clinical data of VREfm cases. Descriptive statistical analyses were conducted to outline patient characteristics and depict possible differences between VREfm-colonised and -infected children. An outbreak investigation determining genetic relatedness among VREfm isolates was performed by core genome multilocus sequence typing (cgMLST). To examine potential transmission pathways, results of genome analysis were compared with epidemiological and clinical data of VREfm positive patients. RESULTS: VREfm acquisition was documented in a total of 33 children (< 18 years). Seven VREfm-colonised patients (21.2%), especially those with a haemato-oncological disease (4/7; p = 0.011), showed signs of clinical infection. cgMLST analysis revealed seven distinct clusters, demonstrating a possible connection within each clonal lineage. Additional eight singletons were identified. Comparison with epidemiological and clinical data provided strong evidence for a link between several VREfm positive patients within the hospital. CONCLUSIONS: A nosocomial spread-at least in part-was the most likely reason for the unusual accumulation of VREfm cases. The study highlights that there is a constant need to increase efforts in hygiene measures, infection control and antibiotic stewardship to combat VREfm transmission events within German paediatric hospitals. Continuous monitoring of adherence to respective policies might reduce the occurrence of clustered cases and prevent future outbreaks.

Aging of Volatile Organic Compounds in October 2017 Northern California Wildfire Plumes.

In the western United States, the number and severity of large wildfires have been growing for decades. Biomass burning (BB) is a major source of volatile organic compounds (VOCs) to the atmosphere both globally and regionally. Following emission, BB VOCs are oxidized while being transported downwind, producing ozone, secondary organic aerosols, and secondary hazardous VOCs. In this research, we measured VOCs using proton transfer reaction time-of-flight mass spectrometry (PTR-ToF-MS) in an urban area 55-65 km downwind of the October 2017 Northern California wildfires. Nonaromatic oxygenated compounds were the dominant component of BB VOCs measured. In the smoke plumes, the VOCs account for 70-75% of the total observed organic carbon, with the remainder being particulate matter (with a diameter of <2.5 µm, PM2.5). We show that the correlation of VOCs with furan (primary BB VOC) and maleic anhydride (secondary BB VOC) can indicate the origin of the VOCs. This was further confirmed by the diurnal variations of the VOCs and their concentration-weighted trajectories. Oxidation during transport consumed highly reactive compounds including benzenoids, furanoids, and terpenoids and produced more oxygenated VOCs. Furthermore, wildfire VOCs altered the ozone formation regime and raised the O3 levels in the San Francisco Bay Area.

Ultra-deep long-read sequencing detects IS-mediated gene duplications as a potential trigger to generate arrays of resistance genes and a mechanism to induce novel gene variants such as blaCTX-M-243.

BACKGROUND: Extended-spectrum ß-lactamases (ESBLs) are enzymes that can render their hosts resistant to various ß-lactam antibiotics. CTX-M-type enzymes are the most prevalent ESBLs and the main cause of resistance to third-generation cephalosporins in Enterobacteriaceae. The number of described CTX-M types is continuously rising, currently comprising over 240 variants. During routine screening we identified a novel blaCTX-M gene. OBJECTIVES: To characterize a novel blaCTX-M variant harboured by a multidrug-resistant Escherichia coli isolate of sequence type ST354. METHODS: Antibiotic susceptibilities were determined using broth microdilution. Genome and plasmid sequences were reconstructed using short- and long-read sequencing. The novel blaCTX-M locus was analysed using long-read and Sanger sequencing. Plasmid polymorphisms were determined in silico on a single plasmid molecule level. RESULTS: The novel blaCTX-M-243 allele was discovered alongside a nearly identical blaCTX-M-104-containing gene array on a 219 kbp IncHI2A plasmid. CTX-M-243 differed from CTX-M-104 by only one amino acid substitution (N109S). Ultra-deep (2300-fold coverage) long-read sequencing revealed dynamic scaling of the blaCTX-M genetic contexts from one to five copies. Further antibiotic resistance genes such as blaTEM-1 also exhibited sequence heterogeneity but were stable in copy number. CONCLUSIONS: We identified the novel ESBL gene blaCTX-M-243 and illustrate a dynamic system of varying blaCTX-M copy numbers. Our results highlight the constant emergence of new CTX-M family enzymes and demonstrate a potential evolutionary platform to generate novel ESBL variants and possibly other antibiotic resistance genes.

TP-0903 Is Active in Preclinical Models of Acute Myeloid Leukemia with TP53 Mutation/Deletion.

Acute myeloid leukemia (AML) with mutations in the tumor suppressor gene TP53 confers a dismal prognosis with 3-year overall survival of <5%. While inhibition of kinases involved in cell cycle regulation induces synthetic lethality in a variety of TP53 mutant cancers, this strategy has not been evaluated in mutant TP53 AML. Previously, we demonstrated that TP-0903 is a novel multikinase inhibitor with low nM activity against AURKA/B, Chk1/2, and other cell cycle regulators. Here, we evaluated the preclinical activity of TP-0903 in TP53 mutant AML cell lines, including a single-cell clone of MV4-11 containing a TP53 mutation (R248W), Kasumi-1 (R248Q), and HL-60 (TP 53 null). TP-0903 inhibited cell viability (IC50, 12−32 nM) and induced apoptosis at 50 nM. By immunoblot, 50 nM TP-0903 upregulated pChk1/2 and pH2AX, suggesting induction of DNA damage. The combination of TP-0903 and decitabine was additive in vitro, and in vivo significantly prolonged median survival compared to single-agent treatments in mice xenografted with HL-60 (vehicle, 46 days; decitabine, 55 days; TP-0903, 63 days; combination, 75 days) or MV4-11 (R248W) (51 days; 62 days; 81 days; 89 days) (p < 0.001). Together, these results provide scientific premise for the clinical evaluation of TP-0903 in combination with decitabine in TP53 mutant AML.

Intentional Modulation of Ibrutinib Pharmacokinetics through CYP3A Inhibition.

Ibrutinib (Imbruvica; PCI-32765) is an orally administered inhibitor of Bruton's tyrosine kinase that has transformed the treatment of B-cell malignancies. However, ibrutinib has very low oral bioavailability that contributes to significant variability in systemic exposure between patients, and this has the potential to affect both efficacy and toxicity. We hypothesized that the oral bioavailability of ibrutinib is limited by CYP3A isoform-mediated metabolism, and that this pathway can be inhibited to improve the pharmacokinetic properties of ibrutinib. Pharmacokinetic studies were performed in wild-type mice and mice genetically engineered to lack all CYP3A isoforms [CYP3A(-/-)] that received ibrutinib alone or in combination with CYP3A inhibitors cobicistat or ketoconazole. Computational modeling was performed to derive doses of ibrutinib that, when given after a CYP3A inhibitor, results in therapeutically-relevant drug levels. Deficiency of CYP3A in mice was associated with a ~10-fold increase in the area under the curve of ibrutinib. This result could be phenocopied by administration of cobicistat before ibrutinib in wild-type mice, but cobicistat did not influence levels of ibrutinib in CYP3A(-/-) mice. Population pharmacokinetic and prospectively validated physiologically-based pharmacokinetic models established preclinical and clinical doses of ibrutinib that could be given safely in combination with cobicistat without negatively affecting anti-leukemic properties. These findings signify a dominant role for CYP3A-mediated metabolism in the elimination of ibrutinib, and suggest a role for pharmacological inhibitors of this pathway to intentionally modulate the plasma levels and improve the therapeutic use of this clinically important agent.

Fluid-Screen as a real time dielectrophoretic method for universal microbial capture.

Bacterial culture methods, e.g. Plate Counting Method (PCM), are a gold standard in the assessment of microbial contamination in multitude of human industries. They are however slow, labor intensive, and prone to manual errors. Dielectrophoresis (DEP) has shown great promise for particle separation for decades; however, it has not yet been widely applied in routine laboratory setting. This paper provides an overview of a new DEP microbial capture and separation method called Fluid-Screen (FS), that achieves very fast, efficient, reliable and repeatable capture and separation of microbial cells. Method verification experiments demonstrated that the FS system captured 100% of bacteria in test samples, a capture efficiency much higher than previously reported for similar technology. Data generated supports the superiority of the FS method as compared to the established Plate Counting Method (PCM), that is routinely used to detect bacterial contamination in healthcare, pharmacological and food industries. We demonstrate that the FS method is universal and can capture and separate different species of bacteria and fungi to viruses, from various sample matrices (i.e. human red blood cells, mammalian cells).

Guidelines for Leading a Safe Medication Error Reporting Culture.

Background: A safe medication error reporting culture is one that promotes, fosters, and rewards the reporting of errors and events across the spectrum of harm (none to significant harm). For this culture to develop, leaders must key department cultural norms. These cultural norms include making employees feel psychologically safe to report errors, and to establish a culture of error review and follow-up that complies with best practices. Objective: This article reviews how pharmacy leaders can establish this environment by describing (1) setting an appropriate vision for safety as a priority; (2) establishing and actively supporting the concept of psychological safety; and (3) implementing medication error review that support an effective safety culture. Finally, the article discusses a case where the relationships between psychological safety, safety culture, and reporting culture are described. Methods: This article reviews the literature and authors' experiences in designing a safety culture for a pharmacy department. Concluson: A safe reporting culture requires leaders to be humble, engage their staff in dialogue, objectively measure culture, consistently provide feedback, and empower its people. Employing these leadership traits with best practices can improve overall medication safety and the quality of patient-centered pharmacy services.

Atmospheric Benzothiazoles in a Coastal Marine Environment.

Organic emissions from coastal waters play an important but poorly understood role in atmospheric chemistry in coastal regions. A mesocosm experiment focusing on facilitated biological blooms in coastal seawater, SeaSCAPE (Sea Spray Chemistry and Particle Evolution), was performed to study emission of volatile gases, primary sea spray aerosol, and formation of secondary marine aerosol as a function of ocean biological and chemical processes. Here, we report observations of aerosol-phase benzothiazoles in a marine atmospheric context with complementary measurements of dissolved-phase benzothiazoles. Though previously reported dissolved in polluted coastal waters, we report the first direct evidence of the transfer of these molecules from seawater into the atmosphere. We also report the first gas-phase observations of benzothiazole in the environment absent a direct industrial, urban, or rubber-based source. From the identities and temporal dynamics of the dissolved and aerosol species, we conclude that the presence of benzothiazoles in the coastal water (and thereby their emissions into the atmosphere) is primarily attributable to anthropogenic sources. Oxidation experiments to explore the atmospheric fate of gas-phase benzothiazole show that it produces secondary aerosol and gas-phase SO2, making it a potential contributor to secondary marine aerosol formation in coastal regions and a participant in atmospheric sulfur chemistry.

Leadership Approaches to Staff Health and Wellness During COVID-19 Pandemic.

Background: COVID-19 disease as caused by a coronavirus called SARS-CoV-2 has taken the world by storm with upwards of 8 million confirmed infections in more than 190 countries. At the writing of this article, over 2 million Americans are confirmed infected and 117,000 have died. Rapid changes to manage COVID-19 care creates significant physical and emotional stress for healthcare employees, including pharmacy staff. Objective: This article provides pharmacy leaders with advice in leading through COVID-19 to promote staff resiliency. Methods: The specific leadership strategies include: (1) identifying and addressing fundamental needs; (2) communicating updated and reliable information; and (3) providing psychological and mental health support. Conclusion: Using various techniques described will help to preserve workforce resilience in providing patient-centered pharmacy services. After reading this article, pharmacy directors will have strategies and resources to maintain employee resiliency during this difficult time.