Total (United States)

the president of the United States declared a national emergency in response to the coronavirus disease 2019 (COVID-19) pandemic (1). With reports of laboratory-confirmed cases in all 50 states by that time (2), disruptions were anticipated in the U.S. health care system's ability to continue providing routine preventive and other nonemergency care. In addition, many states and localities issued shelter-in-place or stay-at-home orders to reduce the spread of COVID-19, limiting movement outside the home to essential activities (3). On March 24, CDC posted guidance emphasizing the importance of routine well child care and immunization, particularly for children aged 24 months, when many childhood vaccines are recommended.* Two data sources were examined to assess the impact of the pandemic on pediatric vaccination in the United States: Vaccines for Children Program (VFC) provider order data from CDC's Vaccine Tracking System and Vaccine Safety Datalink (VSD) vaccine administration data. Vaccination coverage is the traditional metric used to assess vaccine usage; however, provider orders and doses administered represent two immediately available proxy measures.

BACKGROUND: Lipedema is a loose connective tissue disease predominantly in women identified by increased nodular and fibrotic adipose tissue on the buttocks, hips and limbs that develops at times of hormone, weight and shape change including puberty, pregnancy, and menopause. Lipedema tissue may be very painful and can severely impair mobility. Non-lipedema obesity, lymphedema, venous disease, and hypermobile joints are comorbidities. Lipedema tissue is difficult to reduce by diet, exercise, or bariatric surgery. METHODS: This paper is a consensus guideline on lipedema written by a US committee following the Delphi Method. Consensus statements are rated for strength using the GRADE system. RESULTS: Eighty-five consensus statements outline lipedema pathophysiology, and medical, surgical, vascular, and other therapeutic recommendations. Future research topics are suggested. CONCLUSION: These guidelines improve the understanding of the loose connective tissue disease, lipedema, to advance our understanding towards early diagnosis, treatments, and ultimately a cure for affected individuals.

Controlling polymorphism is critical in areas such as pharmaceuticals, biomineralization, and catalysis. Notably, the formation of unwanted polymorphs is a ubiquitous problem in zeolite synthesis. In this study, we propose a new platform for controlling polymorphism in organic-free Na-zeolite synthesis that enables crystal composition and properties to be tailored without sacrificing crystal phase purity. Through systematic adjustment of multiple synthesis parameters, we identified ternary (kinetic) phase diagrams at specific compositions (i.e., Si, Al, and NaOH mole fractions) using colloidal silica and sodium aluminate. Our studies identify multiple stages of zeolite phase transformations involving the framework types FAU, LTA, EMT, GIS, SOD, ANA, CAN, and JBW. We report an initial amorphous-to-crystalline transition of core-shell particles (silica core and alumina shell) to low-density framework types and their subsequent transformation to more dense structures with increasing temperature and/or time. We show that reduced water content facilitates the formation of structures such as EMT that are challenging to synthesize in organic-free media and reduces the synthesis temperature required to achieve higher-density framework types. A hypothesis is proposed for the sequence of phase transformations that is consistent with the Ostwald rule of stages, wherein metastable structures dissolve and recrystallize into more thermodynamically stable structures. The ternary diagrams developed here are a broadly applicable platform for rational design that offers an alternative to time- and cost-intensive methods of ad hoc parameter selection without a priori knowledge of crystal phase behavior.

BACKGROUND: Microbial lipids are produced by many oleaginous organisms including the well-characterized yeast Yarrowia lipolytica, which can be engineered for increased lipid yield by up-regulation of the lipid biosynthetic pathway and down-regulation or deletion of competing pathways. RESULTS: We describe a strain engineering strategy centered on diacylglycerol acyltransferase (DGA) gene overexpression that applied combinatorial screening of overexpression and deletion genetic targets to construct a high lipid producing yeast biocatalyst. The resulting strain, NS432, combines overexpression of a heterologous DGA1 enzyme from Rhodosporidium toruloides, a heterlogous DGA2 enzyme from Claviceps purpurea, and deletion of the native TGL3 lipase regulator. These three genetic modifications, selected for their effect on lipid production, enabled a 77 % lipid content and 0.21 g lipid per g glucose yield in batch fermentation. In fed-batch glucose fermentation NS432 produced 85 g/L lipid at a productivity of 0.73 g/L/h. CONCLUSIONS: The yields, productivities, and titers reported in this study may further support the applied goal of cost-effective, large -scale microbial lipid production for use as biofuels and biochemicals.

BACKGROUND: The main technological impediment to widespread utilization of lignocellulose for the production of fuels and chemicals is the lack of low-cost technologies to overcome its recalcitrance. Organisms that hydrolyze lignocellulose and produce a valuable product such as ethanol at a high rate and titer could significantly reduce the costs of biomass conversion technologies, and will allow separate conversion steps to be combined in a consolidated bioprocess (CBP). Development of Saccharomyces cerevisiae for CBP requires the high level secretion of cellulases, particularly cellobiohydrolases. RESULTS: We expressed various cellobiohydrolases to identify enzymes that were efficiently secreted by S. cerevisiae. For enhanced cellulose hydrolysis, we engineered bimodular derivatives of a well secreted enzyme that naturally lacks the carbohydrate-binding module, and constructed strains expressing combinations of cbh1 and cbh2 genes. Though there was significant variability in the enzyme levels produced, up to approximately 0.3 g/L CBH1 and approximately 1 g/L CBH2 could be produced in high cell density fermentations. Furthermore, we could show activation of the unfolded protein response as a result of cellobiohydrolase production. Finally, we report fermentation of microcrystalline cellulose (Avicel™) to ethanol by CBH-producing S. cerevisiae strains with the addition of beta-glucosidase. CONCLUSIONS: Gene or protein specific features and compatibility with the host are important for efficient cellobiohydrolase secretion in yeast. The present work demonstrated that production of both CBH1 and CBH2 could be improved to levels where the barrier to CBH sufficiency in the hydrolysis of cellulose was overcome.

Seismic inversion is a fundamental tool in geophysical analysis, providing a window into Earth. In particular, it enables the reconstruction of large-scale subsurface Earth models for hydrocarbon exploration, mining, earthquake analysis, shallow hazard assessment, and other geophysical tasks.

The imaging condition used in reverse‐time migration requires that the source wavefield (computed via a forward recursion) and the receiver wavefield (computed via a backwards recursion) must be made available at the same time in an implementation of the algorithm. Several strategies to organize the calculation can be employed, differing in balance between memory and computation. This paper describes and compares these different approaches, and argues that strategies favoring computational complexity over memory (to the point where disk i/o can be avoided) are attractive for 3D prestack migrations. An example of 3D reverse‐time migration applied to wide‐azimuth data from the Gulf of Mexico is presented to support the claim.

Abstract Side effects to antidepressant medications are common and can impact the prognosis of successful treatment outcome in people with major depressive disorder (MDD). However, few studies have investigated the severity of side effects over the course of treatment and their association with treatment outcome. Here we assessed the severity of side effects and the impact of treatment type and anxiety symptoms over the course of treatment, as well as whether side effects were associated with treatment outcome. Participants were N = 1008 adults with a current diagnosis of single-episode or recurrent, nonpsychotic MDD. Participants were randomised to receive escitalopram, sertraline, or venlafaxine-extended release with equal probability and reassessed at 8 weeks regarding Hamilton Rating Scale Depression (HRSD 17 ) and Quick Inventory of Depressive Symptomatology (QIDS-SR 16 ) remission and response. Severity of side effects were assessed using the Frequency, Intensity, and Burden of Side Effects Rating (FIBSER) scale and assessed at day 4 and weeks 2, 4, 6, and 8. Frequency, intensity, and burden of side effects were greatest at week 2, then only frequency and intensity of side effects gradually decreased up to week 6. Treatment type and anxiety symptoms did not impact the severity of side effects. A greater burden—but not frequency or intensity—of side effects was associated with poorer treatment outcome and as early as 4 days post-treatment. Together, this work provides an informative mapping of the progression of side effects throughout the treatment course and their association with treatment outcome. Importantly, the burden of side effects that are present as early as 4 days post-treatment predicts poorer treatment outcome and should be monitored closely. iSPOT-D: Registry name: ClinicalTrials.gov. Registration number: NCT00693849.

The electrochemical reduction of carbon dioxide (CO2RR) to chemical feedstocks, such as ethylene (C2H4), is an attractive means to mitigate emissions and store intermittent renewable electricity. Much research has focused on improving CO2 electrolysis cell efficiency; less attention has been paid to the downstream purification of outlet product streams. In this work, we model the use of mature downstream separation technologies as part of the overall production of polymer-grade C2H4 from CO2. We find that CO2 removal is the most energy-intensive downstream separation step. We identify opportunities to reduce separation energies to ∼22 GJ/tonne C2H4 through necessary improvements in C2H4 selectivity (>57%), cathodic CO2 conversion (>80%), and CO2 crossover (0 mol CO2/mol e–). This work highlights the influence of cell performance parameters on downstream separation costs and motivates the development of new, efficient separation processes better suited to the distinctive outlet streams of CO2 electrolyzers.

The optimal scheduling of crude-oil operations in refineries has been studied by various groups during the past decade leading to different mixed integer linear programming (MILP) or mixed integer nonlinear programming (MINLP) formulations. This paper presents a new continuous-time formulation, called single-operation sequencing (SOS) model, which can be used to solve a crude-oil operations problem introduced in previous publications. It is different from previous formulations as it requires to postulate the number of priority-slots in which operations take place, instead of specifying the number of time intervals or event points to be used in the schedule. This MINLP model is also based on the representation of a crude-oil schedule by a single sequence of transfer operations. It allows breaking symmetries involved in the problem, thus enormously reducing the computational times (all instances can be solved within 2 min). A simple two step MILP-NLP procedure has been used to solve the nonconvex MINLP model leading to an optimality gap lower than 4% in all cases.

Changing the reactor design paradigm for improved CO₂electrolyzers through advanced manufacturing.

Background The purpose of this study was to determine the effect of renal function on the elimination and disposition of mycophenolic acid and its glucuronide metabolite (MPAG) after oral administration of the pro-drug mycophenolate mofetil. In addition, this study sought to examine hemodialysis removal of mycophenolic acid and its MPAG. Methods Subjects were stratified into five groups on the basis of iohexol clearance. After an overnight fast, all subjects received a single 1 gm dose of mycophenolate mofetil. Plasma concentrations of mycophenolic acid and MPAG were measured from 0 to 96 hours after administration. Mycophenolic acid and MPAG maximum plasma concentration (Cmax) and the time to reach Cmax (tmax) for each group were determined from the mean plasma concentration-time profiles. Area under the plasma concentration-time curve values for mycophenolic acid and MPAG were calculated by the trapezoidal rule. The half-lives of mycophenolic acid and MPAG were calculated from the terminal portions of the concentration-time profiles. Results Mycophenolic acid clearance was not associated with changes in glomerular filtration rate (GFR). Cmax tended to increase as GFR declined. MPAG clearance correlated well with GFR (r2 = 0.905). Clearance of mycophenolic acid and MPAG were unaffected by hemodialysis. Conclusions Clearance of mycophenolic acid after a single 1 gm oral dose of mycophenolate mofetil is unaffected by renal function. Clearance of mycophenolic acid is unaffected by hemodialysis. Diminished renal function should not require preemptive adjustment of 1 gm doses of mycophenolate mofetil; however, dosage adjustment may be warranted on the basis of adverse effects or toxicity in individual patients. Mycophenolate mofetil can be administered irrespective of hemodialysis session without effect on mycophenolic acid exposure. Clinical Pharmacology & Therapeutics (1998) 63, 512–518; doi:

Regional structural styles on the continental slope are revealed by well-imaged deep multi-channel seismic profiles from northern Gulf of Mexico and Offshore Nigeria in Gulf of Guinea. Both provinces are situated on passive continental margins developed during the breakup of Gondwana. The northern Gulf of Mexico as well as Offshore Nigeria are underlain by complex systems of thin skinned upslope extensional fault systems, downslope contractional fold and thrust systems along with large scale salt or shale structures. The interactions between the deformation of mid-Jurassic salt and various stages and patterns of sedimentation on the continental slope are responsible for both extensional growth faults and Tertiary contractional fold and thrust systems in the northern Gulf of Mexico. The slope tectonics style of the northern Gulf of Mexico passive margin is characterized by perennial upslope extension since mid-Jurassic, associated with multi-stage autochthonous and allochthonous salt deformations along with brief periods of late Tertiary shortening in the down-dip fold belts. Offshore Nigeria is a salt-free progradational margin characterized by upslope extension, various shale structures and downslope toe-thrust systems. Gravity spreading and gliding in response to rapidly prograding Tertiary sedimentation over under-compacted shales resulted in the structural styles of the slope of Offshore Nigeria. Large upslope extensional tectonics are linked to coeval and balanced downslope contractional deformations in the form of shale ridges, massifs and diapirs, and deep basin toe thrusts. Late Miocene-Early Pliocene contractional deformation is widespread across the entire foldbelt, and with later shortening, folding migrated in a landward direction.

Limonene, a major component of citrus peel oil, has a number of applications related to microbiology. The antimicrobial properties of limonene make it a popular disinfectant and food preservative, while its potential as a biofuel component has made it the target of renewable production efforts through microbial metabolic engineering. For both applications, an understanding of microbial sensitivity or tolerance to limonene is crucial, but the mechanism of limonene toxicity remains enigmatic. In this study, we characterized a limonene-tolerant strain of Escherichia coli and found a mutation in ahpC, encoding alkyl hydroperoxidase, which alleviated limonene toxicity. We show that the acute toxicity previously attributed to limonene is largely due to the common oxidation product limonene hydroperoxide, which forms spontaneously in aerobic environments. The mutant AhpC protein with an L-to-Q change at position 177 (AhpC(L177Q)) was able to alleviate this toxicity by reducing the hydroperoxide to a more benign compound. We show that the degree of limonene toxicity is a function of its oxidation level and that nonoxidized limonene has relatively little toxicity to wild-type E. coli cells. Our results have implications for both the renewable production of limonene and the applications of limonene as an antimicrobial.

Reinforcement Learning (RL) algorithms have had tremendous success in simulated domains. These algorithms, however, often cannot be directly applied to physical systems, especially in cases where there are constraints to satisfy (e.g. to ensure safety or limit resource consumption). In standard RL, the agent is incentivized to explore any policy with the sole goal of maximizing reward; in the real world, however, ensuring satisfaction of certain constraints in the process is also necessary and essential. In this article, we overview existing approaches addressing constraints in model-free reinforcement learning. We model the problem of learning with constraints as a Constrained Markov Decision Process and consider two main types of constraints: cumulative and instantaneous. We summarize existing approaches and discuss their pros and cons. To evaluate policy performance under constraints, we introduce a set of standard benchmarks and metrics. We also summarize limitations of current methods and present open questions for future research.

Polyolefins including linear low density polyethylene (LLDPE), high density polyethylene (HDPE), and isotactic polypropylene (iPP) account for nearly 2/3 of the worldwide plastics market. With wide-ranging applications, often short term in nature such as packaging, recycling of polyolefins is becoming increasingly important in developing a sustainable worldwide plastics market. However, it is difficult to separate polyolefins in mixed recycle streams; it would be advantageous to melt blend them, but their immiscibility leads to blends with poor properties. Here we demonstrate the role of synthetic history (i.e., site specific metallocene vs heterogeneous Ziegler–Natta catalyzed) on the oligomer content of HDPE, LLDPE, and iPP and its influence on adhesion between PE and iPP. Using a range of polymers and processing conditions, we identify four classes of such interfaces with a wide range of interfacial adhesion strengths (GIC): excess oligomer (GIC < 30 N/m), easy chain pullout (GIC ≅ 100 N/m), kinetically trapped entanglements (GIC ≅ 600 N/m), and crystallization across the interface (GIC > 1200 N/m). Using molecular weight distribution data, we identified a critical oligomer content where the interfacial failure mechanism transitions from cohesive failure (GIC > 1200 N/m) to adhesive failure (GIC ≅ 100 N/m). Transmission electron microscopy (TEM) and atomic force microscopy (AFM) highlight distinct interfacial semicrystalline morphologies for each class of polyolefin interface which are defined by molecular parameters and processing conditions. Polyolefin blends were compression molded to highlight the role of interfacial strength in blends formed from mixed polyolefin streams; weak interfaces resulting from excess oligomer buildup yielded brittle failure while superior interfacial adhesion resulted in ductile blend failure.

Gene targeting is a challenge in organisms where non-homologous end-joining is the predominant form of recombination. We show that cell division cycle synchronization can be applied to significantly increase the rate of homologous recombination during transformation. Using hydroxyurea-mediated cell cycle arrest, we obtained improved gene targeting rates in Yarrowia lipolytica, Arxula adeninivorans, Saccharomyces cerevisiae, Kluyveromyces lactis and Pichia pastoris demonstrating the broad applicability of the method. Hydroxyurea treatment enriches for S-phase cells that are active in homologous recombination and enables previously unattainable genomic modifications.

The long-term success rate of cemented sockets in total hip arthroplasty has been well documented in patients who are 60 years of age and older and who have had a followup of as many as 16 years. The failures with cemented sockets have been observed in young patients, patients with poor bone stock (rheumatoid and dysplastic hips) with metal backed components, and in revision surgery with loss of acetabular bone. Ranawat et al have shown that most mechanical failures of cemented socket fixation within 10 years of primary operation is attributable to failure to achieve a good fixation initially of the cement and bone. Volumetric wear of the polyethylene of a cemented socket against a 22- or 28-mm femoral head is compared with the metal backed cemented and noncemented cups. The increase in volumetric polyethylene particles with metal backed cemented sockets and noncemented sockets will induce histiocytic response. The mechanism of histiocytic invasion should be similar for cemented all polyethylene sockets and noncemented sockets. It manifests itself in the cemented socket as global radiolucency when the socket is loose and as osteolysis when it is well fixed for noncemented and cemented sockets. If the number of particles coming out in a noncemented and hybrid total hip replacement are greater, osteolysis would be expected to increase with longer followup. The technique of cemented polyethylene sockets requires organization of the surgical team and hypotensive epidural anesthesia. Under these conditions the procedure is very reproducible. As far as cost is concerned, the all polyethylene socket is significantly less expensive. It seems that cemented total hip replacement is most suitable and perhaps is the right kind of operation for treating osteoarthritis of the hip for patients who are 60 years of age and older because the procedure is reproducible, the quality of arthroplasty is excellent, and it is durable, lasting as many as 15 years in 90% to 95% of the cases.

Carbon dioxide (CO2) electrolysis powered with renewable electricity can help close the carbon cycle by converting emissions into chemicals and fuels. Two key advancements are required to bridge the technological gaps for industrial implementation: pilot plant demonstrations with detailed performance data; and chemical engineering process models built and tested with lab- and pilot-scale data. Here, we develop a semi-empirical electrolyzer model in Aspen Custom Modeler which is trained on a 5 cm2 lab-scale CO2 electrolyzer. We then scale to a pilot-scale 800 cm2 single cell and 10 × 800 cm2 stack and use the results to validate the model; at 100 mA cm–2, the model can predict six of seven cell performance metrics within 16% absolute error and three of five stack metrics within 11% absolute error. With the combination of the electrolyzer model and the pilot-scale data, this work provides the prerequisites for further scaling of CO2 electrolysis.

Full-waveform inversion (FWI) is a powerful method for estimating the earth’s material properties. We demonstrate that surface-wave-driven FWI is well-suited to recovering near-surface structures and effective at providing S-wave speed starting models for use in conventional body-wave FWI. Using a synthetic example based on the SEG Advanced Modeling phase II foothills model, we started with an envelope-based objective function to invert for shallow large-scale heterogeneities. Then we used a waveform-difference objective function to obtain a higher-resolution model. To accurately model surface waves in the presence of complex tomography, we used a spectral-element wave-propagation solver. Envelope misfit functions are found to be effective at minimizing cycle-skipping issues in surface-wave inversions, and surface waves themselves are found to be useful for constraining complex near-surface features.