COVID-19 Models for Hospital Surge Capacity Planning: A Systematic Review

Objective: Health system preparedness for coronavirus disease (COVID-19) includes projecting the number and timing of cases requiring various types of treatment. Several tools were developed to assist in this planning process. This review highlights models that project both caseload and hospital capacity requirements over time. Methods: We systematically reviewed the medical and engineering literature according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We completed searches using PubMed, EMBASE, ISI Web of Science, Google Scholar, and the Google search engine. Results: The search strategy identified 690 articles. For a detailed review, we selected 6 models that met our predefined criteria. Half of the models did not include age-stratified parameters, and only 1 included the option to represent a second wave. Hospital patient flow was simplified in all models; however, some considered more complex patient pathways. One model included fatality ratios with length of stay (LOS) adjustments for survivors versus those who die, and accommodated different LOS for critical care patients with or without a ventilator. Conclusion: The results of our study provide information to physicians, hospital administrators, emergency response personnel, and governmental agencies on available models for preparing scenario-based plans for responding to the COVID-19 or similar type of outbreak

Gamma and pulsed electron radiolysis studies of CyMe4BTBP and CyMe4BTPhen: Identification of radiolysis products and effects on the hydrometallurgical separation of trivalent actinides and lanthanides

The radiolytic stability of the highly selective ligands CyMe4BTBP and CyMe4BTPhen against ionizing gamma radiation was studied in 1-octanol solution. CyMe4BTBP and CyMe4BTPhen are important extractants for a potential treatment of used nuclear fuel. They were studied under identical experimental conditions to directly compare the effects of gamma and pulsed electron radiolysis on the ligands and systematically study the influence of structural changes in the ligand backbone. Distribution ratios of Am3+, Cm3+ and Eu3+, the residual concentration of CyMe4BTBP and CyMe4BTPhen in solution, and the formation of radiolysis products were studied as a function of absorbed gamma dose and presence of an acidic aqueous phase during irradiation. Quantitative and semi-quantitative analyses were used to elucidate the radiolysis mechanism for both ligands. Addition products of alpha-hydroxyoctyl radicals formed through radiolysis of the 1-octanol diluent to the ligand molecules were identified as the predominant radiolysis products. These addition products also extract trivalent metal ions, as distribution ratios remained high although the parent molecule concentrations decreased. Therefore, the utilization time of a solvent using these extractants under the harsh conditions of used nuclear fuel treatment could be considerably longer than expected. Understanding the radiolysis mechanism is crucial for designing more radiation resistant extractants

Measurement of Superluminal optical tunneling times in double-barrier photonic bandgaps

Tunneling of optical pulses at 1.5 micron wavelength through double-barrier periodic fiber Bragg gratings is experimentally investigated. Tunneling time measurements as a function of barrier distance show that, far from the resonances of the structure, the transit time is paradoxically short, implying Superluminal propagation, and almost independent of the distance between the barriers. These results are in agreement with theoretical predictions based on phase time analysis and also provide an experimental evidence, in the optical context, of the analogous phenomenon expected in Quantum Mechanics for non-resonant superluminal tunneling of particles across two successive potential barriers. [Attention is called, in particular, to our last Figure]. PACS nos.: 42.50.Wm, 03.65.Xp, 42.70.Qs, 03.50.De, 03.65.-w, 73.40.GkComment: LaTeX file (8 pages), plus 5 figure

Solvent Optimization Studies for a New EURO-GANEX Process with 2,2’-Oxybis( N,N -di- n -decylpropanamide) (mTDDGA) and Its Radiolysis Products

The diglycolamide 2,2’-oxybis(N,N-di-n-decylpropanamide) (mTDDGA) is being studied as an extractant for actinides and lanthanides in the European Grouped Actinide Extraction (EURO-GANEX) process. The aim is the development of a more simplified process using a single extractant instead of a mixture of extractants used in the current EURO-GANEX process. This work presents solvent optimization studies of mTDDGA, with regards to the extraction characteristics of the different diastereomers of mTDGA and of mixed diastereomer solutions. Also radiolysis behavior has been studied by irradiation of solvent extraction systems in a gamma irradiation facility using $^{60}$Co. The availability of irradiated organic solutions made it possible to gain valuable insights into the plutonium loading capacity after gamma-irradiation of the solvent up to 445 kGy and to quantify degradation compounds. Solvent extraction characteristic of the major degradation compounds themselves were determined. Like other methylated diglycolamides, we found a remarkable difference in extraction of up to two orders of magnitude between the two diastereomers. High plutonium loading (36 g L$^{−1}$) is feasible using this single extractant, even after absorbing a dose of 445 kGy. This remarkable observation is possibly promoted by the presence of the main degradation compound which extracts plutonium verywell

Modular Microsystem for the Isolation, Enumeration, and Phenotyping of Circulating Tumor Cells in Patients with Pancreatic Cancer

In this manuscript, we discuss the development and clinical use of a thermoplastic modular microsystem for the high-throughput analysis of CTCs directly from whole blood. The modular system offers some innovative features that address challenges currently associated with many CTC platforms; it can exhaustively process 7.5 ml of blood in less than 45 min with recoveries >90%. In addition, the system automates the post-selection CTC processing steps and thus, significantly reduces assay turnaround time (from selection to enumeration 8 h for many reported CTC platforms). The system is comprised of 3 functional modules including; (i) a thermoplastic CTC selection module composed of high aspect ratio (30 μm × 150 μm) channels containing anti-EpCAM antibodies that is scalable in terms of throughput by employing channel numbers ranging from 50 to 320 – the channel number is user selected to accommodate the volume of blood that must be processed; (ii) an impedance sensor module for label-less CTC counting; and (iii) a staining and imaging module for the placement of released cells into a 2D array within a common imaging plane for phenotypic identification. To demonstrate the utility of this system, blood samples from patients with local resectable and metastatic pancreatic ductal adenocarcinoma (PDAC) were analyzed. We demonstrate the ability to select EpCAM positive CTCs from PDAC patients in high purity (>86%) and with excellent yields (mean = 53 CTCs per ml for metastatic PDAC patients) using our modular system. In addition, we demonstrate the ability to detect CTCs in PDAC patients with local resectable disease (mean = 11 CTCs per ml)

Changes in SARS-CoV-2 viral load and mortality during the initial wave of the pandemic in New York City

Funding: This work was partially supported by the National Center for Advancing Translational Sciences of the National Institutes of Health (UL1 TR0023484 to Julianne Imperato-McGinley) and the National Institute of Allergy and Infectious Diseases (UM1 AI069470 to M.E.S).Public health interventions such as social distancing and mask wearing decrease the incidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, but it is unclear whether they decrease the viral load of infected patients and whether changes in viral load impact mortality from coronavirus disease 2019 (COVID-19). We evaluated 6923 patients with COVID-19 at six New York City hospitals from March 15-May 14, 2020, corresponding with the implementation of public health interventions in March. We assessed changes in cycle threshold (CT) values from reverse transcription-polymerase chain reaction tests and in-hospital mortality and modeled the impact of viral load on mortality. Mean CT values increased between March and May, with the proportion of patients with high viral load decreasing from 47.7% to 7.8%. In-hospital mortality increased from 14.9% in March to 28.4% in early April, and then decreased to 8.7% by May. Patients with high viral loads had increased mortality compared to those with low viral loads (adjusted odds ratio 2.34). If viral load had not declined, an estimated 69 additional deaths would have occurred (5.8% higher mortality). SARS-CoV-2 viral load steadily declined among hospitalized patients in the setting of public health interventions, and this correlated with decreases in mortality.Peer reviewe

Hot embossing for fabrication of a microfluidic 3D cell culture

Clinically relevant studies of cell function in vitro require a physiologically-representative microenvironment possessing aspects such as a 3D extracellular matrix (ECM) and controlled biochemical and biophysical parameters. A polydimethylsiloxane (PDMS) microfluidic system with a 3D collagen gel has previously served for analysis of factors inducing different responses of cells in a 3D microenvironment under controlled biochemical and biophysical parameters. In the present study, applying the known commercially-viable manufacturing methods to a cyclic olefin copolymer (COC) material resulted in a microfluidic device with enhanced 3D gel capabilities, controlled surface properties, and improved potential to serve high-volume applications. Hot embossing and roller lamination molded and sealed the microfluidic device. A combination of oxygen plasma and thermal treatments enhanced the sealing, ensured proper placement of the 3D gel, and created controlled and stable surface properties within the device. Culture of cells in the new device indicated no adverse effects of the COC material or processing as compared to previous PDMS devices. The results demonstrate a methodology to transition microfludic devices for 3D cell culture from scientific research to high-volume applications with broad clinical impact.National Cancer Institute (U.S.) (award R21CA140096)Charles Stark Draper Laboratory (IR&D Grant

UV activation of polymeric high aspect ratio microstructures: Ramifications in antibody surface loading for circulating tumor cell selection

The need to activate thermoplastic surfaces using robust and efficient methods has been driven by the fact that replication techniques can be used to produce microfluidic devices in a high production mode and at low cost, making polymer microfluidics invaluable for in vitro diagnostics, such as circulating tumor cell (CTC) analysis, where device disposability is critical to mitigate artifacts associated with sample carryover. Modifying the surface chemistry of thermoplastic devices through activation techniques can be used to increase the wettability of the surface or to produce functional scaffolds to allow for the covalent attachment of biologics, such as antibodies for CTC recognition. Extensive surface characterization tools were used to investigate UV activation of various surfaces to produce uniform and high surface coverage of functional groups, such as carboxylic acids in microchannels of different aspect ratios. We found that the efficiency of the UV activation process is highly dependent on the microchannel aspect ratio and the identity of the thermoplastic substrate. Colorimetric assays and fluorescence imaging of UV-activated microchannels following EDC/NHS coupling of Cy3-labeled oligonucleotides indicated that UV-activation of a PMMA microchannel with an aspect ratio of ???3 was significantly less efficient toward the bottom of the channel compared to the upper sections. This effect was a consequence of the bulk polymer's damping of the modifying UV radiation due to absorption artifacts. In contrast, this effect was less pronounced for COC. Moreover, we observed that after thermal fusion bonding of the device's cover plate to the substrate, many of the generated functional groups buried into the bulk rendering them inaccessible. The propensity of this surface reorganization was found to be higher for PMMA compared to COC. As an example of the effects of material and microchannel aspect ratios on device functionality, thermoplastic devices for the selection of CTCs from whole blood were evaluated, which required the immobilization of monoclonal antibodies to channel walls. From our results, we concluded the CTC yield and purity of isolated CTCs were dependent on the substrate material with COC producing the highest clinical yields for CTCs as well as better purities compared to PMMA.close9

Induction of aromatic ring: cleavage dioxygenases in Stenotrophomonas maltophilia strain KB2 in cometabolic systems

Stenotrophomonas maltophilia KB2 is known to produce different enzymes of dioxygenase family. The aim of our studies was to determine activity of these enzymes after induction by benzoic acids in cometabolic systems with nitrophenols. We have shown that under cometabolic conditions KB2 strain degraded 0.25–0.4 mM of nitrophenols after 14 days of incubation. Simultaneously degradation of 3 mM of growth substrate during 1–3 days was observed depending on substrate as well as cometabolite used. From cometabolic systems with nitrophenols as cometabolites and 3,4-dihydroxybenzoate as a growth substrate, dioxygenases with the highest activity of protocatechuate 3,4-dioxygenase were isolated. Activity of catechol 1,2- dioxygenase and protocatechuate 4,5-dioxygenase was not observed. Catechol 2,3-dioxygenase was active only in cultures with 4-nitrophenol. Ability of KB2 strain to induce and synthesize various dioxygenases depending on substrate present in medium makes this strain useful in bioremediation of sites contaminated with different aromatic compounds