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At least 55 records · Page 3

Madidrop for Passive Silver Dosing

Madidrop is a rectangular ceramic tablet originally designed to dose a 10-20-liter volume of water with silver to act as a biocide for remote communities with unreliable water sources. Silver as a biocide is a proposed method to control bacteria on the International Space Station or future Artemis missions. This would replace iodine currently used due to issues with a dual biocide system in place between Russian and US segments and the extra cost of iodine removal required before consumption. NASA has been reviewing this Madidrop technology and its potential application with a water reclamation system on orbit to dose silver after purifying the water. While there are a couple alternative methods to dosing silver on station, this method is like the existing passive dosing method used currently to dose iodine. Tests conducted characterize the manufacturer’s original intent to leave the tablet in a tank for a specified amount of time before removing and testing alternative passive flow-through methods. Passive flow testing involved two options: keeping the tablet intact or crushing the tablet into smaller particle sizes to increase the surface area while varying particle sizes. The results of these tests revealed a large amount of silver output at first that quickly reduced to a constant lower output within a reasonable dosing concentration range. The initial high concentration peaks after a couple days of quiescence and could be useful for shocking the initial tank water contents. Madidrop used as a passive particle doser could act as a stand-in replacement for iodine in future spaceflight water reclamation systems.

Ryan Ogilvie↗

Feasibility of Patient Reporting of Symptomatic Adverse Events via the Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) in a Chemoradiotherapy Cooperative Group Multicenter Clinical Trial

Purpose: To assess the feasibility of measuring symptomatic adverse events (AEs) in a multicenter clinical trial using the National Cancer Institute's Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE). Methods and Materials: Patients enrolled in NRG Oncology's RTOG 1012 (Prophylactic Manuka Honey for Reduction of Chemoradiation Induced Esophagitis-Related Pain during Treatment of Lung Cancer) were asked to self-report 53 PRO-CTCAE items representing 30 symptomatic AEs at 6 time points (baseline; weekly ×4 during treatment; 12 weeks after treatment). Reporting was conducted via wireless tablet computers in clinic waiting areas. Compliance was defined as the proportion of visits when an expected PRO-CTCAE assessment was completed. Results: Among 226 study sites participating in RTOG 1012, 100% completed 35-minute PRO-CTCAE training for clinical research associates (CRAs); 80 sites enrolled patients, of which 34 (43%) required tablet computers to be provided. All 152 patients in RTOG 1012 agreed to self-report using the PRO-CTCAE (median age 66 years; 47% female; 84% white). Median time for CRAs to learn the system was 60 minutes (range, 30-240 minutes), and median time for CRAs to teach a patient to self-report was 10 minutes (range, 2-60 minutes). Compliance was high, particularly during active treatment, when patients self-reported at 86% of expected time points, although compliance was lower after treatment (72%). Common reasons for noncompliance were institutional errors, such as forgetting to provide computers to participants; patients missing clinic visits; Internet connectivity; and patients feeling “too sick.” Conclusions: Most patients enrolled in a multicenter chemoradiotherapy trial were willing and able to self-report symptomatic AEs at visits using tablet computers. Minimal effort was required by local site staff to support this system. The observed causes of missing data may be obviated by allowing patients to self-report electronically between visits, and by using central compliance monitoring. These approaches are being incorporated into ongoing studies.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Auxiliary glow discharge in the trigger unit of a hollow-cathode thyratron

Results from studies of a low-current glow discharge with a hollow cathode are presented. A specific feature of the discharge conditions was that a highly emissive tablet containing cesium carbonate was placed in the cathode cavity. In the absence of a tablet, the discharge ignition voltage was typically ≥3.5 kV, while the burning voltage was in the range of 500–600 V. The use of the tablet made it possible to decrease the ignition voltage to 280 V and maintain the discharge burning voltage at a level of about 130 V. A model of the current sustainment in a hollow-cathode discharge is proposed. Instead of the conventional secondary emission yield, the model uses a generalized emission yield that takes into account not only ion bombardment of the cathode, but also the emission current from an external source. The model is used to interpret the observed current−voltage characteristics. The results of calculations agree well with the experimental data. It is shown that, in some discharge modes, the external emission current from the cathode can reach 25% of the total discharge current.

70 PLASMA PHYSICS AND FUSION TECHNOLOGY↗

Origination and Transformation of the Monoclinic and Orthorhombic Phases in Reactor Powders of Ultrahigh Molecular Weight Polyethylene

Using powerful synchrotron X-ray radiation of the beamline “Belok” operated by the National Research Center “Kurchatov Institute,” we perform X-ray diffraction (XRD) study of an intact, virgin (not subjected to any external mechanical loads) particle isolated from reactor powder of ultrahigh molecular weight polyethylene. Along with the peaks originating from the orthorhombic phase, we detect the peaks characteristic of the monoclinic phase that is stable only under mechanical stress, suggesting that the mechanical stress that leads to the formation of the monoclinic phase and persists at room temperature develops during the polymer synthesis. The monoclinic phase gradually disappears when the particle is heated stepwise in increments of 5 K, and its peaks become undetectable when the temperature reaches 340 K. We contrast the results obtained for the phase composition of the virgin particle to those for a tablet prepared by compaction of the same reactor powder at room temperature. XRD analyses of the tablet were performed on D2 Phaser (Bruker) instrument. The monoclinic phase that originates during the polymer synthesis and the one that forms in the tablet during compaction have different parameters. We discuss the mechanisms by which these two different monoclinic phases originate during the processes involved.

75 CONDENSED MATTER PHYSICS, SUPERCONDUCTIVITY AND↗

Cardiovascular deconditioning during space flight and the use of saline as a countermeasure to orthostatic intolerance

Results are reported of trials with oral hydration by astronauts before reentry of the Orbiter. The experiments were run to evaluate hydration as a means of offsetting the loss of lower body negative pressure experienced after several days in space. The rehydration was carried out by 17 astronauts who ingested salt tablets and water prior to the end of the first eight STS mission orbital phases; nine astronauts abstained. Pulse and blood pressure data were collected from 1-2 hr post landing. Measurements were also made of the extent of cardiac deconditioning and the response to orthostatic stress (standing). Ingestion of the salt tablets reduced the heart rate response to stress an average of 29 percent. The statistical significance of the difference has encouraged adoption of the salt tablet countermeasure as an operational procedure by Shuttle astronauts.

Bungo, M. W.↗

Refinement of ground reference data with segmented image data

One of the ways to determine ground reference data (GRD) for satellite remote sensing data is to photo-interpret low altitude aerial photographs and then digitize the cover types on a digitized tablet and register them to 7.5 minute U.S.G.S. maps (that were themselves digitized). The resulting GRD can be registered to the satellite image or, vice versa. Unfortunately, there are many opportunities for error when using digitizing tablet and the resolution of the edges for the GRD depends on the spacing of the points selected on the digitizing tablet. One of the consequences of this is that when overlaid on the image, errors and missed detail in the GRD become evident. An approach is discussed for correcting these errors and adding detail to the GRD through the use of a highly interactive, visually oriented process. This process involves the use of overlaid visual displays of the satellite image data, the GRD, and a segmentation of the satellite image data. Several prototype programs were implemented which provide means of taking a segmented image and using the edges from the reference data to mask out these segment edges that are beyond a certain distance from the reference data edges. Then using the reference data edges as a guide, those segment edges that remain and that are judged not to be image versions of the reference edges are manually marked and removed. The prototype programs that were developed and the algorithmic refinements that facilitate execution of this task are described.

Robinson, Jon W.↗

Challenges in Transitioning Cocrystals from Bench to Bedside: Dissociation in Prototype Drug Product Environment

We report ablets containing a theophylline–glutaric acid (TG) cocrystal dissociated rapidly forming crystalline theophylline (20–30%), following storage at 40 °C/75% RH for 2 weeks. Control tablets of TG cocrystal containing no excipients were stable under the same conditions. The dissociation reaction was water-mediated, and the theophylline concentration (the dissociation product), monitored by synchrotron X-ray diffractometry, was strongly influenced by the formulation composition. Investigation of the binary compacts of the TG cocrystal with each excipient revealed the influence of excipient properties (hydrophilicity, ionizability) on cocrystal stability, providing mechanistic insights into a dissociation reaction. Ionizable excipients with a strong tendency to sorb water, for example, sodium starch glycolate and croscarmellose sodium, caused pronounced dissociation. Microcrystalline cellulose (MCC), while a neutral but hydrophilic excipient, also enabled solution-mediated cocrystal dissociation in intact tablets. Magnesium stearate, an ionizable but hydrophobic excipient, interacted with the cocrystal to form a hygroscopic product. The interaction is believed to be initiated in the disordered cocrystal–excipient particle interface. In contrast, the cocrystal was stable in the presence of lactose, a neutral excipient with no tendency to sorb water. The risk of unintended cocrystal dissociation can be mitigated by avoiding contact with water both during processing and storage.

60 APPLIED LIFE SCIENCES↗

Integration of Biorelevant Pediatric Dissolution Methodology into PBPK Modeling to Predict In Vivo Performance and Bioequivalence of Generic Drugs in Pediatric Populations: a Carbamazepine Case Study

This study investigated the impact of gastro-intestinal fluid volume and bile salt (BS) concentration on the dissolution of carbamazepine (CBZ) immediate release (IR) 100 mg tablets and to integrate these in vitro biorelevant dissolution profiles into physiologically based pharmacokinetic modelling (PBPK) in pediatric and adult populations to determine the biopredictive dissolution profile. Dissolution profiles of CBZ IR tablets (100 mg) were generated in 50–900 mL biorelevant adult fasted state simulated gastric and intestinal fluid (Ad-FaSSGF and Ad-FaSSIF), also in three alternative compositions of biorelevant pediatric FaSSGF and FaSSIF medias at 200 mL. This study found that CBZ dissolution was poorly sensitive to changes in the composition of the biorelevant media, where dissimilar dissolution (F2 = 46.2) was only observed when the BS concentration was changed from 3000 to 89 μM (Ad-FaSSIF vs Ped-FaSSIF 50% 14 BS). PBPK modeling demonstrated the most predictive dissolution volume and media composition to forecast the PK was 500 mL of Ad-FaSSGF/Ad-FaSSIF media for adults and 200 mL Ped-FaSSGF/FaSSIF media for pediatrics. A virtual bioequivalence simulation was conducted by using Ad-FaSSGF and/or Ad-FaSSIF 500 mL or Ped-FaSSGF and/or Ped-FaSSIF 200 mL dissolution data for CBZ 100 mg (reference and generic test) IR product. The CBZ PBPK models showed bioequivalence of the product. This study demonstrates that the integration of biorelevant dissolution data can predict the PK profile of a poorly soluble drug in both populations. Further work using more pediatric drug products is needed to verify biorelevant dissolution data to predict the in vivo performance in pediatrics.

60 APPLIED LIFE SCIENCES↗

Enabling Real-Time Volume Rendering of Functional Magnetic Resonance Imaging on an iOS Device

Powerful non-invasive imaging technologies like computed tomography (CT), ultrasound, and magnetic resonance imaging (MRI) are used daily by medical professionals to diagnose and treat patients. While 2D slice viewers have long been the standard, many tools allowing 3D representations of digital medical data are now available. The newest imaging advancement, functional MRI (fMRI) technology, has changed medical imaging from viewing static to dynamic physiology (4D) over time, particularly to study brain activity. Add this to the rapid adoption of mobile devices for everyday work and the need to visualize fMRI data on tablets or smartphones arises. However, there are few mobile tools available to visualize 3D MRI data, let alone 4D fMRI data. Building volume rendering tools on mobile devices to visualize 3D and 4D medical data is challenging given the limited computational power of the devices. This paper describes research that explored the feasibility of performing real-time 3D and 4D volume raycasting on a tablet device. The prototype application was tested on a 9.7” iPad Pro using two different fMRI datasets of brain activity. The results show that mobile raycasting is able to achieve between 20 and 40 frames per second for traditional 3D datasets, depending on the sampling interval, and up to 9 frames per second for 4D data. While the prototype application did not always achieve true real-time interaction, these results clearly demonstrated that visualizing 3D and 4D digital medical data is feasible with a properly constructed software framework.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Quantitative Analysis of Drugs with Highly Different Concentrations of Pharmaceutical Components Using Spectral Subtraction Techniques

Two simple spectrophotometric methods were developed for determination of empagliflozin and metformin by manipulating their ratio spectra with application on a recently approved pharmaceutical combination, Synjardy® tablets. A spiking technique was used to increase the concentration of empagliflozin after extraction from the tablets to allow its simultaneous determination with metformin. Validation parameters according to ICH guidelines were acceptable over the concentration range of 2–12 μg/mL for both drugs using constant multiplication and spectrum subtraction methods. The optimized methods are suitable for QC labs.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

Citrus bioflavonoids dipeptidyl peptidase-4 inhibition compared with gliptin antidiabetic medications

Highlights: • The citrus bioflavonoids may possess dipeptidyl peptidase-4 (DPP-4) inhibition activity similar to gliptins. • Various citrus bioflavonoids may have a variable DPP-4 inhibition activity. • The measurement of the DPP-4 inhibition activity can be done using DPP-4 inhibition kit. • Commercial citrus bioflavonoid supplements contain various citrus bioflavonoids with different DPP-4 inhibition activities. This study compared dipeptidyl peptidase-4 (DPP-4) inhibitory activity of citrus bioflavonoid nutraceuticals compared with three gliptins. Citrus bioflavonoid standards and three commercially available citrus bioflavonoid supplements (Thompson's Super Bioflavonoid Complex{sup ®}(SB), Ethical Nutrients Bioflavonoids Plus Vitamin C{sup ®}(EN), and Country Life Citrus Bioflavonoids and Rutin{sup ®}(CB)) were considered in this study. Ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) analysis was undertaken to identify and quantitate the citrus bioflavonoids present in each supplement. The DPP-4 inhibitory activity was determined by fluorometric assay. All of the tested individual citrus flavonoids demonstrated DPP-4 inhibitory activity, with IC{sub 50} values ranging from 485 μM (rutin) to 5700 μM (hesperitin and eriodictyol). Similarly, the flavonoid supplements had IC{sub 50} values of 16.9 mg/mL (EN), 3.44 mg/mL (SB) and 2.72 mg/mL (CB). These values compare with gliptin IC{sub 50} values of 0.684 μM (sitagliptin), 0.707 μM (saxagliptin) and 2.286 μM (vildagliptin). The supplement flavonoid content varied from 11.98% (CB) to 5.26% (EN) and 14.51% (SB) of tablet mass, corresponding to daily flavonoid doses of around 300, 150 and 400 mg, respectively, with CB and SB containing rutin at levels of 7.0% and 7.5% of tablet mass, respectively. While our data demonstrated that citrus bioflavonoid based supplements do possess DPP-4 inhibitory activity, they are several orders of magnitude less potent than gliptins. Further studies using higher concentrations of citrus bioflavonoids, as well as investigations into antioxidant properties which may add additional benefit are warranted.

60 APPLIED LIFE SCIENCES↗

The effect of food vehicles on in vitro performance of pantoprazole sodium delayed release sprinkle formulation

Certain patient populations, including children, the elderly or people with dysphagia, find swallowing whole medications such as tablets and capsules difficult. To facilitate oral administration of drugs in such patients, a common practice is to sprinkle the drug products (e.g., usually after crushing the tablet or opening the capsule) on food vehicles before consumption which improves swallowability. Thus, evaluation of the impact of food vehicles on the potency and stability of the administered drug product is important. Here, the aim of the current study was to evaluate the physicochemical properties (viscosity, pH, and water content) of common food vehicles used for sprinkle administration (e.g., apple juice, applesauce, pudding, yogurt, and milk) and their impacts on the in vitro performance (i.e., dissolution) of pantoprazole sodium delayed release (DR) drug products. The food vehicles evaluated exhibited marked difference in viscosity, pH and water content. Notably, the pH of the food as well as the interaction between food vehicle pH and drug-food contact time were the most significant factors affecting the in vitro performance of pantoprazole sodium DR granules. For example, the dissolution of pantoprazole sodium DR granules sprinkled on food vehicles of low pH (e.g., apple juice or applesauce) for short durations remained unchanged compared with the control group (i.e., without mixing with food vehicles). However, use of high pH food vehicles (e.g., milk) with prolonged contact time (e.g., 2h) resulted in accelerated pantoprazole release, drug degradation and loss of potency. Overall, a thorough assessment of physicochemical properties of food vehicles and formulation characteristics are a necessary part of the development of sprinkle formulations.

60 APPLIED LIFE SCIENCES↗

Hyperspectral interference tomography of nacre

Significance We invented an optical technique—hyperspectral interference tomography—that rapidly and nondestructively extracts nanoscale structural information across large samples of nacre (mother-of-pearl) and other layered materials by combining multiangle and polarization-resolved hyperspectral imaging with optical-interference modeling. We investigated nacre in mollusk shells from two different species, red abalone and rainbow abalone, and discovered a previously unknown relationship between the age of the mollusk and the thickness of aragonite tablets in nacre. Hyperspectral interference tomography will have applications in climate science, since nacre tablet thickness in fossil shells is a proxy for ancient seawater temperature, and in bioinspired mechanics, because the layered structure of nacre inspires engineered materials with exceptional strength and toughness.

47 OTHER INSTRUMENTATION↗

Evaluation of large volume yeast interfering RNA lure-and-kill ovitraps for attraction and control of Aedes mosquitoes

Aedes mosquitoes (Diptera: Culicidae), principle vectors of several arboviruses, typically lay eggs in man-made water-filled containers located near human dwellings. Given the widespread emergence of insecticide resistance, stable and biofriendly alternatives for mosquito larviciding are needed. Laboratory studies have demonstrated that inactivated yeast interfering RNA tablets targeting key larval developmental genes can be used to facilitate effective larvicidal activity while also promoting selective gravid female oviposition behaviour. In this work, we examined the efficacy of transferring this technology toward development of lure-and-kill ovitraps targeting Aedes aegypti (L.) and Aedes albopictus (Skuse) female mosquitoes. Insectary, simulated field and semi-field experiments demonstrated that two mosquito-specific yeast interfering RNA pesticides induce high levels of mortality among larvae of both species in treated large volume containers. Small-scale field trials conducted in Trinidad, West Indies demonstrated that large volume ovitrap containers baited with inactivated yeast tablets lure significantly more gravid females than traps containing only water and were highly attractive to both A. aegypti and A. albopictus females. Finally, these studies indicate that development of biorational yeast interfering RNA-baited ovitraps may represent a new tool for control of Aedes mosquitoes, including deployment in existing lure-and-kill ovitrap technologies or traditional container larviciding programs.

59 BASIC BIOLOGICAL SCIENCES↗

The mechanical properties of as-grown noncubic organic molecular crystals assessed by nanoindentation

Organic molecular crystals are often noncubic and contain significant steric hindrance within their structure to resist dislocation motion. Plastic deformation in these systems can be imparted during processing (tableting and comminution of powders), and the defect density impacts subsequent properties and performance. This paper measured the elastic and plastic properties of representative monoclinic, orthorhombic, and triclinic molecular crystalline structures using nanoindentation of as-grown sub-mm single crystals. The variation in modulus due to in-plane rotational orientation, relative to a Berkovich tip, was approximately equal to the variation of a given crystal at a fixed orientation. The onset of plasticity occurs consistently at shear stresses between 1 and 5% of the elastic modulus in all three crystal systems, and the hardness to modulus ratio suggests conventional Berkovich tips do not generate fully self-similar plastic zones in these materials. Finally, this provides guidance for mechanical models of tableting, machining, and property assessment of molecular crystals.

36 MATERIALS SCIENCE↗

Renal function and water balance

Routine urinalyses, including microscopic examination, were performed periodically. Protein, sugar, and pH were determined using Hema-Combistix reagent strips manufactured by the Ames Company. When the presence of albumin was suspected from a doubtful reaction of the reagent strip, the sulfasalicylic acid turbidity test for protein was also done. Likewise, to rule out a false positive reaction for glucose, the presence or absence of the latter was also determined using Clinitest Reagent Tablets (Ames). Specific gravity was determined using an urinometer, and acetate with Acetest Tablets (Ames Company). Serum and urinary creatinine clearance were determined once every three days. Methods used in all of the above tests were taken from standard Navy laboratory manuals published by the U. S. Naval Medical School, National Naval Medical Center, Bethesda, Md.

CREATININE↗

Inventory of forest and rangeland and detection of forest stress

The author has identified the following significant results. At the Atlanta site (226B) it was found that bulk color composites for October 15, 1972, and April 13, 1973, can be interpreted together to disclose the location of the perennial Kudzu vine (Pyeraria lobata). Land managers concerned with Kudzu eradication could use ERTS-1 to inventory locations over 200 meters (660 feet) square. Microdensitometer data collected on ERTS-1 Bulk photographic products for the Manitou test site (226C) have shown that the 15-step gray-scale tablets are not of systematic equal values corresponding to 1/14 the maximum radiant energy incident on the MSS sensor. The gray-scale values present a third-order polynomial function rather than a direct linear relationship. Although data collected on step tablets for precision photographic products appear more discrete, the density variation within blocks in almost as great as variations between blocks. These system errors will cause problems when attempting to analyze radiometric variances among vegetation and land use classes.

Heller, R. C.↗

Technical consulting services for earth resources program

Evaluations of several sets of test data which show a normal amount of variability in gamma and Dmax on KODAK Aerial Duplicating Film (ESTAR Base) SO-467 are reported. Kodak is now furnishing to engineers at GSFC a full set of test data for each coating of SO-467 film. Glass-enclosed sensitometer step tablets which are being made for the Herrnfeld instrument at GSFC are discussed. These tablets include a gray scale and uniformity check areas as well as tribar resolution patterns imaged in a durable chromium layer. It is recommended that the Sioux Falls EDC procure four new enlarging printers and study the value and economics of a system for printer automation based on edge coding.

Source record↗