SciCombinator

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Concept: Dispensing

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Although developments in liquid dispensers have made the use of 1536-well plates for high-throughput screening (HTS) standard, there is still a gap in dispenser technology for performing matrix experiments with several components. Experiments such as those performed during assay development and enzymological studies are therefore still performed by manual pipetting in lower-density plates. We have evaluated a new dispenser, the Certus liquid dispenser (Gyger Fluidics GmbH, Switzerland), that is capable of flexible dispensing in 1536-well format, with a dead volume of less than 200 µL. Taking advantage of the precision of the dispenser for volumes down to 50 nL, we have created concentration gradients on plates by dispensing different volumes of reagent and then backfilling with buffer. Using this method and the flexibility of the dispenser software, we have performed several multidimensional experiments varying two to three components, including an assay development for an HTS, a mode of inhibition study, and a cofactor optimization, in which we determined 32 K(M) values. Overall, the flexibility of the plate layout for multiple components, the accuracy to dispense volumes ranging 2 log orders, and minimal reagent usage enable this dispenser for complex biochemical experiments.

Concepts: Dispensing, Z-factor, Performance, Sphere, Density, Volume, Dispenser, Dispensation

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To assess pharmacists' willingness to initiate the dispensing of naloxone. As of 2015, Kentucky law permits certified pharmacists to dispense naloxone under a physician-approved protocol.

Concepts: Opioid, Dispensing, Naloxone, Drug overdose

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Section 340B of the Public Health Service Act provides qualified organizations serving vulnerable populations with deep discounts for some outpatient medications. A 2010 regulatory change widely expanded the 340B program’s reach, allowing these organizations to contract with retail pharmacies to dispense medications for eligible patients. Little is known about which medications are dispensed by contract pharmacies under the expanded program. We provide the first comparison of 340B prescriptions and all prescriptions dispensed in contract pharmacies. We used 2012 data from Walgreens, the national leader in 340B contract pharmacies. Medications used to treat chronic conditions such as diabetes, high cholesterol levels, asthma, and depression accounted for an overwhelming majority of all prescriptions dispensed at Walgreens as part of the 340B program. A higher percentage of antiretrovirals used to treat HIV/AIDS were dispensed through 340B prescriptions than through all prescriptions dispensed at Walgreens. The majority of 340B prescriptions dispensed at Walgreens originated at tuberculosis clinics, consolidated health centers, disproportionate-share hospitals, and Ryan White clinics. Our results suggest that 340B contract pharmacies dispense medications used to treat Americans' chronic disease burden and disproportionately dispense medications used by key vulnerable populations targeted by the program.

Concepts: Health care, AIDS, Dispensation, Asthma, Hospital, Dispensing, Public health, Medicine

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we compared the self-reported medication adherence and knowledge of older patients receiving their drugs via multidose drug dispensing (MDD users) with patients receiving manually dispensed drugs (non-MDD users).

Concepts: Drug addiction, Drugs, Dispensing, Illness, Pharmaceutical drug, Drug, Pharmacology

1

BACKGROUND: Recent evidence suggests that the use of leukotriene receptor antagonists (LTRAs) in addition to inhaled corticosteroids (ICSs) in asthmatic patients provides comparable benefits to the addition of long-acting β-agonists (LABAs) to ICSs. OBJECTIVE: We sought to compare, in a unified framework, adherence, outcomes, and costs associated with ICS+LTRA versus ICS+LABA as step-up therapies for asthma. METHODS: Using the administrative databases of British Columbia, Canada (years 1997-2007), we created a propensity score-matched sample of asthmatic patients (12-45 years old) receiving ICS+LTRA therapy versus ICS+LABA therapy after a period of monotherapy with an ICS. We compared the outcomes using 2 analyses: an intention-to-treat (ITT) analysis that followed subjects for a fixed period of 2 years and an uninterrupted treatment analysis that followed subjects for as long as they continuously dispensed their index medications. RESULTS: The matched cohort consisted of 1032 subjects in each group (mean age at entry, 27.4 years; 52.5% female). Adherence, which was defined as the proportion of days covered, was higher in the ICS+LABA group compared with the ICS+LTRA group. In both the ITT and uninterrupted treatment analyses, use of ICS+LTRA therapy was associated with more asthma-related outpatient visits, asthma-related medication dispensations, and dispensation of reliever medications. Dispensation of oral corticosteroids and rate of asthma exacerbations were higher in the ICS+LTRA group in the uninterrupted treatment analysis but not in the ITT analysis. CONCLUSIONS: In a real-world clinical setting subjects were more adherent to ICS+LABA therapy than ICS+LTRA therapy. ICS+LABA therapy seems to be more effective than ICS+LTRA therapy in the management of asthma, regardless of adherence.

Concepts: Medicine, Receptor antagonist, Dispensation, Dispensing, Pharmaceutical drug, Corticosteroid, Asthma, Leukotriene

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Critical to maintaining quality control in high-throughput screening is the need for constant monitoring of liquid-dispensing fidelity. Traditional methods involve operator intervention with gravimetric analysis to monitor the gross accuracy of full plate dispenses, visual verification of contents, or dedicated weigh stations on screening platforms that introduce potential bottlenecks and increase the plate-processing cycle time. We present a unique solution using open-source hardware, software, and 3D printing to automate dispenser accuracy determination by providing real-time dispense weight measurements via a network-connected precision balance. This system uses an Arduino microcontroller to connect a precision balance to a local network. By integrating the precision balance as an Internet of Things (IoT) device, it gains the ability to provide real-time gravimetric summaries of dispensing, generate timely alerts when problems are detected, and capture historical dispensing data for future analysis. All collected data can then be accessed via a web interface for reviewing alerts and dispensing information in real time or remotely for timely intervention of dispense errors. The development of this system also leveraged 3D printing to rapidly prototype sensor brackets, mounting solutions, and component enclosures.

Concepts: Weight, Laboratory automation, Mass, Force, Measurement, Time, Dispensing, Dispensation

0

We report a fluorescent carbon nanoparticle (FCN)-based lateral flow biosensor for ultrasensitive detection of DNA. Fluorescent carbon nanoparticle with a diameter of around 15nm was used as a tag to label a detection DNA probe, which was complementary with the part of target DNA. A capture DNA probe was immobilized on the test zone of the lateral flow biosensor. Sandwich-type hybridization reactions among the FCN-labeled DNA probe, target DNA and capture DNA probe were performed on the lateral flow biosensor. In the presence of target DNA, FCNs were captured on the test zone of the biosensor and the fluorescent intensity of the captured FCNs was measured with a portable fluorescent reader. After systematic optimizations of experimental parameters (the components of running buffers, the concentration of detection DNA probe used in the preparation of FCN-DNA conjugates, the amount of FCN-DNA dispensed on the conjugate pad and the dispensing cycles of the capture DNA probes on the test-zone), the biosensor could detect a minimum concentration of 0.4 fM DNA. This study provides a rapid and low-cost approach for DNA detection with high sensitivity, showing great promise for clinical application and biomedical diagnosis.

Concepts: Southern blot, Space probe, Dispensing, Hybridization probe, Ultraviolet, Polymerase chain reaction, Phosphorus, Molecular biology

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We have taken advantage of a natural experiment to measure the impact of the phased abolition of prescription co-payments in Wales. We investigated 3 study periods covering the phased abolition: from £6 to £4, £4 to £3, and £3 to £0. A difference-in-difference modelling was adopted and applied to monthly UK general practice level dispensing data on 14 selected medicines which had the highest percentage of items dispensed subject to a co-payment prior to abolition. Dispensing from a comparator region (North East of England) with similar health and socio-economic characteristics to Wales, and where prescription co-payments continued during the study periods, was used to isolate any non-price effects on dispensing in Wales. Results show a small increase in dispensing of 14 selected medicines versus the comparator. Compared with NE England, monthly average Welsh dispensing was increased by 11.93 items (7.67%; 95% CI [7.2%, 8.1%]), 6.37 items (3.38%; 95% CI [2.9%, 3.7%]) and 9.18 items (4.54%; 95% CI [4.2%, 4.9%]) per practice per 1,000 population during the periods when co-payment was reduced. Price elasticities of the selected medicines utilisation were -0.23, -0.13, and -0.04 in 3 analyses, suggesting the abolition of co-payment had small effect on Welsh dispensing.

Concepts: Welsh people, Experiment, Dispensing, Welsh language, United Kingdom, Wales, Pharmacology, England

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A method for performing droplet actuation, splitting, and dispensing using only magnetic force and physical confinement is reported. The combination of low-friction superhydrophobic surfaces and droplets containing superparamagnetic particles is demonstrated to reliably dispense droplets with a precision (≤6%) similar to standard air-displacement pipettes. The 3D printed microfluidic chips incorporate individual wells, a weir structure and differential channel depths to facilitate droplet splitting in differing ratios. Both empirical observations and numerical simulations show that the splitting is a combination of wetting and pressure differences. The method enables a parent drop to be dispensed and split into droplets ranging in size from 5-20 μL using different well volumes. Once dispensed/split the droplets can be further actuated, merged and mixed. An EDTA-based complexometric colorimetric titration for water hardness is conducted on-chip. The degree of colour change is then determined utilizing a cell phone camera and image analysis and used to calculate water hardness; this measurement was found to agree with the traditional, larger scale method. The simple, robust dispensing method is adaptable to other digital microfluidic assays.

Concepts: Microfluidics, Assay, Dispensing, Drop, Liquid, Magnetism, Titration, Surface tension

0

There is a growing need for power-free methods to manipulate small volumes of liquids and thereby enable use of diagnostic assays in resource-limited settings. Most existing self-powered devices provide analog manipulation of fluids using paper, capillary or pressure-driven pumps. These strategies are well-suited to manipulating larger micro- and milliliter-scale volumes at constant flow rates; however, they fail to enable the manipulation of nanoliter and picoliter volumes required in assays using droplets, capillary sampling (e.g. finger prick), or expensive reagents. Here we report a device, termed the Digit Chip, that provides programmable and power-free digital manipulation of sub-nanoliter volumes. The device consists of a user-friendly button interface and a series of chambers connected by capillary valves that serve as digitization elements. Via a button press, the user dispenses and actuates ultra-small, quantitatively-programmed volumes. The device geometry is optimized using design models and experiments and precisely dispenses volumes as low as 21 pL with 97% accuracy. The volume dispensed can be tuned in 10 discrete steps across one order-of-magnitude with 98% accuracy. As a proof-of-principle that nanoliter-scale reagents can be precisely actuated and combined on-chip, we deploy the device to construct a precise concentration gradient with 10 discrete concentrations. Additionally, we apply this device alongside an inexpensive smartphone-based fluorescence imaging platform to perform a titration of E. coli with ampicillin. We observe the onset of bacterial death at a concentration of 5 μg mL(-1), increasing to a maximum at 50 μg mL(-1). These results establish the utility of the Digit Chip for diagnostic applications in low-resource environments.

Concepts: Escherichia coli, Sampling, Dispensation, Cubic metre, Dispensing, Litre, Liquid, Volume