Coiled coil interactions for the targeting of liposomes for nucleic acid delivery

Supramolecular & Biomaterials Chemistr

Voluntarily reported prescribing, monitoring and medication transfer errors in intensive care units in The Netherlands

Background Medication errors occur frequently in intensive care units (ICU). Voluntarily reported medication errors form an easily available source of information. Objective This study aimed to characterize prescribing, monitoring and medication transfer errors that were voluntarily reported in the ICU, in order to reveal medication safety issues. Setting This retrospective data analysis study included reports of medication errors from eleven Dutch ICU's from January 2016 to December 2017. Method We used data extractions from the incident reporting systems of the participating ICU's. The reports were transferred into one database and categorized into type of error, cause, medication (groups), and patient harm. Descriptive statistics were used to calculate the proportion of medication errors and the distribution of subcategories. Based on the analysis, ICU medication safety issues were revealed. Main outcome measure The main outcome measure was the proportion of prescribing, monitoring and medication transfer error reports. Results Prescribing errors were reported most frequently (n = 233, 33%), followed by medication transfer errors (n = 85, 12%) and monitoring errors (n = 27, 4%). Other findings were: medication transfer errors frequently caused serious harm, especially the omission of home medication involving the central nervous system and proton pump inhibitors; omissions and dosing errors occurred most frequently; protocol problems caused a quarter of the medication errors; and medications needing blood level monitoring (e.g. tacrolimus, vancomycin, heparin and insulin) were frequently involved. Conclusion This analysis of voluntarily reported prescribing, monitoring and medication transfer errors warrants several improvement measures in these processes, which may help to increase medication safety in the ICU

The Storage and In-Use Stability of mRNA Vaccines and Therapeutics: Not A Cold Case

The remarkable impact of mRNA vaccines on mitigating disease and improving public health has been amply demonstrated during the COVID-19 pandemic. Many new mRNA-based vaccine and therapeutic candidates are in development, yet the current reality of their stability limitations requires their frozen storage. Numerous challenges remain to improve formulated mRNA stability and enable refrigerator storage, and this review provides an update on developments to tackle this multi-faceted stability challenge. We describe the chemistry underlying mRNA degradation during storage and highlight how lipid nanoparticle (LNP) formulations are a double-edged sword: while LNPs protect mRNA against enzymatic degradation, interactions with and between LNP excipients introduce additional risks for mRNA degradation. We also discuss strategies to improve mRNA stability both as a drug substance (DS) and a drug product (DP) including the (1) design of the mRNA molecule (nucleotide selection, primary and secondary structures), (2) physical state of the mRNA-LNP complexes, (3) formulation composition and purity of the components, and (4) DS and DP manufacturing processes. Finally, we summarize analytical control strategies to monitor and assure the stability of mRNA-based candidates, and advocate for an integrated analytical and formulation development approach to further improve their storage, transport, and in-use stability profiles

Radiating Effectiveness of Annular-Finned Space Radiators, Including Mutual Irradiation between Radiator Elements

the authors also provide an approximate quantitative number for the accuracy of the numerical results. Based on the authors' results of Figs. 8 and 9, the fully developed periodic flow is achieved at x/L = 4 and 30 for Re = 200 and 1600 respectively for L/H = 1. Would the authors first quantitatively define the periodic fully developed flow, and then provide the tabular values of x/L as functions of L/H and Re for L/H = 0.2,0.5,1,2 and 5, and the covered range of Re. A research task remains further refining the analytical model to correlate better the performance of interrupted wall surface with the experimental results. Subsequently, the more complex heat exchanger surfaces could be analyzed. In the meanwhile, this paper by Prof. Sparrow and his colleagues serves as a reminder that the flow and heat transfer phenomena in a compact heat exchanger are too complex to analyze. A better quantitative understanding of the flow phenomena is essential for better correlations and improved heat exchanger design. Additional Reference Authors' Closure We are appreciative of the perspectives conveyed by Dr. Shah's Discussion. With regard to the role of vortices and wakes, there are, assuredly, conditions where they will affect both the heat transfer and friction. On the other hand, there are conditions for which no significant effect will be felt. Perspectives on these conditions are conveyed in references [11] and [12]. In connection with the identification of the periodically developed regime in Figs. 8 and 9, there is considerable latitude depending on the selected criterion. Since all portions of a velocity or temperature profile do not develop with equal rapidity, there are various criteria that can be employed. It was for this reason that we did not quote development lengths in the paper. Additional References 11 Kottke, V., Blenke, H., and Schmidt, K. G., "The Influence of Nose Section and Turbulence Intensity on the Flow Around Thick Plates in Parallel Flow," Warme-und Stoffubertragung, Vol. 10,1977, pp. 159-174. 12 Loehrke, R. I., Roadman, R. E., and Read, G. W" ASME Paper The purpose of this discussion is to point out how one of Minning's results can be generalized. In his analysis of the inverted conical frustrum, Minning has chosen to express his results in terms of four variables-the cone half angle fi, the height of the frustrum h, the radial location of the differential element p, and the vertical distance from the differential element to the extended frustrums' vertex s. In my view, this last choice is not the natural one and indeed it obscures the generality of the result expressed by equation It appears that a better choice of variable would be the radius of the frustrum in the plane of the element or ring, which is given by r = -s tan fi. If s is thereby eliminated from equation With respect to this latter point, one may note, as was done for a cylinder by Sparrow, et al. [1] that the shape factor in question can be considered as the sum of two parts-one being a circular segment and, in this case, the other being a tilted triangular plate frustrum. 1 By C. P. Minning, published in the August, 1977 issue of the JOURNAL OP HEAT TRANSFER, Vol. 99, No. 3, The Aerospace Corporation, El Segundo, CA 90245. Since the former is known [2], the latter can be readily obtained and subsequently expressed in variables more suitable for that configuration. This, of course, introduces new possibilities too numerous to mention. Finally, since Minning does not mention any analytical checks of his result, it is pointed out that, when /3 = 0, it reduces to a form equivalent to that for the cylinder [1]. Additional References 1 Sparrow, E. M., Miller, G. B., and Jonsson, V. K., "Radiating Effectiveness of Annular-Finned Space Radiators, Including Mutual Irradiation between Radiator Elements," Journal Aerospace Sciences, Vol. 29, 1962, pp. 1291-1299 2 Sparrow, E. M., "A New and Simpler Formulation for Radiative Angle Factors," ASME JOURNAL OF HEAT TRANSFER, Vol. 85,1963, pp. 81-88. Author's Closure I appreciate Dr. Nelson's pointing out that the applicability of equation An alternate expression that avoids this confusion can be derived by substitution of the relation r = -s tanjtf, as suggested by Dr. Nelson, and the relation a = (7r/2) -fi into equation C^)] [(h cot a + r) -In this expression, a is the angle between the plane of dAi and the sloping side of the conical frustrum. Values of a are always positive and lie in the range 0 < « < TT. For 0 < « < 7r/2, the frustrum opens upward away from the plane of dA\. For 7r/2 < a < w, the frustrum opens downward toward the plane of dAi. The special case, a = it 12

Een patiënt met verminderde gevoeligheid voor acenocoumarol tijdens gebruik van sondevoeding

Een 69-jarige man werd geopereerd aan een subduraal hematoom, ontstaan tijdens acenocoumarolgebruik. Direct na de operatie kreeg de patiënt sondevoeding; de toediening van acenocoumarol werd later herstart. De benodigde dosering acenocoumarol voor een goede instelling van de INR was tijdens toediening van de sondevoeding 2 maal zo hoog als daarvóór. Dit was niet toe te schrijven aan interacties met geneesmiddelen. Na de overgang van sondevoeding naar orale voeding was de oude dosis acenocoumarol weer voldoende. De hogere benodigde dosering was waarschijnlijk veroorzaakt door een verhoogde binding aan eiwitten in de sondevoeding. Patiënt werd opgenomen in het verpleeghuis. De combinatie acenocoumarol en sondevoeding komt vaak voor bij revaliderende patiënten. Het is belangrijk de INR te controleren bij het starten, het afbouwen en het beëindigen van sondevoeding