475 research outputs found
Instructional Designer Perspectives of the Usefulness of an Instructional Design Process When Designing E-Learning
Though the number of instructional design models has increased, the usefulness of an instructional design process (linear or iterative) when making design decisions for e-learning solutions remains uncertain. This basic qualitative study was used to explore the perspectives of corporate instructional designers who were mandated to move from a linear to an iterative instructional design process for developing e-learning. The research questions address their perspectives of the usefulness of an instructional design process when making design decisions for e-learning solutions. Data were collected using semistructured interviews with nine instructional designers. Data were analyzed inductively using in vivo and pattern coding to develop themes related to the conceptual framework of the technological pedagogical content knowledge model. The findings indicated the instructional designers use a linear instructional design process for making e-learning designs decision when time is allotted to conduct an analysis and get buy-in from stakeholders, when the opportunity to work independently exists, and when the content is known and less likely to change. Additionally, the instructional designers use an iterative instructional design process for making e-learning design decision when time is allotted for prototyping and getting buy-in from stakeholders as well as when the content is unknown and more likely to change, and they use this iterative process for approving e-learning design decisions about content, presentation, and technology when there are multiple decision-makers. Positive social change might occur if educational leaders and instructional designers leverage the findings to gain insight into the practical application of instructional design processes when designing e-learning solutions
East Ballidu Catchment Report
It will require the total cooperation of all members of the Soil Conservation District to remedy the area\u27s problems. The first priority is for the control and better use of water on the recharge areas. The wheat/wheat/lupin rotation at present offers the best economic option. Lupins are well suited to the areas of lighter land. If lupins are planted on waterlogged soils or otherwise unsuitable soils, problems will arise and perhaps prejudice their use on the widespread suitable areas. The use of trees below rocky outcrops is an important measure to prevent excessive recharge of the deeper aquifers. Where trees already exist they need to be fenced to allow them to regenerate. Grants are now available for the fencing of remnant areas and is one line that the group members should vigorously explore. All remnants of bush and forest should be identified and protected in the catchment
Intestinal CFTR expression alleviates meconium ileus in cystic fibrosis pigs
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Innate immune activation by inhaled lipopolysaccharide, independent of oxidative stress, exacerbates silica-induced pulmonary fibrosis in mice
Acute exacerbations of pulmonary fibrosis are characterized by rapid decrements in lung function. Environmental factors that may contribute to acute exacerbations remain poorly understood. We have previously demonstrated that exposure to inhaled lipopolysaccharide (LPS) induces expression of genes associated with fibrosis. To address whether exposure to LPS could exacerbate fibrosis, we exposed male C57BL/6 mice to crystalline silica, or vehicle, followed 28 days later by LPS or saline inhalation. We observed that mice receiving both silica and LPS had significantly more total inflammatory cells, more whole lung lavage MCP-1, MIP-2, KC and IL-1β, more evidence of oxidative stress and more total lung hydroxyproline than mice receiving either LPS alone, or silica alone. Blocking oxidative stress with N-acetylcysteine attenuated whole lung inflammation but had no effect on total lung hydroxyproline. These observations suggest that exposure to innate immune stimuli, such as LPS in the environment, may exacerbate stable pulmonary fibrosis via mechanisms that are independent of inflammation and oxidative stress. © 2012 Brass et al
Implementing Person-Centred Lean Six Sigma to Transform Dermatology Waiting Lists: A Case Study from a Major Teaching Hospital in Dublin, Ireland
From Crossref journal articles via Jisc Publications RouterHistory: epub 2024-11-04, issued 2024-11-04Article version: VoRPublication status: PublishedSeán Paul Teeling - ORCID: 0000-0002-4102-7280
https://orcid.org/0000-0002-4102-7280The study site, a major teaching hospital in Dublin, Ireland, addressed significant challenges within its dermatology service through a comprehensive improvement initiative using a person-centred Lean Six Sigma methodology. Initially, the hospital’s dermatology department faced excessive outpatient waiting times, with 3736 patients awaiting appointments, and 1615 waiting over 12 months. The person-centred Lean Six Sigma approach, which combines Lean techniques to reduce non-value add and Six Sigma methods to eliminate variation through a person-centred lens, was applied to overhaul the referral, triage, and scheduling processes. Key interventions included standardising triage categories, centralising the triage process, and redistributing referrals equitably among consultants. A new centralised triage system was established, leading to a more efficient allocation of appointments and better management of urgent cases. Post-implementation data showed a 40% reduction in the overall waiting list and a 60% reduction in the number of patients waiting over 12 months. The initiative significantly decreased the wait times across all urgency categories, with the most notable improvements in soon and urgent referrals. These changes were also the impetus for a follow-up design-led innovation phase, where the team worked with partners across the educational and healthcare system to enable disruptive change. The success of this project provides a scalable model for improvements in similar healthcare settings.pubpu
In Silico, in Vitro, and in Vivo Evaluation of Precipitation Inhibitors in Supersaturated Lipid-Based Formulations of Venetoclax
The concept of using precipitation inhibitors (PIs) to sustain supersaturation is well established for amorphous formulations but less in the case of lipid-based formulations (LBF). This study applied a systematic in silico-in vitro-in vivo approach to assess the merits of incorporating PIs in supersaturated LBFs (sLBF) using the model drug venetoclax. sLBFs containing hydroxypropyl methylcellulose (HPMC), hydroxypropyl methylcellulose acetate succinate (HPMCAS), polyvinylpyrrolidone (PVP), PVP-co-vinyl acetate (PVP/VA), Pluronic F108, and Eudragit EPO were assessed in silico calculating a drug-excipient mixing enthalpy, in vitro using a PI solvent shift test, and finally, bioavailability was assessed in vivo in landrace pigs. The estimation of pure interaction enthalpies of the drug and the excipient was deemed useful in determining the most promising PIs for venetoclax. The sLBF alone (i.e., no PI present) displayed a high initial drug concentration in the aqueous phase during in vitro screening. sLBF with Pluronic F108 displayed the highest venetoclax concentration in the aqueous phase and sLBF with Eudragit EPO the lowest. In vivo, the sLBF alone showed the highest bioavailability of 26.3 ± 14.2%. Interestingly, a trend toward a decreasing bioavailability was observed for sLBF containing PIs, with PVP/VA being significantly lower compared to sLBF alone. In conclusion, the ability of a sLBF to generate supersaturated concentrations of venetoclax in vitro was translated into increased absorption in vivo. While in silico and in vitro PI screening suggested benefits in terms of prolonged supersaturation, the addition of a PI did not increase in vivo bioavailability. The findings of this study are of particular relevance to pre-clinical drug development, where the high in vivo exposure of venetoclax was achieved using a sLBF approach, and despite the perceived risk of drug precipitation from a sLBF, including a PI may not be merited in all cases
Machine learning methods for prediction of food effects on bioavailability: A comparison of Support Vector Machines and Artificial Neural Networks
Despite countless advances in recent decades across various in vitro, in vivo and in silico tools, anticipation of whether a drug will show a human food effect (FE) remains challenging. One means to predict potential FE involves probing any dependence between FE and drug properties. Accordingly, this study explored the potential for two machine learning (ML) algorithms to predict likely FE. Using a collated database of drugs licensed from 2016-2020, drugs were classified into three groups; positive, negative or no FE. Greater than 250 drug properties were predicted for each drug which were used to train predictive models using Support Vector Machine (SVM) and Artificial Neural Network (ANN) algorithms. When compared, ANN outperformed SVM for FE classification upon training (82%, 72%) and testing (72%, 69%). Both models demonstrated higher FE prediction accuracy than the Biopharmaceutics Classification System (BCS) (46%). This exploratory work provided new insights into the connection between FE and drug properties as the Octanol Water Partition Coefficient (S+logP), Number of Hydrogen Bond Donors (HBD), Topological Polar Surface Area (T_PSA) and Dose (mg) were all significant for prediction. Overall, this study demonstrated the utility of ML to facilitate early anticipation of likely FE in pre-clinical development using four well-known drug properties
Characterization of gastrointestinal transit and luminal conditions in pigs using a telemetric motility capsule
Within preclinical research, the pig has become an important model in regulatory toxicology and pharmacokinetics, to assess oral dosage forms and to compare different formulation strategies. In addition, there are emerging application of the pig model to asses clinical dosing conditions in the fasted and fed state. In this study, the gastrointestinal transit conditions in male landrace pigs were studied with a telemetric motility capsule under fasted and postprandial conditions. The whole gut transit time (WGTT) was determined by administering a SmartPill® capsule to four landrace pigs, under both fasted and fed state conditions in a cross-over study design. Overall, this study found that small intestinal transit in landrace pigs ranged from 2.3 – 4.0 h, and was broadly similar to reported human estimates and was not affected by the intake conditions. Gastric emptying was highly variable and prolonged in landrace pigs ranging from 20 – 233 h and up to 264 h in one specific case. Under dynamic conditions pigs have a low gastric pH comparable to humans, however a high variability under fasted conditions could be observed. The comparison of the data from this study with a recent similar study in beagle dogs revealed major differences between gastric maximum pressures observed in landrace pigs and dogs. In the porcine stomach maximum pressures of up to 402 mbar were observed, which are comparable to reported human data. Intestinal maximum pressures in landrace pigs were in the same range as in humans. Overall, the study provides new insights of gastrointestinal conditions in landrace pigs, which can lead to more accurate interpretation of in vivo results obtained of pharmacokinetic studies in preclinical models. While small intestinal transit conditions, GI pH and pressures were similar to humans, the prolonged gastric emptying observed in pigs need to be considered in assessing the suitability of the pig model for assessing in vivo performance of large non-disintegrated oral drug products.
A retrospective biopharmaceutical analysis of >800 approved oral drug products: Are drug properties of solid dispersions and lipid-based formulations distinctive?
Increasing numbers of poorly water soluble drugs in development has intensified need for bio-enabling formulations including Lipid-Based Formulations (LBF) and Solid Dispersions (SD). Resultantly, a data-driven approach is required to increase formulation development efficiency. This review provides a retrospective analysis of molecular and biopharmaceutical properties of drugs commercialised as LBFs or SDs. A comprehensive stepwise statistical analysis of LBF and SD drug properties was conducted and compared to drugs not commercialised via either technology (Others), aiming to identify key predictors of successful formulation development. This review demonstrates LBF and SD drugs differ significantly in molecular weight, polar surface area, rotatable bonds and hydrogen bond acceptor count. Meanwhile, LBF and SD drugs display significantly different aqueous solubility, lipophilicity, size, molecular flexibility, hydrogen bonding capacity and rule-of-5 violations versus Others. LBF and SDs were 3 and 5 times more likely to display >1 rule-of-5 violation versus Others, over 55% of LBF drugs exceeded the reported melting point guide of 10 Hydrogen Bond Acceptors. Overall, by focusing on successfully commercialised drugs, this review provides improved understanding of links between drug properties and successful SD/LBF approaches, providing a framework for guiding pharmaceutical development on formulation approaches
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