Pharmacokinetics of pimobendan following oral administration to New Zealand White rabbits (Oryctolagus cuniculus)

OBJECTIVE To determine the pharmacokinetics and potential adverse effects of pimobendan after oral administration in New Zealand White rabbits (Ocytolagus cuniculi). ANIMALS 10 adult sexually intact (5 males and 5 females) rabbits. PROCEDURES 2 pilot studies were performed with a pimobendan suspension or oral tablets. Eight rabbits received 7.5 mg of pimobendan (mean 2.08 mg/kg) suspended in a critical care feeding formula. Plasma concentrations of pimobendan and O-demethylpimobendan (ODMP) were measured, and pharmacokinetic parameters were calculated for pimobendan by noncompartmental analysis. Body weight, food and water consumption, mentation, urine, and fecal output were monitored. RESULTS Mean ± SD maximum concentration following pimobendan administration was 15.7 ± 7.54 ng/mL and was detected at 2.79 ± 1.25 hours. The half-life was 3.54 ± 1.32 hours. Plasma concentrations of pimobendan were detectable for up to 24 hours. The active metabolite, ODMP, was detected in rabbits for 24 to 36 hours. An adverse event occurred following administration of pimobendan in tablet form in 1 pilot study, resulting in death secondary to aspiration. No other adverse events occurred. CLINICAL RELEVANCE Plasma concentrations of pimobendan were lower than previously reported for dogs and cats, despite administration of higher doses, and had longer time to maximum concentration and half-life. Based on this study, 2 mg/kg of pimobendan in a critical care feeding formulation should maintain above a target plasma concentration for 12 to 24 hours. However, further studies evaluating multiple-dose administration as well as pharmacodynamic studies and clinical trials in rabbits with congestive heart failure are needed to determine accurate dose and frequency recommendations.

Canine Epidermal Keratinocytes (CPEK) Grown in Monolayer Are Not Representative of Normal Canine Keratinocytes for Permeability Studies: Pilot Studies

Canine progenitor epidermal keratinocytes (CPEK) are used as canine keratinocyte cell line. Their suitability for skin barrier studies is unknown. Measurement of transepithelial electric resistance (TEER) evaluates epithelial permeability. We compared TEER and tight junction (TJ) expression in CPEKs and normal keratinocytes (NK) harvested from biopsies of normal dogs. CPEKs and NK were grown until confluence (D0) and for 13 additional days. Slides were fixed on D0 and stained with ZO-1 and claudin-1 antibodies. Five images/antibody were taken, randomized and evaluated blindly by three investigators for intensity, staining location, granularity, and continuousness. Cell size and variability were evaluated. TEER increased overtime to 2000 Ohms/cm in NK, while remained around 100–150 Ohms/cm in CPEK. ANOVA showed significant effect of time (p < 0.0001), group (p < 0.0001) and group x time interaction (p < 0.0001) for TEER. Size of CPEKs was significantly (p < 0.0001) smaller and less variable (p = 0.0078) than NK. Intensity of claudin-1 staining was greater in CPEKs (p < 0.0001) while granularity was less in CPEKs (p = 0.0012). For ZO-1, cytoplasmic staining was greater in CPEK (p < 0.0001) while membrane continuousness of staining was greater in NK (p = 0.0002). We conclude that CPEKs grown in monolayer are not representative of NK for permeability studies.

Design and methods for a quasi-experimental pilot study to evaluate the impact of dual active ingredient insecticide-treated nets on malaria burden in five regions in sub-Saharan Africa

Background Vector control tools have contributed significantly to a reduction in malaria burden since 2000, primarily through insecticidal-treated bed nets (ITNs) and indoor residual spraying. In the face of increasing insecticide resistance in key malaria vector species, global progress in malaria control has stalled. Innovative tools, such as dual active ingredient (dual-AI) ITNs that are effective at killing insecticide-resistant mosquitoes have recently been introduced. However, large-scale uptake has been slow for several reasons, including higher costs and limited evidence on their incremental effectiveness and cost-effectiveness. The present report describes the design of several observational studies aimed to determine the effectiveness and cost-effectiveness of dual-AI ITNs, compared to standard pyrethroid-only ITNs, at reducing malaria transmission across a variety of transmission settings. Methods Observational pilot studies are ongoing in Burkina Faso, Mozambique, Nigeria, and Rwanda, leveraging dual-AI ITN rollouts nested within the 2019 and 2020 mass distribution campaigns in each country. Enhanced surveillance occurring in select study districts include annual cross-sectional surveys during peak transmission seasons, monthly entomological surveillance, passive case detection using routine health facility surveillance systems, and studies on human behaviour and ITN use patterns. Data will compare changes in malaria transmission and disease burden in districts receiving dual-AI ITNs to similar districts receiving standard pyrethroid-only ITNs over three years. The costs of net distribution will be calculated using the provider perspective including financial and economic costs, and a cost-effectiveness analysis will assess incremental cost-effectiveness ratios for Interceptor® G2, Royal Guard®, and piperonyl butoxide ITNs in comparison to standard pyrethroid-only ITNs, based on incidence rate ratios calculated from routine data. Conclusions Evidence of the effectiveness and cost-effectiveness of the dual-AI ITNs from these pilot studies will complement evidence from two contemporary cluster randomized control trials, one in Benin and one in Tanzania, to provide key information to malaria control programmes, policymakers, and donors to help guide decision-making and planning for local malaria control and elimination strategies. Understanding the breadth of contexts where these dual-AI ITNs are most effective and collecting robust information on factors influencing comparative effectiveness could improve uptake and availability and help maximize their impact.

Dance wherever you are: the evolution of multi-modal delivery for social inclusion of rural older adults

Background and Objectives Older adult social inclusion involves meaningful participation that is increasingly mediated by information communication technology (ICT) and in rural areas requires understanding of older adults’ experiences in the context of the digital divide. This paper examines how the multi-modal streaming (live, pre-recorded, blended in-person) of the Sharing Dance Older Adults program developed by Canada's National Ballet School (NBS) and Baycrest, influenced social inclusion processes and outcomes in rural settings. Research Design and Methods Data were collected from on-site observations of dance sessions, research team reflections, focus groups and interviews with older adult participants and their carers in pilot studies in the Peterborough Region of Ontario, and the Westman Region of Manitoba, Canada (2017-2019). There were 289 participants including older adults, people living with dementia, family carers, long-term-care staff, community facilitators, and volunteers. Analytic themes were framed in the context of rural older adult social exclusion. Results Remote delivery addressed barriers of physical distance by providing access to the arts-based program and enhancing opportunities for participation. Constraints were introduced by the use of technology in rural areas and mitigated by in-person facilitators and different streaming options. Meaningful engagement in dynamic interactions in the dance was achieved by involving local staff and volunteers in facilitation of and feedback on the program and its delivery. Different streaming technologies influenced social inclusion in different ways: live-stream enhanced connectedness, but constrained technical challenges; pre-recorded was reliable, but less social; blended delivery provided options, but personalization was unsustainable. Discussion and Implications Understanding different participants’ experiences of different technologies will contribute to more effective remote delivery of arts-based programs with options to use technology in various contexts depending on individual and organizational capacities.

Cross-disciplinary, collaborative and student-led: developing a change process for diversifying reading lists

Increasingly across many UK higher education institutions staff and students are questioning and challenging systemic inequalities that affect racially minoritised groups in their learning and sense of belonging within the curriculum. Students are calling for inclusion of diverse sources of knowledge and perspectives, especially from scholars of colour and from the Global South, to enrich what is currently perceived to be a Eurocentric canon. One way to promote more culturally aligned pedagogy is through diversifying reading lists. This article presents findings from two pilot studies that explored the reading lists in one department in social sciences and one in the humanities at the University of Kent, UK. Applying critical race theory as a guiding framework, the first part of the article examines the ways in which a diverse curriculum must include the voices of the marginalised. It then describes the methods: a desk-based review of the reading lists, interviews with academics to inform the work, disseminate the findings, instigate further action and identify future needs, and student focus groups. Crucially, the project resulted from the collaboration between students and staff, and across departments and disciplines. We found that reading lists in both departments overwhelmingly comprised items by White male authors. Students and staff both reflected on the importance of not only curriculum diversification but also barriers to diversification and decolonisation. The article discusses the impact of this project, which has led to a Diversity Mark process, and the Diversity Mark Toolkit, which can be used in any discipline when putting together reading lists to create a more culturally competent curriculum. It concludes by considering other systemic changes needed, with particular attention to changes needed in library services and collections.

Social Robots for Pedagogical Rehabilitation

The use of robots as educational learning tools is quite extensive worldwide, yet it is rather limited in special education. In particular, the use of robots in the field of special education is under skepticism since robots are frequently believed to be expensive with limited capacity. The latter may change with the advent of social robots, which can be used in special education as affordable tools for delivering sophisticated stimuli to children with learning difficulties also due to preexisting conditions. Pilot studies occasionally demonstrate the effectiveness of social robots in specific domains. This chapter overviews the engagement of social robots in special education including the authors' preliminary work in this field; moreover, it discusses their proposal for potential future extensions involving more autonomous (i.e., intelligent) social robots as well as feedback from human brain signals.

2.2.2-Cryptand complexes of neptunium(iii) and plutonium(iii)

The THF-soluble [An(crypt)(OTf)2][OTf] complexes for An = Np and Pu were synthesized from AnI3(THF)4 starting materials based on pilot studies of the An = U system. 5f3 U(iii), 5f4 Np(iii), and 5f5 Pu(iii) electron configurations are indicated by DFT analysis of their UV-visible-NIR spectra.

Estimation of critical gaps and follow-up times at median uncontrolled T-intersection

The efficiency of the entire transportation system depends on the capacity of the individual elements that make up the given network. Point-type elements of the road and street network include intersections of different types. Critical gaps and follow-up times related to individual movements are important determinants of the capacity of such objects. There are many ways to estimate such times. The article discusses the assumptions and scheme one of them - the Siegloch method. The objective of the article is to analyze the process of determining critical gaps and follow-up times at the median uncontrolled T-intersections that are rare in the road and street network and have been studied to a limited extent. The commonly used HCM, HBS, and Polish (MOP SBS) methods in their current form do not consider the speci-ficity of such intersections and thus may not give reliable results. Due to their characteristics in terms of geometry conditions, there is a need for an individual approach to estimate both critical gaps and follow-up times. The article contains the results of empirical research conducted on a selected real object in the Upper Silesian agglomeration in Poland. The intersection under study is located in one of the central districts of Katowice city, in the built-up area serving commercial and service functions. The analysis of the behavior of individual drivers waiting for the possibility to continue driving was conducted separately for each minor traffic movement. The values of critical gaps and follow-up times were determined for all four subordinate movements. The values obtained are different from those contained in the Polish manual, which is recommended for use. The research should be considered as pilot studies that justify the need to develop a separate approach to the estimation of the critical gaps and follow-up times at median uncontrolled T-intersections.

Evaluating the effectiveness of machine translation of audio description: the results of two pilot studies in the English-Dutch language pair

The field of translation is undergoing various profound changes. On the one hand it is being thoroughly reshaped by the advent and constant improvement of new technologies. On the other hand, new forms of translation are starting to see the light of day in the wake of social and legal developments that require that products and content that are created, are accessible for everybody. One of these new forms of translation, is audio description (AD), a service that is aimed at making audiovisual content accessible to people with sight loss. New legislation requires that this content is accessible by 2025, which constitutes a tremendous task given the limited number of people that are at present trained as audio describers. A possible solution would be to use machine translation to translate existing audio descriptions into different languages. Since AD is characterized by short sentences and simple, concrete language, it could be a good candidate for machine translation. In the present study, we want to test this hypothesis for the English-Dutch language pair. Three 30 minute AD excerpts of different Dutch movies that were originally audio described in English, were translated into Dutch using DeepL. The translations were analysed using the harmonized DQF-MQM error typology and taking into account the specific multimodal nature of the source text and the intersemiotic dimension of the original audio description process. The analysis showed that the MT output had a relatively high error rate, particularly in the categories of Accuracy – mistranslation and Fluency – grammar. This seems to indicate that extensive post-editing will be needed, before the text can be used in a professional context.