Multidimensional Methods: Applications in Drug-Enzyme Intrinsic Clearance Determination and Comprehensive Two-Dimensional Liquid Chromatography Peak Volume Determination

The goal of the first project was to evaluate strategies for determining the in vitro intrinsic clearance (CLint) of dextrorphan (DR) as metabolized by the UGT2B7 enzyme to obtain dextrorphan glucuronide (DR-G). A direct injection liquid chromatography-mass spectrometry (LC-MS) method was used to monitor products using the pseudo-first-order (PFO) model. Standard enzymatic incubations were also quantified using LC-MS. These data were fit utilizing both PFO and Michaelis-Menten (MM) models to determine estimates of kinetic parameters. The CLint was determined to be 0.28 (± 0.08) µL/min/mg protein for a baculovirus insect cell-expressed UGT2B7 enzyme. This is the first confirmation that dextrorphan is specifically metabolized by UGT2B7 and the first report of these kinetic parameters. Simulated chromatographic data were used to determine the precision and accuracy in the estimation of peak volumes in comprehensive two-dimensional liquid chromatography (2D-LC). Volumes were determined both by summing the areas in the second dimension chromatograms via the moments method and by fitting the second dimension areas to a Gaussian peak. When only two second dimension signals are substantially above baseline, the accuracy and precision are poor because the solution to the Gaussian fitting algorithm is indeterminate. The fit of a Gaussian peak to the areas of the second dimension peaks is better at predicting the peak volume when there are at least three second dimension injections above the limit of detection. Based on simulations where the sampling interval and sampling phase were varied, we conclude for well-resolved peaks that the optimum precision in peak volumes in 2D separations will be obtained when the sampling ratio is approximately two. This provides an RSD of approximately 2 % for the signal-to-noise (S/N) used in this work. The precision of peak volume estimation for experimental data was also assessed, and RSD values were in the 4-5 % range. We conclude that the poorer precision found in the 2D-LC experimental data as compared to 1D-LC is due to a combination of factors, including variations in the first dimension peak shape related to undersampling and loss in S/N due to the injection of multiple smaller peaks onto the second dimension column

Chondromyxoid Fibroma of the Rib: A Rare Benign Tumor With Potential for Local Recurrence

Chondromyxoid fibroma (CMF) is a benign cartilaginous tumor that typically occurs in the long bones of young adult males, with the clinical presentation varying from asymptomatic to localized pain, swelling, and movement restriction. We report an unusual presentation of CMF involving a rib, along with a literature review of the management of CMF. Although benign, local recurrence is not uncommon, and malignant transformation has been reported on rare occasions. En bloc surgical excision, with adequate tumor-free resection margins, of radiologically suspected chondromyxoid fibroma is crucial for the treatment and confirmation of diagnosis. A high index of suspicion, adequate treatment, and follow-up are critical for the successful management of these uncommon benign chondroid tumors

Expert advocacy for the marginalised: how and why democratic mediation matters to deepening democracy in the global South

The paper argues that the practice of democratic mediation is an increasingly common, yet under-researched, component of engagements between citizens and public authorities across the globe. While the actors who mediate (and their tactics) are diverse and are not necessarily of the marginalised group, they share a commitment to overcoming representational, knowledge or ideological deficits in decision-making for the marginalised group. While the ‘speaking for’ nature of democratic mediation clearly opens up critical legitimacy problems, the practice of democratic mediation appears to be remarkably common, and even effective. The paper demonstrates this by surveying at least three kinds of democratic mediation observed across a large number of cases. First is ‘mediationas professional advocacy’. The mediator in these cases is more an ‘interested intermediary’ in contentious policy politics. In a context of skewed power relations where certain groups remain systematically marginalised, not least through knowledge and representational deficits, a degree of advocacy is required to get more egalitarian policy dialogue. Second is ‘mediation as representational entrepreneurship’. This refers to engagements between citizens and forms of public authority that stretch from the local to the global level. In more ‘global-local’ mobilisations, mediators are often experts, professionals, and international NGOs. In more ‘local – global’ movements, the mediators are ‘hybrid activists’ deeply rooted in the local identities and associations. However, in either case the actor is distinguished by the taking of initiative to include the voices of the marginalised in a domain of power-relations which is multi-level. Lastly, ‘mediation as citizenship development’ refers to forms of activism typically associated with community and capacity development, and usually involves limited advocacy by civil society organisations (CSOs). Hence there may be little by way of explicit mediation in local governance decision-making in these cases, although the empowerment of communities has a demonstrable and mostly positive impact on local governance

Assessing the effectiveness of retrograde autologous priming of the cardiopulmonary bypass machine in isolated coronary artery bypass grafts

Introduction Currently, around 35–80% of patients undergoing cardiac surgery in the UK receive a blood transfusion. Retrograde autologous priming (RAP) of the cardiopulmonary bypass circuit has been suggested as a possible strategy to reduce blood transfusion during cardiac surgery. Methods Data from 101 consecutive patients undergoing isolated coronary artery bypass grafts (where RAP was used) were collected prospectively and compared with 92 historic patients prior to RAP use in our centre. Results Baseline characteristics (ie age, preoperative haemoglobin [Hb] etc) were not significantly different between the RAP and non-RAP groups. The mean pump priming volume of 1,013ml in the RAP group was significantly lower (p&lt;0.001) than that of 2,450ml in the non-RAP group. The mean Hb level at initiation of bypass of 9.1g/dl in patients having RAP was significantly higher (p&lt;0.001) than that of 7.7g/dl in those who did not have RAP. There was no significant difference between the RAP and non-RAP groups in transfusion of red cells, platelets and fresh frozen plasma, 30-day mortality, re-exploration rate and predischarge Hb level. The median durations of cardiac intensive care unit stay and in-hospital stay of 1 day (interquartile range [IQR]: 1–2 days) and 5 days (IQR: 4–6 days) in the RAP group were significantly shorter than those of the non-RAP group (2 days [IQR: 1–3 days] and 6 days [IQR: 5–9 days]). Conclusions In the population group studied, RAP did not influence blood transfusion rates but was associated with a reduction in duration of hospital stay. </jats:sec

So what difference does it make? Mapping the outcomes of citizen engagement

Over the last two decades, the idea that citizen engagement and participation can contribute to improved governance and development outcomes has been mainstreamed in development policy and discourse. Yet despite the normative beliefs that underpin this approach, the impact of participation on improved democratic and developmental outcomes has proved difficult to assess. Where previous research studies have attempted to demonstrate impact, they tend to be limited to single interventions, a small number of country contexts or by various conceptual and methodological constraints. In this paper, we report on a meta-case study analysis of a ten-year research programme on citizenship, participation and accountability which analysed a nonrandomised sample of 100 research studies of four types of citizen engagement in 20 countries. By mapping the observable effects of citizen participation through a close reading of these studies, we created a typology of four democratic and developmental outcomes, including (a) the construction of citizenship, (b) the strengthening of practices of participation, (c) the strengthening of responsive and accountable states, and (d) the development of inclusive and cohesive societies. We find that citizen participation produces positive effects across these outcome types, though in each category there are also examples of negative outcomes of citizen participation. We also find that these outcomes vary according to the type of citizen engagement and to political context. These findings have important implications for the design of and support for participatory programmes meant to improve state responsiveness and effectiveness

Engaging fringe stakeholders in business and society research: applying visual participatory research methods

Business and society (B&S) researchers, as well as practitioners, have been critiqued for ignoring those with less voice and power (e.g. women, non-literate or indigenous peoples) often referred to as ‘fringe stakeholders’. Existing methods used in B&S research often fail to address issues of meaningful participation, voice and power, especially in developing countries. In this article we stress the utility of visual participatory research (VPR) methods in B&S research to fill this gap. Through a case study on engaging Ghanaian cocoa farmers on gender inequality issues we explore how VPR methods may be used by researchers to achieve more inclusive, and thus more credible, stakeholder research that can improve decision-making within businesses. Furthermore, we argue that ingrained social and environmental problems tackled by B&S research and the unique context in which they occur may open up new opportunities to develop participatory visual methods for social change

Eumasia venefica sp. nov. a new species of the subfamily Eumasiinae (Lepidoptera Psychidae) from India with atypical larval ecology

Unnikrishnan, Usha Ayyath, Sobczyk, Thomas, Jose, Roby Thekkudan, Jose, Joyce (2023): Eumasia venefica sp. nov. a new species of the subfamily Eumasiinae (Lepidoptera Psychidae) from India with atypical larval ecology. Zootaxa 5352 (4): 521-536, DOI: 10.11646/zootaxa.5352.4.4, URL: http://dx.doi.org/10.11646/zootaxa.5352.4.