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Choice of LC-MS methods for the absolute quantification of drug-metabolizing enzymes and transporters in human tissue: A comparative cost analysis
No full textIntroduction: The quantification of drug-metabolizing cytochrome P450 (P450) and uridine 5ꞌ-diphospho-glucuronosyltransferase (UGT) enzymes and transporters is important for in vitro-in vivo extrapolation (IVIVE) of xenobiotic clearance, which has become an integral part of drug development. There are different mass spectrometry-based techniques used for quantitative proteomics, and as more laboratories are opting for the use of these methods, selecting the most appropriate tool is becoming a concern. For the first time, we attempt to determine the significance of cost of different LC-MS methods of quantitative analysis of these proteins and to present a framework to objectively assess the choice of the techniques. Based on our analysis, quantification using labeled internal standards is more expensive per sample but provides higher quality data than label free quantification. Quantification using absolute quantification (AQUA) synthetic peptides is the approach of choice for analyzing less than nine proteins, whereas when quantifying a defined set of proteins (10-50), such as enzymes, in a reasonably large number of samples (20-100), the quantification concatemer (QconCAT) technique is more economical, followed by label-free quantification. When analyzing proteomes or sub-proteomes (≥ 500 proteins), label-free quantification is more cost-effective than the use of labeled internal standards. A cost-benefit approach is described to assess the choice of the most appropriate mass spectrometry based approach for the quantification of proteins relevant to IVIVE
The Presence of Social Justice Principles Within Professional and Ethical Guidelines in International Psychology
No full textThe ethical guidelines produced by organisations such as the American Psychological Association help establish the identity of, and to some extent publicly represent, psychological professions. This paper examines guidelines from the USA and the UK with reference to the way in which they engage with “social justice” values and practice. Specifically, the codes of the American Psychological Association, and the British Psychological Society, and the standards of the (UK’s) Health and Care Professions Council are discussed. While the professional and ethical codes, standards and guidelines of these two countries do reflect some level of engagement with social justice, the American Psychological Association appears to be further ahead than its UK counterparts in embracing a social justice perspective. Additionally, the limited engagement with social justice in such documents, particularly in the UK, raises questions in relation to the identity of the profession of psychology and whether or not that identity even features social justice. The article concludes that if social justice is a priority for psychology then, as a starting point, the aspirational elements of such ethical guidelines should be amended to reflect such a commitment
The Influence of Prolonged Natural Aging on the Subsequent Artificial Aging Response of the AA6111 Automotive Alloy
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Hyperspectral remote sensing of peatland floristic gradients
No full textPrevious studies have shown that the floristic composition of northern peatlands provides important information regarding ecosystem processes and their responses to environmental change. Remote sensing is the most expeditious method of obtaining floristic information at landscape and regional scales, but the spatial complexity of many northern peatlands and the spectral similarity of a number of peatland vegetation species is such that the success of traditional methods of vegetation classification is often limited. Here, we assessed whether ordination and regression analyses may be a useful alternative method for mapping peatland plant communities from remote sensing data. We used isometric feature mapping (Isomap) to describe the community structure of the peatland vegetation and related the identified continuous floristic gradients to hyperspectral imagery (AISA Eagle) using partial least squares regression (PLSR). We performed the same analysis at two hierarchical levels of species aggregation in order to map continuous gradients in the composition of both species and plant functional types (PFTs), the latter of which is the most widely used level of aggregation in northern ecosystems. Isomap was able to transfer 82% and more than 96% of the observed ground-based observations to the ordination space for plots characterised by species and PFT; respectively. The modelled floristic gradients showed good agreement with ground-based species and PFT observations although the strength of the agreement was proportional to the amount of floristic variation explained by each ordination axis (r2val = 0.74, 0.45 and 0.30 for the first three ordination axes and r2val = 0.68 and 0.66 for the first two ordination axes; for species and PFT floristic gradients respectively). We also found that how a PFT is defined has an important influence on the success with which it can be mapped. The resultant mapped floristic gradients enabled visualisation of homogeneous vegetation stands, heterogeneous mixtures of different key species and PFTs, and the presence of continuous and abrupt floristic transitions, without the need for unique spectral signatures or the collection of data characterising ancillary environmental variables
Investigating the framing-effects of risk attributes in a discrete choice experiment for a national breast screening programme
No full textPurpose: To understand if, and how, the framing of risk in a discrete choice experiment (DCE) affects preferences for a national breast screening programme (NBSP).Method: An online DCE was designed and piloted (n=124) to elicit the preferences of female members of the public (recruited via an internet panel provider) for a NBSP described by two risk attributes (probability of detecting a cancer and risk of unnecessary follow-up per 100 women screened) and a cost attribute (out-of-pocket expense). Two survey versions presented the risk attributes as: (A) percentage only or (B) percentage and an icon array. The unlabelled DCE was blocked into two surveys, each containing 11 sets of choices between two screening programmes and an opt-out. The design, generated using Ngene, included an internal validity test through the inclusion of a dominant choice set. The DCE data were analysed using heteroskedastic conditional logit (HCLM) and scale-adjusted latent class (SALC) models.Result: 1007 women (version A =501; B=506) completed the DCE. The results of the HCLM suggested that all attribute coefficients, but no two-way interactions, were significant and had the expected signs. Interactions of attributes with risk framing version were not significant and the risk framing version had no significant impact on the scale parameter. SALC analysis revealed heterogeneity in preferences, with five latent classes and three scale classes providing the best fit. The class probabilities indicate 84% of respondents were members of three large classes where all scale-adjusted attribute coefficients were significant: 31% in class 1 (probability of detecting a cancer most important), 27% in class 2 (cost of screening most important), 25% in class 3 (risk of unnecessary follow-up most important). The remaining 17% were split between classes 4 (9%) and 5 (8%). Class 1 members tended to be aware and concerned about their risk of breast cancer. Class 2 members were less likely to be older (over 50). Class 3 individuals tended to be younger (25-34) and have experience of cancer in their family. Risk framing version was not a predictor of class membership.Conclusion: This study found the framing of risk attributes did not impact respondents’ choices in a DCE. However, other sources of heterogeneity were found in women’s preferences for the balance between the risks and benefits of a NBSP
