Protein sensing and discrimination using highly functionalised ruthenium( ii ) tris(bipyridyl) protein surface mimetics in an array format

Ruthenium(II) tris(bipyridyl) protein surface mimetics are used in an array format to sense and discriminate proteins including therapeutically relevant targets, hDM2 and MCL-1, using linear discriminant analysis (LDA)

Simplicial gauge theory on spacetime

We define a discrete gauge-invariant Yang-Mills-Higgs action on spacetime simplicial meshes. The formulation is a generalization of classical lattice gauge theory, and we prove consistency of the action in the sense of approximation theory. In addition, we perform numerical tests of convergence towards exact continuum results for several choices of gauge fields in pure gauge theory.Comment: 18 pages, 2 figure

A coherent middle Pliocene magnetostratigraphy, Wanganui Basin, New Zealand

We document magnetostratigraphies for three river sections (Turakina, Rangitikei, Wanganui) in Wanganui Basin and interpret them as corresponding to the Upper Gilbert, the Gauss and lower Matuyama Chrons of the Geomagnetic Polarity Timescale, in agreement with foraminiferal biostratigraphic datums. The Gauss-Gilbert transition (3.58 Ma) is located in both the Turakina and Wanganui River sections, while the Gauss-Matuyama transition (2.58 Ma) is located in all three sections, as are the lower and upper boundaries of the Mammoth (3.33–3.22 Ma) and Kaena (3.11–3.04 Ma) Subchrons. Our interpretations are based in part on the re-analysis of existing datasets and in part on the acquisition and analysis of new data, particularly for the Wanganui River section. The palaeomagnetic dates of these six horizons provide the only numerical age control for a thick (up to 2000 m) mudstone succession (Tangahoe Mudstone) that accumulated chiefly in upper bathyal and outer neritic palaeoenvironments. In the Wanganui River section the mean sediment accumulation rate is estimated to have been about 1.8 m/k.y., in the Turakina section it was about 1.5 m/k.y., and in the Rangitikei section, the mean rate from the beginning of the Mammoth Subchron to the Hautawa Shellbed was about 1.1 m/k.y. The high rates may be associated with the progradation of slope clinoforms northward through the basin. This new palaeomagnetic timescale allows revised correlations to be made between cyclothems in the Rangitikei River section and the global Oxygen Isotope Stages (OIS) as represented in Ocean Drilling Program (ODP) Site 846. The 16 depositional sequences between the end of the Mammoth Subchron and the Gauss-Matuyama Boundary are correlated with OIS MG2 to 100. The cyclothems average 39 k.y. in duration in our age model, which is close to the 41 k.y. duration of the orbital obliquity cycles. We support the arguments advanced recently in defence of the need for local New Zealand stages as a means of classifying New Zealand sedimentary successions, and strongly oppose the proposal to move stage boundaries to selected geomagnetic polarity transitions. The primary magnetisation of New Zealand mudstone is frequently overprinted with secondary components of diagenetic origin, and hence it is often difficult to obtain reliable magnetostratigraphic records. We suggest specific approaches, analytical methods, and criteria to help ensure robustness and coherency in the palaeomagnetic identification of chron boundaries in typical New Zealand Cenozoic mudstone successions

Similarity solutions for unsteady shear-stress-driven flow of Newtonian and power-law fluids : slender rivulets and dry patches

Unsteady flow of a thin film of a Newtonian fluid or a non-Newtonian power-law fluid with power-law index N driven by a constant shear stress applied at the free surface, on a plane inclined at an angle α to the horizontal, is considered. Unsteady similarity solutions representing flow of slender rivulets and flow around slender dry patches are obtained. Specifically, solutions are obtained for converging sessile rivulets (0 < α < π/2) and converging dry patches in a pendent film (π/2 < α < π), as well as for diverging pendent rivulets and diverging dry patches in a sessile film. These solutions predict that at any time t, the rivulet and dry patch widen or narrow according to |x|3/2, and the film thickens or thins according to |x|, where x denotes distance down the plane, and that at any station x, the rivulet and dry patch widen or narrow like |t|−1, and the film thickens or thins like |t|−1, independent of N

CAD in mammography: lesion-level versus case-level analysis of the effects of prompts on human decisions

Object: To understand decision processes in CAD-supported breast screening by analysing how prompts affect readers’ judgements of individual mammographic features (lesions). To this end we analysed hitherto unexamined details of reports completed by mammogram readers in an earlier evaluation of a CAD tool. Material and methods: Assessments of lesions were extracted from 5,839 reports for 59 cancer cases. Statistical analyses of these data focused on what features readers considered when recalling a cancer case and how readers reacted to CAD prompts. Results: About 13.5% of recall decisions were found to be caused by responses to features other than those indicating actual cancer. Effects of CAD: lesions were more likely to be examined if prompted; the presence of a prompt on a cancer increased the probability of both detection and recall especially for less accurate readers in subtler cases; lack of prompts made cancer features less likely to be detected; false prompts made non-cancer features more likely to be classified as cancer. Conclusion: The apparent lack of impact reported for CAD in some studies is plausibly due to CAD systematically affecting readers’ identification of individual features, in a beneficial way for certain combinations of readers and features and a damaging way for others. Mammogram readers do not ignore prompts. Methodologically, assessing CAD by numbers of recalled cancer cases may be misleading

A ‘quiet revolution’? The impact of Training Schools on initial teacher training partnerships

This paper discusses the impact on initial teacher training of a new policy initiative in England: the introduction of Training Schools. First, the Training School project is set in context by exploring the evolution of a partnership approach to initial teacher training in England. Ways in which Training Schools represent a break with established practice are considered together with their implications for the dominant mode of partnership led by higher education institutions (HEIs). The capacity of Training Schools to achieve their own policy objectives is examined, especially their efficacy as a strategy for managing innovation and the dissemination of innovation. The paper ends by focusing on a particular Training School project which has adopted an unusual approach to its work and enquires whether this alternative approach could offer a more profitable way forward. During the course of the paper, five different models of partnership are considered: collaborative, complementary, HEI-led, school-led and partnership within a partnership

Inspiratory muscle warm-up does not improve cycling time-trial performance

Purpose: This study examined the effects of an active cycling warm-up, with and without the addition of an inspiratory muscle warm-up (IMW), on 10-km cycling time-trial performance

The analysis of acetaminophen (paracetamol) and seven metabolites in rat, pig and human plasma by U(H)PLC–MS

A U(H)PLC–MS/MS method is described for the analysis of acetaminophen and its sulphate, glucuronide, glutathione, cysteinyl and N-acetylcysteinyl metabolites in plasma using stable isotope-labeled internal standards. P-Aminophenol glucuronide and 3-methoxyacetaminophen were monitored and semi-quantified using external standards. The assay takes 7.5 min/sample, requires only 5 μl of plasma and involves minimal sample preparation. The method was validated for rat plasma and cross validated for human and pig plasma and mouse serum. LOQ in plasma for these analytes were 0.44 μg/ml (APAP-C), 0.58 μg/ml (APAP-SG), 0.84 μg/ml (APAP-NAC), 2.75 μg/ml (APAP-S), 3.00 μg/ml (APAP-G) and 16 μg/ml (APAP). Application of the method is illustrated by the analysis of plasma following oral administration of APAP to male Han Wistar rats

A Decision Analysis Evaluating Screening for Kidney Cancer Using Focused Renal Ultrasound

Background Screening for renal cell carcinoma (RCC) has been identified as a key research priority; however, no randomised control trials have been performed. Value of information analysis can determine whether further research on this topic is of value. Objective To determine (1) whether current evidence suggests that screening is potentially cost effective and, if so, (2) in which age/sex groups, (3) identify evidence gaps, and (4) estimate the value of further research to close those gaps. Design, setting, and participants A decision model was developed evaluating screening in asymptomatic individuals in the UK. A National Health Service perspective was adopted. Intervention A single focused renal ultrasound scan compared with standard of care (no screening). Outcome measurements and statistical analysis Expected lifetime costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratio (ICER), discounted at 3.5% per annum. Results and limitations Given a prevalence of RCC of 0.34% (0.18–0.54%), screening 60-yr-old men resulted in an ICER of £18 092/QALY (€22 843/QALY). Given a prevalence of RCC of 0.16% (0.08–0.25%), screening 60-yr-old women resulted in an ICER of £37 327/QALY (€47 129/QALY). In the one-way sensitivity analysis, the ICER was <£30 000/QALY as long as the prevalence of RCC was ≥0.25% for men and ≥0.2% for women at age 60 yr. Given the willingness to pay a threshold of £30 000/QALY (€37 878/QALY), the population-expected values of perfect information were £194 million (€244 million) and £97 million (€123 million) for 60-yr-old men and women, respectively. The expected value of perfect parameter information suggests that the prevalence of RCC and stage shift associated with screening are key research priorities. Conclusions Current evidence suggests that one-off screening of 60-yr-old men is potentially cost effective and that further research into this topic would be of value to society. Patient summary Economic modelling suggests that screening 60-yr-old men for kidney cancer using ultrasound may be a good use of resources and that further research on this topic should be performed