Seeing through the Effects of Crustal Assimilation to Assess the Source Composition beneath the Southern Lesser Antilles Arc

Assessing the impact of crustal assimilation on the composition of oceanic arc lavas is important if source composition is to be correctly interpreted. This is particularly the case in the Lesser Antilles where lavas encompass a very large range in radiogenic isotope compositions. Here we present new 176Hf/177Hf and trace element data for a suite of samples from St Lucia in the southern Lesser Antilles arc where assimilation of sediments located within the arc crust has been shown to influence significantly Sr–Nd–Pb isotope compositions. We show that a high rate of assimilation (r = 0·8) of sediment is responsible for the co-variation of Th/Th*, La/Sm, 87Sr/86Sr, 206/207/208Pb/204Pb, 143Nd/144Nd and 176Hf/177Hf towards extreme ‘continental’ compositions. Lavas that escaped sediment assimilation have a typical oceanic arc signature and provide the best indication of mantle source characteristics beneath St Lucia. They display similar Ba/Th, La/Sm and Nd isotopic compositions to lavas further north in the arc, but with slightly more radiogenic Sr and Pb. Addition of less than 2% of local bulk subducting sediment, or less than 3·5% of sediment partial melt or fluid, to the mantle wedge can explain these compositions; these estimates are similar to those previously proposed for the northern arc. After correction for the effects of sediment assimilation, the St Lucia lavas have only slightly more radiogenic Pb and Sr isotope signatures compared with the northern islands; this can be attributed to differences in the isotopic composition of the local subducting sediment rather than to greater sediment input, as has been previously proposed. Comparison of St Lucia with the other southern Lesser Antilles islands suggests that similar mantle source compositions exist beneath Martinique, St Vincent and perhaps Bequia, whereas a more ‘continental’ source might characterize Ile de Caille, Kick ’em Jenny and Grenada

Repeated sprints: an independent not dependent variable

The ability to repeatedly perform sprints has traditionally been viewed as a key performance measure in team sports, and the relationship between repeated-sprint ability (RSA) and performance has been explored extensively. However, when reviewing the repeated-sprint profile of team-sports match play it appears that the occurrence of repeated-sprint bouts is sparse, indicating that RSA is not as important to performance as commonly believed. Repeated sprints are, however, a potent and time-efficient training strategy, effective in developing acceleration, speed, explosive leg power, aerobic power, and high-intensity-running performance—all of which are crucial to team-sport performance. As such, we propose that repeated-sprint exercise in team sports should be viewed as an independent variable (eg, a means of developing fitness) as opposed to a dependent variable (eg, a means of assessing fitness/performance)

Participant recruitment to FiCTION, a primary dental care trial – survey of facilitators and barriers

Objective To identify reasons behind a lower than expected participant recruitment rate within the FiCTION trial, a multi-centre paediatric primary dental care randomised controlled trial (RCT). Subjects (materials) and methods An online survey, based on a previously published tool, consisting of both quantitative and qualitative responses, completed by staff in dental practices recruiting to FiCTION. Ratings from quantitative responses were aggregated to give overall scores for factors related to participant recruitment. Qualitative responses were independently grouped into themes. Results Thirty-nine anonymous responses were received. Main facilitators related to the support received from the central research team and importance of the research question. The main barriers related to low child eligibility rates and the integration of trial processes within routine workloads. Conclusions These findings have directed strategies for enhancing participant recruitment at existing practices and informed recruitment of further practices. The results help provide a profile of the features required of practices to successfully screen and recruit participants. Future trials in this setting should consider the level of interest in the research question within practices, and ensure trial processes are as streamlined as possible. Research teams should actively support practices with participant recruitment and maintain enthusiasm among the entire practice team

The Holographic Dual of 2+1 Dimensional QFTs with N=1 SUSY and Massive Fundamental Flavours

The Maldacena Nastase solution is generalised to include massive fundamental matter through the addition of a flavour profile. This gives a holographic dual to N=1 SYM-CS with massive fundamental matter with a singularity free IR. We study this solution in some detail confirming confinement and asymptotic freedom. A recently proposed solution generating technique is then applied which results in a new type-IIA supergravity solution. In a certain limit the geometry of this solution is asymptotically AdS_4X Y, where Y is the metric at the base of the Bryant-Salamon G_2 cone, which has topology S^3XS^3.Comment: 31 pages plus appendices, 6 figures. v3: Typos corrected, version to appear in JHE

Phase I study of TP300 in patients with advanced solid tumors with pharmacokinetic, pharmacogenetic and pharmacodynamic analyses

Background: A Phase I dose escalation first in man study assessed maximum tolerated dose (MTD), dose-limiting toxicity (DLT) and recommended Phase II dose of TP300, a water soluble prodrug of the Topo-1 inhibitor TP3076, and active metabolite, TP3011. <p/>Methods: Eligible patients with refractory advanced solid tumors, adequate performance status, haematologic, renal, and hepatic function. TP300 was given as a 1-hour i.v. infusion 3-weekly and pharmacokinetic (PK) profiles of TP300, TP3076 and TP3011 were analysed. Polymorphisms in CYP2D6, AOX1 and UGT1A1 were studied and DNA strand-breaks measured in peripheral blood mononuclear cells (PBMCs). <p/>Results: 32 patients received TP300 at 1, 2, 4, 6, 8, 10, 12 mg/m2. MTD was 10 mg/m2; DLTs at 12 (2/4 patients) and 10 mg/m2 (3/12) included thrombocytopenia and febrile neutropenia; diarrhea was uncommon. Six patients (five had received irinotecan), had stable disease for 1.5-5 months. TP3076 showed dose proportionality in AUC and Cmax from 1--10 mg/m2. Genetic polymorphisms had no apparent influence on exposure. DNA strand-breaks were detected after TP300 infusion. <p/>Conclusions: TP300 had predictable hematologic toxicity, and diarrhea was uncommon. AUC at MTD is substantially greater than for SN38. TP3076 and TP3011 are equi-potent with SN38, suggesting a PK advantage

Comparison and relative utility of inequality measurements: as applied to Scotland’s child dental health

This study compared and assessed the utility of tests of inequality on a series of very large population caries datasets. National cross-sectional caries datasets for Scotland’s 5-year-olds in 1993/94 (n = 5,078); 1995/96 (n = 6,240); 1997/98 (n = 6,584); 1999/00 (n = 6,781); 2002/03 (n = 9,747); 2003/04 (n = 10,956); 2005/06 (n = 10,945) and 2007/08 (n = 12,067) were obtained. Outcomes were based on the d3mft metric (i.e. the number of decayed, missing and filled teeth). An area-based deprivation category (DepCat) measured the subjects’ socioeconomic status (SES). Simple absolute and relative inequality, Odds Ratios and the Significant Caries Index (SIC) as advocated by the World Health Organization were calculated. The measures of complex inequality applied to data were: the Slope Index of Inequality (absolute) and a variety of relative inequality tests i.e. Gini coefficient; Relative Index of Inequality; concentration curve; Koolman and Doorslaer’s transformed Concentration Index; Receiver Operator Curve and Population Attributable Risk (PAR). Additional tests used were plots of SIC deciles (SIC10) and a Scottish Caries Inequality Metric (SCIM10). Over the period, mean d3mft improved from 3.1(95%CI 3.0–3.2) to 1.9(95%CI 1.8–1.9) and d3mft = 0% from 41.1(95%CI 39.8–42.3) to 58.3(95%CI 57.8–59.7). Absolute simple and complex inequality decreased. Relative simple and complex inequality remained comparatively stable. Our results support the use of the SII and RII to measure complex absolute and relative SES inequalities alongside additional tests of complex relative inequality such as PAR and Koolman and Doorslaer’s transformed CI. The latter two have clear interpretations which may influence policy makers. Specialised dental metrics (i.e. SIC, SIC10 and SCIM10) permit the exploration of other important inequalities not determined by SES, and could be applied to many other types of disease where ranking of morbidity is possible e.g. obesity. More generally, the approaches described may be applied to study patterns of health inequality affecting worldwide populations

Eyetracking Metrics in Young Onset Alzheimer’s Disease: A Window into Cognitive Visual Functions

Young onset Alzheimer’s disease (YOAD) is defined as symptom onset before the age of 65 years and is particularly associated with phenotypic heterogeneity. Atypical presentations, such as the clinic-radiological visual syndrome posterior cortical atrophy (PCA), often lead to delays in accurate diagnosis. Eyetracking has been used to demonstrate basic oculomotor impairments in individuals with dementia. In the present study, we aim to explore the relationship between eyetracking metrics and standard tests of visual cognition in individuals with YOAD. Fifty-seven participants were included: 36 individuals with YOAD (n =  26 typical AD; n =  10 PCA) and 21 age-matched healthy controls. Participants completed three eyetracking experiments: fixation, pro-saccade, and smooth pursuit tasks. Summary metrics were used as outcome measures and their predictive value explored looking at correlations with visuoperceptual and visuospatial metrics. Significant correlations between eyetracking metrics and standard visual cognitive estimates are reported. A machine-learning approach using a classification method based on the smooth pursuit raw eyetracking data discriminates with approximately 95% accuracy patients and controls in cross-validation tests. Results suggest that the eyetracking paradigms of a relatively simple and specific nature provide measures not only reflecting basic oculomotor characteristics but also predicting higher order visuospatial and visuoperceptual impairments. Eyetracking measures can represent extremely useful markers during the diagnostic phase and may be exploited as potential outcome measures for clinical trials

Evidence for Pervasive Adaptive Protein Evolution in Wild Mice

The relative contributions of neutral and adaptive substitutions to molecular evolution has been one of the most controversial issues in evolutionary biology for more than 40 years. The analysis of within-species nucleotide polymorphism and between-species divergence data supports a widespread role for adaptive protein evolution in certain taxa. For example, estimates of the proportion of adaptive amino acid substitutions (alpha) are 50% or more in enteric bacteria and Drosophila. In contrast, recent estimates of alpha for hominids have been at most 13%. Here, we estimate alpha for protein sequences of murid rodents based on nucleotide polymorphism data from multiple genes in a population of the house mouse subspecies Mus musculus castaneus, which inhabits the ancestral range of the Mus species complex and nucleotide divergence between M. m. castaneus and M. famulus or the rat. We estimate that 57% of amino acid substitutions in murids have been driven by positive selection. Hominids, therefore, are exceptional in having low apparent levels of adaptive protein evolution. The high frequency of adaptive amino acid substitutions in wild mice is consistent with their large effective population size, leading to effective natural selection at the molecular level. Effective natural selection also manifests itself as a paucity of effectively neutral nonsynonymous mutations in M. m. castaneus compared to humans

ApoE influences regional white-matter axonal density loss in Alzheimer's disease

Mechanisms underlying phenotypic heterogeneity in young onset Alzheimer disease (YOAD) are poorly understood. We used diffusion tensor imaging and neurite orientation dispersion and density imaging (NODDI) with tract-based spatial statistics to investigate apolipoprotein (APOE) ε4 modulation of white-matter damage in 37 patients with YOAD (22, 59% APOE ε4 positive) and 23 age-matched controls. Correlation between neurite density index (NDI) and neuropsychological performance was assessed in 4 white-matter regions of interest. White-matter disruption was more widespread in ε4+ individuals but more focal (posterior predominant) in the absence of an ε4 allele. NODDI metrics indicate fractional anisotropy changes are underpinned by combinations of axonal loss and morphological change. Regional NDI in parieto-occipital white matter correlated with visual object and spatial perception battery performance (right and left, both p = 0.02), and performance (nonverbal) intelligence (WASI matrices, right, p = 0.04). NODDI provides tissue-specific microstructural metrics of white-matter tract damage in YOAD, including NDI which correlates with focal cognitive deficits, and APOEε4 status is associated with different patterns of white-matter neurodegeneration

Field theory aspects of non-Abelian T-duality and N = 2 linear quivers

In this paper we propose a linear quiver with gauge groups of increasing rank as field theory dual to the AdS 5 background constructed by Sfetsos and Thompson through non-Abelian T-duality. The formalism to study 4d N = 2 SUSY CFTs developed by Gaiotto and Maldacena is essential for our proposal. We point out an interesting relation between (Hopf) Abelian and non-Abelian T-dual backgrounds that allows to see both backgrounds as different limits of a solution constructed by Maldacena and Núñez. This suggests different completions of the long quiver describing the CFT dual to the nonAbelian T-dual background that match different observables