Improved methods for high-precision Pb-Pb dating of extra-terrestrial materials

Dating meteoritic materials by the Pb–Pb isochron method depends on constructing linear arrays typically defined by mixtures of initial and radiogenic Pb after the removal of terrestrial contaminant Pb. The method also depends on minimizing the amount of laboratory Pb blank added to the sample during processing and analyses. With the aim to analyze smaller sample sizes and decrease processing times, we have devised a new method for the construction of isochrons using the stepwise dissolution of meteoritic materials that better defines reduced amounts of Pb blank, reduces the risk of random anomalous Pb contamination, and increases sample throughput. Samples are processed in a PFA Teflon™ pipette tip fitted with a frit inside a heated, sealed chamber that can be manually over-pressured to expel reagents directly into a PFA Teflon™ vial below. With four independent chambers, three samples can be processed simultaneously with a fourth position to assess the Pb contribution of the combined blank and spike for each step. The matched blank-spike Pb for each step provides a specific blank estimate for each step that ensures a more accurate correction for non-sample Pb and, therefore, reduces the uncertainty on each analysis. We assess the performance of this new method by reporting the results of dating a fragment of a chondrule from the well-characterized CBa chondrite Gujba and compare these results with previously published data for this meteorite. The improvements reduce the minimum sample sizes that can be successfully dated by the Pb–Pb method, an important development for size-limited materials such as small chondrules and samples returned from space missions

Morphology, adipocyte size, and fatty acid analysis of dairy cattle digital cushions, and the effect of body condition score and age

The digital cushion is an essential part of maintaining a healthy foot, working to dissipate foot strike and body weight forces and lameness from claw horn disruption lesions. Despite the importance of the digital cushion, little is known about the basic anatomy, adipocyte morphology, and fatty acid composition in relation to age, limb position, and body condition score. In total, 60 claws (from 17 cows) were selected and collected from a herd, ensuring that body condition score data and computed micro-tomography were known for each animal. Digital cushion tissue underwent histological staining combined with stereology, systematic random sampling, and cell morphology analysis, in addition to lipid extraction followed by fatty acid analysis. The results describe digital cushion architecture and adipocyte sizes. Adipocyte size was similar across all 4 claws (distal left lateral and medial and distal right lateral and medial) and across the ages (aged 2–7 yr); however, animals with body condition score of 3.00 or more at slaughter had a significantly increased cell size in comparison to those with a score of less than 2.50. Of 37 fatty acid methyl esters identified, 5 differed between either the body condition score or different age groups. C10:0 capric acid, C14:0 myristic acid, C15:0 pentadecanoic acid, and C20:0 arachidic acid percentages were all lesser in lower body condition score cows, whereas C22:1n-9 erucic acid measurements were lesser in younger cows. Saturated fatty acid, monounsaturated fatty acid, and polyunsaturated fatty acid percentages were not altered in the different claws, ages, or body condition score groups. Triglyceride quantities did not differ for claw position or age but had decreased quantities in lower body condition score animals. Digital cushion anatomy, cellular morphology, and fatty acid composition have been described in general and also in animals with differing ages, body condition scores, and in the differing claws. Understanding fat deposition, mobilization, and composition are essential in not only understanding the roles that the digital cushion plays but also in preventing disorders and maintaining cattle health and welfare

'I'm sure we made it a better study…': Experiences of adults with intellectual disabilities and parent carers of patient and public involvement in a health research study.

Patient and public involvement is considered integral to health research in the United Kingdom; however, studies documenting the involvement of adults with intellectual disabilities and parent carers in health research studies are scarce. Through group interviews, this study explored the perspectives and experiences of a group of adults with intellectual disabilities and a group of parent carers about their collaborative/participatory involvement in a 3-year study which explored the effectiveness of annual health checks for adults with intellectual disabilities. Thematic analysis identified five key themes consistent across both groups; authenticity of participation, working together, generating new outcome measures, dissemination of findings and involvement in future research. Although reported anecdotally rather than originating from the analysis, increased self-confidence is also discussed. The groups' unique perspectives led to insights not previously considered by the research team which led to important recommendations to inform healthcare practice

Statistical HOmogeneous Cluster SpectroscopY (SHOCSY): an optimized statistical approach for clustering of ¹H NMR spectral data to reduce interference and enhance robust biomarkers selection.

We propose a novel statistical approach to improve the reliability of (1)H NMR spectral analysis in complex metabolic studies. The Statistical HOmogeneous Cluster SpectroscopY (SHOCSY) algorithm aims to reduce the variation within biological classes by selecting subsets of homogeneous (1)H NMR spectra that contain specific spectroscopic metabolic signatures related to each biological class in a study. In SHOCSY, we used a clustering method to categorize the whole data set into a number of clusters of samples with each cluster showing a similar spectral feature and hence biochemical composition, and we then used an enrichment test to identify the associations between the clusters and the biological classes in the data set. We evaluated the performance of the SHOCSY algorithm using a simulated (1)H NMR data set to emulate renal tubule toxicity and further exemplified this method with a (1)H NMR spectroscopic study of hydrazine-induced liver toxicity study in rats. The SHOCSY algorithm improved the predictive ability of the orthogonal partial least-squares discriminatory analysis (OPLS-DA) model through the use of "truly" representative samples in each biological class (i.e., homogeneous subsets). This method ensures that the analyses are no longer confounded by idiosyncratic responders and thus improves the reliability of biomarker extraction. SHOCSY is a useful tool for removing irrelevant variation that interfere with the interpretation and predictive ability of models and has widespread applicability to other spectroscopic data, as well as other "omics" type of data

CAR-T cell. the long and winding road to solid tumors

Adoptive cell therapy of solid tumors with reprogrammed T cells can be considered the "next generation" of cancer hallmarks. CAR-T cells fail to be as effective as in liquid tumors for the inability to reach and survive in the microenvironment surrounding the neoplastic foci. The intricate net of cross-interactions occurring between tumor components, stromal and immune cells leads to an ineffective anergic status favoring the evasion from the host's defenses. Our goal is hereby to trace the road imposed by solid tumors to CAR-T cells, highlighting pitfalls and strategies to be developed and refined to possibly overcome these hurdles

POPPIE : protocol for a randomised controlled pilot trial of continuity of midwifery care for women at increased risk of preterm birth

© 2019 The Author(s). Background: High rates of preterm births remain a UK public health concern. Preterm birth is a major determinant of adverse infant and longer-term outcomes, including survival, quality of life, psychosocial effects on the family and health care costs. We aim to test whether a model of care combining continuity of midwife care with rapid referral to a specialist obstetric clinic throughout pregnancy, intrapartum and the postpartum period is feasible and improves experience and outcomes for women at increased risk of preterm birth. Methods: This pilot, hybrid, type 2 randomised controlled implementation trial will recruit 350 pregnant women at increased risk of preterm birth to a midwifery continuity of care intervention or standard care. The intervention will be provided from recruitment (antenatal), labour, birth and the postnatal period, in hospital and community settings and in collaboration with specialist obstetric clinic care, when required. Standard care will be the current maternity care provision by NHS midwives and obstetricians at the study site. Participants will be followed up until 6-8 weeks postpartum. The composite primary outcome is the appropriate initiation of any specified interventions related to the prevention and/or management of preterm labour and birth. Secondary outcomes are related to: recruitment and attrition rates; implementation; acceptability to women, health care professionals and stakeholders; health in pregnancy and other complications; intrapartum outcomes; maternal and neonatal postnatal outcomes; psycho-social health; quality of care; women's experiences and health economic analysis. The trial has 80% power to detect a 15% increase in the rate of appropriate interventions (40 to 55%). The analysis will be by 'intention to treat' analysis. Discussion: Little is known about the underlying reasons why and how models of midwifery continuity of care are associated with fewer preterm births, better maternal and infant outcomes and more positive experiences; nor how these models of care can be implemented successfully in the health services. This will be the first study to provide direct evidence regarding the effectiveness, implementation and evaluation of a midwifery continuity of care model and rapid access to specialist obstetric services for women at increased risk of preterm birth. Trial registration: ISRCTN37733900. Retrospectively registered on 21 August 2017

Panorganismal metabolic response modeling of an experimental Echinostoma caproni infection in the mouse.

Published versio