Additive manufacturing using extra-terrestrial multi-component ceramic materials

Powder Bed Fusion (PBF) based Additive Manufacturing (AM) is a category of advanced manufacturing technologies that can fabricate three-dimensional assets directly from CAD data, on a successive layer-by-layer strategy by using thermal energy from a laser source, to irradiate and fuse particles on a powder bed. The aim of this research was to investigate the application of this advanced manufacturing technique to laser process ceramic multicomponent materials into 3D layered structures. These ceramic materials matched those found on the Lunar and/or Martian surface. These indigenous extra-terrestrial materials could potentially be used for manufacturing physical assets onsite (i.e. off World) on future planetary exploration missions and could cover a range of potential applications including infrastructure, radiation shielding, thermal storage, etc. JSC-1A Lunar and JSC-Mars-1A Martian soil simulants, mimicking the mineralogical and basic properties of these planetary indigenous materials were used for the purpose of this study and processed with commercially available laser additive manufacturing equipment. The results of the laser processing were investigated and quantified through mechanical hardness testing, optical and scanning electron microscopy (SEM) and energy dispersive x-ray spectroscopy (EDS). The research resulted in the identification of a range of parameters that resulted in the successful manufacture of three-dimensional components from Lunar and Martian ceramic multicomponent simulant materials. The feasibility of using thermal based additive manufacturing with multi-component ceramic materials has therefore been established which represents a potential solution to off-world bulk structure manufacture due to there being no requirement for additional materials and resources other than the manufacturing equipment to be shipped off-world

A concise and scalable strategy for the total synthesis of dictyodendrin B based on sequential C-H functionalization.

A sequential CH functionalization strategy for the synthesis of the marine alkaloid dictyodendrin B is reported. Our synthesis begins from commercially available 4-bromoindole and involves six direct functionalizations around the heteroarene core as part of a gram-scale strategy towards the natural product.We are grateful to AstraZeneca, Pfizer, and EPSRC (A.K.P., F.O. and R.H.S.) and the ERC and EPSRC for fellowships (M.J.G.).This is the author accepted manuscript. The final version is available from Wiley at http://onlinelibrary.wiley.com/doi/10.1002/anie.201500067/abstract

Rivastigmine for gait stability in patients with Parkinson's disease (ReSPonD): a randomised, double-blind, placebo-controlled, phase 2 trial

Background Falls are a frequent and serious complication of Parkinson's disease and are related partly to an underlying cholinergic deficit that contributes to gait and cognitive dysfunction in these patients. Gait dysfunction can lead to an increased variability of gait from one step to another, raising the likelihood of falls. In the ReSPonD trial we aimed to assess whether ameliorating this cholinergic deficit with the acetylcholinesterase inhibitor rivastigmine would reduce gait variability. Methods We did this randomised, double-blind, placebo-controlled, phase 2 trial at the North Bristol NHS Trust Hospital, Bristol, UK, in patients with Parkinson's disease recruited from community and hospital settings in the UK. We included patients who had fallen at least once in the year before enrolment, were able to walk 18 m without an aid, had no previous exposure to an acetylcholinesterase inhibitor, and did not have dementia. Our clinical trials unit randomly assigned (1:1) patients to oral rivastigmine or placebo capsules (both taken twice a day) using a computer-generated randomisation sequence and web-based allocation. Rivastigmine was uptitrated from 3 mg per day to the target dose of 12 mg per day over 12 weeks. Both the trial team and patients were masked to treatment allocation. Masking was achieved with matched placebo capsules and a dummy uptitration schedule. The primary endpoint was difference in step time variability between the two groups at 32 weeks, adjusted for baseline age, cognition, step time variability, and number of falls in the previous year. We measured step time variability with a triaxial accelerometer during an 18 m walking task in three conditions: normal walking, simple dual task with phonemic verbal fluency (walking while naming words beginning with a single letter), and complex dual task switching with phonemic verbal fluency (walking while naming words, alternating between two letters of the alphabet). Analysis was by modified intention to treat; we excluded from the primary analysis patients who withdrew, died, or did not attend the 32 week assessment. This trial is registered with ISRCTN, number 19880883. Findings Between Oct 4, 2012 and March 28, 2013, we enrolled 130 patients and randomly assigned 65 to the rivastigmine group and 65 to the placebo group. At week 32, compared with patients assigned to placebo (59 assessed), those assigned to rivastigmine (55 assessed) had improved step time variability for normal walking (ratio of geometric means 0·72, 95% CI 0·58–0·88; p=0·002) and the simple dual task (0·79; 0·62–0·99; p=0·045). Improvements in step time variability for the complex dual task did not differ between groups (0·81, 0·60–1·09; p=0·17). Gastrointestinal side-effects were more common in the rivastigmine group than in the placebo group (p<0·0001); 20 (31%) patients in the rivastigmine group versus three (5%) in the placebo group had nausea and 15 (17%) versus three (5%) had vomiting

Overcoming the barriers to implementing urban road user charging schemes

Urban road user charging offers the potential to achieve significant improvements in urban transport, but is notoriously difficult to implement. Cities need guidance on the range of factors to be considered in planning and implementing such schemes. This paper summarises the results of a 3 year programme which has collated evidence on the issues of most concern to cities. A state of the art report has provided evidence on 14 themes, ranging from objectives and design to implementation and evaluation. A set of 16 case studies has reviewed experience in design and implementation across Europe. The paper summarises their findings, provides references to more detailed information, presents the resulting policy recommendations to European, national and local government, and outlines the areas in which further research is needed

Plutonium coordination and redox chemistry with the CyMe4-BTPhen polydentate N-donor extractant ligand

Complexation of Pu(IV) with the actinide extractant CyMe4-BTPhen (2,9-bis(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-1,2,4-benzotriazin-3-yl)-1,10-phenanthroline) was followed by vis-NIR spectroscopy in acetonitrile solution. The solid-state structure of the crystallized product suggests that Pu(IV) is reduced to Pu(III) upon complexation. Analysis by DFT modeling is consistent with metal-based rather than ligand-based reduction

Feature Selection To Facilitate Surgical Planning From MRI Of Placenta Accreta Spectrum Disorder

Feature Selection Models provide a ranking of pathological MRI markers able to predict the outcome of Placenta Accreta Spectrum Disorder, which could be used to aid in clinical decision-making and improve maternal outcome. The potential being to reduce the workload of radiologists by establishing the most clinically relevant pathological MRI markers that predict outcome. Our results found three pathological markers to have the highest ranking to the outcomes with an average accuracy of 75% using a Random Forest Selection Model and Boruta algorithm

Epigenome-wide change and variation in DNA methylation in childhood:Trajectories from birth to late adolescence

DNA methylation (DNAm) is known to play a pivotal role in childhood health and development, but a comprehensive characterization of genome-wide DNAm trajectories across this age period is currently lacking. We have therefore performed a series of epigenome-wide association studies in 5019 blood samples collected at multiple time-points from birth to late adolescence from 2348 participants of two large independent cohorts. DNAm profiles of autosomal CpG sites (CpGs) were generated using the Illumina Infinium HumanMethylation450 BeadChip. Change over time was widespread, observed at over one-half (53%) of CpGs. In most cases, DNAm was decreasing (36% of CpGs). Inter-individual variation in linear trajectories was similarly widespread (27% of CpGs). Evidence for non-linear change and inter-individual variation in non-linear trajectories was somewhat less common (11 and 8% of CpGs, respectively). Very little inter-individual variation in change was explained by sex differences (0.4% of CpGs) even though sex-specific DNAm was observed at 5% of CpGs. DNAm trajectories were distributed non-randomly across the genome. For example, CpGs with decreasing DNAm were enriched in gene bodies and enhancers and were annotated to genes enriched in immune-developmental functions. In contrast, CpGs with increasing DNAm were enriched in promoter regions and annotated to genes enriched in neurodevelopmental functions. These findings depict a methylome undergoing widespread and often non-linear change throughout childhood. They support a developmental role for DNA methylation that extends beyond birth into late adolescence and has implications for understanding life-long health and disease. DNAm trajectories can be visualized at http://epidelta.mrcieu.ac.uk.</p

Epigenome-wide change and variation in DNA methylation in childhood:Trajectories from birth to late adolescence

DNA methylation (DNAm) is known to play a pivotal role in childhood health and development, but a comprehensive characterization of genome-wide DNAm trajectories across this age period is currently lacking. We have therefore performed a series of epigenome-wide association studies in 5019 blood samples collected at multiple time-points from birth to late adolescence from 2348 participants of two large independent cohorts. DNAm profiles of autosomal CpG sites (CpGs) were generated using the Illumina Infinium HumanMethylation450 BeadChip. Change over time was widespread, observed at over one-half (53%) of CpGs. In most cases, DNAm was decreasing (36% of CpGs). Inter-individual variation in linear trajectories was similarly widespread (27% of CpGs). Evidence for non-linear change and inter-individual variation in non-linear trajectories was somewhat less common (11 and 8% of CpGs, respectively). Very little inter-individual variation in change was explained by sex differences (0.4% of CpGs) even though sex-specific DNAm was observed at 5% of CpGs. DNAm trajectories were distributed non-randomly across the genome. For example, CpGs with decreasing DNAm were enriched in gene bodies and enhancers and were annotated to genes enriched in immune-developmental functions. In contrast, CpGs with increasing DNAm were enriched in promoter regions and annotated to genes enriched in neurodevelopmental functions. These findings depict a methylome undergoing widespread and often non-linear change throughout childhood. They support a developmental role for DNA methylation that extends beyond birth into late adolescence and has implications for understanding life-long health and disease. DNAm trajectories can be visualized at http://epidelta.mrcieu.ac.uk