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Multi-layered composite electrodes of high power Li4Ti5O12 and high capacity SnO2 for smart lithium ion storage
No full textDiscrete layering of high power Li4Ti5O12 and high capacity SnO2 in a through-thickness multi-layered composite electrode was achieved using a layer-by-layer spray printing approach in order to explore new capacity-power combinations for lithium ion based electrochemical energy storage. Electrochemical behavior of multi-layered electrodes was optimized as a function of the thickness of the discrete SnO2 layer, in the range 2 to 6 µm, interleaved between two layers of low volume expansion Li4Ti5O12. Three discrete layers of 2 µm SnO2 were then interleaved evenly between Li4Ti5O12 layers to produce a “layer cake” negative electrode cross-section that offered remarkable rate capability when coupled with a spray printed LiFePO4 positive electrode in a lithium ion battery arrangement. The multi-layered negative electrode was also coupled with a spray printed activated carbon positive electrode in a lithium ion capacitor configuration, providing significant improvements in energy density. The double-sided fabrication of the multi-layer electrode over a 20 × 20 cm2 current collector area suggested a possible hybrid electrochemical device that combines attributes of high capacity lithium ion batteries and high power lithium ion capacitors
Reporting quality of trial protocols improved for non-regulated interventions but not regulated interventions: a repeated cross-sectional study
No full textObjectives
To investigate the adherence of randomised controlled trial (RCT) protocols evaluating non-regulated interventions (including dietary interventions, surgical procedures, behavioural and lifestyle interventions, and exercise programmes) in comparison with regulated interventions to the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) 2013 Statement.
Methods
We conducted a repeated cross-sectional investigation in a random sample of RCT protocols approved in 2012 (n = 257) or 2016 (n = 292) by research ethics committees in Switzerland, Germany, or Canada. We investigated the proportion of accurately reported SPIRIT checklist items in protocols of trials with non-regulated as compared to regulated interventions.
Results
Overall, 131 (24%) of trial protocols tested non-regulated interventions. In 2012, the median proportion of SPIRIT items reported in these protocols (59%, interquartile range [IQR], 53%-69%) was lower than in protocols with regulated interventions (median, 74%, IQR, 66%-80%). In 2016, the reporting quality of protocols with non-regulated interventions (median, 75%, IQR, 62%-83%) improved to the level of regulated intervention protocols, which had not changed on average.
Conclusions
Reporting of RCT protocols evaluating non-regulated interventions improved between 2012 and 2016, although remained suboptimal. SPIRIT recommendations need to be further endorsed by researchers, ethics committees, funding agencies, and journals to optimize reporting of RCT protocols
The TAZRP speed process
No full textIn (Ann. Probab. 39 (4) (2011) 1205–1242) Amir, Angel and Valkó studied a multi-type version of the totally asymmetric simple exclusion process (TASEP) and introduced the TASEP speed process, which allowed them to answer delicate questions about the joint distribution of the speed of several second-class particles in the TASEP rarefaction fan. In this paper we introduce the analogue of the TASEP speed process for the totally asymmetric zero-range process (TAZRP), and use it to obtain new results on the joint distribution of the speed of several second-class particles in the TAZRP with a reservoir. These is a close link from the speed process to questions about stationary distributions of multi-type versions of the TAZRP; for example we are able to give a precise description of the contents of a single site in equilibrium for a multi-type TAZRP with continuous labels
Metabolic consequences for mice lacking Endosialin: LC–MS/MS-based metabolic phenotyping of serum from C56Bl/6J Control and CD248 knock‐out mice
No full textIntroduction
The Endosialin/CD248/TEM1 protein is expressed in adipose tissue and its expression increases with obesity. Recently, genetic deletion of CD248 has been shown to protect mice against atherosclerosis on a high fat diet.
Objectives
We investigated the effect of high fat diet feeding on visceral fat pads and circulating lipid profiles in CD248 knockout mice compared to controls.
Methods
From 10 weeks old, CD248−/− and +/+ mice were fed either chow (normal) diet or a high fat diet for 13 weeks. After 13 weeks the metabolic profiles and relative quantities of circulating lipid species were assessed using ultra high performance liquid chromatography-quadrupole time-of flight mass spectrometry (UHPLC–MS) with high resolution accurate mass (HRAM) capability.
Results
We demonstrate a specific reduction in the size of the perirenal fat pad in CD248−/− mice compared to CD248+/+, despite similar food intake. More strikingly, we identify significant, diet-dependent differences in the serum metabolic phenotypes of CD248 null compared to age and sex-matched wildtype control mice. Generalised protection from HFD-induced lipid accumulation was observed in CD248 null mice compared to wildtype, with particular reduction noted in the lysophosphatidylcholines, phosphatidylcholines, cholesterol and carnitine.
Conclusions
Overall these results show a clear and protective metabolic consequence of CD248 deletion in mice, implicating CD248 in lipid metabolism or trafficking and opening new avenues for further investigation using anti-CD248 targeting agents
"The challenges made me stronger": What contributes to young people's resilience in Ethiopia?
No full textThis working paper explores the meanings and experiences of resilience, and its gender dimensions, among a cohort of Ethiopian children exposed to poverty and adversity across the early life course. It asks why some girls and some boys seem to fare well as they transition to adulthood, despite the challenges and obstacles they had faced, while others do less well.
Qualitative analysis revealed how children’s lives did not follow linear paths, and were easily derailed by unplanned events and shocks, including: climatic shocks, societal influences, school transitions and relations, household changes; and child health and social development. It also identifed significant resilience factors, including: supportive and facilitative relationships (especially elder siblings); enabling and protective systems and environments; government and NGO support; young people’s inner resources and pro-social skills; and second chances. A combination of well-timed, mutually reinforcing factors within holistic support systems, rather than a single factor, appeared to make the most difference.
This working paper and the accompanying policy brief are part of a set of eight working papers and eight policy briefs on gendered transitions into young adulthood in Ethiopia
Using electronic health records to inform trial feasibility in a rare autoimmune blistering skin disease in England
No full textBackground
Trials of novel agents are required to improve the care of patients with rare diseases, but trial feasibility may be uncertain due to concerns over insufficient patient numbers. We aimed to determine the size of the pool of potential participants in England 2015–2017 for trials in the autoimmune blistering skin disease bullous pemphigoid.
Methods
The size of the pool of potential participants was estimated using routinely collected healthcare data from linked primary care (Clinical Practice Research Datalink; CPRD) and secondary care (Hospital Episode Statistics; HES) databases. Thirteen consultant dermatologists were surveyed to determine the likelihood that a patient would be eligible for a trial based on the presence of cautions or contra-indications to prednisolone use. These criteria were applied to determine how they influenced the potential pool of participants.
Results
Extrapolated to the population of England, we would expect approximately 10,800 (point estimate 10,747; 95% CI 7191 to 17,239) new cases of bullous pemphigoid to be identified in a three-year period. For a future trial involving oral prednisolone (standard care), the application of cautions to its use as exclusion criteria would result in approximately 365 potential participants unlikely to be recruited, a further 5332 could be recruited with caution, and 5104 in whom recruitment is still possible. 11–17% of potential participants may have pre-existing dementia and require an alternative consent process.
Conclusions
Routinely collected electronic health records can be used to inform the feasibility of clinical trials in rare diseases, such as whether recruitment is feasible nationally and how long recruitment might take to meet recruitment targets. Future trials of bullous pemphigoid in England may use the data presented to inform trial design, including eligibility criteria and consent processes for enrolling people with dementia
Substituted aryl benzylamines as potent and selective inhibitors of 17β-hydroxysteroid dehydrogenase type 3
No full text17β-Hydroxysteroid dehydrogenase type 3 (17β-HSD3) is expressed at high levels in testes and seminal vesicles and is also present in prostate tissue and involved in gonadal and non-gonadal testosterone biosynthesis. The enzyme is membrane-bound and a crystal structure is not yet available. Selective aryl benzylamine-based inhibitors were designed and synthesized as potential agents for prostate cancer therapeutics through structure-based design, using a previously built homology model with docking studies. Potent, selective, low nanomolar IC50 17β-HSD3 inhibitors were discovered using N-(2-([2-(4-chlorophenoxy)phenylamino]methyl)phenyl)acetamide (1). The most potent compounds have IC50 values of approximately 75nM. Compound 29, N-[2-(1-Acetylpiperidin-4-ylamino)benzyl]-N-[2-(4-chlorophenoxy)phenyl]acetamide has an IC50 of 76nM and 30 N-(2-(1-[2-(4-chlorophenoxy)- phenylamino]ethyl)phenyl)acetamide has IC50 of 74nM. Racemic C-allyl derivative 26 (IC50 of 520nM) was easily formed from 1 in good yield and, to determine binding directionality, its enantiomers were separated by chiral chromatography. Absolute configuration was determined using single crystal X-ray crystallography. Only the S-(+)-enantiomer (32) was active with an IC50 of 370nM. Binding directionality was predictable through our in silico docking studies, giving confidence to our model. Importantly, all novel inhibitors are selective over the type 2 isozyme 17β-HSD2 and show <20% inhibition when tested at 10µM. Lead compounds from this series are worthy of further optimisation and development as inhibitors of testosterone production by 17β-HSD3 and inhibition of prostate cancer cell growth
On the Roman-Byzantine adoption of the stirrup once more: a new find from seventh-century Aphrodisias
No full textArchaeological evidence and the text of the Strategikon show that it was only in the late sixth century AD that the Roman-Byzantine military adopted the stirrup. It is now widely argued that the Avars, who settled in the Carpathian basin in the sixth century, played a key role in introducing iron stirrups to the Roman-Byzantine world. However, the evidence to support this assertion is limited. Although hundreds of stirrups have been found in Avar graves in the Carpathian basin, very few stirrups of sixth- or seventh-century date are known from the Roman-Byzantine empire - no more than seven - and only two of these are of definitively Avar type. The text of the Strategikon, sometimes argued to support this Avar source, can be interpreted differently, as indeed can the archaeological evidence. While the debate about the Roman-Byzantine adoption of the stirrup has focused mostly on finds from the Balkans, two early stirrups are known from Asia Minor, from Pergamon and Sardis. This paper presents a third, previously unpublished stirrup, from a seventh-century deposit at Aphrodisias in Caria; this is the first stirrup found in Asia Minor from a datable context. Here we present this find and its context, and use it to reconsider the model of solely Avar stirrup transmission that has dominated scholarship to date. So varied are the early stirrups that multiple sources of influence, Avar and other, and even a degree of experimentation, seem more likely to underpin the Roman-Byzantine adoption of this technology
Combined constraints on Majorana masses from neutrinoless double beta decay experiments
No full textCombined bounds on the Majorana neutrino mass for light and heavy neutrino exchange mechanisms are derived from current neutrinoless double beta decay (0νββ) search results for a variety of nuclear matrix element (NME) models. The approach requires self-consistency of a given model to predict NMEs across different isotopes. The derived bounds are notably stronger than those from any single experiment and show less model-to-model variation, highlighting the advantages of using multiple isotopes in such searches. Projections indicate that the combination of near-term experiments should be able to probe well into the inverted neutrino mass hierarchy region. A method to visually represent 0νββ experimental results is also suggested to more transparently compare across different isotopes and explicitly track model dependencies