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The OxEon team led the development of solid oxide electrolysis cell(SOEC) stacks to convert atmospheric CO2 to pure O2 for the Mars Perseverance Rover mission. The cathode material set was not redox tolerant, therefore a recycle loop was implemented to include reducing CO gas in the stack feed. Since then, OxEon has investigated a combination of materials and engineering solutions to improve redox tolerance of the cathode materials so that 100% dryCO2 (or steam without H2) could be fed directly into a stack without harm. The developed set of cathode materials exhibit remarkable robustness through extreme redox cycling and thermal cycling, as well as higher coking tolerance from preliminary testing. This enables simpler operation (no recycle) and prevents damage from unintended system changes, providing a new solution to operational challenges in SOEC systems. Steam redox tolerance was independently verified from collaboration with Pacific Northwest National Laboratory (PNNL).

In this work, strontium-free copper-doped nickelates, La2Ni1-xCuxO4 (x=0.1-0.3), were synthesized using solid state synthesis method and tested as potential oxygen electrodes in solid oxide electrolysis cells (SOEC). Similar to the parent compound, the Ruddlesden-Popper (RP) La2NiO4 oxide, the Cu-doped compositions were confirmed to crystallize with tetragonal crystal structure with I4/mmm space group. The electrochemical performance of La2Ni1-xCuxO4 electrodes was studied using Ni-YSZ electrode-supported button cells in SOEC mode and compared to the state-of-the-art (La0.6Sr0.4)0.95Co0.0.8O3-δ (LSCF)-doped ceria composite electrodes. Electrochemical tests were conducted at 750oC with the Ni-YSZ hydrogen electrode exposed to 50% steam in hydrogen. The polarization resistance of SOEC with the La2Ni0.8Cu0.2O4 (LNCuO-20) electrode was lower than that with LSCF. LNCuO-20 showed stable current density output over 800 hours tested, while cell with LSCF showed more degradation.

What effect does political instability in the form of a potential secession from a political union have on business formation? Using newly collected data on business creation, we show that entrepreneurial activity in Ireland in the late nineteenth century was much lower than Scotland, and this divergence fluctuated over time. Several factors may have contributed to this, but we argue that political uncertainty about the prospect of a devolved government in Ireland played a role. The effects were most acute in the North of Ireland, the region that was most concerned by potential changes.

What shapes and drives capital market development over the long run? In this paper, using the asset portfolios of UK life assurers, we examine the role of regulation, historical contingency, and political reactions to events on the long-run development of the UK capital market. Government response to events such as war, hegemony-secured peace, and the wider macroeconomic environment was the ultimate determinant of major changes in asset allocation since 1800. Furthermore, when we compare the UK with the United States, we find that regulation played a limited role in shaping the asset portfolios of the UK life assurance industry.

In the nineteenth century, the Liverpool Cotton Brokers' Association (CBA) coordinated the dramatic growth of Liverpool's raw cotton market. This article shows how the CBA achieved this through the development of a private-order institutional framework that improved information flows, introduced standardization and contracting regimes, and regulated market exchange platforms. These developments corresponded with significantly improved market coordination, which facilitated the growth of the largest raw cotton market in the world. The article's findings demonstrate and quantify the importance of nonstate actors in creating institutions of global exchange central to the first wave of globalization.

Background:\ud Carboplatin and paclitaxel administered every 3 weeks is standard-of-care first-line chemotherapy for epithelial ovarian cancer. The Japanese JGOG3016 trial showed a significant improvement in progression-free and overall survival with dose-dense weekly paclitaxel and 3-weekly carboplatin. In this study, we aimed to compare efficacy and safety of two dose-dense weekly regimens to standard 3-weekly chemotherapy in a predominantly European population with epithelial ovarian cancer.\ud Methods:\ud In this phase 3 trial, women with newly diagnosed International Federation of Gynecology and Obstetrics stage IC–IV epithelial ovarian cancer were randomly assigned to group 1 (carboplatin area under the curve [AUC]5 or AUC6 and 175 mg/m2 paclitaxel every 3 weeks), group 2 (carboplatin AUC5 or AUC6 every 3 weeks and 80 mg/m2 paclitaxel weekly), or group 3 (carboplatin AUC2 and 80 mg/m2 paclitaxel weekly). Written informed consent was provided by all women who entered the trial. The protocol had the appropriate national research ethics committee approval for the countries where the study was conducted. Patients entered the trial after immediate primary surgery, or before neoadjuvant chemotherapy with subsequent planned delayed primary surgery. The trial coprimary outcomes were progression-free survival and overall survival. Data analyses were done on an intention-to-treat basis, and were powered to detect a hazard ratio of 0·75 in progression-free survival. The main comparisons were between the control group (group 1) and each of the weekly research groups (groups 2 and 3).\ud Findings:\ud Between June 6, 2011, and Nov 28, 2014, 1566 women were randomly assigned to treatment. 72% (365), completed six protocol-defined treatment cycles in group 1, 60% (305) in group 2, and 63% (322) in group 3, although 90% (454), 89% (454), and 85% (437) completed six platinum-based chemotherapy cycles, respectively. Paclitaxel dose intensification was achieved with weekly treatment (median total paclitaxel dose 1010 mg/m2 in group 1; 1233 mg/m2 in group 2; 1274 mg/m2 in group 3). By February, 2017, 1018 (65%) patients had experienced disease progression. No significant progression-free survival increase was observed with either weekly regimen (restricted mean survival time 24·4 months [97·5% CI 23·0–26·0] in group 1, 24·9 months [24·0–25·9] in group 2, 25·3 months [23·9–26·9] in group 3; median progression-free survival 17·7 months [IQR 10·6–not reached] in group 1, 20·8 months [11·9–59·0] in group 2, 21·0 months [12·0–54·0] in group 3; log-rank p=0·35 for group 2 vs group 1; group 3 vs 1 p=0·51). Although grade 3 or 4 toxic effects increased with weekly treatment, these effects were predominantly uncomplicated. Febrile neutropenia and sensory neuropathy incidences were similar across groups.\ud Interpretation:\ud Weekly dose-dense chemotherapy can be delivered successfully as first-line treatment for epithelial ovarian cancer but does not significantly improve progression-free survival compared with standard 3-weekly chemotherapy in predominantly European populations.\ud Funding:\ud Cancer Research UK, Medical Research Council, Health Research Board in Ireland, Irish Cancer Society, Cancer Australia.

In this article, using new estimates of the size of the UK's capital market, we examine financial development and investor protection laws in Britain c.1900 to test the influential law and finance hypothesis. Our evidence suggests that there was not a close correlation between financial development and investor protection laws c.1900 and that the size of the UK's share market is a puzzle given the paucity of statutory investor protection. To illustrate that Britain was not unique in its approach to investor protection in this era, we examine investor protection laws across legal families c.1900.

Using a hand-collected dataset, we examine share trading activity over the period 1882 to 1920 for the North British and Mercantile Insurance Company, one of the largest UK companies of the time. Our main finding is that the steady flow of rentiers into the shareholding constituency of this company stymied share trading activity. Another important finding is that share trading still occurred during the closure of the Stock Exchange in 1914, but on a much-reduced scale. We also find that there was a substantial boom in share trading and in insurance stock prices after World War I.

This paper addresses three questions: (1) How severe were the episodes of banking instability experienced by the UK over the past two centuries? (2) What have been the macroeconomic indicators of UK banking instability? and (3) What have been the consequences of UK banking instability for the cost of credit? Using a unique dataset of bank share prices from 1830 to 2010 to assess the stability of the UK banking system, we find that banking instability has grown more severe since the 1970s. We also find that interest rates, inflation, lending growth, and equity prices are consistent macroeconomic indicators of UK banking instability over the long run. Furthermore, utilising a unique dataset of corporate-bond yields for the period 1860 to 2010, we find that there is a significant long-run relationship between banking instability and the credit-risk premium faced by businesses.

In this paper, using new estimates of the size of the UK’s capital market, we examine financial development and investor protection laws in Britain c.1900 to test the influential law and finance hypothesis. Our evidence suggests that there was not a close correlation between financial development and investor protection laws c.1900 and that the size of the UK’s share market is a puzzle given the paucity of statutory investor protection. To illustrate that Britain was not unique in its approach to investor protection in this era, we examine investor protection laws across legal families c.1900.

Prior literature provides conflicting evidence about the impact of speculation on gold futures returns, volatility, and the relationship between market fundamentals and prices. In this paper, we exploit trade volume information to determine the most appropriate family of factors to adopt when modelling gold futures. Using the Disaggregated Commitment of Traders report, we find that extreme levels of speculation are informative in that they signify a shift in the relative modelling accuracy of macroeconomic and latent factors. A simple composite prediction framework, incorporating the changing level of speculation, empirically demonstrates the uncovered phenomenon and offers improved predictive accuracy for gold futures prices. Furthermore, our findings are shown to be robust to alternative latent and macroeconomic model specifications.

Background Transrectal ultrasound-guided prostate biopsies are prone to detection errors. Multi-parametric MRI (MP-MRI) may improve the diagnostic pathway. Methods PROMIS is a prospective validating paired-cohort study that meets criteria for level 1 evidence in diagnostic test evaluation. PROMIS will investigate whether multi-parametric (MP)-MRI can discriminate between men with and without clinically-significant prostate cancer who are at risk prior to first biopsy. Up to 714 men will have MP-MRI (index), 10–12 core TRUS-biopsy (standard) and 5 mm transperineal template mapping (TPM) biopsies (reference). The conduct and reporting of each test will be blinded to the others. Results PROMIS will measure and compare sensitivity, specificity, and positive and negative predictive values of both MP-MRI and TRUS-biopsy against TPM biopsies. The MP-MRI results will be used to determine the proportion of men who could safely avoid biopsy without compromising detection of clinically-significant cancers. For the primary outcome, significant cancer on TPM is defined as Gleason grade >/= 4 + 3 and/or maximum cancer core length of ≥ 6 mm. PROMIS will also assess inter-observer variability among radiologists among other secondary outcomes. Cost-effectiveness of MP-MRI prior to biopsy will also be evaluated. Conclusions PROMIS will determine whether MP-MRI of the prostate prior to first biopsy improves the detection accuracy of clinically-significant cancer.

Some psychiatric diseases in children and young adults are thought to originate from adverse exposures during fetal life, including hypoxia and hypoxia/reoxygenation. The mechanism is not understood. Several authors have emphasised that the placenta is likely to play an important role as the key interface between mother and fetus. Here we have explored whether a first trimester human placenta or model barrier of primary human cytototrophoblasts might secrete factors, in response to hypoxia or hypoxia/reoxygenation, that could damage neurones. We find that the secretions in conditioned media caused an increase of [Ca2 +]i and mitochondrial free radicals and a decrease of dendritic lengths, branching complexity, spine density and synaptic activity in dissociated neurones from embryonic rat cerebral cortex. There was altered staining of glutamate and GABA receptors. We identify glutamate as an active factor within the conditioned media and demonstrate a specific release of glutamate from the placenta/cytotrophoblast barriers in vitro after hypoxia or hypoxia/reoxygenation. Injection of conditioned media into developing brains of P4 rats reduced the numerical density of parvalbumin-containing neurones in cortex, hippocampus and reticular nucleus, reduced immunostaining of glutamate receptors and altered cellular turnover. These results show that the placenta is able to release factors, in response to altered oxygen, that can damage developing neurones under experimental conditions.

Cationic host defence peptides (CHDP; also known as antimicrobial peptides) are key components of the immune response in the female reproductive tract. The role of the placental trophoblast in ovine host defence remains poorly understood. This study characterises expression of genes for cathelicidin and defensin peptides in primary ovine placental tissues, the ovine trophoblast cell line (AH-1) and in response to the TLR-4 ligand LPS, the abortifacient organism Waddlia chondrophila and 1alpha,25-dihydroxyvitamin D3. Using RT-PCR, expression of the CHDP SMAP-29, sBD-1 and sBD-2 was assessed in the AH-1 cell line in response to LPS, 1alpha,25-dihydroxyvitamin D3 exposure (a known stimulator of cathelicidin gene expression), or W. chondrophila infection. Expression of cathelicidin in the trophoblast compartment of the ovine placenta and in the ovine trophoblast cell line (AH-1) was also established. AH-1 cells did not upregulate expression of CHDP in response to LPS, but sBD-1 and sBD-2 expression was significantly increased in response to W. chondrophila infection. SMAP-29 expression was not altered by in vitro exposure to 1alpha,25-dihydroxyvitamin D3. This study demonstrates that the ovine trophoblast expresses cathelicidins, but does not upregulate expression of CHDP in response to LPS. Ovine trophoblasts are shown to differentially regulate expression of CHDP and lack a demonstrable vitamin D-mediated cathelicidin response.

Introduction Erythema nodosum is often associated with a distressing symptomatology, including painful subcutaneous nodules, polyarthropathy, and significant fatigue. Whilst it is a well-documented side-effect of estrogen therapy in females, we describe what we believe to be the first report in the literature of erythema nodosum as a result of estrogen therapy in a male. Case presentation A 64-year-old Afro-Caribbean man with locally advanced carcinoma of the prostate agreed to participate in a randomized controlled trial comparing estrogen patches with luteinizing hormone-releasing hormone analogs to achieve androgen deprivation, and was allocated to the group receiving estrogen patches. One month later he presented with tender lesions on his shins and painful swelling of his ankles, wrists, and left shoulder. This was followed by progressive severe fatigue that required hospital admission, where he was diagnosed with erythema nodosum by a rheumatologist. Two months after discontinuing the estrogen patches the erythema nodosum, and associated symptoms, had fully resolved, and to date he remains well with no further recurrence. Conclusion Trial results may establish transdermal estrogen as an alternative to luteinizing hormone-releasing hormone analogs in the management of prostate cancer, and has already been established as a therapy for male to female transsexuals. It is essential to record the toxicity profile of transdermal estrogen in men to ensure accurate safety information. This case report highlights a previously undocumented toxicity of estrogen therapy in men, of which oncologists, urologists, and endocrinologists need to be aware. Rheumatologists and dermatologists should add estrogen therapy to their differential diagnosis of men presenting with erythema nodosum.

In the last 15 years of the nineteenth century c.300 British brewers incorporated and floated securities on the stock market. Subsequently, in the 1900s, the industry suffered a long-lived hangover. In this article, we establish the stylised facts of this transformation and estimate the gains enjoyed by brewery investors during the boom as well as the losses suffered by investors during the bust of the 1900s. However, not all brewery equity shares suffered alike. We find that post-1900 performance correlates positively with capital-market discipline and good corporate governance and negatively with family control, but does not correlate with indebtedness.

This article examines the role of creditor protection in the development of the U.K. corporate bond market. This market grew rapidly in the late nineteenth century, but in the twentieth century it experienced a reversal, albeit with a short-lived post-1945 renaissance. Such was the extent of the reversal that the market from the 1970s onwards was smaller than it had been in 1870. We find that law does not explain the variation in the size of this market over time. Alternatively, our evidence suggests that inflation and taxation policies were major drivers of this market in the post-1945 era. Copyright © The Economic History Association 2013

A 200-ml., round-bottomed flask equipped with a magnetic stirring bar is charged with 11.6 g. (0.100 mole) of hexanoic acid (Note 1) and 10 ml. of carbon tetrachloride. After 46.9 g. (28.8 ml., 0.394 mole) of thionyl chloride (Note 2) is added to the solution, an efficient reflux condenser with an attached drying tube is fitted to the flask. The solution is stirred and heated with an oil bath at 65° for 30 minutes (Note 3). The flask is removed from the oil bath and cooled to room temperature. To the reaction mixture are added successively 21.4 g. (0.120 mole) of finely powdered N-bromosuccinimide (Note 4), 50 ml. of carbon tetrachloride, and 7 drops of 48% hydrogen bromide (Note 5). The flask is heated at 70° for 10 minutes (Note 6), before the temperature of the bath is increased to 85°, until the color of the reaction becomes light yellow (ca. 1.5 hours; (Note 7). The reaction mixture is cooled to room temperature, and the carbon tetrachloride and excess thionyl chloride are removed under reduced pressure (Note 8). The residue is suction filtered, the solid (Note 9) is washed several times with carbon tetrachloride (total 20 ml.) and the combined filtrate collected in a 50-ml. flask. The solvent is removed from the solution as before, and the residue is distilled into a dry ice-cooled receiver (short-path column), giving, after a small forerun, 16.1–17.1 g. (76–80%) of 2-bromohexanoyl chloride, b.p. 44– 47° (1.5 mm.) as a clear, slightly yellow oil, n 22 1.4707. This material is of sufficient purity for most synthetic purposes (Note 10). The yellow product (Note 11) is decolorized by dissolving it in an equal volume of carbon tetrachloride (ca. 12 ml.) and vigorously shaking the solution thus obtained with 1.5 ml. of freshly prepared aqueous 35% sodium thiosulfate. The two layers are completely separated after 5 minutes. The colorless bottom layer is drawn off into a 50-ml. Erlenmeyer flask. The top layer is extracted three times with 1.5 ml. of carbon tetrachloride. The combined carbon tetrachloride extracts are dried over 0.5 g. (Note 12) of anhydrous magnesium sulfate for 30 minutes. The solution is filtered into a 50-ml. anhydrous magnesium sulfate for 30 minutes. The solution is filtered into a 50-ml. distilling flask, and the magnesium sulfate is washed several times with carbon tetrachloride (total 5 ml.). The solvent is removed, and the colorless product is distilled as described above, affording 14.7–15.8 g. (69–74% overall, based on hexanoic acid; 88–92% for the decolorization step) of colorless 2-bromohexanoyl chloride, b.p. 45–47° (1.5 mm.), n 22 1.4706 (Note 13), d 24 1.4017 (Note 14) and (Note 15).

BACKGROUND Waddlia chondrophila (W. chondrophila) is an emerging abortifacient organism which has been identified in the placentae of humans and cattle. The organism is a member of the order Chlamydiales, and shares many similarities at the genome level and in growth studies with other well-characterised zoonotic chlamydial abortifacients, such as Chlamydia abortus (C. abortus). This study investigates the growth of the organism and its effects upon pro-inflammatory cytokine expression in a ruminant placental cell line which we have previously utilised in a model of C. abortus pathogenicity. METHODOLOGY/PRINCIPAL FINDINGS Using qPCR, fluorescent immunocytochemistry and electron microscopy, we characterised the infection and growth of W. chondrophila within the ovine trophoblast AH-1 cell line. Inclusions were visible from 6 h post-infection (p.i.) and exponential growth of the organism could be observed over a 60 h time-course, with significant levels of host cell lysis being observed only after 36 h p.i. Expression of CXCL8, TNF-α, IL-1α and IL-1β were determined 24 h p.i. A statistically significant response in the expression of CXCL8, TNF-α and IL-1β could be observed following active infection with W. chondrophila. However a significant increase in IL-1β expression was also observed following the exposure of cells to UV-killed organisms, indicating the stimulation of multiple innate recognition pathways. CONCLUSIONS/SIGNIFICANCE W. chondrophila infects and grows in the ruminant trophoblast AH-1 cell line exhibiting a complete chlamydial replicative cycle. Infection of the trophoblasts resulted in the expression of pro-inflammatory cytokines in a dose-dependent manner similar to that observed with C. abortus in previous studies, suggesting similarities in the pathogenesis of infection between the two organisms.

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