The use of linear motor technology to increase capacity in conventional railway systems

PhD ThesisWheel/rail adhesion is an important constraint on the design and operation of conventional railways. The research question considered for this thesis is whether linear motor technology can improve the performance of railway systems by reducing the dependence of tractive and braking effort on the available wheel/rail adhesion. The two principal contributions of the research are an analysis of the influence of several different linear motor technologies on the capacity of conventional railways, and the development of a new design concept for train braking (named LEMUR – Linear Electromagnetic Machine Using Rails). Multi-train simulation of three different railway networks was used to investigate the capacity benefits and energy consumption of the LEMUR concept, along with four other existing or proposed implementations of linear induction motor technology with the running rail used as the secondary component of the motor. A model of each network was built using OpenTrack software, and Monte Carlo simulation with pseudorandom distributions of initial delays to train services was carried out to compare train movements under the influence of the delays typically encountered during day-to-day operation. An indication of the improvements in railway capacity possible with different linear motor technology options was then derived from these simulations. The results of the experiments indicate that the LEMUR concept provided the greatest increase in capacity and the lowest energy consumption of the five linear motor technology options tested. Although the limitations of the study do introduce some uncertainty into the precise values of capacity and energy consumption obtained, the experimental methods were considered sufficiently robust for this conclusion to remain valid. The most promising application in the study was suburban passenger services that are part of busy mixed-traffic networks. Here, the capacity benefits of the LEMUR concept appear to show sufficient promise to justify further development and application

The regulation of copper stress response genes in the Polychaete Nereis diversicolor during prolonged extreme copper contamination

Polychaetes are frequented in toxicological studies, one reason being that some members occupy shallow burrows in sediments and are maximally exposed to the contaminants that accumulate within them. We have been studying one population of the polychaete Nereis (Hediste) diversicolor exhibiting inheritable tolerance to extreme copper contamination in estuarine sediment. Using transcriptome sequencing data we have identified a suite of genes with putative roles in metal detoxification and tolerance, and measured their regulation. Copper tolerant individuals display significantly different gene expression profiles compared to animals from a nearby population living without remarkable copper levels. Gene transcripts encoding principle copper homeostasis proteins including membrane copper ion transporters, copper ion chaperones and putative metallothionein-like proteins were significantly more abundant in tolerant animals occupying contaminated sediment. In contrast, those encoding antioxidants and cellular repair pathways were unchanged. Nontolerant animals living in contaminated sediment showed no difference in copper homeostasis-related gene expression but did have significantly elevated levels of mRNAs encoding Glutathione Peroxidase enzymes. This study represents the first use of functional genomics to investigate the copper tolerance trait in this species and provides insight into the mechanism used by these individuals to survive and flourish in conditions which are lethal to their conspecifics

Ramsløg og tyttebær skal erstatte zink til smågrise

Introducerende artikel omkring MAFFRA projektets baggrund, formål og indhold

Sedimentology and stratigraphy of the Kellaways Sand Member (Lower Callovian), Burythorpe, North Yorkshire, UK

In the Burythorpe area of the Howardian Hills, located on the northern margin of the Market Weighton High, the Callovian succession is represented only by Lower Callovian sediments. These belong to the Kellaways Sand Member (Kellaways Formation), up to 12 m thick, but thinning southwards to 5 m. This contrasts with the more complete Callovian succession (Osgodby Formation) on the Yorkshire coast (Cleveland Basin) which is up to 32.5 m thick. At Burythorpe Quarry the Kellaways Sand Member has yielded palynomorphs and ammonites confirming an Early Callovian (Koenigi Zone) age with depositional hiatuses above and below. The sequence consists of a yellow-white, poorly cemented, fine-to medium grained, unimodal uncemented sand (moulding sand) with sparse grey clay beds and laminae, in marked contrast to the broadly coeval Red Cliff Rock Member (Osgodby Formation) of the Cleveland Basin. The depositional environment is interpreted as a tidally influenced shallow sea on the margin of the Market Weighton High, in a shallow sub-tidal regime, similar to the sub-tidal sand-mud lithofacies in the Heligoland region of the present-day North Sea. Winnowing of the sand in highly mobile substrate resulted in a unimodal grain size, lack of impurities, and sparse shelly- and ichnofaunas. However, during quieter water phases, grey clay laminae were deposited at the base of channels, allowing colonization of the substrate by burrowing ichnofauna and deposition of palynomorphs. Sparse, calcite-cemented tabular beds with a benthic shelly fauna, ammonites, Planolites burrows and mudstone rip-up clasts are interpreted as the deposits of periodic storm events. The marked local variation in thickness of the Kellaways Sand Member in the Howardian Hills is probably due to synsedimentary east–west-trending faulting related to the Flamborough Fault Zone

Effectiveness and safety of vedolizumab in inflammatory bowel disease patients aged 60 and over: an observational multicenter UK experience.

BACKGROUND: The GEMINI trials established the efficacy of vedolizumab in moderate-to-severe inflammatory bowel disease (IBD) and demonstrated a favorable safety profile, suggesting it may be advantageous in older patients at greater risk of treatment-related complications. However, there is a paucity of data exploring the outcomes of vedolizumab in this group. Our objective was to determine the clinical effectiveness and safety of vedolizumab in older IBD patients within a real-world multicenter UK cohort. METHODS: A retrospective review of electronic records across 6 UK hospitals was undertaken to evaluate the clinical effectiveness and safety outcomes of vedolizumab in IBD patients aged ≥60 at start of therapy. Rates of clinical response, remission and corticosteroid-free remission were assessed at weeks 14 and 52, using validated clinical indices, and were compared to historical controls from real-world vedolizumab-treated cohorts unstratified by age. RESULTS: Of 74 patients aged 60 years or above (median 66 years), 48 were included in our effectiveness analysis (29 ulcerative colitis, 19 Crohn's disease). Rates of clinical response, remission and corticosteroid-free remission at week 14 were 64%, 48% and 30%, respectively. By week 52, the rates of clinical response, remission, and corticosteroid-free remission were 52%, 38%, and 32%, respectively. Six (8%) patients experienced adverse effects. Effectiveness and safety outcomes were comparable to those of age-unstratified vedolizumab-treated cohorts. CONCLUSION: Our 1-year outcome data suggests that vedolizumab is safe and effective in older IBD patients and broadly comparable to cohorts unselected by age

A Scientific Name for Pacific Oysters

WOS:000447083800041International audienc

Jumping on the Bandwagon: Differentiation and Security Defection during Conflict

When confronted with mass uprisings, governments deploy their security forces for crowd control or repression. However, sometimes security agencies choose to side with the opposition movement. Recent work shows that “fragmentation” contributes to defection: fragmenting the security forces into parallel units leads to oversight problems and grievances among soldiers, which raises the risk of members of the security forces defecting to the opposition movement. However, I argue that the effect on defection is strongly moderated by the circumstances under which states choose to fragment their military: fragmentation for the purpose of security specialization, called “differentiation,” even decreases its risk. Employing Bayesian multilevel modeling, the findings corroborate this distinction. The study contributes to the fundamental discussion on civil–military relations, shedding light on why some conflict situations see security defections while others do not. Understanding this phenomenon is a pivotal element to explaining how conflicts develop, escalate, and end

Interleukin 6 increases production of cytokines by colonic innate lymphoid cells in mice and patients with chronic intestinal inflammation

Background & Aims: Innate lymphoid cells (ILCs) are a heterogeneous group of mucosal inflammatory cells that participate in chronic intestinal inflammation. We investigated the role of interleukin 6 (IL6) in inducing activation of ILCs in mice and in human beings with chronic intestinal inflammation. Methods: ILCs were isolated from colons of Tbx21-/- × Rag2-/- mice (TRUC), which develop colitis; patients with inflammatory bowel disease (IBD); and patients without colon inflammation (controls). ILCs were characterized by flow cytometry; cytokine production was measured by enzyme-linked immunosorbent assay and cytokine bead arrays. Mice were given intraperitoneal injections of depleting (CD4, CD90), neutralizing (IL6), or control antibodies. Isolated colon tissues were analyzed by histology, explant organ culture, and cell culture. Bacterial DNA was extracted from mouse fecal samples to assess the intestinal microbiota. Results: IL17A- and IL22-producing, natural cytotoxicity receptor-negative, ILC3 were the major subset of ILCs detected in colons of TRUC mice. Combinations of IL23 and IL1α induced production of cytokines by these cells, which increased further after administration of IL6. Antibodies against IL6 reduced colitis in TRUC mice without significantly affecting the structure of their intestinal microbiota. Addition of IL6 increased production of IL17A, IL22, and interferon-γ by human intestinal CD3-negative, IL7-receptor-positive cells, in a dose-dependent manner. Conclusions: IL6 contributes to activation of colonic natural cytotoxicity receptor-negative, CD4-negative, ILC3s in mice with chronic intestinal inflammation (TRUC mice) by increasing IL23- and IL1α-induced production of IL17A and IL22. This pathway might be targeted to treat patients with IBD because IL6, which is highly produced in colonic tissue by some IBD patients, also increased the production of IL17A, IL22, and interferon-γ by cultured human colon CD3-negative, IL7-receptor-positive cells

Rucaparib maintenance treatment for recurrent ovarian carcinoma after response to platinum therapy (ARIEL3): a randomised, double-blind, placebo-controlled, phase 3 trial

Background: Rucaparib, a poly(ADP-ribose) polymerase inhibitor, has anticancer activity in recurrent ovarian carcinoma harbouring a BRCA mutation or high percentage of genome-wide loss of heterozygosity. In this trial we assessed rucaparib versus placebo after response to second-line or later platinum-based chemotherapy in patients with high-grade, recurrent, platinum-sensitive ovarian carcinoma. Methods: In this randomised, double-blind, placebo-controlled, phase 3 trial, we recruited patients from 87 hospitals and cancer centres across 11 countries. Eligible patients were aged 18 years or older, had a platinum-sensitive, high-grade serous or endometrioid ovarian, primary peritoneal, or fallopian tube carcinoma, had received at least two previous platinum-based chemotherapy regimens, had achieved complete or partial response to their last platinum-based regimen, had a cancer antigen 125 concentration of less than the upper limit of normal, had a performance status of 0–1, and had adequate organ function. Patients were ineligible if they had symptomatic or untreated central nervous system metastases, had received anticancer therapy 14 days or fewer before starting the study, or had received previous treatment with a poly(ADP-ribose) polymerase inhibitor. We randomly allocated patients 2:1 to receive oral rucaparib 600 mg twice daily or placebo in 28 day cycles using a computer-generated sequence (block size of six, stratified by homologous recombination repair gene mutation status, progression-free interval after the penultimate platinum-based regimen, and best response to the most recent platinum-based regimen). Patients, investigators, site staff, assessors, and the funder were masked to assignments. The primary outcome was investigator-assessed progression-free survival evaluated with use of an ordered step-down procedure for three nested cohorts: patients with BRCA mutations (carcinoma associated with deleterious germline or somatic BRCA mutations), patients with homologous recombination deficiencies (BRCA mutant or BRCA wild-type and high loss of heterozygosity), and the intention-to-treat population, assessed at screening and every 12 weeks thereafter. This trial is registered with ClinicalTrials.gov, number NCT01968213; enrolment is complete. Findings: Between April 7, 2014, and July 19, 2016, we randomly allocated 564 patients: 375 (66%) to rucaparib and 189 (34%) to placebo. Median progression-free survival in patients with a BRCA-mutant carcinoma was 16·6 months (95% CI 13·4–22·9; 130 [35%] patients) in the rucaparib group versus 5·4 months (3·4–6·7; 66 [35%] patients) in the placebo group (hazard ratio 0·23 [95% CI 0·16–0·34]; p<0·0001). In patients with a homologous recombination deficient carcinoma (236 [63%] vs 118 [62%]), it was 13·6 months (10·9–16·2) versus 5·4 months (5·1–5·6; 0·32 [0·24–0·42]; p<0·0001). In the intention-to-treat population, it was 10·8 months (8·3–11·4) versus 5·4 months (5·3–5·5; 0·36 [0·30–0·45]; p<0·0001). Treatment-emergent adverse events of grade 3 or higher in the safety population (372 [99%] patients in the rucaparib group vs 189 [100%] in the placebo group) were reported in 209 (56%) patients in the rucaparib group versus 28 (15%) in the placebo group, the most common of which were anaemia or decreased haemoglobin concentration (70 [19%] vs one [1%]) and increased alanine or aspartate aminotransferase concentration (39 [10%] vs none). Interpretation: Across all primary analysis groups, rucaparib significantly improved progression-free survival in patients with platinum-sensitive ovarian cancer who had achieved a response to platinum-based chemotherapy. ARIEL3 provides further evidence that use of a poly(ADP-ribose) polymerase inhibitor in the maintenance treatment setting versus placebo could be considered a new standard of care for women with platinum-sensitive ovarian cancer following a complete or partial response to second-line or later platinum-based chemotherapy. Funding: Clovis Oncology