938 research outputs found
A closed loop cryogenic environment pressure regulating system
Nonlinear closed loop control system to regulate the pressure in a cryogenic environment is described. System employs four position contactor with two control bands to react to the signals. Diagrams of element transfer function and required equipment are included
A panel analysis of UK industrial company failure
We examine the failure determinants for large quoted UK industrials using a panel data set
comprising 539 firms observed over the period 1988-93. The empirical design employs data
from company accounts and is based on Chamberlain’s conditional binomial logit model,
which allows for unobservable, firm-specific, time-invariant factors associated with failure
risk. We find a noticeable degree of heterogeneity across the sample companies. Our panel
results show that, after controlling for unobservables, lower liquidity measured by the quick
assets ratio, slower turnover proxied by the ratio of debtors turnover, and profitability were
linked to the higher risk of insolvency in the analysis period. The findings appear to support
the proposition that the current cash-flow considerations, rather than the future prospects of
the firm, determined company failures over the 1990s recession
Faecal haemoglobin can define risk of colorectal neoplasia at surveillance colonoscopy in patients at increased risk of colorectal cancer.
Links between topography, wind, deflation, lakes and dust: The case of the Bodélé Depression, Chad
The Bodélé Depression, Chad is the planet's largest single source of dust. Deflation from the Bodélé could be seen as a simple coincidence of two key prerequisites: strong surface winds and a large source of suitable sediment. But here we hypothesise that long term links between topography, winds, deflation and dust ensure the maintenance of the dust source such that these two apparently coincidental key ingredients are connected by land-atmosphere processes with topography acting as the overall controlling agent. We use a variety of observational and numerical techniques, including a regional climate model, to show that: 1) contemporary deflation from the Bodélé is delineated by topography and a surface wind stress maximum; 2) the Tibesti and Ennedi mountains play a key role in the generation of the erosive winds in the form of the Bodélé Low Level Jet (LLJ); 3) enhanced deflation from a stronger Bodélé LLJ during drier phases, for example, the Last Glacial Maximum, was probably sufficient to create the shallow lake in which diatoms lived during wetter phases, such as the Holocene pluvial. Winds may therefore have helped to create the depression in which erodible diatom material accumulated. Instead of a simple coincidence of nature, dust from the world's largest source may result from the operation of long term processes on paleo timescales which have led to ideal conditions for dust generation in the world's largest dust source. Similar processes plausibly operate in other dust hotspots in topographic depressions
Electrification of granular systems of identical insulators
Insulating particles can become highly electrified during powder handling,
volcanic eruptions, and the wind-blown transport of dust, sand, and snow.
Measurements in these granular systems have found that smaller particles
generally charge negatively, while larger particles charge positively. These
observations are puzzling, since particles in these systems are generally
chemically identical, and thus have no contact potential difference. We show
here that simple geometry leads to a net transfer of electrons from larger to
smaller particles, in agreement with these observations. We integrate this
charging mechanism into the first quantitative charging scheme for a granular
system of identical insulators, and show that its predictions are in agreement
with measurements. Our theory thus seems to provide an explanation for the
hitherto puzzling phenomenon of the size-dependent charging of granular systems
of identical insulators.Comment: 8 pages, 5 figures, published in Physical Review
Faecal haemoglobin concentration in adenoma, before and after polypectomy, approaches the ideal tumour marker
BACKGROUND: Polypectomy may be performed at colonoscopy and then subsequent surveillance undertaken. It is thought that faecal haemoglobin concentration (f-Hb), estimated by quantitative faecal immunochemical tests (FIT), might be a useful tumour marker. METHODS: Consecutive patients enrolled in colonoscopy surveillance were approached at two hospitals. A specimen for FIT was provided before colonoscopy and, ideally after 3 weeks, a second FIT sample from those who had polypectomy. A single FIT system (OC-Sensor io, Eiken Chemical Co., Ltd) was used to generate f-Hb. RESULTS: 1103 Patients were invited; 643 returned a FIT device (uptake: 58.3%). Four patients had known inflammatory bowel disease (IBD) and were excluded, leaving 639 (57.9%) with an age range of 25–90 years (median 64 years), 54.6% male. Of 593 patients who had a f-Hb result and completed colonoscopy, advanced neoplasia was found in 41 (6.9%); four colorectal cancer (CRC): 0.7% and 37 advanced adenoma (AA): 6.3%, and a further 127 (21.4%) had non-advanced adenoma (NAA). The median f-Hb was significantly greater in AA as compared to NAA; 6.0 versus 1.0 μg Hb/g faeces, p < 0.0001.134/164 (81.7%) of invited patients returned a second FIT device: 28 were patients with AA in whom median pre-polypectomy f-Hb was 19.2, falling to 3.5 μg Hb/g faeces post-polypectomy, p = 0.01, and 106 with NAA had median pre-polypectomy f-Hb 0.8 compared to 1.0 μg Hb/g faeces post-polypectomy, p = 0.96. CONCLUSIONS: Quantitative FIT could provide a good tumour marker in post-polypectomy surveillance, reduce colonoscopy requirements and minimise potential risk to patients
Thrombocytopenic, thromboembolic and haemorrhagic events following second dose with BNT162b2 and ChAdOx1: self-controlled case series analysis of the English national sentinel cohort
Thrombosis associated with thrombocytopenia was a matter of concern post first and second doses of BNT162b2 and ChAdOx1 COVID-19 vaccines. Therefore, it is important to investigate the risk of thrombocytopenic, thromboembolic and haemorrhagic events following a second dose of BNT162b2 and ChAdOx1 COVID-19 vaccines. We conducted a large-scale self-controlled case series analysis, using routine primary care data linked to hospital data, among 12.3 million individuals (16 years old and above) in England. We used the nationally representative Oxford-Royal College of General Practitioners (RCGP) sentinel network database with baseline and risk periods between 8th December 2020 and 11th June 2022. We included individuals who received two vaccine (primary) doses of the BNT162b2 mRNA (Pfizer-BioNTech) and two vaccine doses of ChAdOx1 nCoV-19 (Oxford-AstraZeneca) vaccines in our analyses. We carried out a self-controlled case series (SCCS) analysis for each outcome using a conditional Poisson regression model with an offset for the length of risk period. We reported the incidence rate ratios (IRRs) and 95% confidence intervals (CI) of thrombocytopenic, thromboembolic (including arterial and venous events) and haemorrhagic events, in the period of 0-27 days after receiving a second dose of BNT162b2 or ChAdOx1 vaccines compared to the baseline period (14 or more days prior to first dose, 28 or more days after the second dose and the time between 28 or more days after the first and 14 or more days prior to the second dose). We adjusted for a range of potential confounders, including age, sex, comorbidities and deprivation. Between December 8, 2020 and February 11, 2022, 6,306,306 individuals were vaccinated with two doses of BNT162b2 and 6,046,785 individuals were vaccinated with two doses of ChAdOx1. Compared to the baseline, our analysis show no increased risk of venous thromboembolic events (VTE) for both BNT162b2 (IRR 0.71, 95% CI: 0.65-0.770) and ChAdOx1 (IRR 0.91, 95% CI: 0.84-0.98); and similarly there was no increased risk for cerebral venous sinus thrombosis (CVST) for both BNT162b2 (IRR 0.87, 95% CI: 0.41-1.85) and ChAdOx1 (IRR 1.73, 95% CI: 0.82-3.68). We additionally report no difference in IRR for pulmonary embolus, and deep vein thrombosis, thrombocytopenia, including idiopathic thrombocytopenic purpura (ITP), and haemorrhagic events post second dose for both BNT162b2. Reassuringly, we found no associations between increased risk of thrombocytopenic, thromboembolic and haemorrhagic events post vaccination with second dose for either of these vaccines. Data and Connectivity: COVID-19 Vaccines Pharmacovigilance study
Obesity challenges the hepatoprotective function of the integrated stress response to asparaginase exposure in mice
Obesity increases risk for liver toxicity by the anti-leukemic agent asparaginase, but the mechanism is unknown. Asparaginase activates the integrated stress response (ISR) via sensing amino acid depletion by the eukaryotic initiation factor 2 (eIF2) kinase GCN2. The goal of this work was to discern the impact of obesity, alone versus alongside genetic disruption of the ISR, on mechanisms of liver protection during chronic asparaginase exposure in mice. Following diet-induced obesity, biochemical analysis of livers revealed that asparaginase provoked hepatic steatosis that coincided with activation of another eIF2 kinase PKR-like endoplasmic reticulum kinase (PERK), a major ISR transducer to ER stress. Genetic loss of Gcn2 intensified hepatic PERK activation to asparaginase, yet surprisingly, mRNA levels of key ISR gene targets such as Atf5 and Trib3 failed to increase. Instead, mechanistic target of rapamycin complex 1 (mTORC1) signal transduction was unleashed, and this coincided with liver dysfunction reflected by a failure to maintain hydrogen sulfide production or apolipoprotein B100 (ApoB100) expression. In contrast, obese mice lacking hepatic activating transcription factor 4 (Atf4) showed an exaggerated ISR and greater loss of endogenous hydrogen sulfide but normal inhibition of mTORC1 and maintenance of ApoB100 during asparaginase exposure. In both genetic mouse models, expression and phosphorylation of Sestrin2, an ATF4 gene target, was increased by asparaginase, suggesting mTORC1 inhibition during asparaginase exposure is not driven via eIF2-ATF4-Sestrin2. In conclusion, obesity promotes a maladaptive ISR during asparaginase exposure. GCN2 functions to repress mTORC1 activity and maintain ApoB100 protein levels independently of Atf4 expression, whereas hydrogen sulfide production is promoted via GCN2-ATF4 pathway
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