121 research outputs found
Quantitation of ortho-cresyl phosphate adducts to butyrylcholinesterase in human serum by immunomagnetic-UHPLC-MS/MS
Tri-ortho-cresyl phosphate (ToCP) is an anti-wear, flame retardant additive used in industrial lubricants, hydraulic fluids and gasoline. The neurotoxic effects of ToCP arise fromthe liver-activatedmetabolite 2-(o-cresyl)-4H-1,3,2-benzodioxaphosphoran-2-one (cresyl saligenin phosphate or CBDP),which inhibits esterase enzymes including butyrylcholinesterase (BChE). Following BChE adduction, CBDP undergoes hydrolysis to formthe aged adduct ortho-cresyl phosphoserine (oCP-BChE), thus providing a biomarker of CBDP exposure. Previous studies have identified ToCP in aircraft cabin and cockpit air, but assessing human exposure has been hampered by the lack of a laboratory assay to confirm exposure. This work presents the development of an immunomagnetic- UHPLC-MS/MSmethod for the quantitation of unadducted BChE and the long-term CBDP biomarker, oCP-BChE, in human serum. Themethod has a reportable range from 2.0ng/ml to 150 ng/ml,which is consistent with the sensitivity ofmethods used to detect organophosphorus nerve agent protein adducts. The assay demonstrated high intraday and interday accuracy (≥85%) and precision (RSD≤ 15%) across the calibration range. The method was developed for future analyses of potential human exposure to CBDP. Analysis of human serum inhibited in vitro with CBDP demonstrated that the oCP-BChE adduct was stable for at least 72h at 4, 22 and 37 °C. Compared to a previously reported assay, this method requires 75% less sample volume, reduces analysis time by a factor of 20 and demonstrates a threefold improvement in sensitivity
The HST/ACS Coma Cluster Survey. II. Data Description and Source Catalogs
The Coma cluster was the target of a HST-ACS Treasury program designed for
deep imaging in the F475W and F814W passbands. Although our survey was
interrupted by the ACS instrument failure in 2007, the partially completed
survey still covers ~50% of the core high-density region in Coma. Observations
were performed for 25 fields that extend over a wide range of cluster-centric
radii (~1.75 Mpc) with a total coverage area of 274 arcmin^2. The majority of
the fields are located near the core region of Coma (19/25 pointings) with six
additional fields in the south-west region of the cluster. In this paper we
present reprocessed images and SExtractor source catalogs for our survey
fields, including a detailed description of the methodology used for object
detection and photometry, the subtraction of bright galaxies to measure faint
underlying objects, and the use of simulations to assess the photometric
accuracy and completeness of our catalogs. We also use simulations to perform
aperture corrections for the SExtractor Kron magnitudes based only on the
measured source flux and half-light radius. We have performed photometry for
~73,000 unique objects; one-half of our detections are brighter than the
10-sigma point-source detection limit at F814W=25.8 mag (AB). The slight
majority of objects (60%) are unresolved or only marginally resolved by ACS. We
estimate that Coma members are 5-10% of all source detections, which consist of
a large population of unresolved objects (primarily GCs but also UCDs) and a
wide variety of extended galaxies from a cD galaxy to dwarf LSB galaxies. The
red sequence of Coma member galaxies has a constant slope and dispersion across
9 magnitudes (-21<M_F814W<-13). The initial data release for the HST-ACS Coma
Treasury program was made available to the public in 2008 August. The images
and catalogs described in this study relate to our second data release.Comment: Accepted for publication in ApJS. A high-resolution version is
available at http://archdev.stsci.edu/pub/hlsp/coma/release2/PaperII.pd
Books in the News in Cromwellian England
This article offers detailed analysis of the patterns of book advertising in Marchamont Nedham’s government-sponsored newsbook, Mercurius Politicus. It contends that, for a brief period, Politicus was the nearest thing that the mid-seventeenth century had to a literary periodical and contests standard accounts that Politicus was only successful because government monopoly made it so. Instead I show that Politicus was instrumental in creating an image of the Commonwealth and Protectorate as a Republic of Letters; the cheap print of its small advertisements insisted that the publication of a book was an event, that London was a city of the book, and that its inhabitants might respond to the uncertainty of political revolution by eagerly imagining a future comprised of new books as yet unread
Association of acute toxic encephalopathy with litchi consumption in an outbreak in Muzaffarpur, India, 2014: a case-control study
Background Outbreaks of unexplained illness frequently remain under-investigated. In India, outbreaks of an acute
neurological illness with high mortality among children occur annually in Muzaffarpur, the country’s largest litchi
cultivation region. In 2014, we aimed to investigate the cause and risk factors for this illness.
Methods In this hospital-based surveillance and nested age-matched case-control study, we did laboratory
investigations to assess potential infectious and non-infectious causes of this acute neurological illness. Cases were
children aged 15 years or younger who were admitted to two hospitals in Muzaffarpur with new-onset seizures or
altered sensorium. Age-matched controls were residents of Muzaffarpur who were admitted to the same two hospitals
for a non-neurologic illness within seven days of the date of admission of the case. Clinical specimens (blood,
cerebrospinal fluid, and urine) and environmental specimens (litchis) were tested for evidence of infectious
pathogens, pesticides, toxic metals, and other non-infectious causes, including presence of hypoglycin A or
methylenecyclopropylglycine (MCPG), naturally-occurring fruit-based toxins that cause hypoglycaemia and metabolic
derangement. Matched and unmatched (controlling for age) bivariate analyses were done and risk factors for illness
were expressed as matched odds ratios and odds ratios (unmatched analyses).
Findings Between May 26, and July 17, 2014, 390 patients meeting the case definition were admitted to the two referral
hospitals in Muzaffarpur, of whom 122 (31%) died. On admission, 204 (62%) of 327 had blood glucose concentration
of 70 mg/dL or less. 104 cases were compared with 104 age-matched hospital controls. Litchi consumption (matched
odds ratio [mOR] 9·6 [95% CI 3·6 – 24]) and absence of an evening meal (2·2 [1·2–4·3]) in the 24 h preceding illness
onset were associated with illness. The absence of an evening meal significantly modified the effect of eating litchis
on illness (odds ratio [OR] 7·8 [95% CI 3·3–18·8], without evening meal; OR 3·6 [1·1–11·1] with an evening meal).
Tests for infectious agents and pesticides were negative. Metabolites of hypoglycin A, MCPG, or both were detected in
48 [66%] of 73 urine specimens from case-patients and none from 15 controls; 72 (90%) of 80 case-patient specimens
had abnormal plasma acylcarnitine profiles, consistent with severe disruption of fatty acid metabolism. In 36 litchi
arils tested from Muzaffarpur, hypoglycin A concentrations ranged from 12·4 μg/g to 152·0 μg/g and MCPG ranged
from 44·9 μg/g to 220·0 μg/g.
Interpretation Our investigation suggests an outbreak of acute encephalopathy in Muzaffarpur associated with both
hypoglycin A and MCPG toxicity. To prevent illness and reduce mortality in the region, we recommended minimising
litchi consumption, ensuring receipt of an evening meal and implementing rapid glucose correction for suspected
illness. A comprehensive investigative approach in Muzaffarpur led to timely public health recommendations,
underscoring the importance of using systematic methods in other unexplained illness outbreaks
A many-analysts approach to the relation between religiosity and well-being
The relation between religiosity and well-being is one of the most researched topics in the psychology of religion, yet the directionality and robustness of the effect remains debated. Here, we adopted a many-analysts approach to assess the robustness of this relation based on a new cross-cultural dataset (N=10,535 participants from 24 countries). We recruited 120 analysis teams to investigate (1) whether religious people self-report higher well-being, and (2) whether the relation between religiosity and self-reported well-being depends on perceived cultural norms of religion (i.e., whether it is considered normal and desirable to be religious in a given country). In a two-stage procedure, the teams first created an analysis plan and then executed their planned analysis on the data. For the first research question, all but 3 teams reported positive effect sizes with credible/confidence intervals excluding zero (median reported β=0.120). For the second research question, this was the case for 65% of the teams (median reported β=0.039). While most teams applied (multilevel) linear regression models, there was considerable variability in the choice of items used to construct the independent variables, the dependent variable, and the included covariates
A Many-analysts Approach to the Relation Between Religiosity and Well-being
The relation between religiosity and well-being is one of the most researched topics in the psychology of religion, yet the directionality and robustness of the effect remains debated. Here, we adopted a many-analysts approach to assess the robustness of this relation based on a new cross-cultural dataset (N = 10, 535 participants from 24 countries). We recruited 120 analysis teams to investigate (1) whether religious people self-report higher well-being, and (2) whether the relation between religiosity and self-reported well-being depends on perceived cultural norms of religion (i.e., whether it is considered normal and desirable to be religious in a given country). In a two-stage procedure, the teams first created an analysis plan and then executed their planned analysis on the data. For the first research question, all but 3 teams reported positive effect sizes with credible/confidence intervals excluding zero (median reported β = 0.120). For the second research question, this was the case for 65% of the teams (median reported β = 0.039). While most teams applied (multilevel) linear regression models, there was considerable variability in the choice of items used to construct the independent variables, the dependent variable, and the included covariates
The benefits and harms of intravenous thrombolysis with recombinant tissue plasminogen activator within 6 h of acute ischaemic stroke (the third international stroke trial [IST-3]): a randomised controlled trial
BACKGROUND: Thrombolysis is of net benefit in patients with acute ischaemic stroke, who are younger than 80 years of age and are treated within 4·5 h of onset. The third International Stroke Trial (IST-3) sought to determine whether a wider range of patients might benefit up to 6 h from stroke onset. METHODS: In this international, multicentre, randomised, open-treatment trial, patients were allocated to 0·9 mg/kg intravenous recombinant tissue plasminogen activator (rt-PA) or to control. The primary analysis was of the proportion of patients alive and independent, as defined by an Oxford Handicap Score (OHS) of 0-2 at 6 months. The study is registered, ISRCTN25765518. FINDINGS: 3035 patients were enrolled by 156 hospitals in 12 countries. All of these patients were included in the analyses (1515 in the rt-PA group vs 1520 in the control group), of whom 1617 (53%) were older than 80 years of age. At 6 months, 554 (37%) patients in the rt-PA group versus 534 (35%) in the control group were alive and independent (OHS 0-2; adjusted odds ratio [OR] 1·13, 95% CI 0·95-1·35, p=0·181; a non-significant absolute increase of 14/1000, 95% CI -20 to 48). An ordinal analysis showed a significant shift in OHS scores; common OR 1·27 (95% CI 1·10-1·47, p=0·001). Fatal or non-fatal symptomatic intracranial haemorrhage within 7 days occurred in 104 (7%) patients in the rt-PA group versus 16 (1%) in the control group (adjusted OR 6·94, 95% CI 4·07-11·8; absolute excess 58/1000, 95% CI 44-72). More deaths occurred within 7 days in the rt-PA group (163 [11%]) than in the control group (107 [7%], adjusted OR 1·60, 95% CI 1·22-2·08, p=0·001; absolute increase 37/1000, 95% CI 17-57), but between 7 days and 6 months there were fewer deaths in the rt-PA group than in the control group, so that by 6 months, similar numbers, in total, had died (408 [27%] in the rt-PA group vs 407 [27%] in the control group). INTERPRETATION: For the types of patient recruited in IST-3, despite the early hazards, thrombolysis within 6 h improved functional outcome. Benefit did not seem to be diminished in elderly patients. FUNDING: UK Medical Research Council, Health Foundation UK, Stroke Association UK, Research Council of Norway, Arbetsmarknadens Partners Forsakringsbolag (AFA) Insurances Sweden, Swedish Heart Lung Fund, The Foundation of Marianne and Marcus Wallenberg, Polish Ministry of Science and Education, the Australian Heart Foundation, Australian National Health and Medical Research Council (NHMRC), Swiss National Research Foundation, Swiss Heart Foundation, Assessorato alla Sanita, Regione dell'Umbria, Italy, and Danube University
The James Webb Space Telescope Mission
Twenty-six years ago a small committee report, building on earlier studies,
expounded a compelling and poetic vision for the future of astronomy, calling
for an infrared-optimized space telescope with an aperture of at least .
With the support of their governments in the US, Europe, and Canada, 20,000
people realized that vision as the James Webb Space Telescope. A
generation of astronomers will celebrate their accomplishments for the life of
the mission, potentially as long as 20 years, and beyond. This report and the
scientific discoveries that follow are extended thank-you notes to the 20,000
team members. The telescope is working perfectly, with much better image
quality than expected. In this and accompanying papers, we give a brief
history, describe the observatory, outline its objectives and current observing
program, and discuss the inventions and people who made it possible. We cite
detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space
Telescope Overview, 29 pages, 4 figure
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