Anisotropy studies around the galactic centre at EeV energies with the Auger Observatory

Data from the Pierre Auger Observatory are analyzed to search for anisotropies near the direction of the Galactic Centre at EeV energies. The exposure of the surface array in this part of the sky is already significantly larger than that of the fore-runner experiments. Our results do not support previous findings of localized excesses in the AGASA and SUGAR data. We set an upper bound on a point-like flux of cosmic rays arriving from the Galactic Centre which excludes several scenarios predicting sources of EeV neutrons from Sagittarius $A$. Also the events detected simultaneously by the surface and fluorescence detectors (the `hybrid' data set), which have better pointing accuracy but are less numerous than those of the surface array alone, do not show any significant localized excess from this direction.Comment: Matches published versio

Axial slicing versus bivalving in the pathological examination of pancreatoduodenectomy specimens (APOLLO): a multicentre randomized controlled trial

Background: In pancreatoduodenectomy specimens, dissection method may affect the assessment of primary tumour origin (i.e. pancreatic, distal bile duct or ampullary adenocarcinoma), which is primarily determined macroscopically. This is the first study to prospectively compare the two commonly used techniques, i.e. axial slicing and bivalving. Methods: In four centres, a randomized controlled trial was performed in specimens of patients with a suspected (pre)malignant tumour in the pancreatic head. Primary outcome measure was the level of certainty (scale 0–100) regarding tumour origin by four independent gastrointestinal pathologists based on macroscopic assessment. Secondary outcomes were inter-observer agreement and R1 rate. Results: In total, 128 pancreatoduodenectomy specimens were randomized. The level of certainty in determining the primary tumour origin did not differ between axial slicing and bivalving (mean score 72 [sd 13] vs. 68 [sd 16], p = 0.21), nor did inter-observer agreement, both being moderate (kappa 0.45 vs. 0.47). In pancreatic cancer specimens, R1 rate (60% vs. 55%, p = 0.71) and the number of harvested lymph nodes (median 16 vs. 17, p = 0.58) were similar. Conclusion: This study demonstrated no differences in determining the tumour origin between axial slicing and bivalving. Both techniques performed similarly regarding inter-observer agreement, R1 rate, and lymph node harvest

Non-AIDS defining cancers in the D:A:D Study-time trends and predictors of survival : a cohort study

BACKGROUND:Non-AIDS defining cancers (NADC) are an important cause of morbidity and mortality in HIV-positive individuals. Using data from a large international cohort of HIV-positive individuals, we described the incidence of NADC from 2004-2010, and described subsequent mortality and predictors of these.METHODS:Individuals were followed from 1st January 2004/enrolment in study, until the earliest of a new NADC, 1st February 2010, death or six months after the patient's last visit. Incidence rates were estimated for each year of follow-up, overall and stratified by gender, age and mode of HIV acquisition. Cumulative risk of mortality following NADC diagnosis was summarised using Kaplan-Meier methods, with follow-up for these analyses from the date of NADC diagnosis until the patient's death, 1st February 2010 or 6 months after the patient's last visit. Factors associated with mortality following NADC diagnosis were identified using multivariable Cox proportional hazards regression.RESULTS:Over 176,775 person-years (PY), 880 (2.1%) patients developed a new NADC (incidence: 4.98/1000PY [95% confidence interval 4.65, 5.31]). Over a third of these patients (327, 37.2%) had died by 1st February 2010. Time trends for lung cancer, anal cancer and Hodgkin's lymphoma were broadly consistent. Kaplan-Meier cumulative mortality estimates at 1, 3 and 5 years after NADC diagnosis were 28.2% [95% CI 25.1-31.2], 42.0% [38.2-45.8] and 47.3% [42.4-52.2], respectively. Significant predictors of poorer survival after diagnosis of NADC were lung cancer (compared to other cancer types), male gender, non-white ethnicity, and smoking status. Later year of diagnosis and higher CD4 count at NADC diagnosis were associated with improved survival. The incidence of NADC remained stable over the period 2004-2010 in this large observational cohort.CONCLUSIONS:The prognosis after diagnosis of NADC, in particular lung cancer and disseminated cancer, is poor but has improved somewhat over time. Modifiable risk factors, such as smoking and low CD4 counts, were associated with mortality following a diagnosis of NADC

Low levels of sarin affect the EEG in marmoset monkeys: A pilot study

The main purpose of this pilot study was to estimate the lowest observable adverse effect level (LOAEL) for the electroencephalogram (EEG) upon long-term, low-level exposure of vehicle-pretreated and pyridostigmine-pretreated marmoset monkeys to sarin vapour. This is the C·t value (t = 5 h) of exposure at which the EEG becomes significantly different from that resulting from air exposure of the same animals. The LOAELs for effects on the EEG in vehicle- and pyridostigmine-pretreated marmosets appeared to be 0.2 and 0.1 mg min m -3, respectively. Comparatively, the latter LOAEL values are at least an order of magnitude lower than the previously established LOAEL for miosis and only 2-5 times higher than the lowest observable effect level (LOEL) of bound sarin in blood. The second aim of the study was to analyse the EEG of the same marmosets again during a 5-h exposure to air 1 year after exposure to sarin vapour. All the marmosets still demonstrated significant (P < 0.05) EEG differences. In most vehicle-pretreated marmosets the energy (μV2) per EEG band was higher than that observed 1 year earlier, which might indicate that neurons had become more sensitive to excitation. This phenomenon was less pronounced in pyridostigmine-pretreated animals. Visual examination of the EEG records revealed clear bursts of alpha frequencies (ca. 9 Hz), resembling sleep-spindles, that were present more frequently in both groups of exposed marmosets than in naive animals. These late changes in spindle oscillation might be the result of changes in the cholinergic system due to exposure to sarin vapour 1 year previously. In conclusion, EEG abnormalities persisting for more than 1 year may occur in humans during long-term (5 h) exposure to subclinical levels of sarin that are not detectable by the currently fielded alarm systems. Copyright © 2004 John Wiley & Sons, Ltd

Long-term, low-level exposure of guinea pigs and marmosets to sarin vapor in air: Lowest observable effect level

Realistic scenarios for low-level exposure to nerve agents will often involve exposures over several hours to extremely low doses of agent. In order to expose animals to the lowest controllable concentrations of agent and to increase exposure times until a lowest observable effect level (LOEL) becomes measurable, a validated system was developed for exposing conscious animals to 0.05-1.0 μg/m3 (8-160 ppt) of sarin and other nerve agents. Based on cold trapping of sarin from the exposure air, the concentration could be measured semicontinuously, at 4-min time intervals by means of gas chromatography. We found that the LOEL upon a 5-h whole body exposure of guinea pigs and marmosets to sarin vapor corresponds with the measurement of an internal dose by means of fluoride-induced regeneration of sarin from phosphylated binding sites in plasma, mostly BuChE. For guinea pigs the LOEL was observed at Ct = 0.010 ± 0.002 mg/min/m3, whereas a Ct of 0.04 ± 0.01 mg/min/m3 was established for the LOEL in marmosets. These levels are several orders of magnitude lower than those based on classical measurement of depressed cholinesterase activities. At low exposure levels of guinea pigs and marmosets (≤1 μg/m3), a reasonable linearity was observed between exposure dose and internal dose. The data were addressed in the light of the recently recommended occupational exposure limits to sarin for workers without respiratory protection, which suggests that the exposure limits should be reconsidered if the slightest inhibition of cholinesterases should be prevented. © 2003 Elsevier Science (USA). All rights reserved