Radiocarbon ages, dose rates, water isotopic composition and hydrochemistry of samples from Komakuk Beach and Herschel Island

Terrestrial permafrost archives along the Yukon Coastal Plain (northwest Canada) have recorded landscape development and environmental change since the Late Wisconsinan at the interface of unglaciated Beringia (i.e. Komakuk Beach) and the northwestern limit of the Laurentide Ice Sheet (i.e. Herschel Island). The objective of this paper is to compare the late glacial and Holocene landscape development on both sides of the former ice margin based on permafrost sequences and ground ice. Analyses at these sites involved a multi-proxy approach including: sedimentology, cryostratigraphy, palaeoecology of ostracods, stable water isotopes in ground ice, hydrochemistry, and AMS radiocarbon and infrared stimulated luminescence (IRSL) dating. AMS and IRSL age determinations yielded full glacial ages at Komakuk Beach that is the northeastern limit of ice-free Beringia. Herschel Island to the east marks the Late Wisconsinan limit of the northwest Laurentide Ice Sheet and is composed of ice-thrust sediments containing plant detritus as young as 16.2 cal ka BP that might provide a maximum age on ice arrival. Late Wisconsinan ice wedges with sediment-rich fillings on Herschel Island are depleted in heavy oxygen isotopes (mean d18O of -29.1 per mil); this, together with low d-excess values, indicates colder-than-modern winter temperatures and probably reduced snow depths. Grain-size distribution and fossil ostracod assemblages indicate that deglaciation of the Herschel Island ice-thrust moraine was accompanied by alluvial, proluvial, and eolian sedimentation on the adjacent unglaciated Yukon Coastal Plain until ~11 cal ka BP during a period of low glacio-eustatic sea level. The late glacial-Holocene transition was marked by higher-than-modern summer temperatures leading to permafrost degradation that began no later than 11.2 cal ka BP and caused a regional thaw unconformity. Cryostructures and ice wedges were truncated while organic matter was incorporated and soluble ions were leached in the thaw zone. Thermokarst activity led to the formation of ice-wedge casts and deposition of thermokarst lake sediments. These were subsequently covered by rapidly accumulating peat during the early Holocene Thermal Maximum. A rising permafrost table, reduced peat accumulation, and extensive ice-wedge growth resulted from climate cooling starting in the middle Holocene until the late 20th century. The reconstruction of palaeolandscape dynamics on the Yukon Coastal Plain and the eastern Beringian edge contributes to unraveling the linkages between ice sheet, ocean, and permafrost that have existed since the Late Wisconsinan.

Development of a low cost portable fluorometry technology and quantification of cannabinoids in body fluids. Final report.

National Highway Traffic Safety Administration, Washington, D.C.

Effects of chronic exposure to low-level cadmium on renal tubular function and CYP2A6-mediated coumarin metabolism in healthy human subjects

Relationships between cadmium (Cd) body burden, kidney function and coumarin metabolism were investigated using two groups of 197 and 200 healthy Thais with men and women in nearly equal numbers. A mean age of one group was 30.5 years and it was 39.3 years for the other group. Of 397, 20 subjects (5%) excreted urine Cd between 1.4 mug/g and 3.8 mug/g creatinine and these subjects faced 10-15% increase in the probability of having abnormal urinary excretion of N-acetyl-beta-D-glucosaminidase (NAG-uria). The prevalence of NAG-uria varied with Cd body burden in a dose-dependent manner (chi(2) = 22, P < 0.008). Also NAG-nuria was one of the three kidney effect markers tested that showed the greatest strength of correlation with urine Cd in both men and women (r = 0.48 P < 0.001). In addition, urine Cd excretion of men and women showed a positive correlation (r = 0.46 to 0.54. P < 0.001) with urine 7-hydroxycoumarin (7-OHC) excretion which was used as a marker of liver cytochrome P450 2A6 (CYP2A6) enzyme activity. Urinary CA excretion accounted for 25% of the total variation in urine 7-OHC excretion (P < 0.001). These data suggest that Cd may increase the expression of CYP2A6 in liver, resulting in enhanced coumarin metabolism in subjects with high Cd body burden. (C) 2003 Elsevier Ireland Ltd. All rights reserved.

Urinary arsenic speciation and porphyrins in C57B1/6J mice chronically exposed to low doses of sodium arsenate

Arsenic has been classified as a human carcinogen based on epidemiological data however the mechanism of its carcinogenicity is still unclear. Urinary biomarkers for chronic arsenic exposure would be valuable as an early warning indicator for timely interventions. In this study, young female C57BI/6J mice were given drinking water containing 0, 100, 250 and 500 mug As-v/L as sodium arsenate ad libitum for 12 months. Urine was collected bimonthly for urinary arsenic methylation assay and porphyrin analysis. All detectable arsenic species showed strong linear correlation with administered dosage and the arsenic methylation patterns were similar in all three treatment groups. No significant changes of methylation patterns were observed over time for either the control or test groups. Urinary coproporphyrin III was significantly increased in the 8th month in 250 and 500 mug/L groups and remained significantly dose-related after 10 and 12 months. Coproporphyrin I also showed a significant dose-response relationship after 12 months. Our results confirm that urinary arsenic is a useful biomarker for internal dose. The alteration of porphyrin profile suggests that arsenic can affect the heme metabolism and this may occur prior to the onset of arsenic induced carcinogenesis. (C) 2004 Elsevier Ireland Ltd. All rights reserved.

Area-under-the-curve monitoring of prednisolone for dose optimization in a stable renal transplant population

Background: Renal transplant recipients were noted to appear cushingoid while on low doses of steroid as part of a triple therapy immunosuppression of cyclosporin A (CsA), prednisolone, and azathioprine. Methods: The study group comprised adult renal transplant recipients with stable graft function who had received their renal allograft a minimum of 1 year previously (43 studies undertaken in 22 men and 20 women) with median daily prednisone dose of 7 mg (range 3-10). The control group was healthy nontransplant subjects [median dose 10 mg (10-30)]. Prednisolone bioavailability was measured using a limited 6-hour area under the curve (AUC), with prednisolone measured using specific HPLC assay. Results: The median prednisolone AUC/mg dose for all transplant recipients was significantly greater than the control group by approximately 50% (316 nmol(.)h/L/mg prednisolone versus 218). AUC was significantly higher in female recipients (median 415 versus 297 for men) and in recipients receiving cyclospotin (348 versus 285). The highest AUC was in women on estrogen supplements who were receiving cyclosporin (median 595). A significantly higher proportion of patients on triple therapy had steroid side effects compared with those on steroid and azathioprine (17/27 versus 4/15), more women than men had side effects (14/16 versus 7/22), and the AUC/mg prednisone was greater in those with side effects than without (median 377 versus 288 nmol-h/L/mg). Discussion: The results are consistent with the hypothesis that CsA increases the bioavailability of prednisolone, most likely through inhibition of beta-glycoprotein. The increased exposure to steroid increased the side-effect profile of steroids in the majority of patients. Because the major contributor to AUC is the maximum postdose concentration, it may be possible to use single-point monitoring (2 hours postdose) for routine clinical studies.

Evidence for a non-antioxidant, dose-dependent role of alpha-lipoic acid in caspase-3 and ERK2 activation in endothelial cells

Endothelial cell apoptosis contributes to atherosclerosis and may be exacerbated by oxidative stress. Results from clinical trials using antioxidant supplementation are equivocal and could be enhanced by antioxidants with additional non-antioxidant properties such as a-lipoic acid and alpha-tocopherol. The aim of this study was to investigate the effects of these antioxidants on cytoprotective pathways and endothelial apoptosis. Endothelial cells were incubated with alpha-lipoic acid and alpha-tocopherol, alone or in combination, prior to incubation with H2O2 or staurosporine. alpha-lipoic acid pre-treatment alone increased caspase-3 activity in a dose-dependent manner. Both H2O2 and staurosporine increased DNA fragmentation and caspase-3 activity and pre-treatment of cells with a-lipoic acid and/or a-tocopherol failed to prevent stress-induced apoptosis. Neither antioxidant treatments nor apoptotic inducers alone altered expressions of BcI-2, Bax, HSP70 or pERK1/2 or pJNK. alpha-lipoic decreased pERK2 in staurosporine-treated cells in a dose-dependent manner. These findings indicate that pre-incubation with alpha-lipoic acid and alpha-tocopherol, alone or in combination, does not protect against oxidative- or non-oxidative-induced apoptosis in endothelial cells. Moreover, we have demonstrated a non-antioxidant, dose-dependent role of alpha-lipoic acid in caspase-3 and ERK2 activation. These data provide an insight and indicate caution in the use of high doses of alpha-lipoic acid as an antioxidant.

Nociceptive scores and endorphin-containing cells reduced by low-level laser therapy (LLLT) in inflamed paws of Wistar rat

Objective: This study aimed to investigate how local pain relief is mediated by laser therapy and how dose affects the relationship. Methods: Inflammation was induced in the hind-paws of Wistar rats. Two groups of rats received 780-nm laser therapy (Spectra-Medics Pty Ltd.) at one of two doses (2.5 and 1 J/cm(2)). One group acted as a control. Scores of nociceptive threshold were recorded using paw pressure and paw thermal threshold measures. Results: A dose of 1 J/cm(2) had no statistically significant effect on antinociceptive responses. A dose of 2.5 J/cm(2) demonstrated a statistically significant effect on paw pressure threshold (p < 0.029) compared to controls. There was no difference in paw thermal threshold responses and paw volumes at either dose. Immunohistochemistry in control animals demonstrated normal beta-endorphin containing lymphocytes in control inflamed paws but no beta-endorphin containing lymphocytes in rats that received laser at 2.5 J/cm(2). Conclusion: The results confirm previous findings that the effect of laser therapy is dose-related. The mechanism of effect may occur via a differentiated pressure-sensitive neural pathway rather than a thermal-sensitive neural pathway. The significance of the immunohistochemistry findings remains unknown.

The two-dose measles, mumps, and rubella (MMR) immunisation schedule: factors affecting maternal intention to vaccinate

BACKGROUND: In the light of sub-optimal uptake of the measles, mumps, and rubella (MMR) vaccination, we investigated the factors that influence the intentions of mothers to vaccinate. METHOD: A cross-sectional survey of 300 mothers in Birmingham with children approaching a routine MMR vaccination was conducted using a postal questionnaire to measure: intention to vaccinate, psychological variables, knowledge of the vaccine, and socioeconomic status. The vaccination status of the children was obtained from South Birmingham Child Health Surveillance Unit. RESULTS: The response rate was 59%. Fewer mothers approaching the second MMR vaccination (Group 2) intended to take their children for this vaccination than Group 1 (mothers approaching the first MMR vaccination) (Mann-Whitney U = 2180, P < 0.0001). Group 2 expressed more negative beliefs about the outcome of having the MMR vaccine ('vaccine outcome beliefs') (Mann-Whitney U = 2155, P < 0.0001), were more likely to believe it was 'unsafe' (chi 2 = 9.114, P = 0.004) and that it rarely protected (chi 2 = 6.882, P = 0.014) than Group 1. The commonest side-effect cited was general malaise, but 29.8% cited autism. The most trusted source of information was the general practitioner but the most common source of information on side-effects was television (34.6%). Multiple linear regression revealed that, in Group 1, only 'vaccine outcome beliefs' significantly predicted intention (77.1% of the variance). In Group 2 'vaccine outcome beliefs', attitude to the MMR vaccine, and prior MMR status all predicted intention (93% of the variance). CONCLUSION: A major reason for the low uptake of the MMR vaccination is that it is not perceived to be important for children's health, particularly the second dose. Health education from GPs is likely to have a considerable impact.

Why is it possible to detect doped regions of semiconductors in low voltage SEM:a review and update

There is an urgent need for fast, non-destructive and quantitative two-dimensional dopant profiling of modern and future ultra large-scale semiconductor devices. The low voltage scanning electron microscope (LVSEM) has emerged to satisfy this need, in part, whereby it is possible to detect different secondary electron yield values (brightness in the SEM signal) from the p-type to the n-type doped regions as well as different brightness levels from the same dopant type. The mechanism that gives rise to such a secondary electron (SE) contrast effect is not fully understood, however. A review of the different models that have been proposed to explain this SE contrast is given. We report on new experiments that support the proposal that this contrast is due to the establishment of metal-to-semiconductor surface contacts. Further experiments showing the effect of instrument parameters including the electron dose, the scan speeds and the electron beam energy on the SE contrast are also reported. Preliminary results on the dependence of the SE contrast on the existence of a surface structure featuring metal-oxide semiconductor (MOS) are also reported. Copyright © 2005 John Wiley & Sons, Ltd.

Responses to various protein and energy supplements by steers fed low-quality tropical hay. 2. Effect of stage of maturity of steers

Dose response curves to various supplements were established in two pen-feeding experiments (Exp1 and Exp2) with Bos indicus crossbred steers of two age groups (Young, 10–12 months; Old, 33–36 months) fed low-quality tropical grass hays ad libitum. Diets included supplements based on (Exp1) cottonseed meal (CSM; intake (as fed) 0–10 g/kg liveweight (W).day) and a barley mix (Bar; 0–20 g/kg W.day) and (Exp2) a molasses mix (MUP) and a Bar mix, both fed at 0–20 g/kg W.day. Urea was provided with the Bar mixes and urea/copra meal with the MUP mix. Growth rates of Young steers increased linearly with Bar and MUP supplements but asymptotically with CSM whereas those of Old steers increased asymptotically with all supplement types. With supplement intake expressed on a liveweight basis (g/kg W.day), responses were greater for both steer age groups with CSM compared with Bar (Young, P < 0.001; Old, P < 0.01) and Bar compared with MUP treatments (Young, P < 0.01; Old, P < 0.05). Furthermore, Old steers outperformed their Young counterparts with both CSM (P < 0.05) and Bar (P < 0.001) supplements fed in Exp1 and with Bar and MUP supplements (P < 0.01) fed in Exp2. When supplement intake was expressed in absolute terms (kg/day), growth responses were not different between age groups for different supplements except that Old steers had a higher daily W gain on Bar than their Young counterparts (P < 0.05). Intake of hay (W-corrected) was higher for Young compared with Old steers without supplement but was variably reduced for both steer groups with increasing supplement intake. The results of these experiments have implications for supplement formulation for steers at different stages of maturity grazing low-quality forages.

Low efficacy of Mebendazole Against Hookworm in Vietman: Two Randomized Controlled Trials

Abstract. Vietnam is participating in a global de-worming effort that aims to treat 650 million school children regularly by 2010. The treatment used in Vietnam is single dose oral mebendazole (Phardazone®) 500 mg. We tested the efficacy of single dose mebendazole 500 mg in the therapy of hookworm infection in a randomized double-blind placebo-controlled trial among 271 Vietnamese schoolchildren. The treatment efficacy of single dose mebendazole in children did not differ significantly from placebo, with a reduction in mean eggs per gram of feces relative to placebo of 31% (95% CI - �9 to 56%, P = 0.1). In light of these findings we then carried out a similar randomized trial comparing triple dose mebendazole, single dose albendazole, and triple dose albendazole against placebo in 209 adults in the same area. The estimated reduction in mean post-treatment eggs per gram of feces relative to placebo was 63% (95% CI 30 - 81%) for triple mebendazole, 75% (47 - 88%) for single albendazole, and 88% (58Ã - 97%) for triple albendazole. Our results suggest that single dose oral mebendazole has low efficacy against hookworm infection in Vietnam, and that it should be replaced by albendazole. These findings are of major public health relevance given the opportunity costs of treating entire populations with ineffective therapies. We recommend that efficacy of anti-helminth therapies is pilot tested before implementation of national gut worm control programs.

Low doses of a neonicotinoid insecticide modify pheromone response thresholds of central but not peripheral olfactory neurons in a pest insect

International audience

Glucose-dependent insulinotropic polypeptide (GIP) dose-dependently reduces osteoclast differentiation and resorption

International audience

Aging assessment of polyethylene-based insulated low-voltage cables for nuclear applications

This thesis aims at investigating the evolution of physico-chemical and electrical properties relevant to low-voltage power cables for nuclear application when subjected to typical nuclear power plant (NPP) environments i.e., to gamma radiation and high temperature. This research is part of the European Project Horizon 2020 TeaM Cables, which aims at providing a novel methodology for efficient and reliable NPP cable aging management to NPP operators. The analyzed samples consist of both coaxial and twisted pair cables with different polymeric compounds used as primary insulation. Insulating materials are based on the same silane cross-linked polyethylene matrix with different additives and fillers. In order to characterize the material response to the environmental stresses, various experimental techniques have been used. These characterizations range from the microscale chemical response e.g. by FTIR, OIT and DSC, to the macroscale electrical and mechanical behavior. A significant part of this Thesis is given to the correlation of the response to aging among the different measured properties. It has been shown that it could be possible to connect both the chemical and mechanical properties of the investigated XLPE cables with the electrical ones. In particular, the high-frequency dielectric response allows an effective monitoring of both the early periods of aging, controlled by the antioxidant consumption kinetics, and then the subsequent oxidation of the polymer matrix. Therefore, dielectric spectroscopy showed to be capable of assessing the LV cable aging state and, it might be used as an aging marker for cable diagnostic. The last part of the manuscript focuses on the building of a predictive modelling approach of LV cable conditions subjected to radio-chemical aging. It resulted into obtaining a lifetime curve which relates the aging factor to which the cable is subjected to, namely the dose rate, with the limit value of the considered electrical property (tanδ).

Intermittent Fasting Induces Hypothalamic Modifications Resulting In Low Feeding Efficiency, Low Body Mass And Overeating.

Intermittent fasting (IF) is an often-used intervention to decrease body mass. In male Sprague-Dawley rats, 24 hour cycles of IF result in light caloric restriction, reduced body mass gain, and significant decreases in the efficiency of energy conversion. Here, we study the metabolic effects of IF in order to uncover mechanisms involved in this lower energy conversion efficiency. After 3 weeks, IF animals displayed overeating during fed periods and lower body mass, accompanied by alterations in energy-related tissue mass. The lower efficiency of energy use was not due to uncoupling of muscle mitochondria. Enhanced lipid oxidation was observed during fasting days, whereas fed days were accompanied by higher metabolic rates. Furthermore, an increased expression of orexigenic neurotransmitters AGRP and NPY in the hypothalamus of IF animals was found, even on feeding days, which could explain the overeating pattern. Together, these effects provide a mechanistic explanation for the lower efficiency of energy conversion observed. Overall, we find that IF promotes changes in hypothalamic function that explain differences in body mass and caloric intake.