Practical application of international recommendations and safety standards in the systematic planning and implementation of remediation of sites or areas with residual radioactive material.

The IAEA fundamental safety objective is'to protect people and the environment from harmful effects of ionizing radiation'and this must be done 'without unduly limiting the operation of facilities or the conduct of activities that give rise to radiation risks', while ensuring that people and the environment, present and future are protected against radiation risks (IAEA 2006Fundamental Safety Principles, Safety FundamentalsNo. SF-1). In addition,'protective actions to reduce existing or unregulated radiation risks must be justified and optimized'(IAEA 2006Fundamental Safety Principles, Safety FundamentalsNo. SF-1). An international system of radiological protection can be applied such that processes, such as remediation, can be systematically undertaken to address the wide range of'existing exposure situations'present globally. In doing so, decisions made regarding actions undertaken can be demonstrated to be'justified'and'optimized'(i.e. balanced), such that the amount of effort should be commensurate with the risk (applying a'graded approach'). In addition, protection of people and the environment can be demonstrated by comparing the actual exposure to appropriate criteria over the lifetime of remediation. This paper provides an overview of the current IAEA safety standards on remediation of sites or areas contaminated with residual radioactive material within the international system of radiological protection and provides practical examples of their application through case studies considered in IAEA international model validation programs.

Community volunteers can improve breastfeeding among children under six months of age in the Democratic Republic of Congo crisis.

BACKGROUND: Malnutrition is a major public health problem in developing countries and exclusive breastfeeding is an efficient strategy that can be used to prevent malnutrition and reduce child mortality. The objective of this study is to evaluate the effectiveness of community volunteers in promoting exclusive breastfeeding from birth in an area of endemic malnutrition. METHODS: This evaluation analyzed the impact of the community-based nutrition project in Katana health district of the Democratic Republic of Congo from 2004 to 2006. Each of the villages in this sector had a nutritional village committee made up of five members responsible for continuously working to raise awareness of the importance of exclusive breastfeeding from birth among pregnant women and community leaders in their respective villages. The program worked with community volunteers with a mean age of 37 years, most of whom were married (86%). Eighty percent of the community volunteers had completed secondary school or a higher level of education. Data related to the period of exclusive breastfeeding and to the number of visits made to the health services for 208 children. The data were compared with data from 178 infants collected from another health sector, which had never developed a community-based nutrition program. RESULTS: The duration of exclusive breastfeeding from birth (median, range) was 6 months (2 to 7) in the intervention area compared with 4 months (1 to 6) in the comparison area (p < 0.001). The proportion of infants receiving exclusive breastfeeding at six months of age was higher in the intervention area than in the comparison area: 57.7% (95% Confidence Interval, CI, 50.9 to 64.5) versus 2.7% (95%CI, 1.1 to 6.6) (p < 0.001). The intervention group had a higher mean weight at 12 months (standard deviation): 8.42 kg (1.41) compared to 7.97 kg (1.02), although this difference was not statistically significant (p = 0.055). CONCLUSIONS: The promotion of breastfeeding by community volunteers in an area of endemic malnutrition in rural Democratic Republic of Congo increased the duration of exclusive breastfeeding from birth.

No down-regulation of leaf photosynthesis in mature forest trees after three years of exposure to elevated CO2.

The photosynthetic responses of six species of mature forest trees to long-term exposure to elevated CO2 (ca. 530 ppm) were determined at the Swiss Canopy Crane (SCC) site near Basel, Switzerland. In the third year of growth in elevated CO2, using web-FACE technology, net photosynthesis (As) in fully sunlit, upper canopy foliage was stimulated by ca. 40% compared to ambient controls. This enhancement did not differ from the instantaneous increase in As found in ambient-grown leaves that were temporarily measured at elevated CO2. A complete lack of down-regulation of photosynthesis was found in all species and in both the early and the late growing season. Neither was leaf nitrogen content significantly affected by long-term exposure to elevated CO2. Our results document a persistent enhancement in leaf level photosynthesis in response to elevated CO2 in mature forest trees over a period of three years. Circumstantial evidence suggests that the additional assimilates feed into large sinks other than stem and shoot growth.

Responses of transpiration and photosynthesis to reversible changes in photosynthetic foliage area in western red cedar (Thuja plicata) seedlings.

Experiments were conducted on 1-year-old western red cedar (Thuja plicata Donn.) seedlings to determine the response of illuminated foliage to reversible changes in total photosynthetic foliage area (L(A)). Reductions in L(A) were brought about by either shading the lower foliage or by reducing the ambient CO2 concentration (c(a)) of the air surrounding the lower part of the seedling. In the latter case, the vapor pressure was also changed so that transpiration rates (E) could be manipulated independently of photosynthetic rates (A). We hypothesized that following such treatments, short-term compensatory changes would occur in stomatal conductance (g(s)) and A of the remaining foliage. These changes would occur in response to hydraulic signals generated by changes in the water potential gradient rather than changes in the distribution of sources and sinks of carbon within the seedling. When a portion of the foliage was shaded, there was an immediate reduction in whole-seedling E and a concomitant increase in g(s), A and E in the remaining illuminated foliage. However, the intercellular CO2 concentration did not change. These compensatory effects were fully reversed after the shade was removed. When the lower foliage A was reduced to < 0 micromol m-2 s-1, by shading or lowering c(a), and E was either unchanged or increased (by adjusting the vapor pressure deficit), there was no significant increase in g(s) and A in the remaining foliage. We conclude that compensatory responses in illuminated foliage occur only when reductions in L(A) are accompanied by a reduction in whole-plant E. The relationship between the reduction in whole-seedling E and the increase in A is highly linear (r2 = 0.68) and confirms our hypothesis of the strong regulation of g(s) by hydraulic signals generated within the seedling. We suggest that the mechanism of the compensatory effects is a combination of both increased CO2 supply, resulting from increased g(s), and a response of the rate of carboxylation, possibly related to the activity of Rubisco.

Effects of pro-inflammatory cytokines on apolipoprotein E secretion by a human astrocytoma cell line (CCF-STTG1).

Apolipoprotein (apo) E has been implicated in Alzheimer's disease; however, little is known about the regulation of its secretion in astrocytes. To investigate the effects of pro-inflammatory cytokines such as interleukin-1beta (IL-1beta), tumour necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) on apoE secretion by CCF-STTG1 cells, a sensitive and specific double sandwich Enzyme-Linked ImmunoSorbent Assay (ELISA) was developed. Using a monoclonal anti-human apoE antibody as the capture antibody, this assay was carried out with commercially available reagents. The assay had a sensitivity of 0.013 ng per well, within-run and between-run variation coefficients of 6.0 and 8.6 per cent respectively. There was no cross-reactions between antibodies used and apoAI, apoAII, apoB, apoCI, apoCII and apoCIII. Low apoE concentrations were assessed using a serum-free HepG2 culture medium as secondary calibrator, containing 59 microg l(-1) of apoE. In serum-free medium, CCF-STTG1 cells secreted apoE, the accumulation of which in the cell medium increased linearly with time (27 microg per 48 h). After 48 h of incubation, apoE secretion was inhibited by TNF-alpha but not affected by IL-1beta and IFN-gamma. However, the effect of regulatory factors may depend upon culture conditions since in the presence of 10 per cent fetal calf serum, IFN-gamma significantly inhibited apoE secretion. Thus, apoE secretion by CCF-STTG1 cells is inhibited by specific pro-inflammatory cytokines. This new apoE ELISA presents the great advantage of using commercially available reagents which permit inter-laboratory comparability of results, involves relatively low cost and is adaptable for the measurement of low levels of apoE.

Interspecies scaling of clearance and volume of distribution for horse antivenom F(ab')2.

F(ab')2 fragments are sometimes preferred to whole IgG for therapeutic or diagnostic uses. Preclinical pharmaceutical development studies are necessary before their use in humans. Here we propose an allometric approach among three mammalian species to predict F(ab')2 pharmacokinetic parameters in humans. Plasma disposition of horse antivenom F(ab')2 fragments labeled with iodine 125 was studied at a dose of 10 mg/kg i.v. in mice, rats, and rabbits. Using the allometric method, we demonstrate that the pharmacokinetic parameters that correlated with body weight were distribution volume (Vdc (ml) = 0.125 W0.87; Vdss (ml) = 0.251 W0.87; Vd beta (ml) = 0.290 W0.87, r2 = 1), total clearance (Cltot (ml/h) = 0.049 W0.53, r2 = 0.99), and terminal half-life (t1/2 beta (h) = 4.35 W0.33). The F(ab')2 plasma concentration-time data plotted as a complex Dedrick relationship were superimposable. Using these allometric techniques, Vdss, Vd beta, Cltot, and t1/2 beta were calculated as 4.12 liter, 4.78 liter, 19.07 ml/h, and 7.2 days, respectively, for a human subject of 70 kg body wt. Predicted human pharmacokinetic parameters were comparable for volume of distribution with the value reported by Hnatowich et al. (Cancer Res. 47, 6111-6117, 1987): 3.5 liter. However, the clearance was six-fold lower than values given by Hnatowich et al. (130 ml/h) and Ho et al.

Snake F(ab')2 antivenom from hyperimmunized horse: pharmacokinetics following intravenous and intramuscular administrations in rabbits.

PURPOSE: The pharmacokinetics of a currently available horse F(ab')2 antivenoms to Vipera aspis, V. ammodytes, and V. berus (Ipser Europe) and a new more purified and pasteurized preparation (SAV) was investigated in the rabbit. METHODS: An immunoradiometric assay using an affinity-purified goat IgG horse F(ab')2 specific and the same IgG labelled with iodine 125 as a tracer was developed. The limit of quantification in plasma was 0.032 microgram/ml. Specificity study showed that mouse F(ab')2 and Fab did not cross-react. RESULTS: Pharmacokinetic analysis showed that the plasma F(ab')2 concentration followed a biexponential decline after intravenous bolus administration with distribution and elimination half-lives of 2.66 +/- 0.18 hrs and 49.69 +/- 4.13 hrs, respectively. The total volume of distribution (Vdss or Vd beta) was between 209 and 265 ml.kg-1 and was similar to the volume of the extracellular fluid in the rabbit (300 ml.kg-1). Total body clearance ranged from 3.33 to 3.96 ml.h-1.kg-1. After intramuscular administration which was only investigated with SAV, Tmax was 48 hrs and the absolute bioavailability was 42%. CONCLUSIONS: No difference in pharmacokinetics was observed between the two antivenom preparations following the intravenous administration. In contrast, a reduced rate and extent of absorption was shown following intramuscular administration.

Thyrotropin-releasing hormone: inhibitory function on growth hormone through both somatostatin and growth hormone-releasing factor neurons.

Double labelling immunohistochemistry using antibodies to thyrotropin releasing hormone (TRH) and somatostatin (SS) was undertaken in the anterior hypothalamus in 6 rats. Light microscopic quantitation revealed that 94.5% of SS immunopositive perikarya in the preoptic anterior hypothalamic area (PO/AHA) and 97.5% in the paraventricular nucleus appeared to be contacted by one or more TRH immunopositive terminals. In the chronically cannulated unanaesthetised male rat, unilateral microinjections of a range of doses of TRH were made in the PO/AHA, where SS neurons are located, or in the medial basal hypothalamus, where growth hormone (GH)-releasing factor (GRF) neurons are located. Transient reductions in GH plasma levels occurred only after injections of the highest (10 nmol) dose of TRH in both sites. The function of TRH inputs to both somatostatin and GRF neurons appears to be inhibitory for GH. The physiological conditions in which these inputs function remain to be defined.

A whole-plant cuvette system to measure short-term responses of conifer seedlings to environmental change.

A computer-controlled whole-plant cuvette system is described that allows precise and independent control of temperature (+/- 0.05 degrees C), vapor pressure (+/- 0.02 kPa), CO(2) concentration (+/- 2 micro mol mol(-1)) and photosynthetic photon flux density (+/- 5 micro mol m(-2) s(-1)), and allows the continuous measurement of net photosynthesis and transpiration rates. Vapor pressure is controlled by circulating chamber air through a CaSO(4) desiccant column supported on a digital balance. Transpiration rate is calculated from the change in desiccant mass with time. Photosynthesis rate is measured by integrating the output of a mass flow controller used to inject CO(2) into the chamber to compensate for that assimilated by the plant. The control system can be driven by set points that can be varied, for example, as a function of time, or held constant. We were able to simulate weather data obtained from climate stations and accurately follow, in real time, the output of sensors measuring outside conditions. Experiments on well-watered one- and two-year-old nursery-raised western red cedar (Thuja plicata Donn.) and white spruce (Picea glauca (Moench) Voss) seedlings showed that if the mean daily temperature was increased from 20 to 22 degrees C with vapor pressure remaining constant at 1 kPa, CO(2) concentrations must almost double to compensate for the decrease in net photosynthesis rate.

Microsurgical instrument handling systems. A new approach to instrument budget control.

1. Large portion of a hospital's supply budget is allocated for repair and replacement of surgical instruments. Microsurgical instrumentation can account for 18% or more of a total OR budget. 2. Managing the surgical instrument repair and replacement budgets with greater emphasis on accountability can help demonstrate effective cost containment. Cost savings may be experienced through appropriate use of surgical instrument management systems for handling, sterilization, and storage of microsurgical instruments. 3. Many facilities are implementing quality control programs to minimize replacement and repair costs, to ensure surgical instrument integrity, and to extend the life of their investment. Education, management information systems, improved communication, and appropriate use of instrument handling systems are some components of budget accountability in the operating room.

Rapid and slow release phenytoin in epileptic patients at steady state: comparative plasma levels and toxicity.

Phenytoin plasma level and toxicity data were compared in a three-way crossover study performed in 18 patients at steady state. Formulations compared were a rapid and a slow release capsule and an oral solution. Plasma concentration-time integrals and maximum plasma phenytoin levels were significantly greater for the rapid release capsule and solution than for the slow release capsule. The incidence of nystagmus and toxicity did not differ for the three treatments, but the occurrence of mental symptoms was more frequent for the oral solution, possibly because of the solvent used in this formulation.

Rapid and slow release phenytoin in epileptic patients at steady state: assessment of relative bioavailability utilizing Michaelis-Menten parameters.

The bioavailability of phenytoin from rapid release capsule and oral solution formulations relative to that of a slow release capsule formulation was assessed in five patients who had participated in a three-way crossover study performed at steady state. The subjects then underwent dosage adjustment utilizing the slow release formulation, and estimates of their Michaelis-Menten parameters thus obtained were utilized in calculating the relative bioavailabilities. In addition, expected changes in steady-state plasma phenytoin concentrations were calculated assuming initial levels of 15 mg/liter, with increases and decreases in bioavailability of 10%. The consequences of such alterations in the extent of phenytoin absorption or average content of the dosage form may be clinically significant, particularly where the initial phenytoin level is equal to or greater than the patient's operative Km.