First Observation of CP Violation in B[over ¯]

We report a measurement of the time-dependent CP asymmetry of B[over ¯]^{0}→D_{CP}^{(*)}h^{0} decays, where the light neutral hadron h^{0} is a π^{0}, η, or ω meson, and the neutral D meson is reconstructed in the CP eigenstates K^{+}K^{-}, K_{S}^{0}π^{0}, or K_{S}^{0}ω. The measurement is performed combining the final data samples collected at the ϒ(4S) resonance by the BABAR and Belle experiments at the asymmetric-energy B factories PEP-II at SLAC and KEKB at KEK, respectively. The data samples contain (471±3)×10^{6} BB[over ¯] pairs recorded by the BABAR detector and (772±11)×10^{6} BB[over ¯] pairs recorded by the Belle detector. We measure the CP asymmetry parameters -η_{f}S=+0.66±0.10(stat)±0.06(syst) and C=-0.02±0.07(stat)±0.03(syst). These results correspond to the first observation of CP violation in B[over ¯]^{0}→D_{CP}^{(*)}h^{0} decays. The hypothesis of no mixing-induced CP violation is excluded in these decays at the level of 5.4 standard deviations.

Characterization of particles emitted by incense burning in an experimental house.

The potential health effects of fine and ultrafine particles are of increasing concern. A better understanding of particle characteristics and dispersion behavior is needed. This study aims at characterizing spatial and temporal variations in fine and ultrafine particle dispersion after emission from a model source in an experimental house. Particles emitted by an incense stick burning for 15 min were characterized. Number concentration, specific surface area and mass were measured. Partial chemical analysis of particles was also realized. Near the burning incense stick, the maximum concentration was 25,500 particles/cm(3); the indoor PM(2.5) concentration reached 197 microg/m(3), and the specific surface area concentration was 180 microm(2)/cm(3). The estimated incense smoke density was 1.1 g/cm(3). Time of Flight Aerosol Mass Spectrometer measurements indicated that the organic fraction was predominant in the aerosol mass detected, and other minor components identified were K(+), NO(3)(-), and Cl(-). The combustion of an incense stick in the living room was associated with significant modifications of the concentrations of particles measured in the different rooms of the house. This demonstration of pollution by particle dispersion by a model source of moderate intensity may have significant implications in terms of assessment of indoor exposure to such particles. Practical Implications The particles emitted in a domestic environment by a source of moderate intensity such as burning incense disperse throughout the house, even in rooms with closed doors and in rooms as far away as the next floor. This dispersion has significant implications in terms of evaluating human indoor exposure to fine and ultrafine particles.

External radiation exposure and mortality in a cohort of French nuclear workers.

OBJECTIVE: To analyse the effect of external radiation exposure on the mortality of French nuclear workers. METHODS: A cohort of 29 204 workers employed between 1950 and 1994 at the French Atomic Energy Commission (Commissariat à l'Energie Atomique (CEA)) or at the General Company of Nuclear Fuel (COmpagnie GEnérale des MAtières nucléaires (Cogema, now Areva NC)) was followed up for an average of 17.8 years. Standardised mortality ratios (SMRs) were computed with reference to French mortality rates. Dose-effect relationship were analysed through trend tests and Poisson regression, with linear and log-linear models. RESULTS: The mean exposure to X and gamma radiation was 8.3 mSv (16.9 mSv for exposed worker population). A total of 1842 deaths occurred between 1968 and 1994. A healthy worker effect was observed, the number of deaths in the cohort being 59% of the number expected from national mortality statistics. Among the 21 main cancer sites studied, a statistically significant excess was observed only for skin melanoma, and an excess of borderline statistical significance was observed for multiple myeloma. A dose-effect relationship was observed for leukaemia after exclusion of chronic lymphoid leukaemia (CLL). The relative risk observed for non-CLL leukaemia, n = 20, was 4.1 per 100 mSv (90% CI 1.4 to 12.2), linear model and 2.2 per 100 mSv (90% CI 1.2 to 3.3), log-linear model. Significant dose-effect relationship were also observed for causes of deaths associated with alcohol consumption: mouth and pharynx cancer, cirrhosis and alcoholic psychosis and external causes of death. CONCLUSION: The risk of leukaemia increases with increasing exposure to external radiation; this is consistent with published results on other nuclear workers cohorts.

Acylation of endogenous phospholipids and added lysoderivatives by rat liver plasma membranes.

Phospholipid acyltransferase activities of plasma membranes have been investigated with various acyl-CoA thioesters (palmitoyl, stearoyl, oleoyl, linoleoyl and arachidonoyl) with and without added lysoderivatives. Different patterns of incorporation were observed for each acyl-CoA into endogenous phosphatidylcholine and phosphatidylethanolamine. The turnover rates calculated with tracer amounts of 10 microM acyl-CoA thioesters were five times faster for the polyunsaturated than for the saturated acyl moieties of phosphatidylethanolamine and phosphatidylcholine. Arachidonoyl-CoA was the best acyl donor at low concentrations and the maximal turnover rate was observed at about 25 microM. No saturation appeared at up to 100 microM linoleoyl-CoA. Linoleoyl-CoA transacylase acylated the lyso-compounds in the following order: lysophosphatidylcholine greater than lysophosphatidylserine and lysophosphatidylinositol, while lysophosphatidylethanolamine inhibited linoleate incorporation into the phosphatidylethanolamine itself. Linoleoyl-CoA transacylation was not affected by the fatty acyl moiety at the 1-position of the lysophosphatidylcholine. The results support the view that the plasma membrane acyltransferase activity might contribute to the formation of bile phosphatidylcholines.

Public health benefits of compliance with current E.U. emissions standards for municipal waste incinerators: a health risk assessment with the CalTox multimedia exposure model.

The Angers municipal solid waste incineration plant, in operation since 1974, was upgraded in 2000 to comply with new European standards. This article discusses the risks associated with past and present emissions from the incinerator and its nearby furnace. Emissions of SO(2), HCl, particulate matter, lead, mercury, cadmium and dioxins were studied. We characterised the risks associated with exposure via inhalation and ingestion of locally grown products, before and after the upgrade. Emissions were estimated from regulatory measurements, and ambient air concentrations estimated with a Gaussian dispersion model. The CalTox multimedia model was used to calculate concentrations in the food chain. Food intake rates came from a nationwide survey. Inhalation exposure to respiratory irritants produced a hazard ratio less than 1 in all scenarios, except for SO(2) in the immediate neighbourhood of the incinerator, before the change in furnace fuel and in case of high-pressure weather conditions. The individual excess risk of cancer was less than 10(-6) and the hazard ratios for metals were less than 1. Before compliance, the average dioxin exposure attributable to the incinerator accounted for roughly one quarter of the average total exposure from traffic and other combustion activities. Although the corresponding hazard ratio was less than 1, the individual lifetime excess risk, assuming no change in emissions, was 2 x 10(-4). After compliance, all hazard ratios and future individual lifetime excess risks appear minimal. These results are consistent with environmental data and other studies, but many uncertainties remain, such as intermedia transfer coefficients for dioxins. Nevertheless compliance has vastly reduced the probability of health effects.

Massive overfeeding and energy balance in men: the Guru Walla model.

To determine the magnitude of the thermogenic response to a massive long-term overfeeding, an energy-balance study was carried out in nine lean, young Cameroonian men participating in a traditional fattening session: the Guru Walla. Food intake, body weight, body composition, activity, and metabolic rates were recorded during a 10-d baseline period and over the 61-65 d of fattening. Total energy expenditure (TEE) was measured by using doubly labeled water during the baseline period and the final 10 d of Guru Walla. Cumulative overfeeding consisted of 955 +/- 252 MJ (chi +/- SD) mainly as carbohydrate. Body-weight increase was 17 +/- 4 kg, 64-75% as fat. Metabolic rates increased but TEE did not. However, when accounting for the reduction in physical activity, substantial thermogenesis was observed but its amplitude was not greater than that observed under less extreme carbohydrate-overfeeding conditions. If luxuskonsumption does exist, it is not related to the magnitude of the cumulative overfeeding.

The influence of oestradiol on the metabolism of androgens by human prostatic tissue.

The uptake and metabolism of testosterone, androstenedione and 5alpha-dihydrotestosterone (DHT) by human benign hyperplastic prostates and prostatic carcinomas have been measured in organ culture. DHT was a major metabolite of both testosterone and androstenedione in the benign tissue and the androstanediols were the principal metabolites of DHT. Over half the carcinomas produced less DHT from testosterone than the benign hyperplastic prostates, and carcinomas from the oldest patients showed an enhancement of 17beta-hydroxysteroid dehydrogenation. There was no relationship between these differences in metabolism and the degree of differentiation of the carcinomas. Oestradiol decreased the production of DHT from both testosterone and androstenedione and, at low androgen concentrations, increased the production of androstanediols from testosterone, androstenedione and DHT. Uptake of DHT, but not of the other two androgens, was stimulated by oestradiol.

Metabolism of testosterone by the epithelium and mesenchyme of the rat urogenital sinus.

Testosterone metabolism was measured in separated epithelium and mesenchyme from the urogenital sinuses of 17- and 19-day-old male and female rat embryos and compared with testosterone metabolism in the intact sinus. Both the epithelium and the mesenchyme converted testosterone to 5 alpha-dihydrotestosterone. The epithelium produced much more androstanedione and androsterone but less 3 alpha, 17 beta-androstanediol than did the mesenchyme. The whole sinus synthesized all four metabolites, but in different proportions, producing relatively more androsterone than either of its two component tissues. These data suggest that androsterone is formed by the joint action of epithelium and mesenchyme. Metabolism of testosterone did not differ with sex or foetal age in either of the separated tissues or in the intact sinus, implying that the failure of urogenital mesenchyme from 19-day-old female foetuses to induce prostatic morphogenesis is not due to the loss of 5 alpha-reductase. It is suggested that this lack of inductive capacity may be attributable to a decline in androgen levels with age in female mesenchyme.

Effect of the intra-articular injection of lutetium-177 in chelator liposomes on the progress of an experimental arthritis in rabbits.

The treatment of rheumatoid arthritis by radiosynovectomy has been restricted by the difficulty of preventing leakage of the radioisotope from the joint cavity. We have previously shown that this leakage can be reduced to very low levels by delivering the radioisotope in liposomes containing the lipophilic chelator, 3-cholesteryl 6-[N'-iminobis-(ethylenenitrilo)tetraacetic acid]hexyl ether. The present study investigates the effectiveness of the beta-emitting isotope lutetium-177, delivered in chelator liposomes, in treating an experimental arthritis in rabbits. Chelator liposomes containing 0.35 mCi, 0.175 mCi Or 0.087 mCi of the isotope were injected into the synovial cavities of the knees of rabbits with an established experimental arthritis. The retention of the lutetium and the progress of the arthritis were followed for 47 days, and samples of the joint tissues were taken for histology at the end of the experiment. Results showed that losses of radioactivity averaged less than 1% per day over 47 days and that joints treated with 0.175 mCi showed significant reductions in both diameter and surface temperature compared with controls treated with a non-radioactive preparation. Post-mortem histology revealed that, whereas control joints showed a highly active synovitis, synovia of joints treated with 0.175 or 0.35 mCi lutetium-177 had very little inflammatory activity. Although some joints which had received 0.35 mCi showed signs of damage to the articular cartilage, this damage was not apparent wih either of the two lower doses. We conclude that, in this animal model, chelator liposomes complexed with a suitable radioisotope are capable of effecting an efficient synovectomy.

The retention and distribution in the rabbit knee of a radionuclide complexed with a lipophilic chelator in liposomes.

The application of radiosynovectomy to patients with rheumatoid arthritis has been severely restricted by the difficulty of preventing leakage of the radioisotope from the joint cavity. We have synthesised a lipophilic chelator, 3-cholesteryl 6-[N'-iminobis(ethylenenitrilo)-tetraacetic acid]hexyl ether (Chol-DTTA) which can complex with a variety of beta-emitting radionuclides and is incorporated into the lipid phase of liposomes. The retention in the synovial cavities of rabbit knees of liposomes containing Chol-DTTA, complexed with the gamma-emitting tracer 51Cr, has been measured over a period of 21 days and compared with colloidal and water-soluble preparations. The distribution of the radionuclide between the tissues of the joint was also examined. Results show retention of 51Cr delivered in chelator liposomes to be greater than 99% after 24 h. At this time, over 93% of the radioactivity had become associated with the synovium. We conclude that chelator liposomes offer considerable promise as vehicles for radioisotopes in radiosynovectomy.

The use of a chelating derivative of alpha melanocyte stimulating hormone for the clinical imaging of malignant melanoma.

A novel chelating derivative of alpha melanocyte stimulating hormone, bis MSH-DTPA, has been used for the diagnostic targeting of malignant melanoma. 15 patients were investigated of whom nine were shown by other means to have active disease at the time of the scan. Tumours were imaged in all of these nine patients. Of a total of 46 lesions over 10 mm encountered, 41 (89%) were imaged. There were no false positives and in two cases bisMSH-DTPA was instrumental in reversing diagnoses made using ultrasound. Derivatives of melanocyte stimulating hormone may be of considerable value in targeting melanomas.

An improved imaging agent for malignant melanoma, based on [Nle4,D-Phe7]alpha-melanocyte stimulating hormone.

Two compounds have been synthesized based on [Nle4,D-Phe7]alpha-melanocyte stimulating hormone (NDP-MSH) in which either one or two peptide sequences were covalently linked through their N'-termini to a single molecule of diethylenetriamine pentaacetic acid (DTPA). These two compounds (monoNDP-MSH-DTPA and bisNDP-MSH-DTPA, respectively) bound indium-111 (111In) stably and showed hormonal activity as great or greater than alpha-melanocyte stimulating hormone (alpha-MSH). Both compounds were able to target 111In to Cloudman S91 melanomas in DBA2 mice. MonoNDP-MSH-DTPA gave the highest tumour:blood and tumour:tissue ratios and showed least unspecific radioactivity in the liver and kidney. Radioscintigraphy of mice showed good tumour localization of 111In with both compounds, clear images being obtainable within 2 h of injection. Scans with monoNDP-MSH-DTPA showed some kidney and thyroid but no liver radioactivity, whereas bisNDP-MSH-DTPA gave extensive abdominal radioactivity, most of which was associated with the liver and kidneys. MonoNDP-MSH-DTPA was cleared from the tumour much less rapidly and gave more favourable tumour:blood ratios than other alpha-MSH derivatives previously investigated. It is concluded that monoNDP-MSH-DTPA offers promise as a melanoma imaging agent in man.

[Principles of evaluation of public health risk for environmental exposures]. / Principes de l'évaluation des risques pour la santé publique liés aux expositions environnementales.

Assessing environmental health risk is fraught with difficulties: often, the agents under study are weak pathogens, and exposures are poorly characterised. Direct studies in man are frequently inconclusive (or inconsistent) because of the limited sensitivity of epidemiological studies. Experimental studies raise questions about the validity of animal to man extrapolation. However, taking steps to protect public health is needed and impose the use of all available data. Remaining uncertainties lead the health risk assessor to make assumptions. Such a process implies as much transparency as possible, both for ethical reasons and to allow the public to be involved in the debate. A formalized approach has been proposed by various US agencies in charge of public health. One important matter is a strict separation between risk assessment and risk management. The procedure is divided into four portions: hazard assessment, exposure assessment, dose-response assessment which includes the study of risk at low doses--sometimes through the use of mathematical high to low dose extrapolation modelling--and risk characterisation.

[Accidents, disasters and crises: contribution of epidemiology in th nuclear field]. / Accidents, catastrophes et crises: apports de l'épidémiologie dans le domaine nucléaire.

The experience of the Chernobyl accident has shown the necessity of being prepared for epidemiological assessment of the death consequences of a nuclear or a radiological accident. We discuss the contribution of epidemiology in such situations, in addition to the existing tools designed to assess or manage radiological risks. From a decisional point of view, three issues are distinguished: the protection of the different population groups against ionizing radiations, the achievement of health care and the communication with the public and media. We discuss the input of epidemiological tools in both perspectives. Epidemiology may also contribute to the analysis of health events that may be observed after an accident, i.e. to assess whether these events are not statistical artifacts, whether they are an effect of the exposure to the ionizing radiations or a non specific consequence of any accident. Finally, epidemiological studies should be carried out to improve our knowledge on ionizing radiations effects with a special consideration given to the dose-effect relationships. Examples of past nuclear accidents are used to discuss these issues. The last part of this paper is focused on different research issues that should be developed for preparing epidemiological plans for nuclear accidents.

[Is compliance to current lead regulations safe enough for infants and toddlers?]. / Le respect de la réglementation actuelle permet-il une protection suffisante de la population infantile vis-à-vis du plomb?

BACKGROUND: Neurobehavioural and cognitive impairment may arise from children's exposure to lead. To prevent this risk, a Tolerable Daily Intake (TDI) has been issued by WHO and many regulations addressing lead emission to the environment have been introduced. Taking into account both lead concentrations in soil and the importance of soil in children's exposure, we examined whether compliance to the above current regulations is safe enough for children. METHODS: Exposure scenarios were devised for infants and toddlers, the 2 populations most sensitive to lead toxicity, considering three typical environmental settings, that is, rural, urban, and in the vicinity of lead emitting industrial sites. For all 3 scenarios, we used available data describing the current French levels of both lead contamination in various media (water, air, soil) and lead intake through food. Acute lead intoxication from old lead-containing paints was excluded from this study. RESULTS: We have shown that WHO's TDI is exceeded in several situations for both populations, and thus children may be subject to unacceptable levels of risk. CONCLUSION: We conclude that it may be advisable to take fuller account of the contribution of soil to lead exposure.

Agent orange and the risk of gestational trophoblastic disease in Vietnam.

There have been claims of an increased risk for gestational trophoblastic disease (i.e., hydatidiform mole and choriocarcinoma) in Vietnam since the period of Agent Orange sprayings. In 1990, we conducted a case-control study in Ho Chi Minh City to investigate risk factors for gestational trophoblastic disease in Vietnam. Eighty-seven married women, all of whom had a recent pathologic diagnosis of gestational trophoblastic disease, identified in the Obstetrical and Gynecological Hospital, were included in the study. Eighty-seven married women who were admitted mainly in the surgery departments of the same hospital were the controls, and they were matched to cases for age and area of residence. Odds ratios (ORs), adjusted for matching variables and other potential confounders, were estimated with unconditional logistic regression. A statistically significant trend in risk was observed with previous live births (p = .01). Cases were found to eat less meat per wk (OR = 0.4, 95% confidence interval [95% CI] = 0.2-0.9 for > or = five meat dishes) and to own fewer consumer goods than controls. An increase in risk was associated with the breeding of pigs (OR = 5.7, 95% CI = 1.2-27.6 for raising three or more pigs). A cumulative Agent Orange exposure index was constructed, using the patient's complete residence history. No significant difference was found between cases and controls for this index (OR = 0.7, 95% CI = 0.2-1.8 for high-exposure category), nor was such a difference noted for the agricultural use of pesticides.

[Relations between iron levels in mothers and in their newborn infants]. / Relations entre le statut en fer de la mère et du nouveau-né.

The iron levels were evaluated in 124 pregnant women towards the end of their pregnancies and in their newborn babies in 4 maternity units in Paris and in the surroundings. Two-third of the women studied had total absence of iron reserves (shown by a serum ferritin level less than or equal to 12 micrograms/l). Those who were at the greatest risk of having iron deficiency or anaemia were immigrant, non continental french and multiparous women. The tissue reserves of iron in the newborn are not directly linked to the levels of iron in the mother but are probably linked to the foetal and maternal haemoglobin-synthesis.

[Evaluation of the psychological consequences of environmental catastrophes: a feasibility study based on the 1992 floods in the Vaucluse]. / Evaluation des conséquences psychologiques des catatrophes environnementales: une étude de faisabilité à partir des inondations de 1992 dans le Vaucluse (France).

Scientific studies of environmental disasters, whether human or natural in origin, have shown that the psychological impact of such events may be considerable and long-lasting. Several natural disasters have occurred in France, but their impact on public psychological health has not been assessed. In September 1992, there was a major flood in southeast France (Vaucluse), which caused 38 deaths. Four years later, we performed a pilot cross-sectional study to assess the feasibility of a larger epidemiological study to assess the psychological impact of this flood. Two affected towns were chosen for this study: Vaison-la-Romaine (VLR), where the flood was very sudden and 29 people were killed, and Bédarrides, where the water level rose more slowly. In Bédarrides, households were randomly selected from a list of victims (n = 100) and in Vaison-la-Romaine, households were randomly selected from the telephone directory (n = 140). Exposure to the flood was assessed by a series of questions, the answers to which were used to calculate an exposure score. The questionnaire also included psychometric scales for post-traumatic stress disorder (QE-PTSD), anxiety (Spielberger State-Trait Anxiety Inventory) and depression (Beck Depression Inventory). In Bédarrides, the participation rate was high: 69% of the selected households were successfully contacted and found to be eligible for inclusion and 74% agreed to a face-to-face interview. In Vaison-la-Romaine, 51% of the selected households were contacted and eligible and 50% agreed to the face-to-face interview. Our survey showed that exposure was multidimensional and that it was possible to calculate an exposure score suitable for the analysis of exposure-effect relationships. The PTSD scale was completed well by the interviewees, several of whom did not fill in the depression and anxiety scales correctly. However, analysis of the responses obtained showed that these tools had a high level of internal consistency. Cross-correlations between the various psychological scales used in this study were highly significant (p < 10-4). There was some degree of association between some psychometric scales and exposure. This pilot study shows that a cross-sectional study of the long-term psychological consequences of an environmental disaster could be carried out several years after the event but that the feasibility of such a study depends ultimately on its acceptance by the public and the relevant authorities. It underlines the need to collect exposure data immediately after the event and enabled us to identify and to adapt the tools required for this kind of evaluation. It should encourage public health decision-makers to support such evaluation and to improve the psychological and social support available to people exposed to floods.

[Radon exposure and risks for public health]. / Exposition au radon et risques pour la santé publique.

Radon is a radioactive gas of natural origin. Its principal isotope is radon-222, stemming from uranium-238 present at various concentrations in all soils. Radon is found everywhere in the earth's atmosphere but has low reactivity by itself. Radon particulate daughters are however responsible for alpha irradiation of the bronchial epithelium. Epidemiologic studies on miners have shown long ago that radon exposure causes an increased risk of lung cancer in these workers. More recently, its risk associated with radon exposure was addressed in public dwellings. It is generally agreed that the risk of lung cancer is plausible in this setting. In particular, radon exposure in some dwellings may be comparable to that undergone by several uranium miner populations. However, simple and low-cost steps can be taken to significantly reduce radon exposure in dwellings.

Creation of synthetic homogeneous neighbourhoods using zone design algorithms to explore relationships between asthma and deprivation in Strasbourg, France.

The concept of 'neighbourhood' as a unit of analysis has received considerable research attention over the last decade. Many of these studies raise the question of the influence of local characteristics on variations in health and more recently, researchers have sought to understand how the neighbourhood can influence individual health through individual behaviour. Relatively few studies discuss the question of the borders and definition of a neighbourhood but we know that the results from health or population datasets are very sensitive to how zones are constructed - part of the Modifiable Areal Unit Problem (MAUP). In reality, we know that neighbourhoods are not constrained by artificial statistical boundaries, but rather exist as complex multi-dimensional living communities. This paper tries to better represent the reality on the ground of these communities to better inform studies of health. In this work, we have developed an experimental approach for the automated design of neighbourhoods using a small tessellated cell as a basic building block. Using the software AZTool, we considered population, shape and homogeneity constraints to develop a highly innovative approach to zone construction. The paper reports the challenges and compromises involved in building these new synthetic neighbourhoods. We provide a fully worked example of how our new synthetic homogeneous zones perform using data from Strasbourg, France. We examine data on Asthma reported through calls to the emergency services, and compare these rates with an index of multiple deprivation (NDI) which we have constructed and reported elsewhere. Higher correlations between Asthma and NDI were found using our newly constructed synthetic zones than using the existing French census areas of similar size. The significance of our work is that we show that careful construction of neighbourhoods - which we claim are more realistic than census areas - can greatly aid unpacking our understanding of neighbourhood relationships between health and the social and physical environments.