Approche des transferts de pollution bactérienne dans une crue karstique par l'étude des paramètres physico-chimiques

L'exploitation des systèmes aquifères karstiques est toujours effectuée sous des contraintes liées à leur forte vulnérabilité. Une étude complète d'un épisode de crue de la source du Lez a été réalisée grâce à une coopération entre les Services de Santé et l'Université. Cette étude comporte une observation des paramètres physico-chimiques et bactériologiques sur une période de 15 jours, correspondant à une réponse hydrodynamique impulsionnelle sur la totalité du bassin. Les pas de temps d'échantillonnage varient de 4 à 24 heures.L'interprétation des résultats physico-chimiques met en évidence une disjonction nette entre les variations piézométriques et le passage de différents volumes d'eau. L'écoulement des eaux plus chaudes (16,5 °C) observé lors de l'étiage, eaux d'origine profonde plus chargées chimiquement se poursuit jusque vers le milieu de la décrue pour faire place à l'arrivée d'eaux plus froides correspondant à des infiltrations rapides puis retardées. Les eaux les plus chaudes sont caractérisées par des variations des teneurs en magnésium, les teneurs en calcium restant à peu prés constantes. Inversement; les eaux froides de l'infiltration retardée ont de faibles variations des teneurs en magnésium et sont tracées par une forte augmentation des valeurs en calcium.Le risque sanitaire maximal est lié au début de l'arrivée des eaux froides. Les eaux d'étiage et les eaux profondes sont légèrement contaminées. Les eaux d'infiltration retardée sont peu contaminées. En dehors des zones de perte du réseau hydrographique et des axes d'infiltration rapide, la vulnérabilité de l'aquifère est faible à l'échelle du bassin.The exploitation of karstic aquifer systems for the supply of potable water raises the problem of the evaluation of sanitary risks, in view of their great vulnerability. To supply a great urban tenter, a yield as high as several cubic metres per hour is required, and this magnitude corresponds to that of an underground basin of several km2, so that it is difficult to monitor and protect.Analytical observations from sanitary control platforms on potable water catchments have shown the existence of periods of high bacteriological pollution synchronizing systematically with periods of a rise of water.These bacteriological pollution transfers depend on the general conditions in which the aquifer functions. It seemed interesting, for the prevention of contamination, to examine all these hydrogeologic functions observed during a water rise, using bacteriological parameters.This study was based on observations made during an overall flood period following a prolonged drought throughout the whole basin supplying the city of Montpellier (France). The aim was to carry out a correlation test on the functioning of a karstic aquifer, with regard to :- the variation of the main physico-chemical parameters,- the principal pathogenic germs,- the commonly observed indicators of faecal contamination.This operation, undertaken in close collaboration with the sanitation board and the university authorities, required considerable investment in human, materiat and financial resources.Montpellier, a city with a population of 250 000 inhabitants, is supplied with potable water from the source of the River Lez. The water catchment is-situated upstream of a. major resurgence (12 m3/s during the water rise), tapping water from a principal drainage channel at a depth of 40 metres.The area of the basin feeding the spring was evaluated to be 150 km2 by adjustment to the 450 km2 of Jurassic and Cretaceous outcropping certified limestone, north of Montpellier. Even if the limits of the basin are not precisely defined, some of its parameters are well known. The aquifer consists of different structural zones, almost like independent sub-systems, having in common a rapid drainage network. The response observed at the exurgence is compared globally with the pluviometric signs, as well as with the effects produced in each structural zone, the transfer time, chemistry, temperature, recession, etc.The whole aquifer must be considered under pressure and it is this state of pressure which is probably responsible for the directional flow of the water from the rock matrix and of that circulating in the major karstification areas. The aquifer may be either in a state of injection or drainage and this notion is supported by the chemical and thermal fluctuations at the exurgence point.A one-year experimental programme, based on our knowledge of this aquifer, has been set up in collaboration with forecasters at the National Meteorological Office. All have been on the alert and ready to intervene, equipped with all the necessary staff and apparatus to ensure reliable sampling and analyses. The following procedures were performed :- sampling every 4 hours during the first 48 hours ;- sampling every 12 hours during the following 48 hours.Then until the end of the study, sampling took place every 24 hours with :- 1 bacteriological sample in sterile condition,- 1 sample for physico-chemical analyses in the laboratory,- temperature measurements with a 1/10° mercury thermometer,- resistivity measurements,- pH measurements with two standards,- a limigraphic reading.This period of water rise, hydrologically homogeneous throughout the whote basin in the form of a single impulsive response tasting about 10 days, was characterised by the circulation of two types of water masses : from the rock matrix and resutting from rapid infiltration. The mixture of these two bodies, each with a distinct chemical character, is a function of the state of pressure in the aquifer. At the end of the rise, a third type of water intervenes, that of retarded infiltration.The best criteria for identifying these volumes of water are thermal ones. The most variable elements are magnesium and calcium. Deep waters with a temperature of 16 °5 are characterised by a variation in magnesium, and cold water, by a variation in calcium. The highest value of calcium is related to the passage of water bodies attributed to the influence of retarded infiltration.The geological observations and the processing of results by factorial analyses show a clear distinction between the chemical rise and the piezometric rise. The hydraulic rise point is constituted by water with the saure chemical characteristics as that of the lowest water level. The most important dilution due to rapid transfer in the basin is observed in the middle of the water fait. These synchronized with the highest batteriological pollution rate for most of the elements.This study has provided a global appreciation of the sanitary risks and shows how pollution mechanisms function. Risks are permanent, even during the passage of the deepest water with a long residence time. This phenomenon raises the question of the duration and mode of survive of non encystable bacteria indicators in the karst system. The survival time appeared to be about a year or more.There is always a covariation between the physico-chemical elements and bacteriological pollution where the aquifer is under high pressure and when the water rises or has reached its maximum level, or when the water starts to fall. It is when the level of the water starts to drop that the main peaks of bacteriological pollution are observed. From this moment onwards, the whole basin functions like a drained system and the absence of covariation in the physico-chemical and bacteriological parameters are signs that the flow has become heterogeneous.For sanitation purposes it may be sufficient to monitor temperature and other chemical elements, in order to determine when an additional treatment of the water is required to maintain its potability. An appropriate apparatus is being devised to this end

Estimating the burden of minor ailment consultations in general practices and emergency departments through retrospective review of routine data in North East Scotland

Minor ailment attendances in general practices and emergency departments (EDs) place significant burden on health care resources

A very low geno2pheno false positive rate is associated with poor viro-immunological response in drug-naïve patients starting a first-line HAART.

Background: We previously found that a very low geno2pheno false positive rate (FPR ≤2%) defines a viral population associated with low CD4 cell count and the highest amount of X4-quasispecies. In this study, we aimed at evaluating whether FPR ≤2% might impact on the viro-immunological response in HIV-1 infected patients starting a first-line HAART. Methods: The analysis was performed on 305 HIV-1 B subtype infected drug-naı¨ve patients who started their first-line HAART. Baseline FPR (%) values were stratified according to the following ranges: ≤2; 2–5; 5–10; 10–20; 20–60; >60. The impact of genotypically-inferred tropism on the time to achieve immunological reconstitution (a CD4 cell count gain from HAART initiation ≥150 cells/mm3) and on the time to achieve virological success (the first HIV-RNA measurement <50 copies/mL from HAART initiation) was evaluated by survival analyses. Results: Overall, at therapy start, 27% of patients had FPR ≤10 (6%, FPR ≤2; 7%, FPR 2–5; 14%, FPR 5–10). By 12 months of therapy the rate of immunological reconstitution was overall 75.5%, and it was significantly lower for FPR ≤2 (54.1%) in comparison to other FPR ranks (78.8%, FPR 2–5; 77.5%, FPR 5–10; 71.7%, FPR 10–20; 81.8%, FPR 20–60; 75.1%, FPR >60; p = 0.008). The overall proportion of patients achieving virological success was 95.5% by 12 months of therapy. Multivariable Cox analyses showed that patients having pre-HAART FPR ≤2% had a significant lower relative adjusted hazard [95% C.I.] both to achieve immunological reconstitution (0.37 [0.20–0.71], p = 0.003) and to achieve virological success (0.50 [0.26–0.94], p = 0.031) than those with pre-HAART FPR >60%. Conclusions: Beyond the genotypically-inferred tropism determination, FPR ≤2% predicts both a poor immunological reconstitution and a lower virological response in drug-naı¨ve patients who started their first-line therapy. This parameter could be useful to identify patients potentially with less chance of achieving adequate immunological reconstitution and virological undetectability

Oxaliplatin induces drug resistance more rapidly than cisplatin in H69 small cell lung cancer cells

Cisplatin produces good responses in solid tumours including small cell lung cancer (SCLC) but this is limited by the development of resistance. Oxaliplatin is reported to show activity against some cisplatin-resistant cancers but there is little known about oxaliplatin in SCLC and there are no reports of oxaliplatin resistant SCLC cell lines. Studies of drug resistance mainly focus on the cellular resistance mechanisms rather than how the cells develop resistance. This study examines the development of cisplatin and oxaliplatin resistance in H69 human SCLC cells in response to repeated treatment with clinically relevant doses of cisplatin or oxaliplatin for either 4 days or 2h. Treatments with 200ng/ml cisplatin or 400ng/ml oxaliplatin for 4 days produced sublines (H69CIS200 and H69OX400 respectively) that showed low level (approximately 2-fold) resistance after 8 treatments. Treatments with 1000ng/ml cisplatin or 2000ng/ml oxaliplatin for 2h also produced sublines, however these were not stably resistant suggesting shorter treatment pulses of drug may be more effective. Cells survived the first five treatments without any increase in resistance, by arresting their growth for a period and then regrowing. The period of growth arrest was reduced after the sixth treatment and the H69CIS200 and H69OX400 sublines showed a reduced growth arrest in response to cisplatin and oxaliplatin treatment suggesting that "regrowth resistance" initially protected against drug treatment and this was further upregulated and became part of the resistance phenotype of these sublines. Oxaliplatin dose escalation produced more surviving sublines than cisplatin dose escalation but neither set of sublines were associated with increased resistance as determined by 5-day cytotoxicity assays, also suggesting the involvement of regrowth resistance. The resistant sublines showed no change in platinum accumulation or glutathione levels even though the H69OX400 subline was more sensitive to buthionine sulfoximine treatment. The H69CIS200 cells were cross-resistant to oxaliplatin demonstrating that oxaliplatin does not have activity against low level cisplatin resistance. Relative to the H69 cells, the H69CIS200 and H69OX400 sublines were more sensitive to paclitaxel and taxotere suggests the taxanes may be useful in the treatment of platinum resistant SCLC. These novel cellular models of cisplatin and oxaliplatin resistant SCLC will be useful in developing strategies to treat platinum-resistant SCLC

Boolean Dynamics with Random Couplings

This paper reviews a class of generic dissipative dynamical systems called N-K models. In these models, the dynamics of N elements, defined as Boolean variables, develop step by step, clocked by a discrete time variable. Each of the N Boolean elements at a given time is given a value which depends upon K elements in the previous time step. We review the work of many authors on the behavior of the models, looking particularly at the structure and lengths of their cycles, the sizes of their basins of attraction, and the flow of information through the systems. In the limit of infinite N, there is a phase transition between a chaotic and an ordered phase, with a critical phase in between. We argue that the behavior of this system depends significantly on the topology of the network connections. If the elements are placed upon a lattice with dimension d, the system shows correlations related to the standard percolation or directed percolation phase transition on such a lattice. On the other hand, a very different behavior is seen in the Kauffman net in which all spins are equally likely to be coupled to a given spin. In this situation, coupling loops are mostly suppressed, and the behavior of the system is much more like that of a mean field theory. We also describe possible applications of the models to, for example, genetic networks, cell differentiation, evolution, democracy in social systems and neural networks.Comment: 69 pages, 16 figures, Submitted to Springer Applied Mathematical Sciences Serie

Regulator of G-protein signaling 18 controls both platelet generation and function

RGS18 is a myeloerythroid lineage-specific regulator of G-protein signaling, highly expressed in megakaryocytes (MKs) and platelets. In the present study, we describe the first generation of a RGS18 knockout mouse model (RGS18-/-). Interesting phenotypic differences between RGS18-/- and wild-type (WT) mice were identified, and show that RGS18 plays a significant role in both platelet generation and function. RGS18 deficiency produced a gain of function phenotype in platelets. In resting platelets, the level of CD62P expression was increased in RGS18-/- mice. This increase correlated with a higher level of plasmatic serotonin concentration. RGS18-/- platelets displayed a higher sensitivity to activation in vitro. RGS18 deficiency markedly increased thrombus formation in vivo. In addition, RGS18-/- mice presented a mild thrombocytopenia, accompanied with a marked deficit in MK number in the bone marrow. Analysis of MK maturation in vitro and in vivo revealed a defective megakaryopoiesis in RGS18-/- mice, with a lower bone marrow content of only the most committed MK precursors. Finally, RGS18 deficiency was correlated to a defect of platelet recovery in vivo under acute conditions of thrombocytopenia. Thus, we highlight a role for RGS18 in platelet generation and function, and provide additional insights into the physiology of RGS18

The synthetic peptide P111-136 derived from the C-terminal domain of heparin affin regulatory peptide inhibits tumour growth of prostate cancer PC-3 cells

<p>Abstract</p> <p>Background</p> <p>Heparin affin regulatory peptide (HARP), also called pleiotrophin, is a heparin-binding, secreted factor that is overexpressed in several tumours and associated to tumour growth, angiogenesis and metastasis. The C-terminus part of HARP composed of amino acids 111 to 136 is particularly involved in its biological activities and we previously established that a synthetic peptide composed of the same amino acids (P111-136) was capable of inhibiting the biological activities of HARP. Here we evaluate the ability of P111-136 to inhibit <it>in vitro </it>and <it>in vivo </it>the growth of a human tumour cell line PC-3 which possess an HARP autocrine loop.</p> <p>Methods</p> <p>A total lysate of PC-3 cells was incubated with biotinylated P111-136 and pulled down for the presence of the HARP receptors in Western blot. <it>In vitro</it>, the P111-136 effect on HARP autocrine loop in PC-3 cells was determined by colony formation in soft agar. <it>In vivo</it>, PC-3 cells were inoculated in the flank of athymic nude mice. Animals were treated with P111-136 (5 mg/kg/day) for 25 days. Tumour volume was evaluated during the treatment. After the animal sacrifice, the tumour apoptosis and associated angiogenesis were evaluated by immunohistochemistry. <it>In vivo </it>anti-angiogenic effect was confirmed using a mouse Matrigel™ plug assay.</p> <p>Results</p> <p>Using pull down experiments, we identified the HARP receptors RPTPβ/ζ, ALK and nucleolin as P111-136 binding proteins. <it>In vitro</it>, P111-136 inhibits dose-dependently PC-3 cell colony formation. Treatment with P111-136 inhibits significantly the PC-3 tumour growth in the xenograft model as well as tumour angiogenesis. The angiostatic effect of P111-136 on HARP was also confirmed using an <it>in vivo </it>Matrigel™ plug assay in mice</p> <p>Conclusions</p> <p>Our results demonstrate that P111-136 strongly inhibits the mitogenic effect of HARP on <it>in vitro </it>and <it>in vivo </it>growth of PC-3 cells. This inhibition could be linked to a direct or indirect binding of this peptide to the HARP receptors (ALK, RPTPβ/ζ, nucleolin). <it>In vivo</it>, the P111-136 treatment significantly inhibits both the PC-3 tumour growth and the associated angiogenesis. Thus, P111-136 may be considered as an interesting pharmacological tool to interfere with tumour growth that has now to be evaluated in other cancer types.</p