A comparison of sediment deposition in two adjacent floodplains of the River Adour in southwest France.

Two floodplains within the catchment of the River Adour (SW France) have been examined in order to analyse spatio-temporal variations in discharge and suspended matter flux. Both floodplain zones were found to be excellent sites for the interception of suspended sediment. The narrow riparian vegetative strips (RVS) within each zone were found to retain 92-98% of the sediment trapped within the floodplain during each of three separate flood events. The precise level of sediment deposited within the floodplain was found to be dependent on micro-topographical features and the nature of the vegetation: the wooded areas within the RVS being particularly effective at trapping sediment. Mean masses of sediment collected in the flood plains ranged from 75 kg m(-2) in the RVS to 0.02 kg m(-2) in the areas of the floodplain inundated by back-up flows. Using data on discharge and sediment fluxes within the catchment gathered over a period of 25 years it is possible to discern how hydroclimatic fluctuations have affected the watershed with periods of sediment retention within the floodplain zones alternating with periods of sediment export. Anthropogenic activity, involving river management, including the cutting of meanders, the construction of dykes for flood prevention and the use of water for agricultural purposes, has also had a major impact during this period, particularly in the downstream areas of the catchment.

Comparison of hepatic recurrences after resection or intraoperative radiofrequency ablation indicated by size and topographical characteristics of the metastases.

AIMS: Intraoperative use of radiofrequency ablation (IRFA) to treat liver metastases is controversial. The aim of this study was to compare local recurrence rate and survival after IRFA versus resection. METHODS: Three groups from 99 patients were consecutively operated on for 307 liver metastases with 2years of follow up: group 1, IRFA alone (n=34); group 2, IRFA plus resection (n=28); group 3, resection alone (n=37). The choice of IRFA or resection was made on the basis of the sizes and topographies of the metastases with the goal of achieving R0 treatment. RESULTS: Mortality was zero; morbidity was 9%, 11% and 11% in the three groups respectively. Median follow-up after surgery was 30months. Total hepatic recurrences occurred in 59 (60%) patients. Median survival without hepatic recurrence was 17months with no difference between the three groups (P=0.474). Total local recurrence occurred in 4 (12%) patients in group 1, in 2 (8%) patients in group 2, and in 2 (6%) patients in group 3. Survival at 2years was no different in the three groups. CONCLUSION: Assessing IRFA indications by size and the topographical characteristics of the liver metastases yields identical local recurrence rates to resection after 2years of follow up.

Growing networks under geographical constraints.

Inspired by the structure of technological weblike systems, we discuss network evolution mechanisms which give rise to topological properties found in real spatial networks. Thus, we suggest that the peculiar structure of transport and distribution networks is fundamentally determined by two factors. These are the dependence of the spatial interaction range of vertices on the vertex attractiveness (or importance within the network) and on the inhomogeneous distribution of vertices in space. We propose and analyze numerically a simple model based on these generating mechanisms which seems, for instance, to be able to reproduce known structural features of the Internet.

Relación entre la inteligencia emocional y la motivación para trabajar en Cuidados Paliativos en estudiantes de enfermería / No disponible

Objetivo: averiguar la posible relación existente entre la inteligencia emocional y la motivación para trabajar con enfermos al final de su vida en estudiantes de Enfermería. Método: estudio descriptivo transversal de prevalencia. Participaron 444 estudiantes de enfermería pertenecientes a 3 escuelas de enfermería de Cataluña y Andalucía. Se administraron una serie de cuestionarios, ítems referentes al deseo de trabajar con enfermos en general y con personas al final de su vida. Para evaluar el nivel de Inteligencia Emocional se administró la versión española del Trait Meta-Mood Scale. Resultados: sólo el 8% (con un intervalo de confianza del 95% de 5,5% a 10,5%) de los alumnos, se sienten más preparados emocionalmente para cuidar enfermos terminales que para cuidar enfermos en general. Por otro lado, los alumnos preferirían trabajar con enfermos pediátricos siendo el trabajo con enfermos terminales la opción menos deseada. En relación con la inteligencia emocional, los alumnos andaluces presentan un nivel más elevado de comprensión y regulación de las emociones que sus compañeros catalanes. Así mismo, a mayor comprensión y regulación emocional mayor es el deseo de trabajar con enfermos terminales y menores el miedo a la muerte y a los muertos. Conclusiones: formar y trabajar con la Inteligencia Emocional y en concreto con la regulación emocional, puede incidir en aumentar el número de alumnos que desee trabajar con enfermos terminales al sentirse más competentes a nivel emocional (AU)

Objective: to study the relationship between emotional intelligence and nursing students' motivation to work with terminally ill patients. Method: a cross-sectional, descriptive prevalence study of 444 nursing students from 3 different nursing schools within Catalonia and Andalusia. They were administered a set of items concerning their desire to work with patients in general, and also with the terminally ill specifically. To assess emotional intelligence the Spanish version of the Trait-Mood Scale was administered. Results: only 8% (95% confidence interval: 5.5% to 10.5%) of students felt that they were more emotionally prepared to care for the terminally ill than for any other type of patients. In addition, students reported their preference to work with pediatric patients, whereas caring for the terminally ill was the least desired option. Regarding emotional intelligence, Andalusian students showed both a higher level of understanding and greater emotion regulation versus their Catalonian counterparts. Similarly, greater emotional understanding increases the desire to work with terminally ill patients, and is associated with less fear towards death and the dead. Conclusions: working and training within the emotional intelligence framework –especially considering the importance of the emotional regulation process- may have a beneficial effect upon nursing students. Students' motivation in working with terminally ill patients may increase as they feel increasingly more competent on an emotional basis (AU)

Surgical treatment of liver metastases by radiofrequency ablation, resection, or in combination.

AIMS: Radiofrequency ablation (RFA) has a role in the treatment of unresectable liver metastases either percutaneously or in open surgery. The aim of this study was to determine the feasibility and value using RFA, resection or in combination to cure liver metastases of colorectal or other origin. METHODS: Fifty-two consecutive patients were operated on with the intention to treat their liver metastases using both techniques of RFA and resection in the same curative intent. A CT scan was performed 2 months postoperatively and then every 4 months. RESULTS: Fifty patients with 137 metastases could be treated: 55 lesions were resected and 82 were ablated. Curative treatment of 13 patients could only be achieved by using RFA combined with resection. Morbidity was 16% and local treatment proved insufficient in three cases. Estimated 1-year survival probabilities were, respectively, 0.85 in the colorectal group and 0.80 in the non-colorectal group. CONCLUSIONS: RFA increased resectability of liver metastases and reduced the morbidity. Respective indications of both techniques were complementary and depend on the size and the topography of the lesion to be treated.

Artemin is an RNA-binding protein with high thermal stability and potential RNA chaperone activity.

Encysted embryos of the crustacean, Artemia franciscana, are among the most stress-resistant of all multicellular eukaryotes, due in part to massive amounts of p26, a small heat shock protein, that acts as a molecular chaperone. These embryos contain equally large amounts of another protein called artemin, of previously unknown function, that we report on here. Its thermal stability allows large-scale purification in about a day, using ammonium sulfate fractionation and incubation at 70 degrees C for 7 min, followed by gel filtration. The latter yields an artemin-RNA complex from which the pure protein, apo-artemin, was obtained by anion-exchange chromatography. We evaluated the possibility that artemin acts as a molecular chaperone for proteins, but obtained no evidence for that in vitro. The association of RNA with apo-artemin occurs at high temperatures and, although it is not yet clear whether artemin has a specific role as an RNA chaperone, it does bind non-polyadenylated RNAs which are then translated in vitro. Artemin-RNA is thermostable, some molecules resisting destruction after 30 min at 90 degrees C. The first order rate constant for denaturation and aggregation of artemin-RNA at 85 degrees C is 8.5 x 10(-3)min(-1), which compares well with other thermostable proteins of similar size ( approximately 500 kDa) such as the ferritins with which artemin has amino acid sequence similarity. The amount of artemin extracted from embryos that had been stored dry, under laboratory conditions, since 1951 is comparable to the amount in contemporary embryos, indicating its stability in situ, and supporting the in vitro heating studies.

Reshuffling scale-free networks: from random to assortative.

To analyze the role of assortativity in networks we introduce an algorithm which produces assortative mixing to a desired degree. This degree is governed by one parameter p . Changing this parameter one can construct networks ranging from fully random (p=0) to totally assortative (p=1) . We apply the algorithm to a Barabási-Albert scale-free network and show that the degree of assortativity is an important parameter governing the geometrical and transport properties of networks. Thus, the average path length of the network increases dramatically with the degree of assortativity. Moreover, the concentration dependences of the size of the giant component in the node percolation problem for uncorrelated and assortative networks are strongly different. The behavior of the clustering coefficient is also discussed.

Correlations in scale-free networks: tomography and percolation.

We discuss three related models of scale-free networks with the same degree distribution but different correlation properties. Starting from the Barabási-Albert construction based on growth and preferential attachment we discuss two other networks emerging when randomizing it with respect to links or nodes. We point out that the Barabási-Albert model displays dissortative behavior with respect to the nodes' degrees, while the node-randomized network shows assortative mixing. These kinds of correlations are visualized by discussing the shell structure of the networks around an arbitrary node. In spite of different correlation behaviors, all three constructions exhibit similar percolation properties. This result for percolation is also detected for a network with finite second moment and its corresponding randomized models.

Phase II study of oxaliplatin, fluorouracil, and folinic acid in locally advanced or metastatic gastric cancer patients.

PURPOSE: To evaluate the efficacy and safety of an oxaliplatin, fluorouracil (5-FU), and folinic acid (FA) combination in patients with metastatic or advanced gastric cancer (M/AGC). PATIENTS AND METHODS: Of the 54 eligible patients with measurable or assessable M/AGC, 53 received oxaliplatin 100 mg/m(2) and FA 400 mg/m(2) (2-hour intravenous infusion) followed by 5-FU bolus 400 mg/m(2) (10-minute infusion) and then 5-FU 3,000 mg/m(2) (46-hour continuous infusion) every 14 days. RESULTS: Patients (69% male, 31% female) had a median age of 61 years (range, 31 to 75 years), 89% had a performance status of 0 or 1, 70% had newly diagnosed disease, and 87% had metastatic disease. All had histologically confirmed adenocarcinoma. With a median of three involved organs, disease sites included the lymph nodes (67%), stomach (65%), and liver (61%). A median of 10 cycles per patient and 468 complete cycles were administered. Best responses in the 49 assessable patients were two complete responses and 20 partial responses, giving an overall best response rate of 44.9%. Eight patients underwent complementary treatment with curative intent (six with surgery and two with chemoradiotherapy). Median follow-up, time to progression, and overall survival were 18.6 months, 6.2 months, and 8.6 months, respectively. Grade 3/4 neutropenia, leukopenia, thrombocytopenia, and anemia occurred in 38%, 19%, 4%, and 11% of patients, respectively, and febrile neutropenia occurred in six patients (one episode each). Grade 3 peripheral neuropathy occurred in 21% of patients (oxaliplatin-specific scale). Seven patients withdrew because of treatment-related toxicity. CONCLUSION: This oxaliplatin/5-FU/FA regimen shows good efficacy and an acceptable safety profile in M/AGC patients, and may prove to be a suitable alternative regimen in this indication.

Evolving networks with disadvantaged long-range connections.

We consider a growing network, whose growth algorithm is based on the preferential attachment typical for scale-free constructions, but where the long-range bonds are disadvantaged. Thus, the probability of getting connected to a site at distance d is proportional to d(-alpha), where alpha is a tunable parameter of the model. We show that the properties of the networks grown with alpha<1 are close to those of the genuine scale-free construction, while for alpha>1 the structure of the network is quite different. Thus, in this regime, the node degree distribution is no longer a power law, and it is well represented by a stretched exponential. On the other hand, the small-world property of the growing networks is preserved at all values of alpha.

A biologically based dynamic model for predicting the disposition of methanol and its metabolites in animals and humans.

A multicompartment biologically based dynamic model was developed to describe the time evolution of methanol and its metabolites in the whole body and in accessible biological matrices of rats, monkeys, and humans following different exposure scenarios. The dynamic of intercompartment exchanges was described mathematically by a mass balance differential equation system. The model's conceptual and functional representation was the same for rats, monkeys, and humans, but relevant published data specific to the species of interest served to determine the critical parameters of the kinetics. Simulations provided a close approximation to kinetic data available in the published literature. The average pulmonary absorption fraction of methanol was estimated to be 0.60 in rats, 0.69 in monkeys, and 0.58-0.82 in human volunteers. The corresponding average elimination half-life of absorbed methanol through metabolism to formaldehyde was estimated to be 1.3, 0.7-3.2, and 1.7 h. Saturation of methanol metabolism appeared to occur at a lower exposure in rats than in monkeys and humans. Also, the main species difference in the kinetics was attributed to a metabolism rate constant of whole body formaldehyde to formate estimated to be twice as high in rats as in monkeys. Inversely, in monkeys and in humans, a larger fraction of body burden of formaldehyde is rapidly transferred to a long-term component. The latter represents the formaldehyde that (directly or after oxidation to formate) binds to various endogenous molecules or is taken up by the tetrahydrofolic-acid-dependent one-carbon pathway to become the building block of synthetic pathways. This model can be used to quantitatively relate methanol or its metabolites in biological matrices to the absorbed dose and tissue burden at any point in time in rats, monkeys, and humans for different exposures, thus reducing uncertainties in the dose-response relationship, and animal-to-human and exposure scenario comparisons. The model, adapted to kinetic data in human volunteers exposed acutely to methanol vapors, predicts that 8-h inhalation exposures ranging from 500 to 2000 ppm, without physical activities, are needed to increase concentrations of blood formate and urinary formic acid above mean background values reported by various authors (4.9-10.3 and 6.3-13 mg/liter, respectively). This leaves blood and urinary methanol concentrations as the most sensitive biomarkers of absorbed methanol.

A toxicokinetic model for predicting the tissue distribution and elimination of organic and inorganic mercury following exposure to methyl mercury in animals and humans. II. Application and validation of the model in humans.

The objective of this study was to develop a biologically based dynamical model describing the disposition kinetics of methyl mercury and its inorganic mercury metabolites in humans following different methyl mercury exposure scenarios. The model conceptual and functional representation was similar to that used for rats but relevant data on humans served to determine the critical parameters of the kinetic behavior. It was found that the metabolic rate of methyl mercury was on average 3 to 3.5 times slower in humans than in rats. Also, excretion rates of organic mercury from the whole body into feces and hair were 100 and 40 times smaller in humans, respectively, and urinary excretion of organic mercury in humans was found to be negligible. The human transfer rate of inorganic mercury from blood to hair was found to be 5 times lower than that of rats. On the other hand, retention of inorganic mercury in the kidney appeared more important in humans than in rats: the transfer rate of inorganic mercury from blood to kidney was 19 times higher than in rats and that from kidney to blood 19 times smaller. The excretion rate of inorganic mercury from the kidney to urine in humans was found to be twice that of rats. With these model parameters, simulations accurately predicted human kinetic data available in the published literature for different exposure scenarios. The model relates quantitatively mercury species in biological matrices (blood, hair, and urine) to the absorbed dose and tissue burden at any point in time. Thus, accessible measurements on these matrices allow inferences of past, present, and future burdens. This could prove to be a useful tool in assessing the health risks associated with various circumstances of methyl mercury exposure.

A toxicokinetic model for predicting the tissue distribution and elimination of organic and inorganic mercury following exposure to methyl mercury in animals and humans. I. Development and validation of the model using experimental data in rats.

The objective of this study was to develop a biologically based dynamic model for predicting the distribution and elimination of methyl mercury and its metabolite, inorganic mercury, under a variety of exposure scenarios in rats. A model is proposed based on a multicompartment approach; each compartment represents an organ or a group of organs or an excreta. The model translates into a set of coupled differential equations taking into account interorgan rates of exchanges and excretion together with the biotransformation process. The free parameters of the model are determined from statistical fits to the experimental data of the Farris et al. (Toxicol. Appl. Pharmacol. 119, 74-90, 1993) study on the time profiles of blood and tissue concentrations and cumulative excretions. The vast range of time scales that govern tissue absorption, distribution, biotransformation, and excretion served to solve the model step by step. This interplay of time scales in the rates explains the buildups and slow attrition of inorganic mercury in certain key organs such as the brain and the kidney, which are also the sites of the more important toxic effects. The model was validated on additional experimental data provided by Norseth and Clarkson (Arch. Environ. Health 21, 717-727, 1970) and Thomas et al. (Environ. Res. 41, 219-234, 1986; Environ. Res. 43, 203-216, 1987). This approach, when adapted to humans, allows the reconstruction of the time course of blood and tissue concentrations, starting from easily accessible data on hair, urine, and feces.

A method for estimating time dependent intervention benefits under arbitrarily varying age and exogenous components of hazard.

A method for estimating the dependence of intrinsic intervention benefits on time elapsed since the intervention took place is proposed. The method is aimed at intervention programs against diseases where one or all of the following components of hazard intensity may undergo important and unknown variations: 1) the intervention benefits to a subject are a function of the time elapsed since the intervention took place, or since inception for a continuing treatment, 2) the subjects vulnerability is an unknown function of their age, 3) the exogenous or environmental baseline intensity, to which all are assumed subjected, fluctuates arbitrarily with calendar time. During the time span of a study, these variables interact in a complex way, possibly masking the real contribution of the intervention. However, with very general assumptions about how hazard components interact, the cumulative hazards of subpopulations treated at different times in the past are shown to be described mathematically by a convolution of the time elapsed dependent intervention benefit function with the age and calendar time dependent baseline intensity. Starting from the cumulative hazards of untreated and treated subpopulations that had the intervention at different times in the past, a method of deconvolution through regularization is proposed to reconstruct the time elapsed dependence of the intervention benefit function. The regularization technique used is of the 'penalized least square smoothing' type, it is applied to the solution of Volterra integral equations of the first kind under noisy inputs. Simulations, to test for the reconstruction of different modes of time elapsed variation of the intervention benefits, are carried out on realistically noisy 'data sets' taken to be available at a limited number of time points. The stability of the estimated reconstructions, to measurement errors, is examined through repeated simulations with random noise added to inputs. The method is applied to a Brazilian data set where BCG vaccination resulted in a small reduction in the cumulated risk of leprosy infection.

[Contribution of gemcitabine in the treatment of advanced pancreatic cancer]. / Apport de la gemcitabine dans le traitement du cancer du pancréas avancé.

INTRODUCTION: Pancreatic cancer is one of the most common tumor of the gastrointestinal tract. CURRENT KNOWLEDGE AND KEY POINTS: Because this malignancy is usually diagnosed at an advanced stage, its prognosis is poor, and patients are generally considered incurable at diagnosis. The traditional palliative approach to management of this tumor is chemotherapy. The most widely used agent is 5-FU, alone or in combination. Benefits of the treatment are still poor: the overall survival time rarely exceeds 5 months, and no study has shown a response rate greater than 20%. FUTURE PROSPECTS AND PROJECTS: Gemcitabine, a new antinucleoside agent, has led to promising results, as several phase II and III studies have demonstrated an increase in survival as compared with 5-FU, the overall 1-year survival rates being 18% and 2%, respectively (p < 0.002). Furthermore, even if only discrete results in terms of objective response rate have been achieved, gemcitabine decreases disease-related symptoms, thus benefiting to the patient's quality of life. The concept of clinical benefit therefore appears to be an important judgement criteria in the assessment of chemotherapy efficacy, and will certainly be extended to other malignant neoplasms.

The toxicokinetics of pyrene and its metabolites in rats.

Five experiments were conducted in male Sprague-Dawley rats regarding the kinetic of urinary excretion of 1-hydroxypyrene (1-OHP) following i.v., oral and dermal exposure to 0.5-50 micromol/kg pyrene either as a single substance or as mixture of various polycyclic aromatic hydrocarbons (PAH). Frequent urine collections over 48 h after exposure and a tissue versus time distribution experiment using [14C]pyrene allowed to define the kinetic profile of both pyrene and 1-OHP. For all exposure routes, there is a linear relationship over two orders of magnitude between the dose of pyrene and the urinary excretion of 1-OHP. Differences in biliary/urinary 1-OHP excretion ratio in canulated rats (3) versus faecal/urinary 1-OHP excretion ratio in non-canulated rats (0.6) indicate major enterohepatic recirculation of the metabolite. Half-lives of both pyrene and 1-OHP in all measured tissues were all comprised between 3.1 and 5.4 h, and 5.2-6.7 h, respectively, so that no long term accumulation would be predicted from these values for any tissue. Binary and ternary mixtures involving naphthalene and benzo(a)pyrene in addition to pyrene has no influence on the urinary excretion profile of 1-OHP. All these observations led to the proposal of a dynamic compartment model of pyrene and metabolite flows indicating that following rapid initial distribution to fatty tissues, pyrene is rapidly biotransformed into various metabolites and undergoes major enterohepatic recycling. Part of the initially formed and part of the recirculated 1-OHP eventually undergoes urinary excretion such that close to 60% of pyrene is eliminated as metabolites in urine by 24 h after injection while 20% is excreted in the faeces over the same period.

A non-parametric method for the reconstruction of age- and time-dependent incidence from the prevalence data of irreversible diseases with differential mortality.

A method is proposed for reconstructing the time and age dependence of incidence rates from successive age-prevalence cross sections taken from the sentinel surveys of irreversible diseases when there is an important difference in mortality between the infected and susceptible subpopulations. The prevalence information at different time-age points is used to generate a surface; the time-age variations along the life line profiles of this surface and the difference in mortality rates are used to reconstruct the time and age dependence of the incidence rate. Past attempts were based on specified parametric forms for the incidence or on the hypothesis of time-invariant forms for the age-prevalence cross sections. The proposed method makes no such assumptions and is thus capable of coping with rapidly evolving prevalence situations. In the simulations carried out, it is found to be resilient to important random noise components added to a prescribed incidence rate input. The method is also tested on a real data set of successive HIV age-prevalence cross sections from Burundi coupled to differential mortality data on HIV(+) and HIV(-) individuals. The often-made assumption that the incidence rate can be written as the product of a calendar time component and an age component is also examined. In this case, a pooling procedure is proposed to estimate the time and the age profiles of the incidence rate using the reconstructed incidence rates at all time-age points.

A toxicokinetic model to assess the risk of azinphosmethyl exposure in humans through measures of urinary elimination of alkylphosphates.

Azinphosmethyl (APM) is one of the most common insecticides used in fruit farming. The object of this paper is to develop a quick and practical test for assessing the risk for humans coming into contact with APM. It has been shown that the principal component of occupational and/or accidental exposure is through the skin (C. A. Franklin et al., 1981, J. Toxicol. Environ. Health 7, 715-731), but our approach is applicable to exposures via any route or a combination of routes. The method proposed in the present paper can accommodate a single-event exposure or repeated exposures over long periods. Urinary alkylphosphate (AP) metabolites are reliable bioindicators of the presence of APM in the body; they are easily accessible and can be used to estimate APM body burden. We developed a simple toxicokinetic model to link the time varying APM body burden to absorbed doses and to rates of elimination in the form of AP urinary metabolites. Using this model and data available in the literature, we are able to propose a "no observed adverse effect level" (NOAEL) for APM body levels and for corresponding absorbed doses. We have established that after a single exposure, the safe limit corresponding to the NOAEL is reached at a cumulative 0.215 mumoles AP/kg bw eliminated in urine in the first 24 hours following the beginning of exposure. For repeated daily exposures at steady state, the corresponding urinary AP metabolite level is equal to a cumulative 0.266 mumoles AP/kg bw eliminated per 24 hours.

Dacarbazine, fluorouracil, and leucovorin in patients with advanced neuroendocrine tumors: a phase II trial.

Chemotherapy of neuroendocrine tumors must be improved. The most widely used regimen, which combines streptozotocin with fluorouracil, commonly obtains poor results. The best response rate that has been reported for carcinoid tumors is 33%. From July 1991 through September 1994, 18 patients who had advanced neuroendocrine tumors-including nine carcinoid tumors, seven neuroendocrine tumors of unknown primary site, one insulinoma, and one paraganglioma-were treated with a regimen of dacarbazine, 400 mg/m2/day, plus fluorouracil, 1 g/m2/day, with leucovorin, 200 mg/m2/day, for 2 days every 21 days (DTIC-LVFU2 protocol). The results were assessed according to the World Health Organization criteria of toxicity and response. Toxicity was moderate. The most severe side effects were grade 3 vomiting in two patients, grade 3 leukopenia in three patients, and grade 3 mucositis in one patient. The overall response rate was 27%, with only one partial response for carcinoid tumors but one complete and three partial responses for the other tumor types. Efficacy was insufficient in patients who had carcinoid tumors but the combination of dacarbazine with fluorouracil and leucovorin could be an effective regimen for the treatment of neuroendocrine tumors of unknown primary site.