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SS 433 is a binary system containing a supergiant star that is overflowing its Roche lobe with matter accreting onto a compact object (either a black hole or neutron star)1-3. Two jets of ionized matter with a bulk velocity of approximately 0.26c (where c is the speed of light in vacuum) extend from the binary, perpendicular to the line of sight, and terminate inside W50, a supernova remnant that is being distorted by the jets2,4-8. SS 433 differs from other microquasars (small-scale versions of quasars that are present within our own Galaxy) in that the accretion is believed to be super-Eddington9-11, and the luminosity of the system is about 1040 ergs per second2,9,12,13. The lobes of W50 in which the jets terminate, about 40 parsecs from the central source, are expected to accelerate charged particles, and indeed radio and X-ray emission consistent with electron synchrotron emission in a magnetic field have been observed14-16. At higher energies (greater than 100 gigaelectronvolts), the particle fluxes of γ-rays from X-ray hotspots around SS 433 have been reported as flux upper limits6,17-20. In this energy regime, it has been unclear whether the emission is dominated by electrons that are interacting with photons from the cosmic microwave background through inverse-Compton scattering or by protons that are interacting with the ambient gas. Here we report teraelectronvolt γ-ray observations of the SS 433/W50 system that spatially resolve the lobes. The teraelectronvolt emission is localized to structures in the lobes, far from the centre of the system where the jets are formed. We have measured photon energies of at least 25 teraelectronvolts, and these are certainly not Doppler-boosted, because of the viewing geometry. We conclude that the emission-from radio to teraelectronvolt energies-is consistent with a single population of electrons with energies extending to at least hundreds of teraelectronvolts in a magnetic field of about 16 microgauss.
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In this Letter, owing to a production error, the penultimate version of the PDF was published. The HTML version was always correct. The PDF has been corrected online.
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Neurosarcoidosis is an uncommon but potentially serious disease of the central nervous system that can cause major sequelae. We analyzed the presence and diagnostic usefulness of specific cutaneous lesions in 58 patients with neurosarcoidosis. Sixteen patients (27.6%) had specific cutaneous lesions (14 men and 2 women; mean age, 50 years [range, 20-84 years]). Twenty-four types of neurological lesions were observed: cranial neuropathy (n=7), parenchymal lesions (n=4), meningeal lesions (n=3), myelopathy (n=3), pituitary lesions (n=1), hydrocephalus (n=2), and peripheral neuropathy (n=4). Twenty types of specific cutaneous lesions were observed: maculopapular lesions (n=6), plaques (n=9), lupus pernio (n=1), and scar sarcoidosis (n=4). These last lesions coexisted with maculopapular lesions in 2 patients and plaques in another 2. Specific cutaneous lesions were present at diagnosis of neurosarcoidosis in 13 patients. Recognition of specific cutaneous lesions in a patient with suspected neurosarcoidosis is important as biopsy can accelerate diagnosis.
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Doenças do Sistema Nervoso Central , Sarcoidose , Masculino , Humanos , Feminino , Pessoa de Meia-Idade , Doenças do Sistema Nervoso Central/complicações , Doenças do Sistema Nervoso Central/diagnóstico , Doenças do Sistema Nervoso Central/patologia , Sarcoidose/complicações , Sarcoidose/diagnóstico , Progressão da DoençaRESUMO
We report the first detection of a TeV γ-ray flux from the solar disk (6.3σ), based on 6.1 years of data from the High Altitude Water Cherenkov (HAWC) observatory. The 0.5-2.6 TeV spectrum is well fit by a power law, dN/dE=A(E/1 TeV)^{-γ}, with A=(1.6±0.3)×10^{-12} TeV^{-1} cm^{-2} s^{-1} and γ=3.62±0.14. The flux shows a strong indication of anticorrelation with solar activity. These results extend the bright, hard GeV emission from the disk observed with Fermi-LAT, seemingly due to hadronic Galactic cosmic rays showering on nuclei in the solar atmosphere. However, current theoretical models are unable to explain the details of how solar magnetic fields shape these interactions. HAWC's TeV detection thus deepens the mysteries of the solar-disk emission.
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Cupriavidus necator UYPR2.512 is a rhizobial strain that belongs to the Beta-subclass of proteobacteria, able to establish successful symbiosis with Mimosoid legumes. The initial steps of rhizobium-legumes symbioses involve the reciprocal recognition by chemical signals, being luteolin one of the molecules involved. However, there is a lack of information on the effect of luteolin in beta-rhizobia. In this work, we used long-read sequencing to complete the genome of UYPR2.512 providing evidence for the existence of four closed circular replicons. We used an RNA-Seq approach to analyse the response of UYPR2.512 to luteolin. One hundred and forty-five genes were differentially expressed, with similar numbers of downregulated and upregulated genes. Most repressed genes were mapped to the main chromosome, while the upregulated genes were overrepresented among pCne512e, containing the symbiotic genes. Induced genes included the nod operon and genes implicated in exopolysaccharides and flagellar biosynthesis. We identified many genes involved in iron, copper and other heavy metals metabolism. Among repressed genes, we identified genes involved in basal carbon and nitrogen metabolism. Our results suggest that in response to luteolin, C. necator strain UYPR2.512 reshapes its metabolism in order to be prepared for the forthcoming symbiotic interaction.
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Cupriavidus necator , Cupriavidus , Fabaceae , Rhizobium , Cupriavidus/genética , Cupriavidus necator/genética , Fabaceae/microbiologia , Genômica , Luteolina/metabolismo , Luteolina/farmacologia , Fixação de Nitrogênio , Filogenia , Rhizobium/genética , Simbiose/genética , TranscriptomaRESUMO
Because of the high energies and long distances to the sources, astrophysical observations provide a unique opportunity to test possible signatures of Lorentz invariance violation (LIV). Superluminal LIV enables the decay of photons at high energy. The high altitude water Cherenkov (HAWC) observatory is among the most sensitive gamma-ray instruments currently operating above 10 TeV. HAWC finds evidence of 100 TeV photon emission from at least four astrophysical sources. These observations exclude, for the strongest of the limits set, the LIV energy scale to 2.2×10^{31} eV, over 1800 times the Planck energy and an improvement of 1 to 2 orders of magnitude over previous limits.
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We present the first catalog of gamma-ray sources emitting above 56 and 100 TeV with data from the High Altitude Water Cherenkov Observatory, a wide field-of-view observatory capable of detecting gamma rays up to a few hundred TeV. Nine sources are observed above 56 TeV, all of which are likely galactic in origin. Three sources continue emitting past 100 TeV, making this the highest-energy gamma-ray source catalog to date. We report the integral flux of each of these objects. We also report spectra for three highest-energy sources and discuss the possibility that they are PeVatrons.
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The study of skin color in cattle holds both economic and scientific interest. Several ocular diseases of cattle have been associated with low pigmentation of the eyelids, including ocular squamous cell carcinoma and infectious keratoconjunctivitis, the two most common ocular diseases affecting cattle production. Although low eyelid pigmentation is a well-known risk factor for various ocular diseases, the genetic and biological basis of this relationship is largely unknown. We investigated the transcriptome of eyelid skin in Hereford cattle using RNA-sequencing technology. Two contrasting groups were evaluated: steers that were completely pigmented and steers with no pigmentation in both eyelids. Most of the up-regulated genes in pigmented samples are directly implicated in melanogenesis and melanosome development, whereas up-regulated genes in non-pigmented samples are implicated in cancer development and the immune system, among other functions. Interestingly, network analysis comparing pigmented vs. non-pigmented samples revealed significant differences in the co-expression patterns of genes related to melanosome, pigmentation and defense response to bacteria, showing higher gene activity, greater co-expression patterns and tighter co-regulation mechanisms in pigmented samples. Overall, our findings indicate that bovine eyelid pigmentation depends on the expression of many genes involved not only in pigmentation and melanosome function but also related to inflammatory response, infection and tumoral pathways.
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Bovinos/genética , Pálpebras , Pigmentação/genética , Transcriptoma , Animais , Cruzamento , Oftalmopatias/genética , Oftalmopatias/veterinária , Expressão Gênica , Masculino , Melaninas/biossíntese , Melanossomas/genética , FenótipoRESUMO
The alpha power increase that occurs when the eyes are closed is one of the most well-known effects in human electrophysiology. In particular, previous psychological studies have investigated whether eye closure can boost memory performance under certain circumstances, providing contradictory evidence across sensory input modalities. Although alpha power is modulated during different phases of memory and these modulations are correlated with performance, few studies have reported on the relationship between eye closure, memory, and alpha-band power. The present study investigates the influence of eye closure while participants (nâ¯=â¯21) performed an auditory recognition memory task with spoken words during the recording of magnetoencephalography (MEG) data. Our results showed no evidence for a behavioural effect of eye closure in the performance of the task. In addition, electrophysiological responses to the stimuli showed the expected alpha event-related desynchronization (ERD) 0.5-1â¯s and a high-alpha/beta event-related synchronization (ERS) 1-2â¯s after word onset. The data showed the expected memory effect, i.e. remembered words elicited greater 10â¯Hz ERD than forgotten words in the brain regions typically associated with the language network, suggesting a modulation of tau rhythm. Eye closure modulated alpha rhythm only in posterior-parietal and occipital regions. The lack of interaction and the different localizations found for modulations of tau and classical alpha rhythms suggests that these rhythms play distinct functional roles in memory performance.
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Ritmo alfa , Percepção Auditiva/fisiologia , Encéfalo/fisiologia , Rememoração Mental/fisiologia , Reconhecimento Psicológico/fisiologia , Sincronização Cortical , Olho , Feminino , Humanos , Magnetoencefalografia , MasculinoRESUMO
The Uruguayan Creole cattle population (N = 600) is located in a native habitat in south-east Uruguay. We analyzed its genetic diversity and compared it to other populations of American Creole cattle. A random sample of 64 animals was genotyped for a set of 17 microsatellite loci, and the D-loop hyper-variable region of mtDNA was sequenced for 28 calves of the same generation. We identified an average of 5.59 alleles per locus, with expected heterozygosities between 0.466 and 0.850 and an expected mean heterozygosity of 0.664. The polymorphic information content ranged from 0.360 to 0.820, and the global FIS index was 0.037. The D-loop analysis revealed three haplotypes (UY1, UY2 and UY3), belonging to the European matriline group, with a haplotype diversity of 0.532. The history of the population, changes in the effective population size, bottlenecks, and genetic drift are possible causes of the genetic variability patterns that we detected.
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DNA Mitocondrial/genética , Variação Genética , Repetições de Microssatélites/genética , Alelos , Animais , Cruzamento , Bovinos , Evolução Molecular , Frequência do Gene , Genética Populacional , Haplótipos , FilogeniaRESUMO
INTRODUCTION AND OBJECTIVE: The most frequently studied factors in patients treated by robotic radical prostatectomy are PSA and pathological features of the biopsy and prostatectomy specimen. Studies on the factors associated with the surgical technique are scarce and with controversial results. The objective is to identify all possible surgical factors and their relationship with disease-free and metastasis-free survival. PATIENTS AND METHOD: Prospective study approved by the Ethics Committee, including patients who underwent robotic radical prostatectomy since January 2009 with a minimum follow-up of 5 years. Surgeon, surgical time, blood loss, fascial access, continence techniques, preservation of the fascia, neurovascular bundles, bladder neck, urethra, learning curve and surgical complications, were analyzed as possible prognostic factors. We performed univariate and matched comparisons of survival using Kaplan-Meier estimation and long-rank tests. The significance level for multiple comparisons was established with False Discovery Rate-adjustment (adjusted p). RESULTS: Cohort of 667 patients with a median follow-up of 69 months. In univariate analysis, surgeon (adjp=0.018), preservation of puboprostatic ligaments (adjp=0.02), preservation of endopelvic fascia (adjp=0.001) and performing periurethral suspension (adjp<0.001) are poor prognostic factors for disease-free survival. Fascia preservation also negatively affects metastasis-free survival (adjp=0.04). Previous abdominal surgeries, prostate, surgical time, blood loss, type of residual urethra, middle lobe, fascial access, fascia or bladder neck preservation, have no statistical significance. CONCLUSIONS: The surgeon and specific aspects of the surgical technique are determining factors in disease-free survival. Preservation of the fascia is the only factor that negatively affects metastasis-free survival.
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Procedimentos Cirúrgicos Robóticos , Incontinência Urinária , Masculino , Humanos , Próstata , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Incontinência Urinária/etiologia , Prognóstico , Estudos Prospectivos , Prostatectomia/métodosRESUMO
Scientific community have gained lots of new insights in the genetic and biochemical background of different conditions, rare diseases included, settling the basis for preclinical models that are helping to identify new biomarkers and therapeutic targets. Translational Medicine (TM) is an interdisciplinary area of biomedicine with an essential role in bench-to-bedside transition enhancement, generating a circular flow of knowledge transference between research environment and clinical setting, always centered in patient needs. Here, we present different tools used in TM and an overview of what is being done related to hereditary hemorrhagic telangiectasia (HHT), as a disease's model. This work is focused on how this combination of basic and clinical research impacts in HHT patient's daily clinical management and also looking into the future. Further randomized clinical trials with HHT patients should assess the findings of this bench-to-bedside transition. The benefits of this basic and clinical research combination, may not only be important for HHT patients but for patients with other vascular diseases sharing angiogenic disturbances.
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Telangiectasia Hemorrágica Hereditária , Biomarcadores , Humanos , Telangiectasia Hemorrágica Hereditária/genética , Ciência Translacional BiomédicaRESUMO
BACKGROUND: Adrenomedullin (AM) is a vasoactive peptide mostly secreted by endothelial cells with an important role in preserving endothelial integrity. The relationship between AM and hereditary hemorrhagic telangiectasia (HHT) is unknown. We aimed to compare the serum levels and tissue expression of AM between HHT patients and controls. METHODS: Serum AM levels were measured by radioimmunoassay and compared between control and HHT groups. AM levels were also compared among HHT subgroups according to clinical characteristics. The single nucleotide polymorphism (SNP) rs4910118 was assessed by restriction analysis and sequencing. AM immunohistochemistry was performed on biopsies of cutaneous telangiectasia from eight HHT patients and on the healthy skin from five patients in the control group. RESULTS: Forty-five HHT patients and 50 healthy controls were included, mean age (SD) was 50.7 (14.9) years and 46.4 (9.9) years (p = 0.102), respectively. HHT patients were mostly female (60% vs 38%, p = 0.032). Median [Q1-Q3] serum AM levels were 68.3 [58.1-80.6] pg/mL in the HHT group and 47.7 [43.2-53.8] pg/mL in controls (p<0.001), with an optimal AM cut-off according to Youden's J statistic of 55.32 pg/mL (J:0.729). Serum AM levels were similar in the HHT subgroups. No patient with HHT had the SNP rs4910118. AM immunoreactivity was found with high intensity in the abnormal blood vessels of HHT biopsies. CONCLUSIONS: We detected higher AM serum levels and tissue expression in patients with HHT than in healthy controls. The role of AM in HHT, and whether AM may constitute a novel biomarker and therapeutic target, needs further investigation.
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Telangiectasia Hemorrágica Hereditária , Adrenomedulina/genética , Biomarcadores , Células Endoteliais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Telangiectasia Hemorrágica Hereditária/genéticaRESUMO
INTRODUCTION: Some COVID-19 patients evolve to severe lung injury and systemic hyperinflammatory syndrome triggered by both the coronavirus infection and the subsequent host-immune response. Accordingly, the use of immunomodulatory agents has been suggested but still remains controversial. Our working hypothesis is that methylprednisolone pulses and tacrolimus may be an effective and safety drug combination for treating severe COVID-19 patients. METHODS: and analysis: TACROVID is a randomized, open-label, single-center, phase II trial to evaluate the efficacy and safety of methylprednisolone pulses and tacrolimus plus standard of care (SoC) versus SoC alone, in patients at advanced stage of COVID-19 disease with lung injury and systemic hyperinflammatory response. Patients are randomly assigned (1:1) to one of two arms (42 patients in each group). The primary aim is to assess the time to clinical stability after initiating randomization. Clinical stability is defined as body temperature ≤37.5 °C, and PaO2/FiO2 > 400 and/or SatO2/FiO2 > 300, and respiratory rate ≤24 rpm; for 48 consecutive hours. DISCUSSION: Methylprednisolone and tacrolimus might be beneficial to treat those COVID-19 patients progressing into severe pulmonary failure and systemic hyperinflammatory syndrome. The rationale for its use is the fast effect of methylprednisolone pulses and the ability of tacrolimus to inhibit both the CoV-2 replication and the secondary cytokine storm. Interestingly, both drugs are low-cost and can be manufactured on a large scale; thus, if effective and safe, a large number of patients could be treated in developed and developing countries. TRIAL REGISTRATION NUMBER: NCT04341038 / EudraCT: 2020-001445-39.
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BACKGROUND: Gender differences in organ involvement and clinical severity have been poorly described in hereditary hemorrhagic telangiectasia (HHT). The aim of this study was to describe differences in the severity of HHT manifestations according to gender. METHODS: Severity was measured according to Epistaxis Severity Score (ESS), Simple Clinical Scoring Index for hepatic involvement, a general HHT-score, needing for invasive treatment (pulmonary or brain arteriovenous malformations -AVMs- embolization, liver transplantation or Young's surgery) or the presence of adverse outcomes (severe anemia, emergency department -ED- or hospital admissions and mortality). RESULTS: One hundred forty-two (58.7%) women and 100 (41.3%) men were included with a mean age of 48.9 ± 16.6 and 49 ± 16.5 years, respectively. Women presented hepatic manifestations (7.1% vs 0%) and hepatic involvement (59.8% vs 47%), hepatic AVMs (28.2% vs 13%) and bile duct dilatation (4.9% vs 0%) at abdominal CT, and pulmonary AVMs at thoracic CT (35.2% vs 23%) more often than men. The Simple Clinical Scoring Index was higher in women (3.38 ± 1.2 vs 2.03 ± 1.2), and more men were considered at low risk of harboring clinically significant liver disease than women (61% vs 25.3%). These differences were mantained when considering HHT1 and HHT2 patients separetely. Duodenal telangiectasia were more frequent in men than women (21% vs 9.8%). Invasive treatments were more frequently needed in women (28.2% vs 16%) but men needed attention at the ED more often than women (48% vs 28.2%), with no differences in ESS, HHT-score, anemia hospital admissions or mortality. CONCLUSIONS: HHT women showed more severe hepatic involvement than men, also among HHT1 and HHT2 patients. Women had higher prevalence of pulmonary AVMs and needed invasive procedures more frequently, while men needed attention at the ED more often. These data might help physicians to individualize HHT patients follow-up.
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Malformações Arteriovenosas , Hepatopatias , Telangiectasia Hemorrágica Hereditária , Adulto , Idoso , Epistaxe , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Caracteres SexuaisRESUMO
The reference diagnostic method of human abdominal Cystic Echinococcosis (CE) is imaging, particularly ultrasound, supported by serology when imaging is inconclusive. However, current diagnostic tools are neither optimal nor widely available. The availability of a test detecting circulating biomarkers would considerably improve CE diagnosis and cyst staging (active vs inactive), as well as treatments and follow-up of patients. Exosomes are extracellular vesicles involved in intercellular communication, including immune system responses, and are a recognized source of biomarkers. With the aim of identifying potential biomarkers, plasma pools from patients infected by active or inactive CE, as well as from control subjects, were processed to isolate exosomes for proteomic label-free quantitative analysis. Results were statistically processed and subjected to bioinformatics analysis to define distinct features associated with parasite viability. First, a few parasite proteins were identified that were specifically associated with either active or inactive CE, which represent potential biomarkers to be validated in further studies. Second, numerous identified proteins of human origin were common to active and inactive CE, confirming an overlap of several immune response pathways. However, a subset of human proteins specific to either active or inactive CE, and central in the respective protein-protein interaction networks, were identified. These include the Src family kinases Src and Lyn, and the immune-suppressive cytokine TGF-ß in active CE, and Cdc42 in inactive CE. The Src and Lyn Kinases were confirmed as potential markers of active CE in totally independent plasma pools. In addition, insights were obtained on immune response profiles: largely consistent with previous evidence, our observations hint to a Th1/Th2/regulatory immune environment in patients with active CE and a Th1/inflammatory environment with a component of the wound healing response in the presence of inactive CE. Of note, our results were obtained for the first time from the analysis of samples obtained in vivo from a well-characterized, large cohort of human subjects.
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Equinococose/imunologia , Echinococcus granulosus/metabolismo , Exossomos/imunologia , Adulto , Animais , Biomarcadores/metabolismo , Citocinas/metabolismo , Equinococose/sangue , Feminino , Humanos , Masculino , Espectrometria de Massas , Plasma/metabolismo , ProteômicaRESUMO
In this paper we show how to compute the normalizing and the system matrix terms of the EM-ML reconstruction algorithm for rotating planar detector PET scanners. The method introduced is valid for either pixelated or continuous scintillators. We base our computations in geometrical considerations, but other effects of the PET process can be easily included. In this regard, the intrinsic resolution of the detection system, the depth of interaction (DOI) of the incident gamma rays and the efficiency of the scintillators have been modeled in our development. The computation of the normalizing term and the system matrix is valid for any basis function used for the discrete approximation of the radionuclide concentration. We show that our computations are comparable to those of a Monte Carlo method at a small fraction of the computational cost.
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Algoritmos , Processamento de Imagem Assistida por Computador/métodos , Modelos Biológicos , Tomografia por Emissão de Pósitrons/instrumentação , Rotação , Método de Monte Carlo , Reprodutibilidade dos Testes , IncertezaRESUMO
Carbapenem-resistant Enterobacteriaceae is a growing concern worldwide. Klebsiella pneumoniae is an important nosocomial pathogen with a high capacity for nosocomial spread. We described the occurrence of plasmid-encoded KPC-2-harbouring K. pneumoniae isolates recovered from a neurosurgical centre in Argentina. The blaKPC-2 gene was surrounded by ISkpn6 and ISkpn7.
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Ochrobactrum anthropi, a rare human pathogen, has been isolated predominantly from patients with catheter-related bacteraemia and rarely from other infections. In 2016, six cases of pseudo-bacteraemia caused by carbapenem-resistant O. anthropi isolates were recovered from an Argentinian hospital. The resistant phenotype exposed by the isolates caught our attention and led to an extensive epidemiologic investigation. Here we describe the characterization of a carbapenem-resistant O. anthropi outbreak whose probable cause was by contaminated collection tubes. The genome analysis of one strain revealed the presence of various resistant determinants. Among them, a metal-dependent hydrolase of the ß-lactamase superfamily I, phnP, was found. Lately the recovery of unusual multidrug-resistant pathogens in the clinical setting has increased, thus emphasizing the need to implement standardized infection control practice and epidemiologic investigation to identify the real cause of hospital outbreaks.
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Groundwater represents a very significant source of fresh water for irrigation and drinking purposes and therefore preserving the availability and quality of this resource is extremely important. A first assessment of the amount of pollutants that can be exported to groundwater via soil drainage can be made by a) measuring the amount of contaminants present in the soil solution at the bottom of the soil after a prolonged simulated rainfall event, and b) estimating the amount of drainage water passing the soil bottom during a period of time long enough to include sufficient instances of both, wet and dry episodes inherent to the local climate. Drainage water was estimated by means of a simple infiltration model ("bucket model") which computes on a daily basis the inputs and outputs of soil water through rainfall and evapotranspiration generated by a stochastic model of the local climate along a period of 50-100 years. The methodology was applied in the Guadiamar valley after the toxic spill of a pyrite mine in Aznalcóllar (Spain). The results show that Zn is the dominant contaminant at the site with a 1.2 g m(-2)year(-1) contribution to groundwater. The presence of a gravel rich horizon below 50 cm depth reveals an increase in drainage and the threat to groundwater.