International Olympic Committee consensus statement on thermoregulatory and altitude challenges for high-level athletes

Challenging environmental conditions, including heat and humidity, cold, and altitude, pose particular risks to the health of Olympic and other high-level athletes. As a further commitment to athlete safety, the International Olympic Committee (IOC) Medical Commission convened a panel of experts to review the scientific evidence base, reach consensus, and underscore practical safety guidelines and new research priorities regarding the unique environmental challenges Olympic and other international-level athletes face. For non-aquatic events, external thermal load is dependent on ambient temperature, humidity, wind speed and solar radiation, while clothing and protective gear can measurably increase thermal strain and prompt premature fatigue. In swimmers, body heat loss is the direct result of convection at a rate that is proportional to the effective water velocity around the swimmer and the temperature difference between the skin and the water. Other cold exposure and conditions, such as during Alpine skiing, biathlon and other sliding sports, facilitate body heat transfer to the environment, potentially leading to hypothermia and/or frostbite; although metabolic heat production during these activities usually increases well above the rate of body heat loss, and protective clothing and limited exposure time in certain events reduces these clinical risks as well. Most athletic events are held at altitudes that pose little to no health risks; and training exposures are typically brief and well-tolerated. While these and other environment-related threats to performance and safety can be lessened or averted by implementing a variety of individual and event preventative measures, more research and evidence-based guidelines and recommendations are needed. In the mean time, the IOC Medical Commission and International Sport Federations have implemented new guidelines and taken additional steps to mitigate risk even further.

Energy expenditure by doubly labeled water: validation in humans and proposed calculation.

To further validate the doubly labeled water method for measurement of CO2 production and energy expenditure in humans, we compared it with near-continuous respiratory gas exchange in nine healthy young adult males. Subjects were housed in a respiratory chamber for 4 days. Each received 2H2(18)O at either a low (n = 6) or a moderate (n = 3) isotope dose. Low and moderate doses produced initial 2H enrichments of 5 and 10 X 10(-3) atom percent excess, respectively, and initial 18O enrichments of 2 and 2.5 X 10(-2) atom percent excess, respectively. Total body water was calculated from isotope dilution in saliva collected at 4 and 5 h after the dose. CO2 production was calculated by the two-point method using the isotopic enrichments of urines collected just before each subject entered and left the chamber. Isotope enrichments relative to predose samples were measured by isotope ratio mass spectrometry. At low isotope dose, doubly labeled water overestimated average daily energy expenditure by 8 +/- 9% (SD) (range -7 to 22%). At moderate dose the difference was reduced to +4 +/- 5% (range 0-9%). The isotope elimination curves for 2H and 18O from serial urines collected from one of the subjects showed expected diurnal variations but were otherwise quite smooth. The overestimate may be due to approximations in the corrections for isotope fractionation and isotope dilution. An alternative approach to the corrections is presented that reduces the overestimate to 1%.

Pseudoprogression after high-dose busulfan-thiotepa with autologous stem cell transplantation and radiation therapy in children with brain tumor: impact on survival

Objective: To demonstrate the incidence, time course, predisposing factor and reversibility of neurotoxicity in children with brain tumors treated with high dose busulfan-thiotepa with autologous stem cell transplantation (ASCT) and radiation therapy in our institutional experience.Materials and Methods: We performed a retrospective analysis of prospectively collected data. Between May 1988 and May 2007, 110 patients, median age 3.6 years (range, 1 months-15.3 years), with brain tumors were treated with surgical intervention and conventional chemotherapy. All patients received one course of high-dose busulfan-thiotepa with stem cell rescue, followed or preceded by radiotherapy.Results: Twenty-three patients (21%) developed neuroradiological abnormalities on follow-up imaging studies at a median time of 9.2 months (range, 5.6-17.3 months) after day 0 of ASCT. All MRI-lesions appeared in patients receiving radiotherapy after ASCT and were localized inside the 50-55 Gy isodoses. They disappeared in 14 of 23 patients with a median time of 8 months (range, 3-17 months). The presence of MRI-abnormalities was a favorable prognostic factor for overall survival on univariate analysis (hazard ratio: 0.12, 95% confidence interval [0.04, 0.33]), with a 5-year overall survival in patients with MRI-abnormalities of 84% (95% CI, 62-94), comparedto 27% (95% CI, 19-37) in those without lesions. On multivariate analysis, the presence of MRI-abnormalities was an independent prognostic factor for overall survival.Conclusion: MRI-detectable brain abnormalities are common early findings in children treated with high-dose busulfan-thiotepa followed by radiation therapy, and may mimic early tumor recurrence. They are correlated with a better outcome.

Expression of a plant-derived peptide harboring water-cleaning and antimicrobial activities.

Drinking water is currently a scarce world resource, the preparation of which requires complex treatments that include clarification of suspended particles and disinfection. Seed extracts of Moringa oleifera Lam., a tropical tree, have been proposed as an environment-friendly alternative, due to their traditional use for the clarification of drinking water. However, the precise nature of the active components of the extract and whether they may be produced in recombinant form are unknown. Here we show that recombinant or synthetic forms of a cationic seed polypeptide mediate efficient sedimentation of suspended mineral particles and bacteria. Unexpectedly, the polypeptide was also found to possesses a bactericidal activity capable of disinfecting heavily contaminated water. Furthermore, the polypeptide has been shown to efficiently kill several pathogenic bacteria, including antibiotic-resistant isolates of Staphylococcus, Streptococcus, and Legionella species. Thus, this polypeptide displays the unprecedented feature of combining water purification and disinfectant properties. Identification of an active principle derived from the seed extracts points to a range of potential for drinking water treatment or skin and mucosal disinfection in clinical settings.

Stability analysis of the 2007 Chehalis lake landslide based on long-range terrestrial photogrammetry and airborne LIDAR data

On December 4th 2007, a 3-Mm3 landslide occurred along the northwestern shore of Chehalis Lake. The initiation zone is located at the intersection of the main valley slope and the northern sidewall of a prominent gully. The slope failure caused a displacement wave that ran up to 38 m on the opposite shore of the lake. The landslide is temporally associated with a rain-on-snow meteorological event which is thought to have triggered it. This paper describes the Chehalis Lake landslide and presents a comparison of discontinuity orientation datasets obtained using three techniques: field measurements, terrestrial photogrammetric 3D models and an airborne LiDAR digital elevation model to describe the orientation and characteristics of the five discontinuity sets present. The discontinuity orientation data are used to perform kinematic, surface wedge limit equilibrium and three-dimensional distinct element analyses. The kinematic and surface wedge analyses suggest that the location of the slope failure (intersection of the valley slope and a gully wall) has facilitated the development of the unstable rock mass which initiated as a planar sliding failure. Results from the three-dimensional distinct element analyses suggest that the presence, orientation and high persistence of a discontinuity set dipping obliquely to the slope were critical to the development of the landslide and led to a failure mechanism dominated by planar sliding. The three-dimensional distinct element modelling also suggests that the presence of a steeply dipping discontinuity set striking perpendicular to the slope and associated with a fault exerted a significant control on the volume and extent of the failed rock mass but not on the overall stability of the slope.

Occurrence of Plesiomonas shigelloides in water environments of Rio de Janeiro city

Fresh and salt water samples analyzed in Rio de Janeiro city showed the presence of Plesiomonas shigelloides. Forty-six strains were isolated from both environments. A high incidence of P. shigelloides was achieved in polluted fresh and salt waters as well as in samples from non-polluted streams. P. shigelloides isolates had biochemical characteristics similar to those already described in the literature. None of the isolates analyzed produced enterotoxin in the suckling mouse assay. Hemolytic activity against sheep and human type A erythrocytes was detected in the strains tested. The results of the antibiotic susceptibility tests indicated that all the isolates were susceptible to the cephalosporins, penicillins combined with a beta-lactamase inhibitor, aminoglycosides, imipenem, norfloxacin, tetracycline, chloramphenicol and trimethoprim-sulfamethoxazole. All the isolates were resistant to the penicillins.

Use of High Doses of Quetiapine in Bipolar Disorder Episodes are not Linked to High Activity of Cytochrome P4503A4 and/or Cytochrome P4502D6.

The use of quetiapine for treatment of bipolar disorders at a higher dosage than the licensed range is not unusual in clinical practice. Quetiapine is predominantly metabolised by cytochrome P450 3A4 (CYP3A4) and to a lesser extent by CYP2D6. The large interindividual variability of those isozyme activities could contribute to the variability observed in quetiapine dosage. The aim of the present study is to evaluate if the use of high dosages of quetiapine in some patients, as compared to patients treated with a dosage in the licensed range (up to 800 mg/day), could be explained by a high activity of CYP3A4 and/or of CYP2D6. CYP3A4 activities were determined using the midazolam metabolic ratio in 21 bipolar and schizoaffective bipolar patients genotyped for CYP2D6. 9 patients were treated with a high quetiapine dosage (mean ± SD, median; range: 1467 ± 625, 1200; 1000-3000 mg/day) and 11 with a normal quetiapine dosage (433 ± 274, 350; 100-800 mg/day). One patient in the high dose and one patient in the normal dose groups were genotyped as CYP2D6 ultrarapid metabolizers. CYP3A4 activities were not significantly different between the two groups (midazolam metabolic ratio: 9.4 ± 8.2; 6.2; 1.7-26.8 vs 3.9 ± 2.3; 3.8; 1.5-7.6, in the normal dose group as compared to the high dose group, respectively, NS). The use of high quetiapine dosage for the patients included in the present study cannot be explained by variations in pharmacokinetics parameters such as a high activity of CYP3A4 and/or of CYP2D6.

Recurrence pattern after [(18)F]fluoroethyltyrosine-positron emission tomography-guided radiotherapy for high-grade glioma: a prospective study.

PURPOSE: To assess the failure pattern observed after (18)F fluoroethyltyrosine (FET) planning after chemo- and radiotherapy (RT) for high-grade glioma. METHODS: All patients underwent prospectively RT planning using morphological gross tumour volumes (GTVs) and biological tumour volumes (BTVs). The post-treatment recurrence tumour volumes (RTVs) of 10 patients were transferred on their CT planning. First, failure patterns were defined in terms of percentage of RTV located outside the GTV and BTV. Second, the location of the RTV with respect to the delivered dose distribution was assessed using the RTV's DVHs. Recurrences with >95% of their volume within 95% isodose line were considered as central recurrences. Finally, the relationship between survival and GTV/BTV mismatches was assessed. RESULTS: The median percentages of RTV outside the GTV and BTV were 41.8% (range, 10.5-92.4) and 62.8% (range, 34.2-81.1), respectively. The majority of recurrences (90%) were centrally located. Using a composite target volume planning formalism, the degree of GTV and BTV mismatch did not correlate with survivorship. CONCLUSIONS: The observed failure pattern after FET-PET planning and chemo-RT is primarily central. The target mismatch-survival data suggest that using FET-PET planning may counteract the possibility of BTV-related progression, which may have a detrimental effect on survival.

Exercise induces rapid interstitial lung water accumulation in patients with chronic mountain sickness.

BACKGROUND: Chronic mountain sickness (CMS) is a major public health problem in mountainous regions of the world. In its more advanced stages, exercise intolerance is often found, but the underlying mechanism is not known. Recent evidence indicates that exercise-induced pulmonary hypertension is markedly exaggerated in CMS. We speculated that this problem may cause pulmonary fluid accumulation and aggravate hypoxemia during exercise. METHODS: We assessed extravascular lung water (chest ultrasonography), pulmonary artery pressure, and left ventricular function in 15 patients with CMS and 20 control subjects at rest and during exercise at 3,600 m. RESULTS: Exercise at high altitude rapidly induced pulmonary interstitial fluid accumulation in all patients but one (14 of 15) with CMS and further aggravated the preexisting hypoxemia. In contrast, in healthy high-altitude dwellers exercise did not induce fluid accumulation in the majority of subjects (16 of 20) (P = .002 vs CMS) and did not alter arterial oxygenation. Exercise-induced pulmonary interstitial fluid accumulation and hypoxemia in patients with CMS was accompanied by a more than two times larger increase of pulmonary artery pressure than in control subjects (P < .001), but no evidence of left ventricular dysfunction. Oxygen inhalation markedly attenuated the exercise-induced pulmonary hypertension (P < .01) and interstitial fluid accumulation (P < .05) in patients with CMS but had no detectable effects in control subjects. CONCLUSIONS: To our knowledge, these findings provide the first direct evidence that exercise induces rapid interstitial lung fluid accumulation and hypoxemia in patients with CMS that appear to be related to exaggerated pulmonary hypertension. We suggest that this problem contributes to exercise intolerance in patients with CMS. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT01182792; URL: www.clinicaltrials.gov.

Chemical and carbon isotopic evolution of hydrocarbons during prograde metamorphism from 100°C to 550°C: Case study in the Liassic black shale formation of Central Swiss Alps

Hydrocarbon distributions and stable isotope ratios of carbonates (delta(13)C(car), delta(18)O(car)), kerogen (delta(13)C(ker)), extractable organic matter (delta(13)C(EOM)) and individual hydrocarbons of Liassic black shale samples from a prograde metamorphic sequence in the Swiss Alps were used to identify the major organic reactions with increasing metamorphic grade. The studied samples range from the diagenetic zone (< 100 degrees C) to amphibolite facies (similar to 550 degrees C). The samples within the diagenetic zones (< 100 and 150 degrees C) are characterized by the dominance of C-< 20 n-alkanes, suggesting an origin related with marine and/or bacterial inputs. The metamorphic samples (200 to 550 degrees C) have distributions significantly dominated by C-12 and C-13 n-alkanes, C-14, C-16 and C-18 n-alkylcyclopentanes and to a lesser extend C-15, C-17 and C-21 n-alkylcyclohexanes. The progressive C-13-enrichment (up to 3.9 parts per thousand) with metamorphism of the C-> 17 n-alkanes suggests the occurrence of cracking reactions of high molecular weight compounds. The isotopically heavier (up to 5.6 parts per thousand) C-< 17 n-alkanes in metamorphic samples are likely originated by thermal degradation of long-chain homologous with preferential release of isotopically light C-1 and C-2 radicals. The dominance of specific even C-number n-alkylcyclopentanes suggests an origin related to direct cyclization mechanism (without decarboxylation step) of algal or bacterial fatty acids occurring in reducing aqueous metamorphic fluid conditions. The regular increase of the concentrations of n-alkylcycloalkanes vs. C-> 13 n-alkanes with metamorphism suggests progressive thermal release of kerogen-linked fatty acid precursors and degradation of n-alkanes. Changes of the steroid and terpenoid distributions are clearly related to increasing metamorphic temperatures. The absence of 18 alpha(H)-22,29,30-trisnorneohopane (Ts), the occurrence of 17 beta(H)-trisnorhopane, 17 beta(H), 21 alpha(H)-hopanes in the C-29 to C-31 range and 5 alpha(H),14 alpha(H),17 alpha(H)-20R C-27, C-29 steranes in the low diagenetic samples (< 100 degrees C) are characteristic of immature bitumens. The higher thermal stress within the upper diagenetic zone (150 degrees C) is marked by the presence of Ts, the disappearance of 17 beta(H)-trisnorhopane and thermodynamic equilibrium of the 22S/(22S + 22R) homohopane ratios. The increase of the alpha alpha alpha-sterane 20S/(20S + 20R) and 20R beta beta/(beta beta + alpha alpha) ratios (from 0.0 to 0.55 and from 0.0 to 0.40, respectively) in the upper diagenetic zone indicates the occurrence of isomerization reactions already at < 150 degrees C. However, the isomerization at C-20 (R -> S) reaches thermodynamic equilibrium values already at the upper diagenesis (similar to 150 degrees C) whereas the epimerisation at C-14 and C-17 (alpha alpha ->beta beta) arrives to constant values in the lower anchizone (similar to 200 degrees C). The ratios Ts vs. 17 alpha(H)-22,29,30-trisnorneohopane [(Ts/(Ts + Tm)] and 18 alpha(H)-30-norneohopane (C29Ts) vs. 17 alpha(H),21 beta(H)-30-norhopane [C29Ts/(C29Ts + C-29)] increase until the medium anchizone (200 to 250 degrees C) from 0.0 to 0.96 and from 0.0 to 0.44, respectively. An opposite trend owards lower values is observed in the higher metamorphic samples. The occurrence of specific hydrocarbons (e.g., n-alkylcyclopentanes, cadalene, hydrogenated aromatic compounds) in metamorphic samples points to kerogen degradation reactions most probably occurring in the presence of water and under reducing conditions. The changes of hydrocarbon distributions and carbon isotopic compositions of n-alkanes related to metamorphism suggest that the organic geochemistry may help to evaluate the lowest grades of prograde metamorphism. Copyright (c) 2005 Elsevier Ltd.

Imaging molasse and quaternary sediments in Lake Geneva, Switzerland, with 3-D high-resolution seismic reflection methods: A case study

A high-resolution three-dimensional (3-D) seismic reflection survey was conducted in Lake Geneva, near the city of Lausanne, Switzerland, as part of a project for developing such seismic techniques. Using a single 48-channel streamer, the 3-D site with an area of 1200 m x 600 m was surveyed in 10 days. A variety of complex geologic structures (e.g. thrusts, folds, channel-fill) up to similar to150 m below the water bottom were obtained with a 15 in.(3) water gun. The 3-D data allowed the construction of an accurate velocity model and the distinction of five major seismic facies within the Lower Freshwater Molasse (Aquitanian) and the Quaternary sedimentary units. Additionally, the Plateau Molasse (PM) and Subalpine Molasse (SM) erosional surface, "La Paudeze" thrust fault (PM-SM boundary) and the thickness of Quaternary sediments were accurately delineated in 3-D.

Oligo-Miocene extensional tectonics and fluid flow across the Northern Snake Range detachment system, Nevada

The Northern Snake Range (Nevada) represents a spectacular example of a metamorphic core complex and exposes a complete section from the mylonitic footwall into the hanging wall of a fossil detachment system. Paired geochronological and stable isotopic data of mylonitic quartzite within the detachment footwall reveal that ductile deformation and infiltration of meteoric fluids occurred between 27 and 23 Ma. Ar-40/Ar-39 ages display complex recrystallization-cooling relationships but decrease systematically from 26.9 +/- 0.2 Ma at the top to 21.3 +/- 0.2 Ma at the bottom of footwall mylonite. Hydrogen isotope (delta D) values in white mica are very low (-150 to -145 %) within the top 80-90 m of detachment footwall, in contrast to values obtained from the deeper part of the section where values range from -77 to -64 %, suggesting that time-integrated interaction between rock and meteoric fluid was restricted to the uppermost part of the mylonitic footwall. Pervasive mica-water hydrogen isotope exchange is difficult to reconcile with models of Ar-40 loss during mylonitization solely by volume diffusion. Rather, we interpret the Ar-40/Ar-39 ages of white mica with low-delta D values to date syn-mylonitic hydrogen and argon isotope exchange, and we conclude that the hydrothermal system of the Northern Snake Range was active during late Oligocene (27-23 Ma) and has been exhumed by the combined effects of ductile strain, extensional detachment faulting, and erosion.

Origin of amphibole megacrysts in the Pliocene-Pleistocene basalts of the Carpathian-Pannonian region

Major and trace element compositions, stable H and 0 isotope compositions and Fe 31 contents of amphibole megacrysts of Pliocene-Pleistocene alkaline basalts have been investigated to obtain information on the origin of mantle fluids beneath the Carpathian-Pannonian region. The megacrysts have been regarded as igneous cumulates formed in the mantle and brought to the surface by the basaltic magma. The studied amphiboles have oxygen isotope compositions (5.4 +/- 0.2 %., 1 sigma), supporting their primary mantle origin. Even within the small 6180 variation observed, correlations with major and trace elements are detected. The negative delta(18)O-MgO and the positive delta(18)O-La/Sm(N) correlations are interpreted to have resulted from varying degrees of partial melting. The halogen (F, Cl) contents are very low (< 0.1 wt. %), however, a firm negative (F+Cl)-MgO correlation (R(2) = 0.84) can be related to the Mg-Cl avoidance in the amphibole structure. The relationships between water contents, H isotope compositions and Fe 31 contents of the amphibole megacrysts revealed degassing. Selected undegassed amphibole megacrysts show a wide 813 range from -80 to -20 parts per thousand. The low delta D value is characteristic of the normal mantle, whereas the high delta D values may indicate the influence of fluids released from subducted oceanic crust. The chemical and isotopic evidence collectively suggest that formation of the amphibole megacrysts is related to fluid metasomatism, whereas direct melt addition is insignificant.

Quantitative integration of geophysical and hydraulic data : from the local towards the regional scale range

Des progrès significatifs ont été réalisés dans le domaine de l'intégration quantitative des données géophysique et hydrologique l'échelle locale. Cependant, l'extension à de plus grandes échelles des approches correspondantes constitue encore un défi majeur. Il est néanmoins extrêmement important de relever ce défi pour développer des modèles fiables de flux des eaux souterraines et de transport de contaminant. Pour résoudre ce problème, j'ai développé une technique d'intégration des données hydrogéophysiques basée sur une procédure bayésienne de simulation séquentielle en deux étapes. Cette procédure vise des problèmes à plus grande échelle. L'objectif est de simuler la distribution d'un paramètre hydraulique cible à partir, d'une part, de mesures d'un paramètre géophysique pertinent qui couvrent l'espace de manière exhaustive, mais avec une faible résolution (spatiale) et, d'autre part, de mesures locales de très haute résolution des mêmes paramètres géophysique et hydraulique. Pour cela, mon algorithme lie dans un premier temps les données géophysiques de faible et de haute résolution à travers une procédure de réduction déchelle. Les données géophysiques régionales réduites sont ensuite reliées au champ du paramètre hydraulique à haute résolution. J'illustre d'abord l'application de cette nouvelle approche dintégration des données à une base de données synthétiques réaliste. Celle-ci est constituée de mesures de conductivité hydraulique et électrique de haute résolution réalisées dans les mêmes forages ainsi que destimations des conductivités électriques obtenues à partir de mesures de tomographic de résistivité électrique (ERT) sur l'ensemble de l'espace. Ces dernières mesures ont une faible résolution spatiale. La viabilité globale de cette méthode est testée en effectuant les simulations de flux et de transport au travers du modèle original du champ de conductivité hydraulique ainsi que du modèle simulé. Les simulations sont alors comparées. Les résultats obtenus indiquent que la procédure dintégration des données proposée permet d'obtenir des estimations de la conductivité en adéquation avec la structure à grande échelle ainsi que des predictions fiables des caractéristiques de transports sur des distances de moyenne à grande échelle. Les résultats correspondant au scénario de terrain indiquent que l'approche d'intégration des données nouvellement mise au point est capable d'appréhender correctement les hétérogénéitées à petite échelle aussi bien que les tendances à gande échelle du champ hydraulique prévalent. Les résultats montrent également une flexibilté remarquable et une robustesse de cette nouvelle approche dintégration des données. De ce fait, elle est susceptible d'être appliquée à un large éventail de données géophysiques et hydrologiques, à toutes les gammes déchelles. Dans la deuxième partie de ma thèse, j'évalue en détail la viabilité du réechantillonnage geostatique séquentiel comme mécanisme de proposition pour les méthodes Markov Chain Monte Carlo (MCMC) appliquées à des probmes inverses géophysiques et hydrologiques de grande dimension . L'objectif est de permettre une quantification plus précise et plus réaliste des incertitudes associées aux modèles obtenus. En considérant une série dexemples de tomographic radar puits à puits, j'étudie deux classes de stratégies de rééchantillonnage spatial en considérant leur habilité à générer efficacement et précisément des réalisations de la distribution postérieure bayésienne. Les résultats obtenus montrent que, malgré sa popularité, le réechantillonnage séquentiel est plutôt inefficace à générer des échantillons postérieurs indépendants pour des études de cas synthétiques réalistes, notamment pour le cas assez communs et importants où il existe de fortes corrélations spatiales entre le modèle et les paramètres. Pour résoudre ce problème, j'ai développé un nouvelle approche de perturbation basée sur une déformation progressive. Cette approche est flexible en ce qui concerne le nombre de paramètres du modèle et lintensité de la perturbation. Par rapport au rééchantillonage séquentiel, cette nouvelle approche s'avère être très efficace pour diminuer le nombre requis d'itérations pour générer des échantillons indépendants à partir de la distribution postérieure bayésienne. - Significant progress has been made with regard to the quantitative integration of geophysical and hydrological data at the local scale. However, extending corresponding approaches beyond the local scale still represents a major challenge, yet is critically important for the development of reliable groundwater flow and contaminant transport models. To address this issue, I have developed a hydrogeophysical data integration technique based on a two-step Bayesian sequential simulation procedure that is specifically targeted towards larger-scale problems. The objective is to simulate the distribution of a target hydraulic parameter based on spatially exhaustive, but poorly resolved, measurements of a pertinent geophysical parameter and locally highly resolved, but spatially sparse, measurements of the considered geophysical and hydraulic parameters. To this end, my algorithm links the low- and high-resolution geophysical data via a downscaling procedure before relating the downscaled regional-scale geophysical data to the high-resolution hydraulic parameter field. I first illustrate the application of this novel data integration approach to a realistic synthetic database consisting of collocated high-resolution borehole measurements of the hydraulic and electrical conductivities and spatially exhaustive, low-resolution electrical conductivity estimates obtained from electrical resistivity tomography (ERT). The overall viability of this method is tested and verified by performing and comparing flow and transport simulations through the original and simulated hydraulic conductivity fields. The corresponding results indicate that the proposed data integration procedure does indeed allow for obtaining faithful estimates of the larger-scale hydraulic conductivity structure and reliable predictions of the transport characteristics over medium- to regional-scale distances. The approach is then applied to a corresponding field scenario consisting of collocated high- resolution measurements of the electrical conductivity, as measured using a cone penetrometer testing (CPT) system, and the hydraulic conductivity, as estimated from electromagnetic flowmeter and slug test measurements, in combination with spatially exhaustive low-resolution electrical conductivity estimates obtained from surface-based electrical resistivity tomography (ERT). The corresponding results indicate that the newly developed data integration approach is indeed capable of adequately capturing both the small-scale heterogeneity as well as the larger-scale trend of the prevailing hydraulic conductivity field. The results also indicate that this novel data integration approach is remarkably flexible and robust and hence can be expected to be applicable to a wide range of geophysical and hydrological data at all scale ranges. In the second part of my thesis, I evaluate in detail the viability of sequential geostatistical resampling as a proposal mechanism for Markov Chain Monte Carlo (MCMC) methods applied to high-dimensional geophysical and hydrological inverse problems in order to allow for a more accurate and realistic quantification of the uncertainty associated with the thus inferred models. Focusing on a series of pertinent crosshole georadar tomographic examples, I investigated two classes of geostatistical resampling strategies with regard to their ability to efficiently and accurately generate independent realizations from the Bayesian posterior distribution. The corresponding results indicate that, despite its popularity, sequential resampling is rather inefficient at drawing independent posterior samples for realistic synthetic case studies, notably for the practically common and important scenario of pronounced spatial correlation between model parameters. To address this issue, I have developed a new gradual-deformation-based perturbation approach, which is flexible with regard to the number of model parameters as well as the perturbation strength. Compared to sequential resampling, this newly proposed approach was proven to be highly effective in decreasing the number of iterations required for drawing independent samples from the Bayesian posterior distribution.

High occurrence of hepatitis E virus in samples from wastewater treatment plants in Switzerland and comparison with other enteric viruses.

Hepatitis E virus (HEV) is responsible for many enterically transmitted viral hepatitides around the world. It is currently one of the waterborne diseases of global concern. In industrialized countries, HEV appears to be more common than previously thought, even if it is rarely virulent. In Switzerland, seroprevalence studies revealed that HEV is endemic, but no information was available on its environmental spread. The aim of this study was to investigate -using qPCR- the occurrence and concentration of HEV and three other viruses (norovirus genogroup II, human adenovirus-40 and porcine adenovirus) in influents and effluents of 31 wastewater treatment plants (WWTPs) in Switzerland. Low concentrations of HEV were detected in 40 out of 124 WWTP influent samples, showing that HEV is commonly present in this region. The frequency of HEV occurrence was higher in summer than in winter. No HEV was detected in WWTP effluent samples, which indicates a low risk of environmental contamination. HEV occurrence and concentrations were lower than those of norovirus and adenovirus. The autochthonous HEV genotype 3 was found in all positive samples, but a strain of the non-endemic and highly pathogenic HEV genotype I was isolated in one sample, highlighting the possibility of environmental circulation of this genotype. A porcine fecal marker (porcine adenovirus) was not detected in HEV positive samples, indicating that swine are not the direct source of HEV present in wastewater. Further investigations will be necessary to determine the reservoirs and the routes of dissemination of HEV.