The performance of a plasma real-time PCR (cytomegalovirus CMV PCR kit; Abbott Diagnostics) was compared with that of the antigenemia assay for the surveillance of active CMV infection in 42 ...allogeneic hematopoietic stem cell transplantation (Allo-SCT) recipients. A total of 1,156 samples were analyzed by the two assays. Concordance between the two assays was 82.2%. Plasma DNA levels correlated with the number of pp65-positive cells, particularly prior to the initiation of preemptive therapy. Fifty-seven episodes of active CMV infection were detected in 37 patients: 18 were defined solely by the PCR assay and four were defined on the basis of the antigenemia assay. Either a cutoff of 288 CMV DNA copies/ml or a 2.42-log₁₀ increase of DNAemia levels between two consecutive PCR positive samples was an optimal value to discriminate between patients requiring preemptive therapy and those not requiring therapy on the basis of the antigenemia results. The real-time PCR assay allowed an earlier diagnosis of active CMV infection and was a more reliable marker of successful clearance of CMV from the blood. Analysis of the kinetics of DNAemia levels at a median of 7 days posttreatment allowed the prediction of the response to CMV therapy. Two patients developed CMV colitis. The PCR assay tested positive both before the onset of symptoms and during the disease period. The plasma real-time PCR from Abbott is more suitable than the antigenemia assay for monitoring active CMV infection in Allo-SCT recipients and may be used for guiding preemptive therapy in this clinical setting.
Dilated cardiomyopathy (DCM) is the most frequent cause of heart transplantation (HTx). The genetic basis of DCM among patients undergoing HTx has been poorly characterized. We sought to determine ...the genetic basis of familial DCM HTx and to establish the yield of modern next generation sequencing (NGS) technologies in this setting.
Fifty-two heart-transplanted patients due to familial DCM underwent NGS genetic evaluation with a panel of 126 genes related to cardiac conditions (59 associated with DCM). Genetic variants were initially classified as pathogenic mutations or as variants of uncertain significance (VUS). Final pathogenicity status was determined by familial cosegregation studies.
Initially, 24 pathogenic mutations were found in 21 patients (40%); 25 patients (48%) carried 19 VUS and 6 (12%) did not show any genetic variant. Familial evaluation of 220 relatives from 36 of the 46 families with genetic variants confirmed pathogenicity in 14 patients and allowed reclassification of VUS as pathogenic in 17 patients, and as non-pathogenic in 3 cases. At the end of the study, the DCM-causing mutation was identified in 38 patients (73%) and 5 patients (10%) harbored only VUS. No genetic variants were identified in 9 cases (17%).
The genetic spectrum of familial DCM patients undergoing HTx is heterogeneous and involves multiple genes. NGS technology plus detailed familial studies allow identification of causative mutations in the vast majority of familial DCM cases. Detailed familial studies remain critical to determine the pathogenicity of underlying genetic defects in a substantial number of cases.
Collagen, as the major structural protein of the extracellular matrix in animals, is a versatile biomaterial of great interest in various engineering applications. Electrospun nanofibers of collagen ...are regarded as very promising materials for tissue engineering applications because they can reproduce the morphology of the natural bone but have as a drawback a poor structural consistency in wet conditions. In this paper, a comparative study between the performance of different cross-linking methods such as a milder enzymatic treatment procedure using transglutaminase, the use of N-3-(dimethylamino)propyl-N′-ethylcarbodiimide hydrochloride/N-hydroxysuccinimide, and genipin, and the use of a physical method based on exposure to ultraviolet light was carried out. The chemical and enzymatic treatments provided, in this order, excellent consistency, morphology, cross-linking degree, and osteoblast viability for the collagen nanofibers. Interestingly, the enzymatically cross-linked collagen mats, which are considered to be a more biological treatment, promoted adequate cell adhesion, making the biomaterial biocompatible and with an adequate degree of porosity for cell seeding and in-growth.
•Geochemical study on the fluids discharged in the Cotronei-Caccuri area.•Three different approaches to water geothermometry were adopted.•Geothermal conceptual model was reconstructed.•Implications ...for: seismo-geochemical studies and exploitation of geothermal resources.
Geochemical, geological, and hydrological data suggest, for the Cotronei-Caccuri thermal area (Northern Calabria – Southern Italy), the presence of a deep primary geothermal aquifer hosted in the crystalline basement (at Ponte Coniglio) and two secondary aquifers (at Bruciarello and Repole) developed in the Miocene sedimentary succession. Despite the spatial proximity of the three thermal sites, the waters have different compositions: Na(Ca)-Cl for Ponte Coniglio-Cotronei, Na(Ca)-Cl(SO4) for Bruciarello and Na-SO4(Cl) for Repole.
The composition of the Cotronei-Ponte Coniglio end-member was reconstructed based on conservative constituents and resulted in a Cl concentration of about 1700 mg kg−1. The thermal waters of Bruciarello and Repole are derived from this primary fluid. Geothermometric calculations support a possible dilution affecting the waters studied to different degrees. For the pure (undiluted) thermal end-member, hosted in the primary granitic aquifer, comparable temperature estimations are provided by cationic geothermometers (67 ± 4 °C) and geothermometric simulations (65 ± 4 °C). However, Bruciarello and Repole waters are in equilibrium with anhydrite and fluorite at a temperature (68.5 ± 4 °C) very similar to that obtained for the granitic aquifer suggesting slight cooling during the travel from the primary granitic aquifer and fast equilibration with anhydrite and fluorite favoured by the rapid dissolution kinetics of these solid phases. From the isotopic point of view, the secondary aquifers have δ34SS(6+) values (+23.01‰ and +22.77‰ ± 0.23‰) comparable with those of the Messinian gypsum (average of +21.8‰). The thermal waters of Cotronei, on the other hand, show enriched δ34SS(6+) values (+38.60‰ ± 0.78‰) due to bacterial reduction of sulfate probably also derived from by Messinian evaporates.
Furthermore, the δ18O and δ2H values indicate a meteoric origin for all three thermal sites with an average infiltration altitude of about 1650 – 1850 m asl, which agree with the Sila plateau elevations. Based on the results obtained in this work, assuming a geothermal gradient of about 33 °C/km, a temperature of the deep thermal reservoir of about 65 °C and an average predicted atmospheric temperature of 6 °C in the recharge area (Sila plateau), it follows that the meteoric waters descend to depths of ∼1800 m, where the thermal aquifer of interest is presumably located. This depth is consistent with the location of the primary geothermal reservoir within the crystalline basement. The reconstruction of this conceptual model has been made possible thanks to adopting a "local" approach integrating previously existing and new geological, hydrogeological, and geochemical data. Furthermore, this study has allowed us to identify the presence of an important regional geothermal aquifer hosted in the crystalline basement that, in addition to the carbonate and Upper Triassic evaporite reservoirs (well characterized in previous works), make the Calabria region of high geothermal interest.
This paper presents the mixing modelling results for the hydrogeochemical characterisation of groundwaters in the Laxemar area (Sweden). This area is one of the two sites that have been investigated, ...under the financial patronage of the Swedish Nuclear Waste and Management Co. (SKB), as possible candidates for hosting the proposed repository for the long-term storage of spent nuclear fuel. The classical geochemical modelling, interpreted in the light of the palaeohydrogeological history of the system, has shown that the driving process in the geochemical evolution of this groundwater system is the mixing between four end-member waters: a deep and old saline water, a glacial meltwater, an old marine water, and a meteoric water. In this paper we put the focus on mixing and its effects on the final chemical composition of the groundwaters using a comprehensive methodology that combines principal component analysis with mass balance calculations. This methodology allows us to test several combinations of end member waters and several combinations of compositional variables in order to find optimal solutions in terms of mixing proportions. We have applied this methodology to a dataset of 287 groundwater samples from the Laxemar area collected and analysed by SKB. The best model found uses four conservative elements (Cl, Br, oxygen-18 and deuterium), and computes mixing proportions with respect to three end member waters (saline, glacial and meteoric). Once the first order effect of mixing has been taken into account, water–rock interaction can be used to explain the remaining variability. In this way, the chemistry of each water sample can be obtained by using the mixing proportions for the conservative elements, only affected by mixing, or combining the mixing proportions and the chemical reactions for the non-conservative elements in the system, establishing the basis for predictive calculations.
•Laxemar (Sweden) groundwater is the combined result of several mixing events.•Water–rock interaction processes explain the remaining variability.•Four end-members and four conservative tracers have been used in the mixing analysis.•Mixing analysis has been carried out with M3, a statistical multivariate technique.•A correlation between water type and fraction of each end-member has been established.
The travertines of the Fitero thermal springs, with more than 98% of aragonite in most of the samples, are studied in this paper. The main objective is to improve the general understanding of ...aragonite precipitation, since the deposits of almost pure aragonite are very scarce. This study presents a complete mineralogical and isotopic characterisation, including the evaluation of the δ
18
O and δ
13
C fractionation during precipitation, as valuable information for paleoclimate and paleoenvironmental studies. Samples of a laminated travertine deposit constituted by almost pure aragonite were taken from a pipe discharging water at 40 °C. Waters suffered an important CO
2
outgassing, as suggested by the geochemical calculations and the δ
13
C values of travertines and waters. This outgassing triggers the oversaturation and precipitation of carbonate phases. Temperature seems to be the main factor controlling the precipitation of aragonite or calcite, as checked by studying another travertine sample with higher calcite content. Various δ
18
O isotope fractionation equations for aragonite and calcite were used. The results indicate that precipitation took place close to equilibrium according to some of these equations. The fact that the equilibrium is maintained in a natural system with an important CO
2
loss is surprising. However, it can be explained by an HCO
3
−
–water oxygen isotopic equilibrium and a direct transfer of the HCO
3
−
isotope signal to the carbonate without fractionation due to the fast CO
2
loss and precipitation. Finally, considering other natural aragonite samples, a fractionation equation is defined for natural aragonite in the temperature range between 23 and 80 °C.
The search by SKB (Swedish Nuclear Fuel and Waste Management Co.) for a site to locate the deep geological repository for spent nuclear fuel in Sweden has involved geoscientific investigations at ...several locations since the 1970s. The objectives were to characterise geologically a bedrock volume as well as its hydrogeology and hydrochemistry. To acquire high-quality hydrogeochemical data, a complete system for groundwater sampling and analysis, as well as for interpretation strategies, has been developed through a continuous process of modification and refinement. Since the largest part of the Swedish bedrock is composed of granitoids, the site investigations had to adapt to the special difficulties of fractured crystalline rocks. This paper discusses the problems with groundwater sampling that are specific to fractured crystalline rocks and describes the solutions adopted and methods developed by SKB since the early 2000s during the site investigations. The methodology described in this paper for the characterisation of deep groundwaters in crystalline rocks is not only applicable in the context of radioactive waste disposal but also useful when sampling groundwaters for any purpose in such rocks. Sampling of groundwaters in fractured rocks at depth, often down to approximately 1,000 m, involves special challenges since the natural conditions of the groundwater are easily disturbed, especially by the initial drilling, but also by every subsequent activity performed in the borehole, including the actual groundwater sampling. The sampling strategy presented in this paper shows that planning of the sampling preferably starts already when the drilling procedure is decided. Each following step is described in detail and includes tracing the drilling fluid, selecting the best borehole sections to sample, procedures for the actual sampling, and selection of analytical protocol; all this with the goal of taking representative samples. Although the evaluation of the sampling uncertainties is not a straightforward procedure, an adequate categorisation routine has been established to classify groundwater samples regarding sample quality, representativeness, and suitability for further interpretations and modelling.
•The characterisation of low temperature carbonate geothermal systems is discussed.•Thermodynamic uncertainties in geothermometrical calculations are addressed.•Limitations in mineral equilibria ...assumptions are discussed.•Calcite-dolomite equilibrium is evaluated in detail.
Geothermometrical characterisation of low-temperature, carbonate-evaporitic geothermal systems is usually hampered by the lack of appropriate mineral equilibria to successfully use most of the classical geothermometers and/or by the thermodynamic uncertainties affecting some of the most probable mineral equilibria in low temperature conditions. This situation is further hindered if the thermal waters are additionally affected by secondary processes (e.g., CO2 loss) during their ascent to surface.
All these problems cluster together in the low-temperature Alhama-Jaraba thermal system, hosted in carbonate rocks, with spring temperatures about 30 °C and waters of Ca-Mg−HCO3/SO4 type. This system, one of the largest naturally flowing (600 L/s) low temperature thermal systems in Europe, is used in this paper as a suitable frame to assess the problems in the application of chemical geothermometrical techniques (classical geothermometers and geothermometrical modelling) and to provide a methodology that could be used in this type of geothermal system or in potential CO2 storage sites in similar aquifers.
The results obtained have shown that the effects of the secondary processes can be avoided by selecting the samples unaffected by such processes and, therefore, representative of the conditions at depth, or by applying existing methodologies to reconstruct the original composition, as is usually done for medium to high temperature systems.
The effective mineral equilibria at depth depend on the temperature, the residence time and the specific lithological/mineralogical characteristics of the system studied. In the present case, the mineral equilibria on which classical cation geothermometers are based have not been attained. The low proportion of evaporitic minerals in the hosting aquifer prevents the system from reaching anhydrite equilibrium, otherwise common in carbonate-evaporitic systems and necessary for the specific SO4-F geothermometer or the specially reliable quartz (or chalcedony) – anhydrite equilibrium in the geothermometrical modelling of these geothermal systems.
Under these circumstances, the temperature estimation must rely on quartz (or chalcedony), clay minerals and, especially, calcite and dolomite. However, clay minerals and dolomite present important thermodynamic uncertainties related to possible variations in composition or crystallinity degree for clays and order/disorder degree for dolomite. To deal with these problems, a sensitivity analysis to the thermodynamic data for clay minerals has been carried out, comparing the results obtained when considering different solubility data. The uncertainties associated with dolomite have been addressed by reviewing the solubility data available for dolomites with different order degrees and performing specific calculations for the order degree of the dolomite in the aquifer. This approach can be used to find the most adequate dolomite thermodynamic data for the system under consideration, including medium-high temperature geothermal systems.
Finally, the temperature estimation of the Alhama-Jaraba waters in the deep reservoir has been obtained from simultaneous equilibria of quartz, calcite, partially disordered dolomite and some aluminosilicate phases. The obtained value of 51 ± 14 °C is within the uncertainty range normally affecting this type of estimations and is coherent with independent estimations from geophysical data.
Geothermometrical calculations in low-medium temperature geothermal systems hosted in carbonate-evaporitic rocks are complicated because 1) some of the classical chemical geothermometers are, ...usually, inadequate (since they were developed for higher temperature systems with different mineral-water equilibria at depth) and 2) the chemical geothermometers calibrated for these systems (based on the Ca and Mg or SO4 and F contents) are not free of problems either. The case study of the Arnedillo thermal system, a carbonate-evaporitic system of low temperature, will be used to deal with these problems through the combination of several geothermometrical techniques (chemical and isotopic geothermometers and geochemical modelling).
The reservoir temperature of the Arnedillo geothermal system has been established to be in the range of 87±13°C being the waters in equilibrium with respect to calcite, dolomite, anhydrite, quartz, albite, K-feldspar and other aluminosilicates. Anhydrite and quartz equilibria are highly reliable to stablish the reservoir temperature. Additionally, the anhydrite equilibrium explains the coherent results obtained with the δ18O anhydrite – water geothermometer. The equilibrium with respect to feldspars and other aluminosilicates is unusual in carbonate-evaporitic systems and it is probably related to the presence of detrital material in the aquifer.
The identification of the expected equilibria with calcite and dolomite presents an interesting problem associated to dolomite. Variable order degrees of dolomite can be found in natural systems and this fact affects the associated equilibrium temperature in the geothermometrical modelling and also the results from the Ca-Mg geothermometer. To avoid this uncertainty, the order degree of the dolomite present in the Arnedillo reservoir has been determined and the results indicate 18.4% of ordered dolomite and 81.6% of disordered dolomite.
Overall, the results suggest that this multi-technique approach is very useful to solve some of the problems associated to the study of carbonate-evaporitic geothermal systems.
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•Mineral equilibria in low temperature geothermal systems are discussed.•Consequences on some geothermometrical methods are addressed.•The order degree of the dolomite present in the aquifer is calculated.•A low temperature geothermal system hosted in carbonate rocks is used as an example.
We analysed hepatitis C virus (HCV) reinfection among participants in a prospective registry of HIV/HCV-coinfected patients treated with all-oral direct-acting antiretroviral (DAA)-based therapy in ...the region of Madrid.
An observational cohort study.
The study period started on the date sustained viral response (SVR) was confirmed. The censoring date was 31 December 2017. SVR was defined as negative HCV-RNA 12 weeks after completion of treatment. Reinfection was defined as a positive HCV-RNA test result after achievement of SVR.
Reinfections were detected in 17 of 2359 HIV/HCV-coinfected patients (0.72%) overall, in 12 out of 177 (6.78%) MSM and in five out of 1459 (0.34%) people who inject drugs (PWID). The incidence of reinfection 95% confidence interval (95% CI) per 100 person-years was 0.48 (0.30-0.77) overall, 5.93 (3.37-10.44) for MSM and 0.21 (0.09-0.52) for PWID. Reinfections were detected a median of 15 weeks (interquartile range 13-26) after SVR. In 10 (58.82%) patients, the reinfection was caused by a different HCV genotype. All 12 MSM with reinfection acknowledged unprotected anal intercourse with several partners, seven used chemsex, six reported fisting and four practiced slamming. A concomitant STI was detected in five patients. Four IDU with reinfection reported injecting drugs following SVR.
HCV reinfection is a matter of concern in HIV-positive MSM treated with all-oral DAA therapy in the region of Madrid. Our data suggest that prevention strategies and frequent testing with HCV-RNA should be applied following SVR in MSM who engage in high-risk practices.
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