Coastal groundwater salinization: Focus on the vertical variability in a multi-layered aquifer through a multi-isotope fingerprinting (Roussillon Basin, France).

The Roussillon sedimentary Basin (South France) is a complex multi-layered aquifer, close to the Mediterranean Sea facing seasonally increases of water abstraction and salinization issues. We report geochemical and isotopic vertical variability in this aquifer using groundwater sampled with a Westbay System® at two coastal monitoring sites: Barcarès and Canet. The Westbay sampling allows pointing out and explaining the variation of water quality along vertical profiles, both in productive layers and in the less permeable ones where most of the chemical processes are susceptible to take place. The aquifer layers are not equally impacted by salinization, with electrical conductivity ranging from 460 to 43,000µS·cm(-1). The δ(2)H-δ(18)O signatures show mixing between seawater and freshwater components with long water residence time as evidenced by the lack of contribution from modern water using (3)H, (14)C and CFCs/SF6. S(SO4) isotopes also evidence seawater contribution but some signatures can be related to oxidation of pyrite and/or organically bounded S. In the upper layers (87)Sr/(86)Sr ratios are close to that of seawater and then increase with depth, reflecting water-rock interaction with argillaceous formations while punctual low values reflect interaction with carbonate. Boron isotopes highlight secondary processes such as adsorption/desorption onto clays in addition to mixings. At the Barcarès site (120m deep), the high salinity in some layers appear to be related neither to present day seawater intrusion, nor to Salses-Leucate lagoonwater intrusion. Groundwater chemical composition thus highlights binary mixing between fresh groundwater and inherited salty water together with cation exchange processes, water-rock interactions and, locally, sedimentary organic matter mineralisation probably enhanced by pyrite oxidation. Finally, combining the results of this study and those of Caballero and Ladouche (2015), we discuss the possible future evolution of this aquifer system under global change, as well as the potential management strategies needed to preserve quantitatively and qualitatively this water resource.

Search for Rare Copy-Number Variants in Congenital Heart Defects Identifies Novel Candidate Genes and a Potential Role for FOXC1 in Patients With Coarctation of the Aorta.

BACKGROUND: Congenital heart defects are the most frequent malformations among newborns and a frequent cause of morbidity and mortality. Although genetic variation contributes to congenital heart defects, their precise molecular bases remain unknown in the majority of patients. METHODS AND RESULTS: We analyzed, by high-resolution array comparative genomic hybridization, 316 children with sporadic, nonsyndromic congenital heart defects, including 76 coarctation of the aorta, 159 transposition of the great arteries, and 81 tetralogy of Fallot, as well as their unaffected parents. We identified by array comparative genomic hybridization, and validated by quantitative real-time polymerase chain reaction, 71 rare de novo (n=8) or inherited (n=63) copy-number variants (CNVs; 50 duplications and 21 deletions) in patients. We identified 113 candidate genes for congenital heart defects within these CNVs, including BTRC, CHRNB3, CSRP2BP, ERBB2, ERMARD, GLIS3, PLN, PTPRJ, RLN3, and TCTE3. No de novo CNVs were identified in patients with transposition of the great arteries in contrast to coarctation of the aorta and tetralogy of Fallot (P=0.002; Fisher exact test). A search for transcription factor binding sites showed that 93% of the rare CNVs identified in patients with coarctation of the aorta contained at least 1 gene with FOXC1-binding sites. This significant enrichment (P<0.0001; permutation test) was not observed for the CNVs identified in patients with transposition of the great arteries and tetralogy of Fallot. We hypothesize that these CNVs may alter the expression of genes regulated by FOXC1. Foxc1 belongs to the forkhead transcription factors family, which plays a critical role in cardiovascular development in mice. CONCLUSIONS: These data suggest that deregulation of FOXC1 or its downstream genes play a major role in the pathogenesis of coarctation of the aorta in humans.

Description of 214 cases of autoimmune congenital heart block: Results of the French neonatal lupus syndrome.

BACKGROUND: Cardiac neonatal lupus syndrome is due to anti-SSA or SSB antibodies and mainly includes congenital heart block (CHB) and dilated cardiomyopathy (DCM). Its optimal management is still debated. We report a large series of autoimmune high degree CHB. METHODS: Inclusion criteria in this retrospective study were fetuses or neonates with high-degree CHB associated with maternal anti-SSA/SSB antibodies. RESULTS: 214 CHB were included: 202 detected in utero at a median term of 23 weeks' gestation (WG) [range 16 to 39 WG] and 12 neonatal cases diagnosed at a median age of 0 days [range birth to 8 days]. The 214 cases of CHB included 202 (94.4%) third-degree CHB, 8 (3.7%) second-degree CHB, and 4 (1.9%) intermittent CHB. In multivariate analysis, the factors associated with feto-neonatal deaths (15.7%) were hydrops (p<0.001; hazard ratio [HR] 12.4 [95% confidence interval (95%CI) 4.7-32.7]) and prematurity (p=0.002; HR 17.1 [95%CI 2.8-103.1]). During a median follow-up of 7 years [birth to 36 years], 148 of 187 children born alive (79.1%) had a pacemaker, 35 (18.8%, one missing data) had DCM, and 22 (11.8%) died. In multivariate analysis, factors associated with child death were in utero DCM (p=0.0157; HR 6.37 [95%CI: 1.25-32.44]), postnatal DCM (p<0.0001; HR 227.58[95%CI: 24.33-2128.46]) and pacemaker implantation (p=0.0035; HR 0.11[95%CI: 0.02-0.51]). The use of fluorinated steroids was neither associated with survival nor with regression of 2nd degree CHB. CONCLUSION: In this second largest series of CHB, we confirm some of the previous results. We were unable to find data supporting the routine use of in utero fluorinated steroids.

Integrated onshore-offshore investigation of a Mediterranean layered coastal aquifer.

Most of the Mediterranean coastal porous aquifers are intensively exploited. Because of climatic and anthropogenic effects, understanding the physical and geological controls on groundwater distribution and flow dynamics in such aquifers is crucial. This study presents the results of a structural investigation of a system located along the coastline of the Gulf of Lions (NW Mediterranean). A key aspect of this study relies on an onshore-offshore integrated approach combining outcrops, seismic profiles, and borehole data analysis. This multidisciplinary approach provides constraints on pore-fluid salinity distribution and stratigraphic organization, which are crucial in assessing the modes of groundwater/seawater exchanges. Onshore, Lower Pliocene deposits dip gently seaward. They are unconformably overlain by Holocene clays in the lagoons. Offshore the Pliocene deposits either outcrop at the seabed or are buried below nonconsolidated sands infilling paleo-valleys. Beneath the lido, the groundwater salinity distribution consists of salty pore water, overlying fresher pore water. Active circulation of groundwater masses is inferred from the geophysical results. In particular, offshore outcrops and paleo-valleys may play an important role in salt water intrusion.

Fetal tachycardia: a role for amiodarone as first- or second-line therapy?

BACKGROUND: Fetal tachycardias result in serious prenatal and postnatal morbidity and mortality. Intrauterine treatment can improve prognosis dramatically and the therapeutic protocol is well defined. Currently, amiodarone is used as third-line therapy and is reserved for refractory cases. AIMS: Our aim was to review the management and outcome of fetal tachycardia, giving particular consideration to the efficacy and safety of amiodarone therapy. METHODS: This was a retrospective study of 24 consecutive cases of sustained fetal tachycardia, treated mainly with digoxin and/or amiodarone administered by the transplacental route. RESULTS: The 24 fetal tachycardias comprised 16 supraventricular tachycardias with 1:1 atrioventricular conduction, seven atrial flutters and one ventricular tachycardia. Seven fetuses were hydropic and eight experienced less severe cardiac failure. Digoxin monotherapy converted 5/12 non-hydropic fetuses and 0/2 hydropic fetuses, with one intrauterine death. Amiodarone monotherapy converted 5/5 fetuses, including two hydropic fetuses: one ventricular tachycardia, two atrial flutters and two supraventricular tachycardias. When administered with digoxin, amiodarone converted all but two fetuses (7/9). No deaths were associated with amiodarone, but there was moderate morbidity, with six transient elevations of thyroid stimulating hormone at birth, two of which required short-term thyroid hormonal substitution therapy. CONCLUSION: Maternal oral amiodarone seems to be effective and relatively safe, even in hydropic fetuses. We suggest that this treatment could be used earlier than is currently advised.