Identification of demyelinating lesions and application of McDonald criteria when confronted with white matter lesions on brain MRI.

INTRODUCTION: White matter lesions (WML) on magnetic resonance imaging (MRI) are common in clinical practice. When analyzing WML, radiologists sometimes propose a pathophysiological mechanism to explain the observed MRI abnormalities, which can be a source of anxiety for patients. In some cases, discordance may appear between the patient's clinical symptoms and the identification of the MRI-appearing WML, leading to extensive diagnostic work-up. To avoid misdiagnosis, the analysis of WML should be standardized, and a consensual MRI reading approach is needed. OBJECTIVE: To analyze the MRI WML identification process, associated diagnosis approach, and misinterpretations in physicians involved in WML routine practice. METHODS: Through a survey distributed online to practitioners involved in WML diagnostic work-up, we described the leading causes of MRI expertise misdiagnosis and associated factors: clinical experience, physicians' subspecialty and location of practice, and type of device used to complete the survey. The survey consisted of sixteen T2-weighted images MRI analysis, from which ten were guided (binary response to lesion location identification), four were not shown (multiple possible answers), and two were associated with dissemination in space (DIS) McDonald criteria application. Two independent, experienced practitioners determined the correct answers before the participants' completion. RESULTS: In total, 364 participants from the French Neuro Radiological (SFNR), French Neurological (SFN), and French Multiple Sclerosis (SFSEP) societies completed the survey entirely. According to lesion identification, 34.3% and 16.9% of the participants correctly identified juxtacortical and periventricular lesions, respectively, whereas 56.3% correctly identified non-guided lesions. Application of the 2017 McDonald's DIS criteria was correct for 35.3% of the participants. According to the global survey scoring, factors independently associated with correct answers in multivariate analysis were MS-expert subspecialty (P<0.001), young clinical practitioners (P=0.02), and the use of a computer instead of a smartphone to perform WML analysis (P=0.03). CONCLUSION: Our results highlight the difficulties regarding WML analysis in clinical practice and suggest that radiologists and neurologists should rely on each other to ensure the diagnosis of multiple sclerosis and related disorders and limit misdiagnoses.

Perturbation vectors to evaluate air quality using lichens and bromeliads: a Brazilian case study.

Samples of one lichen species, Parmotrema crinitum, and one bromeliad species, Tillandsia usneoides, were collected in the state of Rio de Janeiro, Brazil, at four sites differently affected by anthropogenic pollution. The concentrations of aluminum, cadmium, copper, iron, lanthanum, lead, sulfur, titanium, zinc, and zirconium were determined by inductively coupled plasma-atomic emission spectroscopy. The environmental diagnosis was established by examining compositional changes via perturbation vectors, an underused family of methods designed to circumvent the problem of closure in any compositional dataset. The perturbation vectors between the reference site and the other three sites were similar for both species, although body concentration levels were different. At each site, perturbation vectors between lichens and bromeliads were approximately the same, whatever the local pollution level. It should thus be possible to combine these organisms, though physiologically different, for air quality surveys, after making all results comparable with appropriate correction. The use of perturbation vectors seems particularly suitable for assessing pollution level by biomonitoring, and for many frequently met situations in environmental geochemistry, where elemental ratios are more relevant than absolute concentrations.

Impact of trace metals from past mining on the aquatic ecosystem: a multi-proxy approach in the Morvan (France).

This study seeks to determine to what extent trace metals resulting from past mining activities are transferred to the aquatic ecosystem, and whether such trace metals still exert deleterious effects on biota. Concentrations of Cd, Cu, Pb and Zn were measured in streambed sediments, transplanted bryophytes and wild brown trout. This study was conducted at two scales: (i) the entire Morvan Regional Nature Park and (ii) three small watersheds selected for their degree of contamination, based on the presence or absence of past mining sites. The overall quality of streambed sediments was assessed using Sediment Quality Indices (SQIs). According to these standard guidelines, more than 96% of the sediments sampled should not represent a threat to biota. Nonetheless, in watersheds where past mining occurred, SQIs are significantly lower. Transplanted bryophytes at these sites consistently present higher trace metal concentrations. For wild brown trout, the scaled mass and liver indices appear to be negatively correlated with liver Pb concentrations, but there are no obvious relationships between past mining and liver metal concentrations or the developmental instability of specimens. Although the impact of past mining and metallurgical works is apparently not as strong as that usually observed in modern mining sites, it is still traceable. For this reason, past mining sites should be monitored, particularly in protected areas erroneously thought to be free of anthropogenic contamination.

Impact of historical mining assessed in soils by kinetic extraction and lead isotopic ratios.

The aim of this study is to estimate the long-term behaviour of trace metals, in two soils differently impacted by past mining. Topsoils from two 1 km(2) zones in the forested Morvan massif (France) were sampled to assess the spatial distribution of Cd, Cu, Pb and Zn. The first zone had been contaminated by historical mining. As expected, it exhibits higher trace-metal levels and greater spatial heterogeneity than the second non-contaminated zone, supposed to represent the local background. One soil profile from each zone was investigated in detail to estimate metal behaviour, and hence, bioavailability. Kinetic extractions were performed using EDTA on three samples: the A horizon from both soil profiles and the B horizon from the contaminated soil. For all three samples, kinetic extractions can be modelled by two first-order reactions. Similar kinetic behaviour was observed for all metals, but more metal was extracted from the contaminated A horizon than from the B horizon. More surprising is the general predominance of the residual fraction over the "labile" and "less labile" pools. Past anthropogenic inputs may have percolated over time through the soil profiles because of acidic pH conditions. Stable organo-metallic complexes may also have been formed over time, reducing metal availability. These processes are not mutually exclusive. After kinetic extraction, the lead isotopic compositions of the samples exhibited different signatures, related to contamination history and intrinsic soil parameters. However, no variation in lead signature was observed during the extraction experiment, demonstrating that the "labile" and "less labile" lead pools do not differ in terms of origin. Even if trace metals resulting from past mining and metallurgy persist in soils long after these activities have ceased, kinetic extractions suggest that metals, at least for these particular forest soils, do not represent a threat for biota.

Wild brown trout affected by historical mining in the Cévennes National Park, France.

In the protected area of the Cévennes National Park (Southern France), 114 wild brown trout (Salmo trutta fario) were captured at six locations affected to different extents by historical mining and metallurgy dating from the Iron Age to Modern Times. Cadmium and lead in trout livers and muscles reflect high sediment contamination, although an age-related effect was also detected for hepatic metal concentrations. Lead isotope signatures confirm exposure to drainage from mining and metallurgical waste. Developmental instability, assessed by fluctuating asymmetry, is significantly correlated with cadmium and lead concentrations in trout tissues, suggesting that local contamination may have affected fish development. Nowadays, the area is among the least industrialized in France. However, our results show that 60% of the specimens at one site exceed EU maximum allowed cadmium or lead concentration in foodstuffs. The mining heritage should not be neglected when establishing strategies for long-term environmental management.

Modeling of 137Cs migration in soils using an 80-year soil archive: role of fertilizers and agricultural amendments.

An 80-year soil archive, the 42-plot experimental design at the INRA in Versailles (France), is used here to study long-term contamination by 137Cs atmospheric deposition and the fate of this radioisotope when associated with various agricultural practices: fallow land, KCl, NH4(NO3), superphosphate fertilizers, horse manure and lime amendments. The pertinence of a simple box model, where radiocaesium is supposed to move downward by convectional mechanisms, is checked using samples from control plots which had been neither amended, nor cultivated since 1928. This simple model presents the advantage of depending on only two parameters: alpha, a proportional factor allowing the historical atmospheric 137Cs fluxes to be reconstructed locally, and k, an annual loss coefficient from the plow horizon. Another pseudo-unknown is however necessary to run the model: the shape of historical 137Cs deposition, but this function can be easily computed by merging several curves previously established by other surveys. A loss of approximately 1.5% per year from the plow horizon, combined with appropriate fluxes, provides good concordance between simulated and measured values. In the 0-25cm horizon, the residence half time is found to be approximately 18yr (including both migration and radioactive decay). Migration rate constants are also calculated for some plots receiving continuous long-term agricultural treatments. Comparison with the control plots reveals significant influence of amendments on 137Cs mobility in these soils developed from a unique genoform.

Environmental impact of early Basque mining and smelting recorded in a high ash minerogenic peat deposit.

More than four metres of core, covering almost 5000 years of deposition, were collected in a high ash minerogenic peat deposit located in the High Aldudes valley (Basque country), an area well known for its mineral abundance, exploited from Roman Times at least. Although minerogenic peatlands are not generally considered as the best archives to reconstruct past atmospheric metal deposition history, lead isotopic geochemistry demonstrates the integrity of the Pb record at least within the three upper meters; that is to say over the last four millennia. Zn, Cd and Cu may have been widely redistributed either by biological cycling, advective groundwater movements, or diffusional processes. Anthropogenic lead input phases are clearly pinpointed by positive shifts in Pb/Sc ratios with concomitant sharp drops in (206)Pb/(207)Pb ratios. They are often accompanied by significant declines in tree taxa, interpreted as increasing demand for wood to supply energy for local mining and/or metallurgical operations. Periods of mining and/or smelting activity are identified during Antiquity and Modern Times, and are also confirmed by textual and field evidence. Inputs from the Rio Tinto (Southern Spain), often invoked as a major lead contributor to the European atmosphere during Roman Times, were not detected here. This remote source was probably masked by local inputs. Other mining and/or smelting phases, only suspected by archaeologists, are here identified as early as the Bronze Age. Although the durations of these phases are possibly overestimated because of detrital inputs consequent to the release of lead from polluted soils over a long period of time after major pollutant inputs, the periods at which pollution peaks occur are in good agreement with archaeological knowledge and palaeo-botanical data. The combination of geochemical and palaeo-botanical techniques with field archaeology, therefore provides a powerful tool in studying the interaction of early human societies with their environment, as regards early mining and smelting.

Modeling lead input and output in soils using lead isotopic geochemistry.

The aim of this study is to model downward migration of lead from the plow layer of an experimental site located in Versailles (about 15 km southwest of Paris, France). Since 1928, samples have been collected annually from the topsoil of three control plots maintained in bare fallow. Thirty samples from 10 different years were analyzed for their lead and scandium contents and lead isotopic compositions. The fluxes are simple because of the well-controlled experimental conditions in Versailles: only one output flux, described as a first-order differential function of the anthropogenic lead pool, was taken into account; the inputs were exclusively ascribed to atmospheric deposition. The combination of concentration and isotopic data allows the rate of migration from the plowed topsoil to the underlying horizon and, to a lesser extent, the atmospheric fluxes to be assessed. Both results are in good agreement with the sparse data available. Indeed, the post-depositional migration of lead appears negligible at the human time scale: less than 0.1% of the potentially mobile lead pool migrates downward, out of the first 25 cm of the soil, each year. Assuming future lead inputs equal to 0, at least 700 yr would be required to halve the amount of accumulated lead pollution. Such a low migration rate is compatible with the persistence of a major anthropogenic lead pool deposited before 1928. Knowledge of pollution history seems therefore to be of primary importance.

History and environmental impact of mining activity in Celtic Aeduan territory recorded in a peat bog (Morvan, France).

The present study aims to document historical mining and smelting activities by means of geochemical and pollen analyses performed in a peat bog core collected around the Bibracte oppidum (Morvan, France), the largest settlement of the great Aeduan Celtic tribe (ca. 180 B.C. to 25 A.D.). The anthropogenic Pb profile indicates local mining operations starting from the Late Bronze Age, ca. cal. 1300 B.C. Lead inputs peaked at the height of Aeduan civilization and then decreased after the Roman conquest of Gaul, when the site was abandoned. Other phases of mining are recognized from the 11th century to modern times. They have all led to modifications in plant cover, probably related in part to forest clearances necessary to supply energy for mining and smelting. Zn, Sb, Cd, and Cu distributions may result from diffusional and biological processes or from the influence of groundwater and underlying mineral soil, precluding their interpretation for historical reconstruction. The abundance of mineral resources, in addition to the strategic location, might explain why early settlers founded the city of Bibracte at that particular place. About 20% of the anthropogenic lead record was accumulated before our era and about 50% before the 18th century, which constitutes a troublesome heritage. Any attempts to develop control strategies in accumulating environments should take into account past human activities in order to not overestimate the impact of contemporary pollution.

Collapsing cristobalitelike structures in silica analogues at high pressure.

The cristobalitelike forms of the ternary silica analogues BPO4 and BAsO4 were investigated at high pressure by x-ray diffraction and theoretical methods. The behavior of these compounds represents an extreme case in which the tilt angle of the constituent tetrahedra increases in a spectacular way at high pressure resulting in a major change in topology from a cristobalitelike framework towards a "collapsed cristobalite" structure. These compounds provide the first examples of the collapse of a framework structure to a close-packed form in a continuous manner without an intervening phase transition.

Synthesis and crystal structure determination of a new pressure-induced iridium ditelluride phase, m-IrTe2, and comparison of the crystal structures and relative stabilities of various IrTe2 polymorphs.

The new monoclinic IrTe2 phase m-IrTe2 was synthesized under pressure, and its structure was determined by X-ray powder diffraction. The relative stabilities of the three known and three hypothetical IrTe2 polymorphs were discussed on the basis of tight binding electronic band structure calculations. m-IrTe2 exhibits structural features of both CdI2- and pyrite-type IrTe2 phases and is expected to be nearly as stable as that of the CdI2-type IrTe2. The hypothetical IrS2- and ramsdellite-type IrTe2 phases are predicted to be more stable than the CdI2-type IrTe2.

Crystal structure of moganite-type phosphorus oxynitride: relationship to other twinned-quartz-based structures.

The structure of moganite-type phosphorus oxynitride quenched from high-pressure high-temperature conditions has been refined using neutron powder diffraction data. This moganite-type structure, space group I2/a, Z = 12, is slightly less distorted with respect to the Imab aristotype than is moganite (a monoclinic form of silica). A close topological relationship has been identified between the moganite-type and orthorhombic BeH(2) structures indicating that SiO(2), PON and BeH(2) all adopt structures belonging to the twinned-quartz-based group. This group represents another possible structure type for systems composed of corner-sharing AX(4) tetrahedra. Structures of this group are obvious candidates for intermediate phases between the cristobalite and quartz types.

The intermediate alleles of the fragile X CGG repeat in patients with mental retardation.

We have analysed the size of the non-expanded FRAXA CGG repeat in 385 male patients affected by mental retardation and in 182 unrelated normal chromosomes as control. The results show that intermediate alleles with more than 40 repeats were not significantly more frequent in patients than in controls. These data do not corroborate previous findings supporting the idea that intermediate alleles may have a deleterious effect on mental retardation.

Analysis of germline variation at the FMR1 CGG repeat shows variation in the normal-premutated borderline range.

In order to characterize the dynamics of CGG repeat instability at the fragile X syndrome locus (FMR1 gene), we have used small pool PCR to estimate the mutation rate within germline (sperm) and somatic tissue (leukocytes) of two normal males, one carrying the most common 29 CGG repeats allele, the other carrying a borderline normal-premutated allele of 55 repeats. Large contractions and moderate expansions of the repeat were found in sperm and blood for the 55 repeat allele while almost no variation was found in sperm or blood with the 29 repeat allele. Somatic blood DNA exhibited fewer expansions and contractions than sperm. Contractions were more frequent than expansions, and all the expansions were found in the +4 to +10 repeats range, while most of the contractions were found in the -10 to -30 range, suggesting that a subset of contractions results from a distinct mechanism. These results also suggest that the dynamics of the CGG repeat could be partly due to germline instability within the high normal or premutated ranges.

Recurrent and unexpected segregation of the FMR1 CGG repeat in a family with fragile X syndrome.

Fragile X syndrome, the most common cause of hereditary mental retardation, results from amplification of a CGG trinucleotide repeat in the FMR1 gene. The transmission of the CGG repeat from premutated individuals to their premutated descendants is usually unstable, showing an increase in the size of the repeat. We report here a family which exhibits recurrent and unexpected transmission of the maternal premutation to three daughters. The first daughter exhibited mosaicism with two premutated alleles, one contracted and the other expanded. The second daughter showed a reversion from the maternal premutation to the normal range, and the third carried an expanded premutated allele associated with an expanded paternal allele within the normal range. These variations in the size of the CGG repeat may result from many different mechanisms such as DNA polymerase slippage on the leading or lagging strand during replication, large contractions of repeats on the parental strand during replication, or recombination through unequal crossover between sister chromatids. Our results suggest that the variation of the CGG premutated alleles in this family may be the result of intrinsic instability associated with a trans-acting factor such as a mismatch repair gene product.

Transition from normal to premutated alleles in fragile X syndrome results from a multistep process.

In fragile X syndrome, the most common cause of inherited mental retardation, phenotypic expression has been linked to a region containing a repetitive sequence, (CGG)n, that appears to lengthen dramatically in fragile X patients and to show length variation in normal individuals. In order to investigate possible mechanisms responsible for further expansion of CGG in the normal population, we selected 31 normal unrelated X chromosomes carrying either the high-risk DX204-AC155 or DX196-AC151 haplotypes, as defined by the flanking microsatellites, DXS548 and FRAXAC2. Nearly 100% of CGGs with more than 35 repeats were found on DX204-AC155 haplotypes, with a mean length significantly higher and much more variable than in normal individuals carrying other haplotypes including the high-risk haplotype DX196-AC151. These findings suggest that the transition from the normal to the abnormal range occurs by a multistep process, a primary event, such as unequal crossing-over, leading to increased size and moderate instability of the repeat, and from which DNA polymerase slippage could lead to recurrent premutations. Our results also suggest that the upper limit of the normal range is roughly 35 repeats in the fragile X gene. The 36-54 repeats range would define an intermediate allele only observed, up to now, in DX204-AC155 fragile X chromosomes.

Carrier detection and prenatal diagnosis of cystic fibrosis using an intragenic TA-repeat polymorphism.

We have analysed the segregation of a TA-repeat polymorphism in intron 17b of the cystic fibrosis transmembrane conductance regulator gene responsible for cystic fibrosis (CF) in 23 French CF families non-informative for the delta F508 mutation (i.e. with at least one parent not carrying delta F508) or closely linked DNA markers. At least 13 different alleles ranging from 7 to 45 repeats were observed and the detected heterozygosity was 89%. Of the 23 families studied, 19 were fully informative for prenatal diagnosis or carrier detection, 3 were partially informative and one was not informative. In 6 families, prenatal diagnosis for CF or carrier detection in siblings of CF cases were performed using this polymorphism.