Inferring the demographic history from DNA sequences: An importance sampling approach based on non-homogeneous processes.

In Ait Kaci Azzou et al. (2015) we introduced an Importance Sampling (IS) approach for estimating the demographic history of a sample of DNA sequences, the skywis plot. More precisely, we proposed a new nonparametric estimate of a population size that changes over time. We showed on simulated data that the skywis plot can work well in typical situations where the effective population size does not undergo very steep changes. In this paper, we introduce an iterative procedure which extends the previous method and gives good estimates under such rapid variations. In the iterative calibrated skywis plot we approximate the effective population size by a piecewise constant function, whose values are re-estimated at each step. These piecewise constant functions are used to generate the waiting times of non homogeneous Poisson processes related to a coalescent process with mutation under a variable population size model. Moreover, the present IS procedure is based on a modified version of the Stephens and Donnelly (2000) proposal distribution. Finally, we apply the iterative calibrated skywis plot method to a simulated data set from a rapidly expanding exponential model, and we show that the method based on this new IS strategy correctly reconstructs the demographic history.

Sequential analysis of hair mercury levels in relation to fish diet of an Amazonian population, Brazil.

Several studies in the Amazonian Basin have shown that riverine populations are exposed to methylmercury through fish consumption. It has been suggested that seasonal variations in hair mercury observed through sequential analyses may be related to the changes in fish species ingested by the local communities. The aim of the present study was to investigate the relationship between fish-eating practices and seasonal variation in mercury exposure. A group of 36 women from a village located on the banks of the Tapajós River, a major tributary of the Amazon, comprised the present study population. An interview-administered questionnaire was used to gather information on socio-demographic characteristics, fish-eating practices and other relevant information. The women also provided hair samples of at least 24 cm in length for mercury analysis. Hair total and inorganic mercury concentration was measured using a cold vapor atomic absorption analytical method. Trigonometric regression analysis was done to assess the seasonal variation of total mercury levels. Variations in inorganic mercury were examined by repeated measures analysis of variance, and analysis of contrast variable with a polynomial transformation. The results showed that hair mercury levels varied with the season. Higher levels were observed in months corresponding to the dry season, with lower levels in the rainy season. Herbivorous fish predominated the diet for 47.2% of the women during the dry season, but this rose to 72.2% during the rainy season. Those who reported eating fish daily had higher mercury levels in hair compared to those who only ate fish a few times per week. Retrospective mercury analyses, evaluated by the quantity of mercury present in each centimeter of hair, indicate that mean mercury level of the population decreased over the 2 years prior to the study. The percentage of inorganic mercury over the total mercury in hair increased towards the extremities of the hair strand. Higher percentages of inorganic mercury were found for the group who ate more fish (on a daily consumption basis). These results support the assumption that there are seasonal variations in methylmercury exposure and also a relationship between type of fish species consumed and the resulting hair mercury levels.

Manganese neurotoxicity, a continuum of dysfunction: results from a community based study.

Excessive manganese (Mn) has been associated with neurobehavioral deficits and neurological and/or neuropsychiatric illness, but the level at which this metal can cause adverse neurotoxic effects, particularly with long-term exposure, is still unknown. The objective of the present study was to assess nervous system functions in residents exposed to manganese from a variety of environmental sources. A random stratified sampling procedure was used to select participants; persons with a history of workplace exposure to Mn and other neurotoxic substances were excluded. A self-administered questionnaire provided data on socio-demographic variables. Blood samples were analyzed for total manganese (MnB), lead, mercury and serum iron. Nervous system assessment included computer and hand-administered neurobehavioral tests, computerized neuromotor tests, sensory evaluation and a neurological examination. The present analyses include 273 persons (151 women and 122 men); MnB range: 2.5 micrograms/L-15.9 micrograms/L (median: 7.3 micrograms/L). Multivariate analyses were used and neuro-outcomes were examined with respect to MnB, taking into account potential confounders and covariables. Results were grouped according to neurofunctional areas and MANOVA analyses revealed that higher MnB (7.5 micrograms/L) was significantly associated with changes in coordinated upper limb movements (Wilks' lambda = 0.92; p = 0.04) and poorer learning and recall (men: Wilks' lambda = 0.77; p = 0.002; women: Wilks' lambda = 0.86; p = 0.04). Further analyses revealed that with increasing log MnB (Simple regression: p < 0.05) performance on a pointing task was poorer, frequency dispersion of hand-arm tremor decreased, while harmonic index increased, and the velocity of a pronation/supination arm movement was slower. An Mn-age interaction was observed for certain motor tasks, with the poorest performance observed among those _50 y and in the higher MnB category. Differences between genders suggest that men may be at greater risk than women, although effects were also observed in women. These findings are consistent with the hypothesis that Mn neurotoxicity can be viewed on a continuum of dysfunction, with early, subtle changes at lower exposure levels.

Bioindicator and exposure data for a population based study of manganese.

Exposure data and bioindicators were obtained for a study whose objective was detection of early manifestations of manganese (Mn) neurotoxicity in a population with potential environmental exposure. The study included persons with no history of neurotoxic workplace exposure in Southwest Quebec, drawn from seven postal code regions, defining a set of geographically contiguous zones. Blood samples were analyzed for total Mn (MnB), lead (PbB), total mercury (HgT) and serum iron (FeS). Drinking water samples from participants' residences were analyzed for manganese (MnW). At 4 sites, limited 24-hour high volume air samples for total particulates (TP) and PM10, were analyzed for Mn and Pb. Sociodemographic and dietary information was obtained by self-administered questionnaire. The geometric mean (GM) for MnB values (n = 297) was 7.14 micrograms/L. Levels of MnB in women (n = 156; GM 7.50 micrograms/L) were significantly higher than in men (n = 141; GM 6.75 micrograms/L). No relationship was found between MnB and PbB or HgT. FeS was significantly higher in men (GM 18.38 mumol/L) than women (GM 15.0 mumol/L). For women, MnB was correlated to FeS, with a tendency to decrease with increasing age. For men, no relationship was found between MnB levels and either FeS or age, although FeS showed a strong inverse relationship with age. The 24-hour mean levels of MnTP at the 4 sites varied between 0.009 microgram/m3 and 0.035 microgram/m3; intersite differences were not significant. For Mn in PM10 (MnPM10), mean values ranged from 0.007 microgram/m3 to 0.019 microgram/m3; intersite differences were significant. A total of 278 MnW samples were obtained, 16 from residences served by wells. The GM for MnW was 4.11 micrograms/L (range: 0.50-71.1 micrograms/L, excluding wells; MnW for wells ranged from non-detectable to 158.9 micrograms/L. Individually, there was no relation between MnW and MnB. Geographic analysis of the MnB and MnW data by an algorithm grouping contiguous postal code zones, combined with air data, lead to definition of a geographic parameter, distinguishing two regions relative to a former manganese alloy plant, which contributed significantly to MnB. A multiple regression model was developed, explaining 6.7% of the variability in MnB (F = 5.12; p < 0.001); when controlling for gender, geographic region with higher levels of airborne manganese and the frequency of consumption of cereals and leaf vegetables contributed positively to MnB levels, while serum iron was negatively related.

Neuropsychiatric effects of manganese on mood.

Adverse mood effects of overexposure to Manganese (Mn) have been described in 15 studies which frequently report an association of Mn exposure with adverse effects in six dimensions of mood: 1) anxiety, nervousness, irritability; 2) psychotic experiences; 3) emotional disturbance; 4) fatigue, lack of vigor, sleep disturbance; 5) impulsive/compulsive behavior; 6) aggression hostility. Only 1:15 studies used a standardized psychological measure of mood, while the current study of environmental Mn exposure used two standardized mood scales in evaluating low levels of Mn exposure and mood sequelae. The Profile of Moods State (POMS) and Brief Symptom Inventory (BSI) were used, and results indicate that men who are older and have higher Mn levels show significant disturbances on four of the six mood dimensions. Increased scores were seen in the anxiety, nervousness, irritability; emotional disturbance; and aggression, hostility dimensions relative to those who had lower levels of Mn. The BSI and POMS are useful adjuncts in the assessment of mood/Mn effects.

Neurotoxic effects of low-level methylmercury contamination in the Amazonian Basin.

Many studies have demonstrated mercury contamination in the Amazonian ecosystem, particularly in fish, a dietary mainstay of populations in this region. The present study focused on potential health effects of this low-level methylmercury exposure. The study was carried out in a village on the Tapajós River, a tributary of the Amazon, on 91 adults inhabitants (15-81 years), whose hair mercury levels were inferior to 50 mu/g. Performance on a neurofunctional test battery and clinical manifestations of nervous system dysfunction were examined in relation to hair mercury concentrations. Near visual contrast sensitivity and manual dexterity, adjusted for age, decreased significantly with hair mercury levels (P < 0.05), while there was a tendency for muscular fatigue to increase and muscular strength to decrease in women. For the most part, clinical examinations were normal, however, hair mercury levels were significantly higher (P < 0.05) for persons who presented disorganized movements on an alternating movement task and for persons with restricted visual fields. These results suggest dose-dependent nervous system alterations at hair mercury levels below 50 micrograms/g, previously considered a threshold for clinical effects. The profile of dysfunction in this adult population is consistent with the current knowledge on methyl-mercury poisoning. The long-term implications of these findings are unknown and need to be addressed.

Preliminary evidence of neurotoxicity associated with eating fish from the Upper St. Lawrence River Lakes.

Pollution of hydrographic basins has affected the flora and fauna that thrive in these aquatic ecosystems, and fish, which constitute an important food resource, often contain a plethora of potentially toxic chemicals. In a major research project on early neurotoxic effects of environmental exposure to manganese among residents in Southwest Quebec, fish consumption from 2 lakes of the Upper St. Lawrence River System, was surveyed as a potential confounding factor. Participants were selected using a random, stratified sampling strategy from lists of the Quebec Health Plan. Following exclusions, 273 men and women between 20-69 years were retained for the present analysis. A total of 103 (37.7%) reported eating fish from the Upper St. Lawrence. Although fisheaters and non-fisheaters were similar for most socio-demographic variables, significantly more fisheaters (65.2%) reported consuming alcoholic beverages as compared to non-fisheaters (42.4%) (Chi Sq. <0.01). To eliminate this possible bias, fisheaters were matched to non-fisheaters for the variables sex, alcohol consumption (never or occasionally vs. regularly), age (+/-5y) and education (+/-2y). A total of 63 matched pairs were thus created. Paired analyses (t-test or Signed Rank) showed that fisheaters had higher levels of blood organic mercury and lead. Analysis of nervous system functions revealed that both groups performed similarly on tests of sensory function, visual memory and recognition, fine motor performance and some motor tests, but fisheaters performed significantly more poorly (p<0.05) on tests requiring cognitive flexibility, word naming, auditory recall, and more complex motor tasks. The profile of deficits is consistent with diminished capacity for information processing. These observations were made within a study that was not specifically designed to examine the effects of fish eating from these two lakes, and the characterization of fish dietary habits has many limitations. Nevertheless, the findings are sufficiently compelling to warrant further studies, since fish from the Upper St. Lawrence Lakes are known to contain multiple neurotoxic substances.

[Mental health deterioration in workers exposed to styrene]. / Détérioration de la santé mentale chez des travailleurs exposés au styrène.

Emotional instability which might be an early symptom of more severe disorders, is one of the first manifestations of chronic exposure to organic solvents. The present study measures the association between exposure to styrene and mood states of active workers. A total of 128 workers (85% of the total population) from 3 factories where styrene is used, participated on a voluntary basis. They filled out the following self-administered questionnaires: Profile of Mood States (POMS), Psychiatric Symptom Index and Well-being Index. The results indicate a significant relationship between post work-shift urinary mandelic acid (biological indicator of styrene exposure) and the scores obtained on the POMS scales of tension-anxiety (Spearman's rank correlation rho = 0.30; p < 0.01), anger-hostility (rho = 0.29; p < 0.01), fatigue-inertie (rho = 0.34; p < 0.01), and confusion-bewilderment (rho = 0.23; p = 0.04), as well as the Psychological Distress Index (rho = 0.30; p < 0.01). All scores were adjusted for the effects of 4 potentially confounding variables: age, schooling, alcohol and cigarette consumption. These indicators of mood states do not constitute a diagnosis of mental disease but reveal progressive deterioration of well being associated with neurotoxic exposure in the workplace.