Dave Saint-Amour
email: saint-amour.dave@uqam.cahighlights

Gina Muckle

Avril Gagnon-Chauvin

Florence Rouget

Christine Monfort

Leah Michineau

Jean-Pierre Thomé

Philippe Kadhel

Luc Multigner

Sylvaine Cordier

Visual contrast sensitivity in school-age Guadeloupean children exposed to chlordecone

 Children at 7 years exposed to chlordecone in Guadeloupe were enrolled  The association between pre-and postnatal chlordecone exposure and visual contrast sensitivity was examined  Prenatal chlordecone exposure was associated with lower contrast sensitivity  Postnatal chlordecone exposure was associated with lower contrast sensitivity but only in boys

Introduction

J o u r n a l P r e -p r o o f Organochlorine (OC) compounds are persistent organic pollutants that were massively used in agriculture and residential settings. Although mostly banned by the late 1970s, humans are still exposed to these industrially synthesized molecules because of their high stability and resistance to environmental degradation. The impact of OC exposure on human health has been studied in particular in the context of metabolic diseases [START_REF] Lee | Prospective associations between persistent organic pollutants and metabolic syndrome: a nested case-control study[END_REF], reproductive health [START_REF] Vested | In utero exposure to persistent organochlorine pollutants and reproductive health in the human male[END_REF] and child development [START_REF] Vrijheid | Environmental pollutants and child health-A review of recent concerns[END_REF]. Although there is strong evidence from longitudinal birth cohorts that prenatal exposure to OC pesticides is associated with impairments of motor and cognitive development [START_REF] Eskenazi | In utero exposure to dichlorodiphenyltrichloroethane (DDT) and dichlorodiphenyldichloroethylene (DDE) and neurodevelopment among young Mexican American children[END_REF][START_REF] Puertas | Prenatal exposure to mirex impairs neurodevelopment at age of 4 years[END_REF][START_REF] Ribas-Fito | Breastfeeding, exposure to organochlorine compounds, and neurodevelopment in infants[END_REF][START_REF] Ribas-Fito | In utero exposure to background concentrations of DDT and cognitive functioning among preschoolers[END_REF][START_REF] Sagiv | Prenatal organochlorine exposure and behaviors associated with attention deficit hyperactivity disorder in school-aged children[END_REF][START_REF] Torres-Sanchez | In utero p,p'-DDE exposure and infant neurodevelopment: a perinatal cohort in Mexico[END_REF], very few studies have investigated the impact on sensory functions [START_REF] Cartier | Prenatal and 5-year p,p'-DDE exposures are associated with altered sensory processing in school-aged children in Nunavik: a visual J o u r n a l P r e -p r o o f evoked potential study[END_REF][START_REF] Riva | Polychlorinated biphenyls in colostral milk and visual function at 12 months of life[END_REF]). Yet, it is very important to understand the neurological burden resulting from environmental contaminant exposure, especially since there are cases in the literature showing no adverse associations with cognitive functions but with alterations of sensory functions, and vice-versa. For instance, in a study that examined the consequences stemming from prenatal exposure to organophosphate insecticides, Cartier and colleagues found no association with altered cognitive function in 6-year-old children from the PELAGIE mother-child cohort in France [START_REF] Cartier | Organophosphate Insecticide Metabolites in Prenatal and Childhood Urine Samples and Intelligence Scores at 6 Years of Age: Results from the Mother-Child PELAGIE Cohort (France)[END_REF], but found significantly decreased visual contrast sensitivity function in those children (boys only) [START_REF] Cartier | Children's contrast sensitivity function in relation to organophosphate insecticide prenatal exposure in the mother-child PELAGIE cohort[END_REF].

Chlordecone, an OC pesticide, was extensively used until 1993 in the French West Indies to control banana root borers. This molecule is highly stable and resistant to J o u r n a l P r e -p r o o f environmental degradation and therefore contaminates soils, water sources and crops for several decades [START_REF] Cabidoche | Long-term pollution by chlordecone of tropical volcanic soils in the French West Indies: a simple leaching model accounts for current residue[END_REF][START_REF] Coat | Organochlorine pollution in tropical rivers (Guadeloupe): role of ecological factors in food web bioaccumulation[END_REF]. As a result, populations of the French West Indies, including pregnant women, are exposed to chlordecone through the consumption of contaminated food and of drinking water [START_REF] Dubuisson | Impact of subsistence production on the management options to reduce the food exposure of the Martinican population to Chlordecone[END_REF]. Since chlordecone is known to cross the placental barrier [START_REF] Kavlock | Comparative tissue distribution of mirex and chlordecone in fetal and neonatal rats[END_REF], in utero exposure from maternal intake might result in a window of higher susceptibility for the offspring, which can be harmful given the well-known sensitivity of the fetus to toxic disturbances [START_REF] Grandjean | Developmental neurotoxicity of industrial chemicals[END_REF]. In addition to prenatal exposure, postnatal exposure can occur via breastfeeding and diet. In fact, in the French West Indies, food-related exposure to chlordecone above the reference dose (i.e., the "no effect threshold" dose) is more common in 3-to-5-year-old children than in adults [START_REF] Godard | Évaluation et gestion du risque alimentaire associé au chlordécone pour les populations de Guadeloupe et de Martinique[END_REF].

The toxicity of chlordecone was first recognized decades ago following an accidental excessive exposure in workers in a chlordecone-producing factory located in Hopewell, United States [START_REF] Cannon | Epidemic kepone poisoning in chemical workers[END_REF][START_REF] Taylor | Chlordecone intoxication in man. I. Clinical observations[END_REF]. In addition to signs of toxicity on the skin, in the liver and in the endocrine system, neurological impairments were also observed, such as tremors, enhanced startle responses, staggering speech, memory loss, and visual disturbances. Visual symptoms were characterized by difficulties in maintaining stable fixation, including nystagmus, and blurred vision, but visual acuity remained within the normal range. Of note, some of the workers complained of neurological symptoms several years after cessation of exposure [START_REF] Taylor | Neurological manifestations in humans exposed to chlordecone and follow-up results[END_REF]. The mechanisms of action causing chlordecone neurotoxicity J o u r n a l P r e -p r o o f involves alterations in cell metabolism, namely in the enzymatic activity of the ATPases and calcium homeostasis [START_REF] End | Neurochemical correlates of chlordecone neurotoxicity[END_REF][START_REF] Komulainen | Modulation of levels of free calcium within synaptosomes by organochlorine insecticides[END_REF], as well as in several neurotransmitter systems [START_REF] J O U R N A L P R E -P R O O F Desaiah | Chlordecone interaction with catecholamine binding and uptake in rat brain synaptosomes[END_REF], altering various functions of the central nervous system. Furthermore, chlordecone possesses well-defined estrogenic activity in vivo and in vitro [START_REF] Hammond | Estrogenic activity of the insecticide chlordecone (Kepone) and interaction with uterine estrogen receptors[END_REF][START_REF] Kuiper | Development of visual acuity in preschool children as measured with Landolt C and Tumbling E charts[END_REF][START_REF] Lemaire | Activation of alpha-and beta-estrogen receptors by persistent pesticides in reporter cell lines[END_REF].

In the early 2000s, two epidemiological studies reported cognitive and motor impairments following chlordecone exposure in Guadeloupean infants from the prospective birth cohort TIMOUN [START_REF] Boucher | Exposure to an organochlorine pesticide (chlordecone) and development of 18-month-old infants[END_REF][START_REF] Dallaire | Cognitive, visual, and motor development of 7-month-old Guadeloupean infants exposed to chlordecone[END_REF]. The authors found an association between pre-and postnatal exposure to chlordecone and short-term memory at 7 months of age, as well as fine motor deficits at 18 months of age.

These results are consistent with reports in Hopewell workers of memory and motor impairments. In the study of [START_REF] Dallaire | Cognitive, visual, and motor development of 7-month-old Guadeloupean infants exposed to chlordecone[END_REF], visual acuity, i.e., the ability to discern fine details, was also measured using the Teller Acuity Cards and no association was detected between infant visual acuity and chlordecone concentrations, for prenatal nor postnatal exposure. Of note, visual acuity was also found to be intact in the chlordecone (Kepone) poisoning workers, where blood levels were about 1000 times higher than those measured in Guadeloupe [START_REF] Cannon | Epidemic kepone poisoning in chemical workers[END_REF]. These results suggest a potential lack of sensitivity of acuity tests in detecting chlordecone-related effects on visual functions.

J o u r n a l P r e -p r o o f

The present study aimed to evaluate the impact of chlordecone exposure on visual functions in school-aged children from the TIMOUN birth cohort by assessing contrast sensitivity. In contrast to visual acuity, which measures the ability to recognize smaller and smaller stimuli at maximal contrast (e.g., a black letter on a white background), contrast sensitivity measures the ability to see a stimulus of decreasing contrast or light intensity. Contrast sensitivity measures have been found to detect subtle changes in postretinal processing, which may not be revealed by visual acuity assessments, as the latter is easily disrupted by refraction errors in the eye. Thus, contrast sensitivity testing is thought to provide a more comprehensive and sensitive measure of visual function (e.g., [START_REF] Fillion | Toxic risks and nutritional benefits of traditional diet on near visual contrast sensitivity and color vision in the Brazilian Amazon[END_REF][START_REF] Frenette | Contrast-sensitivity loss in a group of former microelectronics workers with normal visual acuity[END_REF][START_REF] Till | Vision abnormalities in young children exposed prenatally to organic solvents[END_REF].

Materiel and methods

Participants

The TIMOUN birth cohort was initiated to evaluate the potential impact of prenatal exposure to chlordecone on child development. Between November 2004 and December 2007, 1068 pregnant women were recruited during their third-trimester prenatal visit at public hospitals and antenatal care dispensaries in Guadeloupe. Questionnaires were administered at inclusion to document social, demographic, occupational, and medical family characteristics, as well as lifestyle habits. The maternal characteristics known as potential confounders were used in the present study for statistical control (see section 2.4 below). On the day of delivery, information about dietary habits and alcohol J o u r n a l P r e -p r o o f consumption during pregnancy were collected and a cord blood sample was obtained to document prenatal exposure to chlordecone and other environmental contaminants.

At 7 years of age, 1033 liveborn singleton children were invited to participate in a neuropsychological follow-up study at the hospital, which included an evaluation of their visual functions and the collection of a blood sample. A maternal interview documented major events and behavior during childhood, and the maternal nonverbal intellectual functioning was assessed with the Raven's Progressive Matrices [START_REF] Raven | Manual for Raven's Progressive Matrices and Vocabulary Scales[END_REF]. In total, 444 families could not be contacted or refused to participate. Of the 589 remaining children, all completed a visual function evaluation. Participants were only included in the study analysis if chlordecone concentrations at birth (cord blood) and at the testing time (child blood) were available (n=293). The exclusion criteria for the present analysis were the following: birth before 34 weeks of gestation (n=5), 5-minute Apgar score <7 (n=0), genetic or neurological disorders (n=2; epilepsy, traumatic brain injury), and/or medication intake at testing time (n=1, Ritalin). After applying all exclusion criteria, the final sample amounted to 285 children. Additional children were excluded because of technical problems (n=1), lack of collaboration (n=3) or due to forgetting their glasses at testing time (n=5). All subjects gave informed consent before participating in this study. The appropriate French ethics committees approved all study procedures, including the informed consent forms. Preparation of samples and quantification method were previously described (Multigner et al., 2010). The limit of detection (LOD) was 0.06 μg/L for chlordecone in cord blood, 0.02 for child chlordecone, and 0.05 μg/L for PCB-153 and DDE. Total cholesterol and triglycerides in plasma were determined by standard enzymatic procedures (DiaSys Diagnostoc Systems GmbH; Holzheim, Germany) and total lipid concentrations were calculated as described by Bernert et al. (2007). Blood Hg and Pb concentrations were measured by inductively coupled plasma mass spectrometry (ICP-MS) at the laboratory of the "Centre de toxicologie du Québec". For Hg determination, blood samples were diluted 20-fold in a solution containing ammonium hydroxide before analysis. The LOD for Hg and Pb were 0.4 μg/L and 2 μg/L respectively, and each run of samples included a standard.

Measurements of chlordecone and other contaminants

Functional Acuity Contrast Test (FrACT)

J o u r n a l P r e -p r o o f

Participants were seated at a distance of 2 meters from the computer screen (1024 x 768 pixels). The assessment was conducted by a trained nurse, blind to the participant chlordecone exposure. Participants with prescription glasses were asked to wear them for the duration of the task. Visual acuity and contrast threshold were assessed using the FrACT. The FrACT is an 8-minutes computerized visual screening battery developed by Michael Bach [START_REF] Bach | The Freiburg Visual Acuity test--automatic measurement of visual acuity[END_REF], which has been validated in different populations and for different age groups, including preschool children [START_REF] Dennis | Using the Freiburg Acuity and Contrast Test to measure visual performance in USAF personnel after PRK[END_REF]Lai, Wang, & Hsu, 2011;[START_REF] Loumann Knudsen | Visual acuity testing in diabetic subjects: the decimal progression chart versus the Freiburg visual acuity test[END_REF][START_REF] Molloy | Long-term effect of high-dose supplementation with DHA on visual function at school age in children born at <33 wk gestational age: results from a follow-up of a randomized controlled trial[END_REF][START_REF] Schulze-Bonsel | Visual acuities "hand motion" and "counting fingers" can be quantified with the freiburg visual acuity test[END_REF]; Van den Boomen, de Graaff, de Jong, Kalkman, & Kemner, 2013). Auditory feedback was given on a trial-by-trial basis (high-frequency tones after correct responses, and low-frequency tones after incorrect responses) to enhance each participant's comfort [START_REF] Bach | Visual Acuity Testing: Feedback Affects Neither Outcome nor Reproducibility, but Leaves Participants Happier[END_REF]. A short practice run (about 5 trials) was administrated before testing to make sure that the task was well understood.

First, the visual acuity test, which consists of a ring with a gap ("C" shape optotype), was administrated (Figure 1a). The testing duration was approximately 4 minutes. The optotype was presented randomly among four different positions for each trial.

Participants were instructed to indicate the location of the gap by pressing on a 4-arrow keypad, i.e., up, down, right or left. Perceptual thresholds were obtained from an adaptive staircase procedure implemented into the program (Best-PEST algorithm). The size of the optotype was automatically adjusted across trials according to the participant's performance (e.g., if the participant answered correctly, the stimulus size was reduced on the next trial). The acuity of each participant was calculated as a Snellen fraction score, so that higher scores indicated better performance. Second, contrast thresholds were J o u r n a l P r e -p r o o f tested, i.e., the lowest contrast level at which the the location of the gap was correctly detected (Figure 1b). The testing duration was approximately 4 minutes. Contrast of the optotype (with a constant and large size, i.e. 50 arc minutes width of visual angle) changed automatically across trials according to the participant's performance. Scores were then converted in contrast sensitivity (1/threshold), so that higher scores indicated better performance.

Figure 1. Visual acuity (left) and contrast sensitivity (right) measured using the FrACT. For visual acuity, participants selected the arrow corresponding to the perceived orientation of Landolt-C varying in size (illustrated here by the right gap). For contrast sensitivity, participants selected the arrow corresponding to the perceived orientation of Landolt-C varying in contrast (illustrated here with an up gap).

Potential covariates

The following variables were considered as potential confounders: age (in years), child sex, child birth weight (in grams), breastfeeding (none, <3 months, 3-7 months, >7-18 months or >18 months), age of the mother at the time of birth (in years), maternal educational level (12 th grade (bac) or higher), tobacco smoking (yes/no), alcohol J o u r n a l P r e -p r o o f drinking during pregnancy (at least one drink during the preceding week or one "binge drinking" session in the past three months reported on either one of the two questionnaires administered at enrolment and after delivery), and the Raven's Progressive Matrices maternal score. Prenatal and/or childhood exposure to other contaminants as assessed by cord and child blood concentrations of PCB-153, DDE, Hg and Pb were also examined.

Statistical analysis

Cord and child chlordecone concentrations were categorized into three groups (<LOD, ≥LOD -median, >median) and were also log-transformed and considered as continuous variables. All other exposure variables (PCB-153, DDE, Pb, and Hg blood concentrations) were log-transformed. When chlordecone and other contaminant concentrations were analyzed as continuous variables, we imputed values of blood concentrations below the LOD using the likelihood method [START_REF] Jin | Analysis of lognormally distributed exposure data with repeated measures and values below the limit of detection using SAS[END_REF], under the assumption that contaminant concentration is log-normally distributed. Children's contrast sensitivity scores were also log-transformed.

Multiple linear regressions were used to assess the associations between prenatal and childhood exposure to chlordecone and children's FrACT scores. Age and sex of the child, as well as total blood lipid concentrations were systematically included in the models. Other covariates were included in the models if they were associated with both chlordecone exposure and FrACT scores at p ≤ 0.2 or if they were highly associated (p ≤ 0.05) with FrACT scores alone. Models explored associations with prenatal exposure or J o u r n a l P r e -p r o o f child exposure separately and with mutual adjustment. Since chlordecone is a compound with recognized hormonal activity and since previous sex-specific associations have been reported between chlordecone exposure and child growth [START_REF] Costet | Perinatal exposure to chlordecone and infant growth[END_REF], or neurodevelopment [START_REF] Boucher | Exposure to an organochlorine pesticide (chlordecone) and development of 18-month-old infants[END_REF], we examined the interaction term of sex by chlordecone exposure (continuous variable) in the regression models. A liberal statistical criterion (p < 0.2) of the interaction term was used to justify follow-up sex-specific stratified analysis.

Results

Descriptive characteristics of the participants are presented in Table 1. The proportion of girls in the sample was slightly higher than boys (54.4% and 45.6%, respectively).

Children who needed wearing glasses (29.8%) were as many girls (30.3%) as boys (29.2%). Mothers' ages at the time of delivery ranged from 15.1 to 45.1 years old, and half of them (49.5%) had an education level of 12 th grade (bac) or higher. Alcohol drinking (yes/no) documented twice during pregnancy was reported by 2.5% of the women (at enrolment and after delivery), and only 2.8% reported smoking at the beginning of pregnancy. The average gestation age was 38.5 weeks (Median = 39 weeks) with a range of 34 to 41 weeks. Finally, the majority of participating children (85.3%) were breastfed. Median chlordecone concentrations among detected values were 0.3 µg/L in cord plasma and 0.08 µg/L in child blood samples. Prenatal and postnatal exposures were found to be poorly correlated (r = 0.139, p = .021). As for the FrACT visual assessments scores, the vast majority of children (91%) had visual acuity within the J o u r n a l P r e -p r o o f normal range, i.e., a Snellen fraction ratio of at least 0.8 (i.e., 20/25 or better), with a median of 1.33. The average contrast sensitivity score was 4.5% (median = 3.15%), ranging between 0.14% and 16.67%.

The associations between chlordecone exposure variables and contrast sensitivity scores are illustrated in Table 2. Results show that higher cord plasma chlordecone levels were associated with lower FrACT scores in the continuous adjusted model ( = -0.068, 95% CI = -0.133, -0.002). A similar, although marginal, association was obtained after the additional statistical adjustment for the 7-year-old child exposure ( = -0.062, 95% CI = -0.128, 0.003). The interaction term between sex and chlordecone exposure was null, either in the adjusted models 1 or 2.

No associations were observed between chlordecone child concentrations and contrast sensitivity scores (Table 2), although higher child plasma chlordecone levels were marginally ( p < 0.1) associated with lower FrACT scores in the continuous adjusted model ( = -0.059, 95% CI = -0.128, 0.010). This association vanished after additional adjustment for cord chlordecone concentrations (p > 0.1). Because the interaction terms between sex and chlordecone exposure were at p < 0.2 (see details in Method section), follow-up sex-stratified analyses were conducted. As such, the same continuous adjusted J o u r n a l P r e -p r o o f models were applied in girls (n=135) and boys (n=115), separately. A significant negative association was observed exclusively in boys ( = -0.112, 95% CI = -0.205, -0.018, p = 0.020 versus  = -0.015, 95% CI = -0.118, 0.088, p = 0.773 in girls). The association observed in boys remained significant after controlling for prenatal exposure ( = -0.094, 95% CI = -0.188, 0.000, p = 0.049). Of note, FrACT scores and chlordecone concentrations, pre-and postnatal, did not significantly differ between boys and girls.

A sensitivity analysis was conducted by re-running the continuous adjusted regression models 2 (see Table 2) where exposure to other toxicants (see details in Method section) were found to be correlated with the outcome at p < 0.2, that is child plasma PCB 153 concentrations and child blood Pb. Results using the whole sample were in line with the principal analyses: Cord chlordecone concentrations and contrast sensitivity remained marginally associated ( = -0.054, 95% CI = -0.118, 0.010, p = 0.100), and child chlordecone concentrations remained not associated with contrast sensitivity ( = -0.043, 95% CI = -0.112, 0.026, p = 0.218). Regarding the additional sex-stratified analyses for child exposure, the significant association initially found in boys ( = -0.094, 95% CI = -0.188, 0.000, p = 0.049) was still present ( = -0.101, 95% CI = -0.195, -0.007, p = 0.035).

Discussion

J o u r n a l P r e -p r o o f

The present study aimed to evaluate the association between pre-and postnatal chlordecone exposures on visual contrast sensitivity in school-aged children. Results from continuous adjusted models showed that higher cord plasma chlordecone concentrations were significantly associated with lower contrast sensitivity. Although no association was found with child chlordecone concentrations, further sex-specific stratified analyses revealed a significant decrease in the contrast sensitivity scores of boys, but this reduction was not observed in girls. Interestingly, these findings resisted to the additional statistical adjustment for mutual chlordecone exposure (see Models 2, Table 2). The sensitivity analysis revealed that further adjustments for PCB-153 and Pb co-exposures did not change the results.

A decrease of contrast sensitivity can be due to alterations of ocular and/or retinal/brain processing [START_REF] Waksman | Contrast sensitivity in occupational and environmental neurotoxicology: what does it really mean?[END_REF]. The contribution of ocular refraction errors can be reasonably excluded here. First, all of the tested children were wearing their glasses during the visual evaluation, despite the prescription for some of them not being up to date. Nonetheless, visual acuity was verified and found to be in the normal range for the vast majority (> 90%) of the children. Furthermore, the stimulus size used for contrast sensitivity testing was quite large (low to medium spatial frequencies), which prevents alterations of stimulus visibility caused by potential refractive errors. In fact, deficits in contrast sensitivity observed at low spatial frequencies reflect predominantly defects in post-retinal neural processing [START_REF] Waksman | Contrast sensitivity in occupational and environmental neurotoxicology: what does it really mean?[END_REF]. It is thus likely that the observed decrease in contrast sensitivity is mainly due to altered retinal and/or brain processing.

J o u r n a l P r e -p r o o f

Contrast sensitivity function relies on neural processing along the visual pathway, which involves various synaptic junctions and neurotransmitters. For instance, impaired contrast sensitivity has been found in pharmacological studies using drugs that alter GABAergic transmission, while visual acuity remained relatively intact (Blin et al., 1993;Haris and Phillipson, 1995;Giersch et al., 2006). Dopamine is another important neuromodulator of visual processing at both retinal and cortical levels [START_REF] Albrecht | Sex differences and effects of estrogenic compounds on the expression of inflammatory molecules by astrocytes exposed to the insecticide dimethoate[END_REF][START_REF] J O U R N A L P R E -P R O O F Parkinson | Evidence for a dopaminergic innervation of cat primary visual cortex[END_REF][START_REF] Witkovsky | The organization of dopaminergic neurons in vertebrate retinas[END_REF]. An improvement in contrast sensitivity has been demonstrated following administration of dopaminergic agonists in humans [START_REF] Bulens | Effect of levodopa treatment on contrast sensitivity in Parkinson's disease[END_REF][START_REF] Domenici | Dopaminergic drugs improve human visual contrast sensitivity[END_REF]. Considering that organochlorine pesticides have also been proven to induce oxidative stress, mitochondrial dysfunction and caspase activation in dopaminergic neurons [START_REF] Schuh | Effects of the organochlorine pesticide methoxychlor on dopamine metabolites and transporters in the mouse brain[END_REF][START_REF] Sharma | Organochlorine pesticides dieldrin and lindane induce cooperative toxicity in dopaminergic neurons: role of oxidative stress[END_REF], and, on the other hand, that chlordecone can alter catecholamine activity -including dopamine -by decreasing their synaptic binding and uptake [START_REF] J O U R N A L P R E -P R O O F Desaiah | Chlordecone interaction with catecholamine binding and uptake in rat brain synaptosomes[END_REF], one can reasonably hypothesize that associations between chlordecone exposure and contrast sensitivity dysfunction observed in the current study may potentially be mediated, at least partially, through dopaminergicrelated mechanisms.

Our results highlight the importance of assessing the functional integrity of sensory processing when evaluating chemical neurodevelopmental toxicity. The relevance of sensory assessment is supported by our previous studies in the French mother-child J o u r n a l P r e -p r o o f PELAGIE cohort, showing subtle functional visual processing alterations that were not detectable with cognitive evaluations (e.g., [START_REF] Cartier | Children's contrast sensitivity function in relation to organophosphate insecticide prenatal exposure in the mother-child PELAGIE cohort[END_REF]. Moreover, visual assessments in epidemiological cohort studies together with neuropsychological testing can aid in detecting participants needing adjustments due to potential visual deficits. This visual adjustment may, in turn, provide a better prediction of cognitive dysfunction in association with exposure, as demonstrated in the Faroese children in relation to mercury exposure [START_REF] Grandjean | Impact of contrast sensitivity performance on visually presented J o u r n a l P r e -p r o o f neurobehavioral tests in mercury-exposed children[END_REF].

The pattern of sex-dependent results found in the current study is noteworthy. In the study of [START_REF] Cartier | Children's contrast sensitivity function in relation to organophosphate insecticide prenatal exposure in the mother-child PELAGIE cohort[END_REF], the authors reported a decrease of contrast sensitivity scores in 6-year-old children in association with prenatal exposure to organophosphate pesticides in boys, but not in girls. To our knowledge, this is the only study which has investigated the impact of pesticide exposure during pregnancy on child visual function. Other sex-dependent associations of neurodevelopmental deficits with pesticides in children have also been reported (e.g., [START_REF] Philippat | Prenatal exposure to organophosphate pesticides and risk of autism spectrum disorders and other non-typical development at 3 years in a highrisk cohort[END_REF][START_REF] Rauh | Prenatal exposure to the organophosphate pesticide chlorpyrifos and childhood tremor[END_REF][START_REF] Suarez-Lopez | Acetylcholinesterase activity and neurodevelopment in boys and girls[END_REF][START_REF] Van Wendel De Joode | Pesticide exposure and J o u r n a l P r e -p r o o f neurodevelopment in children aged 6-9 years from Talamanca, Costa Rica[END_REF][START_REF] Wagner-Schuman | Association of pyrethroid pesticide exposure with attention-deficit/hyperactivity disorder in a nationally representative sample of U.S. children[END_REF]. For instance, prenatal exposure to organophosphate pesticides was significantly associated with attention problems, with a stronger association found in the boys of a rural California longitudinal cohort [START_REF] Marks | Organophosphate pesticide exposure and attention in young Mexican-American children: the CHAMACOS study[END_REF]. In another birth cohort study, prenatal exposure to organophosphate pesticides decreased working memory performance in boys, as assessed by the Wechsler Intelligence Scale for Children (WISC-IV), with no apparent deficits in girls [START_REF] Horton | Does the home environment and the sex of the child modify the adverse effects of prenatal exposure to chlorpyrifos on child working memory?[END_REF], although the interaction term between exposure and J o u r n a l P r e -p r o o f child sex was not significant. It is important to note that the sex-specific results from all these studies need to be interpret with caution because of small sample size, differences in measured outcomes, participant characteristics or statistically power.

Although the underlying mechanisms are still unknown, genetic and hormonal factors are generally thought to play an important role in sex-related differences observed in epidemiological studies. A growing body of experimental evidence show multiple levels of sexual dimorphisms in the brain, i.e., sex differences in neurochemical phenotype, synapses, cell genesis, inflammatory mediators, epigenetics, and brain volume [START_REF] Mccarthy | Neuroimmunology and neuroepigenetics in the establishment of sex differences in the brain[END_REF], which form a myriad of targets for neurotoxicants across sexes, providing biological plausibility for sex-specific mechanisms of action. In vivo rodent studies have shown that males are significantly more sensitive to organophosphate pesticides than females [START_REF] Comfort | Sex-Specific Neurotoxic Effects of Organophosphate Pesticides Across the Life Course[END_REF]. For instance, the cellular expression of inflammatory molecules and reactive oxygen species (ROS) has been found to be higher in males compared to female rats following dimethoate exposure (Astiz, [START_REF] Albrecht | Sex differences and effects of estrogenic compounds on the expression of inflammatory molecules by astrocytes exposed to the insecticide dimethoate[END_REF]. Regarding chlordecone, sex-dependent effects of perinatal exposure have frequently been reported in animal studies, particularly in the development of behavioral and/or neural function [START_REF] Cooper | Effects of perinatal Kepone exposure on sexual differentiation of the rat brain[END_REF][START_REF] Mactutus | Evaluation of long-term consequences in behavioral and/or neural function following neonatal chlordecone exposure[END_REF]. These effects have been linked to the well-known property of chlordecone to alter pituitary hormones and estrogenic activity [START_REF] Hammond | Estrogenic activity of the insecticide chlordecone (Kepone) and interaction with uterine estrogen receptors[END_REF][START_REF] Hong | Effects of chlordecone administration on brain and pituitary peptide systems[END_REF][START_REF] Hudson | Estrogen-like activity of chlordecone (kepone) on the hypothalamopituitary axis: effects on the pituitary enkephalin system[END_REF][START_REF] Kuiper | Development of visual acuity in preschool children as measured with Landolt C and Tumbling E charts[END_REF][START_REF] Lemaire | Activation of alpha-and beta-estrogen receptors by persistent pesticides in reporter cell lines[END_REF].

J o u r n a l P r e -p r o o f

While the longitudinal design of the TIMOUN study and the computer-based assessment of visual contrast sensitivity are the primary strengths of our study, it also has limitations.

First, we conducted a large number of analyses with multiple comparisons, which increases the likelihood of spurious associations. Nevertheless, our interpretations focused on the pattern of the results instead of on isolated findings. Second, the FrACT task was based on a single stimulus size, i.e., a large Landolt C optotype, which is composed of a mixture of low to medium spatial frequencies. It is common when measuring contrast sensitivity to use several and specific sine-wave spatial frequencies to estimate visual functions as a whole. For instance, [START_REF] Lebel | Neurotoxic effects of low-level methylmercury contamination in the Amazonian Basin[END_REF] have reported specific deficits in the contrast sensitivity of Amazonian adults exposed to mercury, which were specific to high spatial frequencies, i.e., not detectable at low and medium ones.

Conclusion

Our study showed adverse associations between chlordecone exposures and children's contrast sensitivity scores, pointing to the importance of using visual assessments in cohort studies to better understand the impact of environmental contaminants on the brain integrity of children. The impact of postnatal exposure to chlordecone appeared moderated by child sex, such that the visual performance was decreased as a function of exposure, particularly in boys. Further epidemiological studies are necessary to replicate these findings, as well as laboratory studies to make reasonable causal inferences Model 2: additional adjustment for the complementary chlordecone exposure (i.e., child levels when the cord levels was the variable of interest, and vice versa).

J o u r n a l P r e -p r o o f

J

  o u r n a l P r e -p r o o f Blood samples at birth (cord blood) and at the 7-year visit, were collected in EDTA tubes to document prenatal and childhood exposure to chlordecone respectively, and to other environmental contaminants. Plasma samples were stored at -30 °C in Polypropylene Nunc® tubes following centrifugation. Chlordecone, polychlorinated biphenyl congener 153 (PCB-153), dichlorodiphenyl dichloroethene (DDE) and lipids were measured in plasma. Total mercury (Hg) and lead (Pb) were quantified in whole blood. Determination of chlordecone and PCB-153 concentrations were done by the Center for Analytical and Research Technology at Liege University (Belgium). Contaminant concentrations were analyzed by high-resolution gas chromatography (Thermo Quest Trace 2000).

J

  o u r n a l P r e -p r o o f between chlordecone exposure and the development of brain processing, including sensory functions.

Table 2 .

 2 Associations between chlordecone exposure and visual contrast sensitivity. adjusted for child sex and age, maternal IQ (Raven score), maternal education, maternal alcohol intake during pregrancy and plasma lipids.

Funding sources

This work was supported by grants from the National Institute of Health and Medical Research (INSERM ATC2003-A0313665), the National Research Agency (ANR PNRA2006 2.24), the French Agency for Environmental and Occupational Health Safety (AFSSET APR2003 RD-2004-010), the French Ministry of Environment (PNRPE APR2005 CV05000142), and the General Health Directorate (DGS RMC11129NNA & R17142NN).

Competing financial interests declaration

No conflict of interest.

Declaration of interests

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.


Ronan Gaugne
email: ronan.gaugne@irisa.fr

From the engraved tablet to the digital tablet, history of a fifteenth century music score

Keywords: CCS Concepts:, Applied computing → Arts and humanities;, Computing methodologies → Computer graphics Digital Heritage, Archaeology, Tangible Heritage, Intangible Heritage, Music, Photogrammetry, RTI, ICT technologies in support

This work illustrates the use of three different digitization techniques in order to study and valorize a 15th century engraved tablet discovered during a preventive archaeological excavation in the area of a former convent. The tablet is covered with engraved inscriptions on both sides, and includes a musical score. Digitization allowed for an advanced analysis of the inscriptions, and to generate a complete and precise 3D model of the artifact which was used to produce an interactive application deployed both on tactile tablets and website. The interactive application integrates a musical interpretation of the score that gives access to a testimony of intangible heritage. This interdisciplinary work gathered archaeologists, researchers from computer science and physics, and a professional musician.

INTRODUCTION

At the crossroad of tangible and intangible heritage, we present the study of a fifteenth century engraved tablet that contains a musical score. This tablet was discovered during an important excavation in the center of the city of Rennes in Brittany, France [START_REF] Le | Rennes (Ille-et-Vilaine). Le couvent des Jacobins[END_REF]. Considering the originality of this discovery, further investigations using digital technologies were proposed. In this context, digitization was used (i) to accompany the scientific study of the tablet, (ii) to preserve a fragile artifact, and (iii) to give easy access to this artifact through an interactive 3D application. The discovery of old musical scores is extremely valuable because they are few and they carry a representation of intangible heritage. Many ways of notating music existed throughout the human history [START_REF] Lemberg | A survey of the history of musical notation[END_REF]], and we can find some notable examples of engraved music such as the Mesopotamian Hurrian songs [START_REF] Litchfield | The Babylonian musical notation and the Hurrian melodic texts[END_REF]], [START_REF] Duchesne-Guillemin | Sur la restitution de la musique hourrite[END_REF], dating from 1400 BC, the Greek Seikilos Column [START_REF] Pepys Winnington-Ingram | Ancient Greek Music: A Survey[END_REF], [START_REF] Solomon | The Seikilos inscription: a theoretical analysis[END_REF]] which is approximately 2000 years old. While in the first example of the Hurrian songs, the music interpretation was not completely possible, the score of the Seikilos column is fully interpreted. We can find several musical interpretations of these scores; e.g., for the Hurrian songs the interpretation of by the Ensemble De Organographia [START_REF] De Organographia | Music of the Ancient Sumerians, Egyptians Greeks, new expanded edition. CD recording[END_REF], and for the Seikilos Column an interpretation by Atrium Musicae de Madrid, from 1979 [Atrium Musicae de Madrid and[START_REF] Madrid | Renaissance score engraved in church's exterior[END_REF]. There are also other examples of interpreted engraved music. In 2017, Jones presented in [START_REF] Jones | Renaissance Knives Had Music Engraved on the Blades; Now Hear the Songs Performed by Modern Singers[END_REF]], the example of Renaissance knives with music engraved on their blades, and in 2012, an anonymous article in the Journal of Medieval Art and Architecture, [anonymous 2012], described a Renaissance score engraved on a church's exterior. In both church and knife engravings, the musical interpretations of the scores gave life to the intangible heritage handled by engraves on knives or building. During Renaissance, mensural musical notation was already well established, following the works in 13th and 14th centuries of Franco of Cologne (c. 1280) in his treatise Ars cantus mensurabilis ("The art of measured chant", [START_REF] Franco De Colonia | Ars cantus mensurabilis[END_REF]), and the French stylistic movement of the Ars nova [START_REF] Reese | Music in the Renaissance[END_REF]], [START_REF] Mayer Brown | Music in the Renaissance[END_REF]. The number of lines in a musical stave can be four or five, and notes are represented by squares and diamonds as illustrated in this 15th century musical score kept in the French National Library (Fig. 1) We first detail the discovery context of the tablet, then we present the analysis of the engraves on the tablet, the digitization steps of the tablet, and the development of the interactive application on a tactile tablet. We finish with a discussion of the contributions and open further perspectives.

THE ORIGINAL ENGRAVED TABLET

The original engraved tablet was found during preventive archaeological works at a convent in the center of the city of Rennes.

The excavation of the convent of the Jacobins

From December 2011 to June 2013, a major archaeological excavation was conducted in Rennes, Brittany, France, by Inrap (National Institute of Preventive Archaeological Research) before the development of the former convent of the Jacobins into a congress center (Fig. 2).

The convent of the Jacobins of Rennes was founded in 1368 and was particularly renowned between the fifteenth century (Fig. 3, left) and the seventeenth century (Fig. 3, right). Occupied by the army from the French Revolution, at the end of the eighteenth century, the building has been used as a military store for two centuries before being bought by Rennes-Métropole in 2002. The refectory, a place where the shale plate engraved was discovered, is the largest room in the convent measuring 28 m in length and 7.5 m in width (Fig. 4). Five successive soils were discovered during the excavation. The first three consisted of a single layer of clay while the last two were made of terracotta tiles. It is in the leveling embankment of the first pavement that the engraved tablet of a partition was found.

Description of the tablet

The tablet with the musical score is part of a set of a dozen pieces engraved with more or less complex patterns (Fig. 5). The material, a slate shale of local origin, is particularly suitable for engraving. From the early Middle Ages, these 10 to 20 cm wide slabs (litter size or slate roof) often served as a support to register ideas, accounts, make drawings or caricatures, and were sometimes transformed into a board game. The various dry point drawings were probably created with the help of a metal tool. Similar to a school slate, graffiti, sometimes made by different people, can then be superimposed over time on a single plate.

2.2.1

The plate with the score. Made from a good quality shale plate, the slab is incomplete, with all the edges broken (size 17 x 15 x 0,5 cm). It has graffiti on both sides (Fig. 6). On the first (Fig. 7, top), a musical score is superimposed on a wheel pattern with 11 spokes carrying a succession of ordered numbers on the circular part. The surface has several words or lines of identifiable writing, but clearly corresponding to different handwritings.

On the other side (Fig. 7, bottom), the main element consists of linear lines forming three nested squares, representing a very fashionable game in the Middle Ages known as Nine Men's Morris or Mill game. The lines of the game, certainly drawn first, served as a guide for the engraving of several letters and words, including large Gothic letters near the edge (Fig. 7, bottom).

2.2.2

The music score. The score engraved on the first side, and presented in Figure 8, is in the form of a musical stave with four lines on which a C key is visible on the third line, which means that the notes on the third line starting from the lower line will be C notes. The 39 notes, semi-brief, are diamond shape and without tail, which is not unusual for this period. They correspond to our current quarter notes and are all equal in duration. There is no silence and no text that would guide us to a known musical piece. We do not recognize a known Gregorian melodic formula. The mode, if we consider that the melody is complete, is a natural minor A or aeolian A mode, which does not really appear until the fifteenth century. Religious songs in this period were mainly in four modes: Dorian (D), Phrygian (E), Lydian(F), and Myxolydian (G). The ambitus would be perfect for a sharp, male tenor voice. The musician who created the engraving did not sign it, which is not surprising. In the case of an original melody, the absence of a signature is common to many ancient and religious works for which the author, inspired by God himself, would not allow himself to appropriate the creation of what he sincerely believed was coming from heaven.

DIGITIZATION PROCESS

Among the several engraved tablets discovered during the excavation, it has been decided to digitize the engraved tablet with the music score because of the richness of the engraving on both sides, and because of the presence of the music score that is very particular. Three main motivations guided the choice of digitization, (i) the tablet is very fragile, (ii) digitization may help to better identify some graffiti, and (iii) the digital copy of the tablet would serve as a basis for an interactive valorization application of the tablet.

Digitization techniques

Three different techniques of digitization have been used for the tablet: standard photogrammetry, Reflectance Transformation Imaging, and digital microscopy.

3.1.1 Photogrammetry. Photogrammetry is a well-known technology of image data processing, that allows to produce metric and 3D data from a set of 2D point of views [START_REF] Hallert | Photogrammetry, basic principles and general survey[END_REF]], [START_REF] Edward M Mikhail | Introduction to modern photogrammetry[END_REF]. It is widely used in the heritage domain for recording and documentation [START_REF] Remondino | Heritage recording and 3D modeling with photogrammetry and 3D scanning[END_REF]], [START_REF] Guarnieri | Cultural heritage interactive 3D models on the web: An approach using open source and free software[END_REF]. This technology has been used in particular for rock engravings [START_REF] Mudge | Robust and scientifically reliable rock art documentation from digital photographs[END_REF] where it is combined with Reflectance Transformation Imaging.

Reflectance Transformation Imaging (RTI).

Reflectance Transformation I maging ( RTI) i s a technology developed in the early 2000s by the Cultural Heritage Imaging, a non-profit corporation dedicated to heritage preservation through the dissemination of new technologies (2017). It is a computational photographic method that captures a subject's surface shape and color from a series of frontal photographs under different artificial lighting and enables the interactive re-lighting of the subject from any direction [START_REF] Malzbender | Polynomial texture maps[END_REF]]. This technology is particularly useful in the context of objects with light relief such as paintings [START_REF] Aure | Generating 3D Models of Paintings through the Combination of 2D, 3D and RTI Data[END_REF]. It was thus well suited for the engraved tablet with its very thin carving.

Digital microscopy.

A digital microscopy is a variation of a traditional optical microscopy that uses optics and a digital camera to output an image to a monitor, generally processed by a computer software. Current digital microscopy usually provides advanced processing features such as 3D reconstruction. This technology is already used in cultural heritage [START_REF] Cacciari | 3D digital microscopy for characterizing punchworks on medieval panel paintings[END_REF]], [START_REF] Moretti | Using 3D Microscopy to Analyze Experimental Cut Marks on Animal Bones Produced with Different Stone Tools[END_REF]].

Photogrammetry of the tablet

We used a DSLR Canon 5DmkII, a 21.1-megapixel full-frame CMOS digital single-lens reflex camera, with a lens type Canon EF 85 mm f/1.8 Macro USM. The studio was equipped with 2 flashes, Walimex PRO VC-300 with Softbox, to have a uniform lightening with minimal shadows. The object was presented on a white background, and placed on a turntable. The capture was performed in two passes: first with one side up, and second with reverse side up, to achieve complete coverage of the object. For each pass, the camera was oriented at three different angles with respect to the horizontal. For the first pass, we took 43 photos, and for the second pass, 48 photos. The raw pictures were transformed into jpeg format, with a resolution of 5086×3391px, using Lightroom 5.7, to increase contrast, clarity, and sharpness. We used Agisoft PhotoScan Standard Edition to align the photos and generate a point cloud. For the capture, the software was able to align the totality of the photos. For the first series, we obtained 5168 tie points for alignment, a dense cloud of 8.7 million points (ultra-high quality), and a mesh with 1.7 million faces. For the second series, we obtained 6129 tie points, a dense cloud of 9.2 million points (ultra-high quality), and a mesh with 1.8 million faces. The meshes were cleaned and aligned with Meshlab, blender and CloudCompare. The resulting mesh for the tablet has 967.000 faces (Figure 9).

Reflectance Transformation Imaging (RTI)

We built our own RTI system mostly from the the specification presented in [7], except for the dome for which a plastic salad bowl was used, with matte black paint on the inside. The dome has a diameter of 34cm, and was drilled with 60 holes filled with white leds (Fig. 10).

We used a Canon EOS 6D, a 20.2-megapixel full-frame CMOS digital single-lens reflex camera, with a lens type Canon EF16-35mm f/4L IS USM. The 60 raw pictures, one per led lighting, were transformed into jpeg, with a resolution of 5472 × 3648 px, using the Lightroom 5.7 software, and we used RTI builder 2.0.2, with Hemispherical Harmonics (HSH) fitting algorithm to generate RTI data (Fig. 11,left). We used 2 black marbles from an abalone game as reflective spheres. RTI data was used to produce a precise normal map (Fig. 11, right) of 3361x3193 px in order to be used in the interactive application for dynamic lightening.

Digital microscopy

In order to obtain more precise data for particularly illegible graffiti, we performed digital microscopy with a Keyence VHX 5000 system, equipped with a VH-Z20T Universal Zoom Lens 20x to 200x (Fig. 12,left). With respect to optical data, this system enables features to measure, highlight and agglomerate data on large areas (Fig. 13), and allows for the generation of 3D digital data (Fig. 12, right). The microscopy was operated by a physicist in the presence of two archaeologists who were in charge of the study of the tablet.

Analysis of digital data

Digital data from photogrammetry and RTI is mainly used for the interactive 3D applications. The photogrammetry setup used in the project was not accurate enough to generate a mesh representing the thin engravings. In figure 14, on a close view of the mesh around the score, only the main traces such as the lines of the score are visible. The thinner traces are rendered through the texture. In comparison, the normal map generated from the RTI capture, as presented in figure 15, provides more details on engravings than the same area presented in figure 14. Digital microscopy was used to explore hypotheses on the writings. In particular, one question was raised on the existence of lyrics on top of the music score, and digital microscopy could provide the answer to this question. The structure of the beginning of the score, magnified by the digital microscope, is presented in figure 16. In the red rectangle, two connected circles over a line represent a C score. In the green rectangle, the diamond shapes on and between the lines represent the music notes. In the blue rectangle above the lines, some writings were proposed as potential lyrics for the score. This was not confirmed as the microscope revealed that some characters were engraved prior to the score lines and some were engraved posterior, as shown in figure 17 where the two red rectangles illustrate two different anteriorities of two letters with respect to the upper score line.

INTERACTIVE APPLICATION

An interactive application was developed in order to present the results of the study of the tablet to a wide audience. We targeted an interactive application on tactile tablet to propose intuitive multi-touch interactions. The 3D model of the tablet displayed in the application is the one generated with the photogrammetry. The main functionalities of the application are highlighted visualisation of the graffiti, free manipulation of the 3D tablet, manipulation of a light source, interaction with the musical score, and access to pages of explanations on the object and its discovery.

Interaction with the tablet

The goal of this interaction is to allow the user to manipulate the 3D model of the tablet as naturally as possible in order to visualize both side, and detailed parts of the graffiti. The graffiti on the tablet are highlighted with clickable colored boxes (Fig. 18, top), and an explanation and visualization of the selected graffiti are displayed when the area his touched by the user (Fig. 18,bottom). The different graffiti can also be browsed and displayed through arrows icons at the bottom of the screen. The colored boxes can be hidden for a better visualization of the whole engraved tablet, and standard multi-touch interactions allow to manipulate it: orbital rotation with one finger, planar rotation by rotating one finger around one fixed finger, zoom in/out by bringing two fingers closer/further apart, translation by sliding two fingers.

Interaction with the light

The goal of this interaction is to highlight the reliefs of the tablet and the engravings. The control of the light is activated with the light icon at the bottom, left of the screen. When activated, an active area is displayed in the upper right corner of the screen (Fig. 19, top, right), with a slider to control the intensity of the light, and a representation of the point light position with respect to tablet, which can be moved with one finger. The light rendering is based on the data generated with the RTI digitization.

Interaction with the music

The goal of this interaction is to allow the user to experience the music engraved on the tablet either by playing it or by listening to a prerecorded song of the music. When the musical score area is activated, either through the colored box, or through the area browser, an active graffiti of the score is displayed, with all the notes playable (Fig. 20). When a note is touched, it is highlighted with a colour (Fig. 20, right) and the corresponding sound is produced, either with a piano sound or a voice sound, depending on the mode selected in the lower right corner of the explanation box. A play icon allows to launch an interpretation of the score sung by Dominique Fontaine. A cursor follows the song on the score in order to indicate the note currently played to the user (Fig. 20, left).

Display of explanations

The goal of this interaction is to present the context of the discovery to the user. An "Information" icon opens a succession of 8 pages that displays pictures and explanations (in French) about the context of the discovery (Figure 21). The pages are browsed with back and forward arrows icons, and a "Home" icon allows the user to come back to the interactive application.

Implementation

The application was implemented with the game development platform Unity 3D, and deployed as a PC standalone executable on a Microsoft Surface Pro 4 and a HP ElitePad 1000 tablet. A WebGL version was also generated from Unity to be on the Web.

EXHIBITION

The original tablet was presented together with the two digital tablets to the "science and music day" (http://jsm.irisa.fr), in October 2017, organised by the computer science research laboratory. The form of the presentation was a workshop of 30 minutes, repeated throughout the afternoon for groups of 20 people (Fig. 22). The presentation had four parts: first, the archaeologists presented the archaeological context of the discovery of the tablet. Second, Dominique Fontaine presented the score in its historical context and performed a live interpretation. After the score, the computer scientists presented the digitization process and implementation of the interactive application, and finally, by interacting with the public, both the real and the virtual tablet were presented (Fig. 22,bottom). A total of about 150 visitors followed the presentation during the day. A new exhibition of these two versions of the tablet was performed in June 2019, in a Museum context.

DISCUSSION

The project illustrates the use of several digital technologies on an archaeological object, with three main and distinct goals:

• Preserve a fragile artifact. The stone of the tablet is very fragile, and engravings are subject to erosion and erasure. It is thus important to put in place preservation measures, and digitization provides interesting complementary properties with respect to traditional physical protection measures. In particular, digital data is easily replicable and sharable. The different digitization techniques used on the tablet allowed to perform a detailed recording of the object and to extrapolate different properties which highlight the content of the tablet. • Contribute to the analysis of the artifact. Engravings on the tablet overlap each other, and some inscriptions are barely legible. RTI digitization and digital microscopy enabled a better vizualisation of the graffiti and testing of the proposed hypotheses. In particular, digital data allowed to confirm the presence of the C key which was not obvious in the first studies. It also invalidated a hypothesis about the presence of lyrics for the score. Indeed, some delicate engravings detected with optical binoculars close to the notes could have been interpreted as initials of words. RTI and digital microscopy did not confirm this hypothesis, and digital microscopy indicated that the anteriority of these writings were different. • Valorize an artifact that embeds intangible heritage. The engraved tablets represent an uncommon testimony of the everyday life in a 15th century Covent. In particular, the musical score gives access to an intangible form of heritage that was valorized in that project through an interactive application on a tactile tablet. This application, based on the 3D data obtained from the digitization of the tablet, combined with a record of an interpretation of the score, and a presentation of the analysis of the engravings by archaeologists, creates a comprehensive medium to share the discovery with the public. The application is currently only available on Windows and Android tablets and should be deployed to other tablets through Unity. The adaptation of the application to WebGL could be used for broadcasting it on websites and to reach a wider audience. When dealing with digital data, the question of their durability and preservation must be also handled. The first aspect is the sustainability of the digital medium. In order to have as little dependency to the medium as possible, we chose to store our data on two different NAS systems of our research institutes. The second aspect is the sustainability of the data format. This is related to the ability to access the data through a software. In order to maximize the sustainable accessibility to our data and its interoperability, we kept the raw data of the photos, and two widespread standard formats of images (png and jpeg). The sustainability of the transformed data, such as RTI data or the interactive application, are much more difficult to guarantee. Nevertheless, the transformations of the original data and the implementations on top of the transformed data are reproducible, given the initial digital data.

CONCLUSIONS

The 15th century engraved tablet studied in this manuscript was discovered during preventive archaeological excavations, with about ten other engraved tablets. The presence of a musical score among the engraved inscriptions motivated the digitization of the tablet in order to preserve this fragile artefact, and to help the analysis of the inscriptions. The digitization used photogrammetry to produce a textured 3D model of the tablet, RTI to produce a precise normal map, and 3D digital microscopy to produce a magnification of certain parts of the engravings. The resulting 3D model was used to produce an interactive tactile application on digital tablets that was presented at the science mediation events. The application integrates a musical interpretation of the score performed by a professional singer specialized in Renaissance music. A web version of the application is also proposed to present the results to a wider audience. This work is an interesting example of the value of using 3D digital technology for the preservation, analysis and sharing of an archaeological artefact, and in particular, the valorization of intangible heritage.

AUTHOR CONTRIBUTIONS

Ronan Gaugne led the digitization processes and the implementation of the interactive tablet. Françoise Labaune was the archaeologists in charge of the study of the tablet. Dominique Fontaine performed the study of the musical score and the musical interpretation. Gaétan Le Cloirec was the archaeologist responsible for the excavation of the site. He was the lead researcher of the archaeological study. Valérie Gouranton was the lead researcher of the digital study of the tablet. She is also the coordinator of the INTROSPECT ANR-FRQ-SC project.

Fig. 1 .

 1 Fig. 1. Musical score "Chansonnier cordiforme", (fragment), Savoy, 15th century, BnF, Manuscrits, Rothschild 2973, f° 1v°-2r°© Bibliothèque nationale de France

Fig. 2 .

 2 Fig. 2. Left: excavation at the west courtyard (© H. Paitier / Inrap), Center: excavation at the cloister garden (© G. Le Cloirec / Inrap), Right: excavation at the east wing (cl. H. Paitier / Inrap).

Fig. 3 .

 3 Fig. 3. Schematic organization of the convent in the 15th century (left) and 17th century (right) (3D G. Le Cloirec / Inrap).

Fig. 4 .

 4 Fig. 4. Top, left: West facade of the convent integrating the windows of the refectory surmounted by openings that illuminated the cells of the monks (© T. Bethus / Inrap). Top, right: interior of the refectory facing the West wall with the large windows and the pulpit of the reader (© T. Bethus / Inrap). Bottom, left: first clay floor of the refectory (© T. Bethus / Inrap). Bottom, right: vestiges of the first floor of terracotta of which only the imprints remain in the laying mortar (© T. Bethus / Inrap).

Fig. 5 .

 5 Fig. 5. Left: fragment of a roof slab with a Nine Men's Morris engraving (© F. Labaune-Jean / Inrap). Center: plate with a caricature of person's profile, perhaps a monk (© F. Labaune-S. Jean / Inrap). Right: plate with a drawing of a circle and a horse (© F. Labaune-S. Jean / Inrap).

Fig. 6 .

 6 Fig. 6. The two sides of the tablet (© B. Arnaldi, Irisa).

Fig. 7 .

 7 Fig. 7. Presentation of different graffiti on the first (top) and reverse (bottom) sides (© F. Labaune, S. Jean, Inrap).

Fig. 8 .

 8 Fig. 8. Top: Transcription of the music score (© D. Fontaine, F. Labaune-S. Jean, G. Le Cloirec / Inrap). Bottom: Transcription in modern musical notation, in the G key (transcription D. Fontaine).

Fig. 9 .

 9 Fig. 9. 3D model of the tablet.

Fig. 10 .

 10 Fig. 10. Digitization of the tablet with the RTI dome.

Fig. 11 .

 11 Fig. 11. Specular rendering from RTI builder (left) and normal map (right).

Fig. 12 .

 12 Fig. 12. Left: Digital microscopy on the tablet. Right: 3D rendering of the C key.

Fig. 13 .

 13 Fig. 13. Reconstructed rendering of a graffiti.

Fig. 14 .

 14 Fig. 14. Detailed view of the mesh, with the four lines of the score.

Fig. 15 .

 15 Fig. 15. Detailed view of the normal map, for the same area as shown in figure 14.

Fig. 16 .

 16 Fig. 16. Structure of the score area.

Fig. 17 .

 17 Fig. 17. Details on the writings above the score.

Fig. 18 .

 18 Fig. 18. The interactive tablet. Top: 3D views of both sides of the tablet with different graffiti highlights. Bottom: visualization of a particular area of one inscription (left) and of the wheel pattern (right).

Fig. 19 .

 19 Fig. 19. Interactive manipulation of the light. The user can change the position and intensity of the light source with the interface in the upper right corner.

Fig. 20 .

 20 Fig. 20. The interactive musical score.

Fig. 22 .

 22 Fig. 22. Presentation of the tablet to the public. Top: Presentation conference given by the full team involved in the work. Bottom, left: The interactive tablet. Bottom, right: The original tablet.

ACM J. Comput. Cult. Herit., Vol. 1, No. 1, Article 1. Publication date: January 2020.

ACKNOWLEDGMENTS

This work was partially funded by the ANR-16-FRQSC-0004 INTROSPECT project. The authors whish to thank Quentin Petit, engineer at Inria, and Pierre-Nicolas Eudes, student at INSA Rennes, for their work on digitization and implementation, Bruno Arnaldi, professor at INSA Rennes, for taking the pictures for the photogrammetry, Isabelle Puault, Professor at University of Rennes 1, for taking the pictures for the RTI, Fabrice Célarié, associate professor at University of Rennes 1, for operating the digital microscopy, and Florian Nouviale, research engineer at INSA Rennes, and Ewen Camberlein, engineer at Inria for recording and producing the interpretation by Dominique Fontaine of the music score.

A ONLINE RESOURCES

The webgl implementation of the application is available with this link: http://www.irisa.fr/immersia/tablettejacobins/