Emeline Sabourin

Pilar Alda

Antonio Vázquez

Sylvie Hurtrez-Boussès

Marion Vittecoq

Impact of Human Activities on Fasciolosis Transmission

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Glossary

Disability-adjusted life years (DALYs): one DALY can be thought of as one lost year of 'healthy' life. The sum of these DALYs across the population, or the burden of disease, can be thought of as a measurement of the gap between the current health status and an ideal health situation, in which the entire population lives to an advanced age, free of disease and disability. Integrated parasite control: a system of control which considers the preservation of the ecosystem and human health. It integrates all control methods (chemical, biological, physical etc.), limiting the utilization of chemical products except if no other method is available. Neglected diseases: these diseases include a diverse group of communicable diseases that affect humans in tropical and subtropical countries. They involve more than one billion people and cost developing economies billions of dollars every year. Populations living in poverty, without adequate sanitation, and in close contact with infectious vectors, domestic animals, and wildlife are those worst affected. Preventive chemotherapy: this is defined as the administration of a single safe medicine, either alone or in combination with other medicines, as a public health intervention to prevent selected neglected tropical diseases. Self-fertilization: fertilization of female gametes by male gametes from the same individual, as by sperm from the same animal in hermaphroditic species or by pollen from the same plant.

Fasciolosis is also considered to be a major veterinary problem since it is responsible for important losses in the productive capacity of livestock (meat and milk) [START_REF] Torgerson | Epidemiology and control[END_REF]. For instance, in the Irish and UK farming industry, fasciolosis is responsible for the annual loss of over £80 million [START_REF] Mulcahy | Cathepsin L proteinases as vaccines against infection with Fasciola hepatica (liver fluke) in ruminants[END_REF]. The liver flukes cause serious digestive illness, anaemia, and sometimes cirrhosis, which can be lethal in livestock [START_REF] Fao | Multicriteria-based ranking for risk management of food-borne parasites[END_REF]. Treatmen t is long and expensive, and cases of parasite resistance have been described [START_REF] Kelley | Current threat of triclabendazole resistance in Fasciola hepatica[END_REF]. Liver flukes have a great ability to proliferate in a wide range of different freshwater ecosystems. Indeed, fasciolosis is recognized to have a worldwide latitudinal and longitudinal distribution [30]. This wide distribution makes it possible to study its parasite dynamics in different habitats with diverse definitive and intermediate hosts. Yet, it greatly complicates disease control, because solutions must be adapted to very different environmental and socioeconomic contexts. The purpose of this review is to assess the existing knowledge on the effects of human activities and habits on the risk of fasciolosis. We focus on three groups of human activities that are mentioned in the literature as the main factors affecting fasciolosis: (i) irrigation-system management, (ii) livestock management, and (iii) human diet and hygienic habits. For each of these activities, we gathered available data to highlight knowledge gaps and perspectives and to identify solutions that may help mitigate the risk of fasciolosis transmission through preventive measures and control strategies.

Irrigation-System Management

Similar to other vector-borne diseases, such as malaria or schistosomiasis, the vectors of fasciolosis tend to proliferate in man-made irrigation systems, leading to severe consequences on human and animal health [START_REF] Walker | Population dynamics of the liver fluke, Fasciola hepatica: the effect of time and spatial separation on the genetic diversity of fluke populations in the Netherlands[END_REF][START_REF] Mas-Coma | Epidemiology of fascioliasis in human endemic areas[END_REF][START_REF] Prepelitchi | Gastropoda: Lymnaeidae) in Wetlands of Northeastern Argentina[END_REF]. Liver flukes, unlike most trematodes, infect a wide range of intermediate hosts living in a wide range of freshwater habitats (irrigation canals, ditches, rivers, dams, and lakes) [START_REF] Pointier | Distribution of Lymnaeidae (Mollusca: Pulmonata), intermediate snail hosts of Fasciola hepatica in Venezuela[END_REF][START_REF] Vásquez | Distribución y preferencia de hábitats de moluscos hospederos intermediarios de Fasciola hepatica en Cuba[END_REF]. These intermediate hosts belong to several species of freshwater snails, mainly within the family Lymnaeidae [START_REF] Correa | Bridging gaps in the molecular phylogeny of the Lymnaeidae (Gastropoda: Pulmonata), vectors of Fascioliasis[END_REF], but also within the family Planorbidae [START_REF] Hamed | Natural infection of Fasciola hepatica (Trematoda: Fasciolidae) in Bulinus truncatus (Gastropoda: Planorbidae) in northern Tunisia[END_REF] and the terrestrial group Succineidae [START_REF] Relf | Evidence of Fasciola hepatica infection in Radix peregra and a mollusc of the family Succineidae in Ireland[END_REF]. Most of the snail species recognized to be major vectors of fasciolosis reproduce by self-fertilization, which leads to a great capacity to quickly colonize new habitats or recolonize after extinction events [START_REF] Trouve | Ecological components and evolution of selfing in the freshwater snail Galba truncatula[END_REF][START_REF] Lounnas | Self-fertilization, long-distance flash invasion and biogeography shape the population structure of Pseudosuccinea columella at the worldwide scale[END_REF][START_REF] Meunier | Field and experimental evidence of preferential selfing in the freshwater mollusc Lymnaea truncatula (Gastropoda, Pulmonata)[END_REF]. For example, the vector of fasciolosis, Pseudosuccinea columella, which is probably native to North America, colonized South America, Africa, Europe, and the Pacific islands in less than a century [START_REF] Lounnas | Self-fertilization, long-distance flash invasion and biogeography shape the population structure of Pseudosuccinea columella at the worldwide scale[END_REF]. Another vector, Galba truncatula, invaded the Bolivian Altiplano during the 20th century, inducing the highest hyperendemic level of fasciolosis recorded so far [START_REF] Meunier | Lack of molluscan host diversity and the transmission of an emerging parasitic disease in Bolivia[END_REF]. Human activities linked to freshwater ecosystems are a relevant dispersal factor notably due to natural and artificial connections between rivers and irrigation canals facilitating the installation of freshwater invaders [START_REF] Lodge | Predicting impact of freshwater exotic species on native biodiversity: challenges in spatial scaling[END_REF][START_REF] Loo | Freshwater invasions: Using historical data to analyse spread[END_REF]. This high invasiveness has probably facilitated the worldwide expansion of fasciolosis. For instance, in Senegal, hydroagricultural improvements and dam construction have led to significant environmental modifications (creation of reservoirs and irrigation canals), which in turn have created favourable conditions for the proliferation of the snail species Radix natalensis and Biomphalaria pfeifferi, the intermediate hosts of F. gigantica and Schistosoma mansoni, respectively [START_REF] Diaw | Prolifération de mollusques et incidence sur les trématodoses dans la région du delta et du lac de Guiers après la construction du barrage de Diama sur le fleuve Sénégal[END_REF]. In the Peruvian Altiplano, the construction of irrigation and drainage canals caused the proliferation of lymnaeid snails and consequently a higher prevalence of fasciolosis [START_REF] Esteban | Hyperendemic fascioliasis associated with schistosomiasis in villages in the Nile Delta of Egypt[END_REF]. Unlike irrigation canals that permanently conduct water, drainage canals can become dry so there is no typical aquatic vegetation. However, lymnaeids can live in both habitats because they can survive severe droughts [START_REF] Meunier | Field and experimental evidence of preferential selfing in the freshwater mollusc Lymnaea truncatula (Gastropoda, Pulmonata)[END_REF]. Indeed, lymnaeid species are amphibious; G. truncatula and Galba cubensis can live in dry habitats by burrowing partially or completely into the soil [START_REF] Moukrim | Vertical spatial behabiour patterns of lymnea truncatula in relation with origin of snails, infection with Fasciola hepatica, and experimental environment[END_REF][START_REF] Alba | Assessment of the FasciMol-ELISA in the detection of the trematode Fasciola hepatica in field-collected Galba cubensis: a novel tool for the malacological survey of fasciolosis transmission[END_REF]. In Spain, the government of the autonomous community of Castilla y León has funded the installation of modern irrigation systems to encourage new crops since 1990. Man-made modifications of the environment have contributed to the creation of new habitats for the intermediate hosts and have favoured the emergence of fasciolosis [START_REF] Martínez-Valladares | Prevalence of gastrointestinal nematodes and Fasciola hepatica in sheep in the northwest of Spain: relation to climatic conditions and/or man-made environ-mental modifications[END_REF]. These studies show that such constructions induce a higher sanitary risk. However, irrigation-system management can be combined with other parameters, which can increase the exposure period of infection. For example, in Pakistan, the first annual peak of fasciolosis is associated with artificial irrigation but the second peak is driven by rainfall [START_REF] Afshan | Impact of climate change and man-made irrigation systems on the transmission risk, long-term trend and seasonality of human and animal fascioliasis in Pakistan[END_REF]. Despite some insights into how irrigation-system management promotes snail proliferation and consequently increases the prevalence of fasciolosis, very few studies have been carried out both before and after the installation of irrigation. Preliminary epidemiological studies before the construction are needed to evaluate the epidemiological risks of any man-made irrigation.

Which Solutions Can Limit Intermediate Host Proliferation in Irrigation Systems?

Dams and irrigation canals are used to develop agriculture and the economy. Therefore, we need to assess the trade-off between the benefits and the cost of irrigation systems. One of the solutions proposed to prevent fasciolosis in regions with dams and irrigation canals is to prevent the proliferation of the intermediate host.

One solution is the use of molluscicides, which was highly recommended during the 1970s but has been abandoned because most products are toxic for the macrofauna that inhabit the freshwater environment [START_REF] Torgerson | Epidemiology and control[END_REF][START_REF] Rondelaud | La limnée tronquée: -Un mollusque d'intérêt médical et vétérinaire[END_REF]. Only a few studies have been conducted to test natural molluscicides [54,[START_REF] Hammond | Eucalyptus: A sustainable self delivery molluscicide?[END_REF]. A recent study on a new biomolluscicide, Citrullus colocynthis, shows that it kills the snail vector of fasciolosis, G. truncatula and also the larvae of F. hepatica without affecting the associated fauna of the snail [START_REF] Chawech | A study of the molluscicidal and larvicidal activities of Citrullus colocynthis L. leaf extract and its main cucurbitacins against the mollusc Galba truncatula, intermediate host of Fasciola hepatica[END_REF]. Another solution proposed is the use of biological control. Population dynamics studies are important for biological control strategies because they allow us to know the high mortality and reproduction seasons of freshwater snails; this information is needed for the effective introduction of biological agents (predators, competitors) [START_REF] Perera | Effectiveness of three biological control agents against intermediate hosts of snail-mediated parasites in Cuba[END_REF][START_REF] Perera | Biological control of snail intermediate hosts by competitor thiarid snails in Cuba[END_REF]. Rondelaud et al. [START_REF] Rondelaud | The control of Galba truncatula (Gastropoda: Lymnaeidae) by the terrestrial snail Zonitoides nitidus on acid soils[END_REF] used the predator mollusc Zonitoides nitidus to eliminate lymnaeid snails G. truncatula and Omphiscola glabra. This practice was not effective, probably because of the complexity of applying this method in the wild by nonspecialists, and the variations in snail population dynamics as a function of the environmental conditions (temperature and rainfall).

The last method is physical control, which involves cleaning canals by removing aquatic vegetation. This cleaning can be very effective because it can be durable and selective against specific snail species. The most relevant requirement is to target all the habitats covered by macrophytes and algae where the snails live because a single snail propagule can rapidly recolonize the whole irrigation system. This technique can be applied if canals are regularly cleaned and if they are not damaged. Poor maintenance of canals can lead to rapid recolonization by snails [START_REF] Chlyeh | Spatio-temporal distribution of freshwater snail species in relation to migration and environmental factors in an irrigated area from Morocco[END_REF]. Indeed, if the canals are not cleaned properly, plants containing parasite eggs will be left on site and snails can remain in sediment, allowing them to rapidly recolonize the habitat. Moreover, by dispersing eggs, some birds and aquatic mammals can favour the spread of freshwater snails, leading to the recolonization of certain areas [START_REF] Waterkeyn | Invertebrate dispersal by aquatic mammals: A case study with nutria Myocastor coypus (Rodentia, Mammalia) in Southern France[END_REF][START_REF] Viana | Migratory strategies of waterbirds shape the continental-scale dispersal of aquatic organisms[END_REF].

Any single control strategy cannot effectively reduce fasciolosis transmission. Integrated parasite control programs are needed to limit fasciolosis. In Peru, dairy cattle producers decreased the prevalence of F. hepatica in cattle from 63% to 14% in 2 years by applying an integrated parasite control program [START_REF] Raunelli | Strategic control and prevalence of Fasciola Hepatica in Cajamarca, Peru. A Pilot Study[END_REF]. They achieved this control not only through the improved drainage of ditches, but also through training sessions on fasciolosis, including manuals with calendars stating the correct use and administration of antiparasitic treatment, technical assistance with follow up visits, and strategically timed treatments. Irrigation canals were cleaned and the slope of the canal banks was increased to approximately 130 1 . These steps allowed sun rays to fall on the bottom and sides of the ditches for the longest possible duration, reducing the shaded areas where the snails Galba viator (called Fossaria viatrix in the article) were located.

Livestock Management

Every integrated parasite control program must also take account of the management of the definitive host. The occurrence of fasciolosis in herds is positively correlated with the presence of snail habitats including streams, irrigation canals, and dams [START_REF] Schweizer | Prevalence of Fasciola hepatica in the intermediate host Lymnaea truncatula detected by real time TaqMan PCR in populations from 70 Swiss farms with cattle husbandry[END_REF]. Indeed, herds become infected when eating aquatic plants or drinking water contaminated with Fasciola metacercariae. Grazing and water access are thus key factors in the spread of fasciolosis. It has been shown that the risk of fasciolosis increases in regions with long grazing seasons [START_REF] Novobilskÿ | Impact of meteorological and environmental factors on the spatial distribution of Fasciola hepatica in beef cattle herds in Sweden[END_REF]. In temperate zones, seasonal transmission can be observed when the temperature is appropriate and water is available for snail reproduction, hence, for parasite development [START_REF] Torgerson | Epidemiology and control[END_REF]. In tropical zones, herds are more easily in contact with liver flukes during the rainy season [START_REF] Afshan | Impact of climate change and man-made irrigation systems on the transmission risk, long-term trend and seasonality of human and animal fascioliasis in Pakistan[END_REF]. During the dry season, herd management permits contact between herds and parasites. For instance, in Tanzania, infection rates of F. gigantica and paramphistomes were higher in villages where herds grazed freely in irrigated crops [START_REF] Nzalawahe | Associations between trematode infections in cattle and freshwater snails in highland and lowland areas of Iringa Rural District, Tanzania[END_REF]. All of these factors play a role in the small scale of one farm, but the trade of animals between farms may also contribute to spreading fasciolosis [START_REF] Martins | of bovine fasciolosis and associated factors in south Espírito Santo, Brazil: an update[END_REF][START_REF] Olsen | Prevalence, risk factors and spatial analysis of liver fluke infections in Danish cattle herds[END_REF]. Moreover, the expansion of fasciolosis around the world has been shaped by the continuous export of livestock [30]. For instance, ITS-1 and ITS-2 sequences do not differ between Bolivian and Spanish strains of F. hepatica, and they exhibit only a few differences with liver-fluke samples in other parts of the world [START_REF] Mas-Coma | Fasciola hepatica and lymnaeid snails occurring at very high altitude in South America[END_REF], suggesting recent exchanges between populations, most probably due to livestock trade [START_REF] Semyenova | Genetic differentiation in Eastern European and Western Asian population of the liver fluke, Fasciola hepatica, as revealed by mitochondrial NAD1 andd COX1 genes[END_REF]. Common mitochondrial restriction fragment length polymorphism (RFLP) haplotypes have been consistently found in the Republic of Ireland, Greece, and Australia [START_REF] Walker | Evidence for multiple mitochondrial lineages of Fasciola hepatica (liver fluke) within infrapopulations from cattle and sheep[END_REF]. In many European and African countries, a seasonalmovementofpeople withtheirherds occursbetweenseasons. Forinstance, when animals move from Iranian lowlands (usually contaminated with F. gigantica) to the neighbouring highlands (usually contaminated with F. hepatica), animals become coinfected with both parasite species [START_REF] Ashrafi | Distribution of Fasciola hepatica and F. gigantica in the endemic area of Guilan, Iran: Relationships between zonal overlap and phenotypic traits[END_REF]. The risk of fasciolosis can be limited through the management of those habitats and/or through the adaptation of livestock management. Many methods are available for limiting the transmission of fasciolosis to livestock.

How Can Livestock Management Be Adapted to Controlling Fasciolosis Risk? First, animals, pastures, and periods of high risk should be identified at each farm. Second, a combination of measures adapted to each farm should be taken. Since each farm might experience different conditions, it s essential to identify the risk on each farm, and to set up the appropriate integrated solution. Finally, fasciolosis prevalence and the emergence of anthelmintic resistance should be regularly monitored to assess the effectiveness of the measures and to readapt them if necessary. Measures of control include the regulation of grazing, anthelmintic treatments, and consideration of tolerance or genetic resistance to the parasite. First, farmers can limit the access of herds to snail habitats. It is possible to isolate herds from water sources at risk by fencing [START_REF] Knubben-Schweizer | Veterinary parasitology bovine fasciolosis: control strategies based on the location of Galba truncatula habitats on farms[END_REF], and also by adding water tanks that are regularly cleaned to avoid snail invasion. However, this method is not always effective because, during the rainy season, snails can move to fenced habitats and then develop in ditches made by cattle trampling [START_REF] Rondelaud | La limnée tronquée: -Un mollusque d'intérêt médical et vétérinaire[END_REF]. For example, snail migrations over 30 m have been observed from one spring swamp, in the middle of a pasture grazed by dairy cows, to puddles at the edge of the pasture [START_REF] Knubben-Schweizer | Veterinary parasitology bovine fasciolosis: control strategies based on the location of Galba truncatula habitats on farms[END_REF]. Recent studies have explored the use of very high-resolution satellite and drone imagery to map small water bodies and populations of intermediate host snails in pastures, but further research is required to make this approach operational, and to give advice that is adapted to the situation of a specific local farm [START_REF] De Roeck | Fine-scale mapping of vector habitats using very high resolution satellite imagery: A liver fluke casestudy[END_REF][START_REF] Charlier | Longitudinal study on the temporal and micro-spatial distribution of Galba truncatula in four farms in Belgium as a base for small-scale risk mapping of Fasciola hepatica[END_REF].

Second, the risk of infection can also be reduced by moving animals to uncontaminated pastures and avoiding grazing with fodder supplementation [START_REF] Suon | Seasonal differences in the incidence of infection with Fasciola gigantica in Cambodian cattle[END_REF]. However, resources are sometimes scarce and there are not always enough pastures available to feed animals. Thus, other methods such as anthelmintic treatments can be used. In sub-Saharan Africa, nomadic pastoralists use the banks of Lake Chad as herd pastures. A study shows that animals that have grazed near the lake for long periods have a high risk of infection [START_REF] Vreni | Prevalence of Fasciola gigantica infection in slaughtered animals in south-eastern Lake Chad area in relation to husbandry practices and seasonal water levels[END_REF]. Limiting the access to the lake is impossible since no alternative source of water or grazing resources exist nearby, which means that the alternative solution is to treat cattle with triclabendazole (TCBZ), or other drugs against liver flukes. Yet, there is an increasing resistance of liver flukes to anthelmintics, in particular to TCBZ, which is the most widely used drug [START_REF] Beesley | Fasciola and fasciolosis in ruminants in Europe: Identifying research needs[END_REF]. Before 2011, TCBZ resistance has been reported in sheep and cattle in six farms in Australia, Scotland, Wales, The Netherlands, Spain, and the Republic of Ireland. Since then, 24 other farms have also reported resistance to this anthelmintic in Northern Ireland, Scotland, Wales, Australia, New Zealand, Peru, and Argentina [START_REF] Kelley | Current threat of triclabendazole resistance in Fasciola hepatica[END_REF].

Alternative chemical options are available to target TCBZ-resistant flukes, including treatment with clorsulon, nitroxynil, closantel, albendazole, or oxyclozanide, according to the host species [START_REF] Kelley | Current threat of triclabendazole resistance in Fasciola hepatica[END_REF][START_REF] Beesley | Fasciola and fasciolosis in ruminants in Europe: Identifying research needs[END_REF]. Nevertheless, it is important to use alternative chemicals more strategically than how TCBZ has been used historically to avoid the emergence of new resistances. For example, the annual rotation of drugs usually prevents the development of resistance, particularly if the drugs are from different classes and act differently [START_REF] Fairweather | Reducing the future threat from (liver) fluke: Realistic prospect or quixotic fantasy?[END_REF]. Farmers can also select the animals to be treated. They can treat the most vulnerable animals (for instance, the youngest) to reduce the number of individuals treated and thus the selection pressure leading to resistance. It is also important to set up surveillance systems that monitor infection status at farm level on a regular basis (Box 1). For instance, one study shows that such longitudinal monitoring approaches can be an effective decision support tool for reducing infections on Irish farms [START_REF] Munita | Six-year longitudinal study of Fasciola hepatica bulk milk antibody ELISA in the dairy dense region of the Republic Ireland[END_REF]. However, the increasing resistance to the limited number of available flukicides makes finding an alternative control method crucial. Vaccines have been considered as a promising and economically viable alternative strategy for the control of fasciolosis in livestock [START_REF] Molina-Hernández | Fasciola hepatica vaccine: We may not be there yet but we're on the right road[END_REF][START_REF] Toet | Liver fluke vaccines in ruminants: Strategies, progress and future opportunities[END_REF], but more research is needed before they can be used [START_REF] Beesley | Fasciola and fasciolosis in ruminants in Europe: Identifying research needs[END_REF]. Anthelmintic treatments can be coupled with pasture rotation [START_REF] Knubben-Schweizer | Control of bovine fasciolosis in dairy cattle in Switzerland with emphasis on pasture management[END_REF]. This method is feasible if the habitats of intermediate hosts are well identified and some safe and uncontaminated pastures are available. Cattle can graze in safe pastures during spring and autumn when the risk ofgetting infected is low, and can then be treated before moving to contaminated pastures during summer. However, the risk of promoting resistance to anthelmintics is high, because flukes would be in contact with recently treated cows. Thus, if eggs are eventually shed they will all come from resistant strains [START_REF] Knubben-Schweizer | Veterinary parasitology bovine fasciolosis: control strategies based on the location of Galba truncatula habitats on farms[END_REF]. There are also some alternative methods to chemical treatments, such as deworming plants (Agrimonia eupatoria, Urtica dioica, Calendula officinali), but they must be combined with good livestock management, including the rotation of herds between pastures and safe and uncontaminated food and water iii .

Every integrated parasite control program is a three-step process. First, animals, pastures, and periods of high risk should be identified at each farm. Second, a combination of measures adapted to each farm should be taken. Since each farm might experience different conditions, it is essential to identify the risk on each farm, and to set up the appropriate integrated solution. Finally, fasciolosis prevalence and the emergence of anthelmintic resistance should be regularly monitored to assess the effectiveness of the measures and to readapt them if necessary. Measures of control include the regulation of grazing, anthelmintic treatments, and consideration of tolerance or genetic resistance to the parasite. First, farmers can limit the access of herds to snail habitats. It is possible to isolate herds from water sources at risk by fencing [START_REF] Knubben-Schweizer | Veterinary parasitology bovine fasciolosis: control strategies based on the location of Galba truncatula habitats on farms[END_REF], and also by adding water tanks that are regularly cleaned to avoid snail invasion. However, this method is not always effective because, during the rainy season, snails can move to fenced habitats and then develop in ditches made by ca Finally, another tool for fasciolosis control is to manage herd genetic resources to enhance the resistance or tolerance to fasciolosis in livestock populations. It has been shown that native populations may be resistant to certain diseases. For example, Red Massai sheep are resistant and resilient to gastrointestinal nematodes [START_REF] Baker | Appropriate breeds and breeding schemes for sheep and goats in the tropics[END_REF], and some sheep breeds are resistant to F. giganticasuch as the Indonesian thin-tailed sheep. In contrast, this breed is susceptible to F. hepatica [START_REF] Roberts | Acquisition of resistance against Fasciola gigantica by Indonesian thin tail sheep[END_REF][START_REF] Pleasance | Resistance to liver fluke infection in the natural sheep host is correlated with a type-1 cytokine response[END_REF]. This resistance and resilience can be explained by hundreds of years of coevolution between the parasites and the hosts, but this tool must be part of an integrated management program. Moreover, in rural zones, herds are regularly in contact with humans, promoting the emergence of fasciolosis in human populations. Human Diet and Unhygienic Habits

The transmission of fasciolosis to humans is linked to water and food. Drinking unsafe water, eating raw or undercooked contaminated vegetables, and applying inappropriate agricultural practices are the main reasons for the (re)emergence or persistence of fasciolosis in human populations worldwide [START_REF]Waterborne Zoonoses: Identification, Causes, and Control[END_REF]. In some countries (Vietnam, Bolivia, Iran, Egypt, Ethiopia), high incidence of human fasciolosis is explained by the extensive breeding of livestock in close contact with humans combined with the traditional consumption of watercress, an aquatic plant in which larvae of Fasciola spp. usually become encysted [START_REF] Bui | Current status of fasciolosis in Vietnam: an update and perspectives[END_REF][START_REF] Raissy | Seroprevalence of human fasciolosis in a new-emerging focus of fasciolosis in Yasuj District, Southwest of Iran[END_REF]. Vietnamese rural populations have a higher prevalence of fasciolosis than urban populations because people drink water and eat aquatic plants from water bodies that are in close contact with livestock [START_REF] Bui | Current status of fasciolosis in Vietnam: an update and perspectives[END_REF]. In Argentina, several outbreaks of fasciolosis were caused by the ingestion of watercress naturally growing along river and stream beds that is collected during recreational activities [START_REF] Mera Y Sierra | Human fascioliasis in Argentina: retrospective overview, critical analysis and baseline for future research[END_REF]. Inappropriate agricultural practices can also promote the emergence and persistence of fasciolosis. For instance, farmers in Ethiopia irrigate vegetables during the dry season, promoting a good environment for snail proliferation; it results in the appearance of endemic fasciolosis [START_REF] Fentie | Epidemiology of human fascioliasis and intestinal parasitosis among schoolchildren in lake Tana Basin, northwest Ethiopia[END_REF] (Figure 2). In Ghana and Egypt, unsafe water is used for plant irrigation, leading to the contamination of plants by F. hepatica [START_REF] Amoah | Irrigated urban vegetable production in Ghana: Sources of pathogen contamination and health risk elimination[END_REF]. People can also become infected with Fasciola spp. if they have no access to safe water inside their homes and use water from irrigation and drainage canals for their needs: drinking, cooking, personal hygiene, cleaning, and washing [START_REF] Esteban | High fascioliasis infection in children linked to a man-made irrigation zone in Peru[END_REF][START_REF] Fentie | Epidemiology of human fascioliasis and intestinal parasitosis among schoolchildren in lake Tana Basin, northwest Ethiopia[END_REF]. In most countries, not only habits but also socioeconomic factors can explain the (re)emergence and persistence of fasciolosis. Sometimes, the risk of infection may vary widely among different groups of people and villages, based on cultural, environmental, and socio-economic differences. In Bolivia, people become infected mostly by eating uncooked contaminated aquatic plants. Bolivian children eat watercress and other aquatic plants when they help their parents in farming activities, while in Peru children become infected mostly by drinking contaminated water while playing in drainage canals [START_REF] Esteban | High fascioliasis infection in children linked to a man-made irrigation zone in Peru[END_REF][START_REF] Parkinson | Endemic human fasciolosis in the Bolivian Altiplano[END_REF][START_REF] Esteban | Presence of very high prevalence and intensity of infection with Fasciola hepatica among Aymara children from the Northern Bolivian Altiplano[END_REF]. This illustrates why aquatic plant consumption, irrigation of crops with contaminated water, and the use of irrigation canals for human needs. This example shows that it is important to consider each risk factor to limit disease emergence. Indeed, the factors described above can be linked to each other. In this case, integrated control can be a good solution for the fight against schistosomiasis and fasciolosis transmission in both humans and livestock

Box 1. Fasciolosis Diagnosis

Diagnosis in Humans

There are various diagnostic methods for fasciolosis, depending on different stages and manifestations of the disease: acute phase or chronic phase [START_REF] Nyindo | Fascioliasis: an ongoing zoonotic trematode infection[END_REF].

The typical symptoms in the acute phase include fever, nausea, a swollen liver, and extreme abdominal pain.

During the chronic phase, the symptoms are intermittent pain, jaundice, and anemia.

People with symptoms are usually diagnosed by using several of the complementary diagnostic tests described below.

Imaging (ultrasound) and detection in stools by PCR can also be used.

If there is a potential risk of contamination, systematic screening can be used in a population. In this case only one technique is used, usually based on stool analysis.

Blood Test Diagnosis

During the acute phase, a simple blood test is possible; fasciolosis is suspected if a high number of specific white blood cells (called eosinophils) are found.

Diagnosis by Detecting Eggs in Faeces

The Kato-Katz technique is a quantitative method for detecting parasite eggs in stool samples. It is simple, rapid, and inexpensive, making it an option suitable for field conditions and large-scale studies. It is a specific but not very sensitive diagnostic test that is unable to diagnose the disease during the incubation and acute phases [90].

Diagnosis by ELISA

Immunological tests allow diagnosis of fasciolosis by detecting specific antigens in serum and stool samples, such as FES-Ag (Fasciola excretory-secretory antigens). Serological tests, such as Fas2-ELISA or CL1-ELISA, are able to detect the circulating IgG antibodies. These techniques are highly sensitive and specific [90]. The intermittent clinical signs and symptoms of fascioliasis can be confused with those of other hepatobiliary disorders, causing delayed and difficult diagnosis.

Diagnosis in Animals

Animal symptoms are anaemia, weight loss, decreased fertility, and mortality in young individuals [START_REF] Torgerson | Epidemiology and control[END_REF].

The health of the herd can be tested by sampling faeces randomly or by using an immunological test on milk. Individuals can also be tested if they show symptoms.

Diagnosis by Detecting Eggs in Faeces

Coprological sedimentation methods are routinely used for diagnosis of animal infection, and methods such as FLOTAC [START_REF] Cringoli | FLOTAC: New multivalent techniques for qualitative and quantitative copromicroscopic diagnosis of parasites in animals and humans[END_REF] are available.

Diagnosis by ELISA

Many immunological techniques having high sensitivity, reproducibility, and cost-effectiveness can be used on stools, milk, or serum samples [START_REF] Beesley | Fasciola and fasciolosis in ruminants in Europe: Identifying research needs[END_REF]. A few examples of these tests are the SVANOVIR ELISA, MM3-Sero ELISA, and MM3-COPRO ELISA [START_REF] Charlier | Associations between anti-Fasciola hepatica antibody levels in bulk-tank milk samples and production parameters in dairy herds[END_REF][START_REF] Mezo | Field evaluation of the MM3-SERO ELISA for detection of anti-Fasciola IgG antibodies in milk samples from individual cows and bulk milk tanks[END_REF][START_REF] Mezo | An ultrasensitive capture ELISA for detection of Fasciola hepatica coproantigens in sheep and cattle using a new monoclonal antibody (Mm3)[END_REF][START_REF] Martínez-Sernández | Rapid enhanced MM3 COPRO ELISA for detection of Fasciola coproantigens[END_REF].

Innovations

Molecular diagnostic methods are still under development to increase the sensitivity and the specificity of conventional diagnostic tests. One of the new methods is the loop-mediated isothermal amplification (LAMP) assay which would make it possible to detect fluke DNA in stool faster and easier than by PCR, but with an equal level of sensitivity [START_REF] Martínez-Valladares | Loopmediated isothermal amplification (LAMP) assay for the diagnosis of fasciolosis in sheep and its application under field conditions[END_REF].

Which Strategies Can Be Implemented to Prevent Fasciolosis in Humans?

Once the risk factors are identified, several strategies can be used to prevent fasciolosis. Educational campaigns encouraging people to eat cooked vegetables rather than raw ones can be developed [START_REF] Esteban | Hyperendemic fascioliasis associated with schistosomiasis in villages in the Nile Delta of Egypt[END_REF]. Indeed, health education is crucial for preventing diseases. For instance, in Central Vietnam, in a community where the prevalence of fasciolosis is high, health volunteers take training courses to improve their skills and knowledge of fasciolosis diagnosis, treatment, surveillance, and management in order to detect and manage cases of fasciolosis (Box 1). At the same time, in the community and at schools, a campaign has been organized to raise public awareness about the parasite's life cycle, transmission, impacts, and control measures (Tran Minh Quy, Doctor of Public Health thesis, University of Wollongong, 2016). Health education was combined with human chemotherapy, vector control, pasture management, and animal treatment, permitting a significant decrease in the prevalence of fasciolosis. The establishment of a drinking water and sewage-treatment system besides irrigation canals is very important [START_REF] Fentie | Epidemiology of human fascioliasis and intestinal parasitosis among schoolchildren in lake Tana Basin, northwest Ethiopia[END_REF][START_REF] Esteban | Hyperendemic fascioliasis associated with schistosomiasis in villages in the Nile Delta of Egypt[END_REF], and preventive chemotherapy with TCBZ [90] is also possible. This method is used by the WHO as the main way to control most of the trematodes, which has proven effective and safe when the medicine is administered as a single-dose tablet in highlyendemic areas (where individual diagnosis is complicated) [90]. TCBZ reduces the rate of egg production, but it must be coupled with other preventive strategies in order to be 100% effective. Most of the anthelmintics protect patients for only a short time; thus, this method should be part of a global preventive and treatment approach. Limiting the risk of fasciolosis infection is essential for patients. Monitoring the effectiveness of prevention methods with the implementation of regular diagnoses can reduce disease and help to better target treatments. Indeed, establishing a good diagnosis is essential.

Various methods exist, but the most common one is stool examination for egg detection, which is still considered to be a conclusive diagnosis despite its low sensitivity [90]. Others methods include testing for eosinophilia,

, ELISA, and molecular approaches (Box 1). Such approaches detect infections rapidly and more accurately, but they are often more expensive and complicated [START_REF] Beesley | Fasciola and fasciolosis in ruminants in Europe: Identifying research needs[END_REF]90,[START_REF] Cwiklinski | A prospective view of animal and human fasciolosis[END_REF]. If good preventative strategies have not been taken and humans are infected, they can be treated with TCBZ [90] or nitazoxanide. The latter is another drug used during the chronic stage of fasciolosis and for patients with low parasite burdens [START_REF] Zumaquero-Ríos | Fascioliasis and intestinal parasitoses affecting schoolchildren in Atlixco, Puebla State, Mexico: epidemiology and treatment with Nitazoxanide[END_REF]. TCBZ resistance concerning humans has been reported in some endemic areas in The Netherlands, Chile, Turkey, and Peru [START_REF] Kelley | Current threat of triclabendazole resistance in Fasciola hepatica[END_REF].

Concluding Remarks

Man-made constructions and livestock management can create good conditions for liver-fluke transmission. These new habitats can also favour the emergence of the disease in human populations due to human diets and unhygienic habits. The challenge of controlling fasciolosis can be met only if we deal with the complex interactions between the environment, hosts (snails, livestock, wildlife, humans), and human activities (see Outstanding Questions). It is essential to consider all of these factors, which are involved in a constantly changing world (climate, habitat fragmentation, pollution). The socioeconomic and ecological context of each country, region, city, and farm should be considered to prevent fasciolosis. Indeed, many studies focusing on schistosomiasis and other neglected tropical diseases have shown that applying an integrated control program is the most effective solution for preventing disease (re) emergence. The literature is still scarce regarding fasciolosis, and more systematic studies are needed. However, we believe that the key to successfully controlling this disease lies in applying good integrated control programs and local adaptive management practices.

Figure

  Figure 1Fasciola spp. Transmission Cycle. (A) First unembryonated eggs are released via the faeces of the definitive host. Once in the water, the eggs become embryonated and release miracidium larvae that will swim to the intermediate host, a freshwater snail. (C) The cercariae encyst, preferably on the vegetation or on the surface of the water. The encysted stages are metacercariae. (D) These metacercariae will be ingested by the definitive host, through drinking water or eating aquatic plants. Once in the mammal, the metacercariae migrate into the bile ducts to reach their adult form. Sexual reproduction then takes place and produce eggs that come out through the digestive tract and faeces.

Figure 2 .

 2 Figure 2 . A Case Study, the Work of Fentie et al. in Ethiopia [19]. Growing vegetables is crucial in the region (A). Irrigation canals are built to irrigate fields, but these canals can also favour fasciolosis transmission because they can be contaminated by animal faeces and are good habitats for freshwater snails. Fields can be contaminated during irrigation, infesting the people who consume raw vegetables or drink unsafe water due to no access to safe water. (B) Local people breed sheep, cattle, or horses. Animals are close to humans. Ç,D) Domestic animals drink in irrigation canals and rivers, which are also used by humans. Moreover, in this study, the same factors play a role in both fasciolosis and schistosomiasis transmission. This example shows that it is important to consider each risk factor to limit disease emergence. Indeed, the factors described above can be linked to each other. In this case, integrated control can be a good solution for the fight against schistosomiasis and fasciolosis transmission in both humans and livestock

  Finally, in order to reduce the prevalence of the disease, it is important to control different factors and use several methods, such as vector control, health education, improvement of local health systems and chemotherapy [92] (Figure 3, Key Figure). In Central Vietnam, a study reported the effectiveness of an integrated control program on fasciolosis. This model could feasibly inform the initiatives in other countries where fasciolosis is prevalent (Tran Minh Quy, Doctor of Public Health thesis, University of Wollongong, 2016).

Figure 3

 3 Figure 3 The three compartments of (i) water access (blue), (ii) livestock (green), and (iii) human habits (purple) can be linked to each other. It is important to have good management of all of these compartments to limit the emergence of fasciolosis. For that purpose, it is possible to monitor and prevent its circulation with several methods in the three parts. Treatments can be used for prevention in certain endemic areas in humans and animals. It is also important to promote transdisciplinary and integrated parasite control.

Acknowledgments

We would like to express our gratitude to Jean-Pierre Pointier for valuable discussions on earlier drafts of the manuscript as well as to the reviewers for their constructive remarks. This study was financially supported by Labex CeMeb, the Tour du Valat, and the INEE CNRS through the Ecosan funding program.

Resources

i http://who.int/neglected_diseases/preventive_chemotherapy/Newsletter10.pdf ii www.fao.org/fileadmin/user_upload/agns/news_events/Parasite%20report%20final%20draft-25October2012.pdf iii www.parc-camargue.fr/newsletter/guide_technique_2.pdf


Anahita Basirat
email: anahita.basirat@univ-lille2.fr

Word segmentation in phonemically identical and prosodically different sequences using cochlear implants: A case study

Keywords: word segmentation, prosody, cochlear implant, audiovisual speech

Word segmentation in phonemically identical and prosodically different sequences using cochlear implants: A case study

Anahita Basirat

INTRODUCTION

In clinical and experimental studies with cochlear implant (CI) users, their general abilities in speech recognition, such as disyllabic word recognition and sentence comprehension, are often reported while their abilities in processing speech prosody usually remain unknown.

However, the correct recognition of prosody is essential in speech communication since it conveys meaning, to some extent. For example, intonational cues enable us to distinguish between questions and statements with the same syntactic structures (e.g. "She is sleeping."

versus "She is sleeping?"). The role of prosody is extremely important in tonal languages such as Mandarin in which prosodic cues provide listeners with information to differentiate word meanings. Moreover, prosody cues play a role in emotion recognition in speech. The present study focused on speech segmentation using prosodic cues in French. In order to segment a continuous speech signal into words, listeners use different types of information including lexical, segmental (e.g. phonotactic constraints) and prosodic cues [START_REF] Mattys | Integration of multiple speech segmentation cues: a hierarchical framework[END_REF]. In English, most content words (nouns, adjectives, etc.) begin with stressed syllables [START_REF] Cutler | The predominance of strong initial syllables in the English vocabulary[END_REF]. This stress pattern is used by English listeners to detect word boundaries and to segment speech [START_REF] Cutler | The role of strong syllables in segmentation for lexical access[END_REF] especially in noisy conditions [START_REF] Mattys | Integration of multiple speech segmentation cues: a hierarchical framework[END_REF]. In French, this word stress pattern does not exist. However, a specific prosodic cue can be used by French listeners to segment speech: a nonsense sequence like [me.la.mɔɔ.din] is interpreted by French listeners as a single sequence "mélamondine" if the fundamental frequency (F0) rise starts at the first syllable (i.e. [me]) and as two distinct sequences "mes lamondine" (my lamondine) when the F0 rise starts at the second syllable (i.e. [la]) [START_REF] Welby | The role of early fundamental frequency rises and elbows in French word segmentation[END_REF]. In sentences without contextual information, French listeners make use of this cue to segment sequences of words that are phonemically identical and prosodically different such as "l'affiche" (the poster) and "la fiche" (the sheet), both [lafiʃ] [START_REF] Spinelli | An intonational cue to segmentation in phonemically identical sequences[END_REF]. In fact, the vowel /a/ has a greater F0 in a word beginning with a vowel (e.g. "l'affiche") than in its phonemically equivalent word beginning with a consonant (e.g. "la fiche") [START_REF] Spinelli | Fine-grained access to targets and competitors in phonemically identical spoken sequences: The case of French elision[END_REF]. These results confirm that in the absence of semantic/lexical/segmental cues, French listeners rely on prosodic cues to segment speech.

Several studies have shown that adult and pediatric CI users perform less well in prosody recognition compared to normal hearing (NH) listeners (e.g. [START_REF] Chatterjee | Processing F0 with cochlear implants: Modulation frequency discrimination and speech intonation recognition[END_REF][START_REF] Van Zyl | Perception of vowels and prosody by cochlear implant recipients in noise[END_REF][START_REF] Peng | Production and perception of speech intonation in pediatric cochlear implant recipients and individuals with normal hearing[END_REF][START_REF] See | Speech intonation and melodic contour recognition in children with cochlear implants and with normal hearing[END_REF]. This poor performance can be due to the limitations of CI devices in conveying fine structure information (for a review, see [START_REF] Wilson | Cochlear implants: a remarkable past and a brilliant future[END_REF]). However, it seems that prosodic cues could, to some extent, be available to CI users. [START_REF] Spitzer | The use of fundamental frequency for lexical segmentation in listeners with cochlear implants[END_REF] studied the performance of adult CI users in using lexical stress cues to find boundaries between words in continuous speech. The authors analyzed the lexical boundary errors of CI users when they listened to sentences in English. If the listeners used syllabic stress, they would commit some predicted errors. For example, they would insert lexical boundaries before strong syllables as these indicate word-onsets in English [START_REF] Cutler | The predominance of strong initial syllables in the English vocabulary[END_REF]. Their results showed that adult CI users committed the same type of segmentation errors as predicted, suggesting that they use lexical stress cues for speech segmentation. These cues seem to be processed by CI users very early during development. Using a habituation-test procedure, [START_REF] Segal | Auditory discrimination of lexical stress patterns in hearing-impaired infants with cochlear implants compared with normal hearing: influence of acoustic cues and listening experience to the ambient language[END_REF] observed that CI infants (mean age = 18 months) were able to discriminate nonsense CVCV sequences, which differed only in their stress pattern. In this study, infants were presented with several repetitions of a CVCV sequence with a stress on either the first or the second syllable (habituation phase). Then, they were presented with the same structure as in the habituation phase with either the same or a different stress pattern. Infants detected the change in the stress pattern when the stress pattern of the novel sequence differed from that of the habituated sequence. This suggests that CI infants can process lexical stress cues.

Intonational cues also seem to be processed by CI users to some extent. In a longitudinal study, [START_REF] Snow | Children's development of intonation during the first year of cochlear implant experience[END_REF] [START_REF] Meister | Use of intonation contours for speech recognition in noise by cochlear implant recipients[END_REF] showed that adult CI users could extract intonational cues in adverse listening conditions. The authors presented CI users with sentences with regular and inverted F0-contours in noise. Participants were asked to recognise sentences and to repeat as many words as possible. Despite the poorer performance of CI users compared to NH listeners, speech recognition was better in the regular F0 condition than in the inverted F0contours condition in both populations. These results suggest that CI users could make use of intonational cues despite the limitations of CI devices in conveying these cues. Interestingly, there is a significant variability between CI users in processing intonational cues, which has been reported in both adult [START_REF] Chatterjee | Processing F0 with cochlear implants: Modulation frequency discrimination and speech intonation recognition[END_REF] and pediatric CI users [START_REF] Peng | Production and perception of speech intonation in pediatric cochlear implant recipients and individuals with normal hearing[END_REF]. The variability between adult CI users could be related to their hearing experience before deafness or their residual hearing: intonation recognition seems less challenging for post-lingually deaf adults (Peng, Chatterjee and Luc, 2012) and those with residual hearing after implantation (Marx et al., 2015).

To our knowledge, the abilities of CI users in word segmentation relying only on intonational cues are not known. Given that these cues are, to some extent, available to CI users, our hypothesis was that exceptional CI users might be able to segment continuous speech through intonation identification. We thus tested the performance of an exceptional CI user in segmenting phonemically identical and prosodically different sequences (e.g. "l'affiche" (the poster) versus "la fiche" (the sheet), both [lafiʃ]) embedded in neutral sentence contexts.

Sentences were presented in both auditory-only and audiovisual presentation modalities. NH listeners seem to be able to extract prosodic cues such as F0 variations from visual speech [START_REF] Munhall | Visual prosody and speech intelligibility. Head movement improves auditory speech perception[END_REF][START_REF] Cavé | About the relationship between eyebrow movements and F0 variations[END_REF].

Moreover, seeing lip movements can bias the segmentation of ambiguous French sequences [START_REF] Strauß | Visual lip information supports auditory word segmentation[END_REF]. In the latter study, NH listeners were presented with auditory sequences that were phonemically and prosodically ambiguous as they were compatible with two French words such as "l'affiche" (the poster) and "la fiche" (the sheet). These sequences were deliberately produced in an ambiguous way (and not in a natural way) such that listeners could use no auditory intonational cues to segment them. Thus, two word segmentations were possible for each auditory sequence. The authors dubbed the visual lip movements of hyper-articulated words beginning with a vowel (e.g. "l'affiche") or beginning with a consonant (e.g. "la fiche") onto the corresponding auditory ambiguous sequences. In a segmentation task, participants reported more segmentation compatible with vowel-beginning words when they were presented with the lip movements of vowelbeginning words and more segmentation compatible with consonant-beginning words when they were presented with the lip movements of consonant-beginning words. This suggests that NH listeners can make use of visual cues to segment auditory ambiguous sequences. In the present study, we expected that word segmentation using intonational cues would be possible, to some extent, for exceptional CI users. Moreover, we expected that audiovisual speech would facilitate the extraction of these cues and thus improve word segmentation.

MATERIALS AND METHODS

Subjects

An exceptionally good CI user (23-year-old female) participated in this study ("Ms. C"). She was a French native speaker. She reported a sudden profound hearing loss at 22 years of age caused by meningitis. She was bilaterally implanted 1 month after her hearing loss. Both devices were a Neurelec Digisonic SP implant with a Saphyr processor. Seven months after CI implantation, her scores using the PAV2L assessment tool, which is used in Lille Hospital in France [START_REF] Tourmel | Validation du PAV2L: évaluation de la Perception auditive verbale et de la lecture labiale de l'adulte devenu sourd[END_REF], were very good (e.g. disyllabic word recognition = 100% correct without lip-reading; oral text comprehension (level 3) = 96% without lip-reading and 100% with lip-reading). In everyday life, she communicated regularly on the telephone, watched TV and listened to music. She had corrected-to-normal vision. She took part in this study 13 months after CI implantation while she was a graduate student. Twenty-two adults (mean age = 26.6 years, SD = 7, fourteen females) without a diagnosed hearing problem served as controls (NH group). They were native French speakers. They all had normal or corrected-tonormal vision. The study was conducted in accordance with the Helsinki Declaration and the ethical guidelines of the Department of Speech and Language Therapy of Lille University.

Before testing, all participants were informed about the experiment by a written document and signed a consent statement.

Stimuli

Twenty-nine phonemically identical and prosodically different pairs from Spinelli et al.

(2010) such as "l'affiche" (= the poster) and "la fiche" (= the sheet), both [lafiʃ], and twentynine minimal pairs such as "la bouche" [labuʃ] (= the mouth) and "la douche" [laduʃ] (= the shower) were selected. The minimal pairs differed in articulation place (16 pairs) or in voicing (13 pairs). These sequences were inserted into a neutral carrier sentence "c'est ... dont je t'ai parlé" (= it's … about which I spoke to you). Stimuli were produced by a female native French speaker and recorded audiovisually by a camera in front of her. The head and neck of the speaker were visible in the videos.

Procedure

The experiment was conducted in two sessions, one in the auditory-only and the other in the audiovisual modality. In the auditory-only session, NH participants were asked to listen to the sentences through headphones. In the audiovisual session, they were asked to listen to the stimuli through headphones and to watch the videos. The sound was presented at a comfortable level and the screen was placed at about 50 cm from the participants. Each trial began with the presentation of a sentence containing one member of the fifty-eight pairs. Then, the two members of each pair were presented on the screen. The participants were asked to identify the word they perceived. They made a forced choice between two possible words by pressing one of the two response keys on the keyboard (F and J keys). Only one member of each pair was presented to each participant. The participants were presented with the same items in the auditory-only and audiovisual sessions. The word presentation order was randomised. The order of the auditory-only and audiovisual sessions was counterbalanced across NH participants. The second session was about two weeks after the first session in order to minimise the response bias. All participants carried out 6 familiarisation trials before the experimental trials. "Ms C" followed the same presentation procedure. The stimuli were presented through two loudspeakers. During the first session, she was presented with the audiovisual stimuli.

Eighteen days later, she was presented with the auditory-only stimuli. "Ms. C" took part in the experiment after the participation of the NH group in the study.

RESULTS

The mean percentages of correct responses of the NH group are presented in Table 1. We will focus on the performance of participants in the identification of phonemically identical and prosodically different sequences. The performance of the NH group was above the chance level in both the auditory-only and audiovisual presentation modalities (A: mean = 80.56%, t(21) = 15.3, p<0.001; AV: mean = 82.13%, t(21) = 13.65, p<0.001). An ANOVA with modality as within-subject and session order as between-subject factors showed no significant effect (modality: F(1,20) = 0.47, n.s.; session order: F(1,20) = 0.72, n.s.; two-way interaction: F(1,20) = 4.03, p<0.1).

Phonemically identical and prosodically different sequences

DISCUSSION

The results show that NH listeners can segment phonemically identical and prosodically different sequences above the chance level, at 80%, in the auditory-only presentation modality. This is in line with the study of [START_REF] Spinelli | Fine-grained access to targets and competitors in phonemically identical spoken sequences: The case of French elision[END_REF]. Our results show no differences between the auditory-only and audiovisual presentation modalities. In fact, [START_REF] Strauß | Visual lip information supports auditory word segmentation[END_REF] observed that seeing the speaker's lip movements plays a role in word segmentation. The absence of such an effect in our study can be explained by the fact that our stimuli were acoustically and visually different from theirs. [START_REF] Strauß | Visual lip information supports auditory word segmentation[END_REF] used hyperarticulated visual lip movements with ambiguous auditory sequences without relevant acoustical cues for segmentation. Therefore, the visual cues were very important. In our study, we asked the speaker to utter the sentences in a natural way. Thus, compared to the stimuli of [START_REF] Strauß | Visual lip information supports auditory word segmentation[END_REF], the auditory cues were more important and the visual cues less so. Compared to auditory speech, natural visual speech does not seem to provide NH listeners with additional intonational cues to segment phonemically identical and prosodically different sequences. Regarding the performance of "Ms. C", as expected from clinical observations, she was very good at discriminating between minimal pairs. However, her performance in segmenting phonemically identical and prosodically different sequences did not differ from the chance level. She was unable to make use of intonational cues in word segmentation. Although CI users are better than NH listeners at using visual speech [START_REF] Rouger | Evidence that cochlear-implanted deaf patients are better multisensory integrators[END_REF], no performance gain was observed in the audiovisual presentation modality. The absence of visual benefit in this study could be explained by the fact that "Ms. C" received her bilateral CIs soon (one month) after her hearing loss and did not practice lip-reading alone for a long period. However, NH individuals, without any explicit lip-reading practice, benefit from visual speech especially in adverse conditions such as noise (Peelle and Sommers, 2015, for a review). Regarding the segmentation of phonemically identical and prosodically different sequences, we believe that reliable intonational cues for segmenting these sequences are not very important in visual speech. This is why visual hyper-articulated stimuli dubbed onto auditory ambiguous sequences influence segmentation in NH listeners [START_REF] Strauß | Visual lip information supports auditory word segmentation[END_REF] but not when utterances are produced naturally as in our study. In summary, despite an excellent rehabilitation of some aspects of speech processing, "Ms. C" seemed unable to segment natural speech by using auditory intonational cues. Visual cues were not salient enough to improve her performance.

This finding has implications for speech-language pathologists. It points to the importance of assessing the skills of CI users in the fine processing of auditory and visual prosody, as recommended in other speech and language pathologies [START_REF] Peppé | Why is prosody in speech-language pathology so difficult?[END_REF][START_REF] Swerts | The relevance of visual prosody for studies in language and speechlanguage pathology[END_REF]. In fact, an excellent rehabilitation in speech understanding based on phoneme/word recognition with CIs is not necessarily accompanied by a good performance in the extraction of speech prosodic cues. Although fine structure information transmitted by CI devices is degraded, prosodic cues are not completely absent [START_REF] Wilson | Cochlear implants: a remarkable past and a brilliant future[END_REF] and CI users can process auditory prosodic cues to some extent (e.g. [START_REF] Spitzer | The use of fundamental frequency for lexical segmentation in listeners with cochlear implants[END_REF][START_REF] Meister | Use of intonation contours for speech recognition in noise by cochlear implant recipients[END_REF][START_REF] Snow | Children's development of intonation during the first year of cochlear implant experience[END_REF][START_REF] Segal | Auditory discrimination of lexical stress patterns in hearing-impaired infants with cochlear implants compared with normal hearing: influence of acoustic cues and listening experience to the ambient language[END_REF]. Training in this aspect of speech is therefore feasible and needs to be systematically included in rehabilitation programmes.

  analyzed the accent range (i.e. the amount of F0 change used in falling or rising contours) during the spontaneous speech production of CI children. They observed similar skills in CI children to those predicted by a model of early intonation development in NH children. In a sentence recognition task, Meister, Landwehr, Pyschny,

Table 1 :

 1 Mean percentages of correct responses of the NH group for the identification of phonemically identical and prosodically different sequences and minimal pairs. SE =

	Minimal pairs

Table 2 :

 2 Percentages of correct responses of "Ms. C" for the identification of phonemically identical and prosodically different sequences and minimal pairs.

ACKNOWLEDGMENTS

The author thanks "Ms. C" and normal-hearing subjects for their participation in this study, Pierre-François Tournade and Amandine Lepachelet for their help in recording the stimuli, and Fanny Heurtebise and Muriel Lefeuvre for their help in collecting the data.