Bernard Lété

MANULEX: A lexical database from French readers

: number of phonemes, of syllables, the syllabic units and frequency. MANULEX is intended to provide a useful tool for linguistic analyses and/or to select testing stimuli. It can also be used by researchers in Artificial Intelligence as a source of information on natural language processing to simulate child written language acquisition.

INTRODUCTION

The history of lexicographical studies based on quantitative data is not recent, one of the most often quoted ancestor being [START_REF] Käding | Häufigkeiteswörterbuch der deutschen Sprache[END_REF] who established a lexical database in order to help those in charge of shorthand writing of political, administrative and commercial speeches in German. It was also in a pragmatic purpose, educational in this case, that [START_REF] Thorndike | Teacher's word book[END_REF] established his English teacher's word book. A few years later, Thorndike participated in a conference held in New-York which was focussed on the establishment of a basic English for language teaching and language diffusion, the core idea being to determine a basic vocabulary, thus necessitating to take into account word frequencies [START_REF] Thorndike | A teacher's word book of 20,000 words[END_REF].

The main goal of these first studies is quite different of that of the recent studies in the same field, that mainly aim to create tools to help linguistic and psycholinguistic researches, the most often quoted tools for American English being the word frequency lists of the Brown Corpus [START_REF] Kučera | Computational analysis of present-day American English[END_REF], the American Heritage Word Frequency Book (Carroll, Davis, & Richman, 1971) and the Thorndike-Lorge Count [START_REF] Thorndike | The Teacher's word book of 30,000 words[END_REF]. This paper presents MANULEX, the first French linguistic tool providing grade-level frequency based lists (1 st to 5 th grade) established from the 1,9 million words of the main French readers. It contains 48,886 non-lemmatized entries and 23,812 lemmatized entries.

It was compiled with the aim to catch up the works in English language as the latest studies of [START_REF] Zeno | The educator's word frequency guide[END_REF]. It should provide a useful tool for linguistic analyses and/or to select testing stimuli. It should also be used by researchers in artificial intelligence as a source of information on natural language processing to simulate child written French language acquisition. Finally, it should be used in an educational purpose for language instruction, vocabulary grading, syllabus design and materials writing.

Short history of French language lexical databases

Concerning the francophone countries, word frequency tables were established since the beginning of the last century, mainly to help teachers. The first was set-up by [START_REF] Henmon | A French word book based on a count of 400,000 running words[END_REF] who wanted to scientifically determine which really were the most usual words and their degree of frequency. This work was mainly based on texts selected in the French literature of the second half of the 19th century. Ten years later, Vander [START_REF] Vander Beke | French word book[END_REF] studied a wider corpus by introducing a proportion of non literary texts, particularly lexical database from readers -5 scientific texts and newspaper articles. The main interest of the work were the account of an index of dispersion of words across corpora (a word which appears once in five different corpora being more significant than a word which appears ten times in only one corpus).

The preceding corpora were mainly established from texts for adults. One of the first works including texts written forand even bychildren was presented in the dissertation thesis of [START_REF] Aristizabal | Détermination expérimentale du vocabulaire écrit pour servir à l'enregistrement de l'orthographe à l'école primaire[END_REF] based on 4,100 schoolchildren written productions. The Dubois and Buyse scale (1940) was derived from this work: 3,724 words of the Aristizabal's corpus were dictated to 59,469 primary schoolchildren and classified into 43 steps based on the words correctly spelled. The scale was updated into 40 steps by [START_REF] Ters | L'échelle Dubois-Buyse d'orthographe usuelle française[END_REF]. In the same line were the study of Dottrens and Massarenti (n.d.) in Switzerland which was based on [START_REF] Prescott | Vocabulaire des enfants et des manuels de lecture[END_REF] work, and of [START_REF] Préfontaine | Échelle du vocabulaire oral des enfants de 5 à 8 ans au Canada Français[END_REF] in Québec who first established a list based on 5 to 8 year-olds' spoken language, list which was after used to select the words for their teaching reading method.

The idea of a basic French vocabulary based on spoken corpora was also at the core of the work of [START_REF] Gougenheim | L'élaboration du français fondamental (1° degré)[END_REF] which contains the frequency of 7,995 everyday conversation words, established from 275 recorded conversations (only the 1,063 most frequent words were retained for the publication). [START_REF] Catach | Les listes orthographiques de base du français (LOB). Les mots les plus fréquents et leurs formes fléchies les plus fréquentes[END_REF] relied on this work, as on two others based on written texts, [START_REF] Imbs | Dictionnaire des fréquences. Vocabulaire littéraire des XIXe et XXe siècles, I-Table alphabétique, II-Table des fréquences décroissantes[END_REF] and [START_REF] Juilland | Frequency dictionary of French words[END_REF], the originality of the latter being to take into account the frequency of lemmatized and non lemmatized words. On these bases, [START_REF] Catach | Les listes orthographiques de base du français (LOB). Les mots les plus fréquents et leurs formes fléchies les plus fréquentes[END_REF] established a list of the most frequent French words and of their most frequent flexional forms (2,357 entries). This rapid presentation shows that French researchers in child language development, and French teachers, have poor little tools to do their job. These "databases" are very dated but are still in used because no other alternative exists for child language studies. Researchers essentially rely upon adult language databases (see below). More important, these linguistic materials were extracted from children written productions or adults speech productions. As pointed out by [START_REF] Robert | On the comprehension/production dilemma in child language[END_REF], the fact that children's linguistic ability in production lags dramatically behind their ability in comprehension poses a long-standing conceptual dilemma for studies of language acquisition. Children's productions do not reflect their competence in basically the same way as is assumed for adults, and there is a dramatically greater competence/performance gap for children. As a result, the used of Dubois-Buyse scale or Catach lists to select items for studying, for example, word lexical database from readers -6 recognition in French, raises several methodological and theoretical problems. However, these works have opened the way to new French computerized databases which are presented below.

Current computerized language corpora and lexical databases

English language

In English, computerized lexical database were available since the beginning of the sixties.

The Brown Corpus of Standard American English was the first of the modern, computer readable, general corpora. It was compiled by [START_REF] Kučera | Computational analysis of present-day American English[END_REF], at Brown University (Providence). The corpus consisted of one million words of American English texts printed in 1961 and sampled from 15 different text categories to make it a standard reference. Today, this corpus is considered as small, and slightly dated, but is still in used.

The British National Corpus (BNC) is a 100 million word collection of samples of written (90%) and spoken (10%) language from a large range of sources, designed to represent a wide cross-section of current British English. The BNC is a unique snapshot of the English language, presented so as to render possible almost any kind of computer-based research on language. Leech, Rayson and Wilson (2001) have recently published a word-frequency book derived from the BNC. It includes frequencies for writing and for present-day speech (including everyday conversation). Some corpora have been compiled in specific lexical databases. The MRC Psycholinguistic Database [START_REF] Coltheart | The MRC psycholinguistic database[END_REF] contains 150,837 English words likely to be used in psycholinguistic research and provides information about 26 different linguistic properties. It was established from different sources that took into account most of the factors influencing lexical processing: the Associative Thesaurus [START_REF] Kiss | An associated thesaurus of English and its computer analysis[END_REF], Jones' Pronouncing Dictionary of the English Language [START_REF] Jones | Everyman's English pronouncing dictionary[END_REF]), Paivio's ratings of the concreteness, imagery and meaningfulness of words [START_REF] Paivio | Concreteness, imagery and meaningfulness values for 925 words[END_REF]), Gilhooly and Logie's ratings based on age of acquisition, imagery, concreteness, familiarity and ambiguity measures [START_REF] Gilhooly | Age of acquisition, imagery, concreteness, familiarity and ambiguity measures for 1944 words[END_REF], the Colorado norms which deal with word meaningfulness [START_REF] Toglia | Handbook of semantic word norms[END_REF], the word frequency counts of [START_REF] Kučera | Computational analysis of present-day American English[END_REF] and those of [START_REF] Thorndike | The Teacher's word book of 30,000 words[END_REF] and the Shorter Oxford English Dictionary database [START_REF] Dolby | A tape dictionary for linguistic experiments[END_REF].

The American Heritage Intermediate (AHI: Carroll, Davies & Richman 1971) is based on a survey of US schools. It contains 5,09 million words from publications which were widely read among American schoolchildren aged 7 to 15 years. The set of 86,741 distinct words was created from 500-word samples taken from over 6,000 titles of books. The authors lexical database from readers -7 have computed 4 statistics to describe the frequency of occurrence of the words in their corpus. The statistics are F (frequency), D (distribution or dispersion), U (number of adjusted occurrences per million) and SFI (standard frequency index). These statistics are computed in MANULEX and are described below. The Educator's Word Frequency Guide (EWFG; [START_REF] Zeno | The educator's word frequency guide[END_REF] is based on over 17 million tokens and 164,000 types. It is nearly 3 times the size of the corpus in the AHI which is now over 30 years old. The EWFG exceeds the earlier studies not only in number of words, but also in number of samples (60,500) and sampled texts, spanning from kindergarten through college. This comprehensiveness and this diversity give the EWFG corpus better coverage of text in current use across grades than any previously published word frequency study. The guide is divided in four sections. Technical characteristics are described in the first section, followed in section two by an alphabetical list of words with frequencies of 1 or greater. This list includes F, D, U, SFI and frequency by grade-level statistics for each word. Section 3 lists words with frequencies less than 1, and the final section presents the words of the entire corpus in descending order of frequency. In a study on age of acquisition, [START_REF] Zevin | Age of acquisition effects in word reading and other tasks[END_REF] found that the Zeno et al counts are more closely correlated with latencies than are earlier counts such as those of [START_REF] Kučera | Computational analysis of present-day American English[END_REF] and CELEX (see below), presumably because of the larger corpus and their inclusion of texts targeted at younger readers.

Another database, which could be used as a foundation for an extension of MANULEX, is the CELEX database [START_REF] Baayen | The CELEX lexical database (CD-ROM)[END_REF]. For each current language (English, Dutch and German), CELEX provides detailed information on orthography (variations in spelling, hyphenation); phonology (phonetic transcriptions, variations in pronunciation, syllable structure, primary stress); morphology (derivational and compositional structure, inflectional paradigms); syntax (word class, word class-specific subcategorizations, argument structures) and word frequency (summed word and lemma counts, based on recent and representative text corpora). Over the past few years, CELEX data have been successfully used in various types of research and experiments, such as selection of lexical materials for word recognition or word association experiments, study of the mental lexicon through analyses of the distribution of wordlists using several deviation and uniqueness measures, and generation of frequency-based lists of sequences of words, graphemes, phonemes or syllables.

French language lexical database from readers -8

Unlike those for English, computerized corpora and lists for other languages, including French, are limited in number or still under development. As pointed out by [START_REF] Verlinde | Corpus-based versus intuition-based lexicography: Defining a word list for a French learners' dictionary[END_REF], although French lexicographers were among the first to integrate corpusanalysis into the dictionary-making process, with the "Trésor de la langue française" project (TLF; [START_REF] Imbs | Dictionnaire des fréquences. Vocabulaire littéraire des XIXe et XXe siècles, I-Table alphabétique, II-Table des fréquences décroissantes[END_REF] and its corpus of 170 million words, corpus-based lexicography is not a common practice in contemporary lexicography in France (see however here above for the non-computerized French lexical databases).

With the FRANTEXT project, French corpus-based lexicography is in progress.

FRANTEXT is a web-online corpus of 3,241 texts, chosen among 2,330 works of French literature and a large group of non-literary works. The corpus (183 million words) was assembled for the purpose of compiling word occurrences for French dictionary research.

The site was created in 1997 by the INALF (National Institute of the French Language) to present its research programs, particularly its lexicon. FRANTEXT covers all aspects of the French language: literary texts (16 th -20 th centuries), scientific and technical texts (from the 19 th -20 th centuries), and regional variations. Texts can be queried by words, sentences, author, title, genre, date or by any combination. Word frequency distribution tables and collocations are generated for selected words and works.

The BRULEX database for French [START_REF] Content | Brulex: Une base de données lexicales informatisée pour le français écrit et parlé [Brulex: A lexical database for written and spoken French[END_REF] was the first to be machine readable. It contains 35,746 entries based on the Micro Robert dictionary [START_REF] Robert | On the comprehension/production dilemma in child language[END_REF]. The token frequencies are those of the TLF for a corpus of 23,5 million words of literary texts published between 1919 and 1964.

The LEXIQUE database [START_REF] New | Une base de données lexicales du français contemporain sur Internet: LEXIQUE [A lexical database of contemporary French: LEXIQUE[END_REF] is the current reference tool in French psycholinguistic research. A corpus of texts written since 1950 has been extracted from the FRANTEXT corpus (31 million words). The database contains 128,942 wordform entries (inflected forms of verbs, nouns and adjectives) and 54,196 lemma entries. Each entry provides several linguistic informations including frequency (per million), gender, number, phonological form, graphemic and phonemic unicity points.

Proper names, symbols, abbreviations and foreign language words have been excluded. LEXIQUE provides two token frequency computations: one based on the 31 million words of the FRANTEXT sub-corpus; the other on a Web frequency count. The wordforms were submitted to the 15 million French Web pages of FastSearch; the number of pages where the token was found gives the token frequency. For the authors, this count provides an estimation of the word usage. Lemmatization tools were used to obtain the set of lemmas. lexical database from readers -9

Finally, two specific adult databases for psycholinguistic research in French can be mentioned. LEXOP [START_REF] Peereman | LEXOP. A lexical database providing orthographyphonology statistics for French monosyllabic words[END_REF] The NOVLEX database [START_REF] Lambert | NOVLEX: Une base de données lexicales pour les élèves de primaire [Novlex: A lexical database for elementary grades pupils[END_REF] provides an estimation of the vocabulary of written material in use in French primary schools, but only for third graders.

With the help of teachers, the authors have selected 38 books (19 reading books of third grade and 19 children's storybooks). The corpus leads to a total of 417,000 words. The database has 20,600 wordform entries and 9,300 lemma entries. For each entry, are provided the frequency of occurrence per 100 million, and the syntactic category.

THE MANULEX DATABASE

The MANULEX database is a word frequency list based on a corpus of readers used in French primary schools, from 1 st to 5 th grades. It involves three sub-corpora of 1 st , 2 nd and 3 rd to 5 th grade and the overall corpus of books (hereafter called G1, G2, G3-5, and G1-5, respectively). It contains two lexicons: the wordform lexicon and the lemma lexicon.

Sampling and Representativeness

McEnery and Wilson (2001) described a modern corpus as any collection of more than one text with four main characteristics: sampling and representativeness, finite size, machine-readable form, and status as standard reference. Two of these are present apriori in our dataset: it is of finite size and machine readable. Our main concern will be assessing sampling and representativeness. lexical database from readers -10 Our corpus consists in reading, spelling and books published by the French leading publishers (see Appendix for a complete list and additional information). The book selection was made on the basis of the sales for the year 1996. We have computed the cumulative frequency of the sales for the set of books at each grade and we have retained a sample that covered 75% of the sales. So, for each grade, the sample is reasonably representative of printed school French materials for schoolchildren aged 6 to 11 years. This leads to a total of 54 books: 13 in G1, 13 in G2 and 28 in G3-G5. The books cover a range of topic areas, each with a credible size of data coming from different type of texts (from novels to various kinds of fiction; from newspaper reportage to technical writing; from poetry to theater play) written by different authors coming from a variety of backgrounds. This is the reason why we have not incorporated others pieces of written materials, as children's books, because their contents were sufficiently represented in our corpus.

The books were entirely scanned (8,774 pages). The text of the illegible pages was rekeyed. An optical character recognition software was applied to the pages to extract the texts in an ASCII format. All page areas were included in the process except page numbers and some chapter headlines.

Tagging and lemmatization

The term "tagged" (annotated) corpus is used for a corpus which contains not only a sequence of words but also comprises additional information. Typically, this includes linguistic information which is associated with the particular wordforms in the corpus. The most common linguistic tags are lemma (the basic wordform), and the respective grammatical categories.

The most reasonable way to build large annotated corpora is an automatic tagging of the texts by computer programs. However, as pointed out by Ide and Véronis (1998), natural languages display rather complex structure and therefore it is not surprising that attempts to process them by simple deterministic algorithms do not always yield satisfactory results.

The result is that the present tagging programs are not able to give fully reliable results and there are many ambiguities in their output.

We have used a tagger that more and more teams use in France, since it performs well Understanding Consortium, an international group of linguistic technology experts in five main European languages (English, French, German, Italian, Portuguese, and Spanish).

Cordial Analyseur® uses statistical data and explicit rules with two types of dictionaries: orthographical dictionaries which comprise the lemma of each word (more than 117,000 on the whole) and grammatical indications (category, gender and number). For the verbs, a number indicates the type of conjugation. In addition, the analyzer uses another type of dictionary, known as grammatical, which comprises a whole of variables for each word and their directions if they are polysemous. In addition, Cordial Analyseur® has many options, which make possible to regulate in a fine way the regrouping of the words in phrases, to display the lemmas and to obtain various information beyond the simple morpho-syntactic labeling: grammatical functions (subject, object, attribute, etc.) or semantic labels, although obviously this information has not the reliability of the morpho-syntactic labels as pointed out by [START_REF] Valli | Étiquetage grammatical de corpus oraux: Problèmes et perspectives[END_REF]. The set of labels used by Cordial is rather detailed, since it comprises 130 different labels, corresponding to the majority of the morpho-syntactic distinctions of French.

As a result of lemmatizing the corpus, the counts for all inflectional variants of a word are collapsed together into a single lexeme count. Other types of inflectional morphology conflated by lemmatization are gender and plural suffixes (e.g. chat (cat), chats, chatte, chattes), and adjective forms (e.g. corrigé (corrected), corrigés, corrigée, corrigées).

Lemmatization was motivated by the observation that meaning is normally preserved across the inflectional variants of a lexeme, whereas derivational morphological variants are often semantically opaque. There is some evidence that lexical processing draws upon lexeme frequency (also referred to as stem or summed wordform frequency) information, in preference to surface wordform statistics. Studies on word recognition demonstrated lexeme frequency to be a better predictor of processing time than simple surface frequency. For example, although shoe and fork are matched for corpus frequency, shoe is recognized faster than fork because shoes is much more frequent than forks [START_REF] Taft | Recognition of affixed words and the word frequency effect[END_REF]. This finding suggests that the basic unit of lexical representation is the lexeme, rather the surface wordform. More recently, [START_REF] Baayen | Singulars and plurals in Dutch: Evidence for a parallel dual-route model[END_REF] showed that lexical decision latencies for singular Dutch nouns of differing surface frequency were statistically equivalent when the items were matched for lexeme frequency. However, this was not the case for plural nouns, for which surface frequency effects were found. [START_REF] Baayen | Singulars and plurals in Dutch: Evidence for a parallel dual-route model[END_REF] propose that it is more efficient for some lexical database from readers -12 morphologically complex words to be stored as wholes due to orthographic form ambiguity. For instance, in French, some nouns or adjectives (ending in -ant or -ent) may also correspond to verb sharing the same stem, and therefore are ambiguous (courantcourant, current-running; excellent-(ils) excellent, excellent-(they) excel).

Frequency computations

Corpus frequency is an established, robust predictor of word recognition performance. The word frequency effect is one of the earliest empirical observations in cognitive psychology which was made by [START_REF] Cattell | The time taken up by cerebral operations[END_REF]. He demonstrate that the frequency of occurrence of a word in a language affects even the most basic processing of that word, its speed of recognition. Since Cattell's pioneering work, word frequency has been a persisting subject of study for investigators concerned with the recognition of words: high frequency words are recognized more quickly and with greater accuracy than low frequency words, whatever the chronometric measure (fixation duration, naming, lexical decision, etc.; see [START_REF] Monsell | The nature and locus of word frequency effects in reading[END_REF], for a review).

Word-frequency counts are the first useful output of a corpus [START_REF] Nation | Learning vocabulary in another language[END_REF]. But, as pointed out by [START_REF] Nagy | How many words are there in printed school English ?[END_REF], the frequency of a word reflects different factors, one of them being the conceptual difficulty of the word. In general, it might be said that a word's frequency reflects the range of contexts in which the word might appear. Yet, [START_REF] Francis | Frequency analysis of English usage[END_REF] noted that the distribution of words in different type of texts is not equal. They pointed out that unlike high frequency words, low frequency words tend to occur in a smaller number of type of texts. That is, they seem to be context specific. This notion has some important considerations here.Indeed, particularly in 1 st grade, there is a great diversity among books because editors want their books to be attractive and appealing in their design and illustrations. The content is not always selected considering the aim of teaching, and the readability seems to be understood differently by the writers. If a word frequency list should reflect individual child's exposure to written words, the frequency computed for a word should not underestimated its apparition in a corpus of indefinitely large size.

In MANULEX, for a given word, are indicated, first, the total number of occurrences in all books and, secondly, its distribution across the different books. This is important in order to ensure that words are not limited to a specific corpus. For instance, in MANULEX, the word point (point) was found 276 times in G1 but with an occurrence of 242 in only one book; whereas the word papa (daddy) was found 270 times in G1 and had an even distribution over the set of books.

lexical database from readers -13

For the index computations, we have followed the methods described in Carroll et al. (1971) and used recently by [START_REF] Zeno | The educator's word frequency guide[END_REF] in the EWFG (see also [START_REF] Breland | Word frequency and word difficulty: A comparison of counts in four corpora[END_REF]. The Carroll's (1971) statistics were computed in MANULEX (wordform lexicon and lemma lexicon) for the three sub-corpora (G1, G2, and G3-5) and the overall corpus of the books. F -Frequency, the number of times the word type occurred in the corpus. D -Dispersion, which can take values from .0000 to 1.000, based on the dispersion of the frequencies over the books. D takes the value .0000 when all occurrences of the word are found in a single book, regardless of the frequency. It would take the value 1.000 if the frequencies were distributed over the books exactly proportionally to the total numbers of tokens (words) in the component lists. Values between .0000 and 1.0000 indicate degrees of dispersion between these extremes. As an example, in the lemma lexicon, "à" has an equal distribution across the 13 books in G1, and thus has a D value of 0.96. "abattre", as another example, occurred only once in G1 and thus has a D value of 0.000; the same word occurred 93 times in G3-5 and had a D value of 0.90, meaning that it occurred with a mean frequency of 4 in each book.

The formula for calculating D may be given as:

D = [ log ( p i ) -[( p i log p i ) /  p i ] ] / log (n)
where: n: amount of books in the corpus (n = 13 in G1; 13 in G2; 28 in G3-5; and 54 in the overall corpus) i: book number (i = 1, 2, ..., n) p i : frequency of a token in the ith book, and p i log p i = 0 if p i = 0.) U -the estimated frequency per 1 million tokens, derived from F with an adjustment for D.

When D equals 1, U is computed simply as the frequency per 1 million tokens. But when D is less than 1, the value of U is adjusted downward. When D is 0, U has a minimum value based on the average weighted probability of the word type over the books. It is believed that U better reflects the true frequency-per-million that would be found in a corpus of indefinitely large size, thus permitting possible direct comparison to values given by the four corpora.

The adjustment is made by the following formula:

U = (1,000,000 / N) [FD + (1-D) * f min ]
where: lexical database from readers -14 N: total number of tokens in the corpus (172,248 in G1; 351,024 in G2; 1,386,546 in G3-5; and 1,909,918 in the overall corpus) F: frequency of the word in the corpus D: index of dispersion f min: 1/N times the sum of the products of fi and si, where fi is the frequency in the book i and si is the number of tokens in the book. SFI -Standard Frequency Index is derived directly from U and hence has some of the same characteristics as U. It is believed that the user will find this index to be a simple and convenient way of indicating word frequencies, once it is understood. A word type with SFI = 90 would be expected to occur once in every 10 tokens; one with SFI = 80 would be expected to occur once in every 100 tokens, etc. A convenient mental reference point is provided by SFI = 40, the value for a word that would occur once in a million tokens. Each unit of SFI represents an increase of about 25.9% in probability or frequency. SFI is computed from U with the formula:

SFI = 10 * [log 10 (U) + 4]
As an example, we have seen that point and papa have the same frequency in G1 (276 and 270, respectively). However, they have a different D value (.24 and .79), and an estimated frequency per 1 million of 507 and 1270, respectively. Hence, their SFI value is 67.05 and 71.04.

Description of the files

The MANULEX database is downloadable at htpp://www… under three formats: ASCII texts (two lexicon files downloadable), Microsoft®Excel, and Microsoft®Access.

When starting to use the database, the user first has to choose between two lexicon types hereafter called the MANULEX-wordforms lexicon (48,886 entries) and the MANULEXlemmas lexicon (23,812 entries).

The database entries (either wordforms or lemmas) vary according to their syntactic category: noun (NC), proper name (NP), verb (VER), adjective (ADJ), adverb (ADV), pronoun (PRO), preposition (PRE), conjunction (CON), interjection (INT), determiner (DET), abbreviation (ABR) and euphonic string (UEUPH). The database contains 4 special categories of words that are often excluded from frequency counts: proper names (essentially surnames and countries), compounds containing numbers (dix-huit), abbreviations and interjections. Unlike some vocabulary researchers, we consider that if a word actually occurs in the corpus, children encounter it in their reading, and we consider lexical database from readers -15 this a justifiable operational criterion for including these words in the database (see also [START_REF] Nagy | How many words are there in printed school English ?[END_REF], for a similar point of view).The MANULEX-wordforms lexicon yields all possible inflected words; so, the lexicon contains words like "livre", "livres", "livrer" and so on. In the MANULEX-lemmas lexicon, all inflected wordforms are converted to their lemmas (for nouns and adjectives, the singular; for verbs, the infinitive).

For each sub-corpora (G1, G2, G3-5) and the overall corpus (G1-5), and after the word

Descriptive statistics

The information about the size of the corpus and the lexicons is displayed in Table 1.

INSERT TABLE 1 ABOUT HERE

The corpus provided a total of 8,898,283 characters and a total of 1,925,854 words. The database contained 1,909,918 tokens (digits were removed from the frequency count process). Table 1 also shows that 31% of wordforms and 24% of lemmas are hapax legomena. Generally hapax constitute nearly 50% of the words in a corpus, ratio which is representative of highly varied vocabulary. The present value is in agreement with the need of repeated vocabulary in learning to read. Table 3 provides the mean, mode and percentile values (10,25,50,75,90) for SFI in the MANULEX, NOVLEX, and LEXIQUE databases (lemma lexicons). The statistics are also given for MANULEX when proper names are removed from the lexicon, which gives a more direct comparison with the other databases.

INSERT TABLE 3 ABOUT HERE

The log transformation of SFI approximates a symmetric distribution with the mean close to the median at each level. So, in experiments, the percentile values may be used as cut-offs for the selection of high-frequency and low-frequency words (upper and lower quartile, respectively, for example). The mean SFI reflects the conceptual difficulty of written words addressed to schoolchildren, the decreasing of the means and the modes showing increasing vocabulary difficulties. An important drop is observed at the G3-5 level, the values approaching those of the LEXIQUE database. The significant values (mean, mode, upper and lower quartile) become closed to the adult database when the overall corpus (G1-5 level) is taken. The NOVLEX database (3 rd grade) contains much more frequent words than MANULEX G1 lexicon: in G1, mean and mode SFI are 49 and 38, respectively, whereas NOVLEX shows 51 and 44.

Table 4 gives the percentages of non-overlapping and overlapping lemma entries at each level, for the main syntactic categories (open-class items) and for the closed-class items.

INSERT TABLE 4 ABOUT HERE

Non-overlapping lemma entries are in the G3-5 sub-corpus, 51% of them (essentially open-class items) being not present in the two other levels. This result shows that it is important to have a lexicon below 3 rd grade because half of the words found in books started at 8 year old are not present in 1 st and 2 nd grade. Overlapping entries are mainly concern with closed-class items, but 27% of the nouns and 34% of the verbs overlap the 3 levels. These entries can help to construct a new basic vocabulary for French language.

Extensions

Computations of surface wordform statistics are planned at each level (letter, bigram, trigram and syllable frequencies). Table 5 provides statistics about mean number of letters, of phonemes, of syllables for open-class entries and for all types of words in MANULEXwordforms lexicon.

INSERT TABLE 5 ABOUT HERE

Descriptions of relations between orthography and phonology based on the work of [START_REF] Peereman | LEXOP. A lexical database providing orthographyphonology statistics for French monosyllabic words[END_REF]

  is a computerized lexical database which provides quantitative descriptors of the relation between orthography and phonology for French monosyllabic words. Three main classes of variables are considered: consistency of print-to-sound and sound-to-print associations, frequency of orthography-phonology correspondences, and word neighborhood characteristics. VOCOLEX (Dufour, Peereman, Pallier & Radeau, in press) is a lexical database which provides several statistical indexes of phonological similarity between French words (phonological neighbours). Two recent works on child language can be mentioned. Arabia-Guidet, Chevrie-Muller and Louis (2000) have analyzed 118 recent books (100 storybooks, 18 picture books) for preschool children (3-5 years old). The corpus contains 24,936 words (8,479 wordform entries). No tagging was made to obtain lemmas. The most frequent words (254 in storybooks and 101 in picture books) are listed. The count was calculated from the number of books where the word was encountered which provides an indice of the word usage in the sample books (as the FastSearch frequency count of LEXIQUE).

under

  Microsoft® Windows, and does not require any training. It is commercially distributed, but very cheap for research. It is called Cordial Analyseur®, and is developed by Synapse Development who also developed the Microsoft® Word 2000 spelling and grammatical tools. The company is one of the founding members of the Natural Language lexical database from readers -11

  length and the syntactic category (noted NLET and SYNT, respectively), other columns show the frequency of the word in the corpus and the three Carroll's computations: D, U and SFI (noted G1 F; G1 D; G1 U; G1 SFI; …; G1-5 SFI). Empty cells correspond to words not present in a corpus. The frequency values of LEXIQUE have been added to give a comparison point of the MANULEX entries with a corpus based on adult language. We have only retained the FRANTEXT frequencies (given per 1 million). FRANTFREQPARM values (FRANTEXT frequencies per million) were added in MANULEX-wordforms; and FRANTFREQCUM values (FRANTEXT cumulative frequencies per million) were added in MANULEX-lemmas (86% and 76% of values recovered, respectively; missing values essentially concern proper names.) Finally, for each entry recovered, three other fields of LEXIQUE have been added: the number of phonemes, the number of syllables and the phonetic transcriptions syllabified (values corrected by Peereman & Dufour, in press).

Table 2

 2

	provides the distribution of lemmas by syntactic categories at each level (N and
	percentages).
	INSERT TABLE 2 ABOUT HERE
	Whatever the level, half of the lemma entries are concerned with nouns, and near 98% of
	them are open-class entries.

Table 3 :

 3 are planned. The computation should take into account, on the one hand, grapheme-phoneme correspondences (for reading) and, on the other hand, phoneme-grapheme correspondences (for spelling). The study of Peereman and Content only included monosyllabic items. In French, monosyllabic words are very few as provided by our MANULEX count: monosyllabic words are very few (6.70%) and the mean number of syllables of the written words is two. So the Peereman and Content's work needs more Mean, mode and percentile values for SFI in MANULEX-lemmas, NOVLEX a and LEXIQUE b databases. Significant data are listed in bold italics.

	in depth analyses.

Table 4 :

 4 Percentages of non-overlapping and overlapping lemma entries at each level with mean SFI, as a function of open-class and close-class items.

	Non-overlapping entries

Table 5 :

 5 Statistics about mean number of letters, mean number of phonemes and mean number of syllables for open-class entries and all types of words in MANULEX-wordforms lexicon. Appendix: List of reading books used in the present data collection.

	Syntactic		G1 G2 G3-5
	Category
	Noun	No. of letters	7.0 7.4	8.0
		No. of phonemes	5.0 5.3	5.8
		No. of syllables	2.0 2.2	2.4
	Verb	No. of letters	7.5 7.7	8.0
		No. of phonemes	5.8 6.0	6.2
		No. of syllables	2.6 2.7	2.8
	Adjective No. of letters	7.0 7.6	8.3
		No. of phonemes	5.1 5.6	6.2
		No. of syllables	2.2 2.4	2.7
	Adverb	No. of letters	7.7 8.9 10.4
		No. of phonemes	5.2 6.2	7.3
		No. of syllables	2.2 2.7	3.2
	All types	No. of letters	7.0 7.5	8.0
		No. of phonemes	5.0 5.4	5.8
		No. of syllables	2.1 2.3	2.5

The lemma lexicon was used. The SFI formula was computed after calculation of the frequencies per million (field/100).

b: We have used the FRANTEXT frequencies per million of the overall entries of the lemma database (FRANTFREQCUM field); the SFI formula was computed.


B N Dicte Clin

Pascal Andujar

Issam Abd

Al Samad

Chantal Azpitarte

Fran Oise Le Pimpec-Barthes

Marie-Annick Billon-Galland

Claire Danel

Fran Oise Galateau-Salle

Bruno Housset

Karinne Legrand-Cattan

Mireille Matrat

Isabelle Monnet

Marc Riquet

Jean-Claude Pairon

Pulmonary carcinoid tumors and asbestos exposure

Keywords: Adult, Aged, Asbestos, toxicity, Carcinoid Tumor, etiology, pathology, Case-Control Studies, Female, Humans, Lung Neoplasms, etiology, pathology, Male, Middle Aged, Occupational Diseases, etiology, pathology, Occupational Exposure, adverse effects, analysis, Paris, Questionnaires, Retrospective Studies asbestos, lung cancer, pulmonary carcinoid tumor, occupational exposure

Objectives

The hypothesis that asbestos exposure may have more specific associations with particular histological types of lung cancer remains controversial. The aim of this study was to analyze the relationships between asbestos exposure and pulmonary carcinoid tumors.

Methods

A retrospective case-control study was conducted in 28 cases undergoing surgery for pulmonary carcinoid tumors and aged over 40 years, and in 56 controls with lung cancer of a different histological type, matched for gender and age, from 1994 to 1999, recruited in 2 hospitals in the region of Paris. Asbestos exposure was assessed via expertise of a standardized occupational questionnaire and mineralogical analysis of lung tissue, with quantification of asbestos bodies (AB).

Results

Definite asbestos exposure was identified in 25 of cases and 14 of controls (ns). Cumulative asbestos exposure was significantly % % higher in cases than in controls (p<0.05), and results of the quantification of AB tended to be higher in cases than in controls (24 and % 9 had more than 1,000 AB/g dry lung tissue, respectively, p 0.09). Mean cumulative smoking was lower in cases than in controls % = (p<0.05).

Conclusion

This study argues in favor of a relationship between asbestos exposure and certain pulmonary carcinoid tumors.

INTRODUCTION

The malignant pathologies linked to asbestos exposure include pleural, peritoneal, pericardic and/or testicular tunica vaginalis mesothelioma, lung cancers, together with ovarian and laryngeal cancers (American [START_REF] Thoracic | Diagnosis and initial management of nonmalignant diseases related to asbestos[END_REF][START_REF] Straif | A review of humans carcinogens Part C: metals, arsenic, dusts, and fibers[END_REF].

In France, lung cancer is the leading cause of mortality by cancer among men and current estimates suggest that asbestos is responsible for 5 to 15 of lung cancers (Expertise collective INSERM, 1997;[START_REF] Boffetta | An estimate of cancers attributable to occupational exposures in France[END_REF][START_REF] Guida | Risk of Lung Cancer and Occupational History: Results of a French Population-Based Case-Control Study, the ICARE Study[END_REF]. No clinical, % % histological, topographical or radiological characteristic differentiates lung cancer linked to asbestos exposure from other lung cancers [START_REF] Ives | Environmental associations and histopathologic patterns of carcinoma of the lung: the challenge and dilemna in epidemiologic studies[END_REF][START_REF] Lee | Association of cigarette smoking and asbestos exposure with location and histology of lung cancer[END_REF][START_REF] Mollo | The attribution of lung cancer to asbestos exposure : a pathologic study of 924 unselected cases[END_REF]. Among these cancers, typical or atypical pulmonary carcinoid tumors are considered as low-grade malignant neoplasms comprised of neuroendocrine cells. These pulmonary carcinoid tumors account for 1 to 2 of all lung % tumors, hence the relative rarity of studies on this type of tumor [START_REF] Galofre | Pathologic classification and surgical treatment of bronchogenic carcinoma[END_REF][START_REF] Godwin | Comparative epidemiology of carcinoid and oat-cell tumors of the lung[END_REF][START_REF] Blondal | Aryrophil carcinoid tumors of the lung. Incidence, clinical study, and follow-up of 46 patients[END_REF][START_REF] Mccaughan | Bronchial carcinoids. Review of 124 cases[END_REF][START_REF] Fink | Presentation, diagnosis, and outcome in 142 cases in Israel and review of 640 cases from litterature[END_REF]. A male predominance (2/1) is observed for atypical carcinoid tumors [START_REF] Quaedvlieg | Epidemiology and survival in patients with carcinoid disease in the Netherlands. An epidemiological study with 2391 patients[END_REF].

Typical carcinoid tumors, which represent 90 of pulmonary carcinoid tumors, are characterized by neuroendocrine histological % differentiation, no tumoral necrosis and rare mitoses [START_REF] Davila | Bronchial carcinoid tumors[END_REF][START_REF] Travis | World Health Organization. Classification of tumours[END_REF]. Age at diagnosis is generally between 35 and 50 years, whereas atypical carcinoid tumors, characterized by neuroendocrine histological differentiation, tumoral necrosis and an increase in mitotic activity, occur in older subjects, generally aged between 55 and 60 years [START_REF] Struyf | Atypical bronchial carcinoid tumours[END_REF][START_REF] Arrigoni | Atypical carcinoid tumors of the lung[END_REF][START_REF] Thomas Cf | Typical and atypical pulmonary carcinoids: outcoma in patients presenting with regional lymph node involvement[END_REF]. Although certain studies suggest that tobacco smoking could be a risk factor for atypical pulmonary carcinoid tumors [START_REF] Mccaughan | Bronchial carcinoids. Review of 124 cases[END_REF][START_REF] Fink | Presentation, diagnosis, and outcome in 142 cases in Israel and review of 640 cases from litterature[END_REF][START_REF] Valli | Atypical carcinoid tumour of the lung: a study of 33 cases with prognostic features[END_REF][START_REF] Kayser | Carcinoid tumors of the lung: immuno-and ligandohistochemistry, analysis of integrated optical density, syntactic structure analysis, clinical data, and prognosis of patients treated surgically[END_REF] the etiology of carcinoid tumors, pulmonary or not, still remains unknown [START_REF] Hemminki | Incidence trends and risk factors of carcinoid tumors. A nationwide epidemiologic study from Sweden[END_REF][START_REF] Modlin | A 5-decade analyse of 13,715 carcinoid tumors[END_REF]. The aim of our study was to evaluate occupational asbestos exposure among subjects presenting with pulmonary carcinoid tumor, in order to analyze the relationships between asbestos and this type of lung cancer.

METHODS

Study population

A retrospective case-control study was conducted in subjects undergoing surgery for lung cancer, recruited in 2 hospitals in the Paris region from 1994 to 1999. Cases were subjects presenting with pulmonary carcinoid tumors and having volunteered to answer an occupational questionnaire (Group 1). A group of controls presenting with lung cancer of a different histological type was selected among subjects (Group 2), matched for gender and age, more or less 3 years. Indeed, for each case, 2 controls were randomly identified among files of subjects undergoing surgery for incident primary lung cancer (other than carcinoid), in the same hospitals and during the same period; these subjects also volunteered to answer an occupational questionnaire. To be eligible, cases and controls had to live in the Paris Recherches Biom dicales) Cr teil-Henri Mondor (authorization n 94-052). All patients received information on the study and gave their é é °written informed consent.

Data collection

Demographic data, asbestos exposure and tobacco consumption

For each included subject, date of birth, gender and tobacco status were collected. Subjects were classified into three categories according to tobacco consumption: smokers, ex-smokers (defined as those having stopped smoking since at least one year), and non-smokers. Age at beginning of tobacco smoking, duration and cumulative tobacco smoking in pack years were also collected.

Evaluation of individual asbestos exposure was performed using data from a standardized questionnaire describing all job positions occupied throughout the individual s occupational history. The evaluation of each job period of a duration in excess of 6 months was ' classified according to the probability, intensity (i.e. estimated level of exposure to asbestos, in f/ml, based on known airborne levels in similar situations) and frequency of exposure to asbestos. Since no measurements of airborne levels were available, all estimations of exposure parameters were based on experts subjectivity, i.e. semiquantification, to which weighting factors were assigned [START_REF] Iwatsubo | Pleural mesothelioma: dose-response relation at low levels of asbestos exposure in a French population-based case-control study[END_REF]. Categories of intensity were established using the following semiquantitative scale -probability of exposure: not exposed, possible, probable, definite; frequency: sporadic (less than 5 percent of working time), irregular (5 50 percent of working time), continuous (more than 50 percent of working time); intensity: low (less than 1 fiber/ml), moderate (1 2 fibers/ml), high (2 10 fibers/ml), very high (>10 -fibers/ml). Weighting factors were attributed to each exposure category in order to calculate an exposure index: probability: null 0, = possible 0.5, definite 1; frequency: sporadic 0.025, irregular 0.25, continuous 0.75; intensity: low 0.1, moderate 1, high 10 and very

= = = = = = = =
high 100. The CEI (Cumulative Exposure Index) is the life-time sum of the products of probability, frequency, intensity and duration for = each job period expressed in unit exposure x years. Expertise of this occupational questionnaire was performed by a practitioner specialized in occupational diseases, blinded to case/control status.

A fragment of tumor-free dry lung tissue, sampled during lobectomy or pneumonectomy, was used for mineralogical analysis performed by the Laboratoire d Etude des Particules Inhalees de la Ville de Paris (LEPI). Technical modalities for analysis were the same ' as those routinely used by the laboratory [START_REF] Pairon | Retention of asbestos bodies in the lungs of welders[END_REF]. Each mineralogical analysis was performed for samples of at least 10 mg of dry lung tissue. AB concentrations were expressed per gram of dry tissue and significant lung retention of AB was defined in our laboratory as more than 1,000 AB per gram of dry lung tissue. This value was chosen as the cut-off point since it has been considered as indicative of a nontrivial exposure to asbestos [START_REF] Sebastien | Asbestos bodies in bronchoalveolar lavage fluid and in lung parenchyma[END_REF].

Diagnosis of cases and controls

Histological classification of pulmonary carcinoid tumors was assessed using pathologic examination after lung tumor resection.

Typical and atypical pulmonary carcinoid tumors were differentiated according the IASCL (International Association for the Study of Lung Cancer) 2004 classification [START_REF] Travis | World Health Organization. Classification of tumours[END_REF]).

Statistical analysis

Qualitative, i.e. categorical variables were compared using the Chi-square test or the Fisher test to compare proportions, and

" " " "
quantitative variables using the Student s T test or Non parametric Wilcoxon test . Significant probability for these tests was defined as:

" ' " " "
p 0.05.

≤

RESULTS

Thirty-four subjects presenting with pulmonary carcinoid tumors were recruited (28 were aged over 40 years, Group 1A), and 56 controls aged over 40 years presenting with a different histological type of lung cancer.

The characteristics of these populations are described in table 1.

Among the 34 cases, 25 (74 ) presented with a typical pulmonary carcinoid tumor. Mean age was 49.5 years (standard deviation, SD

% =
15.8 years). The mean age of the 9 subjects presenting with an atypical pulmonary carcinoid tumor was 55 years (SD 14.4 years). No = significant difference was observed between these 2 populations concerning age, gender, tobacco consumption and cumulative asbestos exposure (table 2).

Among cases for which mineralogical analysis was performed, 5 showed significant retention of asbestos bodies ( 1,000 AB per gram ≥ of dry lung tissue).

All controls had mineralogical analysis of lung tissue. Five analyses (9 ) showed significant retention of asbestos bodies.

%

We compared the characteristics of the 28 cases aged over 40 years with controls (Table 3). Definite asbestos exposure was identified in 25 of cases and 14.3 of controls (NS). Cumulative exposure to asbestos (mean and median) was higher in cases aged over 40 years % % than in controls (p<0.05), and results of the quantification of AB tended to be higher in cases than in controls (24 and 9 had more than % %

1,000 AB/g dry lung tissue, respectively, p 0.09). Mean cumulative smoking was lower in cases than in controls (p<0.05). For subjects = with conformed asbestos exposure, the mean latency period after the beginning of such exposure was 44 years (SD 6.16) for cases and 48 = years (SD 6.63) for controls. For subjects with mineralogical analysis 1,000 AB per gram of dry lung tissue, this mean latency was

= ≥
roughly similar (43 years (SD 6.82) for cases and 44 years (SD 6.74) for controls).

= =

DISCUSSION

Our results are in favor of a relationship between occupational asbestos exposure and certain pulmonary carcinoid tumors. Indeed, we observed that cumulative exposure to asbestos evaluated by a practitioner specialized in occupational diseases was higher in cases of carcinoid tumor aged over 40 years than in controls, and results of the quantification of AB tended to be higher in cases than in controls. In contrast, mean cumulative smoking was lower in cases than in controls (p<0.05).

There was no significant difference between cases and controls with regard to age and gender, indicating a satisfactory match between cases and controls. Mean age of cases at diagnosis was 51.1 years, which is consistent with scientific data concerning pulmonary carcinoid tumors [START_REF] Mccaughan | Bronchial carcinoids. Review of 124 cases[END_REF][START_REF] Struyf | Atypical bronchial carcinoid tumours[END_REF][START_REF] Arrigoni | Atypical carcinoid tumors of the lung[END_REF][START_REF] Thomas Cf | Typical and atypical pulmonary carcinoids: outcoma in patients presenting with regional lymph node involvement[END_REF]. Distribution of typical and atypical pulmonary carcinoid tumors and their characteristics (age, gender, and tobacco consumption) were also similar to previously published data [START_REF] Fink | Presentation, diagnosis, and outcome in 142 cases in Israel and review of 640 cases from litterature[END_REF][START_REF] Struyf | Atypical bronchial carcinoid tumours[END_REF][START_REF] Arrigoni | Atypical carcinoid tumors of the lung[END_REF][START_REF] Thomas Cf | Typical and atypical pulmonary carcinoids: outcoma in patients presenting with regional lymph node involvement[END_REF][START_REF] Paillas | Bronchial carcinoid tumors: role of imaging for diagnosis and local staging[END_REF][START_REF] Thomas | Clinico-pathologic study of pulmonary carcinoid tumours A restrospective analysis and review of literature[END_REF].

Since lung cancer may be asbestos-related, the choice of subjects with lung cancer of a different histological type as controls, is subject for debate. Indeed, it may have been more appropriate to choose controls among subjects with diseases not known to have any relationship with asbestos exposure. Nevertheless, our aim was to select subjects for whom information on asbestos exposure was available, via both data from the occupational questionnaire and mineralogical analysis of asbestos bodies in lung tissue. Similarly to cases, they had to live in the Paris region to allow easy access for an interview for the occupational questionnaire. The choice of possible populations consequently conducted to lung cancer patients. This bias was conservative and the significantly higher cumulative asbestos exposure observed in cases compared to controls enhances the plausibility of a relationship between asbestos exposure and pulmonary carcinoid tumors.

The hypothesis that certain risk factors for lung cancer, such as asbestos exposure, may have more specific associations with particular histological types still remains controversial. Occupational asbestos exposure associated with lung cancer has been suspected to be more specifically associated with adenocarcinoma; however, authors have reported that these findings are not conclusive [START_REF] Henderson | Asbestos and lung cancer . Asbestos, asbestosis and cancer[END_REF][START_REF] Karjalainen | Asbestos exposure and the risk of lung cancer in a general urban population[END_REF][START_REF] Raffn | Lung cancer in asbestos cement workers in Denmark[END_REF][START_REF] Mollo | Lung adenocarcinoma and indicators of asbestos exposure[END_REF]. In the study conducted by Raffn in a cohort of asbestos cement et al.

workers, the excess risk of lung cancer was shared almost equally between different histological types of lung cancer during the first 25 years after the start of employment, whereas the risk of adenocarcinoma increased after this point [START_REF] Raffn | Lung cancer in asbestos cement workers in Denmark[END_REF]. Nevertheless, another study demonstrated an excess risk of other histological types of lung cancer in subjects having been exposed to asbestos [START_REF] Klerk | Exposure to crocidolite and the incidence of different histological types of lung cancer[END_REF]. Indeed, in the study conducted by De Klerk , the incidence of both squamous cell carcinoma and adenocarcinoma of the et al.

lung was higher in subjects with the highest levels of exposure to crocidolite and, after adjustment for smoking characteristics, the increase in incidence of lung cancer with increasing exposure to crocidolite was greater for squamous cell carcinoma than for adenocarcinoma. A recent study analyzed possible associations between adenocarcinoma and gender, age, smoking characteristics and selected occupational carcinogens, such as asbestos, in relation to other histological types [START_REF] Paris | Relationships between lung adenocarcinoma and gender, age, smoking and occupational risk factors: A case-control study[END_REF]. A total of 1,493 subjects presenting with lung cancer, including 489 cases of adenocarcinoma were included. No association was observed between adenocarcinoma and asbestos exposure. To date, no specific agent, such as asbestos, has been identified as being particularly significant for a specific histological type of lung cancer [START_REF] Henderson | Asbestos and lung cancer . Asbestos, asbestosis and cancer[END_REF] and, to our knowledge, only a few authors have studied the relationships between asbestos exposure and carcinoid tumors [START_REF] Fisseler-Eckhoff | Carcinoid tumors of the lung and asbestos. Clinical aspects for insurance medicine[END_REF][START_REF] Neumann | Carcinoid tumours of the lung and definition of the medico-legal term lung cancer used in the list of occupational disease in " " Germany--results of the German Mesothelioma Register[END_REF]. In a descriptive study previously conducted in 1998 in Germany [START_REF] Fisseler-Eckhoff | Carcinoid tumors of the lung and asbestos. Clinical aspects for insurance medicine[END_REF], 28 subjects undergoing surgery for pulmonary carcinoid tumor were studied for occupational asbestos exposure and retention of AB. The authors reported that there was no evidence in support of the correlation between increased chronic asbestos load of the lungs and the development of typical carcinoid tumors of the lung. However, this study included no controls. In a further German study, based on the examination of lung tissue from 108 patients with carcinoid tumors, the authors failed to demonstrate a higher incidence of carcinoid tumors in patients exposed to asbestos, since no higher incidence of carcinoid tumors (1.3 ) in the % population of the German mesothelioma register was observed, compared to the incidence in the population of all lung carcinomas (1 2 ) -% [START_REF] Neumann | Carcinoid tumours of the lung and definition of the medico-legal term lung cancer used in the list of occupational disease in " " Germany--results of the German Mesothelioma Register[END_REF].

One of our study s limitations is the low number of cases, which impacts its statistical power. This was due to the fact that pulmonary ' carcinoid tumors are rare. Furthermore, eligible cases recruited in this series were all consecutive cases undergoing surgery in 2 hospitals and living in the Paris region.

Our study s strengths include the analysis of asbestos exposure by a practitioner specialized in occupational diseases, which enabled us ' to quantify the probability of asbestos exposure and cumulative asbestos exposure for each subject included in the cohort, and the mineralogical analysis of dry lung samples, which enabled us to precisely quantify the retention of asbestos bodies of cases and controls.

CONCLUSION

This study argues in favor of a relationship between occupational asbestos exposure and certain pulmonary carcinoid tumors. These results prompt the continuation of research in this field, with the use of additional controls free of lung cancer, in order to confirm the observed trends. Since the distribution of histological types of lung cancer can reflect underlying biological mechanisms, these resultsshould they be formally established -may suggest the need to study the molecular pathways involved in lung cancer and asbestos exposure.

The subject of this paper has only very rarely been previously investigated in the literature; however, the study of a potential link between asbestos and pulmonary carcinoid tumors is of major interest, both from a scientific and medico-legal point of view, with regard to modalities concerning the potential compensation for associated cases of cancer. Furthermore, considering the results of our study, clinicians should pay particular attention to the need to systematically investigate for occupational asbestos exposure in subjects presenting with any histological type of lung cancer, including pulmonary carcinoid tumor, given the potential for individual compensation as an occupational disease.

Acknowledgements:

All of the authors of this article have made substantial contributions to its conception and design, to data acquisition, analysis and interpretation, and have drafted the article or critically revised it with regard to its important intellectual content and have approved the final version of the article for publication.

'é

  Paris Descartes , 20 rue Leblanc, Paris 75015, FR LEPI, Laboratoire d Etude des Particules Inhal es 7 Ville de Paris , 11 rue George Eastman 75013 Paris, FR Service d Anatomie et Cytologie Pathologique 8 ' H pital Bichat -Claude Bernard ô , Assistance publique -H pitaux de Paris (AP-HP) ô , Universit Paris VII -Paris Diderot é , 46 Rue Henri Huchard 75018 Paris, FR Service d Anatomie Pathologique Caen 9 ' [ ] CHU Caen , Avenue de la C te de Nacre -CS30001 -14033 Caen cedex 9, FR ô Service de Sant au Travail 10 é P le Sant Travail -M tropole Nord ô é é , 118 rue Solf rino -CS 71365 -59014 Lille Cedex, FR

Table 1

 1 Characteristics of cases and controls.

	Cases (Group 1)

%

SD: Standard deviation

Table 2

 2 Comparison between subject groups presenting either with typical pulmonary carcinoid tumor or atypical pulmonary carcinoid tumor. Analysis not available in 9 cases because of insufficient material

	Typical pulmonary carcinoid tumors	Atypical pulmonary carcinoid tumors	p-value a

current smokers: n ( ) -former smokers: n ( )

probable: n ( ) -null: n ( ) -Range min-maxi

Table 3

 3 Comparison of cases for demographic data, smoking and occupational exposure to asbestos, and controls.

	Group

1A Pulmonary carcinoid tumors aged over 40 years Group 2 Lung cancer controls p-value a

  Analysis not available in 7 cases because of insufficient material

	Number of subjects				28	56
	Gender
	-Male: n ( ) %				14 (50)	28 (50.0)	NS
	-Female: n ( ) %				14 (50)	28 (50.0)
	Mean age	(SD) (years)			56.6 (10.3)	57.1 (10.1)	NS
	Smoking status				NS
	-non-smokers: n ( ) %			9 (32.1)	8 (14.3)
			%			19 (67.9)	48 (85.7)
	Cumulated tobacco smoking in pack-years:	mean (SD)	28.2 (30.5)	43.2 (21.1)	<0.05
	Probability of asbestos exposure
	-definite: n ( ) %				7 (25.0)	8 (14.3)
		%				1 (3.6)	2 (3.6)	NS
		%				3 (10.7)	8 (14.3)
		%				17 (60.7)	38 (67.8)
	Cumulative exposure index to asbestos	(unit of exposure x years) in exposed subjects
	-Mean (SD)				3.5 (4.5)	0.3 (0.5)	<0.05
	-Median				2.28	0.22
		[	]			[0.01 14.25 -]	[0.13 2.18 -	]
	Mineralogical analysis b
	-1000 AB/g: n ( ) ≥ %			5 (23.8)	5 (8.9)	0.09
	-< 1000 AB/g: n ( ) %			16 (76.2)	51 (91.1)
	AB: Asbestos Bodies
	NS: Non Significant
	SD: Standard Deviation a : Chi-square or Fisher test b

former and current smokers: n ( )

probable: n ( ) -possible: n ( ) -null: n ( ) -Range min-maxi

8

The authors would like to thank C Aouicha, I Boussarsar, F Carnot, S Chamming s, Y Iwatsubo and M Maloisel, for their contribution to this ' study.

FUNDING

This study was supported by grants from the French Ministry of Labor and Social Relations (convention P53-C94) and the Ligue nationale contre le cancer (National league against cancer).

Footnotes:

CONFLICT OF INTEREST They authors declare that they have no competing interests, or other interests that might be perceived to influence the results and discussion reported in this paper.