Logistic regression to estimate the welfare of broiler breeders in relation to environmental and behavioral variables

The increasing demand of consumer markets for the welfare of birds in poultry house has motivated many scientific researches to monitor and classify the welfare according to the production environment. Given the complexity between the birds and the environment of the aviary, the correct interpretation of the conduct becomes an important way to estimate the welfare of these birds. This study obtained multiple logistic regression models with capacity of estimating the welfare of broiler breeders in relation to the environment of the aviaries and behaviors expressed by the birds. In the experiment, were observed several behaviors expressed by breeders housed in a climatic chamber under controlled temperatures and three different ammonia concentrations from the air monitored daily. From the analysis of the data it was obtained two logistic regression models, of which the first model uses a value of ammonia concentration measured by unit and the second model uses a binary value to classify the ammonia concentration that is assigned by a person through his olfactory perception. The analysis showed that both models classified the broiler breeder's welfare successfully.

The Power of Data - Advocating for Library by Showing Evidence of Impact

Markku Laitinen's keynote presentation in the QQML conference in Limerick, Ireland the 23rd of April, 2012.

Retrospective canine skin peripheral nerve sheath tumors data with emphasis on histologic, immunohistochemical and prognostic factors

Abstract: In this retrospective study was determined the frequency of canine skin peripheral nerve sheath tumors (PNST) in cases diagnosed by the Setor de Patologia Veterinária of the Universidade Federal do Rio Grande do Sul (SPV-UFRGS), Brazil, between the years 2000 and 2012. The canine profiles, as well as histological, immunohistochemical and prognostic aspects of the tumors were based on 70 samples, comprising 40 females, 29 males and one unspecified sample. Between 2000 and 2012, 2,984 skin tumors of dogs were diagnosed in the SPV-UFRGS, totaling 2.34% of skin neoplasms in dogs. Animals that comprised the largest amount of samples (43%) were those with no breed (SRD), followed by German Shepherds (10%). Females were more affected than males (40/70 - 57% and 29/70 - 41% respectively). Skin PNST of this research showed predominant localization on the limbs (40% in the forelimbs and 29% in the hindlimbs); affecting adult dogs, mostly aged between 8 and 11 years (54%). The samples were routinely processed for hematoxylin and eosin, and were also evaluated by toluidine blue and Masson's trichrome staining, and immunohistochemistry (IHC) anti-vimentin, -S-100, -GFAP, -actin, von Willebrand factor and neurofilament. Anisocytosis and anisokaryosis, mitotic index, intratumoral necrosis, invasion of adjacent tissues, tumor location, local recurrence and metastasis were related to the diagnosis of benign (49/70) or malignant tumor (21/70). The Antoni A histological pattern was observed more frequently in benign tumors. The immunohistochemistry helped to diagnose PNST, and anti-vimentin and anti-protein S-100 showed the highest rates of immunostaining. Throughout statistical analysis of animals with tumor recurrence, it was found that the chance of an animal with a malignant peripheral nerve sheath tumor to develop recurrence is 4.61 times higher than in an animal that had a benign tumor.

GIS assessing traditional and modern agricultural land use/land cover change. A case study 1959-2005: Rekijoki, Somero, SW-Finland

Finland’s rural landscape has gone through remarkable changes from the 1950’s, due to agricultural developments. Changed farming practices have influenced especially traditional landscape management, and modifications in the arable land structure and grasslands transitions are notable. The review of the previous studies reveal the importance of the rural landscape composition and structure to species and landscape diversity, whereas including the relevance in presence of the open ditches, size of the field and meadow patches, topology of the natural and agricultural landscape. This land-change study includes applying remote sensed data from two time series and empirical geospatial analysis in Geographic Information Systems (GIS). The aims of this retrospective research is to detect agricultural landscape use and land cover change (LULCC) dynamics and discuss the consequences of agricultural intensification to landscape structure covering from the aspects of landscape ecology. Measurements of LULC are derived directly from pre-processed aerial images by a variety of analytical procedures, including statistical methods and image interpretation. The methodological challenges are confronted in the process of landscape classification and combining change detection approaches with landscape indices. Particular importance is paid on detecting agricultural landscape features at a small scale, demanding comprehensive understanding of such agroecosystems. Topological properties of the classified arable land and valley are determined in order to provide insight and emphasize the aspect the field edges in the agricultural landscape as important habitat. Change detection dynamics are presented with change matrix and additional calculations of gain, loss, swap, net change, change rate and tendencies are made. Transition’s possibility is computed following Markov’s probability model and presented with matrix, as well. Thesis’s spatial aspect is revealed with illustrative maps providing knowledge of location of the classified landscape categories and location of the dynamics of the changes occurred. It was assured that in Rekijoki valley’s landscape, remarkable changes in landscape has occurred. Landscape diversity has been strongly influenced by modern agricultural landscape change, as NP of open ditches has decreased and the MPS of the arable plot has decreased. Overall change in the diversity of the landscape is determined with the decrease of SHDI. Valley landscape considered as traditional land use area has experienced major transitional changes, as meadows class has lost almost one third of the area due to afforestation. Also, remarkable transitions have occurred from forest to meadow and arable land to built area. Boundaries measurement between modern and traditional landscape has indicated noticeable proportional increase in arable land-forest edge type and decrease in arable land-meadow edge type. Probability calculations predict higher future changes for traditional landscape, but also for arable land turning into built area.

The Effects of the Breast Cancer Mammography Screening Programme in Women aged 40 to 84 years in Turku, Finland (1987-2009)

The objective of this thesis was to evaluate whether a more extensive mammography screening programme (TurkuMSP) conducted by the city of Turku, had an effect on breast cancer (BC) incidence, survival, or mortality in years 1987 to 2009. Despite the fact that some studies have suggested a 20 percent reduction in BC mortality due to mammography screening, there are findings of harm to subjects, which are claimed to negate the benefits of screening. Thus, the aims of this study are most pertinent. A total of 176 908 screening examinations were performed in 36 000 women aged 40−74 during the years 1987−1997. In all, 685 primary BCs were found in the screened women, either screen-detected (n=531) or during screening intervals (n=154). Survival and BC recurrence rate of women with screen-detected BC was compared to 184 women with clinical BCs detected among individuals who did not take part in the screening. The invitation interval, which may influence the outcome, was studied in the age group 40 to 49 by inviting those born in even calendar years annually for mammography screening and those born in odd years, triennially. In addition, BC incidence and mortality in the total female population of Turku aged 40 to 84 years was compared with the respective figures of Helsinki and the rest of Finland, both during the pre-screening era (1976-1986) and the screening era (1987-2009). The study was designed to compare women by age groups, because women aged 50 to 59 were generally screened in all of Finland, whereas only in Turku women aged 40 to 49 and 60 to 74 were screened in addition. Data regarding cancer recurrence were derived from the Finnish Cancer Registry and data on deaths were collected from Statistics Finland. In survival analyses, screened women with invasive BC had a significantly higher survival rate than the women with clinical BC. The survival benefit started to appear already during the first follow-up years and was evident in all age groups. A marginal survival extension was also seen in screened women when BC had spread to ipsilateral axillary nodes already at diagnosis. Recurrence-free survival rate after BC treatment was significantly more favorable among the screened women compared with women with BC found clinically. The screening invitation interval did not significantly influence BC mortality in the subset of women aged 40 to 49 years. There were no consistent differences in the changes of BC incidence between Turku and the comparison areas during the screening era. In Turku, the BC mortality incidence in women aged 55−69 years was significantly lower during the screening era (from 1987 to 1997) compared with the pre-screening era, whereas no such change was found in the city of Helsinki or Tampere. When comparing the changes in incidence-based BC mortality during years 1987 to 2009 in Turku to those of Helsinki and the rest of Finland, there was a suggestion of more than 20 percent lower mortality in Turku among oldest age group (75-84 years) compared with the reference residential areas, but the differences were not consistently significant. Interpretation of the study results should be made with caution because there were no random control groups, and on the other hand, the number of cases in subgroups was fairly low to yield definite conclusions. Also due to the many statistical analyses, some of the findings may be due to chance. The results are, however, suggestive for a decrease of BC mortality in the elderly age groups due to wide mammography screening. This finding needs confirmation in further studies before recommending an expansion of mammography screening to women up to the age of 74 years

Normative data for the Brazilian population in the Boston Diagnostic Aphasia Examination: influence of schooling

In Neurolinguistics, the use of diagnostic tests developed in other countries can create difficulties in the interpretation of results due to cultural, demographic and linguistic differences. In a country such as Brazil, with great social contrasts, schooling exerts a powerful influence on the abilities of normal individuals. The objective of the present study was to identify the influence of schooling on the performance of normal Brazilian individuals in the Boston Diagnostic Aphasia Examination (BDAE), in order to obtain reference values for the Brazilian population. We studied 107 normal subjects ranging in age from 15 to 84 years (mean ± SD = 47.2 ± 17.6 years), with educational level ranging from 1 to 24 years (9.9 ± 4.8 years). Subjects were compared for scores obtained in the 28 subtests of the BDAE after being divided into groups according to age (15 to 30, N = 24, 31 to 50, N = 33 and 51 years or more, N = 50) and education (1 to 4, N = 26, 5 to 8, N = 17 and 9 years or more, N = 61). Subjects with 4 years or less of education performed poorer in Word Discrimination, Visual Confrontation Naming, Reading of Sentences and Paragraphs, and Primer-Level Dictation (P < 0.05). When breakdown by schooling was 8 years or less, subjects performed poorer in all subtests (P < 0.05), except Responsive Naming, Word Recognition and Word-Picture Matching. The elderly performed poorer (P < 0.05) in Complex Ideational Material, Visual Confrontation Naming, Comprehension of Oral Spelling, Written Confrontation Naming, and Sentences to Dictation. We present the reference values for the cut-off scores according to educational level.

The effect of performing corrections on reported uterine cancer mortality data in the city of São Paulo

Reports of uterine cancer deaths that do not specify the subsite of the tumor threaten the quality of the epidemiologic appraisal of corpus and cervix uteri cancer mortality. The present study assessed the impact of correcting the estimated corpus and cervix uteri cancer mortality in the city of São Paulo, Brazil. The epidemiologic assessment of death rates comprised the estimation of magnitudes, trends (1980-2003), and area-level distribution based on three strategies: i) using uncorrected death certificate information; ii) correcting estimates of corpus and cervix uteri mortality by fully reallocating unspecified deaths to either one of these categories, and iii) partially correcting specified estimates by maintaining as unspecified a fraction of deaths certified as due to cancer of "uterus not otherwise specified". The proportion of uterine cancer deaths without subsite specification decreased from 42.9% in 1984 to 20.8% in 2003. Partial and full corrections resulted in considerable increases of cervix (31.3 and 48.8%, respectively) and corpus uteri (34.4 and 55.2%) cancer mortality. Partial correction did not change trends for subsite-specific uterine cancer mortality, whereas full correction did, thus representing an early indication of decrease for cervical neoplasms and stability for tumors of the corpus uteri in this population. Ecologic correlations between mortality and socioeconomic indices were unchanged for both strategies of correcting estimates. Reallocating unspecified uterine cancer mortality in contexts with a high proportion of these deaths has a considerable impact on the epidemiologic profile of mortality and provides more reliable estimates of cervix and corpus uteri cancer death rates and trends.

Manual and semi-automatic quantification of in vivo ¹H-MRS data for the classification of human primary brain tumors

In vivo proton magnetic resonance spectroscopy (¹H-MRS) is a technique capable of assessing biochemical content and pathways in normal and pathological tissue. In the brain, ¹H-MRS complements the information given by magnetic resonance images. The main goal of the present study was to assess the accuracy of ¹H-MRS for the classification of brain tumors in a pilot study comparing results obtained by manual and semi-automatic quantification of metabolites. In vivo single-voxel ¹H-MRS was performed in 24 control subjects and 26 patients with brain neoplasms that included meningiomas, high-grade neuroglial tumors and pilocytic astrocytomas. Seven metabolite groups (lactate, lipids, N-acetyl-aspartate, glutamate and glutamine group, total creatine, total choline, myo-inositol) were evaluated in all spectra by two methods: a manual one consisting of integration of manually defined peak areas, and the advanced method for accurate, robust and efficient spectral fitting (AMARES), a semi-automatic quantification method implemented in the jMRUI software. Statistical methods included discriminant analysis and the leave-one-out cross-validation method. Both manual and semi-automatic analyses detected differences in metabolite content between tumor groups and controls (P < 0.005). The classification accuracy obtained with the manual method was 75% for high-grade neuroglial tumors, 55% for meningiomas and 56% for pilocytic astrocytomas, while for the semi-automatic method it was 78, 70, and 98%, respectively. Both methods classified all control subjects correctly. The study demonstrated that ¹H-MRS accurately differentiated normal from tumoral brain tissue and confirmed the superiority of the semi-automatic quantification method.

STATISTICAL ANALYSYS OF THE SCFE OF A BRAZILAN MINERAL COAL

The influence of some process variables on the productivity of the fractions (liquid yield times fraction percent) obtained from SCFE of a Brazilian mineral coal using isopropanol and ethanol as primary solvents is analyzed using statistical techniques. A full factorial 23 experimental design was adopted to investigate the effects of process variables (temperature, pressure and cosolvent concentration) on the extraction products. The extracts were analyzed by the Preparative Liquid Chromatography-8 fractions method (PLC-8), a reliable, non destructive solvent fractionation method, especially developed for coal-derived liquids. Empirical statistical modeling was carried out in order to reproduce the experimental data. Correlations obtained were always greater than 0.98. Four specific process criteria were used to allow process optimization. Results obtained show that it is not possible to maximize both extract productivity and purity (through the minimization of heavy fraction content) simultaneously by manipulating the mentioned process variables.

Maanpuolustustahto asevelvollisen koulutuksen ja palveluksen onnistumista selittävänä tekijänä

Lähtökohta tälle tutkimukselle oli havainto siitä, että varusmiehillä maanpuolustustahto ja taisteluluottamus korreloivat. Tämä huomio oli mahdollista tehdä aikaisemmissa varusmiesaineistoilla tehdyissä tutkimuksissa, joissa olin ollut mukana. Tutkimuksen aineistoina olivat useat puolustusvoimissa kerätyt varusmiesten kyselytutkimusaineistot. Vertailuaineistoina käytin reserviläisille kertausharjoituksissa tehtyjen kyselyiden aineistoja. Olennaista oli selvittää, säilyikö havaittu riippuvuus kun muita mahdollisia tekijöitä otettiin huomioon. Tutkimus oli aikaisemmin kerättyjen aineistojen sekundaarianalyysi ja tutkijana en ollut voinut vaikuttaa kyselyjen sisältöön tai käytettyjen muuttujien ja mittareiden valintaan. Aineistot on kerätty kuvaileviin tarkoituksiin ja tästä syystä tämä tutkimus oli tilastollisesti kuvaileva. Keskeiset käytetyt aineistot olivat varusmiesten kotiuttamiskyselyiden eli loppukyselyiden aineistot kaikista varuskunnista vuosilta 2000 – 2008 sekä vuonna 2010 Siilasmaan työryhmää varten kerätty aineisto kolmesta varuskunnasta. Vuoden 2010 varusmiestutkimus oli toteutettu siten, että kysely tehtiin sekä palveluksen alussa että lopussa. Tässä aineistossa käytettiin monipuolisesti varusmiesten psykososiaalisen toimintakyvyn erilaisia mittareita. Maanpuolustustahto on käsitteellisesti laaja kokonaisuus, kuitenkin tässä tutkimuksessa se oli operationalisoitava käytettävissä olleiden osioiden avulla. Maanpuolustustahtoa tarkasteltiin sekä henkilökohtaisena että yleisenä maanpuolustustahtona sekä niiden yhdistelmänä, josta käytettiin myös nimitystä maanpuolustusajattelu. Käsitteellisesti suppeampi taisteluluottamus operationalisoitiin siten, että muuttujana se kuvasi varusmiehen luottamusta aseisiinsa, saamaansa koulutukseen sekä lähiryhmäänsä. Taisteluluottamuksen mittaamisen taustalla oli ajatus siitä, että tämän yksilökohtaisen mittarin keskiarvo on joukon koulutuksen onnistuneisuuden estimaatti. Taisteluluottamus oli tutkimuksessa varsinainen tulosmuuttuja. Tulosten perusteella yksittäisten varusmiesten psykososiaalisessa toimintakyvyssä on eroja. Erityisesti erottui yksittäisenä tekijänä sosiaalisuus, joka summamuuttujana oli muodostettu varusmiestutkimus 2010:n aineistossa Maanpuolustuskorkeakoulun Käyttäytymistieteen laitoksen laatimista osioista. Sosiaalisuus ennusti voimakkaasti varusmiehen etenemistä koulutuksessa aina johtajakoulutukseen saakka. Sosiaalisuuden kontrollointi tilastollisesti ei poistanut maanpuolustusajattelun ja taisteluluottamuksen välistä riippuvuutta. Varusmiestutkimus 2010 aineistossa oli mahdollista tarkastella maanpuolustusajattelun muutosta palvelusaikana ja muutoksen yhteyttä psykososiaalisen toimintakyvyn kuvaajiin. Stressaantumistaipumus ja neuroottisuus olivat yhteydessä maanpuolustustahdon laskuun. Tunteiden hallinnan kyky tuki varusmiehen maanpuolustustahdon ja taisteluluottamuksen kehittymistä. Tilastollinen kuvaus toteutettiin Mplus-ohjelmistolla lasketulla rakenneyhtälömallilla. Aineistoon sopiva malli oli mahdollista löytää. Mallin mukaan sosiaalinen pääoman yksilökohtaisena resurssina antaa mahdollisuuden kehittää ja säilyttää maanpuolustusajattelua, joka on yhteydessä itseluottamuksen luontoiseen taisteluluottamukseen varusmieskoulutuksen päättyessä. Koulutuksen aikana joukkoon kehittynyt kiinteys ja luottamus tukevat tätä kehitystä. Joukkotuotantomallilla saadaan aikaan joukkoja, joissa taisteluluottamus on yleensä tarvittavalla tasolla ja niitä voidaan käyttää osoitettuihin tehtäviin. Kertausharjoitukset ylläpitävät kiinteyttä, taisteluluottamusta ja sitä kautta joukon suorituskykyä. Tutkimuksessa havaittiin myös, että pysyvissä miehistön ryhmissä, joissa ryhmänjohtaja ja/tai jäseniä ei vaihtunut, koulutuksen tulokset olivat parempia kuin muuttuneissa ryhmissä. Edelleen havaittiin, että 12 kuukautta palvelleiden miehistön jäsenten joukossa palvelusmotivaatio laski enemmän kuin muissa varusmiesryhmissä. Yhdestätoista koulutuksen ja tutkimuksen asiantuntijasta koottu ryhmä arvioi tutkimuksen tuloksia sovelletulla Q-menetelmällä Facilitate Pro -ohjelmistoa käyttäen. Menettely tuotti lisänäkökohtia tulosten arviointiin sekä niiden soveltamiseen.

Comparison of baseline data between chronic kidney disease patients starting hemodialysis who live near and far from the dialysis center

Introduction: The treatment offered to chronic kidney disease (CKD) patients before starting hemodialysis (HD) impacts prognosis. Objective: We seek differences among incident HD patients according to the distance between home and the dialysis center. Methods: We included 179 CKD patients undergoing HD. Patients were stratified in two groups: "living near the dialysis center" (patients whose hometown was in cities up to 100 km from the dialysis center) or as "living far from the dialysis center" (patients whose hometown was more than 100 km from the dialysis center). Socioeconomic status, laboratory results, awareness of CKD before starting HD, consultation with nephrologist before the first HD session, and type of vascular access when starting HD were compared between the two groups. Comparisons of continuous and categorical variables were performed using Student's t-test and the Chi-square test, respectively. Results: Ninety (50.3%) patients were classified as "living near the dialysis center" and 89 (49.7%) as "living far from the dialysis center". Patients living near the dialysis center were more likely to know about their condition of CKD than those living far from the dialysis center, respectively 46.6% versus 28.0% (p = 0.015). Although without statistical significance, patients living near the dialysis center had more frequent previous consultation with nephrologists (55.5% versus 42.6%; p = 0.116) and first HD by fistula (30.0% versus 19.1%; p = 0.128) than those living far from the dialysis center. Conclusion: There are potential advantages of CKD awareness, referral to nephrologists and starting HD through fistula among patients living near the dialysis center.

Utilization of Statistical Methods for Management in the Forest Industry

The strongest wish of the customer concerning chemical pulp features is consistent, uniform quality. Variation may be controlled and reduced by using statistical methods. However, studies addressing the application and benefits of statistical methods in forest product sector are scarce. Thus, the customer wish is the root cause of the motivation behind this dissertation. The research problem addressed by this dissertation is that companies in the chemical forest product sector require new knowledge for improving their utilization of statistical methods. To gain this new knowledge, the research problem is studied from five complementary viewpoints – challenges and success factors, organizational learning, problem solving, economic benefit, and statistical methods as management tools. The five research questions generated on the basis of these viewpoints are answered in four research papers, which are case studies based on empirical data collection. This research as a whole complements the literature dealing with the use of statistical methods in the forest products industry. Practical examples of the application of statistical process control, case-based reasoning, the cross-industry standard process for data mining, and performance measurement methods in the context of chemical forest products manufacturing are brought to the public knowledge of the scientific community. The benefit of the application of these methods is estimated or demonstrated. The purpose of this dissertation is to find pragmatic ideas for companies in the chemical forest product sector in order for them to improve their utilization of statistical methods. The main practical implications of this doctoral dissertation can be summarized in four points: 1. It is beneficial to reduce variation in chemical forest product manufacturing processes 2. Statistical tools can be used to reduce this variation 3. Problem-solving in chemical forest product manufacturing processes can be intensified through the use of statistical methods 4. There are certain success factors and challenges that need to be addressed when implementing statistical methods

Modelling ecological values in heterogeneous and dynamic landscapes with geospatial data

Our surrounding landscape is in a constantly dynamic state, but recently the rate of changes and their effects on the environment have considerably increased. In terms of the impact on nature, this development has not been entirely positive, but has rather caused a decline in valuable species, habitats, and general biodiversity. Regardless of recognizing the problem and its high importance, plans and actions of how to stop the detrimental development are largely lacking. This partly originates from a lack of genuine will, but is also due to difficulties in detecting many valuable landscape components and their consequent neglect. To support knowledge extraction, various digital environmental data sources may be of substantial help, but only if all the relevant background factors are known and the data is processed in a suitable way. This dissertation concentrates on detecting ecologically valuable landscape components by using geospatial data sources, and applies this knowledge to support spatial planning and management activities. In other words, the focus is on observing regionally valuable species, habitats, and biotopes with GIS and remote sensing data, using suitable methods for their analysis. Primary emphasis is given to the hemiboreal vegetation zone and the drastic decline in its semi-natural grasslands, which were created by a long trajectory of traditional grazing and management activities. However, the applied perspective is largely methodological, and allows for the application of the obtained results in various contexts. Models based on statistical dependencies and correlations of multiple variables, which are able to extract desired properties from a large mass of initial data, are emphasized in the dissertation. In addition, the papers included combine several data sets from different sources and dates together, with the aim of detecting a wider range of environmental characteristics, as well as pointing out their temporal dynamics. The results of the dissertation emphasise the multidimensionality and dynamics of landscapes, which need to be understood in order to be able to recognise their ecologically valuable components. This not only requires knowledge about the emergence of these components and an understanding of the used data, but also the need to focus the observations on minute details that are able to indicate the existence of fragmented and partly overlapping landscape targets. In addition, this pinpoints the fact that most of the existing classifications are too generalised as such to provide all the required details, but they can be utilized at various steps along a longer processing chain. The dissertation also emphases the importance of landscape history as an important factor, which both creates and preserves ecological values, and which sets an essential standpoint for understanding the present landscape characteristics. The obtained results are significant both in terms of preserving semi-natural grasslands, as well as general methodological development, giving support to science-based framework in order to evaluate ecological values and guide spatial planning.

Lung cancer risk associated with occupational exposure to nickel, chromium VI, and cadmium in two population-based case-control studies in Montreal.

Cancer du poumon associé à l’exposition au nickel, au chrome VI et au cadmium dans le milieu de travail utilisant deux études populationnelles cas-témoins à Montréal. Au début des années 1990, le nickel, le chrome VI et le cadmium ont été classés en tant qu’agents cancérigènes de classe 1 par le CIRC (Centre International de Recherche sur le Cancer). Cependant, les résultats des études ayant permis la classification de ces métaux n’ont pas toujours été reproduits, et d’importantes questions demeurent quant aux effets de ces métaux à de faibles niveaux d’exposition. Un plus grand nombre de recherches empiriques est donc nécessaire afin de réaffirmer la cancérogénicité de ces agents, et d’identifier les circonstances dans lesquelles ils peuvent être néfastes. L'objectif de cette étude était d'explorer la relation entre l’exposition à un des métaux (soit le nickel, le chrome VI, ou le cadmium) et les risques subséquents de développer un cancer du poumon chez des travailleurs provenant de différents milieux de travail qui sont exposés à ces métaux à de différents degrés. Deux études cas-témoins de base populationnelle menées à Montréal ont fourni les données nécessaires pour examiner la cancérogénicité de ces métaux. La première étude était menée entre 1979 et 1986 chez des hommes âgés de 35 à 70 ans ayant un cancer dans l’un de 19 sites anatomiques de cancer sélectionnés. La seconde étude était menée entre 1996 et 2001 chez des hommes et des femmes âgés de 35 à 75 ans, avec un diagnostic de tumeur maligne au poumon. Dans ces deux études, les cas ont été recensés dans tous les hôpitaux de l'île de Montréal, tandis que les contrôles populationnels appariés par âge et stratifiés par sexe, ont été sélectionnés des listes électorales. Une entrevue avec chaque sujet a permis d'obtenir un historique d'emploi détaillé ainsi que des informations précises sur les facteurs de risques socio-économiques et personnels. Les descriptions de poste ont été évaluées par une équipe d'experts chimistes et hygiénistes afin de déterminer si le sujet a été exposé à chaque agent, et pour mesurer à la fois la concentration et la durée de chaque exposition, ainsi que l’exposition cumulative tout au long de la vie de chaque participant. Pour déterminer si une exposition à l’un des trois métaux en cause était associée à une augmentation de l'incidence du cancer du poumon, des données ont été analysées par régression logistique : des ajustements ont été effectués pour des facteurs de confusion pertinents incluant un historique détaillé du tabagisme. Des mesures catégoriques d'exposition cumulée ont été également analysées, ainsi que la modification des effets par le tabagisme. Les deux études ont été analysées séparément, puis par la suite combinées afin d'augmenter la puissance statistique. Les niveaux d'exposition mesurés dans cette population ne semblaient pas poser un excès de risque de cancer du poumon pour les travailleurs exposés au chrome VI. Cependant, ceux qui ont été exposés au nickel ont subi une augmentation significative du risque, et ce, quel que soit leur niveau d'exposition. Le risque de développer un cancer du poumon suite à une exposition au cadmium était élevé, mais pas de manière significative. Pour chacun des trois métaux, le risque de cancer du poumon était très élevé parmi les non-fumeurs, mais pas parmi les fumeurs. L’effet combiné du tabagisme et de l’exposition aux métaux était compatible avec un excès de risque additif. Cependant, les intervalles de confiance dans cette étude tendaient à être larges, et une faiblesse de puissance statistique peut limiter l’interprétation de certains résultats. Cette étude est unique dans la mesure où elle a fourni des preuves empiriques sur les risques de développer le cancer du poumon liés aux faibles niveaux d’exposition au nickel, au chrome VI, ou au cadmium provenant de divers contextes de travail. Dans la plupart des autres études, la majorité des expositions pertinentes n’ont pas été bien contrôlées. À l'inverse, cette étude a bénéficié de la collecte et de la disponibilité d'information détaillée concernant le tabagisme et d’autres facteurs de risque. Les résultats de cette étude ont d'importantes conséquences pour la santé publique, tant au niveau de la détermination des risques pour les travailleurs actuellement exposés à ces métaux, qu'au niveau de l’évaluation des risques pour la population en général, elle-même exposée à ces métaux par le biais de la pollution et de la fumée de cigarette. Cette analyse contribuera fort probablement à une réévaluation par le CIRC de la cancérogénicité de ces métaux. L'exploration de la relation entre les risques de cancer du poumon et l'exposition au nickel, au chrome VI et au cadmium est donc opportune et pertinente.

New statistical methods to assess the effect of time-dependent exposures in case-control studies

Contexte. Les études cas-témoins sont très fréquemment utilisées par les épidémiologistes pour évaluer l’impact de certaines expositions sur une maladie particulière. Ces expositions peuvent être représentées par plusieurs variables dépendant du temps, et de nouvelles méthodes sont nécessaires pour estimer de manière précise leurs effets. En effet, la régression logistique qui est la méthode conventionnelle pour analyser les données cas-témoins ne tient pas directement compte des changements de valeurs des covariables au cours du temps. Par opposition, les méthodes d’analyse des données de survie telles que le modèle de Cox à risques instantanés proportionnels peuvent directement incorporer des covariables dépendant du temps représentant les histoires individuelles d’exposition. Cependant, cela nécessite de manipuler les ensembles de sujets à risque avec précaution à cause du sur-échantillonnage des cas, en comparaison avec les témoins, dans les études cas-témoins. Comme montré dans une étude de simulation précédente, la définition optimale des ensembles de sujets à risque pour l’analyse des données cas-témoins reste encore à être élucidée, et à être étudiée dans le cas des variables dépendant du temps. Objectif: L’objectif général est de proposer et d’étudier de nouvelles versions du modèle de Cox pour estimer l’impact d’expositions variant dans le temps dans les études cas-témoins, et de les appliquer à des données réelles cas-témoins sur le cancer du poumon et le tabac. Méthodes. J’ai identifié de nouvelles définitions d’ensemble de sujets à risque, potentiellement optimales (le Weighted Cox model and le Simple weighted Cox model), dans lesquelles différentes pondérations ont été affectées aux cas et aux témoins, afin de refléter les proportions de cas et de non cas dans la population source. Les propriétés des estimateurs des effets d’exposition ont été étudiées par simulation. Différents aspects d’exposition ont été générés (intensité, durée, valeur cumulée d’exposition). Les données cas-témoins générées ont été ensuite analysées avec différentes versions du modèle de Cox, incluant les définitions anciennes et nouvelles des ensembles de sujets à risque, ainsi qu’avec la régression logistique conventionnelle, à des fins de comparaison. Les différents modèles de régression ont ensuite été appliqués sur des données réelles cas-témoins sur le cancer du poumon. Les estimations des effets de différentes variables de tabac, obtenues avec les différentes méthodes, ont été comparées entre elles, et comparées aux résultats des simulations. Résultats. Les résultats des simulations montrent que les estimations des nouveaux modèles de Cox pondérés proposés, surtout celles du Weighted Cox model, sont bien moins biaisées que les estimations des modèles de Cox existants qui incluent ou excluent simplement les futurs cas de chaque ensemble de sujets à risque. De plus, les estimations du Weighted Cox model étaient légèrement, mais systématiquement, moins biaisées que celles de la régression logistique. L’application aux données réelles montre de plus grandes différences entre les estimations de la régression logistique et des modèles de Cox pondérés, pour quelques variables de tabac dépendant du temps. Conclusions. Les résultats suggèrent que le nouveau modèle de Cox pondéré propose pourrait être une alternative intéressante au modèle de régression logistique, pour estimer les effets d’expositions dépendant du temps dans les études cas-témoins