Weakly Supervised Learning using Attention gates for colon cancer histopathological image segmentation.

Recently, Artificial Intelligence namely Deep Learning methods have revolutionized a wide range of domains and applications. Besides, Digital Pathology has so far played a major role in the diagnosis and the prognosis of tumors. However, the characteristics of the Whole Slide Images namely the gigapixel size, high resolution and the shortage of richly labeled samples have hindered the efficiency of classical Machine Learning methods. That goes without saying that traditional methods are poor in generalization to different tasks and data contents. Regarding the success of Deep learning when dealing with Large Scale applications, we have resorted to the use of such models for histopathological image segmentation tasks. First, we review and compare the classical UNet and Att-UNet models for colon cancer WSI segmentation in a sparsely annotated data scenario. Then, we introduce novel enhanced models of the Att-UNet where different schemes are proposed for the skip connections and spatial attention gates positions in the network. In fact, spatial attention gates assist the training process and enable the model to avoid irrelevant feature learning. Alternating the presence of such modules namely in our Alter-AttUNet model adds robustness and ensures better image segmentation results. In order to cope with the lack of richly annotated data in our AiCOLO colon cancer dataset, we suggest the use of a multi-step training strategy that also deals with the WSI sparse annotations and unbalanced class issues. All proposed methods outperform state-of-the-art approaches but Alter-AttUNet generates the best compromise between accurate results and light network. The model achieves 95.88% accuracy with our sparse AiCOLO colon cancer datasets. Finally, to evaluate and validate our proposed architectures we resort to publicly available WSI data: the NCT-CRC-HE-100K, the CRC-5000 and the Warwick colon cancer histopathological dataset. Respective accuracies of 99.65%, 99.73% and 79.03% were reached. A comparison with state-of-art approaches is established to view and compare the key solutions for histopathological image segmentation.

Deep learning for colon cancer histopathological images analysis.

Nowadays, digital pathology plays a major role in the diagnosis and prognosis of tumours. Unfortunately, existing methods remain limited when faced with the high resolution and size of Whole Slide Images (WSIs) coupled with the lack of richly annotated datasets. Regarding the ability of the Deep Learning (DL) methods to cope with the large scale applications, such models seem like an appealing solution for tissue classification and segmentation in histopathological images. This paper focuses on the use of DL architectures to classify and highlight colon cancer regions in a sparsely annotated histopathological data context. First, we review and compare state-of-the-art Convolutional Neural networks (CNN) including the AlexNet, vgg, ResNet, DenseNet and Inception models. To cope with the shortage of rich WSI datasets, we have resorted to the use of transfer learning techniques. This strategy comes with the hallmark of relying on a large size computer vision dataset (ImageNet) to train the network and generate a rich collection of learnt features. The testing and evaluation of such models on our AiCOLO colon cancer dataset ensure accurate patch-level classification results reaching up to 96.98% accuracy rate with ResNet. The CNN models have also been tested and evaluated with the CRC-5000, nct-crc-he-100k and merged datasets. ResNet respectively achieves 96.77%, 99.76% and 99.98% for the three publicly available datasets. Then, we present a pixel-wise segmentation strategy for colon cancer WSIs through the use of both UNet and SegNet models. We introduce a multi-step training strategy as a remedy for the sparse annotation of histopathological images. UNet and SegNet are used and tested in different training scenarios including data augmentation and transfer learning and ensure up to 76.18% and 81.22% accuracy rates. Besides, we test our training strategy and models on the CRC-5000, nct-crc-he-100k and Warwick datasets. Respective accuracy rates of 98.66%, 99.12% and 78.39% were achieved by SegNet. Finally, we analyze the existing models to discover the most suitable network and the most effective training strategy for our colon tumour segmentation case study.1.

Congenital anomalies in Tunisia: Frequency and risk factors.

BACKGROUND: Despite the high risk of recurrence of congenital malformations, there are no well-accepted preventive measures in developing countries like Tunisia. It is recommended that thorough epidemiological studies of congenital anomalies in this country are needed. The aim of this study is to assess the frequency and types of congenital anomalies in Tunisia and research some risk factors associated with occurrence of these anomalies. METHODS: In this retrospective study, all the fetuses who were autopsied during 21years period from February 1991 to December 2011 (n=9678) at Service of embryofetopathology in the Center of Maternity and Neonatology of Tunis (CMNT) were studied. The classification of malformations was based upon the anatomical system affected. The differences in fetal/maternal characteristics between cases with or without congenital malformations were assessed using Chi2 test. RESULTS: Of the all 9678 autopsied fetuses, 4498 (46.47%) were diagnosed as being malformed fetuses. Anomalies of limbs (22.71%) and digestive and abdominal wall defects (14.76%) were mostly detected, followed by congenital brain defects (13.41%) and nephrourologic abnormalities (11.23%). A marked association of parental consanguinity with increased congenital anomalies rates was found (P<10-6, OR=1.89, CI=1.69-2.13). CONCLUSION: In Tunisia, surveillance and epidemiological evaluation of congenital anomalies underline the high frequency of these events. This will help to better target congenital anomalies prevention and screening policies in our population.

[Cigarette smoking initiation among Tunisian adolescents: Risk and protective factors]. / Les facteurs de risque et de protection de l'initiation à la cigarette chez les adolescents tunisiens.

BACKGROUND: Since smoking is a major public health problem among Tunisian teenagers, it is important to identify the underlying risk and protective factors associated with initiation of this behavior. METHODS: A cross-sectional, school-based survey of students was conducted by the Tunisian Ministry of Health among a nationally representative sample of 4172 adolescents aged between 12 and 20 years attending public, private, and professional secondary schools across Tunisia who participated in the Survey of the Health of Tunisian adolescents in 2000. For data analysis, we first calculated crude odds ratios (OR) followed by calculating adjusted OR after using multivariate logistic regression models. RESULTS: Almost one-third of respondents had already started smoking at an average age of 13 years, 6.4% among them smoked daily. Demographic vulnerabilities to smoking behavior were gender (boys more than girls), age and residence in urban areas and particularly in Greater Tunis and the North East. Familial and school factors were parental divorce, poor relationship with parents, poor integration into the peer group, and poor school investment. Psychological and behavioral factors were low self-esteem level and the occurrence of stressful life events, risk taking and alcohol consumption when there was no association with the depression, anxiety and body image. Protective factors against the experimental cigarettes were mainly sports and reading. CONCLUSION: There are many factors associated with smoking behavior among adolescents. All of these predictors need to be considered in smoking prevention among Tunisian teenagers.

Spatial Resolution Improvement of EEG Source Reconstruction Using swLORETA.

Electroencephalography (EEG) and magnetic resonance imaging (MRI) are noninvasive neuro-imaging modalities largely used in neurology explorations. MRI is considered as a static modality and could be so important for anatomy by its high spatial resolution. EEG, on the other hand, is an important tool permitting to image temporal dynamic activities of the human brain. Fusion of these two essential modalities would be hence a so emerging research domain targeting to explore brain activities with the MRI static modality. Our present research investigates a sophisticated approach for localization of the cerebral activity that could be involved by the dynamic EEG modality and carefully illustrated within MRI static modality. Such careful cerebral activity localization would be first based on an advanced methodology yielding therefore a singular value decomposition-based lead field weighting to sLORETA method formalism, for solving in fact the inverse problem in the EEG. The conceived method for source localization, carried out on different cases of simulated dipoles experiments, showed satisfactory results. Different cases of simulated dipoles experiments and metrics were used to confirm the reliability of the proposed method. The experimental results confirm that our method presents a flexible and robust tool for EEG source imaging.

Breast Cancer Ultrasound Images' Sequence Exploration Using BI-RADS Features' Extraction: Towards an Advanced Clinical Aided Tool for Precise Lesion Characterization.

This research concerned a clinical need for precise breast cancer lesion characterization imaged by ultrasound sequences. Using therefore BI-RADS features that would be carefully extracted, the purpose of this study could be mainly to prove and to demonstrate the possibility of surveying precisely the changing characteristics of a breast cancer lesion within a considered ultrasound images' sequence. This was in fact a clinical need of a computer aided diagnosis (CAD) system permitting flexible and convivial clinical analysis of multi-slices' ultrasound breast cancer lesion with greater precision. The obtained results of our images' sequence breast cancer ultrasound analysis had shown the lesion form changing depending on the treated slice, as well as the values' differences for the morphological and the textural features. This would allow extracting more information about breast cancer lesions helping then radiologist to converge more rapidly and with a certain reinforced precision to the accurate clinical action to conduct. Such results would be reassembled and rearranged for constituting one computer aided diagnosis (CAD) system that could be provided for clinical explorations permitting on the other hand to avoid possible confusion between benign and malignant masses.

[Reasons for using emergency departments of major hospitals in Greater Tunis]. / Motifs du recours aux services d'urgence des principaux hôpitaux du Grand Tunis.

Tunisia, similar to many countries, has a problem of overcrowding of the emergency departments (ED). This study aimed to analyse the reasons for using EDs, and to describe the seriousness of the attendees' condition and their itinerary before their arrival at ED. This cross-sectional study in 2009 was conducted in ED of 4 hospitals in GreaterTunis and targeted 1058 patients of both sexes, aged 18 years, with stratification according to time of day of presentation to ED (morning, afternoon and evening). Information was recorded on the sociodemographic characteristics of the study participants, reasons for choosing ED, time of and reason for consultation, diagnosis and severity of illness. Over half the patients (52.5%) were male and the mean age was 46.0 (SD 18.1) years. The main reasons for choosing the ED were: speed (54.0%) and ease of access (47.7%) of ER and occurrence of an acute episode (26.4%). Patients with serious illness accounted for only 6.3% of those interviewed. Implementation of good practices and better coordination between public and private services and the ED are needed to reduce unnecessary visits to ED.

Screening of ΔF508 mutation and IVS8-poly T polymorphism in CFTR gene in Tunisian infertile men without CBAVD.

It is well established that cystic fibrosis transmembrane conductance regulator gene (CFTR) mutations are involved in congenital bilateral absence of the vas deferens (CBAVD), causing obstructive azoospermia and male infertility. Also, several studies reported a relatively high prevalence of CFTR gene mutations in healthy men presenting reduced sperm quality. In this study, we investigate ΔF508 mutation and IVS8-polyT polymorphism in CFTR gene in Tunisian infertile men without CBAVD. Genetic analyses were performed in 148 infertile patients and 126 fertile individuals. The polymorphic IVS8-polyT tract in CFTR gene was analysed in only 129 infertile patients and 54 individuals of control group. As well, we screened for Y chromosome microdeletions in all infertile patients. No ΔF508 mutation was diagnosed either in infertile patients or in control group. 5T allele of IVS8-polyT tract was found in both infertile men (4.26%) and fertile individuals (8.33%). 5T/5T genotype was observed only in two azoospermic patients without Y microdeletions. The most frequent genotype of IVS8-polyT tract in infertile men and controls was 7T/7T (69.75% and 59.25% respectively). There was no association between IVS8-polyT polymorphism and reduced semen quality. Neither ΔF508 mutation nor 5T allele is involved in pathogenesis of male infertility in Tunisian infertile patients without CBAVD.

[Hemogram reference values: study of 1000 healthy adults from Sfax]. / Valeurs de référence de l'hémogramme: étude chez 1000 adultes sains de la region de Sfax.

The aims of this study is to determine the hemogram reference values in a population of healthy adults of the region of Sfax, to compare our results with those from the literature, to estimate the age and sex variations in the blood count. The hemogram parameters were analyzed in 1000 blood donors. Hemogram was performed using Coulter ACT10's analyser. The differential leukocyte count was manually performed. The means of erythrocyte count, hemoglobin, haematocrit and red cell indices were significantly lower in women than in men. There was a significant variation in the red blood cell count, hemoglobin and haematocrit with age. There is also sex and age differences of the leukocyte count. The neutrophil and eiosinophil counts were higher in women than in men. The lymphocytes decreased with age in both sexes. The platelet count was significantly higher in women than in men. These results can be applied only to our local population of adults. The definition of reference values for the Tunisian population requires a study on a more diversified population, including more important number of individuals from various regions of the country.

Reasons for using emergency departments of major hospitals in Greater Tunis

Tunisia, similar to many countries, has a problem of overcrowd ing of the emergency departments [ED]. This study aimed to analyse the reasons for using EDs, and to describe the seriousness of the attendees' condition and their itinerary before their arrival at ED. This cross-sectional study in 2009 was conducted in ED of 4 hospitals in GreaterTunis and targeted 1058 patients of both sexes, aged >/= 18 years, with stratification according to time of day of presentation to ED [morning, afternoon and evening]. Information was recorded on the sociodemographic characteristics of the study participants, reasons for choosing ED, time of and reason for consultation, diagnosis and severity of illness. Over half the patients [52.5%] were male and the mean age was 46.0 [SD 18.1] years. The main reasons for choosing the ED were: speed [54.0%] and ease of access [47.7%] of ER and occurrence of an acute episode [26.4%], Patients with serious illness accounted for only 6.3% of those interviewed. Implementation of good practices and better coordination between public and private services and the ED are needed to reduce unnecessary visits to ED

[Results and evaluation of 3 years of a large scale mammography program in the Ariana area of Tunisia]. / Résultats et évaluation de 3 années de pratique mammographique à grande échelle dans le gouvernorat de l'Ariana en Tunisie.

OBJECTIVE: To asses and analyse the results of 3 years large scale mammography screening of breast cancer in Ariana state in Tunisia. MATERIALS AND METHODS: This program, managed by the Family and Population National Office, was addressing to women aged from 49 to 69 years old residing in a area with adds up a population of 459 700 inhabitants including 52,729 women in the target age population. The screening was including a breast clinical examination and a mammography with two incidences face and external profile. The women was invited at their residence or were sensitized in the reproductive health centers, care and base health centers or by a close relation which heard of the program. An enlightened assent was submitted to the women who wished to profit from the screening. RESULTS: In three years, 9093 mammography were carried out of which 8244 were retained in the analyses, that is to say a rate participation of 9.6%. The rate of women recalled for suspect test was of 18.1% and it was of 13.1% among women of more than 50 years. The rate of practiced surgical biopsies was of 0.5% and the positive predictive value was of 45.5%. The average time between the date of screening and the result of the screening was 9.7 days, more important in the event of tests requiring a complementary assessment (61.7 days). On the whole 40 cancers were detected by the program, that is to say a rough rate of detected cancers, of 4.9 per thousand, in conformity with the recommendations. The percentage of invasive cancers < or = 10 mm was of 24.3 whereas percentages of in situ cancers and of cancers without ganglionic invasion were respectively of 7.7% and of 50.0%. CONCLUSIONS: The weakness of our study lay primarily in the rate of participation which remained weak. The methodology adopted for the sensitizing of the women is proven not very effective and did not allow inviting all eligible women. Results of the study are encouraging in spite of its limited impact and made it possible to detect an important rate of cancers of which cancers infra-private clinics.

[Preliminary results and analysis of the feasibility of mammographic breast cancer screening in women younger than 50 years of the Ariana area in Tunisia]. / Résultats préliminaires et faisabilité du dépistage mammographique du cancer du sein chez les femmes de moins de 50 ans du gouvernorat de l'Ariana en Tunisie.

OBJECTIVE: To report the preliminary results of the feasibility of breast cancer mammographic screening among women younger than 50 years from the l'Ariana state of Tunisia. MATERIAL AND METHODS: The National office of the Family and Population (ONFP) launched a protocol on feasibility of breast cancer mammographic screening targeting asymptomatic women aged 40-69 years, from the l'Ariana state in Tunisia. We practiced two oblique and face incidences at the mammography screening unit of the ONFP, whose equipment and control system of quality answered to the European Communitiy for breast cancer screening. RESULTS: We did 5325 mammograms between April 2004 and March 2006. Our targeted population had a 48.9 years mean age (CI 95% = [48.7-49.1]), 60.3% of them younger than 50 years. There were more young women with high breast denisty (8.2%) compared to the group from 50 to 69 years (2.1%). The women arising from the 40-49 years cohort had a socio-economic and educational level higher. The complementary rate of examination/explorations was higher in this cohort (19.5%) vs 11.5% for the 50-69 years. The youngest women presented a more often positive test (7.0 vs 5.2%) than the oldest women (p<0.01). CONCLUSION: The option to screen breast cancer by mammography in women younger than 40 years in Tunisia is partially justified by the relatively high frequency of this cancer in this age group. Our feasibility poorly useful in screening will be used to sensibilise females to the problematic of breast cancer to obtain a better compliance compared to the older age group of 50-59 years.

[Estimation of years of life gained within the pilot screening program of the Ariana area of Tunisia]. / Estimation du nombre potentiel d'années de vie sauvées à travers l'expérience pilote de dépistage de masse du cancer du sein à l'Ariana.

Breast cancer is the principle cancer among female cancer in Tunisia. It represents 30% of the woman's cancers with about 1000 new cases per year. The main intervention control is mass screening using mammography in to reduce breast cancer mortality. Breast cancer screening efficacy in term of breast cancer mortality reduction is closely related to incidence and survival of this cancer. National Office of Family and Population (ONFP) conducted a pilot experience of breast cancer mass screening using the mammography in place. The main objective of this study is to calculate the potential number of life years saved through this pilot experience of the ONFP. For the methodology, we used the software Dismod (Disease Model) for the evaluation of the prevalence and the duration of the cancer of the breast in the governorate, as well as to estimate the number of life years saved. The potential breast cancer mortality reduction is 30% for women aged of 50 at 69 years, and 10% for those aged of 40 at 49 years. Breast cancer incidence in Ariana according to age for the period 1995-1998, has been calculated from the data base of cancer registry of the North of Tunisia. According to Dismod, mean duration in the absence of screening, is 11.12 years for the age group 40 to 49 years and 9.57 for the age group 50 at 69 years. Screening would increase these duration means of 2.22 years and 1.71 years, respectively for age groups 40 to 49 years and 50 at 69 years. The number of life years saved for 1000 women is of 2.97 years. In conclusion breast cancer screening using mammography would be actually little benefit in Tunisia. Mammography should be reserved for the diagnosis of the suspected cases and screening for high risk women.

[Health transition in Tunisia over the past 50 years]. / La transition sanitaire en Tunisie au cours des 50 dernières années.

We describe the dramatic demographic, socioeconomic and health changes witnessed in Tunisia over the past 50 years. Demographically, the gross mortality rate and the infant mortality rate have gone from 19 per 1000 and 150 per 1000 respectively in 1956 to 5.7 per 1000 and 26.2 per 1000 now, and life expectancy at birth going from 50 to 72 years for the same period. Socioeconomically, the urban population has risen from 25% to 62%, the literacy rate from 15% to 73%, and the per capita income has increased 5-fold in real terms. Epidemiologically, the infectious and perinatal diseases prevailing in the 1960s have decreased whereas chronic and degenerative diseases have risen. The proportion of the GNP related to health expenditure has risen from 3.8% to 6.2%. The implication of these changes on the Tunisian health system and the need to adapt in terms of curative care and prevention of risks are discussed.

[Arthritis of the hip in spondylarthorpathy: retrospective study about 126 cases]. / Les coxites au cours des spondylarthropathies: Etude rétrospective à propos de 126 observations.

PURPOSE: To determine epidemiological and clinical features of arthritis of the hip in a Tunisian population of spondylarthrpathy (SA). PATIENTS AND METHODS: This is a retrospective study about patients suffering from SA treated in a rheumatology unit. A radiological investigation of the pelvis was systematically performed on each patient. RESULTS: The study in involved 126 cases of SA (83 men and 43 women), with a middle age of 32.6 years. Arthritis of the hip showed within 3.8 years. Total hip arthroplasty was indicated in 18% of cases. Arthritis of the hip in spondylarthropathy is an important cause of functional disability. We insist in our study on the frequency of arthritis of the hip in North Africa and particularly in patients aged under 16 years.

[Health transition in Tunisia over the past 50 years]

We describe the dramatic demographic, socioeconomic and health changes witnessed in Tunisia over the past 50 years. Demographically, the gross mortality rate and the infant mortality rate have gone from 19 per 1000 and 150 per 1000 respectively in 1956 to 5.7 per 1000 and 26.2 per 1000 now, and life expectancy at birth going from 50 to 72 years for the same period. Socioeconomically, the urban population has risen from 25% to 62%, the literacy rate from 15% to 73%, and the per capita income has increased 5-fold in real terms. Epidemiologically, the infectious and perinatal diseases prevailing in the 1960s have decreased whereas chronic and degenerative diseases have risen. The proportion of the GNP related to health expenditure has risen from 3.8% to 6.2%. The implication of these changes on the Tunisian health system and the need to adapt in terms of curative care and prevention of risks are discussed

Calcipotriol and PUVA as treatment for vitiligo.

We performed a prospective study to evaluate efficacy of the combination of calcipotriol and psoralen plus ultraviolet A (PUVA) in the treatment of vitiligo. Twenty-three patients with essentially bilateral symmetrical lesions of vitiligo were included. Calcipotriol (0.005 %) ointment was applied twice daily over the right side of the body, and the other side was not treated. PUVA was performed three times per week. All patients received at least forty five sessions of PUVA. Patients were evaluated clinically and photographed all fifteen weeks. At the fifteenth session, 69 percent of the patients had minimal to moderate improvement on the calcipotriol side compared to 52 percent on the PUVA-only side (p = 0.015). At the forty-fifth session, 52 percent showed marked improvement on the calcipotriol side compared to 30 percent on the PUVA-only side (p = 0.13), with more intense repigmentation on calcipotriol-treated areas. Treatment was well tolerated, and no adverse effect was noted. This combination was an effective treatment for vitiligo, especially in initiating repigmentation.

[Receptivity of the Tunisian to malaria after its eradication: analysis of the situation for adequacy of the surveillance]. / Réceptivité de la Tunisie au paludisme après son éradication: analyse de la situation pour une adéquation de la surveillance.

In Tunisia, there has been no local transmission of malaria since 1979. Although the disease has been eradicated, its re-emergence is not considered impossible. An epidemiological evaluation has been conducted in order to evaluate the current level of receptivity. A. labranchiae and A. sergenti, the former vectors of malaria in the country, are still present and the anopheline population in the country is increasing following the building of dams and manmade lakes. It is hoped that Tunisian vectors are refractory to sub-Saharan strains of malaria parasites. According to the data collected regarding malaria history, climate, geography and socio-economic development, we assume that the receptivity level of the country is low and the risk of re-emergence of local foci is small.

[Health indicators in Tunisia, trends in regional disparities over the last thirty years]. / Indicateurs de sante en tunisie, evolution des disparites inter-regionales au cours des trente dernieres annees.

The measure of health indicators on a regional-scale seems more interesting then the measure on a national-scale. It allows us to study differences between regions and their evolution. In order to know the time trend's disparities between regions, we have studied seven indicators, concerning different types of the World Health Organisation's classification, using data from yearly statistics and results of decennial census. Regional disparities are evaluated by a ratio between the highest regional value and the lowest regional value. This study showed us a global trend to the decline of regional disparities about indicators that we have studied. The improvement of health care resources indicators and socioeconomic's indicators, in the process of time, is associated with the improvement of health status indicators. The study of regional disparities makes possible to target actions for health in order to promote health's equity between regions.

Multisorbent plasma perfusion in fulminant hepatic failure: effects of duration and frequency of treatment in rats with grade III hepatic coma.

Using the model of galactosamine-induced fulminant hepatic failure in the rat, the effects of multisorbent plasma perfusion over Asahi uncoated spherical charcoal, Plasorba (BR-350) resin, and an endotoxin removing adsorbent (polymyxin B-sepharose) were determined in Grade III hepatic coma animals by studying survival as influenced by timing, duration, and frequency of treatment. The effects of treatment on liver cell proliferation and endotoxin removal also were examined. The results demonstrate that duration and frequency of treatment are major contributing factors in the successful application of nonbiological membrane-based multisorbent liver support systems. Examination of the regenerative activity in the liver indicates an enhanced proliferative response following multisorbent plasma perfusion compared with untreated fulminant hepatic failure (FHF) paired controls. Utilizing an endotoxin removal adsorbent alone, a marked reduction in systemic levels of endotoxin in FHF was demonstrated compared with nonperfused FHF paired controls. Despite current emphasis on bioartificial liver support systems, plasma purification by multisorbent systems offers a simple method for the removal of circulating toxic metabolites in general together with specific toxin removal.