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International audience; Objective To determine long-term predictors of bronchial hyperresponsiveness (BHR) and forced expiratory volume in one second (FEV1) decline.Methods A longitudinal study in 110 bakers in 4 industrial bakeries and 38 non-exposed workers was conducted at the workplace with a mean of 3.3 visits per subject over a period of 13 years and a mean duration of follow-up of 6 years in bakers and 8 years in non-exposed subjects. A respiratory health questionnaire was administered; occupational allergen skin prick tests, spirometry and a methacholine bronchial challenge test were performed at each visit. In each bakery, full-shift dust samples of the inhalable fraction were obtained in order to assess the exposure of each job assignment. The repeated measurements of BHR and FEV1 were analyzed using mixed effects logistic and linear regression models in subjects seen at least twice.Results BHR, respiratory symptoms and their simultaneous occurrence depended on the duration of exposure. FEV1 significantly decreased with duration of exposure and BHR at a preceding visit. This result persisted when adjusting for the effect of BHR at the current visit. The measured exposure levels were not a significant predictor for any outcome. Occupational sensitization was only a predictor of a decline in FEV1 when duration of exposure was not included.Conclusion In flour-exposed industrial bakers, length of exposure and smoking are long-term determinants of BHR and of the decrease in FEV1. BHR at a preceding visit predicted lower FEV1 even when accounting for the effect of BHR at the current visit.

Hepatitis C Virus (HCV) is one virus that has a high mutation rate in the world. To predict the mutation can be used fundamental analysis and technical analysis. Fundamental analysis relies on external factors such as attributes attached to the primer and the isolate. While technical analysis learns the movement of the mutation itself by relying on graphs and mathematical formulas. This study combines fundamental analysis and technical analysis in predicting HCV mutations. Application of Recurrent Neural Network (RNN) method as a form of technical analysis and fundamental analysis is applied in the form of including some fundamental factor data as training datasets. RNN is a neural network that has a feedback connection to the neuron itself, or a previous neuron. RNN is able to reactivate actual data values in the past to be re-entered with actual data values at the moment. This study used Elman network architecture with Back Propagation Through Time learning algorithm (BPTT) and used Linear normalization. The problem when predicting HCV mutations is how to determine the best learning rate value. Therefore the fundamental approach will also be incorporated into the neural network. On the backward process, to calculate the value of weight correction is to multiply the value of learning rate with hidden neuron value. We propose that each neuron has an adaptive learning rate according to the condition of the neuron. Where each input neuron from this study is the result of the HCV primer normalized in preliminary research. Each primer has attributes that can be developed as decision support. Test results show the smallest error of the prediction process by RMSE are 0.0163000, with accuracy prediction value are 99%.

Purpose While new strategies for the treatment of invasive breast cancer (BC) are emerging, radiotherapy (RT) modalities are still under debate. The French expert review board of Nice-Saint-Paul de Vence was asked firstly to conduct a qualitative evidence-based systematic review and then to establish clinical practice guidelines for the use of post operative RT in invasive BC. Methods and materials A search to identify eligible studies was undertaken using the Medline® database. All phase III randomized trials and systematic reviews evaluating the role and modalities of RT in invasive BC were included, together with some noncontrolled studies if no randomized trials were identified. The quality and clinical relevance of the studies were evaluated to determine the level of evidence. Results The maximum delay between surgery and RT should ≤8 weeks when chemotherapy (CT) is not indicated. This should not exceed 24 weeks when adjuvant CT is administered. Whole breast RT delivering 50 Gy in 25 fractions followed by a boost of 10–16 Gy remains the standard of care after conservative surgery (CS). In the elderly population, for certain cases presenting comorbidities associated with a limited life expectancy, RT indication (even hypofractioned) and boost delivery may be unnecessary in the light of an unfavourable risk/benefit ratio. RT technique and indications should not vary in case of neoadjuvant CT followed by CS. After total mastectomy, RT should be indicated in N+ and in N− patients with high risk of local recurrence. The experts recommend to initiate tamoxifen at the end of RT, while aromatase inhibitors could be administered either concomitantly or sequentially with RT. There is no consistent data to delay (or suspend) trastuzumab administration during RT. As for all patients, in case of concurrent RT-trastuzumab administration, reduction of cardiac tissues exposure is highly recommended. After breast reconstruction, RT should be delivered as after standard CS without boost. Conclusion Due to significant variations in practice in the treatment of patients with BC, our group aimed to provide guidelines for clinical practice. The systematic review of the literature formed the basis of our evidence-based recommendations; however expert agreements were necessary on those subjects that are still under debate. Our group will update these guidelines every 4 years, taking in consideration new advances in technology, new drugs administration, biologic tools and innovative therapeutic options.

An important early stage in the research of sperm analysis is the phase of sperm detection or separating sperm objects from images/video obtained from observations on semen. The success rate in separating sperm objects from semen fluids has an important role for further analysis of sperm objects. Algorithm or Background subtraction method is a process that can be used to separate moving objects (foreground) and background on sperm video data that tend to uni-modal. In this research, some of the subproject model statistics of substrata model are Gaussian single, Gaussian Mixture Model (GMM), Kernel Density Estimation and compared with some basic subtraction model background algorithm in detecting and counting the number of active spermatozoa. From the results of the tests, the Grimson GMM method has an f-measure value of 0.8265 and succeeded in extracting the sperm form near its original form compared to other methods

It has been suggested that solvent exposure may have a role in the progression of glomerulonephritis (GN) to end-stage renal failure (ESRD), but this has never been tested with an appropriate cohort study design. We included 338 nonESRD patients with a first biopsy for primary GN between 1994 and 2001: 194 IgA nephropathies (IgAN), 75 membranous nephropathies (MN) and 69 focal and segmental glomerulosclerosis (FSGS). ESRD, defined as an estimated glomerular filtration rate < 15 mL/min/1.73m2 or dialysis, was registered over a mean follow-up period of 5 years. Patients’ lifelong solvent exposures before and after diagnosis were recorded by interview and assessed by industrial hygienist experts. We used Cox models to estimate adjusted hazard ratios (HR) of ESRD related to exposures. Overall, 15% of the patients had been exposed at a low level before diagnosis and 14% at a high level. Forty-two with IgA N reached ESRD, 12 with MN, and 22 with FSGS. A graded relationship was observed for MN: age- and gender-adjusted HR [95% confidence interval] for low exposure vs none 3.1 [0.5–18.2], and for high exposure vs none 8.2 [1.9–34.7], as well as for IgA N: 1.6 [0.7–3.9] and 2.2 [1.0–4.8], respectively, but not for FSGS. Solvent risk was only partly mediated by baseline proteinuria: adjusted HR for high exposure vs none = 5.5 [1.3 – 23.9] for MN and 1.8 [0.8 – 3.9] for IgA N. In patients with IgA N, there was a trend in increasing HR with exposure duration before and its persistence after diagnosis. These findings support the hypothesized association of solvent exposure with the progression of GN to ESRD. They should prompt clinicians to give greater attention to patients’ occupational exposures and possibly to consider professional reclassification.

Purpose We reviewed follow-up of patients treated in 19 randomized trials of adjuvant epirubicin in early breast cancer to determine incidence, risk, and risk factors for subsequent acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). Patients and Methods The patients (N = 9,796) were observed from the start of adjuvant treatment (53,080 patient-years). Cases of AML or MDS (AML/MDS) were reported, with disease characteristics. Incidence and cumulative risk were compared for possible risk factors, for assigned regimens, and for administered cumulative doses of epirubicin and cyclophosphamide. Results In 7,110 patients treated with epirubicin-containing regimens (92% of whom also received cyclophosphamide), 8-year cumulative probability of AML/MDS was 0.55% (95% CI, 0.33% to 0.78%). The risk of developing AML/MDS increased in relation to planned epirubicin dose per cycle, planned epirubicin dose-intensity, and administered cumulative doses of epirubicin and cyclophosphamide. Patients with administered cumulative doses of both epirubicin and cyclophosphamide not exceeding those used in standard regimens (≤ 720 mg/m2 and ≤ 6,300 mg/m2, respectively) had an 8-year cumulative probability of developing AML/MDS of 0.37% (95% CI, 0.13% to 0.61%) compared with 4.97% (95% CI, 2.06% to 7.87%) for patients administered higher cumulative doses of both epirubicin and cyclophosphamide. Conclusion Patients treated with standard cumulative doses of adjuvant epirubicin (≤ 720 mg/m2) and cyclophosphamide (≤ 6,300 mg/m2) for early breast cancer have a lower probability of secondary leukemia than patients treated with higher cumulative doses. Increased risk of secondary leukemia must be considered when assessing the potential benefit to risk ratio of higher than standard doses.

Summary Aim: Immediate adjuvant tamoxifen reduces disease recurrence and improves survival in patients with early breast cancer. However, is it too late to administer tamoxifen to patients who have already undergone treatment, but were unable to benefit from this adjuvant therapy? The French National Cancer Centers (FNCLCC) have investigated the efficacy of delayed tamoxifen administration in a randomized controlled trial. Patients and methods: From September 1986 to October 1989, women with primary breast cancer, who had undergone surgery, radiotherapy, and/or received adjuvant chemotherapy but not hormone therapy more than two years earlier, were randomized to receive either 30 mg/day tamoxifen or no treatment. The 10-year disease-free and overall survival rates of the two groups of patients and of various subgroups were determined according to the Kaplan-Meyer method and compared by the log-rank test. Results: This intention-to-treat analysis comprised 250 women in the tamoxifen group and 244 in the control group. Patient characteristics (age, T stage, number of positive nodes, receptor status, and interval since tumor treatment) were comparable in both groups. Delayed adjuvant tamoxifen significantly improved overall survival only in node-positive patients and in patients with estrogen receptor-positive (ER+) or progesterone receptor-positive (PR+) tumors. Disease-free survival, however, was significantly improved in the global population and in several patient subgroups (node-positive, ER+, PR+). Patients in whom the interval between primary treatment and delayed adjuvant tamoxifen was greater than five years also had significantly improved disease-free survival. Conclusions: Overall and disease-free survival results indicate that delayed adjuvant tamoxifen administration (30 mg/day) is justified in women with early breast cancer, even if this treatment is initiated two or more years after primary treatment.

The exposure of employees of different contracting firms to chemical pollutants was assessed during the five-week biennial maintenance shut-down of an isocyanate (TDI) synthesis plant. This assessment was mainly based on personal sampling, but work-related constraints occasionally required that area samples be used instead. Many tasks were carried out during the shut-down procedure (dismantling of reactors, installation of insulation, refection of kilns, cleaning, painting, electricity, etc.), thereby causing the employees of the contracting firms to be exposed to different kinds of pollutants, including products used or manufactured in the process (solvents, TDI and its synthesis intermediates), and products specific to the contractors' activity (welding fumes, crystalline silica, mineral fibers of heat insulation). The highest level of exposure (mainly to TDI) was found for the mechanical engineering activities undertaken during the dismantling of reactors and for cleaning activities. It was demonstrated that there was much variability in day-to-day exposure levels, and occasionally in the exposure levels encountered during a given shift. Cases of concomitant exposure to TDI (mainly short-term exposures) and other pollutants due to simultaneous activities from different tasks in the same area (co-activity) were also observed. Both the need for, and limitations of personal protective equipment (mainly respiratory) are stressed. Special emphasis is put on the responsibility of the owner of the facilities in helping the contractors in the organization of a health and safety policy.

International audience; Cleaning products may cause work-related asthma, but information regarding the specific exposures involved is scarce. We aimed to determine the associations between asthma and occupational exposure to cleaning agents in hospital workers. Analyses were conducted in 179 (136 women) hospital workers and a reference population of 545 subjects (18-79 years) from the French case-control and familial Epidemiological study on the Genetics and Environment of Asthma (2003-2007). Exposures to cleaning agents were estimated using three methods: self-report, expert assessment and an asthma-specific job-exposure matrix (JEM). Associations between cleaning products and current asthma were evaluated by logistic regressions, stratified by sex and adjusted for age and smoking status. According to expert assessment, 55% of male and 81% of female hospital workers were exposed to cleaning/disinfecting tasks weekly (p

Summary Background The role of exposure to substances in the workplace in new-onset asthma is not well characterised in population-based studies. We therefore aimed to estimate the relative and attributable risks of new-onset asthma in relation to occupations, work-related exposures, and inhalation accidents. Methods We studied prospectively 6837 participants from 13 countries who previously took part in the European Community Respiratory Health Survey (1990–95) and did not report respiratory symptoms or a history of asthma at the time of the fi rst study. Asthma was assessed by methacholine challenge test and by questionnaire data on asthma symptoms. Exposures were defi ned by high-risk occupations, an asthma-specifi c job exposure matrix with additional expert judgment, and through self-report of acute inhalation events. Relative risks for new onset asthma were calculated with log-binomial models adjusted for age, sex, smoking, and study centre. Findings A signifi cant excess asthma risk was seen after exposure to substances known to cause occupational asthma (Relative risk=1·6, 95% CI 1·1–2·3, p=0·017). Risks were highest for asthma defi ned by bronchial hyper-reactivity in addition to symptoms (2·4, 1·3–4·6, p=0·008). Of common occupations, a signifi cant excess risk of asthma was seen for nursing (2·2, 1·3–4·0, p=0·007). Asthma risk was also increased in participants who reported an acute symptomatic inhalation event such as fi re, mixing cleaning products, or chemical spills (RR=3·3, 95% CI 1·0–11·1, p=0·051). The population-attributable risk for adult asthma due to occupational exposures ranged from 10% to 25%, equivalent to an incidence of new-onset occupational asthma of 250–300 cases per million people per year. Interpretation Occupational exposures account for a substantial proportion of adult asthma incidence. The increased risk of asthma after inhalation accidents suggests that workers who have such accidents should be monitored closely.

The purpose of this study was to determine a subpopulation of node-negative breast cancer patients at high risk of metastases and to analyse the relationship between conventional prognostic factors and the onset of metastatic disease. Patients with node-negative breast cancer, who were not receiving systemic adjuvant therapy, were prospectively enrolled into a multicentre study. We studied the onset of metastatic disease in relation to family history, age, and tumour characteristics of 2683 registered patients, 2213 were available for analysis. Median follow-up was 100 months. Metastatic disease-free survival was 88% at 5 years and 80% at 10 years. The two strongest prognostic factors in a multivariate analysis tumour Scraff, Bloom and Richardson (SBR) grade (P0.0001) and size (P0.02), were used to classify patients into three groups with different risks of relapse at 10 years: (1) lowest (8.4%) risk: SBR I andor =1 cm; (2) intermediate (20%) risk: SBR I and1 cm or SBR II or SBR III andor =2 cm; (3) highest (32%) risk: SBR II or SBR III and2 cm. A peak in the incidence of metastases was noted between 2 and 4 years, and a nadir between 6 and 8 years, after surgery. SBR grade is a highly predictive factor in node-negative breast cancer. The time course of the appearance of metastases is not linear. Prognostic factors are related to the height of an early peak in the occurrence of metastases rather than to the timing of this peak.

OBJECTIVES: To measure the levels of exposure to nitrogen trichloride (NCl3) in the atmosphere of indoor swimming pools and to examine how they relate to irritant and chronic respiratory symptoms, indices of pulmonary function, and bronchial hyperresponsiveness to methacholine in lifeguards working in the pools. METHOD: 334 lifeguards (256 men; 78 women) recruited from 46 public swimming pools (n = 228) and 17 leisure centre swimming pools (n = 106) were examined. Concentrations of NCl3 were measured with area samplers. Symptoms were assessed by questionnaire and methacholine bronchial challenge (MBC) test by an abbreviated method. Subjects were labelled MBC+ if forced expiratory volume in one second (FEV1) fell by > or = 20%. The linear dose- response slope was calculated as the percentage fall in FEV1 at the last dose divided by the total dose given. RESULTS: 1262 samples were taken in the 63 pools. Mean NCl3 concentrations were greater in leisure than in public pools. A significant concentration-response relation was found between irritant eye, nasal, and throat symptoms-but not chronic respiratory symptoms-and exposure concentrations. Among women, the prevalence of MBC+ was twice as great as in men. Overall, no relation was found between bronchial hyperresponsiveness and exposure. CONCLUSIONS: The data show that lifeguards exposed to NCl3 in indoor swimming pools are at risk of developing irritant eye, nasal, and throat symptoms. Exposure to NCl3 does not seem to carry the risk of developing permanent bronchial hyperresponsiveness, but this association might have been influenced by self selection. The possibility that subjects exposed to NCl3 are at risk of developing transient bronchial hyperresponsiveness cannot be confidently ruled out.

From 1960 to 1986, 397 cases of non-metastatic male breast cancer (MBC) treated in 14 French regional cancer centres were reviewed. The median age was 64 years (range 25-93). TNM classification (UICC, 1978) showed seven T0, 79 T1, 162 T2, 31 T3, 74 T4 and 44 unclassified tumours (Tx). Clinical positive lymph nodes were found in 31% of the patients. 24 patients received radiotherapy only, and 373 underwent surgery, 247 of these with postoperative irradiation. Adjuvant chemotherapy and hormonal therapy were used in 71 and 68 patients, respectively. There were 382 infiltrating carcinomas and 15 pure ductal carcinoma in situ. Lymph node involvement was found in 56% of infiltrating carcinoma. The oestrogen (ER) and progesterone (PgR) receptors were positive in 79% and 77%, respectively, of examined cases. Isolated local and regional recurrence were observed in 8.8% and 4.5% of cases, respectively and 40% of patients developed metastases. The crude survival rates by Kaplan-Meier method were 65% and 38% at 5 and 10 years, respectively, and the disease-specific survival rates (without death due to intercurrent disease or second cancer) was 74% at 5 years and 51% at 10 years. The disease-specific survival rate for pN- and pN+ groups were 77% and 39% at 10 years. The prognostic factors were clinical size (T) and histological axillary status (pN-/pN+). The relative risk of death for pN- was 1.0, 2.0 and 3.2 in the T0-T1, T2 and T3-T4 groups, respectively. For pN+, these relative risks increased 1.9, 3.9 and 6.0 in the same groups. The optimal treatment include modified radical mastectomy and irradiation for cases with risk factors of local relapse (nodal invasion, large tumour with cutaneous or muscular involvement). Locoregional failure had unfavourable prognosis. First-line adjuvant treatment seems to be tamoxifen, due to the very high rate of positive hormonal receptors and the old age of the patients, which contraindicate chemotherapy in many cases. The prognosis of patients with breast cancer is the same in male and female patients when disease-specific survival rate, tumour size and axillary involvement are compared.

The exposure of workers to metallic catalyst dust was assessed in manufacturing and reprocessing industries, and during catalyst handling in the chemical industry. The level of exposure was found to be generally low during the manufacturing and reprocessing activities taking place in permanent installations, and extremely variable during catalyst handling performed by workers of sub-contracting specialized firms. The difficulties in treating the occupational hygiene problems of these workers are pointed out.

Material From 1960 to 1990, 581 cases of male breast cancer (MBC) were reviewed in 19 Cancer Institutes in France. 23 (4%) were pure DCIS. The median age was 56.5 years (ext. 26–77). Five patients had less than 40 years (22%). Gynecomastia was found in 10 out of 23 patients (43%). Three had family history of B. C. According to TNM classification, we found 6 impalpable lesions (T0) discovered by serosanguineous nipple discharge, 7 T1, 6 T2, and 4 Tx. Treatment The surgery consisted of 3 lumpectomies, 16 modified, 2 subcutaneous and 2 radical mastectomies. 16 patients had axillary dissections and 6 irradiation on the chest wall. Histology All cases were pure DCIS: in 14 the subtype was clearly identified: papillary (4), papillary intracystic (3), mixed papillary and cribriform (3), comedocarcinoma (2), cribriform (1), apocrine (1). Three patients had local recurrences: two occurred in the patients initially treated by lumpectomy alone: the first was again a DCIS, but the second was an infiltrating carcinoma; this patient died by metastases. The last relapse occurred on the chest wall in a patient treated by mastectomy. One patient developed a contralateral DCIS. Two patients developed a lung and kidney cancer respectively. In the literature the rate of DCIS in man varies from 0 to 16%. The serosanguineous nipple discharge seems a frequent symptom, especially in young men. The main histologic subtype is papillary (pure or intracystic). Mastectomy is the treatment of choice.

SUMMARY Implantation of oestradiol into adult rats of both sexes induced different patterns of LH secretion depending on the time at which gonadectomy or testosterone injection were performed. Castration 2 h after birth allowed an LH peak to occur daily at 18.00 h, but its amplitude was lower than that of adult gonadectomized female rats treated with oestradiol. Castration 24 h after birth elicited two kinds of response; a circadian discharge of LH lower than that of male rats gonadectomized 2 h after birth or a steady low level of LH. The LH rhythmicity induced by implantation of oestradiol was not seen after castration at 8 weeks of age. Neonatal administration of testosterone to female rats prevented the LH peak induced by oestradiol that was seen in adult ovariectomized rats. Neonatal or adult ovariectomy did not interfere with the rhythmical response of LH after implantation of oestradiol. Thus, it is concluded that sexual differentiation of the hypothalamus is primarily of masculine origin.

It has been shown that all-solvent exposure is associated with the progression of primary glomerulonephritis to end-stage renal disease (ESRD), but little is known about the type of solvents that are high risk. The aim of this study was to investigate the role of solvents by occupation, product and type.Using a retrospective cohort design, the authors studied 269 patients with non-end-stage and biopsy-proven primary glomerulonephritis diagnosed between 1994 and 2001 in Paris and its suburbs. Two industrial hygienists evaluated patients' exposures from lifetime occupational histories collected by interview from 2002-4, and using a list of the 30 most common solvents. The studied outcome was ESRD, defined as glomerular filtration rate15 ml/mn/1.73 m(2) or dialysis. It was recorded during a mean follow-up of five years. Cox models were used to estimate adjusted hazard ratios (HR) of ESRD related to exposures.Eighteen per cent of the patients had ever been exposed to solvents. Those with the highest risk of progression to ESRD were exposed machinery fitters and machine assemblers (HR 4.7, 95% CI 1.2 to 17.4) and plumbers/welders (HR 4.2, 95% CI 1.3 to 13.6), as compared to never exposed patients, as well as those who ever handled printing inks and petroleum products (HR 12.6 (95% CI 1.7 to 94.9) and 3.2 (95% CI 1.4 to 7.2), respectively). Among solvents, the highest risks were found for: toluene/xylene (HR 5.1, 95% CI 1.8 to 14.8), gasoline, fuel and gas-oil (HR 8.6, 95% CI 2.7 to 27.4), and ketones (HR 13.3, 95% CI 1.4 to 123.5).This study highlights the potential nephrotoxicity of several solvents. Intervention to promote screening for proteinuria in exposed workers may prevent the progression of glomerulonephritis to ESRD.