Breast cancer time to treatment in Martinique: predictive factors and effect on survival.

BACKGROUND: Martinique is the second French Region with the lowest physician-to-population ratio, which may affect waiting times for access to care. OBJECTIVES: To assess (i) factors influencing waiting times from diagnosis to cancer-related treatments in breast cancer women in Martinique, and (ii) the impact of waiting times on patients' survival. STUDY DESIGN: Retrospective observational study. METHODS: Data on women diagnosed with invasive breast cancer between 1st January 2013 and 31st December 2017 and initially treated by surgery were extracted from the Martinique population-based registry. A cox model was performed to find predictive factors for waiting times. A log-rank test was used to compare time-to-treatment between groups. RESULTS: In total, 713 patients were included (mean age: 58 ± 13). Median time from diagnosis to surgery was 40 [25-60] days. Age at diagnosis was found to predict variations in waiting times. Patients > 75 had longer waiting time to surgery than those < 40 or [40-50] (P = 0.016 and P < 0.001, respectively). Women with a time-to-treatment ≥ 4 months had a significant lower survival (P < 0.01). CONCLUSIONS: Specific interventions are needed to improve waiting time from diagnosis to initial treatment, as they are longer than recommended and affect survival time.

Epidemiology and survival of cervical cancer in the French West-Indies: data from the Martinique Cancer Registry (2002-2011).

BACKGROUND: The Caribbean ranks seventh among world regions most affected by cervical cancer. Social health inequalities, such as differences in access to screening services, engender disparities in incidence and mortality between low- and middle-income countries and industrialized countries. The French National Cancer Plan 2014-2019 focuses on reducing inequalities in cervical cancer. OBJECTIVE: The aim of this study was to describe the geographical distribution and overall survival of cervical cancer, based on data from a population-based cancer registry in Martinique (French West-Indies). METHODS: We included all cases of cervical cancer diagnosed between 2002 and 2011. The geographical distribution was described by zone of residence and by aggregated units for statistical information (IRIS). Based on the results of the model, standardized incidence rates (SIRs) were calculated using a Gamma Poisson model. Survival rates were calculated using the Kaplan-Meier method. Cox proportional hazards models were used to investigate the risk factors for cervical cancer mortality. RESULTS: A total of 1253 cases were analyzed (947 in situ tumors and 306 invasive cancers). 1230 cases with geolocalization were used to map the distribution of the incidence of in situ and invasive cervical cancers. Five IRIS were significantly over-incident. The 5-year overall survival rate was 55%, with a median survival of 6.5 years [95% CI: 4.9-10.1]. Multivariate analysis confirmed age at diagnosis (HR = 2.15 [1.50-3.09]; p < 0.0001), FIGO stage (HR = 3.53 [2.50-4.99]; p < 0.0001) and zone of residence (HR = 1.51 [1.06-2.13]; p = 0.02) as risk factors. CONCLUSIONS: Prognostic factors suggest that cervical cancer needs to be diagnosed at an early stage. Our results could allow cervical cancer screening programs to clearly identify geographical areas that would benefit from targeted interventions with a view to reducing incidence and mortality of cervical cancer in the Caribbean.

Trends in colorectal cancer in the Caribbean: A population-based study in Martinique, 1982-2011.

BACKGROUND: We aimed to describe incidence and mortality from colorectal cancer, and temporal trends between 1982 and 2011 in Martinique (French West-Indies). METHODS: This was a descriptive, longitudinal, observational study based on data from the Martinique cancer registry. The study included all incident cases of colorectal cancer between 1982 and 2011. We recorded sociodemographic data and clinical variables (histology, site according to the WHO classification). Cancer cases were recorded in strict conformity with the international standards. Annual rate of change was calculated, direct standardisation was used for incidence and mortality age standardised rates (ASR). The comparative incidence figure and comparative mortality figure (95% confidence intervals) were calculated. RESULTS: In total, 2530 patients were included in our study; 1243 died. In the period 2007-2011, a considerable increase in incidence was observed, making colorectal cancer the second leading cause of cancer deaths in both sexes (8.9% and 10.5%). In men, ASR for incidence increased from 9.6/100,000 person-years in the period 1982-1986 to 27.2/100,000 person-years in the period 2007-2011, with a notable acceleration of the increase. In women, ASR increased from 8.4 to 19.8/100,000 person-years over the same periods. For the latest period 2007-2011, mortality rates were 9.9 and 7.6/100,000 person-years for men and for women respectively. Regardless of the sex, there was a strong increase in the incidence of right colon cancer, which became the most common colorectal site in women in Martinique. CONCLUSION: Our findings confirm the increase in the incidence of colorectal cancer that started in the 2000s. Trends observed reflect a salient epidemiological transition of the Caribbean.

Influence of avian reproduction ecotoxicological endpoints in the assessment of plant protection products.

The aim of this paper is to examine the statistical relevance of bird species on the endpoints of avian long-term toxicity studies (eggs laid, eggs set, eggs hatching, embryo survivor, 14-day old survivors and eggshell thickness). Data from 561 animals of three different species (Colinus virginianus, Anas platyrynchos and Coturnix coturnix japonica) tested with five different pesticides were analyzed in this study. The substances considered were: Thiamethoxam (EZ-3-(2-chloro-1,3-thiazol-5-ylmethyl)-5-methyl-1,3,5-oxadiazinan-4-ylidene(nitro)amine), Thiacloprid ((Z)-3-(6-chloro-3-pyridylmethyl)-1,3-thiazolidin-2-ylidenecyanamide), Acetamiprid ((E)-N(1)-[(6-chloro-3-pyridyl)methyl]-N(2)-cyano-N(1)-methylacetamidine), Phosmet (O,O-dimethyl S-phthalimidomethyl phosphorodithioate) and Dicofol (2,2,2-trichloro-1,1-bis(4-chlorophenyl)ethanol). Several general lineal mixed models were conducted to evaluate the factors affecting variables used in long-term reproductive toxicity tests. Test significance was p < 0.01 in all models tested. Model R(2) value was high (0.80) for all variables except for eggs laid (R(2) = 0.42) for the three species studied. Tukey studentized range test showed significant differences among species and pesticides. For pre-hatching period the differences were significant for eggs laid and eggs set among species. C. japonica showed statistical differences for egg hatching. With respect to embryo survivor and 14 days old survival, significant different were found for C.virginianus and A. platyrynchos, respectively. These results indicate that the selected species have an influence in the endpoints to be used for risk assessment.

[Colorectal cancers in Martinique: incidence and mortality rates over a period of 20 years]. / Cancers colorectaux en Martinique: incidence et mortalité durant une période de 20 ans.

BACKGROUND: Colorectal cancer is the second leading cause of cancer death in Western countries, with an incidence progressively increasing in developing countries. Worldwide, colorectal cancer is the second and third leading cause of death by cancer in females and males respectively. According to the Martinique Cancer Register data, colorectal cancer is the second leading cause of death by cancer in women, and the fourth in men. Colorectal cancer exhibits a variable distribution worldwide. This study was conducted to observe variations in colorectal incidence and mortality rates observed over a twenty-year period. Such data will be useful for monitoring changing trends related to onset of an organized screening program. METHOD: Patients with colorectal cancer diagnosed from 1981 to 2000 in Martinique were included in this study. Data are obtained from the Martinique Cancer Register. RESULTS: The incidence of colorectal cancer in Martinique (16/100,000 and 17/100,000 in the female and male population respectively in the year 2000) is intermediary compared with other countries worlwide. There is a current trend towards increased incidence and mortality. The incidence has increased for cancers localized in the proximal colon, the sigmoid colon and the rectum. CONCLUSION: The increasing incidence of colorectal cancer in all localisations raises concern in Martinique. A significant predominance of colorectal cancer incidence among the male population in Martinique was not observed. Gender and age do not appear to imply any preferential localisation of colorectal cancer.

Optimal growth of Dunaliella primolecta in axenic conditions to assay herbicides.

To develop an assay for herbicides in marine environments using microalgae, we have optimized the specie, cell culture media and physical conditions to obtain maximal cellular densities in a 96 well micro format to allow mass assays. We first surveyed several species of 7 unicellular eukaryotic algae genera (Dunaliella, Tetraselmis, Chlorella, Ellipsoidon, Isochrysis, Nannochloropsis, and Phaeodactylum) for vigorous in vitro axenic growth. Once the genus Dunaliella was selected, Dunaliella primolecta was preferred among 9 species (bioculata, minuta, parva, peircei, polymorpha, primolecta, quartolecta, salina and tertiolecta) because it showed the highest growth rates. The components (oligo elements, sugars, amino acids and vitamins) and conditions (light, CO(2), temperature) of the culture media were further optimized to obtain the highest cellular densities (up to 60x10(6)cellsml(-1)) and the shortest cell cycle duration ( approximately 12h) for D. primolecta. Then the toxicity of four representative herbicides, alloxydim, and sethoxydim (inhibitors of acetyl-coA carboxilase), metamitron (inhibitor of photosynthesis) and clopyralid (inhibitor of respiration), were assayed on the optimal culture conditions for D. primolecta during 96h. The results showed that D. primolecta was susceptible to those herbicides in the following order: metamitron > sethoxydim > alloxydim. In contrast, clopyralid did not have any effects. Therefore, D. primolecta microcultures can be used to assay a large number of samples for the presence of herbicides under a saline environment.

Bioassay for determining sensitivity to sulfosulfuron on seven plant species.

This study presents a bioassay procedure, based on the root and shoot growth parameters, for the determination of the herbicide sulfosulfuron (1-(4,6 dimethoxypyrimidin-2-yl)-3-(2-ethylsulfonylimidazo[1,2-a]pyridin-3-ylsulfonil)urea) sensitivity on seven vegetal species. Plant response to sulfosulfuron was calculated with the equations fitted to the root growth data as a function of the logarithm of the herbicide concentration by non-linear regression and was used to calculate the doses for 10, 30 and 50% inhibition of root growth (EC10, EC30 and EC50). The results indicate that the phytotoxic effect of sulfosulfuron in all the species assayed followed the order: flax > maize > onion > vetch > lepidium sativum > tomato > barley. These species showed phytotoxicity at low levels of sulfosulfuron and flax appeared to be the most susceptible species to sulfosulfuron (0.001 mg/L).

Residue levels of captan and trichlorfon in field-treated kaki fruits, individual versus composite samples, and after household processing.

The dissipation of residue levels of captan and trichlorfon in field-treated kaki crops was studied according to good laboratory practices to propose maximum residue limits (MRLs). Residue levels of captan and trichlorfon were analysed by GC/MS and LC-MS/MS, respectively. Residue levels of captan and trichlorfon permitted one to propose MRLs in kaki of 3 and 5 mg kg(-1), respectively. The behaviour of these residues was also studied after peeling and cooking, and in individual fruits versus composite samples. Residue levels of these compounds for individual fruits suggested that a variability factor up to three could be set for the acute risk assessment. Levels of captan decreased by more than 90% after peeling and completely after cooking. Trichlorfon penetrates into the flesh in a proportion of 70% of the residue at the pre-harvest interval. Cooking resulted in a decrease of 27% of residue levels of trichlorfon.

Analytical study of trichlorfon residues in Kaki fruit and cauliflower samples by liquid chromatography-electrospray tandem mass spectrometry.

A detailed analytical study on trichlorfon residues in selected vegetables samples has been carried out, focused on the reliable quantification and confirmation of this compound, and on stability of residues under storage. As a consequence, a rapid and sensitive LC-ESI-MS/MS method has been developed for the determination of residues of this insecticide in kaki fruit (flesh and peel) and cauliflower samples. Extraction was performed with acetonitrile using a high-speed blender. After 4-fold dilution of the extract with water, 20 microL was directly injected in the LC-ESI-MS/MS system (triple quadrupole), using matrix-matched standards calibration for quantification. Under optimized MS/MS conditions, limit of detections between 0.006 and 0.013 mg/kg were reached, and a limit of quantification of 0.05 mg/kg was established, with a runtime of only 15 min. Recoveries from spiked blank samples at 0.05 and 0.5 mg/kg were in the range 83-101% with relative standard deviations lower than 10%. The method was applied to treated and untreated samples collected from field residues trials, using quality control samples analysis for the evaluation of the method. Despite the acquisition of two MS/MS transitions in selected reaction monitoring mode, the analysis of treated samples revealed the presence of a chromatographic peak close to the analyte that corresponded to a trichlorfon isobaric compound that shared the same MS/MS transitions. This unusual situation in LC-MS/MS-based procedures required the application of an efficient chromatographic separation to avoid this interference. All experiments have been made in compliance with the principles of Good Laboratory Practices (GLP) and following the European SANCO guidelines for pesticides residue analysis (PRA).

Hexazinone and simazine dissipation in forestry field nurseries.

Hexazinone and simazine field dissipation was studied in two different soils from Spain (Toledo and Burgos), devoted to forest nurseries for Pinus nigra. Laboratory experiments (adsorption-desorption isotherms, leaching experiment and degradation study) were carried out to determine possible mechanisms of dissipation. Higher adsorption was observed for hexazinone in Toledo (KfT = 0.69) compare to in Burgos soil (KfB = 0.20) probably due to the higher organic matter (OM) content of Toledo soil. No differences in adsorption were obtained for simazine in both soils (KfT = 1.27; KfB = 1.34). In every case, adsorption was higher for simazine than for hexazinone, in both soils. The total recovery of hexazinone in the leachates from handpacked soil columns was higher in Burgos (100%) than in Toledo (80%), because of the larger adsorption of hexazinone in this last soil. No differences in simazine leaching between both soils were found, although the total amount of pesticide recovered in leachates (40% in the two soils) was lower for simazine than for hexazinone. Finally, lower degradation was found in Burgos (t1/2 = 91 d) vs Toledo (t1/2 = 47 d), directly related with the high OM content of Toledo. No half-life was calculated for simazine in Toledo because no changes in herbicide soil content were observed during the period of time studied. In the case of Burgos, the half-life for simazine was 50 days. The field residues study showed larger persistence of simazine than hexazinone mainly due to the higher adsorption and lower mobility of simazine in the two soils. The lower persistence of hexazinone in Toledo soil than in Burgos soil is related to the larger rainfall occurred in this soil besides the higher degradation of this herbicide observed in Toledo soil. The much lower temperature in Burgos than in Toledo soil during winter contribute to the higher persistence of the two herbicides in Burgos soil.

Effects of Cd and Zn waterborne exposure on the uptake and depuration of 57Co, 110mAg and 134Cs by the Asiatic clam (Corbicula fluminea) and the zebra mussel (Dreissena polymorpha)--whole organism study.

Groups of zebra mussels (Dreissena polymorpha) and asiatic clams (Corbicula fluminea) were exposed to cadmium and zinc with the aim of studying the effect of these metals on the 57Co, 110Ag and 134Cs uptake and depuration by these freshwater bivalves. In the presence of zinc, the 57Co concentration factor for the whole organism of the two species was halved, notably because of a decrease of the uptake parameter. Conversely, Zinc and the Cd + Zn mixture increased the 110mAg uptake process by clams and mussels. The two metals also increased the depuration of this radionuclide in mussels, whereas this phenomenon was only observed in clams exposed to cadmium. In comparison with 57Co and 110mAg, the 134Cs bioconcentration was 5-10 times lower in D. polymorpha and not detected in C. fluminea. This weak contamination by this radionuclide resulted from a lower uptake and a higher depuration parameters.

A hyperpolar, multichromophoric cyclodextrin derivative: synthesis, and linear and nonlinear optical properties.

A chiral, highly polar, multichromophoric supermolecule has been designed by gathering seven push-pull chromophores onto a beta-cyclodextrin assembling unit through covalent flexible linkers. The photophysical and nonlinear optical properties of this mutichromophoric conical bundle were investigated and compared with those of the monomeric chromophore. The strongly absorbing multichromophoric system combines interesting features: it has a high molecular first-order hyperpolarisability and a very large dipolar moment (u = 38 D) which reveal a self-arrangement of the dipolar chromophores within the supermolecule. The confinement of the push-pull chromophores within the nanoscopic bundle affects their optical properties and promotes interactions: the multichromophoric supermolecule is hypochromically and hypsochromically shifted with respect to its monomeric analogue. In addition, the close proximity promotes excitonic coupling, as well as excimer formation phenomena.

Neurodevelopmental status at 1 year predicts neuropsychiatric outcome at 14-15 years of age in very preterm infants.

BACKGROUND: Neurodevelopmental and behavioural problems have been repeatedly reported in very preterm survivors, often showing themselves later in childhood as poor school performance. Early identification of problems would mean that appropriate remedial therapy can be implemented. We have previously shown that neurodevelopmental status at 1 year was predictive of outcome at 8 years in a cohort of preterm infants. The aim of this paper was to see if neurodevelopmental outcome in adolescence could be predicted by assessment by 1 year in the same cohort of preterm infants. STUDY DESIGN: Prospective cohort study. SUBJECTS: 150 adolescents, born before 33 weeks gestation. OUTCOME MEASURES: Neurological examination, developmental quotient, vision and hearing by 1 year. At 14-15 years, neurological examination, school performance questionnaire, Schonnell test of reading age, a premorbid adjustment score, Rutter behavioural score and for those born from 1981, cognitive tests (WISC-R). RESULTS: A highly significant relationship existed between neurological status by 1 year and the need for extra educational provision, overall neurodevelopmental status, cognitive function in those that had their IQs measured and premorbid adjustment score of prepsychotic symptoms in adolescence. However, status at 1 year was not predictive of adolescent reading age or behavioural score. CONCLUSIONS: Neurodevelopmental assessment at 1 year is predictive of school performance and outcome in the adolescent period.

Tetrahedral onsager crosses for solubility improvement and crystallization bypass.

Pure organic molecules exhibiting a suitable concave rigid shape are expected to give porous glasses in the solid state. Such a feature opens new opportunities to avoid crystallization and to improve molecular solubility in relation to the high internal energy of these solid phases. To quantitatively explore the latter strategy, a series of rigid tetrahedral conjugated molecules nC and the corresponding models nR have been synthesized. Related to the present purpose, several properties have been investigated using UV absorption, steady-state fluorescence emission, differential scanning calorimetry, (1)H NMR translational self-diffusion, magic angle spinning (13)C NMR, and multiple-beam interferometry experiments. The present tetrahedral crosses are up to 8 orders of magnitude more soluble than the corresponding model compounds after normalization to the same molecular length. In addition, they give concentrated monomeric solutions that can be used to cover surfaces with homogeneous films whose thickness goes down to the nanometer range. Such attractive features make cross-like molecular architectures promising for many applications.

An analytically solved kinetic model for pesticide degradation in single compartment systems.

An analytical kinetic model was developed to simulate the degradation of pesticides in systems such as soil or water. Based on a single compartment system, a set of simultaneous first-order differential equations was analytically solved by the eigenvalue and eigenvector method. The developed model is capable of simulating the concentrations of parent compound and any net of degradation products connected by irreversible reactions.

A comparision of linear-array and mechanical-sector cranial ultrasound scanning techniques to predict neurodevelopmental outcome at 8 years in preterm newborn infants.

Two methods of neonatal cranial ultrasound (US) scanning, linear-array and mechanical-sector, were compared for their accuracy in predicting neurodevelopmental outcome in a cohort of 854, of whom 782 (92%) infants, all born less than 33 weeks of gestation and cared for on the Neonatal Intensive Care Unit at University College Hospital, London between 1979 and 1988, were included in the analysis. A total of 205 infants were studied by linear-array and 577 infants by mechanical-sector scan. Ultrasound findings were grouped into three risk categories on the basis of the US diagnosis. Outcome was assessed at 8 years of age. The probability estimates for neurologically disabling and nondisabling impairments, extra education and mean IQ were compared for the two US methods. There was no significant difference between the two methods in the accuracy of prediction of neurodevelopmental outcome.

Hepatotoxic effect of metallic pollutants on enzyme histochemical activities of yellow-legged gull Larus cachinnans michahellis liver.

We studied the hepatotoxic effect of heavy metals (cadmium, mercury, copper) on Mg2+ -ATPase, NADH diaphorase, succinic dehydrogenase and acid phosphatase of yellow-legged gull liver, using enzyme histochemical methods. The lysosomal enzyme activity of acid phosphatase was increased in all cases. However, the other enzyme activities appeared to be insensitive to the different metallic pollutants and to their respective levels, in contrast with literature experimental data showing plasma membrane and mitochondrial alterations. This controversy could be explained by the differences in dietary conditions and metal overloads. The molecular basis of the toxicities of metallic pollutants is discussed.

Experimental kinetic rates of food-chain and waterborne radionuclide transfer to freshwater fish: a basis for the construction of fish contamination charts.

A standardized procedure is proposed to obtain from laboratory experiments the kinetic accumulation and release rates necessary to calibrate dynamic models to quantify radionuclide direct and trophic transfer in fish. The model takes into account the food-chain effect, the feeding rate, and the growth of organisms. It takes as examples (54)Mn, (60)Co, and (137)Cs transfer dynamics through a simple pelagic food-chain (phytoplankton, zooplankton, prey fish, and predator fish). The estimated kinetic rates used in quantifying all the transfers of the three radioactive pollutants through the pelagic food chain are compared from the radioecological point of view. For fish, comparison was based on the calculation of concentration factors referring to direct transfer from water and trophic transfer factors. For the prey fish and the predator fish, direct transfer gave the following order for accumulation (60)Co < (137)Cs < (54)Mn. Values reached at equilibrium in L/kg WW were respectively for the prey fish and the predator fish: 8.7 < 27.4 < 107 and 4.14 < 6.59 < 13.4. For the trophic route, (137)Cs is the most accumulated (TTF(eq) = 0.485 in 291 days for the prey fish and TTF(eq) = 1.45 in 17 years for the predator fish). A sensitivity analysis adapted to the case of a chronic contamination scenario of a watercourse was run. It showed that the phytoplankton biomass, the contact time of these drifting particles from a release point to the station where they are ingested and the feeding rates of the fish are the most influential parameter with regard to the concentration in fish, whatever the trophic level. Contamination charts are constructed for the predator fish to illustrate the relationship between the most influential ecological parameters and the radionuclide concentration in fish for simple contamination scenarios. They are shown to be effective tools for helping in the choice of the most relevant value of aggregated concentration factors (ACFs: radionuclide concentration ratio between the organism and the water, referred to steady-state and to all possible transfer pathways) for a given key ecological situation in a given ecosystem. An example is given of a simple chronic release scenario of 1 Bq/L and a phytoplanktonic bloom period. For (137)Cs, the ACF increases with increasing contact time and increasing feeding rate, to nearly 550 L/kg WW at equilibrium. For (54)Mn, ACF reaches 65 L/kg WW. For (60)Co, the general pattern of the relationship is due to the rapid kinetic rates governing the distribution of the radionuclide between dissolved and solid (phytoplankton) phases with a maximum value for ACF of 7.2 L/kg WW for the case study. Analysis of these charts provides a basis for overall guidelines for chronic releases in a given watercourse.