Rhinitis due to acrylates : case report

Background: Acrylates and methacrylates (salts and esters of acrylic and metacrylic acid respectively), are monomers commonly found in polymer plastics, resins and glues, and are widely used in many industry sectors. The first adverse health effects described were skin reactions and asthma. Exposure to acrylates, for instance when using multicomponent glues, is now a well known cause of occupational asthma. Methods: We report the case of a rhinitis - and possible asthma - to acrylates, in a 38-year-old woman, working in a nail beauty salon. She was currently treated for hypertension, and otherwise known for obesity and seasonal rhinoconjunctivitis, but did not have any respiratory problem. Two years after starting this activity, she progressively started to complain of anosmia, rhinitis, and intermittent dyspnea. Her job consisted in decorating nails with a mixture of a polymer powder and a liquid monomer, after removing the previous artificial nail with a small sander. We assessed exposure to acrylates at her working place, both as dust (from sanded nails) and volatile compound (from the mixture described above), and she was asked to measure her peak flow values twice a day for ten days, in order to detect a possible relationship between her occupational activities, the symptoms and the peak flow values. Results: Measures made during the visit of the patient's place of work showed that the existing aspiration system was efficient for eliminating the dust produced by nail sanding, but not for eliminating the volatile components. Thus, occupational exposure to acrylates was demonstrated. Moreover, the peak flow measures showed an average decrease of almost 10 percent when the patient was at work, compared to when she stayed home. We concluded that she actually suffered from professional rhinitis and, possibly, professional asthma (not certain because of the limited number of peak flow measures per day). Conclusion: Although exposure to acrylates is a well known cause of occupational asthma, it should be emphasized that the exact mechanisms of action remain unknown, despite the abundant literature about it. Some professions, which tend to be more frequent nowadays (such as working in a nail beauty salon), can expose the worker to particular risks. This highlights the need of always inquiring not only about the profession, but also the related activities, when facing a case of suspected asthma.

An Introduction to parametric and non-parametric models for bivariate positive insurance claim severity distributions

We present a real data set of claims amounts where costs related to damage are recorded separately from those related to medical expenses. Only claims with positive costs are considered here. Two approaches to density estimation are presented: a classical parametric and a semi-parametric method, based on transformation kernel density estimation. We explore the data set with standard univariate methods. We also propose ways to select the bandwidth and transformation parameters in the univariate case based on Bayesian methods. We indicate how to compare the results of alternative methods both looking at the shape of the overall density domain and exploring the density estimates in the right tail.

History matters: relating paths and rates of landscape change to butterfly species decline

Western European landscapes have drastically changed since the 1950s, with agricultural intensifications and the spread of urban settlements considered the most important drivers of this land-use/land-cover change. Losses of habitat for fauna and flora have been a direct consequence of this development. In the present study, we relate butterfly occurrence to land-use/land-cover changes over five decades between 1951 and 2000. The study area covers the entire Swiss territory. The 10 explanatory variables originate from agricultural statistics and censuses. Both state as well as rate was used as explanatory variables. Species distribution data were obtained from natural history collections. We selected eight butterfly species: four species occur on wetlands and four occur on dry grasslands. We used cluster analysis to track land-use/land-cover changes and to group communes based on similar trajectories of change. Generalized linear models were applied to identify factors that were significantly correlated with the persistence or disappearance of butterfly species. Results showed that decreasing agricultural areas and densities of farms with more than 10 ha of cultivated land are significantly related with wetland species decline, and increasing densities of livestock seem to have favored disappearance of dry grassland species. Moreover, we show that species declines are not only dependent on land-use/land-cover states but also on the rates of change; that is, the higher the transformation rate from small to large farms, the higher the loss of dry grassland species. We suggest that more attention should be paid to the rates of landscape change as feasible drivers of species change and derive some management suggestions.

Inequality across countries in energy intensities: an analysis of the role of energy transformation and final energy consumption

This paper analyzes the role of the energy transformation index and of final energy consumption per GDP unit in the disparities in energy intensity across countries. In that vein, we use a Theil decomposition approach to analyze global primary energy intensity inequality as well as inequality across different regions of the world and inequality within these regions. The paper first demonstrates the pre-eminence of divergence in final energy consumption per GDP unit in explaining global primary energy intensity inequality and its evolution during the 1971-2006 period. Secondly, it shows the lower (albeit non negligible) impact of the transformation index in global primary energy inequality. Thirdly, the relevance of regions as unit of analysis in studying crosscountry energy intensity inequality and their explanatory factors is highlighted. And finally, how regions around the world differ as to the relevance of the energy transformation index in explaining primary energy intensity inequality.

A single mutation in enzyme I of the sugar phosphotransferase system confers penicillin tolerance to Streptococcus gordonii.

Tolerance is a poorly understood phenomenon that allows bacteria exposed to a bactericidal antibiotic to stop their growth and withstand drug-induced killing. This survival ability has been implicated in antibiotic treatment failures. Here, we describe a single nucleotide mutation (tol1) in a tolerant Streptococcus gordonii strain (Tol1) that is sufficient to provide tolerance in vitro and in vivo. It induces a proline-to-arginine substitution (P483R) in the homodimerization interface of enzyme I of the sugar phosphotransferase system, resulting in diminished sugar uptake. In vitro, the susceptible wild-type (WT) and Tol1 cultures lost 4.5 and 0.6 log(10) CFU/ml, respectively, after 24 h of penicillin exposure. The introduction of tol1 into the WT (WT P483R) conferred tolerance (a loss of 0.7 log(10) CFU/ml/24 h), whereas restitution of the parent sequence in Tol1 (Tol1 R483P) restored antibiotic susceptibility. Moreover, penicillin treatment of rats in an experimental model of endocarditis showed a complete inversion in the outcome, with a failure of therapy in rats infected with WT P483R and the complete disappearance of bacteria in animals infected with Tol1 R483P.

Deciding where to belong: gender differences in educational trajectories and migration in a rural Spanish town

From an anthropological perspective, formal post-secondary schooling is not an abstractentity with an intrinsic value that everyone finds desirable, but rather one alternative among many that young people evaluate from their different positions in the social field. The problem discussed in this paper is the diverging life trajectories that young men and women in a concrete rural context, at the end of the 20th century, shape for themselves at the ages of 14-16, a moment of decision created by national legislation regarding mandatory education (LGE, 1970, General Education Law, and LOGSE, 1990, General Organic Law of the Education System). Despite a strong cultural norm of equal inheritance divided among all children, male and female, and despite the equal educational opportunities provided by the Spanish State, different meanings of possession and use-rights over land and the resulting culturally accepted gendered division of work converge to orient men and women differently towards post-secondary schooling. Observation of the age, gender, and civil status structure of the population led to the preliminary query: Why do men and women, in this town, behave differently with respect to migration and marriage? The main hypothesis was that women’s longer school trajectories and resulting migration and men’s anchoring in the town and their higher rates of celibacy were not drastic changes in values, in the positional-relational sense of Bourdieu (1988, 2002), but the current outcome of previously existing dissimilar relations to property that produce dissimilar mobility. Through their schooling and work choices, young men and women, at very early ages, locate themselves in, or decide to belong to, different contexts that later reveal very different possibilities of finding marriage partners. This paper is based on an ethnographic study of a small rural town (302 inhabitants in 1950; 193 in 2000) near Leon. Although this paper deals with the situation in the final decades of the 20th century, we must also consider the first half of the century, where some elements that shape this situation have their roots. Fieldwork was carried out between 1988 and 2001, in periods of differing length and intensity. The social subjects discussed here are the domestic unit and its component members. They were studied in conjunction, analyzing the life-trajectory decisions of specific persons in the framework of the domestic unit and the relations among people and property which comprise it. The tried-and-true methods of ethnographic research –participant observation, interviews, and life-histories, etc.- were employed. Archival research was also important for producing demographic data. Demographic analysis, the analysis of the composition and transformation of domestic units, and the creation of life trajectories were among the principal techniques used. The theoretical analysis was oriented by Bourdieu’s (2002) framework of the social field, habitus, and difference.

Characterization of the Aspergillus nidulans biotin biosynthetic gene cluster and use of the bioDA gene as a new transformation marker.

The genes involved in the biosynthesis of biotin were identified in the hyphal fungus Aspergillus nidulans through homology searches and complementation of Escherichia coli biotin-auxotrophic mutants. Whereas the 7,8-diaminopelargonic acid synthase and dethiobiotin synthetase are encoded by distinct genes in bacteria and the yeast Saccharomyces cerevisiae, both activities are performed in A. nidulans by a single enzyme, encoded by the bifunctional gene bioDA. Such a bifunctional bioDA gene is a genetic feature common to numerous members of the ascomycete filamentous fungi and basidiomycetes, as well as in plants and oömycota. However, unlike in other eukaryota, the three bio genes contributing to the four enzymatic steps from pimeloyl-CoA to biotin are organized in a gene cluster in pezizomycotina. The A. nidulans auxotrophic mutants biA1, biA2 and biA3 were all found to have mutations in the 7,8-diaminopelargonic acid synthase domain of the bioDA gene. Although biotin auxotrophy is an inconvenient marker in classical genetic manipulations due to cross-feeding of biotin, transformation of the biA1 mutant with the bioDA gene from either A. nidulans or Aspergillus fumigatus led to the recovery of well-defined biotin-prototrophic colonies. The usefulness of bioDA gene as a novel and robust transformation marker was demonstrated in co-transformation experiments with a green fluorescent protein reporter, and in the efficient deletion of the laccase (yA) gene via homologous recombination in a mutant lacking non-homologous end-joining activity.

Malignant transformation of DMBA/TPA-induced papillomas and nevi in the skin of mice selectively lacking retinoid-X-receptor alpha in epidermal keratinocytes.

Retinoid-X-receptor alpha (RXRalpha), a member of the nuclear receptor (NR) superfamily, is a ligand-dependent transcriptional regulatory factor. It plays a crucial role in NR signalling through heterodimerization with some 15 NRs. We investigated the role of RXRalpha and its partners on mouse skin tumor formation and malignant progression upon topical DMBA/TPA treatment. In mutants selectively ablated for RXRalpha in keratinocytes, epidermal tumors increased in size and number, and frequently progressed to carcinomas. As keratinocyte-selective peroxisome proliferator-activated receptor gamma (PPARgamma) ablation had similar effects, RXRalpha/PPARgamma heterodimers most probably mediate epidermal tumor suppression. Keratinocyte-selective RXRalpha-null and vitamin-D-receptor null mice also exhibited more numerous dermal melanocytic growths (nevi) than control mice, but only nevi from RXRalpha mutant mice progressed to invasive human-melanoma-like tumors. Distinct RXRalpha-mediated molecular events appear therefore to be involved, in keratinocytes, in cell-autonomous suppression of epidermal tumorigenesis and malignant progression, and in non-cell-autonomous suppression of nevi formation and progression. Our study emphasizes the crucial role of keratinocytes in chemically induced epidermal and melanocytic tumorigenesis, and raises the possibility that they could play a similar role in UV-induced tumorigenesis, notably in nevi formation and progression to melanoma.

CHARACTERISATION OF ARABIDOPSIS THALIANA PERMEABLE CUTICLE MUTANTS SHOWING A STRONG RESISTANCE TO BOTRYTIS CINEREA

La cuticule des plantes, composée de cutine, un polyester lipidique complexe et de cires cuticulaires, couvre l'épiderme de la plupart des parties aériennes des plantes. Elle est constituée d'une barrière hydrophobique primaire qui minimise les pertes en eau et en soluté et protège l'organisme de différents stress environnementaux tels que les rayons UV, la dessiccation et l'infection par des pathogènes. Elle est aussi impliquée dans la délimitation des organes durant le développement. La cutine est un polyester qui, dans la plupart des espèces végétales, est principalement composé d'acides gras ω-hydroxylés composé de 16 à 18 carbones. Cependant, la cutine des feuilles d'Arabidopsis a une composition différente et est principalement constituée d'acides dicarboxyliques à 16-18 carbones. Les cires sont présentes dans le polyester de la cutine ou le recouvrent. Chez Arabidopsis, un nombre de mutants, tel que 1er, bdg, hth, att1, wbc11, et des plantes transgéniques avec différents changement dans la structure de la cuticule dans les feuilles et la tige, ont récemment été décrits et servent d'outils pour étudier la relation entre la structure et la fonction de la cuticule.7 mutants d'Arabidopsis ont été isolés par une méthode de coloration qui permet de détecter une augmentation dans la perméabilité cuticulaire. Ces mutants ont été appelés pec pour permeable cuticle.Pour la première partie de mon projet, j'ai principalement travaillé avec pec9/bre1 (permeable cuticle 9/botrytis resistance 1). PEC9/BRE1 a été identifié comme étant LACS2 (LONG CHAIN ACYL-CoA SYNTHETASE 2). Dans ce mutant, la cuticule n'est pas visible sous microscopie électronique et la quantité en acides gras omega- hydroxylés et en leurs dérivés est fortement réduite. Ces altérations conduisent à une plus grande perméabilité de la cuticule qui est mise en évidence par une plus grande sensibilité à la sécheresse et aux xénobiotiques et une coloration plus rapide par bleu de toluidine. Le mutant Iacs2 démontre aussi une grande capacité de résistance à l'infection du champignon nécrotrophique B. cinerea. Cette résistance est due à l'extrusion sur les feuilles d'un composé antifongique durant l'infection. Ce travail a été publié dans EMBO journal (Bessire et al., 2007, EMBO Journal).Mon second projet était principalement concentré sur pec1, un autre mutant isolé par le premier crible. La caractérisation de pec1 a révélé des phénotypes similaires à ceux de Iacs2, mais à chaque fois dans des proportions moindres : sensibilité accrue à la sécheresse et aux herbicides, plus grande perméabilité au bleu de toluidine et au calcofluor white, altération de la structure cuticulaire et résistance à B. cinerea à travers la même activité antifongique. PEC1 a été identifié comme étant AtPDR4. Ce gène code pour un transporteur ABC de la famille PDR ("Pleiotropic Drugs Resistance") qui sont des transporteurs ayants un large spectre de substrats. Le mutant se différencie de Iacs2, en cela que la composition en acides gras de la cuticule n'est pas autant altérée. C'est principalement le dihydroxypalmitate des fleurs dont la quantité est réduite. L'expression du gène marqué avec une GFP sous le contrôle du promoteur endogène a permis de localiser le transporteur au niveau de la membrane plasmique des cellules de l'épiderme, de manière polaire. En effet, la protéine est principalement dirigée vers l'extérieure de la plante, là où se trouve la cuticule, suggérant une implication d'AtPDR4 dans le transport de composants de la cuticule. Ce travail est actuellement soumis à Plant Cell.Une étude phylogénétique a aussi montré qu'AtPDR4 était très proche d'OsPDR6 du riz. Le mutant du riz a d'ailleurs montré des phénotypes de nanisme et de perméabilité similaire au mutant chez Arabidopsis.AbstractThe cuticle, consisting principally of cutin and cuticular waxes, is a hydrophobic layer of lipidic nature, which covers all aerial parts of plants and protects them from different abiotic and biotic stresses. Recently, the research in this area has given us a better understanding of the structure and the formation of the cuticle. The Arabidopsis mutants permeable cuticle 1 (peel) and botrytis resistance 1 (brel) were identified in two screens to identify permeable cuticles. The screens used the fluorescent dye calcofluor to measure permeability and also resistance to the fungal pathogen Botrytis. These mutants have highly permeable cuticle characteristics such as higher water loss, intake of chemicals through the cuticle, higher resistance to Botrytis cinerea infection, and organ fusion.BRE1 was cloned and found to be LACS2, a gene previously identified which is important in the formation and biosynthetic pathway of the cuticle. In brel, the amount of the major component of cutin in Arabidopsis leaves and stems, dicarboxylic acids, is five times lower than in the wild type. Moreover, the permeability of the cuticle allows the release of antifungal compounds at the leaf surface that inhibits the growth of two necrotrophic fungi: Botrytis cinerea and Sclerotinia sclerotiorum.PEC1 was identified as AtPDR4, a gene that codes for a plasma membrane transporter of the Pleiotropic Drug Resistance family, a sub-family of the ABC- transporters. AtPDR4 is strongly expressed in the epidermis of expanding tissues. In the epidermis it is located in a polar manner on the external plasma membrane, facing the cuticle. Analysis of the monomer composition of the cutin reveals that in this mutant the amount of hydroxy-acids and dihydroxy-palmitate is 2-3 times lower in flowers, in which organ these cutin monomers are the major components. Thus AtPDR4 is thought to function as a putative cutin monomer transporter.

Germline transformation of Aedes fluviatilis (Diptera:Culicidae) with the piggyBac transposable element

The technique to generate transgenic mosquitoes requires adaptation for each target species because of aspects related to species biology, sensitivity to manipulation and rearing conditions. Here we tested different parameters on the microinjection procedure in order to obtain a transgenic Neotropical mosquito species. By using a transposon-based strategy we were able to successfully transform Aedes fluviatilis (Lutz), which can be used as an avian malaria model. These results demonstrate the usefulness of the piggyBac transposable element as a transformation vector for Neotropical mosquito species and opens up new research frontiers for South American mosquito vectors.

Transgenic Arabidopsis plants can accumulate polyhydroxybutyrate to up to 4% of their fresh weight.

Transgenic Arabidopsis thaliana (L.) Heynh. plants expressing the three enzymes encoding the biosynthetic route to polyhydroxybutyrate (PHB) are described. These plants accumulated more than 4% of their fresh weight (approximately 40% of their dry weight) in the form of PHB in leaf chloroplasts. These very high producers were obtained and identified following a novel strategy consisting of a rapid GC-MS analysis of a large number of transgenic Arabidopsis plants generated using a triple construct, thus allowing the parallel transfer of all three genes necessary for PHB synthesis in a single transformation event. The level of PHB produced was 4-fold greater than previously published values, thus demonstrating the large potential of plants to produce this renewable resource. However, the high levels of the polymer produced had severe effects on both plant development and metabolism. Stunted growth and a loss of fertility were observed in the high-producing lines. Analysis of the metabolite composition of these lines using a GC-MS method that we have newly developed showed that the accumulation of high levels of PHB was not accompanied by an appreciable change in either the composition or the amount of fatty acids. Substantial changes were, however, observed in the levels of various organic acids, amino acids, sugars and sugar alcohols.

Survival, prognostic factors and rates of leukemic transformation in 381 untreated patients with MDS and del(5q): a multicenter study.

Myelodysplastic syndromes (MDS) with del(5q) are considered to have a benign course of the disease. In order to address the issue of the propensity of those patients to progress to acute myeloid leukemia (AML), data on 381 untreated patients with MDS and del(5q) characterized by low or intermediate I International Prognostic Scoring System (IPSS) risk score were collected from nine centers and registries. Median survival of the entire group was 74 months. Transfusion-dependent patients had a median survival of 44 months vs 97 months for transfusion-independent patients (P<0.0001). Transfusion need at diagnosis was the most important patient characteristic for survival. Of the 381 patients, 48 (12.6%) progressed to AML. The cumulative progression rate calculated using the Kaplan-Meier method was 4.9% at 2 years and 17.6% at 5 years. Factors associated with the risk of AML transformation were high-risk World Health Organization adapted Prognostic Scoring System (WPSS) score, marrow blast count >5% and red-cell transfusion dependency at diagnosis. In conclusion, patients with MDS and del(5q) are facing a considerable risk of AML transformation. More detailed cytogenetic and molecular studies may help to identify the patients at risk of progression.

Application of compositional data analysis to geochemical data of marine sediments

In an earlier investigation (Burger et al., 2000) five sediment cores near the RodriguesTriple Junction in the Indian Ocean were studied applying classical statistical methods(fuzzy c-means clustering, linear mixing model, principal component analysis) for theextraction of endmembers and evaluating the spatial and temporal variation ofgeochemical signals. Three main factors of sedimentation were expected by the marinegeologists: a volcano-genetic, a hydro-hydrothermal and an ultra-basic factor. Thedisplay of fuzzy membership values and/or factor scores versus depth providedconsistent results for two factors only; the ultra-basic component could not beidentified. The reason for this may be that only traditional statistical methods wereapplied, i.e. the untransformed components were used and the cosine-theta coefficient assimilarity measure.During the last decade considerable progress in compositional data analysis was madeand many case studies were published using new tools for exploratory analysis of thesedata. Therefore it makes sense to check if the application of suitable data transformations,reduction of the D-part simplex to two or three factors and visualinterpretation of the factor scores would lead to a revision of earlier results and toanswers to open questions . In this paper we follow the lines of a paper of R. Tolosana-Delgado et al. (2005) starting with a problem-oriented interpretation of the biplotscattergram, extracting compositional factors, ilr-transformation of the components andvisualization of the factor scores in a spatial context: The compositional factors will beplotted versus depth (time) of the core samples in order to facilitate the identification ofthe expected sources of the sedimentary process.Kew words: compositional data analysis, biplot, deep sea sediments

Existential values transformation in all organ transplantation: A qualitative prospective study.

Organ transplantation offers a treatment of choice for patients suffering from end stage illnesses. The aim of this IRB approved prospective qualitative study was to analyze patients’ psychological concerns from their inclusion on the waiting list for first organ transplantation (TX) (T1; N=71; kidney, K=30; liver, Li=11; lung, Lu=15; heart, H=15) and six months after TX (T2; N=49; K=15; Li=10; Lu=14; H=10). Semi-structured interviews were conducted at home or in a place selected by patients. Qualitative pattern analysis (QUAPA) of the verbatim transcriptions was applied. T1 (K) Patients maintained an apparent normality (87%), building emotional protection (23%), and developing a fatalist attitude towards life (43%). (Li) Physical limits were set to spare energy until TX (73%). Illness led to reevaluation of life values (66%). (Lu) Physical and psychological self-protection was prioritized when health declined (67%). Modified life values, fatalism (33%) and spirituality (27 %) were mentioned. (H) Patients husbanded physical (80%) and psychological (67%) resources and self-protection. Modified life values and fatalist attitude towards life were reported (40%). T2 (K) New perspective on life was described, with increase of empathy towards others (20%). (Li) Positive identity and life values modifications (60%), greater openness towards others, closeness to significant ones (30%) and a more self-centered attitude (30%) prioritizing the essential (20%) were reported. Lack of respect of life values generated anger (40%). (Lu) Setting existential priorities and increase in spirituality (64%), along with the development of new life values, greater openness to others (57%) and closeness to significant ones (21%) were underlined. Lack of respect of human values induced negative feelings (36%). Self-centered attitudes, setting limits to other people were mentioned (29%). (H) Change in life values with setting life priorities was reported (70%) with increase in spirituality, and the lack of respect of life values generated anger (50%). Self-centered attitudes were reported (60%). TX not only comes with positive physical benefits, but also with positive existential values and psychological transformation, and the development of a more altruistic attitude and humanistic values.

Lymphoblastic transformation of follicular lymphoma: a clinicopathologic and molecular analysis of 7 patients.

Approximately 30% of patients with follicular lymphoma (FL) transform to a more aggressive malignancy, most commonly diffuse large B cell lymphoma. Rarely, FL transformation results in clinical findings, histology, and immunophenotype reminiscent of B-lymphoblastic leukemia/lymphoma. We report the largest series to date with detailed analysis of 7 such patients. Lymphoblastic transformation occurred on average 2 years after initial diagnosis of FL. Five patients had prior intensive chemotherapy. Two patients developed mature high-grade lymphoma, followed by the lymphoblastic transformation. FL had BCL2 gene rearrangement in 4 of 5 cases. High-grade transformation was accompanied by MYC gene rearrangement (5 of 5). Transformation was characterized by expression of TdT, loss of Bcl6, variable loss of immunoglobulin light chain, and persistence of Pax-5, Bcl2, and CD10. Whole-exome sequencing in 1 case revealed presence of several actionable mutations (CD79B, CCND3, CDK12). FL, aggressive mature B cell lymphoma, and lymphoblastic transformation were clonally related in 6 evaluable cases. After transformation, survival ranged from 1 to 14 months. Four patients died of disease, 2 were in remission after stem cell transplant, and 1 was alive with disease.