Risk assessment of herbicide mixtures in a large European lake

Lake Geneva is one of the largest European lakes with a surface area of 580 km2. Its catchment area covers 7400 km2, of which approximately 20% is arable land. Monitoring campaigns have been carried out in 2004 and 2005 to determine the contamination of the lake by pesticides. The results highlight the widespread presence of herbicides in water, the measured concentrations for most substances remaining constant in 2004 and 2005. However, for some individual herbicides the concentrations increased drastically (e.g., the herbicide foramsulfuron). We assessed the environmental risk of the herbicides detected in the lake using water quality criteria recently determined for the Swiss environmental protection agency. Furthermore, we assessed the risk of herbicide mixtures, grouped based upon their mode of action. Generally, the risk estimated for all single substances is low, except for some sulfonylurea compounds. For these substances, the measured concentrations are higher than the predicted no-effect concentration. Impact on the flora of the lake can therefore not be excluded. When mixtures of pesticides with similar mode of action are taken into account, the risk remains lower than the mixture water quality criteria for all groups, but can reach as high as one third of this quality criteria. A further step would therefore be to assess the risk of the total pesticide mixture, including similar and dissimilar modes of action

Impact of a telenursing service on satisfaction and health outcomes of children with inflammatory rheumatic diseases and their families: a crossover randomized trial study protocol.

BACKGROUND: Pediatric rheumatic diseases have a significant impact on children's quality of life and family functioning. Disease control and management of the symptoms are important to minimize disability and pain. Specialist clinical nurses play a key role in supporting medical teams, recognizing poor disease control and the need for treatment changes, providing a resource to patients on treatment options and access to additional support and advice, and identifying best practices to achieve optimal outcomes for patients and their families. This highlights the importance of investigating follow-up telenursing (TN) consultations with experienced, specialist clinical nurses in rheumatology to provide this support to children and their families. METHODS/DESIGN: This randomized crossover, experimental longitudinal study will compare the effects of standard care against a novel telenursing consultation on children's and family outcomes. It will examine children below 16 years old, recently diagnosed with inflammatory rheumatic diseases, who attend the pediatric rheumatology outpatient clinic of a tertiary referral hospital in western Switzerland, and one of their parents. The telenursing consultation, at least once a month, by a qualified, experienced, specialist nurse in pediatric rheumatology will consist of providing affective support, health information, and aid to decision-making. Cox's Interaction Model of Client Health Behavior serves as the theoretical framework for this study. The primary outcome measure is satisfaction and this will be assessed using mixed methods (quantitative and qualitative data). Secondary outcome measures include disease activity, quality of life, adherence to treatment, use of the telenursing service, and cost. We plan to enroll 56 children. DISCUSSION: The telenursing consultation is designed to support parents and children/adolescents during the course of the disease with regular follow-up. This project is novel because it is based on a theoretical standardized intervention, yet it allows for individualized care. We expect this trial to confirm the importance of support by a clinical specialist nurse in improving outcomes for children and adolescents with inflammatory rheumatisms. TRIAL REGISTRATION: ClinicalTrial.gov identifier: NCT01511341 (December 1st, 2012).

Assessment of volumetric bone mineral density of the femoral neck in postmenopausal women with and without vertebral fractures using quantitative multi-slice CT.

OBJECTIVE: To demonstrate the validity and reliability of volumetric quantitative computed tomography (vQCT) with multi-slice computed tomography (MSCT) and dual energy X-ray absorptiometry (DXA) for hip bone mineral density (BMD) measurements, and to compare the differences between the two techniques in discriminating postmenopausal women with osteoporosis-related vertebral fractures from those without. METHODS: Ninety subjects were enrolled and divided into three groups based on the BMD values of the lumbar spine and/or the femoral neck by DXA. Groups 1 and 2 consisted of postmenopausal women with BMD changes <-2SD, with and without radiographically confirmed vertebral fracture (n=11 and 33, respectively). Group 3 comprised normal controls with BMD changes > or =-1SD (n=46). Post-MSCT (GE, LightSpeed16) scan reconstructed images of the abdominal-pelvic region, 1.25 mm thick per slice, were processed by OsteoCAD software to calculate the following parameters: volumetric BMD values of trabecular bone (TRAB), cortical bone (CORT), and integral bone (INTGL) of the left femoral neck, femoral neck axis length (NAL), and minimum cross-section area (mCSA). DXA BMD measurements of the lumbar spine (AP-SPINE) and the left femoral neck (NECK) also were performed for each subject. RESULTS: The values of all seven parameters were significantly lower in subjects of Groups 1 and 2 than in normal postmenopausal women (P<0.05, respectively). Comparing Groups 1 and 2, 3D-TRAB and 3D-INTGL were significantly lower in postmenopausal women with vertebral fracture(s) [(109.8+/-9.61) and (243.3+/-33.0) mg/cm3, respectively] than in those without [(148.9+/-7.47) and (285.4+/-17.8) mg/cm(3), respectively] (P<0.05, respectively), but no significant differences were evident in AP-SPINE or NECK BMD. CONCLUSION: the femoral neck-derived volumetric BMD parameters using vQCT appeared better than the DXA-derived ones in discriminating osteoporotic postmenopausal women with vertebral fractures from those without. vQCT might be useful to evaluate the effect of osteoporotic vertebral fracture status on changes in bone mass in the femoral neck.

Transmission Fourier transform infrared microspectroscopy allows simultaneous assessment of cutin and cell-wall polysaccharides of Arabidopsis petals.

A procedure for the simultaneous analysis of cell-wall polysaccharides, amides and aliphatic polyesters by transmission Fourier transform infrared microspectroscopy (FTIR) has been established for Arabidopsis petals. The combination of FTIR imaging with spectra derivatization revealed that petals, in contrast to other organs, have a characteristic chemical zoning with high amount of aliphatic compounds and esters in the lamina and of polysaccharides in the stalk of the petal. The hinge region of petals was particular rich in amides as well as in vibrations potentially associated with hemicellulose. In addition, a number of other distribution patterns have been identified. Analyses of mutants in cutin deposition confirmed that vibrations of aliphatic compounds and esters present in the lamina were largely associated with the cuticular polyester. Calculation of spectrotypes, including the standard deviation of intensities, allowed detailed comparison of the spectral features of various mutants. The spectrotypes not only revealed differences in the amount of polyesters in cutin mutants, but also changes in other compound classes. For example, in addition to the expected strong deficiencies in polyester content, the long-chain acyl CoA synthase 2 mutant showed increased intensities of vibrations in a wavelength range that is typical for polysaccharides. Identical spectral features were observed in quasimodo2, a cell-wall mutant of Arabidopsis with a defect in pectin formation that exhibits increased cellulose synthase activity. FTIR thus proved to be a convenient method for the identification and characterization of mutants affected in the deposition of cutin in petals.

Clinical neurophysiological assessment of sepsis-associated brain dysfunction: a systematic review.

IntroductionSeveral studies have reported the presence of electroencephalography (EEG) abnormalities or altered evoked potentials (EPs) during sepsis. However, the role of these tests in the diagnosis and prognostic assessment of sepsis-associated encephalopathy remains unclear.MethodsWe performed a systematic search for studies evaluating EEG and/or EPs in adult (¿18 years) patients with sepsis-associated encephalopathy. The following outcomes were extracted: a) incidence of EEG/EP abnormalities; b) diagnosis of sepsis-associated delirium or encephalopathy with EEG/EP; c) outcome.ResultsAmong 1976 citations, 17 articles met the inclusion criteria. The incidence of EEG abnormalities during sepsis ranged from 12% to 100% for background abnormality and 6% to 12% for presence of triphasic waves. Two studies found that epileptiform discharges and electrographic seizures were more common in critically ill patients with than without sepsis. In one study, EEG background abnormalities were related to the presence and the severity of encephalopathy. Background slowing or suppression and the presence of triphasic waves were also associated with higher mortality. A few studies demonstrated that quantitative EEG analysis and EP could show significant differences in patients with sepsis compared to controls but their association with encephalopathy and outcome was not evaluated.ConclusionsAbnormalities in EEG and EPs are present in the majority of septic patients. There is some evidence to support EEG use in the detection and prognostication of sepsis-associated encephalopathy, but further clinical investigation is needed to confirm this suggestion.

Response Prediction in Chronic Hepatitis C by Assessment of IP-10 and IL28B-Related Single Nucleotide Polymorphisms.

BACKGROUND: High baseline levels of IP-10 predict a slower first phase decline in HCV RNA and a poor outcome following interferon/ribavirin therapy in patients with chronic hepatitis C. Several recent studies report that single nucleotide polymorphisms (SNPs) adjacent to IL28B predict spontaneous resolution of HCV infection and outcome of treatment among HCV genotype 1 infected patients. METHODS AND FINDINGS: In the present study, we correlated the occurrence of variants at three such SNPs (rs12979860, rs12980275, and rs8099917) with pretreatment plasma IP-10 and HCV RNA throughout therapy within a phase III treatment trial (HCV-DITTO) involving 253 Caucasian patients. The favorable SNP variants (CC, AA, and TT, respectively) were associated with lower baseline IP-10 (P = 0.02, P = 0.01, P = 0.04) and were less common among HCV genotype 1 infected patients than genotype 2/3 (P<0.0001, P<0.0001, and P = 0.01). Patients carrying favorable SNP genotypes had higher baseline viral load than those carrying unfavorable variants (P = 0.0013, P = 0.029, P = 0.0004 respectively). Among HCV genotype 1 infected carriers of the favorable C, A, or T alleles, IP-10 below 150 pg/mL significantly predicted a more pronounced reduction of HCV RNA from day 0 to 4 (first phase decline), which translated into increased rates of RVR (62%, 53%, and 39%) and SVR (85%, 76%, and 75% respectively) among homozygous carriers with baseline IP-10 below 150 pg/mL. In multivariate analyses of genotype 1-infected patients, baseline IP-10 and C genotype at rs12979860 independently predicted the first phase viral decline and RVR, which in turn independently predicted SVR. CONCLUSIONS: Concomitant assessment of pretreatment IP-10 and IL28B-related SNPs augments the prediction of the first phase decline in HCV RNA, RVR, and final therapeutic outcome.

BME-based uncertainty assessment of the Chernobyl fallout

The vast territories that have been radioactively contaminated during the 1986 Chernobyl accident provide a substantial data set of radioactive monitoring data, which can be used for the verification and testing of the different spatial estimation (prediction) methods involved in risk assessment studies. Using the Chernobyl data set for such a purpose is motivated by its heterogeneous spatial structure (the data are characterized by large-scale correlations, short-scale variability, spotty features, etc.). The present work is concerned with the application of the Bayesian Maximum Entropy (BME) method to estimate the extent and the magnitude of the radioactive soil contamination by 137Cs due to the Chernobyl fallout. The powerful BME method allows rigorous incorporation of a wide variety of knowledge bases into the spatial estimation procedure leading to informative contamination maps. Exact measurements (?hard? data) are combined with secondary information on local uncertainties (treated as ?soft? data) to generate science-based uncertainty assessment of soil contamination estimates at unsampled locations. BME describes uncertainty in terms of the posterior probability distributions generated across space, whereas no assumption about the underlying distribution is made and non-linear estimators are automatically incorporated. Traditional estimation variances based on the assumption of an underlying Gaussian distribution (analogous, e.g., to the kriging variance) can be derived as a special case of the BME uncertainty analysis. The BME estimates obtained using hard and soft data are compared with the BME estimates obtained using only hard data. The comparison involves both the accuracy of the estimation maps using the exact data and the assessment of the associated uncertainty using repeated measurements. Furthermore, a comparison of the spatial estimation accuracy obtained by the two methods was carried out using a validation data set of hard data. Finally, a separate uncertainty analysis was conducted that evaluated the ability of the posterior probabilities to reproduce the distribution of the raw repeated measurements available in certain populated sites. The analysis provides an illustration of the improvement in mapping accuracy obtained by adding soft data to the existing hard data and, in general, demonstrates that the BME method performs well both in terms of estimation accuracy as well as in terms estimation error assessment, which are both useful features for the Chernobyl fallout study.

Assessment of diesel exhaust particulate exposure and surface characteristics in association with levels of oxidative stress biomarkers

Exposure to PM10 and PM2.5 (particulate matter with aerodynamic diameter smaller than 10 μm and 2.5 μm, respectively) is associated with a range of adverse health effects, including cancer, pulmonary and cardiovascular diseases. Surface characteristics (chemical reactivity, surface area) are considered of prime importance to understand the mechanisms which lead to harmful effects. A hypothetical mechanism to explain these adverse effects is the ability of components (organics, metal ions) adsorbed on these particles to generate Reactive Oxygen Species (ROS), and thereby to cause oxidative stress in biological systems (Donaldson et al., 2003). ROS can attack almost any cellular structure, like DNA or cellular membrane, leading to the formation of a wide variety of degradation products which can be used as a biomarker of oxidative stress. The aim of the present research project is to test whether there is a correlation between the exposure to Diesel Exhaust Particulate (DEP) and the oxidative stress status. For that purpose, a survey has been conducted in real occupational situations where workers were exposed to DEP (bus depots). Different exposure variables have been considered: - particulate number, size distribution and surface area (SMPS); - particulate mass - PM2.5 and PM4 (gravimetry); - elemental and organic carbon (coulometry); - total adsorbed heavy metals - iron, copper, manganese (atomic adsorption); - surface functional groups present on aerosols (Knudsen flow reactor). (Demirdjian et al., 2005). Several biomarkers of oxidative stress (8-hydroxy-2'-deoxyguanosine and several aldehydes) have been determined either in urine or serum of volunteers. Results obtained during the sampling campaign in several bus depots indicated that the occupational exposure to particulates in these places was rather low (40-50 μg/m3 for PM4). Size distributions indicated that particles are within the nanometric range. Surface characteristics of sampled particles varied strongly, depending on the bus depot. They were usually characterized by high carbonyl and low acidic sites content. Among the different biomarkers which have been analyzed within the framework of this study, mean levels of 8- hydroxy-2'-deoxyguanosine and several aldehydes (hexanal, heptanal, octanal, nonanal) increased during two consecutive days of exposure for non-smokers. In order to bring some insight into the relation between the particulate characteristics and the formation of ROS by-products, biomarkers levels will be discussed in relation with exposure variables.

MIBG scintigraphy for the diagnosis and follow-up of children with neuroblastoma.

Neuroblastoma (NBL) is the commonest extra-cranial solid tumor in children and the leading cause of cancer related deaths in childhood between the age of 1 to 4 years. NBL may behave in very different ways, from the less aggressive stage 4S NBL or congenital forms that may resolve without treatment in up to 90% of the children, to the high-risk disseminated stage 4 disease in older children with a cure rate of 35 to 40%. Initial staging is crucial for effective management and radiolabeled metaiodobenzylguanidine (MIBG) with iodine-123 is a powerful tool with a sensitivity around 90% and a specificity close to 100% for the diagnosis of NBL. MIBG scintigraphy is used routinely and is mandatory in most investigational clinical trials both for the initial staging of the disease, the evaluation of the response to treatment, as well as for the detection of recurrence during follow-up. With respect to outcome of children presenting disseminated stage 4 NBL, the role of post-therapeutic [(123)I]MIBG scan has been investigated by several groups but so far there is no consensus whereas a complete or very good partial response as assessed by MIBG may be of prognostic value. NBL needs a multimodality approach at diagnosis and during follow-up and MIBG scintigraphy keeps its pivotal role, in particular with respect to bone marrow involvement and/or cortical bone metastases.

Behavioral phenotyping of glutathione-deficient mice: Relevance to schizophrenia and bipolar disorder.

Redox-dysregulation represents a common pathogenic mechanism in schizophrenia (SZ) and bipolar disorder (BP). It may in part arise from a genetically compromised synthesis of glutathione (GSH), the major cellular antioxidant and redox-regulator. Allelic variants of the genes coding for the rate-limiting GSH synthesizing enzyme glutamate-cysteine-ligase modifier (GCLM) and/or catalytic (GCLC) subunit have been associated with SZ and BP. Using mice knockout (KO) for GCLM we have previously shown that impaired GSH synthesis is associated with morphological, functional and neurochemical anomalies similar to those in patients. Here we asked whether GSH deficit is also associated with SZ- and BP-relevant behavioral and cognitive anomalies. Accordingly, we subjected young adult GCLM-wildtype (WT), heterozygous and KO males to a battery of standard tests. Compared to WT, GCLM-KO mice displayed hyperlocomotion in the open field and forced swim test but normal activity in the home cage, suggesting that hyperlocomotion was selective to environmental novelty and mildly stressful situations. While spatial working memory and latent inhibition remained unaffected, KO mice showed a potentiated hyperlocomotor response to an acute amphetamine injection, impaired sensorymotor gating in the form of prepulse inhibition and altered social behavior compared to WT. These anomalies resemble important aspects of both SZ and the manic component of BP. As such our data support the notion that redox-dysregulation due to GSH deficit is implicated in both disorders. Moreover, our data propose the GCLM-KO mouse as a valuable model to study the behavioral and cognitive consequences of redox dysregulation in the context of psychiatric disease.

Who is at low risk for cardiovascular disease? An assessment of different definitions

Background: There is little information regarding the determinants and trends of the prevalence of low cardiovascular risk factor (RF) profile in the general population. The aim of this study was to assess the prevalence and trends of low RF profile in the Swiss population according to different definitions. Methods: Population-based cross-sectional studies conducted in 1984-6 (N=3300), 1988-9 (N=3331), 1992-3 (N=3133) and 2003-6 (N=6170) and restricted to age group 35-75 years. Seven different definitions of low RF profile were used to assess determinants, while two definitions were used to assess trends. Results: Prevalence of low RF profile varied between 6.5% (95% confidence interval: 5.9-7.1) and 9.7% (9.0-10.5) depending on the definition used. This prevalence was higher than in other countries. Irrespective of the definition used, the prevalence of low RF profile was higher in women and in physically active participants, and decreased with increasing age or in the presence of a family history of cardiovascular disease. Using one definition, the prevalence of low RF profile increased from 3.8% (3.1-4.5) in 1984-6 to 6.7% (6.1-7.3) in 2003-6; using another definition, the results were 5.9% (5.1-6.8) and 9.7% (9.0-10.5), respectively. Conclusion: Switzerland is characterized by a high and increasing prevalence of low RF profile within the age group 35 to 75, irrespective of the criteria used. This high prevalence might partly e

Toward a Statistically Robust Assessment of Social and Solidarity Economy Actors. Conceptual Development and Empirical Validation

Many definitions and debates exist about the core characteristics of social and solidarity economy (SSE) and its actors. Among others, legal forms, profit, geographical scope, and size as criteria for identifying SSE actors often reveal dissents among SSE scholars. Instead of using a dichotomous, either-in-or-out definition of SSE actors, this paper presents an assessment tool that takes into account multiple dimensions to offer a more comprehensive and nuanced view of the field. We first define the core dimensions of the assessment tool by synthesizing the multiple indicators found in the literature. We then empirically test these dimensions and their interrelatedness and seek to identify potential clusters of actors. Finally we discuss the practical implications of our model.