Surface deterioration of dental materials after simulated toothbrushing in relation to brushing time and load.

OBJECTIVES: (1) To evaluate the changes in surface roughness and gloss after simulated toothbrushing of 9 composite materials and 2 ceramic materials in relation to brushing time and load in vitro; (2) to assess the relationship between surface gloss and surface roughness. METHODS: Eight flat specimens of composite materials (microfilled: Adoro, Filtek Supreme, Heliomolar; microhybrid: Four Seasons, Tetric EvoCeram; hybrid: Compoglass F, Targis, Tetric Ceram; macrohybrid: Grandio), two ceramic materials (IPS d.SIGN and IPS Empress polished) were fabricated according to the manufacturer's instructions and optimally polished with up to 4000 grit SiC. The specimens were subjected to a toothbrushing (TB) simulation device (Willytec) with rotating movements, toothpaste slurry and at three different loads (100g/250g/350g). At hourly intervals from 1h to 10h TB, mean surface roughness Ra was measured with an optical sensor and the surface gloss (Gl) with a glossmeter. Statistical analysis was performed for log-transformed Ra data applying two-way ANOVA to evaluate the interaction between load and material and load and brushing time. RESULTS: There was a significant interaction between material and load as well as between load and brushing time (p<0.0001). The microhybrid and hybrid materials demonstrated more surface deterioration with higher loads, whereas with the microfilled resins Heliomolar and Adoro it was vice versa. For ceramic materials, no or little deterioration was observed over time and independent of the load. The ceramic materials and 3 of the composite materials (roughness) showed no further deterioration after 5h of toothbrushing. Mean surface gloss was the parameter which discriminated best between the materials, followed by mean surface roughness Ra. There was a strong correlation between surface gloss and surface roughness for all the materials except the ceramics. The evaluation of the deterioration curves of individual specimens revealed a more or less synchronous course suspecting hinting specific external conditions and not showing the true variability in relation to the tested material. SIGNIFICANCE: The surface roughness and gloss of dental materials changes with brushing time and load and thus results in different material rankings. Apart from Grandio, the hybrid composite resins were more prone to surface changes than microfilled composites. The deterioration potential of a composite material can be quickly assessed by measuring surface gloss. For this purpose, a brushing time of 10h (=72,000 strokes) is needed. In further comparative studies, specimens of different materials should be tested in one series to estimate the true variability.

Bioclimatic constraints to Andean cat distribution: a modelling application for rare species

AimTo identify the bioclimatic niche of the endangered Andean cat (Leopardus jacobita), one of the rarest and least known felids in the world, by developing a species distribution model.LocationSouth America, High Andes and Patagonian steppe. Peru, Bolivia, Chile, Argentina.MethodsWe used 108 Andean cat records to build the models, and 27 to test them, applying the Maxent algorithm to sets of uncorrelated bioclimatic variables from global databases, including elevation. We based our biogeographical interpretations on the examination of the predicted geographic range, the modelled response curves and latitudinal variations in climatic variables associated with the locality data.ResultsSimple bioclimatic models for Andean cats were highly predictive with only 3-4 explanatory variables. The climatic niche of the species was defined by extreme diurnal variations in temperature, cold minimum and moderate maximum temperatures, and aridity, characteristic not only of the Andean highlands but also of the Patagonian steppe. Argentina had the highest representation of suitable climates, and Chile the lowest. The most favourable conditions were centrally located and spanned across international boundaries. Discontinuities in suitable climatic conditions coincided with three biogeographical barriers associated with climatic or topographic transitions.Main conclusionsSimple bioclimatic models can produce useful predictions of suitable climatic conditions for rare species, including major biogeographical constraints. In our study case, these constraints are also known to affect the distribution of other Andean species and the genetic structure of Andean cat populations. We recommend surveys of areas with suitable climates and no Andean cat records, including the corridor connecting two core populations. The inclusion of landscape variables at finer scales, crucially the distribution of Andean cat prey, would contribute to refine our predictions for conservation applications.

A validated assay for measuring doxorubicin in biological fluids and tissues in an isolated lung perfusion model: matrix effect and heparin interference strongly influence doxorubicin measurements.

Doxorubicin is an antineoplasic agent active against sarcoma pulmonary metastasis, but its clinical use is hampered by its myelotoxicity and its cumulative cardiotoxicity, when administered systemically. This limitation may be circumvented using the isolated lung perfusion (ILP) approach, wherein a therapeutic agent is infused locoregionally after vascular isolation of the lung. The influence of the mode of infusion (anterograde (AG): through the pulmonary artery (PA); retrograde (RG): through the pulmonary vein (PV)) on doxorubicin pharmacokinetics and lung distribution was unknown. Therefore, a simple, rapid and sensitive high-performance liquid chromatography method has been developed to quantify doxorubicin in four different biological matrices (infusion effluent, serum, tissues with low or high levels of doxorubicin). The related compound daunorubicin was used as internal standard (I.S.). Following a single-step protein precipitation of 500 microl samples with 250 microl acetone and 50 microl zinc sulfate 70% aqueous solution, the obtained supernatant was evaporated to dryness at 60 degrees C for exactly 45 min under a stream of nitrogen and the solid residue was solubilized in 200 microl of purified water. A 100 microl-volume was subjected to HPLC analysis onto a Nucleosil 100-5 microm C18 AB column equipped with a guard column (Nucleosil 100-5 microm C(6)H(5) (phenyl) end-capped) using a gradient elution of acetonitrile and 1-heptanesulfonic acid 0.2% pH 4: 15/85 at 0 min-->50/50 at 20 min-->100/0 at 22 min-->15/85 at 24 min-->15/85 at 26 min, delivered at 1 ml/min. The analytes were detected by fluorescence detection with excitation and emission wavelength set at 480 and 550 nm, respectively. The calibration curves were linear over the range of 2-1000 ng/ml for effluent and plasma matrices, and 0.1 microg/g-750 microg/g for tissues matrices. The method is precise with inter-day and intra-day relative standard deviation within 0.5 and 6.7% and accurate with inter-day and intra-day deviations between -5.4 and +7.7%. The in vitro stability in all matrices and in processed samples has been studied at -80 degrees C for 1 month, and at 4 degrees C for 48 h, respectively. During initial studies, heparin used as anticoagulant was found to profoundly influence the measurements of doxorubicin in effluents collected from animals under ILP. Moreover, the strong matrix effect observed with tissues samples indicate that it is mandatory to prepare doxorubicin calibration standard samples in biological matrices which would reflect at best the composition of samples to be analyzed. This method was successfully applied in animal studies for the analysis of effluent, serum and tissue samples collected from pigs and rats undergoing ILP.

Präoperative Azidose und Entwicklung von Säuglingen nach Operation angeborener Herzfehler Preoperative acidosis and infant development following surgery for congenital heart disease.

OBJECTIVE: Prenatal diagnosis has been shown to decrease pre-operative acidosis and might prevent the occurrence of disturbed developmental outcome. The aim of this study is to evaluate parameters for acidosis and their predictive value on developmental outcome in newborns with congenital heart disease. METHODS: A total of 117 patients requiring surgery for structural heart disease in the first 31 days of life were included. Diagnosis was established either pre- or postnatally. Preoperative values of lactate, pH and base excess levels were compared to the occurrence of disturbed developmental outcome, i.e. an underperformance of more than 10% on the P90 of a standardized Dutch developmental scale. Patients were divided into groups according to blood levels of acidosis parameters, using receiver operating characteristics curves to determine cut-off values for pH, base excess and lactate. RESULTS: No significant difference in developmental outcome was found using values for pH or base excess as a cut-off level. Preoperative lactate values exceeding 6.1 mmol/l resulted in a significant increase in impaired development compared to infants with a pre-operative lactate lower than 6.1 mmol/l: 40.9% vs 15.1% in (p=0.03). CONCLUSIONS: Pre-operative lactate values might have a prognostic value on developmental outcome in newborns with congenital heart disease. The limited prognostic value of pH can be explained by the fact that pH can be easily corrected, while lactate better reflects the total oxygen debt experienced by these patients.

Growth arrest-specific gene 6 » (Gas6) as an intra-hospital mortality predictor for patients in septic shock

Aim: Gas6 is known to be elevated in sepsis, correlating with the severity of infection and¦organ failure. We aimed to investigate the performance of Gas6 plasma levels at¦admission to predict the risk of mortality in a cohort of septic patients.¦Methods: We used prospectively collected data and plasma samples from the "Sepsis¦Cohorte Romande". Gas6 level was measured by ELISA at admission and expressed in¦percentage relative to its level in a pool of normal plasma.¦Results: Non-survivors (n=21) presented higher Gas6 levels than survivors (n=73) (median¦258% vs 164%, IQR 194 and 117 respectively) (p=0.0027). Gas6 correlated positively with¦different cytokines and was the best mortality predictor, as shown by the ROC curves area.¦In patients with septic shock (n=66), using 249% as a cut-off value, Gas6 measurement¦had a specificity of 67% and a sensitivity of 81% for predicting mortality. ROC curve area¦was 0.75. Positive and negative predictive values were 57% and 87%, respectively.¦Conclusion: Thus, Gas6 plasma level at admission might be a useful tool to predict¦mortality in patients with septic shock. Although Gas6 hold promise as an early sepsis¦marker, its precise implication in sepsis remains to be elucidated. Our observation should¦be further investigated in larger prospective clinical trials.

BIOMOD - a platform for ensemble forecasting of species distributions

BIOMOD is a computer platform for ensemble forecasting of species distributions, enabling the treatment of a range of methodological uncertainties in models and the examination of species-environment relationships. BIOMOD includes the ability to model species distributions with several techniques, test models with a wide range of approaches, project species distributions into different environmental conditions (e.g. climate or land use change scenarios) and dispersal functions. It allows assessing species temporal turnover, plot species response curves, and test the strength of species interactions with predictor variables. BIOMOD is implemented in R and is a freeware, open source, package

Insulin-like growth factor I (IGF I) stimulates DNA synthesis in fetal rat brain cell cultures.

Addition of insulin, IGF I or IGF II to serum-free cultures of fetal rat brain cells (gestation day 15/16) significantly stimulates DNA synthesis. The dose-response curves show that IGF I is more potent than insulin; half maximal stimulation of [3H]thymidine incorporation is obtained at about 0.4 nM IGF I and 14 nM insulin, respectively. Cultures initiated 2 days later (gestation day 17/18) showed a decreased responsiveness to both peptides. No additive effect was observed after combined addition of both peptides at near-maximal doses. Both peptides show a latency of action of about 12-18 h. In the presence of either IGF or insulin, neuronal as well as glial enzymes are increased, suggesting that neuronal and glial precursor cell division is influenced. IGF I and IGF II interact with a specific binding site for which insulin competes very weakly; however IGF I and IGF II bind with relatively high affinity to the insulin specific binding site. The present results support the hypothesis that both insulin and IGF stimulate mitotic activity by interacting with specific somatomedin receptors and suggest a physiological role of IGF in the developing brain.

Improving generalized regression analysis for the spatial prediction of forest communities

Aim This study used data from temperate forest communities to assess: (1) five different stepwise selection methods with generalized additive models, (2) the effect of weighting absences to ensure a prevalence of 0.5, (3) the effect of limiting absences beyond the environmental envelope defined by presences, (4) four different methods for incorporating spatial autocorrelation, and (5) the effect of integrating an interaction factor defined by a regression tree on the residuals of an initial environmental model. Location State of Vaud, western Switzerland. Methods Generalized additive models (GAMs) were fitted using the grasp package (generalized regression analysis and spatial predictions, http://www.cscf.ch/grasp). Results Model selection based on cross-validation appeared to be the best compromise between model stability and performance (parsimony) among the five methods tested. Weighting absences returned models that perform better than models fitted with the original sample prevalence. This appeared to be mainly due to the impact of very low prevalence values on evaluation statistics. Removing zeroes beyond the range of presences on main environmental gradients changed the set of selected predictors, and potentially their response curve shape. Moreover, removing zeroes slightly improved model performance and stability when compared with the baseline model on the same data set. Incorporating a spatial trend predictor improved model performance and stability significantly. Even better models were obtained when including local spatial autocorrelation. A novel approach to include interactions proved to be an efficient way to account for interactions between all predictors at once. Main conclusions Models and spatial predictions of 18 forest communities were significantly improved by using either: (1) cross-validation as a model selection method, (2) weighted absences, (3) limited absences, (4) predictors accounting for spatial autocorrelation, or (5) a factor variable accounting for interactions between all predictors. The final choice of model strategy should depend on the nature of the available data and the specific study aims. Statistical evaluation is useful in searching for the best modelling practice. However, one should not neglect to consider the shapes and interpretability of response curves, as well as the resulting spatial predictions in the final assessment.

Label-free cytotoxicity screening assay by digital holographic microscopy

Abstract We introduce a label-free technology based on digital holographic microscopy (DHM) with applicability for screening by imaging, and we demonstrate its capability for cytotoxicity assessment using mammalian living cells. For this first high content screening compatible application, we automatized a digital holographic microscope for image acquisition of cells using commercially available 96-well plates. Data generated through both label-free DHM imaging and fluorescence-based methods were in good agreement for cell viability identification and a Z'-factor close to 0.9 was determined, validating the robustness of DHM assay for phenotypic screening. Further, an excellent correlation was obtained between experimental cytotoxicity dose-response curves and known IC values for different toxic compounds. For comparable results, DHM has the major advantages of being label free and close to an order of magnitude faster than automated standard fluorescence microscopy.

Evolutionary rates of Jurassic ammonites in relation to sea-level fluctuations

An analysis is presented of the diversity and faunal turnover of Jurassic ammonites related to transgressive /regressive events. The data set contained 400 genera and 1548 species belonging to 67 ammonite zones covering the entire Jurassic System. These data were used in the construction of faunal turnover curves and ammonite diversities, that correlate with sea-level fluctuation curves. Twenty-four events of ammonite faunal turnover are analyzed throughout the Jurassic. The most important took place at the Sinemurian-Carixian boundary, latest Carixian-Middle Domerian, Domerian-Toarcian boundary, latest Middle Toarcian-Late Toarcian, Toarcian-Aalenian boundary, latest Aalenian-earliest Bajocian, latest Early Bajocian-earliest Late Bojocian, Early Bathonian-Middle Bathonian boundary, latest Middle Bathonian-earliest Late Bathonian, latest Bathonian-Early Callovian, earliest Early Oxfordian-Middle Oxfordian, earliest Late Oxfordian-latest Oxfordian, latest Early Kimmeridgian, Late Kimmeridgian, middle Early Tithonian and Early Tithonian-Late Tithonian boundary. More than 75 percent of these turnovers correlate with regressive-transgressive cycles in the Exxon, and /or Hallam's sea-level curves. Inmost cases the extinction events coincide with regressive intervals, whereas origination and radiation events are related to transgressive cycles. The turnovers frequently coincide with major or minor discontinuities in the Subbetic basin (Betic Cordillera).

Automated quantitative pupillometry for the prognostication of coma after cardiac arrest.

BACKGROUND: Sedation and therapeutic hypothermia (TH) delay neurological responses and might reduce the accuracy of clinical examination to predict outcome after cardiac arrest (CA). We examined the accuracy of quantitative pupillary light reactivity (PLR), using an automated infrared pupillometry, to predict outcome of post-CA coma in comparison to standard PLR, EEG, and somato-sensory evoked potentials (SSEP). METHODS: We prospectively studied over a 1-year period (June 2012-June 2013) 50 consecutive comatose CA patients treated with TH (33 °C, 24 h). Quantitative PLR (expressed as the % of pupillary response to a calibrated light stimulus) and standard PLR were measured at day 1 (TH and sedation; on average 16 h after CA) and day 2 (normothermia, off sedation: on average 46 h after CA). Neurological outcome was assessed at 90 days with Cerebral Performance Categories (CPC), dichotomized as good (CPC 1-2) versus poor (CPC 3-5). Predictive performance was analyzed using area under the ROC curves (AUC). RESULTS: Patients with good outcome [n = 23 (46 %)] had higher quantitative PLR than those with poor outcome [n = 27; 16 (range 9-23) vs. 10 (1-30) % at day 1, and 20 (13-39) vs. 11 (1-55) % at day 2, both p < 0.001]. Best cut-off for outcome prediction of quantitative PLR was <13 %. The AUC to predict poor outcome was higher for quantitative than for standard PLR at both time points (day 1, 0.79 vs. 0.56, p = 0.005; day 2, 0.81 vs. 0.64, p = 0.006). Prognostic accuracy of quantitative PLR was comparable to that of EEG and SSEP (0.81 vs. 0.80 and 0.73, respectively, both p > 0.20). CONCLUSIONS: Quantitative PLR is more accurate than standard PLR in predicting outcome of post-anoxic coma, irrespective of temperature and sedation, and has comparable prognostic accuracy than EEG and SSEP.

The IFNL3/4 ΔG variant increases susceptibility to cytomegalovirus retinitis among HIV-infected patients.

BACKGROUND: Cytomegalovirus (CMV) retinitis is a major cause of visual impairment and blindness among patients with uncontrolled HIV infections. Whereas polymorphisms in interferon-lambda 3 (IFNL3, previously named IL28B) strongly influence the clinical course of hepatitis C, few studies examined the role of such polymorphisms in infections due to viruses other than hepatitis C virus. OBJECTIVES: To analyze the association of newly identified IFNL3/4 variant rs368234815 with susceptibility to CMV-associated retinitis in a cohort of HIV-infected patients. DESIGN AND METHODS: This retrospective longitudinal study included 4884 white patients from the Swiss HIV Cohort Study, among whom 1134 were at risk to develop CMV retinitis (CD4 nadir <100 /μl and positive CMV serology). The association of CMV-associated retinitis with rs368234815 was assessed by cumulative incidence curves and multivariate Cox regression models, using the estimated date of HIV infection as a starting point, with censoring at death and/or lost follow-up. RESULTS: A total of 40 individuals among 1134 patients at risk developed CMV retinitis. The minor allele of rs368234815 was associated with a higher risk of CMV retinitis (log-rank test P = 0.007, recessive mode of inheritance). The association was still significant in a multivariate Cox regression model (hazard ratio 2.31, 95% confidence interval 1.09-4.92, P = 0.03), after adjustment for CD4 nadir and slope, HAART and HIV-risk groups. CONCLUSION: We reported for the first time an association between an IFNL3/4 polymorphism and susceptibility to AIDS-related CMV retinitis. IFNL3/4 may influence immunity against viruses other than HCV.

Test of four colon cancer risk-scores in formalin fixed paraffin embedded microarray gene expression data.

BACKGROUND: Prognosis prediction for resected primary colon cancer is based on the T-stage Node Metastasis (TNM) staging system. We investigated if four well-documented gene expression risk scores can improve patient stratification. METHODS: Microarray-based versions of risk-scores were applied to a large independent cohort of 688 stage II/III tumors from the PETACC-3 trial. Prognostic value for relapse-free survival (RFS), survival after relapse (SAR), and overall survival (OS) was assessed by regression analysis. To assess improvement over a reference, prognostic model was assessed with the area under curve (AUC) of receiver operating characteristic (ROC) curves. All statistical tests were two-sided, except the AUC increase. RESULTS: All four risk scores (RSs) showed a statistically significant association (single-test, P < .0167) with OS or RFS in univariate models, but with HRs below 1.38 per interquartile range. Three scores were predictors of shorter RFS, one of shorter SAR. Each RS could only marginally improve an RFS or OS model with the known factors T-stage, N-stage, and microsatellite instability (MSI) status (AUC gains < 0.025 units). The pairwise interscore discordance was never high (maximal Spearman correlation = 0.563) A combined score showed a trend to higher prognostic value and higher AUC increase for OS (HR = 1.74, 95% confidence interval [CI] = 1.44 to 2.10, P < .001, AUC from 0.6918 to 0.7321) and RFS (HR = 1.56, 95% CI = 1.33 to 1.84, P < .001, AUC from 0.6723 to 0.6945) than any single score. CONCLUSIONS: The four tested gene expression-based risk scores provide prognostic information but contribute only marginally to improving models based on established risk factors. A combination of the risk scores might provide more robust information. Predictors of RFS and SAR might need to be different.

Early multimodal outcome prediction after cardiac arrest in patients treated with hypothermia.

OBJECTIVES: Therapeutic hypothermia and pharmacological sedation may influence outcome prediction after cardiac arrest. The use of a multimodal approach, including clinical examination, electroencephalography, somatosensory-evoked potentials, and serum neuron-specific enolase, is recommended; however, no study examined the comparative performance of these predictors or addressed their optimal combination. DESIGN: Prospective cohort study. SETTING: Adult ICU of an academic hospital. PATIENTS: One hundred thirty-four consecutive adults treated with therapeutic hypothermia after cardiac arrest. MEASUREMENTS AND MAIN RESULTS: Variables related to the cardiac arrest (cardiac rhythm, time to return of spontaneous circulation), clinical examination (brainstem reflexes and myoclonus), electroencephalography reactivity during therapeutic hypothermia, somatosensory-evoked potentials, and serum neuron-specific enolase. Models to predict clinical outcome at 3 months (assessed using the Cerebral Performance Categories: 5 = death; 3-5 = poor recovery) were evaluated using ordinal logistic regressions and receiving operator characteristic curves. Seventy-two patients (54%) had a poor outcome (of whom, 62 died), and 62 had a good outcome. Multivariable ordinal logistic regression identified absence of electroencephalography reactivity (p < 0.001), incomplete recovery of brainstem reflexes in normothermia (p = 0.013), and neuron-specific enolase higher than 33 μg/L (p = 0.029), but not somatosensory-evoked potentials, as independent predictors of poor outcome. The combination of clinical examination, electroencephalography reactivity, and neuron-specific enolase yielded the best predictive performance (receiving operator characteristic areas: 0.89 for mortality and 0.88 for poor outcome), with 100% positive predictive value. Addition of somatosensory-evoked potentials to this model did not improve prognostic accuracy. CONCLUSIONS: Combination of clinical examination, electroencephalography reactivity, and serum neuron-specific enolase offers the best outcome predictive performance for prognostication of early postanoxic coma, whereas somatosensory-evoked potentials do not add any complementary information. Although prognostication of poor outcome seems excellent, future studies are needed to further improve prediction of good prognosis, which still remains inaccurate.

Long-term sequelae in children surviving adult respiratory distress syndrome.

Nine children surviving severe adult respiratory distress syndrome were studied 0.9 to 4.2 years after the acute illness. They had received artificial ventilation for a mean of 9.4 days, with an Fio2 greater than 0.5 during a mean time of 34 hours and maximal positive end expiratory pressure levels in the range of 8 to 20 cm H2O. Three children had recurrent respiratory symptoms (moderate exertional dyspnea and cough), and two had evidence of fibrosis on chest radiographs. All patients had abnormal lung function; the most prominent findings were ventilation inequalities, as judged by real-time moment ratio analysis of multibreath nitrogen washout curves (abnormal in eight of nine patients) and hypoxemia (seven of nine). Lung volumes were less abnormal; one patient had restrictive and two had obstructive disease. A significant correlation between intensive care measures (Fio2 greater than 0.5 in hours and peak inspiratory plateau pressure) and lung function abnormalities (moment ratio analysis and hypoxemia) was found. A possibly increased susceptibility of the pediatric age group to the primary insult or respiratory therapy of adult respiratory distress syndrome is suggested.