A concentric analysis of the impact of urbanization on the threatened European tree frog in an agricultural landscape

Pond-breeding amphibians are affected by site-specific factors and regional and landscape-scale patterns of land use. Recent anthropogenic landscape modifications (drainage, agriculture intensification, larger road networks, and increased traffic) affect species by reducing the suitable habitat area and fragmenting remaining populations. Using a robust concentric approach based on permutation tests, we evaluated the impact of recent landscape changes on the presence of the endangered European tree frog (Hyla arborea.) in wetlands. We analyzed the frequency of 1 traffic and 14 land-use indices at 20 circular ranges (from 100-m up to 2-km radii) around 76 ponds identified in western Switzerland. Urban areas and road surfaces had a strong adverse effect on tree frog presence even at relatively great distances (from 100 m up to 1 km). When traffic measurements were considered instead of road surfaces, the effect increased, suggesting a negative impact due to a vehicle-induced effect. Altogether, our results indicate that urbanization and traffic must be taken into account when pond creation is an option in conservation management plans, as is the case for the European tree frog in western Switzerland. We conclude that our easy-to-use and robust concentric method of analysis can successfully assist managers in identifying potential sites for pond creation, where probability of the presence of tree frogs is maximized.

Dimensionality of drinking consequences - cross-cultural comparability and stability over time

Despite the long tradition for asking about the negative social and health consequences of alcohol consumption in surveys, little is known about the dimensionality of these consequences. Analysing cross-sectional and longitudinal data from the Nordic Taxation Study collected for Sweden, Finland, and Denmark in two waves in 2003 and 2004 by means of an explorative principal component analysis for categorical data (CATPCA), it is tested whether consequences have a single underlying dimension across cultures. It further tests the reliability, replicability, concurrent and predictive validity of the consequence scales. A one-dimensional solution was commonly preferable. Whereas the two-dimensional solution was unable to distinguish clearly between different concepts of consequences, the one-dimensional solution resulted in interpretable, generally very stable scales within countries across different samples and time.

Quantitative ultrasound for the detection and management of osteoporosis.

Quantitative ultrasound (QUS) appears to be developing into an acceptable, low-cost and readily-accessible alternative to dual X-ray absorptiometry (DXA) measurements of bone mineral density (BMD) in the detection and management of osteoporosis. Perhaps the major difficulty with their widespread use is that many different QUS devices exist that differ substantially from each other, in terms of the parameters they measure and the strength of empirical evidence supporting their use. But another problem is that virtually no data exist outside of Caucasian or Asian populations. In general, heel QUS appears to be most tested and most effective. Some, but not all heel QUS devices are effective assessing fracture risk in some, but not all populations, the evidence being strongest for Caucasian females > 55 years old, though some evidence exists for Asian females > 55 and for Caucasian and Asian males > 70. Certain devices may allow to estimate the likelihood of osteoporosis, but very limited evidence exists supporting QUS use during the initiation or monitoring of osteoporosis treatment. Likely, QUS is most effective when combined with an assessment of clinical risk factors (CRF); with DXA reserved for individuals who are not identified as either high or low risk using QUS and CRF. However, monitoring and maintenance of test and instrument accuracy, precision and reproducibility are essential if QUS devices are to be used in clinical practice; and further scientific research in non-Caucasian, non-Asian populations clearly is compulsory to validate this tool for more widespread use.

Late Cretaceous and Paleogene Radiolaria from the Nicoya Peninsula, Costa Rica: a tectonostratigraphic application

Detailed field mapping and paleontological dating in the central and southeastern Nicoya Peninsula has revealed Late Cretaceous and Paleogene radiolarian-bearing siliceous mudstones. These rocks belong to two terranes (Matambfi and Manzanillo) that are partially contemporaneous with the Nicoya Complex, but are genetically different. While the Nicoya Complex is formed exclusively by intraplate igneous rocks with associated radiolarites, the studied sections include variable amounts of are-derived volcanic and terrigenous materials. These fore-arc terranes include mafic to intermediate volcaniclastics and associated pelagic and hemipelagic rocks rich in biogenic silica. Radiolarian preservation in these sediments is often enhanced by the presence of silica-saturated volcanic tuffs and debris. Seven out of 29 samples from different outcrops yielded relatively well-preserved radiolarian faunas. In total, 60 species belonging to 34 genera were present in these faunas, ranging in age from middle Turonian-Santonian to late Thanetian-Ypresian.

L'Académie de Lausanne entre Humanisme et Réforme (ca. 1537-1560)

L'Académie de Lausanne est la première école supérieure protestante implantée en territoire francophone. Lausanne constitue ainsi, dès les années 1540, un pôle de première importance dans le monde réformé. De nombreux savants protestants, attirés par la liberté de pratiquer leur foi et par la présence de l'Académie, s'établissent dans cette ville et des étudiants affluent de toute l'Europe. Les structures de l'Académie de Lausanne et son programme d'enseignement, fixés par un règlement daté de 1547, condensent sous une forme nouvelle les réflexions pédagogiques de la Renaissance. Ils constituent un modèle, direct ou indirect, pour toutes les Académies calvinistes fondées aux XVIème et XVIIème siècles, que ce soit à Genève, en France, en Allemagne, aux Pays-Bas, en Écosse, en Pologne ou encore aux États-Unis, dont les trois premiers Colleges, Harvard, William and Mary et Yale, se situent dans la même tradition. Malgré la place fondamentale qu'occupe l'Académie de Lausanne dans l'histoire de l'éducation protestante, la phase de création et de développement de cette institution était encore très mal connue. Cette thèse comble cette lacune de l'historiographie par la mise au jour et par l'analyse de nombreux documents, en grande partie inédits. Elle détruit bon nombre de préjugés entourant la mise en place et les buts de l'Académie de Lausanne à ses débuts. Ainsi, l'Académie de Lausanne n'est pas uniquement une école de pasteurs, comme il a souvent été affirmé jusqu'à ce jour, mais plus largement une institution offrant une formation d'un niveau très élevé dans les trois langues anciennes, (latin, grec et hébreu), en arts libéraux, en philosophie naturelle et morale, et en théologie. Au milieu du XVIème siècle, l'Académie lausannoise est capable de rivaliser avec les meilleures institutions pédagogiques de la Renaissance et d'attirer, dans un rayon très large, non seulement des étudiants qui se destinent au pastorat, mais aussi ceux qui sont formés pour gouverner leurs cités. Plus généralement, cette thèse, qui combine des approches d'histoire intellectuelle, d'histoire politique et d'histoire sociale, reconstitue et analyse les structures de l'Académie de Lausanne jusqu'à 1560, ainsi que ses fonctions éducatives, confessionnelles et politiques.

Notch signaling is required for normal prostatic epithelial cell proliferation and differentiation.

Notch pathway is crucial for stem/progenitor cell maintenance, growth and differentiation in a variety of tissues. Using a transgenic cell ablation approach, we found in our previous study that cells expressing Notch1 are crucial for prostate early development and re-growth. Here, we further define the role of Notch signaling in regulating prostatic epithelial cell growth and differentiation using biochemical and genetic approaches in ex vivo or in vivo systems. Treatment of developing prostate grown in culture with inhibitors of gamma-secretase/presenilin, which is required for Notch cleavage and activation, caused a robust increase in proliferation of epithelial cells co-expressing cytokeratin 8 and 14, lack of luminal/basal layer segregation and dramatically reduced branching morphogenesis. Using conditional Notch1 gene deletion mouse models, we found that inactivation of Notch1 signaling resulted in profound prostatic alterations, including increased tufting, bridging and enhanced epithelial proliferation. Cells within these lesions co-expressed both luminal and basal cell markers, a feature of prostatic epithelial cells in predifferentiation developmental stages. Microarray analysis revealed that the gene expression in a number of genetic networks was altered following Notch1 gene deletion in prostate. Furthermore, expression of Notch1 and its effector Hey-1 gene in human prostate adenocarcinomas were found significantly down-regulated compared to normal control tissues. Taken together, these data suggest that Notch signaling is critical for normal cell proliferation and differentiation in the prostate, and deregulation of this pathway may facilitate prostatic tumorigenesis.

Evaluation of monoenergetic imaging to reduce metallic instrumentation artifacts in computed tomography of the cervical spine.

OBJECT Monoenergetic imaging with dual-energy CT has been proposed to reduce metallic artifacts in comparison with conventional polychromatic CT. The purpose of this study is to systematically evaluate and define the optimal dual-energy CT imaging parameters for specific cervical spinal implant alloy compositions. METHODS Spinal fixation rods of cobalt-chromium or titanium alloy inserted into the cervical spine section of an Alderson Rando anthropomorphic phantom were imaged ex vivo with fast-kilovoltage switching CT at 80 and 140 peak kV. The collimation width and field of view were varied between 20 and 40 mm and medium to large, respectively. Extrapolated monoenergetic images were generated at 70, 90, 110, and 130 kiloelectron volts (keV). The standard deviation of voxel intensities along a circular line profile around the spine was used as an index of the magnitude of metallic artifact. RESULTS The metallic artifact was more conspicuous around the fixation rods made of cobalt-chromium than those of titanium alloy. The magnitude of metallic artifact seen with titanium fixation rods was minimized at monoenergies of 90 keV and higher, using a collimation width of 20 mm and large field of view. The magnitude of metallic artifact with cobalt-chromium fixation rods was minimized at monoenergies of 110 keV and higher; collimation width or field of view had no effect. CONCLUSIONS Optimization of acquisition settings used with monoenergetic CT studies might yield reduced metallic artifacts.

Differentiation of postmitotic neuroblasts into substance P-immunoreactive sensory neurons in dissociated cultures of chick dorsal root ganglion.

Counts performed on dissociated cell cultures of E10 chick embryo dorsal root ganglia (DRG) showed after 4-6 days of culture a pronounced decline of the neuronal population in neuron-enriched cultures and a net gain in the number of ganglion cells in mixed DRG cell cultures (containing both neurons and nonneuronal cells). In the latter case, the increase in the number of neurons was found to depend on NGF and to average 119% in defined medium or 129% in horse serum-supplemented medium after 6 days of culture. The lack of [3H]thymidine incorporation into the neuronal population indicated that the newly formed ganglion cells were not generated by proliferation. On the contrary, the differentiation of postmitotic neuroblasts present in the nonneuronal cell compartment was supported by sequential microphotographs of selected fields taken every hour for 48-55 hr after 3 days of culture. Apparently nonneuronal flat dark cells exhibited morphological changes and gradually evolved into neuronal ovoid and refringent cell bodies with expanding neurites. The ultrastructural organization of these evolving cells corresponded to that of primitive or intermediate neuroblasts. The neuronal nature of these rounding up cell bodies was indeed confirmed by the progressive expression of various neuronal cell markers (150 and 200-kDa neurofilament triplets, neuron specific enolase, and D2/N-CAM). Besides a constant lack of immunoreactivity for tyrosine hydroxylase, somatostatin, parvalbumin, and calbindin-D 28K and a lack of cytoenzymatic activity for carbonic anhydrase, all the newly produced neurons expressed three main phenotypic characteristics: a small cell body, a strong immunoreactivity to MAG, and substance P. Hence, ganglion cells newly differentiated in culture would meet characteristics ascribed to small B sensory neurons and more specifically to a subpopulation of ganglion cells containing substance P-immunoreactive material.

Occipitoaxial spinal interarticular stabilization with vertebral artery preservation for atlantal lateral mass failure.

The treatment of craniocervical instability caused by diverse conditions remains challenging. Different techniques have been described to stabilize the craniocervical junction. The authors present 2 cases in which tumoral destruction of the C-1 lateral mass caused craniocervical instability. A one-stage occipitoaxial spinal interarticular stabilization (OASIS) technique with titanium cages and posterior occipitocervical instrumentation was used to reconstruct the C-1 lateral mass and stabilize the craniocervical junction. The ipsilateral vertebral artery was preserved. The OASIS technique offers single-stage tumor resection, C-1 lateral mass reconstruction, and stabilization with a loadsharing construct. It could be an option in the treatment of select cases of C-1 lateral mass failure.

Safety and accuracy of robot-assisted versus fluoroscopy-guided pedicle screw insertion for degenerative diseases of the lumbar spine: a matched cohort comparison.

Object Recent years have been marked by efforts to improve the quality and safety of pedicle screw placement in spinal instrumentation. The aim of the present study is to compare the accuracy of the SpineAssist robot system with conventional fluoroscopy-guided pedicle screw placement. Methods Ninety-five patients suffering from degenerative disease and requiring elective lumbar instrumentation were included in the study. The robot cohort (Group I; 55 patients, 244 screws) consisted of an initial open robot-assisted subgroup (Subgroup IA; 17 patients, 83 screws) and a percutaneous cohort (Subgroup IB, 38 patients, 161 screws). In these groups, pedicle screws were placed under robotic guidance and lateral fluoroscopic control. In the fluoroscopy-guided cohort (Group II; 40 patients, 163 screws) screws were inserted using anatomical landmarks and lateral fluoroscopic guidance. The primary outcome measure was accuracy of screw placement on the Gertzbein-Robbins scale (Grade A to E and R [revised]). Secondary parameters were duration of surgery, blood loss, cumulative morphine, and length of stay. Results In the robot group (Group I), a perfect trajectory (A) was observed in 204 screws (83.6%). The remaining screws were graded B (n = 19 [7.8%]), C (n = 9 [3.7%]), D (n = 4 [1.6%]), E (n = 2 [0.8%]), and R (n = 6 [2.5%]). In the fluoroscopy-guided group (Group II), a completely intrapedicular course graded A was found in 79.8% (n = 130). The remaining screws were graded B (n = 12 [7.4%]), C (n = 10 [6.1%]), D (n = 6 [3.7%]), and E (n = 5 [3.1%]). The comparison of "clinically acceptable" (that is, A and B screws) was neither different between groups (I vs II [p = 0.19]) nor subgroups (Subgroup IA vs IB [p = 0.81]; Subgroup IA vs Group II [p = 0.53]; Subgroup IB vs Group II [p = 0.20]). Blood loss was lower in the robot-assisted group than in the fluoroscopy-guided group, while duration of surgery, length of stay, and cumulative morphine dose were not statistically different. Conclusions Robot-guided pedicle screw placement is a safe and useful tool for assisting spine surgeons in degenerative spine cases. Nonetheless, technical difficulties remain and fluoroscopy backup is advocated.

Immunohistochemical and flow cytometric analysis of long-term label-retaining cells in the adult heart.

Cardiac-resident stem/progenitor cells have been identified based on expression of stem cell-associated antigens. However, no single surface marker allows to identify a definite cardiac stem/progenitor cell entity. Hence, functional stem cell markers have been extensively searched for. In homeostatic systems, stem cells divide infrequently and therefore retain DNA labels such as 5-bromo-2'-deoxyuridine, which are diluted with division. We used this method to analyze long-term label-retaining cells in the mouse heart after 14 days of 5-bromo-2'-deoxyuridine administration. Labeled cells were detected using immunohistochemical and flow-cytometric methods after varying chasing periods up to 12 months. Using mathematical models, the observed label dilution could consistently be described in the context of a 2-population model, whereby a population of rapidly dividing cells accounted for an accelerated early decline, and a population of slowly dividing cells accounted for decelerated dilution on longer time scales. Label-retaining cells were preferentially localized in the atria and apical region and stained negative for markers of the major cell lineages present in the heart. Most cells with long-term label-retention expressed stem cell antigen-1 (Sca-1). Sca-1(+)CD31(-) cells formed cell aggregates in culture, out of which lineage-negative (Lin(-))Sca-1(+)CD31(-) cells emerged, which could be cultured for many passages. These cells formed cardiospheres and showed differentiation potential into mesenchymal cell lineages. When cultured in cardiomyogenic differentiation medium, they expressed cardiac-specific genes. In conclusion, recognition of slow-cycling cells provides functional evidence of stem/progenitor cells in the heart. Lin(-)Sca-1(+)CD31(-) cardiac-derived progenitors have a potential for differentiation into cardiomyogenic and mesenchymal cell lineages.

Neuronal potential of cells in early postnatal rat sciatic nerve.

A population of undifferentiated cells with neuronal potentialities were revealed in rat sciatic nerve. Explant cultures of sciatic nerve were prepared from newborn or early postnatal rat. Cultures were growth in F14 medium supplemented with 10% of fetal calf serum, incubated in a humidified 3% CO2, 97% air atmosphere. Within 2 weeks, refractile cells exhibiting the morphology of neurons were observed in all examined cultures. These cells had ovoid or multipolar refractile cells bodies with extended cytoplasmic processes. The neuronal nature of these cells was confirmed by their immunostaining with specific neuronal markers: neurofilament triplets, neuron-specific enolase, peripherin, microtubule-associated proteins, and brain spectrin. This neuronal population displayed various phenotypes. The CO2 concentration in the incubator plays an important role, since the number of differentiated neurons was lower in cultures incubated in 5% CO2. Since the sciatic nerve is devoid of nerve cell bodies in vivo, we concluded that early postnatal sciatic nerve contains crest cells with neuronal potentialities differentiating into neurons in response to the culture's environmental cues.

Nouveaux traitements de l'hépatite C: aspects pharmacologiques et potentiel d'interaction [New hepatitis C treatments: pharmacological considerations and potential for drug interactions].

Progress in the understanding of the hepatitis C virus life cycle allowed the development of new, very promising antiviral therapies. Although these new drugs have a favourable profile in terms of efficacy, tolerance and interaction potential, their prescription in the setting of comedication and impaired renal or hepatic function remains a challenge. Here, we provide a summary of pharmacological considerations, focusing on sofosbuvir, simeprevir and daclatasvir. A better understanding of their metabolic pathways and transporters may help the prescriber to identify and manage drug interactions especially in patients under immunosuppressive or anti-HIV therapy. Recommendations for the prescription of these drugs in specific situations are also discussed.

Putative adverse outcome pathways relevant to neurotoxicity.

The Adverse Outcome Pathway (AOP) framework provides a template that facilitates understanding of complex biological systems and the pathways of toxicity that result in adverse outcomes (AOs). The AOP starts with an molecular initiating event (MIE) in which a chemical interacts with a biological target(s), followed by a sequential series of KEs, which are cellular, anatomical, and/or functional changes in biological processes, that ultimately result in an AO manifest in individual organisms and populations. It has been developed as a tool for a knowledge-based safety assessment that relies on understanding mechanisms of toxicity, rather than simply observing its adverse outcome. A large number of cellular and molecular processes are known to be crucial to proper development and function of the central (CNS) and peripheral nervous systems (PNS). However, there are relatively few examples of well-documented pathways that include causally linked MIEs and KEs that result in adverse outcomes in the CNS or PNS. As a first step in applying the AOP framework to adverse health outcomes associated with exposure to exogenous neurotoxic substances, the EU Reference Laboratory for Alternatives to Animal Testing (EURL ECVAM) organized a workshop (March 2013, Ispra, Italy) to identify potential AOPs relevant to neurotoxic and developmental neurotoxic outcomes. Although the AOPs outlined during the workshop are not fully described, they could serve as a basis for further, more detailed AOP development and evaluation that could be useful to support human health risk assessment in a variety of ways.