Self-expandable metal stents in the treatment of acute esophageal variceal bleeding.

Acute variceal bleeding (AVB) is a life-threatening complication in patients with cirrhosis. Hemostatic therapy of AVB includes early administration of vasoactive drugs that should be combined with endoscopic therapy, preferably banding ligation. However, failure to control bleeding or early rebleed within 5 days still occurs in 15-20% of patients with AVB. In these cases, a second endoscopic therapy may be attempted (mild bleeding in a hemodynamically stable patient) or we can use a balloon tamponade as a bridge to definitive derivative treatment (i.e., a transjugular intrahepatic portosystemic shunt). Esophageal balloon tamponade provides initial control in up to 80% of AVB, but it carries a high risk of major complications, especially in cases of long duration of tamponade (>24 h) and when tubes are inserted by inexperienced staff. Preliminary reports suggest that self-expandable covered esophageal metallic stents effectively control refractory AVB (i.e., ongoing bleeding despite pharmacological and endoscopic therapy or massive bleeding precluding endoscopic therapy) with a low incidence of complications. Thus, covered self-expanding metal stents may represent an alternative to the Sengstaken-Blakemore balloon for the temporary control of bleeding in treatment failures. Further studies are required to determine the role of this new device in AVB.

Fusion weld metal solidification:Continuum from weld interface to centerline

We present a brief résumé of the history of solidification research and key factors affecting the solidification of fusion welds. There is a general agreement of the basic solidification theory, albeit differing - even confusing - nomenclatures do exist, and Cases 2 and 3 (the Chalmers' basic boundary conditions for solidification, categorized by Savage as Cases) are variably emphasized. Model Frame, a tool helping to model the continuum of fusion weld solidification from start to end, is proposed. It incorporates the general solidification models, of which the pertinent ones are selected for the actual modeling. The basic models are the main solidification Cases 1…4. These discrete Cases are joined with Sub-Cases: models of Pfann, Flemings and others, bringing needed Sub-Case variables into the model. Model Frame depicts a grain growing from the weld interface to its centerline. Besides modeling, the Model Frame supports education and academic debate. The new mathematical modeling techniques will extend its use into multi-dimensional modeling, introducing new variables and increasing the modeling accuracy. We propose a model: melting/solidification-model (M/S-model) - predicting the solute profile at the start of the solidification of a fusion weld. This Case 3-based Sub-Case takes into account the melting stage, the solute back-diffusion in the solid, and the growth rate acceleration typical to fusion welds. We propose - based on works of Rutter & Chalmers, David & Vitek and our experimental results on copper - that NEGS-EGS-transition is not associated only with cellular-dendritic-transition. Solidification is studied experimentally on pure and doped copper with welding speed range from 0 to 200 cm/min, with one test at 3000 cm/min. Found were only planar and cellular structures, no dendrites - columnar or equiaxed. Cell sub structures: rows of cubic elements we call "cubelettes", "cell-bands" and "micro-cells", as well as an anomalous crack morphology "crack-eye", were detected, as well as microscopic hot crack nucleus we call "grain-lag cracks", caused by a grain slightly lagging behind its neighbors in arrival to the weld centerline. Varestraint test and R-test revealed a change of crack morphologies from centerline cracks to grainand cell boundary cracks with an increasing welding speed. High speed made the cracks invisible to bare eye and hardly detectable with light microscope, while electron microscope often revealed networks of fine micro-cracks.

Drug-eluting stents compared to bare-metal stents improve short-term survival in patients with acute myocardial infarction undergoing primary percutaneous coronary intervention: a nationwide prospective analysis of the AMIS Plus registry.

BACKGROUND: Recently, it has been suggested that the type of stent used in primary percutaneous coronary interventions (pPCI) might impact upon the outcomes of patients with acute myocardial infarction (AMI). Indeed, drug-eluting stents (DES) reduce neointimal hyperplasia compared to bare-metal stents (BMS). Moreover, the later generation DES, due to its biocompatible polymer coatings and stent design, allows for greater deliverability, improved endothelial healing and therefore less restenosis and thrombus generation. However, data on the safety and performance of DES in large cohorts of AMI is still limited. AIM: To compare the early outcome of DES vs. BMS in AMI patients. METHODS: This was a prospective, multicentre analysis containing patients from 64 hospitals in Switzerland with AMI undergoing pPCI between 2005 and 2013. The primary endpoint was in-hospital all-cause death, whereas the secondary endpoint included a composite measure of major adverse cardiac and cerebrovascular events (MACCE) of death, reinfarction, and cerebrovascular event. RESULTS: Of 20,464 patients with a primary diagnosis of AMI and enrolled to the AMIS Plus registry, 15,026 were referred for pPCI and 13,442 received stent implantation. 10,094 patients were implanted with DES and 2,260 with BMS. The overall in-hospital mortality was significantly lower in patients with DES compared to those with BMS implantation (2.6% vs. 7.1%,p < 0.001). The overall in-hospital MACCE after DES was similarly lower compared to BMS (3.5% vs. 7.6%, p < 0.001). After adjusting for all confounding covariables, DES remained an independent predictor for lower in-hospital mortality (OR 0.51,95% CI 0.40-0.67, p < 0.001). Since groups differed as regards to baseline characteristics and pharmacological treatment, we performed a propensity score matching (PSM) to limit potential biases. Even after the PSM, DES implantation remained independently associated with a reduced risk of in-hospital mortality (adjusted OR 0.54, 95% CI 0.39-0.76, p < 0.001). CONCLUSIONS: In unselected patients from a nationwide, real-world cohort, we found DES, compared to BMS, was associated with lower in-hospital mortality and MACCE. The identification of optimal treatment strategies of patients with AMI needs further randomised evaluation; however, our findings suggest a potential benefit with DES.

The initial oxidation of transition metal surfaces

Due to their numerous novel technological applications ranging from the example of exhaust catalysts in the automotive industry to the catalytic production of hydro- gen, surface reactions on transition metal substrates have become to be one of the most essential subjects within the surface science community. Although numerous applications exist, there are many details in the different processes that, after many decades of research, remain unknown. There are perhaps as many applications for the corrosion resistant materials such as stainless steels. A thorough knowledge of the details of the simplest reactions occuring on the surfaces, such as oxidation, play a key role in the design of better catalysts, or corrosion resistant materials in the future. This thesis examines the oxidation of metal surfaces from a computational point of view mostly concentrating on copper as a model material. Oxidation is studied from the initial oxidation to the oxygen precovered surface. Important parameters for the initial sticking and dissociation are obtained. The saturation layer is thoroughly studied and the calculated results arecompared with available experimental results. On the saturated surface, some open questions still remain. The present calculations demonstrate, that the saturated part of the surface is excluded from being chemically reactive towards the oxygen molecules. The results suggest, that the reason for the chemical activity of the saturated surface is due to a strain effect occuring between the saturated areas of the surface.

Moths behaving like butterflies. Evolutionary loss of long range attractant pheromones in Castniid Moths: A Paysandisia archon model

Background: In the course of evolution butterflies and moths developed two different reproductive behaviors. Whereas butterflies rely on visual stimuli for mate location, moths use the"female calling plus male seduction" system, in which females release long-range sex pheromones to attract conspecific males. There are few exceptions from this pattern but in all cases known female moths possess sex pheromone glands which apparently have been lost in female butterflies. In the day-flying moth family Castniidae ("butterfly-moths"), which includes some important crop pests, no pheromones have been found so far. Methodology/Principal Findings: Using a multidisciplinary approach we described the steps involved in the courtship of P. archon, showing that visual cues are the only ones used for mate location; showed that the morphology and fine structure of the antennae of this moth are strikingly similar to those of butterflies, with male sensilla apparently not suited to detect female-released long range pheromones; showed that its females lack pheromone-producing glands, and identified three compounds as putative male sex pheromone (MSP) components of P. archon, released from the proximal halves of male forewings and hindwings. Conclusions/Significance: This study provides evidence for the first time in Lepidoptera that females of a moth do not produce any pheromone to attract males, and that mate location is achieved only visually by patrolling males, which may release a pheromone at short distance, putatively a mixture of Z,E-farnesal, E,E-farnesal, and (E,Z)-2,13-octadecadienol. The outlined behavior, long thought to be unique to butterflies, is likely to be widespread in Castniidae implying a novel, unparalleled butterfly-like reproductive behavior in moths. This will also have practical implications in applied entomology since it signifies that the monitoring/control of castniid pests should not be based on the use of female-produced pheromones, as it is usually done in many moths.

Fast oscillatory activity in the anterior cingulate cortex: dopaminergic modulation and effect of perineuronal net loss.

Dopamine release in the prefrontal cortex plays a critical role in cognitive function such as working memory, attention and planning. Dopamine exerts complex modulation on excitability of pyramidal neurons and interneurons, and regulates excitatory and inhibitory synaptic transmission. Because of the complexity of this modulation, it is difficult to fully comprehend the effect of dopamine on neuronal network activity. In this study, we investigated the effect of dopamine on local high-frequency oscillatory neuronal activity (in β band) in slices of the mouse anterior cingulate cortex (ACC). We found that dopamine enhanced the power of these oscillations induced by kainate and carbachol, but did not affect their peak frequency. Activation of D2R and in a lesser degree D1R increased the oscillation power, while activation of D4R had no effect. These high-frequency oscillations in the ACC relied on both phasic inhibitory and excitatory transmission and functional gap junctions. Thus, dopamine released in the ACC promotes high-frequency synchronized local cortical activity which is known to favor information transfer, fast selection and binding of distributed neuronal responses. Finally, the power of these oscillations was significantly enhanced after degradation of the perineuronal nets (PNNs) enwrapping most parvalbumin interneurons. This study provides new insights for a better understanding of the abnormal prefrontal gamma activity in schizophrenia (SZ) patients who display prefrontal anomalies of both the dopaminergic system and the PNNs.

Systematic review with meta-analysis: self-expanding metal stents in patients with cirrhosis and severe or refractory oesophageal variceal bleeding.

BACKGROUND: The prognosis of patients with cirrhosis and acute variceal bleeding is very poor when the standard-of-care fails to control bleeding. New treatment modalities are needed in these patients. AIM: To synthesise the available evidence on the efficacy of self-expanding metal stents (SEMS) in patients with cirrhosis and severe or refractory oesophageal variceal bleeding. METHODS: Meta-analysis of trials evaluating SEMS in patients with cirrhosis and severe or refractory oesophageal variceal bleeding. RESULTS: Thirteen studies were included. The pooled estimate rates were 0.40 (95% confidence interval, CI = 0.31-0.49) for death, 0.41 (95% CI = 0.29-0.53) for liver-related death and 0.36 (95% CI = 0.26-0.47) for death at day 30, with low heterogeneity between studies. The pooled estimate rates were 0.12 (95% CI = 0.07-0.21) for mortality related to variceal bleeding, and 0.18 (95% CI = 0.11-0.29) for failure to control bleeding with SEMS, with no or low heterogeneity between studies. The pooled estimate rate were 0.16 (95% CI = 0.04-0.48) for rebleeding after stent removal and 0.28 (95% CI = 0.17-0.43) for stent migration, with high heterogeneity. A significant proportion of patients had access to liver transplantation or to TIPSS [pooled estimate rate 0.10 (95% CI = 0.04-0.21) and 0.26 (95% CI = 0.18-0.36), respectively]. CONCLUSIONS: Fewer than 40% of patients treated with SEMS were dead at 1 month. SEMS can be used as a bridge to TIPSS or to liver transplantation in a significant proportion of patients. Additional studies are required to identify potential risk factors leading to a poor prognosis in patients with acute variceal bleeding in whom the use of SEMS could be considered.

Animal modelling for inherited central vision loss.

Disease-causing variants of a large number of genes trigger inherited retinal degeneration leading to photoreceptor loss. Because cones are essential for daylight and central vision such as reading, mobility, and face recognition, this review focuses on a variety of animal models for cone diseases. The pertinence of using these models to reveal genotype/phenotype correlations and to evaluate new therapeutic strategies is discussed. Interestingly, several large animal models recapitulate human diseases and can serve as a strong base from which to study the biology of disease and to assess the scale-up of new therapies. Examples of innovative approaches will be presented such as lentiviral-based transgenesis in pigs and adeno-associated virus (AAV)-gene transfer into the monkey eye to investigate the neural circuitry plasticity of the visual system. The models reported herein permit the exploration of common mechanisms that exist between different species and the identification and highlighting of pathways that may be specific to primates, including humans.

Welfare loss with municipal amalgamations and the willingness-to-pay for the municipality name

Functional advantages and drawbacks are commonly mentioned to rationally justify or condemn municipality amalgamations. However, many consolidation projects are resisted by local governments or citizens on the grounds that amalgamation would dampen local identity. A municipality's name change is probably the most visible sign of the loss of community bond experienced by citizens at amalgamation time. This article aims to put a value on this loss by measuring citizen willingness to pay for their city name. This methodological approach innovates upon the literature on municipal amalgamation and place branding by exploiting the versatility of the so-called contingent valuation method (CVM). CVM confronts respondents, in a survey setting, with a hypothetical market in which a characteristic of interest is exchanged. Here the characteristic is the possibility to retain one's city name for an amalgamated jurisdiction. The article presents the estimates provided by a survey conducted in four Swiss cities.

Fractures de la cheville chez le patient âgé [Ankle fractures in the elderly patient].

Ankle fractures in adults are usually managed by open reduction internal fixation. In elderly patients the surgical dilemma relates to bone quality. Osteoporosis is the enemy of internal fixation, and secure purchase of screws in osteopenic bone may be difficult to achieve. Insufficient screw purchase may lead to loss of reduction, wound breakdown, and infection. Postoperative management after osteosynthesis usually requires an extended period of restricted weight bearing. However, this is not feasible in older patients as a result of their lack of strength in the upper extremities and frequent comorbidities. Therefore, augmen- ted methods of internal fixation and specific surgical techniques have been developed using metal and bone cement. This permits this fragile population to begin early full weight bearing in a removable brace.

Consequences of lineage-specific gene loss on functional evolution of surviving paralogs: ALDH1A and retinoic acid signaling in vertebrate genomes

Genome duplications increase genetic diversity and may facilitate the evolution of gene subfunctions. Little attention, however, has focused on the evolutionary impact of lineage-specific gene loss. Here, we show that identifying lineage-specific gene loss after genome duplication is important for understanding the evolution of gene subfunctions in surviving paralogs and for improving functional connectivity among human and model organism genomes. We examine the general principles of gene loss following duplication, coupled with expression analysis of the retinaldehyde dehydrogenase Aldh1a gene family during retinoic acid signaling in eye development as a case study. Humans have three ALDH1A genes, but teleosts have just one or two. We used comparative genomics and conserved syntenies to identify loss of ohnologs (paralogs derived from genome duplication) and to clarify uncertain phylogenies. Analysis showed that Aldh1a1 and Aldh1a2 form a clade that is sister to Aldh1a3-related genes. Genome comparisons showed secondarily loss of aldh1a1 in teleosts, revealing that Aldh1a1 is not a tetrapod innovation and that aldh1a3 was recently lost in medaka, making it the first known vertebrate with a single aldh1a gene. Interestingly, results revealed asymmetric distribution of surviving ohnologs between co-orthologous teleost chromosome segments, suggesting that local genome architecture can influence ohnolog survival. We propose a model that reconstructs the chromosomal history of the Aldh1a family in the ancestral vertebrate genome, coupled with the evolution of gene functions in surviving Aldh1a ohnologs after R1, R2, and R3 genome duplications. Results provide evidence for early subfunctionalization and late subfunction-partitioning and suggest a mechanistic model based on altered regulation leading to heterochronic gene expression to explain the acquisition or modification of subfunctions by surviving ohnologs that preserve unaltered ancestral developmental programs in the face of gene loss.

Suitability of human and mammalian cells of different origin for the assessment of genotoxicity of metal and polymeric engineered nanoparticles.

Nanogenotoxicity is a crucial endpoint in safety testing of nanomaterials as it addresses potential mutagenicity, which has implications for risks of both genetic disease and carcinogenesis. Within the NanoTEST project, we investigated the genotoxic potential of well-characterised nanoparticles (NPs): titanium dioxide (TiO2) NPs of nominal size 20 nm, iron oxide (8 nm) both uncoated (U-Fe3O4) and oleic acid coated (OC-Fe3O4), rhodamine-labelled amorphous silica 25 (Fl-25 SiO2) and 50 nm (Fl-50 SiO) and polylactic glycolic acid polyethylene oxide polymeric NPs - as well as Endorem® as a negative control for detection of strand breaks and oxidised DNA lesions with the alkaline comet assay. Using primary cells and cell lines derived from blood (human lymphocytes and lymphoblastoid TK6 cells), vascular/central nervous system (human endothelial human cerebral endothelial cells), liver (rat hepatocytes and Kupffer cells), kidney (monkey Cos-1 and human HEK293 cells), lung (human bronchial 16HBE14o cells) and placenta (human BeWo b30), we were interested in which in vitro cell model is sufficient to detect positive (genotoxic) and negative (non-genotoxic) responses. All in vitro studies were harmonized, i.e. NPs from the same batch, and identical dispersion protocols (for TiO2 NPs, two dispersions were used), exposure time, concentration range, culture conditions and time-courses were used. The results from the statistical evaluation show that OC-Fe3O4 and TiO2 NPs are genotoxic in the experimental conditions used. When all NPs were included in the analysis, no differences were seen among cell lines - demonstrating the usefulness of the assay in all cells to identify genotoxic and non-genotoxic NPs. The TK6 cells, human lymphocytes, BeWo b30 and kidney cells seem to be the most reliable for detecting a dose-response.