Consensus Statement on Bone Conduction Devices and Active Middle Ear Implants in Conductive and Mixed Hearing Loss

Nowadays, several options are available to treat patients with conductive or mixed hearing loss. Whenever surgical intervention is not possible or contra-indicated, and amplification by a conventional hearing device (e.g., behind-the-ear device) is not feasible, then implantable hearing devices are an indispensable next option. Implantable bone-conduction devices and middle-ear implants have advantages but also limitations concerning complexity/invasiveness of the surgery, medical complications, and effectiveness. To counsel the patient, the clinician should have a good overview of the options with regard to safety and reliability as well as unequivocal technical performance data. The present consensus document is the outcome of an extensive iterative process including ENT specialists, audiologists, health-policy scientists, and representatives/technicians of the main companies in this field. This document should provide a first framework for procedures and technical characterization to enhance effective communication between these stakeholders, improving health care

Kinetics of 5-aminolevulinic acid-induced fluorescence in organ cultures of bronchial epithelium and tumor

Background: 5-Aminolevulinic acid (5-ALA)-induced protoporphyrin IX (PPIX) fluorescence improves the differentiation of tumor and normal tissue in the bladder, skin and brain. Objective: The kinetics of 5-ALA-induced protoporphyrin IX (PPIX) fluorescence in organ cultures of normal human bronchial epithelium and cocultures of bronchial epithelium and tumor have been studied. Methods: Cultured biopsies of bronchial epithelium were exposed for 5 or 15 min, or continuously to 5-ALA. PPIX fluorescence was quantified for up to 300 min by spectroscopy. Cocultures of normal bronchial epithelium and a non-small-cell lung cancer cell line (EPLC-32M1) were incubated with 5-ALA. Space-resolved fluorescence microscopy was used to quantify PPIX fluorescence kinetics in the tumor and normal epithelium. Results: In cultures of normal epithelium, PPIX fluorescence kinetics were shown to depend on the duration of exposure to 5-ALA. There was a trend to higher fluorescence intensities with longer exposure times. In cocultures of bronchial epithelium and tumor, increases of fluorescence intensity were significantly greater in the tumor. Best tumor/normal tissue fluorescence ratios were found between 110 and 160 min after exposure to 5-ALA. Conclusion: Data obtained in this coculture system of bronchial epithelium and tumor is valuable to optimize modalities of fluorescence bronchoscopy for the diagnosis of early bronchial carcinoma. Copyright (C) 2002 S. Karger AG, Basel

Molecular data reveal hidden diversity in the central Andean species Weberbauera spathulifolia (Thelypodieae: Brassicaceae)

Weberbauera (Brassicaceae, tribe Thelypodieae) comprises 18 species distributed along the central Andes of Argentina, Bolivia, Chile and Peru. Of these species, W. spathulifolia has the largest geographical range in the genus, extending c. 3000 km along the Andean highlands from La Rioja Province in Argentina to Ancash Department in Peru. This species also shows the greatest morphological variation in the genus. However, whether this geographical and morphological variation represents one or more lineages remains unclear. In this study, we analyse W. spathulifolia across its entire distribution range using molecular, morphological and ecological data. Because there is no phylogenetic analysis for the genus, we generated a comprehensive molecular sampling using nuclear (ITS) and plastid (trnL-F and trnH-psbA) sequences for other Weberbauera spp. and representatives of South American Thelypodieae. Results support the presence of two different lineages within W. spathulifolia, one in the northern part of the species range and the other distributed across its southern and central range. In addition to the morphological differences and the allopatric distribution, these lineages also differ in their climatic niches. Therefore, we propose here to retain the northern lineage under W. spathulifolia and to treat the southern-central lineage under W. orophila, comb. nov. Phylogenetic placement of Weberbauera spp. among the South American Thelypodieae is also analysed and discussed. Results of this study contribute to understanding the biodiversity and evolution of the Andean Brassicaceae.Fil: Salariato, Diego Leonel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Botánica Darwinion. Academia Nacional de Ciencias Exactas, Físicas y Naturales. Instituto de Botánica Darwinion; ArgentinaFil: Trinidad, Huber. Universidad Nacional Mayor de San Marcos; PerúFil: Cano, Asunción. Universidad Nacional Mayor de San Marcos; PerúFil: Zuloaga, Fernando Omar. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Botánica Darwinion. Academia Nacional de Ciencias Exactas, Físicas y Naturales. Instituto de Botánica Darwinion; ArgentinaFil: Al Shehbaz, Ihsan. Missouri Botanical Garden; Estados Unido

Nucleosomes indicate the in vitro radiosensitivity of irradiated bronchoepithelial and lung cancer cells

Nucleosomes, which are typical cell death products, are elevated in the serum of cancer patients and are known to rapidly increase during radiotherapy. As both normal and malignant cells are damaged by irradiation, we investigated to which extent both cell types contribute to the release of nucleosomes. We cultured monolayers of normal bronchoepithelial lung cells (BEAS-2B, n = 18) and epithelial lung cancer cells (EPLC, n = 18), exposed them to various radiation doses (0, 10 and 30 Gy) and observed them for 5 days. Culture medium was changed every 24 h. Subsequently, nucleosomes were determined in the supernatant by the Cell Death Detection-ELISA(plus) ( Roche Diagnostics). Additionally, the cell number was estimated after harvesting the cells in a second preparation. After 5 days, the cell number of BEAS-2B cultures in the irradiated groups (10 Gy: median 0.03 x 10(6) cells/culture, range 0.02-0.08 x 10(6) cells/culture; 30 Gy: median 0.08 x 10(6) cells/culture, range 0.02-0.14 x 10(6) cells/culture) decreased significantly (10 Gy: p = 0.005; 30 Gy p = 0.005; Wilcoxon test) compared to the non-irradiated control group (median 4.81 x 10(6) cells/culture, range 1.50-9.54 x 10(6) cells/culture). Consistently, nucleosomes remained low in the supernatant of nonirradiated BEAS-2B. However, at 10 Gy, BEAS-2B showed a considerably increasing release of nucleosomes, with a maximum at 72 h ( before irradiation: 0.24 x 10(3) arbitrary units, AU, range 0.13-4.09 x 10(3) AU, and after 72 h: 1.94 x 10(3) AU, range 0.11-5.70 x 10(3) AU). At 30 Gy, the release was even stronger, reaching the maximum earlier (at 48 h, 11.09 x 10(3) AU, range 6.89-18.28 x 10(3) AU). In non-irradiated EPLC, nucleosomes constantly increased slightly. At 10 Gy, we observed a considerably higher release of nucleosomes in EPLC, with a maximum at 72 h (before irradiation: 2.79 x 10(3) AU, range 2.42-3.80 x 10(3) AU, and after 72 h: 7.16 x 10(3) AU, range 4.30-16.20 x 10(3) AU), which was more than 3.5 times higher than in BEAS-2B. At 30 Gy, the maximum (6.22 x 10(3) AU, range 5.13-9.71 x 10(3) AU) was observed already after 24 h. These results indicate that normal bronchoepithelial and malignant lung cancer cells contribute to the release of nucleosomes during irradiation in a dose-and time-dependent manner with cancer cells having a stronger impact at low doses. Copyright (C) 2004 S. Karger AG, Basel

The terroir of the finch: How spatial and temporal variation shapes phenotypic traits in Darwin\u27s finches

The term terroir is used in viticulture to emphasize how the biotic and abiotic characteristics of a local site influence grape physiology and thus the properties of wine. In ecology and evolution, such terroir (i.e., the effect of space or “site”) is expected to play an important role in shaping phenotypic traits. Just how important is the pure spatial effect of terroir (e.g., differences between sites that persist across years) in comparison to temporal variation (e.g., differences between years that persist across sites), and the interaction between space and time (e.g., differences between sites change across years)? We answer this question by analyzing beak and body traits of 4388 medium ground finches (Geospiza fortis) collected across 10 years at three locations in Galápagos. Analyses of variance indicated that phenotypic variation was mostly explained by site for beak size (η2 = 0.42) and body size (η2 = 0.43), with a smaller contribution for beak shape (η2 = 0.05) and body shape (η2 = 0.12), but still higher compared to year and site-by-year effects. As such, the effect of terroir seems to be very strong in Darwin\u27s finches, notwithstanding the oft-emphasized interannual variation. However, these results changed dramatically when we excluded data from Daphne Major, indicating that the strong effect of terroir was mostly driven by that particular population. These phenotypic results were largely paralleled in analyses of environmental variables (rainfall and vegetation indices) expected to shape terroir in this system. These findings affirm the evolutionary importance of terroir, while also revealing its dependence on other factors, such as geographical isolation

Cytoprotective Activated Protein C Averts Nlrp3 Inflammasome–Induced Ischemia-Reperfusion Injury Via Mtorc1 Inhibition

Cytoprotection by activated protein C (aPC) after ischemia-reperfusion injury (IRI) is associated with apoptosis inhibition. However, IRI is hallmarked by inflammation, and hence, cell-death forms disjunct from immunologically silent apoptosis are, in theory, more likely to be relevant. Because pyroptosis (ie, cell death resulting from inflammasome activation) is typically observed in IRI, we speculated that aPC ameliorates IRI by inhibiting inflammasome activation. Here we analyzed the impact of aPC on inflammasome activity in myocardial and renal IRIs. aPC treatment before or after myocardial IRI reduced infarct size and Nlrp3 inflammasome activation in mice. Kinetic in vivo analyses revealed that Nlrp3 inflammasome activation preceded myocardial injury and apoptosis, corroborating a pathogenic role of the Nlrp3 inflammasome. The constitutively active Nlrp3A350V mutation abolished the protective effect of aPC, demonstrating that Nlrp3 suppression is required for aPC-mediated protection from IRI. In vitro aPC inhibited inflammasome activation in macrophages, cardiomyocytes, and cardiac fibroblasts via proteinase-activated receptor 1 (PAR-1) and mammalian target of rapamycin complex 1 (mTORC1) signaling. Accordingly, inhibiting PAR-1 signaling, but not the anticoagulant properties of aPC, abolished the ability of aPC to restrict Nlrp3 inflammasome activity and tissue damage in myocardial IRI. Targeting biased PAR-1 signaling via parmodulin-2 restricted mTORC1 and Nlrp3 inflammasome activation and limited myocardial IRI as efficiently as aPC. The relevance of aPC-mediated Nlrp3 inflammasome suppression after IRI was corroborated in renal IRI, where the tissue protective effect of aPC was likewise dependent on Nlrp3 inflammasome suppression. These studies reveal that aPC protects from IRI by restricting mTORC1-dependent inflammasome activation and that mimicking biased aPC PAR-1 signaling using parmodulins may be a feasible therapeutic approach to combat IRI

Photodissociation of water in crystalline ice: a molecular dynamics study

Ultraviolet irradiation of ice is of great interest for understanding the chemistry in both atmospheric and astrophysical environments. In interstellar space, photodissociation of H2O molecules can be a driving force behind the chemistry on icy dust grains in dense, cold molecular clouds even though the flux of UV photons is extremely low. The mechanisms of such photoinduced processes are poorly understood, however. In this work the photodissociation dynamics of a water molecule in crystalline ice at 10 K is studied computationally using classical molecular dynamics. Photodissociation in the first bilayer leads mainly to H atoms desorbing (65%), while in the third bilayer trapping of H and OH dominates (51%). The kinetic energy distribution of the desorbing H atoms is much broader than that for the corresponding gas-phase photodissociation. The H atoms on average move 11 Angstroms before becoming trapped, while OH radicals typically move 2 Angstroms. In accordance with experiments a blueshift of the absorption spectrum is obtained relative to gas-phase water.Comment: 23 pages, 5 figure

First clinical experience in 14 patients treated with ADVOS: a study on feasibility, safety and efficacy of a new type of albumin dialysis

Background: Liver failure (LF) is associated with prolonged hospital stay, increased cost and substantial mortality. Due to the limited number of donor organs, extracorporeal liver support is suggested as an appealing concept to "bridge to transplant" or to avoid transplant in case of recovery. ADVanced Organ Support (ADVOS) is a new type of albumin dialysis, that provides rapid regeneration of toxin-binding albumin by two purification circuits altering the binding capacities of albumin by biochemical (changing of pH) and physical (changing of temperature) modulation of the dialysate. It was the aim of this study to evaluate feasibility, efficacy and safety of ADVOS in the first 14 patients ever treated with this procedure. Methods: Patients included suffered from acute on chronic LF (n = 9) or "secondary" LF (n = 5) which resulted from non-hepatic diseases such as sepsis. The primary endpoint was the change of serum bilirubin, creatinine and serum BUN levels before and after the first treatment with ADVOS. The Wilcoxon Signed Rank test for paired samples was used to analyze the data. Results: A total of 239 treatments (1 up to 101 per patient) were performed in 14 patients (6 female, 8 male). Mean age 54 +/- 13;MELD-score 34 +/- 7;CLIF-SOFA 15 +/- 3. Serum bilirubin levels were significantly decreased by 32% during the first session (26.0 +/- 15.4 vs. 17.7 +/- 10.5 mg/dl;p = 0.001). Similarly, serum creatinine (2.2 +/- 0.8 vs. 1.6 +/- 0.7 mg/dl;p = 0.005) and serum BUN (49.4 +/- 23.3 vs. 31.1 +/- 19.7 mg/dl;p = 0.003), were significantly lowered by 27% and 37%, respectively. None of the treatment sessions had to be interrupted due to side effects related to the procedure. Conclusion: ADVOS efficiently eliminates water-and protein-bound toxins in humans with LF. ADVOS is feasible in patients with advanced LF which is emphasized by a total number of more than 100 treatment sessions in one single patient

Charming CP Violation and Dipole Operators from RS Flavor Anarchy

Recently the LHCb collaboration reported evidence for direct CP violation in charm decays. The value is sufficiently large that either substantially enhanced Standard Model contributions or non-Standard Model physics is required to explain it. In the latter case only a limited number of possibilities would be consistent with other existing flavor-changing constraints. We show that warped extra dimensional models that explain the quark spectrum through flavor anarchy can naturally give rise to contributions of the size required to explain the the LHCb result. The D meson asymmetry arises through a sizable CP-violating contribution to a chromomagnetic dipole operator. This happens naturally without introducing inconsistencies with existing constraints in the up quark sector. We discuss some subtleties in the loop calculation that are similar to those in Higgs to \gamma\gamma. Loop-induced dipole operators in warped scenarios and their composite analogs exhibit non-trivial dependence on the Higgs profile, with the contributions monotonically decreasing when the Higgs is pushed away from the IR brane. We show that the size of the dipole operator quickly saturates as the Higgs profile approaches the IR brane, implying small dependence on the precise details of the Higgs profile when it is quasi IR localized. We also explain why the calculation of the coefficient of the lowest dimension 5D operator is guaranteed to be finite. This is true not only in the charm sector but also with other radiative processes such as electric dipole moments, b to s\gamma, \epsilon'/\epsilon_K and \mu\ to e\gamma. We furthermore discuss the interpretation of this contribution within the framework of partial compositeness in four dimensions and highlight some qualitative differences between the generic result of composite models and that obtained for dynamics that reproduces the warped scenario.Comment: 14 page

Bivalirudin started during emergency transport for primary PCI.

BACKGROUND: Bivalirudin, as compared with heparin and glycoprotein IIb/IIIa inhibitors, has been shown to reduce rates of bleeding and death in patients undergoing primary percutaneous coronary intervention (PCI). Whether these benefits persist in contemporary practice characterized by prehospital initiation of treatment, optional use of glycoprotein IIb/IIIa inhibitors and novel P2Y12 inhibitors, and radial-artery PCI access use is unknown. METHODS: We randomly assigned 2218 patients with ST-segment elevation myocardial infarction (STEMI) who were being transported for primary PCI to receive either bivalirudin or unfractionated or low-molecular-weight heparin with optional glycoprotein IIb/IIIa inhibitors (control group). The primary outcome at 30 days was a composite of death or major bleeding not associated with coronary-artery bypass grafting (CABG), and the principal secondary outcome was a composite of death, reinfarction, or non-CABG major bleeding. RESULTS: Bivalirudin, as compared with the control intervention, reduced the risk of the primary outcome (5.1% vs. 8.5%; relative risk, 0.60; 95% confidence interval [CI], 0.43 to 0.82; P=0.001) and the principal secondary outcome (6.6% vs. 9.2%; relative risk, 0.72; 95% CI, 0.54 to 0.96; P=0.02). Bivalirudin also reduced the risk of major bleeding (2.6% vs. 6.0%; relative risk, 0.43; 95% CI, 0.28 to 0.66; P<0.001). The risk of acute stent thrombosis was higher with bivalirudin (1.1% vs. 0.2%; relative risk, 6.11; 95% CI, 1.37 to 27.24; P=0.007). There was no significant difference in rates of death (2.9% vs. 3.1%) or reinfarction (1.7% vs. 0.9%). Results were consistent across subgroups of patients. CONCLUSIONS: Bivalirudin, started during transport for primary PCI, improved 30-day clinical outcomes with a reduction in major bleeding but with an increase in acute stent thrombosis. (Funded by the Medicines Company; EUROMAX ClinicalTrials.gov number, NCT01087723.)