Laryngopharyngeal reflux (LPR) symptoms are often resistant to management and cause significant quality of life impairment to patients with this disease. This study assesses the utility of a sleep-positioning device (SPD) in treating LPR.
http://ift.tt/2tQcL4l
Medicine by Alexandros G.Sfakianakis,Anapafseos 5 Agios Nikolaos,Crete 72100,Greece,tel :00302841026182 & 00306932607174
Δευτέρα 26 Ιουνίου 2017
Treatment of laryngopharyngeal reflux using a sleep positioning device: A prospective cohort study
Lateral cervical approach for supracricoid partial laryngectomy
The supracricoid partial laryngectomy has been described for the treatment of T3 laryngeal glottic and supraglottic tumors as well as upfront and salvage surgery. Good oncological and functional outcomes are expected, while the post-operative rehabilitation can be quite difficult for the patient. Early and late complications can occur especially in salvage surgery. Neck dissection according to the T stage is often associated with the resection of the primary tumor.
http://ift.tt/2tgUjoo
Optimized DNA Vaccine Enhanced by Adjuvant IL28B Induces Protective Immune Responses Against Herpes Simplex Virus Type 2 in Mice
Viral Immunology , Vol. 0, No. 0.
http://ift.tt/2tfp7FT
Genetic Polymorphisms of Tumor Necrosis Factor Alpha and Susceptibility to Dengue Virus Infection in a Mexican Population
Viral Immunology , Vol. 0, No. 0.
http://ift.tt/2rVVJ3n
The Johns Hopkins Children’s Center Ranked Among the Top U.S. Children’s Hospitals by U.S. News & World Report
Johns Hopkins Children's Center was ranked #5 in the nation by U.S. News & World Report on its 2017–18 Best Children's Hospitals Honor Roll. Johns Hopkins Children's Center has the distinction of being the only children's hospital integrated with an adult facility to make the honor roll this year, and continues to be the highest-ranked pediatric hospital in the state of Maryland.
http://ift.tt/2tQ1dOq
Adult cancer-related hemophagocytic lymphohistiocytosis – a challenging diagnosis: a case report
Adult hemophagocytic lymphohistiocytosis is a secondary immunopathologic phenomenon, mainly secondary to malignancy, infection, or autoimmune disorders.
http://ift.tt/2tfmfJ7
Ocular vestibular evoked myogenic potential in patients with myasthenia gravis
Myasthenia gravis (MG) is an archetypic disorder of neuromuscular junctions (NMJs) and autoantibody-mediated disease causing fatigable weakness of skeletal muscles with an ocular onset in up to 85%. The aim of this study was to detect extra ocular muscles (EOMs) abnormalities in MG patients using ocular vestibular evoked myogenic potential (oVEMP) n10 response.
http://ift.tt/2rW1QEL
Prospective analysis of 231 elective neck dissections in oral squamous cell carcinoma with node negative neck—To decide the extent of neck dissection
To evaluate the incidence of level IIB and IV lymph node metastases in patients of oral carcinoma with N0 necks. This study will help to decide the extent and need of routine comprehensive removal of these specific lymph node groups in selective neck dissection.
http://ift.tt/2tfbCpJ
Complete DNA Sequence of IncM1 Plasmid Bearing the Novel qnrE1 PMQR Variant and blaCTX-M-8 from Klebsiella pneumoniae ST147 [PublishAheadOfPrint]
The recent article by Albornoz et al. (1), reported a member of a new family of plasmid-mediated quinolone resistance genes, named qnrE1, originating from the chromosome of Enterobacter spp....
http://ift.tt/2sbswG0
Nifurtimox is ineffective against drug-resistant mycobacteria [PublishAheadOfPrint]
Multi- and extensively drug-resistant tuberculosis (XDR-TB) and diseases caused by the naturally drug-resistant nontuberculous mycobacteria (NTM) are emerging health threats....
http://ift.tt/2sVhh1f
Preclinical characterization of the inhaled small molecule respiratory syncytial virus L-protein polymerase inhibitor, PC786 [PublishAheadOfPrint]
Although respiratory syncytial virus (RSV) is the most common cause of lower respiratory tract infection in infants and young children, attempts to develop an effective therapy have so far proved unsuccessful. Herein we report the preclinical profiles of PC786, a potent non-nucleoside RSV L-protein polymerase inhibitor, designed for inhalation treatment of RSV infection. PC786 demonstrated a potent and selective anti-viral activity against laboratory adapted or clinical isolates of RSVA (IC50: <0.09 - 0.71 nM) and RSVB (IC50: 1.3 - 50.6 nM), which were determined by inhibition of cytopathic effects in HEp-2 cells without causing detectable cytotoxicity. The underlying inhibition of virus replication was confirmed by PCR analysis. The effects of PC786 were largely unaffected by the multiplicity of infection (MOI) and were retained in the face of established RSV replication in a time-of-addition study. Persistent anti-RSV effects of PC786 were also demonstrated in human bronchial epithelial cells. In vivo intranasal once daily dosing with PC786 was able to reduce the virus load to undetectable levels in lung homogenates from RSV infected mice and cotton rats. Treatment with escalating concentrations identified a dominant mutation in the L protein (Y1631H) in vitro. In addition, PC786 potently inhibited RSV RNA-dependent RNA polymerase (RdRp) activity in a cell-free enzyme assay and mini-genome assay in HEp-2 cells (IC50: 2.1 and 0.5 nM, respectively). Thus, PC786 was shown to be a potent anti-RSV agent via inhibition of RdRp activity, making topical treatment with this compound a novel potential therapy for the treatment of human RSV infections.
http://ift.tt/2sbii8D
Characterization of the Activities of Dinuclear Thiolato-Bridged Arene Ruthenium Complexes against Toxoplasma gondii [PublishAheadOfPrint]
The in vitro effects of 18 dinuclear-thiolato bridged arene ruthenium complexes, (1 mono-, 4 di- and 13-tri-thiolato compounds), originally designed as anti-cancer agents, were studied in the apicomplexan parasite Toxoplasma gondii grown in human foreskin fibroblast host cells (HFF). Some tri-thiolato compounds exhibited anti-parasitic efficacy at 250 nM and below. Among those, complex 1 and complex 2 inhibited T. gondii proliferation with IC50 values of 34 and 62 nM, respectively, and they did not affect HFF at dosages of 200 μM or above, resulting in selectivity indices of > 23' 000. The IC50 values of complex 9 were 1.2 nM for T. gondii and above 5 μM for HFF. TEM detected ultrastructural alterations in the matrix of the parasite mitochondria at the early stages of treatment, followed by more pronounced destruction of tachyzoites. However, all three compounds applied at 250 nM for 15 days were not parasiticidal. By affinity chromatography using complex 9 coupled to epoxy-activated sepharose followed by mass spectrometry, T. gondii translation elongation factor-1 alpha and two ribosomal proteins, RPS18, and RPL27 were identified as potential binding proteins. In conclusion, organometallic ruthenium complexes exhibit promising activities against Toxoplasma, and potential mechanisms of action of these compounds as well as their prospective applications for the treatment of toxoplasmosis are discussed.
http://ift.tt/2sVsQpx
Relationship between the Minimum Inhibitory Concentration of Carbapenems and the Clinical Outcome of Patients with Acinetobacter Bacteremia: A Multicenter Study [PublishAheadOfPrint]
The Clinical and Laboratory Standards Institute (CLSI) and the European Committee on Antimicrobial Susceptibility Testing (EUCAST) offer different recommendations for carbapenem minimal inhibitory concentration (MIC) susceptibility breakpoints for Acinetobacter spp. In addition, the clinical efficacy of the intermediate category remains uncertain. This study was designed to determine the optimal predictive breakpoints based on survival of patients with Acinetobacter bacteremia treated with a carbapenem. We analyzed the thirty-day mortality rates of 224 adults who received initial carbapenem monotherapy for treatment of Acinetobacter bacteremia at 4 medical centers over a 5-year period according to the carbapenem MICs of the initial isolates. The thirty-day mortality was about 2-fold greater in patients whose isolates had carbapenem MICs ≥8 mg/L than those with ≤4 mg/L. The differences were significant by bivariate analysis (53.1% [60/113] vs. 25.2% [28/111]; P < 0.001) and on survival analysis by the log-rank test (P < 0.001). Classification and regression tree analysis revealed a split between MICs of 4 and 8 mg/L and predicted the same difference in mortality, P < 0.001. Carbapenem treatment for Acinetobacter bacteremia caused by isolates with carbapenem MICs ≥8 mg/L was an independent predictor of 30-day mortality (odds ratio, 4.218; 95% confidence interval, 2.213--8.039; P < 0.001). This study revealed that patients with Acinetobacter bacteremia treated with a carbapenem had a more favorable outcome when the carbapenem MICs of their isolates were ≤4 mg/L compared to those isolates with MIC ≥8 mg/L.
http://ift.tt/2sbtxhm
Meropenem-Vaborbactam Tested against Contemporary Gram-Negative Isolates Collected Worldwide During 2014, Including Carbapenem-Resistant, KPC-Producing, Multidrug-Resistant, and Extensively Drug-Resistant Enterobacteriaceae [PublishAheadOfPrint]
We evaluated the activity of meropenem-vaborbactam against contemporary non-fastidious gram-negative clinical isolates, including resistant phenotypes and carbapenemase genotypes of Enterobacteriaceae. Meropenem-vaborbactam (inhibitor at 8 μg/ml) and comparators were susceptibility tested using reference broth microdilution methods against 14,304 gram-negative clinical isolates collected worldwide during 2014. Carbapenemase encoding genes were screened by PCR/sequencing. Meropenem-vaborbactam (MIC50/90, ≤0.015/0.06 μg/ml) inhibited 99.1 and 99.3% of the 10,426 Enterobacteriaceae isolates tested at ≤1 and ≤2 μg/ml, respectively. Meropenem inhibited 97.3 and 97.7% of these isolates at the same concentrations. Against Enterobacteriaceae displaying carbapenem resistance (CRE) (n=265), multidrug (MDR) (n=1,210) or extensively drug (XDR) (n=161) resistant phenotypes, meropenem-vaborbactam displayed MIC50/90 values at 0.5/32, 0.03/1 and 0.5/32 μg/ml, respectively, whereas meropenem activity was 16/>32, 0.06/32 and 0.5/32 μg/ml, respectively. Among all geographic regions, the highest meropenem-vaborbactam activity was observed for CRE and MDR isolates from the U.S. (MIC50/90, 0.03/1 and 0.03/0.12 μg/ml, respectively). Meropenem-vaborbactam was very active against 135 KPC-producers, and all isolates were inhibited by ≤8 μg/ml (133 isolates at ≤2 μg/ml). This combination had limited activity against isolates producing metallo-β-lactamases (including 25 NDM-1- and 16 VIM-producers) and/or oxacillinases (27 OXA-48/-163) that were detected mainly in Asia-Pacific and some European countries. The activity of meropenem-vaborbactam was similar to that of meropenem alone against Pseudomonas aeruginosa, Acinetobacter spp. and Stenotrophomonas maltophilia. Meropenem-vaborbactam was active against contemporary Enterobacteriaceae collected worldwide, and this combination demonstrated enhanced activity when compared to meropenem and most comparator agents against CRE and KPC-producers that are often MDR.
http://ift.tt/2sVf5Hf
Potent inhibition of HIV-1 replication in resting CD4 T cells by resveratrol and pterostilbene [PublishAheadOfPrint]
HIV-1 infection of resting CD4 T cells plays a crucial and numerically dominant role during virus transmission at mucosal sites and during subsequent acute replication and T cell depletion. Resveratrol and pterostilbene are plant stilbenoids associated with several health promoting benefits. Resveratrol has been shown to inhibit replication of several viruses, including herpes simplex 1 and 2, papillomaviruses, SARS virus and influenza virus. Alone, resveratrol does not inhibit HIV-1 infection of activated T cells, but it does synergize with nucleoside reverse transcriptase inhibitors in these cells to inhibit reverse transcription. Here, we demonstrate that resveratrol and pterostilbene completely block HIV-1 infection at low micromolar dose in resting CD4 T cells, primarily at the reverse transcription step. The anti-HIV effect was fully reversed by exogenous deoxynucleosides and Vpx, a simian immunodeficiency virus protein that increases dNTP levels. These findings are consistent with the reported ability of resveratrol to inhibit ribonucleotide reductase and to lower dNTP levels in cells. This study supports the potential use of resveratrol, pterostilbene or related compounds as adjuvants in anti-HIV pre-exposure prophylaxis (PrEP) formulations.
http://ift.tt/2sb0lXA
The Candidate Antimalarial Drug MMV665909 Causes Oxygen-Dependent mRNA Mistranslation and Synergises with Quinoline-Derived Antimalarials [PublishAheadOfPrint]
To cope with growing resistance to current antimalarials, new drugs with novel modes of action are urgently needed. Molecules targeting protein synthesis appear to be promising candidates. We identified a compound (MMV665909) from the MMV Malaria Box of candidate antimalarials that could produce synergistic growth inhibition with the aminoglycoside antibiotic paromomycin, suggesting a possible action of the compound in mRNA mistranslation. This mechanism of action was substantiated with the yeast cell model using available reporters of mistranslation and other genetic tools. Mistranslation induced by MMV665909 was oxygen-dependent, suggesting a role for reactive oxygen species (ROS). Overexpression of Rli1 (a ROS-sensitive, conserved FeS protein essential in mRNA translation) rescued inhibition by MMV665909, consistent with the drug's action on translation fidelity being mediated through Rli1. The MMV drug also synergised with major quinoline-derived antimalarials which can perturb amino acid availability or promote ROS stress: chloroquine, amodiaquine and primaquine. The data collectively suggest translation-fidelity as a novel target of antimalarial action and support MMV665909 as a promising drug candidate.
http://ift.tt/2sVnFFP
Outbreak of CTX-M-15-producing enterotoxigenic Escherichia coli O159:H20 in the Republic of Korea, 2016 [PublishAheadOfPrint]
We investigated an outbreak of enterotoxigenic Escherichia coli (ETEC) O159:H20 associated with the consumption of a tossed noodle dish in a high school in 2016. Thirty-three ETEC strains isolated from both clinical and food samples were genetically indistinguishable. The outbreak strains were resistant to third-generation cephalosporins and harbored a blaCTX-M-15 gene on a 97-kb self-transferable IncK plasmid. This is the first outbreak caused by CTX-M-15-producing ETEC strains.
http://ift.tt/2sbslu2
Characterization of a Francisella tularensis-Caenorhabditis elegans pathosystem for the evaluation of therapeutic compounds [PublishAheadOfPrint]
Francisella tularensis is a highly infectious Gram-negative intracellular pathogen that causes tularemia. Because of its potential as a bioterrorism agent, there is a need for new therapeutic agents. We therefore developed a whole animal Caenorhabditis elegans-F. tularensis pathosystem for high throughput screening to identify and characterize potential therapeutic compounds. We found that the C. elegans p38 MAP kinase cascade is involved in the immune response to F. tularensis and we developed a robust F. tularensis-mediated C. elegans killing assay with a Z'-factor consistently >0.5, which was then utilized to screen a library of FDA approved compounds that included 1,760 small molecules. In addition to clinically used antibiotics, 5 FDA-approved drugs were also identified as potential hits, including the anti-inflammatory drug diflunisal that showed anti-F. tularensis activity in vitro. Moreover, the NSAID diflunisal, at 4X MIC, blocked the replication of a F. tularensis live vaccine strain (LVS) in primary human macrophages and non-phagocytic cells. Diflunisal was non-toxic to human erythrocytes and HepG2 human liver cells at concentrations ≥32-μg/ml. Finally, diflunisal exhibited synergetic activity with the antibiotic ciprofloxacin in both a checkerboard assay and a macrophage infection assay. In conclusion, the liquid C. elegans — F. tularensis LVS assay described here allows screening for anti-F. tularensis compounds and suggests that diflunisal could potentially be repurposed for the management of tularemia.
http://ift.tt/2ubD44o
Targeting homoserine dehydrogenase from Paracoccidioides Genus against systemic fungal infections [PublishAheadOfPrint]
This work evaluated new potential inhibitors of the enzyme homoserine dehydrogenase (HSD) from Paracoccidioides brasiliensis, one of the etiological agent of paracoccidioidomycosis. The tertiary structure of the protein bonded to the analogue NAD and L-homoserine was modeled by homology. The best output model was subjected to gradient minimization, redocking and molecular dynamics. Virtual screening simulations with 187,841 purchasable molecules from the Zinc database were performed. After the screenings, 14 molecules were selected and analyzed by ADMETox criteria, resulting in four compounds for in vitro assays. The molecules HS1 and HS2 were promising, exhibiting MICs of 64 and 32 μg.mL-1 respectively for the Pb18 isolate of P. brasilensis, 64 μg.mL-1 for two isolates of P. lutzii and also synergy with itraconazole. The application of these molecules in human pathogenic fungi confirmed that the HSD enzyme may be used as a target for the development of drugs with specific action against paracoccidioidomycosis; moreover these compounds may serve as leads in the design of new antifungals.
http://ift.tt/2tdBQbG
Synthetic cyclic peptomers as type III secretion system inhibitors [PublishAheadOfPrint]
Antibiotic resistant bacteria are an emerging threat to global public health. New classes of antibiotics and tools for antimicrobial discovery are urgently needed. The type III secretion system (T3SS), which is required by dozens of Gram-negative bacteria for virulence but largely absent from non-pathogenic bacteria, is a promising virulence blocker target. The ability of mammalian cells to recognize the presence of a functional T3SS and trigger NFB activation provides a rapid and sensitive method to identify chemical inhibitors of T3SS activity. In this study, we generated a HEK293 stable cell line expressing Green Fluorescence Protein (GFP) driven by a promoter containing NFB enhancer elements to serve as a readout of T3SS function. We have identified a family of synthetic cyclic peptide-peptoid hybrid molecules (peptomers) that exhibited dose-dependent inhibition of T3SS effector secretion in Yersinia pseudotuberculosis and Pseudomonas aeruginosa without affecting bacterial growth or motility. Among these inhibitors, EpD-3' N, EpD-1,2N, EpD-1,3' N, EpD-1,2,3' N, and EpD-1,2,4' N exhibited a strong inhibitory effect on translocation of the Yersinia YopM effector protein into mammalian cells (>40% translocation inhibition at 7.5 μM) and showed no toxicity to mammalian cells at 240 μM. In addition, EpD-3' N and EpD-1,2,4' N reduced rounding of HeLa cells caused by the activity of effector proteins from Yersinia that target the actin cytoskeleton. In summary, we have discovered a family of novel cyclic peptomers that inhibit the injectisome T3SS but not the flagellar T3SS.
http://ift.tt/2ub9nAt
Prophylactic Treatment with VT-1161 Protects Immunosuppressed Mice from Rhizopus arrhizus var. arrhizus Infection [PublishAheadOfPrint]
We compared prophylactic or continuous therapy of the investigational drug VT-1161 to posaconazole in treating murine mucormycosis due to Rhizopus arrhizus var. arrhizus. In the prophylaxis studies, only VT-1161 resulted in improved survival and lowered tissue fungal burden of immunosuppressed infected mice. In the continuous therapy, VT-1161 outperformed posaconazole in prolonging mice survival time despite their comparable effect in lowering tissue fungal burden. These results support the further development of VT-1161 against mucormycosis.
http://ift.tt/2tdM8bV
THE NON-ANTIBIOTIC MACROLIDE EM703 IMPROVES SURVIVAL IN A MODEL OF QUINOLONE-TREATED PSEUDOMONAS AERUGINOSA AIRWAY INFECTION [PublishAheadOfPrint]
Macrolide antibiotics are used as anti-inflammatory agents, e.g. for prevention of exacerbations in COPD and cystic fibrosis. Several studies have shown improved outcomes after addition of macrolides to beta-lactam antibiotics when treating severe community-acquired pneumonia. However, a beneficial effect of macrolides when treating Gram-negative bacterial airway infections, e.g. those caused by Pseudomonas aeruginosa, remains to be shown. Macrolide antibiotics have significant side effects, in particular motility-stimulating activity of the gastrointestinal tract and promotion of bacterial resistance. In this study, EM703, a modified macrolide lacking antibiotic and motility-stimulating activities, but with retained anti-inflammatory properties, was used as an adjunct treatment of experimental P. aeruginosa lung infection in combination with a conventional antibiotic. Airway infection in BALB/cJRj mice was induced by nasal instillation of P. aeruginosa. This was followed by treatment with the quinolone levofloxacin in the absence or presence of EM703. Survival, inflammatory responses, and cellular influx to the airways were monitored. Both pretreatment and simultaneous administration of EM703 dramatically improved survival in levofloxacin-treated mice with P. aeruginosa airway infection. In addition, EM703 reduced the levels of proinflammatory cytokines, increased the number of leukocytes in bronchoalveolar fluid, and reduced the number of neutrophils present in the lung tissue. In summary, the findings of this study show that the immunomodulatory properties of the modified macrolide EM703 can be important when treating Gram-negative pneumonia, as exemplified by P. aeruginosa infection in this study.
http://ift.tt/2ubfy7A
proBAMconvert: A Conversion Tool for proBAM/proBed
The introduction of new standard formats, proBAM and proBed, improves the integration of genomics and proteomics information, thus aiding proteogenomics applications. These novel formats enable peptide spectrum matches (PSM) to be stored, inspected, and analyzed within the context of the genome. However, an easy-to-use and transparent tool to convert mass spectrometry identification files to these new formats is indispensable. proBAMconvert enables the conversion of common identification file formats (mzIdentML, mzTab, and pepXML) to proBAM/proBed using an intuitive interface. Furthermore, ProBAMconvert enables information to be output both at the PSM and peptide levels and has a command line interface next to the graphical user interface. Detailed documentation and a completely worked-out tutorial is available at http://probam.biobix.be.
http://ift.tt/2sg54T8
Anesthetic management of spontaneous cervical epidural hematoma during pregnancy: a case report
Spontaneous spinal epidural hematoma during pregnancy is a quite rare event requiring emergent decompressive surgery in the majority of cases to prevent permanent neurological damage. Therefore, there is littl...
http://ift.tt/2sUucAH
Johns Hopkins Kimmel Cancer Center and WellSpan Collaborate to Fight Cancer
The Johns Hopkins Kimmel Cancer Center and WellSpan Health today announced a new clinical collaboration that will benefit patients living with cancer in central Pennsylvania's Adams, Lancaster, Lebanon and York counties.
http://ift.tt/2teQbp6
Quantitative Pneumatic Otoscopy Using a Light-Based Ranging Technique
Abstract
Otitis media is the leading cause of hearing loss in children. It is commonly associated with fluid in the ear, which can result in up to 45 dB of hearing loss for extended periods of time during a child's most important developmental years. Accurate assessment of middle ear effusions is an important part of understanding otitis media. Current technologies used to diagnose otitis media with effusion are pneumatic otoscopy, tympanometry, and acoustic reflectometry. While all of these techniques can reasonably diagnose the presence of an effusion, they provide limited information about the infection present behind the tympanic membrane.
We have developed a technique based on low-coherence interferometry—a non-invasive optical ranging technique capable of sensing depth-resolved microscopic scattering features through the eardrum—to quantify eardrum thickness and integrity, as well as detect any effusion, purulence, or biofilm behind the tympanic membrane. In this manuscript, the technique is coupled with a pneumatic otoscope to measure minute deflections of the tympanic membrane from insufflation pressure stimuli. This results in quantitative measurements of tympanic membrane mobility, which may be used to gain a better understanding of the impact of infection on the membrane dynamics. A small pilot study of 15 subjects demonstrates the ability of pneumatic low-coherence interferometry to quantitatively differentiate normal ears from ears with effusions present. Analysis of the strengths and weaknesses of the technique, as well as focus areas of future research, is also discussed.
http://ift.tt/2sTUdjH
Quantitative Pneumatic Otoscopy Using a Light-Based Ranging Technique
Abstract
Otitis media is the leading cause of hearing loss in children. It is commonly associated with fluid in the ear, which can result in up to 45 dB of hearing loss for extended periods of time during a child's most important developmental years. Accurate assessment of middle ear effusions is an important part of understanding otitis media. Current technologies used to diagnose otitis media with effusion are pneumatic otoscopy, tympanometry, and acoustic reflectometry. While all of these techniques can reasonably diagnose the presence of an effusion, they provide limited information about the infection present behind the tympanic membrane.
We have developed a technique based on low-coherence interferometry—a non-invasive optical ranging technique capable of sensing depth-resolved microscopic scattering features through the eardrum—to quantify eardrum thickness and integrity, as well as detect any effusion, purulence, or biofilm behind the tympanic membrane. In this manuscript, the technique is coupled with a pneumatic otoscope to measure minute deflections of the tympanic membrane from insufflation pressure stimuli. This results in quantitative measurements of tympanic membrane mobility, which may be used to gain a better understanding of the impact of infection on the membrane dynamics. A small pilot study of 15 subjects demonstrates the ability of pneumatic low-coherence interferometry to quantitatively differentiate normal ears from ears with effusions present. Analysis of the strengths and weaknesses of the technique, as well as focus areas of future research, is also discussed.
http://ift.tt/2sTUdjH
Intranasal Administration of Whole Inactivated Influenza Virus Vaccine as a Promising Influenza Vaccine Candidate
Viral Immunology , Vol. 0, No. 0.
http://ift.tt/2s9bxnP
Helper T Cell Responses to Respiratory Viruses in the Lung: Development, Virus Suppression, and Pathogenesis
Viral Immunology , Vol. 0, No. 0.
http://ift.tt/2sTGKIJ
Catheter-related right internal jugular vein thrombosis after chest surgery
Abstract
Background: Central venous catheters (CVCs) are frequently used for monitoring haemodynamic status and rapidly delivering fluid therapy during the peri- and postoperative periods. Indwelling CVCs are typically used 7–14 days postoperatively for additional monitoring and treatment, but patients may develop asymptomatic catheter-related thrombosis, leading to life-threatening pulmonary embolism and death. Early detection helps to avoid such complications.Methods: This prospective observational study investigated the risk factors associated with catheter-related right internal jugular vein thrombosis in patients undergoing chest surgery. The study enrolled 24 patients who were scheduled to receive chest surgeries during which catheters were needed. To detect thrombus formation, Doppler ultrasound examinations from the thyroid cartilage level to the supraclavicular region were used after CVC placement and on each of the following days until the catheter was removed.Results: No thrombosis was found in patients before surgery, but it appeared in 75% (18/24) after surgery. The risks of thrombosis increased with a longer duration of anaesthesia, greater amounts of bleeding, and use of postoperative ventilator support.Conclusions: Earlier catheter removal may reduce the risk of catheter-related thrombosis and avoid possibly fatal complications after catheter-related thrombosis.http://ift.tt/2s9qk1H
Checklists, cognitive aids, and the future of patient safety
On Wednesday, October 30, 1935, an evaluation flight of the Boeing Model 299 was undertaken at Wright Field, northeast of Dayton, OH, USA. The Model 299 was the most technologically sophisticated aircraft of its time and was nicknamed the Flying Fortress because of the extent of its armaments. Major Ployer P. Hill was the pilot, and it was his first flight in the new aircraft. The aircraft appeared to ascend normally, but suddenly stalled, turned on one wing, and crashed, killing two of the aircraft's five crew, including Major Hill. The investigation into the crash discovered that Major Hill had omitted a crucial step during the preflight preparation; he forgot to release a catch, which on the ground locked the aircraft's control flaps.1 Once in the air, this mistake rendered the aircraft uncontrollable. The crash investigators knew that there was probably no one better qualified to fly the new aircraft than Major Hill—his co-pilot was also highly qualified—yet despite this, the fatal error was still made. The investigators concluded that given the experience of the pilots, further training would not be an effective response to prevent such an event from happening again; a response that is very different from that which often occurs in health care when a mistake is made.2 Some commentators initially believed that this meant the new aircraft was simply too complicated to fly reliably. A new approach was needed, and it took the form of a simple list of crucial tasks that must be completed before the aircraft could leave the ground. The first aviation checklist had been devised.1 With the checklist in use, despite the aircraft's sophistication, the Model 299 (and later versions of it) performed safely for many years.
http://ift.tt/2sTskZ9
http://ift.tt/2sTskZ9
What Happens to Baby in The Delivery Room?
What is skin to skin, and why is it important? What does it matter when Baby gets his first bath? And what's that gel that goes on her eyes? Abby and Dr. Emily Fishman answer all your questions live on Belly to Baby.
The post What Happens to Baby in The Delivery Room? appeared first on ChildrensMD.
http://ift.tt/2sdY7C5
An architecture for large-scale IP telephony networks
Terzis, D; (2006) An architecture for large-scale IP telephony networks. Doctoral thesis, UCL (University College London). Green open access
http://ift.tt/2sdChP6
Encapsulation and Polymerization of White Phosphorus Inside Single-Wall Carbon Nanotubes
Hart, M; White, ER; Chen, J; McGilvery, CM; Pickard, CJ; Michaelides, A; Sella, A; Hart, M; White, ER; Chen, J; McGilvery, CM; Pickard, CJ; Michaelides, A; Sella, A; Shaffer, MSP; Salzmann, CG; - view fewer (2017) Encapsulation and Polymerization of White Phosphorus Inside Single-Wall Carbon Nanotubes. Angewandte Chemie International Edition 10.1002/anie.201703585 . (In press).
http://ift.tt/2sIkMK8
An agent-based approach to spatial epidemics through GIS
De Almeida Simones, JM; (2007) An agent-based approach to spatial epidemics through GIS. Doctoral thesis, UCL (University College London). Green open access
http://ift.tt/2sdQuM1
Review of Janet Stewart, Simon Ward, Blueprints for No-Man's Land. Connections in Contemporary Austrian Culture. (British and Irish Studies in German Language and Literature 37), in Culture and Politics in Red Vienna, ed. by Judith Beniston and Robert Vilain
Liebscher, M; (2006) Review of Janet Stewart, Simon Ward, Blueprints for No-Man's Land. Connections in Contemporary Austrian Culture. (British and Irish Studies in German Language and Literature 37), in Culture and Politics in Red Vienna, ed. by Judith Beniston and Robert Vilain. Austrian Studies , 14 pp. 380-381. 10.2307/27944832 .
http://ift.tt/2sIAvcf
Persistence of Fimbrial Tissue on the Ovarian Surface Following Salpingectomy
Gan, C; Chenoy, R; Chandrasekaran, D; Brockbank, E; Hollingworth, A; Vimplis, S; Lawrence, AC; Gan, C; Chenoy, R; Chandrasekaran, D; Brockbank, E; Hollingworth, A; Vimplis, S; Lawrence, AC; Jeyarajah, AR; Oram, D; Deo, N; Saravanamuthu, J; Lam, SS; Faruqi, A; Singh, N; Manchanda, R; - view fewer (2017) Persistence of Fimbrial Tissue on the Ovarian Surface Following Salpingectomy. American Journal of Obstetrics and Gynecology 10.1016/j.ajog.2017.06.004 . (In press).
http://ift.tt/2se9Z70
Atomic layer deposition of B-doped ZnO using triisopropyl borate as the boron precursor and comparison with Al-doped ZnO
Garcia-Alonso, D; Potts, SE; Van Helvoirt, CAA; Verheijen, MA; Kessels, WMM; (2015) Atomic layer deposition of B-doped ZnO using triisopropyl borate as the boron precursor and comparison with Al-doped ZnO. Journal of Materials Chemistry C , 3 (13) pp. 3095-3107. 10.1039/c4tc02707h . Green open access
http://ift.tt/2sIwTH8
Anatomy-driven multiple trajectory planning (ADMTP) of intracranial electrodes for epilepsy surgery
Sparks, R; Vakharia, V; Rodionov, R; Vos, SB; Diehl, B; Wehner, T; Miserocchi, A; Sparks, R; Vakharia, V; Rodionov, R; Vos, SB; Diehl, B; Wehner, T; Miserocchi, A; McEvoy, AW; Duncan, JS; Ourselin, S; - view fewer (2017) Anatomy-driven multiple trajectory planning (ADMTP) of intracranial electrodes for epilepsy surgery. International Journal of Computer Assisted Radiology and Surgery 10.1007/s11548-017-1628-z . (In press). Green open access
http://ift.tt/2sdQpId
Albumin dialysis in liver failure
Sen, S; (2006) Albumin dialysis in liver failure. Doctoral thesis, UCL (University College London). Green open access
http://ift.tt/2sIDtNP
Crystal structure of the DNA-binding domain of Myelin-gene Regulatory Factor
Zhen, X; Li, B; Hu, F; Yan, S; Meloni, G; Li, H; Shi, N; (2017) Crystal structure of the DNA-binding domain of Myelin-gene Regulatory Factor. Scientific Reports , 7 , Article 3696. 10.1038/s41598-017-03768-9 . Green open access
http://ift.tt/2sdCilS
Lowering IceCube’s energy threshold for point source searches in the southern sky
Observation of a point source of astrophysical neutrinos would be a "smoking gun" signature of a cosmic-ray accelerator. While IceCube has recently discovered a diffuse flux of astrophysical neutrinos, no localized point source has been observed. Previous IceCube searches for point sources in the southern sky were restricted by either an energy threshold above a few hundred TeV or poor neutrino angular resolution. Here we present a search for southern sky point sources with greatly improved sensitivities to neutrinos with energies below 100 TeV. By selecting charged-current nu(mu) interacting inside the detector, we reduce the atmospheric background while retaining efficiency for astrophysical neutrino-induced events reconstructed with sub-degree angular resolution. The new event sample covers three years of detector data and leads to a factor of 10 improvement in sensitivity to point sources emitting below 100 TeV in the southern sky. No statistically significant evidence of point sources was found, and upper limits are set on neutrino emission from individual sources. A posteriori analysis of the highest-energy (similar to 100 TeV) starting event in the sample found that this event alone represents a 2.8 sigma deviation from the hypothesis that the data consists only of atmospheric background.
http://ift.tt/2tMXuBd
Observation and characterization of a cosmic muon neutrino flux from the Northern Hemisphere using six years of IceCube data
The IceCube Collaboration has previously discovered a high-energy astrophysical neutrino flux using neutrino events with interaction vertices contained within the instrumented volume of the IceCube detector. We present a complementary measurement using charged current muon neutrino events where the interaction vertex can be outside this volume. As a consequence of the large muon range the effective area is significantly larger but the field of view is restricted to the Northern Hemisphere. IceCube data from 2009 through 2015 have been analyzed using a likelihood approach based on the reconstructed muon energy and zenith angle. At the highest neutrino energies between 194 TeV and 7.8 PeV a significant astrophysical contribution is observed, excluding a purely atmospheric origin of these events at 5.6 sigma significance. The data are well described by an isotropic, unbroken power-law flux with a normalization at 100 TeV neutrino energy of (0.90(-0.27)(+0.30)) x 10(-18) GeV-1 cm(-2) s(-1) sr(-1) and a hard spectral index of gamma = 2.13 +/- 0.13. The observed spectrum is harder in comparison to previous IceCube analyses with lower energy thresholds which may indicate a break in the astrophysical neutrino spectrum of unknown origin. The highest-energy event observed has a reconstructed muon energy of (4.5 +/- 1.2) PeV which implies a probability of less than 0.005% for this event to be of atmospheric origin. Analyzing the arrival directions of all events with reconstructed muon energies above 200 TeV no correlation with known gamma-ray sources was found. Using the high statistics of atmospheric neutrinos we report the current best constraints on a prompt atmospheric muon neutrino flux originating from charmed meson decays which is below 1.06 in units of the flux normalization of the model in Enberg et al.
http://ift.tt/2tMAUsE
Towards a bacterial treatment for armpit malodour
Axillary malodour is a frustrating condition for many people. It can lead to significant discomforts and various psychological effects. The underarm microbiome plays a major role in axillary malodour formation. Not only the bacteria on the epidermis, but also and especially those living in the sweat glands, sweat pores and hair follicles play a pivotal role in malodour development. To treat underarm malodour, this viewpoint article envisions a bacterial treatment. Replacing the autochthonous malodour-causing microbiome with a non-odour- causing microbiome, through an armpit bacterial transplantation or direct application of probiotics/non-odour- causing bacteria, could resolve the condition. Selective steering of the microbiome with prebiotics, biochemicals or plant extracts can likewise greatly help in improving the underarm odour. Elimination/ inhibition of the "bad bugs" and application/stimulation of the "good bugs" will be part of the future treatment for axillary body odour.
http://ift.tt/2tdq3uK
Nintedanib as a novel treatment option in hereditary haemorrhagic telangiectasia
A 70-year-old patient with known hereditary haemorrhagictelangiectasia (HHT) was seen regularly in our outpatient clinic. He underwent multiple therapeutical interventions, including both surgical and medical, for the treatment of recurrent epistaxis without sustained success. Due to a concurrent diagnosis of idiopathic pulmonary fibrosis, treatment with the tyrosine kinase inhibitor nintedanib was initiated, after which point the patient reported a dramatic and unanticipated improvement in his epistaxis and skin telangiectasia. On the basis of this case report, we propose that nintedanib may be a potential treatment option for refractory epistaxis in HHT.
http://ift.tt/2tcCbeT
Long non-coding RNAs in cutaneous melanoma: clinical perspectives
Metastatic melanoma of the skin has a high mortality despite the recent introduction of targeted therapy and immunotherapy. Long non-coding RNAs (lncRNAs) are defined as transcripts of more than 200 nucleotides in length that lack protein-coding potential. There is growing evidence that lncRNAs play an important role in gene regulation, including oncogenesis. We present 13 lncRNA genes involved in the pathogenesis of cutaneous melanoma through a variety of pathways and molecular interactions. Some of these lncRNAs are possible biomarkers or therapeutic targets for malignant melanoma.
http://ift.tt/2tdvoC6
A phase II trial of stereotactic body radiotherapy with concurrent anti-PD1 treatment in metastatic melanoma: evaluation of clinical and immunologic response
Background: Antibodies blocking programmed cell death 1 (PD-1) have encouraging responses in patients with metastatic melanoma. Response to anti-PD-1 treatment requires pre-existing CD8+ T cells that are negatively regulated by PD-1-mediated adaptive immune resistance. Unfortunately, less than half of melanoma tumours have these characteristics. Combining anti-PD-1 treatment with other immunomodulating treatments to activate CD8+ T cells is therefore of vital importance to increase response rates and long-term survival benefit in melanoma patients. Both preclinical and retrospective clinical data support the hypothesis that radiotherapy increases the response rates to anti-PD-1 treatment by stimulating the accumulation and activation of CD8+ T cells in the tumour microenvironment. Combining radiotherapy with a PD-1 blocking antibody might therefore increase response rates and even induce long-term survival. The current phase II study will be testing these hypotheses and aims to improve local and distant tumour responses by exploiting the pro-immunogenic effects of radiotherapy in addition to anti-PD-1 treatment. Methods: The trial will be conducted in patients with metastatic melanoma. Nivolumab or pembrolizumab, both antibodies that target PD-1, will be administrated according to the recommended dosing schedule. Prior to the 2nd cycle, radiotherapy will be delivered in three fractions of 8 Gy to the largest FDG-avid metastatic lesion. The primary endpoint is the proportion of patients with a partial or complete response in non-irradiated metastases according to RECIST v1.1. Secondary endpoints include response rate according to immune related response criteria, metabolic response, local control and survival. To identify peripheral blood biomarkers, peripheral blood mononuclear cells and serum samples will be collected prospectively before, during and after treatment and subjected to flow cytometry and cytokine measurement. Discussion: The current phase II trial aims at exploring the suggested benefits of combining anti-PD-1 treatment and radiotherapy. The translational focus on immunologic markers might be suitable for predicting efficacy and monitoring the effect so to improve patient selection for future clinical applications.
http://ift.tt/2tMGhYS
The rationale of indoleamine 2,3-dioxygenase inhibition for cancer therapy
Metastatic melanoma of the skin has a high mortality despite the recent introduction of targeted therapy and immunotherapy. Long non-coding RNAs (lncRNAs) are defined as transcripts of more than 200 nucleotides in length that lack protein-coding potential. There is growing evidence that lncRNAs play an important role in gene regulation, including oncogenesis. We present 13 lncRNA genes involved in the pathogenesis of cutaneous melanoma through a variety of pathways and molecular interactions. Some of these lncRNAs are possible biomarkers or therapeutic targets for malignant melanoma.
http://ift.tt/2tdeKmq
An all-sky search for three flavors of neutrinos from gamma-ray bursts with the IceCube Neutrino Observatory
We present the results and methodology of a search for neutrinos produced in the decay of charged pions created in interactions between protons and gamma-rays during the prompt emission of 807 gamma-ray bursts (GRBs) over the entire sky. This three-year search is the first in IceCube for shower-like Cherenkov light patterns from electron, muon, and tau neutrinos correlated with GRBs. We detect five low-significance events correlated with five GRBs. These events are consistent with the background expectation from atmospheric muons and neutrinos. The results of this search in combination with those of IceCube's four years of searches for track-like Cherenkov light patterns from muon neutrinos correlated with Northern-Hemisphere GRBs produce limits that tightly constrain current models of neutrino and ultra high energy cosmic ray production in GRB fireballs.
http://ift.tt/2tdgCeI
Distant metastases in head and neck cancer
ABSTRACT
Background
Most trials in head and neck cancer emphasize locoregional control, as this is the main pattern of therapy failure. However, up to 15% of patients develop distant metastases. The purpose of this study was to present the investigated factors associated with distant metastasis in a single-center patient cohort.
Methods
A retrospective analysis of a single-center patient cohort over an 18-year period has been performed. We report on prevalence and incidence of distant metastasis, timing in relation to locoregional failure, Kaplan–Meier analysis for actuarial distant control rates, and univariate analysis taking into account histological, etiologic, surgical, site-dependent, stage-dependent characteristics, modality of primary therapy, and locoregional control.
Results
Of 1022 patients, 141 (13.8%) were diagnosed with distant metastases involving 283 sites. Actuarial rates of distant control were 88%, 84%, 80%, and 79% at 1, 2, 5, and 10 years, respectively. Factors associated with distant metastasis are stage grouping and regional node positivity, extranodal extension, locoregional residual disease, and human papillomavirus (HPV) negative status in oropharyngeal squamous cell carcinoma.
Conclusion
Distant metastases in head and neck cancer led to dismal prognosis. Factors associated with distant metastasis are related to characteristics of the primary tumor. © 2017 Wiley Periodicals, Inc. Head Neck, 2017
http://ift.tt/2tac3Rs
A systematic review of the relationship between glycemic control and necrobiosis lipoidica diabeticorum in patients with diabetes mellitus
Abstract
The association of specific skin disorders with diabetes mellitus (DM) has been well established. Current literature suggests that approximately 30–91% of patients with diabetes will experience at least one cutaneous manifestation of this systemic disease in their lifetime. To date, there are limited articles summarizing the link between necrobiosis lipoidica diabeticorum (NLD) prognosis and glycemic control in patients with diabetes. The objective of the study is to summarize and appraise the available evidence assessing the relationship between glycemic control and NLD. A literature search was conducted based on MEDLINE (1946–2015), EMBASE (1980–2015), Google Scholar, and PubMed for publications that described the results of diabetes control and NLD. Further studies were identified from bibliographies of all relevant studies, gray literature, and annual scientific assemblies. All studies investigating the relationship between DM (type 1 and type 2) management and NLD were included. Two reviewers independently extracted data including demographics, type of diabetes management measures (glucose, HbA1c, insulin), comorbidities, and outcome. A total of 622 studies were identified, and 10 studies met the inclusion and exclusion criteria: two case series and eight case reports. Of the 24 patients with NLD, 13 patients reported resolution of NLD after implementing various methods of glycemic control (diabetic diet consisting of 1600 kcal/day [1 patient], insulin regimen [3 patients], and pancreatic transplantation [9 patients]). Glycemic control may have a role in influencing the prognosis of necrobiosis lipoidica in patients with diabetes; however, there is currently insufficient evidence to support or refute this claim.
http://ift.tt/2s8iWnh
JAK3 as an Emerging Target for Topical Treatment of Inflammatory Skin Diseases
The recent interest and elucidation of the JAK/STAT signaling pathway created new targets for the treatment of inflammatory skin diseases (ISDs). JAK inhibitors in oral and topical formulations have shown beneficial results in psoriasis and alopecia areata. Patients suffering from other ISDs might also benefit from JAK inhibition. Given the development of specific JAK inhibitors, the expression patterns of JAKs in different ISDs needs to be clarified. We aimed to analyze the expression of JAK/STAT family members in a set of prevalent ISDs: psoriasis, lichen planus (LP), cutaneous lupus erythematosus (CLE), atopic dermatitis (AD), pyoderma gangrenosum (PG) and alopecia areata (AA) versus healthy controls for (p)JAK1, (p)JAK2, (p)JAK3, (p)TYK2, pSTAT1, pSTAT2 and pSTAT3. The epidermis carried in all ISDs, except for CLE, a strong JAK3 signature. The dermal infiltrate showed a more diverse expression pattern. JAK1, JAK2 and JAK3 were significantly overexpressed in PG and AD suggesting the need for pan-JAK inhibitors. In contrast, psoriasis and LP showed only JAK1 and JAK3 upregulation, while AA and CLE were characterized by a single dermal JAK signal (pJAK3 and pJAK1, respectively). This indicates that the latter diseases may benefit from more targeted JAK inhibitors. Our in vitro keratinocyte psoriasis model displayed reversal of the psoriatic JAK profile following tofacitinib treatment. This direct interaction with keratinocytes may decrease the need for deep skin penetration of topical JAK inhibitors in order to exert its effects on dermal immune cells. In conclusion, these results point to the important contribution of the JAK/STAT pathway in several ISDs. Considering the epidermal JAK3 expression levels, great interest should go to the investigation of topical JAK3 inhibitors as therapeutic option of ISDs.
http://ift.tt/2t9X8XB
Age- and strain-dependent differences in the outcome of experimental infections of domestic pigs with wild boar pseudorabies virus isolates
Although pseudorabies virus (PRV) has been eradicated in domestic swine in many countries, its presence in wild boars remains a threat for a reintroduction into the currently unprotected swine population. To assess the possible impact of such a reintroduction in a naive herd, an in vivo infection study using two genetically characterized wild boar PRV isolates (BEL24043 and BEL20075) representative for wild boar strains circulating in south-western and central Europe and the virulent NIA3 reference strain was performed in 2- and 15-week-old domestic pigs. Our study revealed an attenuated nature of both wild boar strains in 15-week-old pigs. In contrast, it showed the capacity of strain BEL24043 to induce severe clinical symptoms and mortality in young piglets, thereby confirming that the known age dependency of disease outcome after PRV infection also holds for wild boar isolates. Despite the absence of clinical disease in 15-week-old sows, both wild boar PRV strains were able to induce seroconversion, but to a different extent. Importantly, differences in infection and transmission capacity of both strains were observed in 15-week-old sows. Strain BEL24043 induced a more prolonged and disseminated infection than strain BEL20075 and was able to spread efficiently to contact animals, indicative of its capacity to induce a sustained infection. In conclusion, it was shown that a reintroduction of a wild boar isolate into the domestic swine population could have serious economic consequences due to the induction of clinical symptoms in piglets and by jeopardizing the PRV-negative status.
http://ift.tt/2u7onPS
Electrocardiographic differentiation of idiopathic right ventricular outflow tract ectopy from early arrhythmogenic right ventricular cardiomyopathy
Novak, J; Zorzi, A; Castelletti, S; Pantasis, A; Rigato, I; Corrado, D; Mckenna, W; Novak, J; Zorzi, A; Castelletti, S; Pantasis, A; Rigato, I; Corrado, D; Mckenna, W; Lambiase, PD; - view fewer (2016) Electrocardiographic differentiation of idiopathic right ventricular outflow tract ectopy from early arrhythmogenic right ventricular cardiomyopathy. Europace , 19 (4) pp. 622-628. 10.1093/europace/euw018 . Green open access
http://ift.tt/2ta2odB
Agriculture and trade amongst the Garamantes and the Fezzanese: 3000 years of archaeobotanical data from the Sahara and its margins
Pelling, RE; (2007) Agriculture and trade amongst the Garamantes and the Fezzanese: 3000 years of archaeobotanical data from the Sahara and its margins. Doctoral thesis, UCL (University College London). Green open access
http://ift.tt/2u7P0Ea
Ontology with Chinese characteristics Homology as a mode of identification
Matthews, WE; (2017) Ontology with Chinese characteristics Homology as a mode of identification. HAU : Journal of Ethnographic Theory , 7 (1) pp. 265-285. 10.14318/hau7.1.020 . Green open access
http://ift.tt/2ta1Zb9
Work-family life courses and metabolic markers in mid-life: evidence from the British National Child Development Study
McMunn, A; Lacey, RE; Kumari, M; Worts, D; McDonough, P; Sacker, A; (2016) Work-family life courses and metabolic markers in mid-life: evidence from the British National Child Development Study. Journal Of Epidemiology And Community Health , 70 (5) pp. 481-487. 10.1136/jech-2015-206036 . Green open access
http://ift.tt/2u7Ff8W
A 667-year record of co-seismic and interseismic Coulomb stress changes in central Italy reveals the role of fault interaction in controlling irregular earthquake recurrence intervals
Wedmore, LNJ; Faure Walker, JP; Roberts, GP; Sammonds, PR; McCaffrey, KJW; Cowie, PA; (2017) A 667-year record of co-seismic and interseismic Coulomb stress changes in central Italy reveals the role of fault interaction in controlling irregular earthquake recurrence intervals. Journal of Geophysical Research: Solid Earth 10.1002/2017JB014054 . (In press).
http://ift.tt/2t9HKui
Concreteness and abstraction in everyday explanation
Bechlivanidis, C; Lagnado, DA; Zemla, JC; Sloman, S; (2017) Concreteness and abstraction in everyday explanation. Psychonomic Bulletin & Review 10.3758/s13423-017-1299-3 . (In press). Green open access
http://ift.tt/2u7VWRY
Planum temporale asymmetry in people who stutter
Gough, PM; Connally, EL; Howell, P; Ward, D; Chesters, J; Watkins, KE; (2017) Planum temporale asymmetry in people who stutter. Journal of Fluency Disorders 10.1016/j.jfludis.2017.06.003 . (In press). Green open access
http://ift.tt/2t9PBIo
Enhanced Atomic Desorption of 209 and 210 Francium from Organic Coating
Agustsson, S; Bianchi, G; Calabrese, R; Corradi, L; Dainelli, A; Khanbekyan, A; Marinelli, C; Agustsson, S; Bianchi, G; Calabrese, R; Corradi, L; Dainelli, A; Khanbekyan, A; Marinelli, C; Mariotti, E; Marmugi, L; Ricci, L; Stiaccini, L; Tomassetti, L; Vanella, A; - view fewer (2017) Enhanced Atomic Desorption of 209 and 210 Francium from Organic Coating. Scientific Reports , 7 , Article 4207. 10.1038/s41598-017-04397-y . Green open access
http://ift.tt/2u7S2IH
Accent features and idiodictionaries: on improving accuracy for accented speakers in ASR
Tjalve, M; (2007) Accent features and idiodictionaries: on improving accuracy for accented speakers in ASR. Doctoral thesis, UCL (University College London). Green open access
http://ift.tt/2ta9yPj
Neurogenic pulmonary oedema: a rare cause of maternal collapse
Acute pulmonary oedema is a significant cause of morbidity and mortality in pregnant and postpartum women. We present an unusual case of near-fatal acute pulmonary oedema in a pregnant woman, which was attributed to the acute onset of neurogenic pulmonary oedema secondary to epileptic seizure activity. The patient required supportive management in the intensive care setting for a short period and subsequently made complete recovery with regular neurological follow-up arranged for the management of her epilepsy.
http://ift.tt/2sHS5wQ
Higher Education & Contemporary Working Conditions: a Comparative Approach
Social epidemiological research is dominated by a rather optimistic view on the mental health status of the higher educated. Despite the consistency of this observation, recent empirical research points to some counteracting evidence as elevated forms of mental health complaints have been found for several higher educational professions and these are often directly linked to their working conditions. This issue is mainly studied from a micro perspective with a strong focus on working conditions as such but little attention has been paid to the potential influence of macro-processes. This research tries to fill this gap by focusing on how labor market competition among the higher educated influences their working conditions and hence their mental health status. Analysis are based on a subsample (N = 8848), aged between 18 and 65, of the European Working Condition Survey (5th edition, 2015). Results, from 30 European countries, indicate that increasing labor market competition among the higher educated is related to an amelioration of the mental health status for the employed higher educated. Furthermore, we see that labor market competition moderates the relationship between certain working conditions and mental health. It has been shown, for example, that managerial quality or support becomes more important the more a country's labor market is characterized by competition among the higher educated. The results are discussed in the light of literature on the expansion of tertiary education.
http://ift.tt/2tbj0T2
Form removal aspects on the waviness parameters for steel sheet in automotive applications: Fourier filtering versus polynomial regression
Premium car makers attach great importance to the visual appearance of the painted car skin as an indication of product quality. The "orange peel" phenomenon constitutes a major problem here. It is not only depending on the paint's chemical composition and application method, but also on possible waviness components in the sheet substrate. Therefore one is searching hard for a valuable waviness parameter to quantify the substrate's fitness for purpose. A technically emerging problem is how to remove the form from the measured signal, which is indeed not significant to the orange peel phenomenon. This paper will compare two commonly used approaches: i.e. Fourier filtering versus polynomial regression and will reveal and quantify some common aspects in terms of wavelengths.
http://ift.tt/2sdiWNU
Fibroblast-derived exosomes promote epithelial cell proliferation through TGF-β2 signaling pathway in severe asthma
Abstract
Background
Bronchial fibroblasts play a key role in airway remodeling in asthma. They regulate epithelial cell functions such as proliferation through growth factors, cytokines, chemokines and exosomes. The role of exosomes in the communication between epithelial cells and fibroblasts by vehiculing these mediators in asthma remains to be determined.
Objective
To evaluate the role of exosomes released by bronchial fibroblasts on epithelial cell proliferation in severe asthma.
Methods
Exosomes were obtained from culture media of primary bronchial fibroblasts and characterized using Western blot, electron microscopy and flow cytometry. Uptake profile of fluorescent-labeled exosomes in epithelial cells was assessed by flow cytometry. Exosome cytokine content was analysed by Cytokine Arrays. Bronchial epithelial cell proliferation was evaluated by BrdU incorporation test. Exosomes biogenesis/release was blocked by using sphingomyelinase inhibitor. Plasmid transfection was used to modulate TGF-β2 gene expression.
Results
We showed that bronchial fibroblasts secreted exosomes, which were internalized by bronchial epithelial cells. Exosomes of severe asthmatic subjects' fibroblasts showed a lower level of TGF-β2 and significantly increased the epithelial cells proliferation of both healthy and severe asthmatic subjects compared to healthy controls' exosomes. Overexpression of TGF-β2 in severe asthmatics' fibroblasts induced enhanced TGF-β2 in exosomes leading to a reduced proliferation of epithelial cells, whereas knockdown of TGF-β2 enhanced epithelial cell proliferation.
Conclusion
Our study shows that exosomes are involved in fine-tuning intercellular communication in asthma. Exosomes of severe eosinophilic asthmatics' fibroblasts can contribute to airway remodeling, at least in part, by modulating epithelial cell proliferation observed in severe asthma.
This article is protected by copyright. All rights reserved.
http://ift.tt/2rSEY9a
RAS screening in colorectal cancer: a comprehensive analysis of the results from the UK NEQAS colorectal cancer external quality assurance schemes (2009–2016)
Abstract
Evidence strongly indicates that extended RAS testing should be undertaken in mCRC patients, prior to prescribing anti-EGFR therapies. With more laboratories implementing testing, the requirement for External Quality Assurance schemes increases, thus ensuring high standards of molecular analysis. Data was analysed from 15 United Kingdom National External Quality Assessment Service (UK NEQAS) for Molecular Genetics Colorectal cancer external quality assurance (EQA) schemes, delivered between 2009 and 2016. Laboratories were provided annually with nine colorectal tumour samples for genotyping. Information on methodology and extent of testing coverage was requested, and scores given for genotyping, interpretation and clerical accuracy. There has been a sixfold increase in laboratory participation (18 in 2009 to 108 in 2016). For RAS genotyping, fewer laboratories now use Roche cobas®, pyrosequencing and Sanger sequencing, with more moving to next generation sequencing (NGS). NGS is the most commonly employed technology for BRAF and PIK3CA mutation screening. KRAS genotyping errors were seen in ≤10% laboratories, until the 2014–2015 scheme, when there was an increase to 16.7%, corresponding to a large increase in scheme participants. NRAS genotyping errors peaked at 25.6% in the first 2015–2016 scheme but subsequently dropped to below 5%. Interpretation and clerical accuracy scores have been consistently good throughout. Within this EQA scheme, we have observed that the quality of molecular analysis for colorectal cancer has continued to improve, despite changes in the required targets, the volume of testing and the technologies employed. It is reassuring to know that laboratories clearly recognise the importance of participating in EQA schemes.
http://ift.tt/2sS1YXf
Moving sounds and sonic moves : exploring interaction quality of embodied music mediation technologies through a user-centered perspective
This research project deals with the user-experience related to embodied music mediation technologies. More specifically, adoption and policy problems surrounding new media (art) are considered, which arise from the usability issues that to date pervade new interfaces for musical expression. Since the emergence of new wireless mediators and control devices for musical expression, there is an explicit aspiration of the creative industries and various research centers to embed such technologies into different areas of the cultural industries. The number of applications and their uses have exponentially increased over the last decade. Conversely, many of the applications to date still suffer from severe usability problems, which not only hinder the adoption by the cultural sector, but also make culture participants take a rather cautious, hesitant, or even downright negative stance towards these technologies. Therefore, this thesis takes a vantage point that is in part sociological in nature, yet has a link to cultural studies as well. It combines this with a musicological frame of reference to which it introduces empirical user-oriented approaches, predominantly taken from the field of human-computer-interaction studies. This interdisciplinary strategy is adopted to cope with the complex nature of digital embodied music controlling technologies. Within the Flanders cultural (and creative) industries, opportunities of systems affiliated with embodied interaction are created and examined. This constitutes an epistemological jigsaw that looks into 1) "which stakeholders require what various levels of involvement, what interactive means and what artistic possibilities?", 2) "the way in which artistic aspirations, cultural prerequisites and operational necessities of (prospective) users can be defined?", 3) "how functional, artistic and aesthetic requirements can be accommodated?", and 4) "how quality of use and quality of experience can be achieved, quantified, evaluated and, eventually, improved?". Within this multi-facetted problem, the eventual aim is to assess the applicability of the foresaid technology, both from a theoretically and empirically sound basis, and to facilitate widening and enhancing the adoption of said technologies. Methodologically, this is achieved by 1) applied experimentation, 2) interview techniques, 3) self-reporting and survey research, 4) usability evaluation of existing devices, and 5) human-computer interaction methods applied – and attuned – to the specific case of embodied music mediation technologies. Within that scope, concepts related to usability, flow, presence, goal assessment and game enjoyment are scrutinized and applied, and both task- and experience-oriented heuristics and metrics are developed and tested. In the first part, covering three chapters, the general context of the thesis is given. In the first chapter, an introduction to the topic is offered and the current problems are enumerated. In the second chapter, a broader theoretical background is presented of the concepts that underpin the project, namely 1) the paradigm of embodiment and its connection to musicology, 2) a state of the arts concerning new interfaces for musical expression, 3) an introduction into HCI-usability and its application domain in systematic musicology, 4) an insight into user-centered digital design procedures, and 5) the challenges brought about by e-culture and digitization for the cultural-creative industries. In the third chapter, the state of the arts concerning the available methodologies related to the thesis' endeavor is discussed, a set of literature-based design guidelines are enumerated and from this a conceptual model is deduced which is gradually presented throughout the thesis, and fully deployed in the "SoundField"-project (as described in Chapter 9). The following chapters, contained in the second part of the thesis, give a quasi-chronological overview of how methodological concepts have been applied throughout the empirical case studies, aimed specifically at the exploration of the various aspects of the complex status quaestionis. In the fourth chapter, a series of application-based tests, predominantly revolving around interface evaluation, illustrate the complex relation between gestural interfaces and meaningful musical expression, advocating a more user-centered development approach to be adopted. In the fifth chapter, a multi-purpose questionnaire dubbed "What Moves You" is discussed, which aimed at creating a survey of the (prospective) end-users of embodied music mediation technologies. Therefore, it primarily focused on cultural background, musical profile and preferences, views on embodied interaction, literacy of and attitudes towards new technology and participation in digital culture. In the sixth chapter, the ethnographical studies that accompanied the exhibition of two interactive art pieces, entitled "Heart as an Ocean" & "Lament", are discussed. In these studies, the use of interview and questionnaire methodologies together with the presentation and reception of interactive art pieces, are probed. In the seventh chapter, the development of the collaboratively controlled music-game "Sync-In-Team" is presented, in which interface evaluation, presence, game enjoyment and goal assessment are the pivotal topics. In the eighth chapter, two usability studies are considered, that were conducted on prototype systems/interfaces, namely a heuristic evaluation of the "Virtual String" and a usability metrics evaluation on the "Multi-Level Sonification Tool". The findings of these two studies in conjunction with the exploratory studies performed in association with the interactive art pieces, finally gave rise to the "SoundField"-project, which is recounted in full throughout the ninth chapter. The integrated participatory design and evaluation method, presented in the conceptual model is fully applied over the course of the "SoundField"-project, in which technological opportunities and ecological validity and applicability are investigated through user-informed development of numerous use cases. The third and last part of the thesis renders the final conclusions of this research project. The tenth chapter sets out with an epilogue in which a brief overview is given on how the state of the arts has evolved since the end of the project (as the research ended in 2012, but the research field has obviously moved on), and attempts to consolidate the implications of the research studies with some of the realities of the Flemish cultural-creative industries. Chapter eleven continues by discussing the strengths and weaknesses of the conceptual model throughout the various stages of the project. Also, it comprises the evaluation of the hypotheses, how the assumptions that were made held up, and how the research questions eventually could be assessed. Finally, the twelfth and last chapter concludes with the most important findings of the project. Also, it discusses some of the implications on cultural production, artistic research policy and offers an outlook on future research beyond the scope of the "SoundField" project.
http://ift.tt/2rSjxoZ
Towards understanding rain infiltration in historic brickwork
Historic masonry walls are typically afflicted with uncertainties and defects which might induce significant rain water infiltrations. Insight in these moisture transport mechanisms in brickwork is important because the moisture content of brickwork is the predominant parameter for damage functions for frost, mold, and corrosion, and also affects heat flux. Given the increased focus on low-energy retrofits, interior insulation is becoming more popular. However, this typically decreases the drying potential of the wall and might consequently induce even more moisture-related pathologies. The insulation causes the exterior surface of the brickwork to be saturated more often, and this renders it possible for a runoff water film to develop during heavy rainfall. Although it is well known that this water film can penetrate through defects in the brickwork, the amount of water that penetrates remains a big question mark. Consequently, this important transport mechanism is typically omitted in hygrothermal simulations of (historical) brickwork. To obtain quantitative information, a series of laboratory tests is conducted. In a test setup a runoff film is applied in combination with a range of air pressure differences on a surface with different types of deficiencies representing imperfections in the facade. In this first phase, as an abstraction of the real saturated masonry construction a PMMA surface was used. The applied runoff film is imposed precisely and the water infiltration rate through the deficiencies is measured gravimetrically. Finally, the laboratory results are analyzed and preliminary linear relations between pressure and infiltration rate are found.
http://ift.tt/2rSo8XZ
Analysis of different frost indexes and their potential to assess frost based on HAM simulations
To reach the climate goals of 2020 our buildings have to become a lot more energy-efficient. This challenge rests mainly on the shoulders of the renovation sector because new buildings are only a small part of our building stock. Old buildings mainly cannot get insulated on the outside because the facade is historically valuable or because of urban planning restrictions. In those cases interior insulation or - if possible - cavity insulation are the only options. However, these renovation strategies may induce severe risks for the existing structure. One of the main risks is frost damage: the interior insulation lowers the temperature of the exterior facade and decreases the drying potential to the inside which leads to an increased risk of frost damage. Most of the studies that assess the risk of frost damage struggle with the dependency of the highly variable material properties of the façade.
http://ift.tt/2tbqzcb
Factors determining fatigue in the chronic fatigue syndrome : a path analysis
Objectives: To explore the interrelationship of different dimensions (fatigue, neuroticism, sleep quality, global mental and physical health) in patients with chronic fatigue syndrome (CFS). Methods: Patients meeting the Fukuda criteria of CFS filled out two independent fatigue scales (Fatigue Questionnaire, FQ and Checklist Individual Strength, CIS), NEO-Five Factor Inventory (NEO-FFI), Pittsburgh Sleep Quality Index (PSQI) and Medical Outcomes Study 36-item Short Form Health Survey (SF36). Exploratory and confirmatory path analyses were performed. Results: Out of 226 eligible patients, 167 subjects were included (mean age 39.13years, SD 10.14, 92% female). In a first exploratory path analysis, using FQ for assessment of fatigue, night-time PSQI sleep quality had a direct effect on SF36 physical quality of life (PQoL) and no effect on FQ fatigue. This was confirmed by a subsequent path analysis with CIS fatigue and by confirmatory path analyses in 81 patients. These unexpected results raised the question whether FQ or CIS fatigue sufficiently operationalizes fatigue in CFS patients. Conclusions: Poor sleep quality seems to directly impact on mental quality of life (MQoL) and PQoL without mediation of fatigue assessed with FQ and CIS. A more cohesive framework needs to be developed with more comprehensive clinical tools for the different dimensions in the construct of CFS.
http://ift.tt/2tbqhBY
Fire testing of insulated RC beams strengthened with near surface mounted FRP reinforcement
Seventeen NSM FRP (Near Surface Mounted Fibre Reinforced Polymer) strengthened and insulated full-scale beams, and two unstrengthened and unprotected beams, were subjected to fire tests. Insulation material type and dimensions and the insulation configuration were examined in order to develop practical methods for protecting FRP during fire exposure. Structural testing up to failure at room temperature of the fire tested beams has been carried out in order to evaluate their residual strength after one and two hours of fire exposure. The test program included the design and fabrication of steel reinforced concrete beams with rectangular cross-section. The experimental data demonstrated that all the insulated beams obtained the fire endurance ratings of 2h and 1h by satisfying both thermal and load bearing criteria. The paper will discuss the obtained test results.
http://ift.tt/2t8wu14
The clinical utility of narrow-band chirp auditory brainstem responses: inter- rater reliability and threshold estimation.
Background Tone-burst auditory brainstem responses (TB ABR) have traditionally been used to estimate the configuration of hearing loss in infants. However, more recent studies show that narrow-band (NB) chirps have several advantages over TB ABR. This study compares the reliability of NB-chirp and TB ABR. Methods ABRs were obtained in 23 adults using TBs and NB chirps with center frequencies at 0.5, 1, 2, and 4 kHz. First, we assessed inter-rater reliability of NB-chirp and TB ABR. Second, we compared signal-to- noise ratios of TB and NB-chirp ABR. Finally, we compared thresholds obtained by pure-tone audiometry, TB ABR, and NB-chirp ABR. Results Good inter-rater reliability was found for all frequencies. This holds true at maximal as well as threshold level. A preliminary analysis suggests that NB chirps elicits better responses than TBs for all center frequencies except 0.5 kHz, which seems to be difficult to interpret for both TBs and NB chirps. Conclusions NB chirps can be obtained with good inter-rater reliability. Further statistical analyses and comparisons between behavioral, TB ABR, and NB-chirp ABR thresholds will be presented and discussed.
http://ift.tt/2tbsJbR
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