Αρχειοθήκη ιστολογίου

Τρίτη 25 Απριλίου 2017

Systemic lupus erythematosus with Degos disease: role of dermatoscopy in diagnosis



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Skull base osteomyelitis secondary to malignant otitis externa mimicking advanced nasopharyngeal cancer: MR imaging features at initial presentation

Skull base osteomyelitis (SBOM) is an inflammatory process which often arises from malignant otitis externa (MOE); the diffuse skull base and adjacent soft tissue involvement may be mistaken at initial imaging for advanced nasopharyngeal carcinoma (NPC), especially if there is no prior knowledge of MOE, direct spread from the sphenoid sinus or in atypical presentations of MOE. This study aims to evaluate imaging features on MR that may differentiate SBOM from NPC.

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Teaching and practice patterns of lateral osteotomies for rhinoplasty

Lateral osteotomies are important during rhinoplasty and represent a challenging technique that otolaryngology and plastic surgery trainees must learn. The approaches for osteotomies are difficult to teach as they are accomplished through tactile feedback. Trends in teaching and practice patterns of lateral osteotomies are poorly described in the literature, and this study aims to fill this knowledge gap.

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Neue Ansätze zur Prävention aktinischer Keratosen

Zusammenfassung

Aktinische Keratosen gehören zu den häufigsten Hautkrankheiten. Aufgrund der aktuellen demografischen Entwicklung ist von einem weiteren Häufigkeitsanstieg auszugehen. Ihrer Prävention kommt daher zunehmende Bedeutung zu. Die mit Abstand wichtigste Ursache ist die chronische, kumulative Bestrahlung der menschlichen Haut mit ultravioletter B‑ und A‑Strahlung des natürlichen Sonnenlichts. Es besteht kein Zweifel, dass die Anwendung von Sonnenschutzmitteln das Risiko, aktinische Keratosen zu entwickeln, reduzieren kann. Zudem weisen neuere Studien darauf hin, dass insbesondere für Hochrisikogruppen die regelmäßige Anwendung von Medizinprodukten, die über einen sehr hohen Lichtschutzfaktor verfügen und zudem liposomal verpackte DNS-Reparaturenzyme beinhalten, selbst bei einer bestehenden Feldkanzerisierung das Auftreten neuer aktinischer Keratosen verhindern kann. Darüber hinaus scheinen auch orale photoprotektive Strategien, wie z. B. die Einnahme von Vitamin B3, für die Prävention aktinischer Keratosen geeignet zu sein.



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Identification of Three Novel Fusion Oncogenes, SQSTM1/NTRK3, AFAP1L2/RET, and PPFIBP2/RET, in Thyroid Cancers of Young Patients in Fukushima

Thyroid , Vol. 0, No. 0.


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Plasma-derived exosomes contribute to inflammation via the TLR9-NF-κB pathway in chronic heart failure patients

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Publication date: July 2017
Source:Molecular Immunology, Volume 87
Author(s): Wei Ye, Xiaojun Tang, Zhengquan Yang, Chu Liu, Xin Zhang, Jing Jin, Jianxin Lyu
Exosomes are small vesicles that contain proteins, DNA and RNA, and play an important role in inflammation; however, the underlying mechanism remains unclear. In the present study, we found increased plasma-derived exosomes in chronic heart failure patients compared with healthy controls. Further, our data demonstrated that plasma-derived exosomes carried mtDNA, and triggered an inflammatory response via the TLR9-NF-κB pathway, as well, the inflammatory effect was closely related to exosomal mtDNA copy number. However, the effect could be blocked by chloroquine (CQ), a TLR9 inhibitor. These findings reveal a new mechanism of exosome-induced inflammation, and provide a new perspective for intervention and treatment of inflammation-related diseases, such as chronic heart failure.



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Quantitative proteomic profiling for clarification of the crucial roles of lysosomes in microbial infections

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Publication date: July 2017
Source:Molecular Immunology, Volume 87
Author(s): Benhong Xu, Yanpan Gao, Shaohua Zhan, Wei Ge
Lysosomes play vital roles in both innate and adaptive immunity. It is widely accepted that lysosomes do not function exclusively as a digestive organelle. It is also involved in the process of immune cells against pathogens. However, the changes in the lysosomal proteome caused by infection with various microbes are still largely unknown, and our understanding of the proteome of the purified lysosome is another obstacle that needs to be resolved. Here, we performed a proteomic study on lysosomes enriched from THP1 cells after infection with Listeria monocytogenes (L.m), Herpes Simplex Virus 1 (HSV-1) and Vesicular Stomatitis Virus (VSV). In combination with the gene ontology (GO) analysis, we identified 284 lysosomal-related proteins from a total of 4560 proteins. We also constructed the protein-protein interaction networks for the differentially expressed proteins and revealed the core lysosomal proteins, including SRC in the L. m treated group, SRC, GLB1, HEXA and HEXB in the HSV-1 treated group and GLB1, CTSA, CTSB, HEXA and HEXB in the VSV treated group, which are involved in responding to diverse microbial infections. This study not only reveals variable lysosome responses depending on the bacterial or virus infection, but also provides the evidence based on which we propose a novel approach to proteome research for investigation of the function of the enriched organelles.



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IL-37 induces autophagy in hepatocellular carcinoma cells by inhibiting the PI3K/AKT/mTOR pathway

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Publication date: July 2017
Source:Molecular Immunology, Volume 87
Author(s): Ting-Ting Li, Di Zhu, Tong Mou, Zhen Guo, Jun-Liang Pu, Qing-Song Chen, Xu-Fu Wei, Zhong-Jun Wu
Autophagy is an intracellular "self-eating" process that is closely related to inflammation and cellular immunity. New studies indicate that autophagy is also involved in tumor suppression. The anti-inflammatory cytokine interleukin-37 (IL-37) has been shown to have tumor-suppressive abilities in hepatocellular carcinoma (HCC). Notably, autophagy appears to play a dual role in the development of HCC and may be involved in both tumorigenesis and tumor suppression. However, the potential role of IL-37 in autophagy is currently unknown. In this study, we investigated the effect of IL-37 on autophagy in multiple HCC cell lines. In doing so, we found that IL-37 inhibits proliferation in HCC cells and also induces autophagy and apoptosis in the SMMC-7721 and Huh-7 cell lines. Further experiments revealed that IL-37 treatment reduced the levels of phosphorylated protein kinase B (p-AKT), phosphorylated mammalian target of rapamycin (p-mTOR), phosphorylated p70 ribosomal protein s6 kinase (p-p70S6K) and phosphorylated 4E-binding protein 1 (4E-BP1). Moreover, treatment with an AKT agonist, insulin-like growth factor 1 (IGF-1), reversed these IL-37-mediated effects on autophagy, and treatment with an phosphoinositide-3-kinase (PI3K)/AKT inhibitor, LY294002, mimicked the effects of IL-37. Taken together, these results indicate that IL-37 regulates autophagy in SMMC-7721 and Huh-7 cells via inhibition of the PI3K/AKT/mTOR signaling pathway.



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Identification of a Macrobrachium nipponense C-type lectin with a close evolutionary relationship to vertebrate lectins

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Publication date: July 2017
Source:Molecular Immunology, Volume 87
Author(s): Xin Huang, Tingting Li, Min Jin, Shaowu Yin, Wen Wang, Qian Ren
C-type lectins (CTLs) are involved in the innate immune defense of vertebrates and invertebrates against invading pathogens. This study cloned and characterized a novel C-type lectin (MnCTL) of the oriental river prawn, Macrobrachium nipponense. The cloned MnCTL cDNA encompasses an open reading frame of 774 nucleotides and encodes polypeptides of 257 residues. The deduced MnCTL protein contains a single carbohydrate recognition domain (CRD) with an EPN (Glu-Pro-Asn) motif in calcium-binding site 2. Phylogenetic analysis indicated that MnCTL has a closer evolutionary relationship with vertebrate lectins than with invertebrate lectins. Tissue expression analysis showed that high levels of MnCTL are ubiquitously distributed in the gills and stomach of M. nipponense. Quantitative real-time RT-PCR (qRT-PCR) analysis showed that MnCTL expression was up-regulated by bacteria or white spot syndrome virus (WSSV) challenge. Knock-down of the MnCTL gene in WSSV-challenged prawns significantly decreased MnALF1 and MnALF2 transcript levels. The recombinant MnCRD (rMnCRD) agglutinated both Gram-positive (Staphylococcus aureus) and Gram-negative bacteria (Vibrio parahaemolyticus) in the presence of calcium. Furthermore, rMnCRD could bind to all the tested bacteria with different activities. The sugar-binding assay showed that rMnCRD was able to bind lipopolysaccharide and peptidoglycan in a concentration-dependent manner. In addition, rMnCRD could accelerate bacterial clearance. On the contrary, MnCTL silencing by dsRNA interference could weaken the bacterial clearance ability. All these findings implicated MnCTL were involved in the antiviral and antibacterial innate immunity of M. nipponense.



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Adipose-derived stem cells were impaired in restricting CD4+T cell proliferation and polarization in type 2 diabetic ApoE−/− mouse

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Publication date: July 2017
Source:Molecular Immunology, Volume 87
Author(s): Ming-hao Liu, Ya Li, Lu Han, Yao-yuan Zhang, Di Wang, Zhi-hao Wang, Hui-min Zhou, Ming Song, Yi-hui Li, Meng-xiong Tang, Wei Zhang, Ming Zhong
BackgroundAtherosclerosis (AS) is the most common and serious complication of type 2 diabetes mellitus (T2DM) and is accelerated via chronic systemic inflammation rather than hyperglycemia. Adipose tissue is the major source of systemic inflammation in abnormal metabolic state. Pro-inflammatory CD4+T cells play pivotal role in promoting adipose inflammation. Adipose-derived stem cells (ADSCs) for fat regeneration have potent ability of immunosuppression and restricting CD4+T cells as well. Whether T2DM ADSCs are impaired in antagonizing CD4+T cell proliferation and polarization remains unclear.MethodsWe constructed type 2 diabetic ApoE−/− mouse models and tested infiltration and subgroups of CD4+T cell in stromal-vascular fraction (SVF) in vivo. Normal/T2DM ADSCs and normal splenocytes with or without CD4 sorting were separated and co-cultured at different scales ex vivo. Immune phenotypes of pro- and anti-inflammation of ADSCs were also investigated. Flow cytometry (FCM) and ELISA were applied in the experiments above.ResultsCD4+T cells performed a more pro-inflammatory phenotype in adipose tissue in T2DM ApoE−/− mice in vivo. Restriction to CD4+T cell proliferation and polarization was manifested obviously weakened after co-cultured with T2DM ADSCs ex vivo. No obvious distinctions were found in morphology and growth type of both ADSCs. However, T2DM ADSCs acquired a pro-inflammatory immune phenotype, with secreting less PGE2 and expressing higher MHC-II and co-stimulatory molecules (CD40, CD80). Normal ADSCs could also obtain the phenotypic change after cultured with T2DM SVF supernatant.ConclusionCD4+T cell infiltration and pro-inflammatory polarization exist in adipose tissue in type 2 diabetic ApoE−/− mice. T2DM ADSCs had impaired function in restricting CD4+T lymphocyte proliferation and pro-inflammatory polarization due to immune phenotypic changes.



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Low Levels Of “Memory Protein” Linked to Cognitive Decline in Alzheimer’s Disease

Working with human brain tissue samples and genetically engineered mice, Johns Hopkins Medicine researchers together with colleagues at the National Institutes of Health, the University of California San Diego Shiley-Marcos Alzheimer's Disease Research Center, Columbia University, and the Institute for Basic Research in Staten Island say that consequences of low levels of the protein NPTX2 in the brains of people with Alzheimer's disease (AD) may change the pattern of neural activity in ways that lead to the learning and memory loss that are hallmarks of the disease.



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The Influence of Head and Neck Position on Performance of Ambu AuraGainTM in Children

Condition:   General Anesthesia
Interventions:   Other: Neutral position;   Other: Extension;   Other: Flexion;   Other: Rotation;   Device: Ambu AuraGain TM
Sponsor:   Seoul National University Hospital
Not yet recruiting - verified April 2017

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QUILT-3.040: ETBX-011 (Ad5 [E1-, E2b-]-CEA(6D)) Vaccine in Combination With ALT-803 (Super-agonist IL-15) in Subjects Having CEA-Expressing Cancer

Conditions:   Thyroid Cancer;   Colon Cancer;   Ovarian Cancer;   Breast Cancer;   Lung Cancer;   Pancreatic Cancer
Interventions:   Biological: ETBX-011;   Biological: ALT-803
Sponsor:   NantCell, Inc.
Not yet recruiting - verified April 2017

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Fusion UltraSound Imaging Of the Thyroid GlaNd With I-124 PET. Evaluation of Nodule Allocation.

Conditions:   Thyroid Nodule;   Thyroid Diseases;   Thyroid Goitre
Intervention:   Other: Assessment of already preacquired I-124 PET/US
Sponsors:   Jena University Hospital;   GE Healthcare
Recruiting - verified April 2017

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Correction for Pishesha et al., Engineered erythrocytes covalently linked to antigenic peptides can protect against autoimmune disease [Correction]

IMMUNOLOGY AND INFLAMMATION Correction for "Engineered erythrocytes covalently linked to antigenic peptides can protect against autoimmune disease," by Novalia Pishesha, Angelina M. Bilate, Marsha C. Wibowo, Nai-Jia Huang, Zeyang Li, Rhogerry Dhesycka, Djenet Bousbaine, Hojun Li, Heide C. Patterson, Stephanie K. Dougan, Takeshi Maruyama, Harvey F. Lodish, and Hidde L....

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SAGA complex mediates the transcriptional up-regulation of antiviral RNA silencing [Microbiology]

Pathogen recognition and transcriptional activation of defense-related genes are crucial steps in cellular defense responses. RNA silencing (RNAi) functions as an antiviral defense in eukaryotic organisms. Several RNAi-related genes are known to be transcriptionally up-regulated upon virus infection in some host organisms, but little is known about their induction mechanism....

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Malate-dependent Fe accumulation is a critical checkpoint in the root developmental response to low phosphate [Plant Biology]

Low phosphate (Pi) availability constrains plant development and seed production in both natural and agricultural ecosystems. When Pi is scarce, modifications of root system architecture (RSA) enhance the soil exploration ability of the plant and lead to an increase in Pi uptake. In Arabidopsis, an iron-dependent mechanism reprograms primary root...

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PIF4-controlled auxin pathway contributes to hybrid vigor in Arabidopsis thaliana [Plant Biology]

F1 hybrids in Arabidopsis and crop species are uniform and high yielding. The F2 generation loses much of the yield advantage and the plants have heterogeneous phenotypes. We generated pure breeding hybrid mimic lines by recurrent selection and also selected a pure breeding small phenotype line. The hybrid mimics are...

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Dual optical control and mechanistic insights into photoswitchable group II and III metabotropic glutamate receptors [Physiology]

G protein-coupled receptor (GPCR) signaling occurs in complex spatiotemporal patterns that are difficult to probe using standard pharmacological and genetic approaches. A powerful approach for dissecting GPCRs is to use light-controlled pharmacological agents that are tethered covalently and specifically to genetically engineered receptors. However, deficits in our understanding of the...

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Intranasal MSC-derived A1-exosomes ease inflammation, and prevent abnormal neurogenesis and memory dysfunction after status epilepticus [Neuroscience]

Status epilepticus (SE), a medical emergency that is typically terminated through antiepileptic drug treatment, leads to hippocampus dysfunction typified by neurodegeneration, inflammation, altered neurogenesis, as well as cognitive and memory deficits. Here, we examined the effects of intranasal (IN) administration of extracellular vesicles (EVs) secreted from human bone marrow-derived mesenchymal...

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Correction to Supporting Information for Falahati and Wieschaus, Independent active and thermodynamic processes govern the nucleolus assembly in vivo [SI Correction]

CELL BIOLOGY, APPLIED PHYSICAL SCIENCES Correction to Supporting Information for "Independent active and thermodynamic processes govern the nucleolus assembly in vivo," by Hanieh Falahati and Eric Wieschaus, which appeared in issue 6, February 7, 2017, of Proc Natl Acad Sci USA (114:1335–1340; first published January 23, 2017; 10.1073/pnas.1615395114). The authors...

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Correction for Padilla et al., AgRP to Kiss1 neuron signaling links nutritional state and fertility [Correction]

PHYSIOLOGY Correction for "AgRP to Kiss1 neuron signaling links nutritional state and fertility," by Stephanie L. Padilla, Jian Qiu, Casey C Nestor, Chunguang Zhang, Arik W. Smith, Benjamin B. Whiddon, Oline K. Rønnekleiv, Martin J. Kelly, and Richard D. Palmiter, which appeared in issue 9, February 28, 2017, of Proc...

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Variations in crowding, saccadic precision, and spatial localization reveal the shared topology of spatial vision [Psychological and Cognitive Sciences]

Visual sensitivity varies across the visual field in several characteristic ways. For example, sensitivity declines sharply in peripheral (vs. foveal) vision and is typically worse in the upper (vs. lower) visual field. These variations can affect processes ranging from acuity and crowding (the deleterious effect of clutter on object recognition)...

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Hepatitis C virus triggers Golgi fragmentation and autophagy through the immunity-related GTPase M [Immunology and Inflammation]

Positive-stranded RNA viruses, such as hepatitis C virus (HCV), assemble their viral replication complexes by remodeling host intracellular membranes to a membranous web. The precise composition of these replication complexes and the detailed mechanisms by which they are formed are incompletely understood. Here we show that the human immunity-related GTPase...

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Reply to Brown and Behrmann, Cox, et al., and Kessler et al.: Data and code sharing is the way forward for fMRI [Biological Sciences]

We are glad that our paper (1) has generated intense discussions in the fMRI field (2–4), on how to analyze fMRI data, and how to correct for multiple comparisons. The goal of the paper was not to disparage any specific fMRI software, but to point out that parametric statistical methods...

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Uplift-driven diversification in the Hengduan Mountains, a temperate biodiversity hotspot [Evolution]

A common hypothesis for the rich biodiversity found in mountains is uplift-driven diversification—that orogeny creates conditions favoring rapid in situ speciation of resident lineages. We tested this hypothesis in the context of the Qinghai–Tibetan Plateau (QTP) and adjoining mountain ranges, using the phylogenetic and geographic histories of multiple groups of...

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Roles of the TRAF6 and Pellino E3 ligases in MyD88 and RANKL signaling [Immunology and Inflammation]

It is widely accepted that the essential role of TRAF6 in vivo is to generate the Lys63-linked ubiquitin (K63-Ub) chains needed to activate the "master" protein kinase TAK1. Here, we report that TRAF6 E3 ligase activity contributes to but is not essential for the IL-1–dependent formation of K63-Ub chains, TAK1...

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Achiral symmetry breaking and positive Gaussian modulus lead to scalloped colloidal membranes [Applied Physical Sciences]

In the presence of a nonadsorbing polymer, monodisperse rod-like particles assemble into colloidal membranes, which are one-rod-length–thick liquid-like monolayers of aligned rods. Unlike 3D edgeless bilayer vesicles, colloidal monolayer membranes form open structures with an exposed edge, thus presenting an opportunity to study elasticity of fluid sheets. Membranes assembled from...

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Context-dependent spatially periodic activity in the human entorhinal cortex [Neuroscience]

The spatially periodic activity of grid cells in the entorhinal cortex (EC) of the rodent, primate, and human provides a coordinate system that, together with the hippocampus, informs an individual of its location relative to the environment and encodes the memory of that location. Among the most defining features of...

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Automated glycan assembly using the Glyconeer 2.1 synthesizer [Chemistry]

Reliable and rapid access to defined biopolymers by automated DNA and peptide synthesis has fundamentally altered biological research and medical practice. Similarly, the procurement of defined glycans is key to establishing structure–activity relationships and thereby progress in the glycosciences. Here, we describe the rapid assembly of oligosaccharides using the commercially...

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PIK3CA mutant tumors depend on oxoglutarate dehydrogenase [Cell Biology]

Oncogenic PIK3CA mutations are found in a significant fraction of human cancers, but therapeutic inhibition of PI3K has only shown limited success in clinical trials. To understand how mutant PIK3CA contributes to cancer cell proliferation, we used genome scale loss-of-function screening in a large number of genomically annotated cancer cell...

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Pseudomagnetic fields for sound at the nanoscale [Physics]

There is a growing effort in creating chiral transport of sound waves. However, most approaches so far have been confined to the macroscopic scale. Here, we propose an approach suitable to the nanoscale that is based on pseudomagnetic fields. These pseudomagnetic fields for sound waves are the analogue of what...

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Parallel adaptive evolution of geographically distant herring populations on both sides of the North Atlantic Ocean [Genetics]

Atlantic herring is an excellent species for studying the genetic basis of adaptation in geographically distant populations because of its characteristically large population sizes and low genetic drift. In this study we compared whole-genome resequencing data of Atlantic herring populations from both sides of the Atlantic Ocean. An important finding...

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The cryo-EM structure of YjeQ bound to the 30S subunit suggests a fidelity checkpoint function for this protein in ribosome assembly [Biochemistry]

Recent work suggests that bacterial YjeQ (RsgA) participates in the late stages of assembly of the 30S subunit and aids the assembly of the decoding center but also binds the mature 30S subunit with high affinity. To determine the function and mechanisms of YjeQ in the context of the mature...

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NH4NO3 removal from condensate - The efficiency of ED and RO and the impact on corrosion behavior



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verzekeringen

eenvoudige analyse van de verzekeringen voor startende zelfstandigen

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Architecture, absolutely critical: how to identify a promising new urban configuration?



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Poiesis or semiosis in architectural design practice



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Theory by design: architectural research made explicit in the design studio

As a result of the Bologna Process, the need to connect higher education with research has become an important issue. For a discipline such as architecture, this seems to put the traditional and well-established equilibrium between theory and praxis under pressure, or even under threat. Research is undertaken in order to construct knowledge through the acquisition of insight and understanding, with the aim of sharing the results. In architecture schools, design lies at the heart of the educational programme, with the design studio being the central locus. Since design and research are inextricably linked, the relationship between knowledge production and the design process has become a subject of investigation. The interweaving of research and design-based architectural education also affects the relationship between teaching and design. This book focuses explicitly on connections: the connections between the construction of knowledge and theory, teaching and learning, design and research. In doing so, it broadens the research spectrum and others new approaches to research and teaching. This inspiring essay volume demonstrates the predilection for experiment within the design studio, the ceaseless impulse for change, the reorientation of studio assignments, and the power inherent in the enquiring minds of the hugely dedicated studio teachers.

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Skin manifestations among GATA2-deficient patients

Abstract

GATA2 mutations have been identified in various diseases, such as monoMAC syndrome, Emberger syndrome, familial myelodysplastic syndrome, acute myeloid leukemia, and dendritic cell, monocyte, B and NK cell deficiency. These syndromes present a wide range of clinical features, dominated by severe infections and haematological disorders such as myelodysplastic syndrome. Up to 70% of GATA2-mutated patients have dermatological features, mainly genital or extra-genital warts, panniculitis or erythema nodosum, and lymphedema. We report 3 patients presenting with common dermatological and haematological features leading to the diagnosis of GATA2 deficiency, but also with skin manifestations that have not been previously described: gingival hypertrophy, macroglossitis and glossitis, and granulomatous lupoid facial lesions. Dermatologists can encounter GATA2-mutated patients and should recognize this disorder.

This article is protected by copyright. All rights reserved.



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The experience of immune checkpoint inhibitors in Chinese patients with metastatic melanoma: a retrospective case series

Abstract

Melanomas in Chinese patients show relatively higher rates of acral and mucosal types than in other populations. However, the efficacy of checkpoint inhibitor therapies against these melanoma subtypes is not well defined. We analyzed 52 patients treated with ipilimumab, pembrolizumab, or a combination of both to evaluate the efficacy and safety of checkpoint inhibitors in Chinese patients with advanced melanoma, particularly those with acral and mucosal types. The objective response rates (ORRs) were 0, 25, and 20% for ipilimumab, pembrolizumab, and pembrolizumab plus ipilimumab, respectively. Pembrolizumab contained therapy was as effective in acral and mucosal melanoma patients (ORR 26.7 and 20%, respectively) as in non-acral cutaneous melanoma patients (ORR 26.7%). Baseline lactate dehydrogenase levels and relative lymphocyte counts were independent prognostic factors for PFS and OS. The incidences of grade 3–4 adverse events were 14% in the two monotherapy groups and 30% in the combined therapy group. The most frequent adverse events were elevation of aminotransferase, skin toxicity, thyroid dysfunction, pyrexia, and fatigue. Treatment-related rash or vitiligo was associated with a better prognosis. In summary, pembrolizumab-based therapy resulted in meaningful efficacy and good tolerability in Chinese patients with melanoma, including those with acral and mucosal types.



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Inflammatory gene expression profile and defective interferon-γ and granzyme K in natural killer cells from systemic juvenile idiopathic arthritis patients

Objective: Systemic juvenile idiopathic arthritis (JIA) is an immunoinflammatory disease characterized by arthritis and systemic manifestations. The role of natural killer (NK) cells in the pathogenesis of systemic JIA remains unclear. The purpose of this study was to perform a comprehensive analysis of NK cell phenotype and functionality in patients with systemic JIA. Methods: Transcriptional alterations specific to NK cells were investigated by RNA sequencing of highly purified NK cells from 6 patients with active systemic JIA and 6 age-matched healthy controls. Cytokines (NK cell-stimulating and others) were quantified in plasma samples (n=18). NK cell phenotype and cytotoxic activity against tumor cells were determined (n=10), together with their interferon-gamma (IFN gamma)-producing function (n=8). Results: NK cells from the systemic JIA patients showed an altered gene expression profile compared to cells from the healthy controls, with enrichment of immunoinflammatory pathways, increased expression of innate genes including TLR4 and S100A9, and decreased expression of immune-regulating genes such as IL10RA and GZMK. In the patients' plasma, interleukin-18 (IL-18) levels were increased, and a decreased ratio of IFN gamma to IL-18 was observed. NK cells from the patients exhibited specific alterations in the balance of inhibitory and activating receptors, with decreased killer cell lectin-like receptor G1 and increased NKp44 expression. Although NK cells from the patients showed increased granzyme B expression, consistent with intact cytotoxicity and degranulation against a tumor cell line, decreased granzyme K expression in CD56(bright) NK cells and defective IL-18-induced IFN gamma production and signaling were demonstrated. Conclusion: NK cells are active players in the inflammatory environment typical of systemic JIA. Although their cytotoxic function is globally intact, subtle defects in NK-related pathways, such as granzyme K expression and IL-18-driven IFN gamma production, may contribute to the immunoinflammatory dysregulation in this disease.

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An update on the surgical treatment for transgender patients



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Use of a new low profile Occlutech PLD device for closure of Fontan fenestrations



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Tacrolimus predose concentration is associated with hypertension in pediatric liver transplant recipients

Background: The aim of the study was to analyze the incidence of hypertension in pediatric liver transplantation (LT) recipients using ambulatory blood pressure measurements (ABPM) and to identify factors associated with hypertension. We also investigated whether hypertension or tacrolimus predose concentration (TAC C-0) was associated with increased left ventricular (LV) wall thickness. atients and Methods: On a retrospective longitudinal base, we included 39 pediatric LT recipients. Median time since transplantation was 65 months (range: 11-183). Two consecutive ABPM were analyzed with a median time interval of 13 months. Data from echocardiographic evaluation parallel to the baseline ABPM were analyzed. All patients except 1 were prescribed tacrolimus. The median TAC C-0 was 4 ng/mL (range 0.9-11.2). Univariate and multivariate logistic regression models were fitted to identify factors associated with systolic and diastolic hypertension and LV wall thickness. Results: Twenty-two of 39 children were hypertensive at baseline and 19 of 32 were hypertensive at follow-up. At baseline 10 (26%) children had masked systolic hypertension. TAC C-0 was associated with systolic (P=0.007, Exp(B) 2.02, 95% CI 1.2-3.3) and diastolic (P=0.044, Exp(B) 1.48, 95% CI 1.0-2.2) hypertension. LV wall thickness was increased in children after LT compared with healthy population, but it was not associated with hypertension or TAC C(0.) Conclusions: Given the high prevalence of masked hypertension, ABPM should be performed in all pediatric LT recipients. Systolic and diastolic hypertension is associated with TAC C-0; therefore, children with a higher target TAC C-0 require a more intensive blood pressure surveillance.

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Are there really different monthly desire patterns in users of hormonal and non-hormonal contraceptive methods?



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Sexual desire in trans persons: associations with sex reassignment treatment

Introduction : Sex steroids and genital surgery are known to affect sexual desire, but little research has focused on the effects of cross-sex hormone therapy and sex reassignment surgery on sexual desire in trans persons. Aim : This study aims to explore associations between sex reassignment therapy (SRT) and sexual desire in a large cohort of trans persons. Methods : A cross-sectional single specialized center study including 214 trans women (male-to-female trans persons) and 138 trans men (female-to-male trans persons). Main Outcome Measures : Questionnaires assessing demographics, medical history, frequency of sexual desire, hypoactive sexual desire disorder (HSDD), and treatment satisfaction. Results : In retrospect, 62.4% of trans women reported a decrease in sexual desire after SRT. Seventy-three percent of trans women never or rarely experienced spontaneous and responsive sexual desire. A third reported associated personal or relational distress resulting in a prevalence of HSDD of 22%. Respondents who had undergone vaginoplasty experienced more spontaneous sexual desire compared with those who planned this surgery but had not yet undergone it (P = 0.03). In retrospect, the majority of trans men (71.0%) reported an increase in sexual desire after SRT. Thirty percent of trans men never or rarely felt sexual desire; 39.7% from time to time, and 30.6% often or always. Five percent of trans men met the criteria for HSDD. Trans men who were less satisfied with the phalloplasty had a higher prevalence of HSDD (P = 0.02). Trans persons who were more satisfied with the hormonal therapy had a lower prevalence of HSDD (P = 0.02). Conclusion : HSDD was more prevalent in trans women compared with trans men. The majority of trans women reported a decrease in sexual desire after SRT, whereas the opposite was observed in trans men. Our results show a significant sexual impact of surgical interventions and both hormonal and surgical treatment satisfaction on the sexual desire in trans persons.

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Karyotyping, is it worthwhile in transsexualism?

Introduction. Karyotyping is often performed in transsexual individuals. Aim. Quantification and characterization of karyotype findings and abnormalities in transsexual persons. Main Outcome Measures. Karyotypes were listed both in male-to-female and in female-to-male transsexual persons. Methods. The data were collected through a retrospective study. Results. Karyotypes of 368 transsexual individuals (251 male-to-female, 117 female-to-male) are described. Normal findings were found in 97.55%. Prevalence of abnormal karyotypes was 3.19% among male-to-female, and 0.85% among female-to-male transsexuals. Nine karyotypes showed variations; Klinefelter syndrome was confirmed in three persons, whereas others displayed autosomal aberrations. Conclusion. Karyotyping is only of very limited information in the transsexual population.

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Vitamin D binding protein in cystic fibrosis patients in relation to serum vitamin D



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Subject to Contract: Carey Young's artistic work in relation to creative developments in IP law. Paper given within the context of an international workshop on the future of copyright law in relation to art. Harvard University.

Young, CSR; (2016) Subject to Contract: Carey Young's artistic work in relation to creative developments in IP law. Paper given within the context of an international workshop on the future of copyright law in relation to art. Harvard University. [Lecture]. Presented at: Art ≠ Law? Creative Responses to Intellectual Property in the 21st Century, Cambridge, MA, USA.

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Palais de Justice

Young, CSR; (2017) Palais de Justice. HD video, 17 mins 58 secs. Green open access

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Shark personalities? Repeatability of social network traits in a widely distributed predatory fish

Jacoby, D; Fear, LN; Sims, DW; Croft, DP; (2014) Shark personalities? Repeatability of social network traits in a widely distributed predatory fish. Behavioral Ecology and Sociobiology , 68 (12) pp. 1995-2003. 10.1007/s00265-014-1805-9 . Green open access

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Black Square (Cell)

Young, CSR; (2017) Black Square (Cell). [Artefact]. Photography. New York City. Green open access

http://ift.tt/2pvZYoC

An RRM-ZnF RNA recognition module targets RBM10 to exonic sequences to promote exon exclusion

Collins, KM; Kainov, YA; Christodolou, E; Ray, D; Morris, Q; Hughes, T; Taylor, IA; Collins, KM; Kainov, YA; Christodolou, E; Ray, D; Morris, Q; Hughes, T; Taylor, IA; Makeyev, EV; Ramos, A; - view fewer (2017) An RRM-ZnF RNA recognition module targets RBM10 to exonic sequences to promote exon exclusion. Nucleic Acids Research , Article 1. 10.1093/nar/gkx225 . (In press). Green open access

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Unfinished Business: Notes toward an Artist Statement

Young, C; (2013) Unfinished Business: Notes toward an Artist Statement. Social Text , 31 (2 115) pp. 145-152. 10.1215/01642472-2081166 .

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Contracts and Consideration: Law as Art (conference keynote)

Young, CSR; (2017) Contracts and Consideration: Law as Art (conference keynote). [Lecture]. Presented at: Law into Art, Art into Law, Perth, Australia.

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Home-ownership as a social norm and positional good: Subjective wellbeing evidence from panel data

Foye, C; Clapham, D; Gabrieli, T; (2017) Home-ownership as a social norm and positional good: Subjective wellbeing evidence from panel data. Urban Studies 10.1177/0042098017695478 . Green open access

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Towards multi-modal anticipatory monitoring of depressive states through the analysis of human-smartphone interaction

Mehrotra, A; Hendley, R; Musolesi, M; (2016) Towards multi-modal anticipatory monitoring of depressive states through the analysis of human-smartphone interaction. In: (Proceedings) 2016 ACM International Joint Conference on Pervasive and Ubiquitous Computing: Adjunct. (pp. pp. 1132-1138). ACM, New York, USA Green open access

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Free Schools in England: ‘Not unlike other schools’?

Wiborg, S; Green, F; Taylor-Gooby, P; Wilde, R; Free Schools in England: 'Not unlike other schools'? Journal of Social Policy (In press). Green open access

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Binocular rivalry in children on the autism spectrum

Karaminis, T; Lunghi, C; Neil, L; Burr, D; Pellicano, E; (2017) Binocular rivalry in children on the autism spectrum. Autism Research 10.1002/aur.1749 . (In press). Green open access

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Antarctica and the strategic plan for biodiversity

Chown, SL; Brooks, CM; Terauds, A; Le Bohec, C; van Klaveren-Impagliazzo, C; Whittington, JD; Butchart, SHM; Chown, SL; Brooks, CM; Terauds, A; Le Bohec, C; van Klaveren-Impagliazzo, C; Whittington, JD; Butchart, SHM; Coetzee, BWT; Collen, B; Convey, P; Gaston, KJ; Gilbert, N; Gill, M; Hoft, R; Johnston, S; Kennicutt, MC; Kriesell, HJ; Le Maho, Y; Lynch, HJ; Palomares, M; Puig-Marco, R; Stoett, P; McGeoch, MA; - view fewer (2017) Antarctica and the strategic plan for biodiversity. PLOS Biology , 15 (3) , Article e2001656. 10.1371/journal.pbio.2001656 . Green open access

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Female brain size affects the assessment of male attractiveness during mate choice

Corral-López, A; Bloch, NI; Kotrschal, A; van der Bijl, W; Buechel, SD; Mank, JE; Kolm, N; (2017) Female brain size affects the assessment of male attractiveness during mate choice. Science Advances , 3 (3) , Article e1601990. 10.1126/sciadv.1601990 . Green open access

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Portosystemic shunts in cirrhosis are associated to more complications and deteriorated quality of life. An international cohort study

Simon-Talero, M; Roccarina, D; Majumdar, A; Tsochatzis, EA; Martinez, J; Picon, C; Albillos, A; Simon-Talero, M; Roccarina, D; Majumdar, A; Tsochatzis, EA; Martinez, J; Picon, C; Albillos, A; Lampichler, K; Toth, D; Reiberger, T; Baiges, A; Darnell, A; Hernandez-Gea, V; Low, G; Abraldes, JG; Tandon, P; Llop, E; Lopez, M; Calleja, JL; Praktiknjo, M; Kukuk, G; Trebicka, J; Maurer, M; Berzigotti, A; Zipprich, A; Ripoll, C; Triolo, M; La Mura, V; Vangrinsven, G; Laleman, W; Garcia-Martinez, R; Banares, R; Dam, A; Krag, A; Augustin, S; Genesca, J; - view fewer (2017) Portosystemic shunts in cirrhosis are associated to more complications and deteriorated quality of life. An international cohort study. In: (pp. e65-e65). ELSEVIER SCIENCE INC

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The Role of Histone Protein Modifications and Mutations in Histone Modifiers in Pediatric B-Cell Progenitor Acute Lymphoblastic Leukemia

Janczar, S; Janczar, K; Pastorczak, A; Harb, H; Paige, AJW; Zalewska-Szewczyk, B; Danilewicz, M; Janczar, S; Janczar, K; Pastorczak, A; Harb, H; Paige, AJW; Zalewska-Szewczyk, B; Danilewicz, M; Mlynarski, W; - view fewer (2017) The Role of Histone Protein Modifications and Mutations in Histone Modifiers in Pediatric B-Cell Progenitor Acute Lymphoblastic Leukemia. [Review]. Cancers , 9 (1) , Article 2. 10.3390/cancers9010002 . Green open access

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Effects of extreme temperatures on cardiovascular emergency hospitalizations in a Mediterranean region: a self-controlled case series study

Ponjoan, A; Blanch, J; Alves-Cabratosa, L; Martí-Lluch, R; Comas-Cufí, M; Parramon, D; del Mar Garcia-Gil, M; Ponjoan, A; Blanch, J; Alves-Cabratosa, L; Martí-Lluch, R; Comas-Cufí, M; Parramon, D; del Mar Garcia-Gil, M; Ramos, R; Petersen, I; - view fewer (2017) Effects of extreme temperatures on cardiovascular emergency hospitalizations in a Mediterranean region: a self-controlled case series study. Environmental Health , 16 , Article 32. 10.1186/s12940-017-0238-0 . Green open access

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Dentists' use of validated child dental anxiety measures in clinical practice: a mixed methods study

Alshammasi, H; Buchanan, H; Ashley, P; (2017) Dentists' use of validated child dental anxiety measures in clinical practice: a mixed methods study. International Journal of Paediatric Dentistry 10.1111/ipd.12302 . (In press).

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Prevalence of Frailty in Mild to Moderate Alzheimer's Disease: A Systematic Review and Meta-analysis

Kojima, G; Liljas, A; Iliffe, S; Walters, K; (2017) Prevalence of Frailty in Mild to Moderate Alzheimer's Disease: A Systematic Review and Meta-analysis. Current Alzheimer Research 10.2174/1567205014666170417104236 . (In press).

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Dexmedetomidine Combined with Therapeutic Hypothermia Is Associated with Cardiovascular Instability and Neurotoxicity in a Piglet Model of Perinatal Asphyxia

Ezzati, M; Kawano, G; Rocha-Ferreira, E; Alonso-Alconada, D; Hassell, JK; Broad, KD; Fierens, I; Ezzati, M; Kawano, G; Rocha-Ferreira, E; Alonso-Alconada, D; Hassell, JK; Broad, KD; Fierens, I; Fleiss, B; Bainbridge, A; Price, DL; Kaynezhad, P; Anderson, B; Hristova, M; Tachtsidis, I; Golay, X; Gressens, P; Sanders, RD; Robertson, NJ; - view fewer (2017) Dexmedetomidine Combined with Therapeutic Hypothermia Is Associated with Cardiovascular Instability and Neurotoxicity in a Piglet Model of Perinatal Asphyxia. Developmental Neuroscience 10.1159/000458438 . (In press). Green open access

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Pilot study on the effects of oral health education for caregivers in a residential setting for people with intellectual disabilities : a randomized controlled trial



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When Hollywood Met Neurosurgery

A team of computer engineers and neurosurgeons, with an assist from Hollywood special effects experts, reports successful early tests of a novel, lifelike 3D simulator designed to teach surgeons to perform a delicate, minimally invasive brain operation.



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Dalcroze meets technology. Integrating music, movement and visuals with the Music Paint Machine.



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PLXTRM: Prediction-Led eXtended-guitar Tool for Real-time Music applications and live performance



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Gestures in Contemporary Music Performance: A Method to Assist the Performer’s Artistic Process



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Review article: dose optimisation of infliximab for acute severe ulcerative colitis



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Effects of different sterilization methods on the physico-chemical and bioresponsive properties of plasma-treated polycaprolactone films



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K.B. and Others v. Croatia: the Court’s first steps to tackle parental alienation



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Assessment of faecal microbial transfer in irritable bowel syndrome with severe bloating



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T84 monolayers are superior to Caco-2 as a model system of colonocytes



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Is having sex with other men a risk factor for transfusion-transmissible infections in male blood donors in Western countries?: a systematic review

Background : Although increased prevalence of transfusion transmissible infections (TTI) among "men who have sex with men" (MSM) has been well documented, the exclusion of MSM as blood donors is contested. The aim of this systematic review is to find studies that describe the risk of TTI in MSM blood donors. Methods : We searched MEDLINE, Embase, The Cochrane Central Register of Controlled Trials, Cinahl, and Web of Science, and used GRADE for determining evidence quality. We included studies comparing MSM and non-MSM blood donors (or people eligible to give blood), living in areas most relevant for our Blood Service. Results : Out of 18 987 articles, 14 observational studies were included. Two studies directly compared MSM with non-MSM donors showing that MSM donors have a statistically significant higher risk of HIV-1 infections. In one of these studies it was shown that this was related to recent (< 12 months) MSM contact. In two additional studies no evidence was shown in favour of a certain deferral period for MSM. Ten studies, applying permanent deferral for MSM, compared infected versus non-infected donors. One study found that MSM is a statistically significant risk factor for HIV-1 infection in blood donors. For other TTI such as HBV or HCV, an increased risk of infection could not be demonstrated, because the precision of the results was affected by the low numbers of donors with MSM as risk factor, or because of risk of bias in the included studies. All studies included low level evidence, because of risk of bias and imprecision of the results. Conclusions : High-quality studies investigating the risk of TTI in MSM who donate blood are scarce. The available evidence suggests a link between MSM blood donors and HIV-1 infection, but is too limited to be able to unambiguously/clearly recommend a certain deferral policy.

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Safety and efficacy of azacitidine in Belgian patients with high-risk myelodysplastic syndromes, acute myeloid leukaemia, or chronic myelomonocytic leukaemia: results of a real-life, non-interventional post-marketing survey

Objectives: We evaluated azacitidine (Vidaza (R)) safety and efficacy in patients with myelodysplastic syndrome (MDS), acute myeloid leukaemia (AML), and chronic myelomonocytic leukaemia (CMML), in a real-life setting. Treatment response, dose, and schedule were assessed. Methods: This non-interventional, post-marketing survey included 49/50 patients receiving azacitidine at 14 Belgian haematology centres from 2010-2012. Treatment-emergent adverse events (TEAEs), including treatment-related TEAEs, and serious TEAEs (TESAEs) were recorded throughout the study. Treatment response [complete response (CR), partial response (PR), haematological improvement (HI), stable disease (SD), treatment failure (TF)) and transfusion-independence (TI) were evaluated at completion of a 1-year observation period (1YOP) or at treatment discontinuation, and overall survival (OS), at study conclusion. Results: The median age of patients was 74.7 (range: 43.9-87.8) years; 69.4% had MDS, 26.5% had primary or secondary AML, and 4.1% had CMML. Treatment-related TEAEs, grade 3-4 TEAEs, and TESAEs were reported in 67.3%, 28.6%, and 18.4% of patients, respectively. During 1YOP, patients received a median of 7 (1-12) treatment cycles. Treatment response was assessed for 38/49 patients. Among MDS and CMML patients (n=29), 41.4% had CR, PR, or HI, 41.4% had SD, and 17.2% had TF. Among AML patients (n=9), 44.4% had CR or PR, 33.3% had SD, and 22.2% had TF. TI was observed in 14/32 (43.8%) patients who were transfusion-dependent at baseline. Median (95% confidence interval) OS was 490 (326-555) days; 1-year OS estimate was 0.571 (0.422-0.696). Conclusions: Our data support previous findings that azacitidine has a clinically acceptable safety profile and shows efficacy.

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T-cell receptor Vβ skewing frequently occurs in refractory cytopenia of childhood and is associated with an expansion of effector cytotoxic T cells: a prospective study by EWOG-MDS

Immunosuppressive therapy (IST), consisting of antithymocyte globulin and cyclosporine A, is effective in refractory cytopenia of childhood (RCC), suggesting that, similar to low-grade myelodysplastic syndromes in adult patients, T lymphocytes are involved in suppressing hematopoiesis in a subset of RCC patients. However, the potential role of a T-cell-mediated pathophysiology in RCC remains poorly explored. In a cohort of 92 RCC patients, we prospectively assessed the frequency of T-cell receptor (TCR) b-chain variable (Vb) domain skewing in bone marrow and peripheral blood by heteroduplex PCR, and analyzed T-cell subsets in peripheral blood by flow cytometry. TCRVb skewing was present in 40% of RCC patients. TCRVb skewing did not correlate with bone marrow cellularity, karyotype, transfusion history, HLA-DR15 or the presence of a PNH clone. In 28 patients treated with IST, TCRVb skewing was not clearly related with treatment response. However, TCRVb skewing did correlate with a disturbed CD4(+)/ CD8(+) T-cell ratio, a reduction in naive CD8(+) T cells, an expansion of effector CD8(+) T cells and an increase in activated CD8(+) T cells (defined as HLA-DR+, CD57(+) or CD56(+)). These data suggest that T lymphocytes contribute to RCC pathogenesis in a proportion of patients, and provide a rationale for treatment with IST in selected patients with RCC.

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Efficacy and safety of Privigen® in patients with chronic inflammatory demyelinating polyneuropathy: results of a prospective, single-arm, open-label Phase III study (the PRIMA study)

This prospective, multicenter, single-arm, open-label Phase III study aimed to evaluate the efficacy and safety of Privigen (R) (10% liquid human intravenous immunoglobulin [IVIG], stabilized with l-proline) in patients with chronic inflammatory demyelinating polyneuropathy (CIDP). Patients received one induction dose of Privigen (2g/kg body weight [bw]) and up to seven maintenance doses (1g/kg bw) at 3-week intervals. The primary efficacy endpoint was the responder rate at completion, defined as improvement of 1 point on the adjusted Inflammatory Neuropathy Cause and Treatment (INCAT) disability scale. The preset success criterion was the responder rate being 35%. Of the 31 screened patients, 28 patients were enrolled including 13 (46.4%) IVIG-pretreated patients. The overall responder rate at completion was 60.7% (95% confidence interval [CI]: 42.41%-76.43%). IVIG-pretreated patients demonstrated a higher responder rate than IVIG-naive patients (76.9% vs. 46.7%). The median (25%-75% quantile) INCAT score improved from 3.5 (3.0-4.5) points at baseline to 2.5 (1.0-3.0) points at completion, as did the mean (standard deviation [SD]) maximum grip strength (66.7 [37.24] kPa vs. 80.9 [31.06] kPa) and the median Medical Research Council sum score (67.0 [61.5-72.0] points vs. 75.5 [71.5-79.5] points). Of 108 adverse events (AEs; 0.417 AEs per infusion), 95 AEs (88.0%) were mild or moderate in intensity and resolved by the end of study. Two serious AEs of hemolysis were reported that resolved after discontinuation of treatment. Thus, Privigen provided efficacious and well-tolerated induction and maintenance treatment in patients with CIDP.

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Hemato-critical issues in quantitative analysis of dried blood spots: challenges and solutions

Dried blood spot (DBS) sampling for quantitative determination of drugs in blood has entered the bioanalytical arena at a fast pace during the last decade, primarily owing to progress in analytical instrumentation. Despite the many advantages associated with this new sampling strategy, several issues remain, of which the hematocrit issue is undoubtedly the most widely discussed challenge, since strongly deviating hematocrit values may significantly impact DBS-based quantitation. In this review, an overview is given of the different aspects of the hematocrit problem' in quantitative DBS analysis. The different strategies that try to cope with this problem are discussed, along with their potential and limitations. Implementation of some of these strategies in practice may help to overcome this important hurdle in DBS assays, further allowing DBS to become an established part of routine quantitative bioanalysis.

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Relation between central venous pressure (CVP) and need for blood transfusion during partial liver resections: a retrospective study



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A final analysis from the CHOICE study examining darbepoetin alfa use for chemotherapy-induced anaemia in current European clinical practice

Objectives: The CHOICE study was a prospective, multicentre, observational study designed to assess the level of adherence in current clinical practice to the European product label and the EORTC guidelines for the treatment of chemotherapy-induced anaemia with darbepoetin alfa (DA). Methods: Hb levels and red blood cell (RBC) transfusion requirements were evaluated among 1900 patients with solid tumours in 11 European countries. The primary outcome measure was the proportion of patients with a target Hb level of >= 10- <= 12 g/dL after 9 weeks' DA treatment. Results: The full analysis set (FAS) comprised 1887 patients (mean +/- SD age 62.4 +/- 11.4 years) divided into categories by baseline Hb < 9 g/dL (n=281); 9-<10 g/dL (n=70); 10-<11 g/dL (n=95); >= 11 g/dL (n = 114). The proportion of patients who remained on the study at week 9 achieving the target Hb level was 37% (n = 60), 48% (n = 217), 54% (n = 210) and 38% (n = 23) in the subgroups with a baseline Hb level of <9 g/dL, 9-<10 g/dL, 10-<11 g/dL and >= 11 g/dL, respectively. In the <9 g/dL, 9-<10 g/dL, 10-<11 g/dL and >= 11 g/dL subgroups of the FAS, the number of patients maintaining Hb levels >= 10 g/dL after their first achievement of an Hb value of 10 g/dL was 95 (34%), 372 (48%), 476 (68%) and 87 (76%), respectively. The Kaplan-Meier percentages of patients who required an RBC transfusion from week 5 until end of treatment period were: 29%, 20%, 12% and 17% in the <9 g/dL, 9-<10 g/dL, 10-<11 g/dL and >= 11 g/dL subgroups, respectively. Kaplan-Meier percentages of patients reaching an Hb level of >13 g/dL were 10%, 9%, 21% and 29%, respectively. Potential bias could not be excluded due to the study's observational nature. Conclusions: DA initiation and target Hb ranges adhered to current guidelines in the majority of patients. Furthermore, this study demonstrates faster achievement of the target range and reduced transfusion requirements are associated with initiation of DA at Hb levels of 9-<10 g/dL and 10-<11 g/dL rather than <9 g/dL.

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Use of darbepoetin alfa in European clinical practice for the management of chemotherapy-induced anaemia in four tumour types: final data from the CHOICE study

Objectives: The CHOICE study was a prospective, multicentre, observational study designed to assess levels of adherence in current clinical practice to the European product label and EORTC guidelines for the treatment of chemotherapy-induced anaemia (CIA) with darbepoetin alfa (DA). Here we present data split by tumour types: breast, colorectal, ovarian and lung. Methods: Haemoglobin (Hb) levels and red blood cell transfusion requirements were evaluated among patients with solid tumours in 11 European countries. The primary outcome measure was the proportion of patients with a target Hb level of >= 10-<= 12 g/dL. Results: The full analysis set included 1887 patients (mean +/- SD 62.4 +/- 11.4 years); 1585 (84%) had a current disease stage of >= 3. Common chemotherapy regimens were non-platinum + non-taxane based (n = 696 [37%]) or platinum + non-taxane based (n = 660 [35%]). Breast cancer (n = 575): The mean +/- SD Hb level at baseline was 9.9 +/- 0.8 g/dL (n = 568). Target Hb level was reached by 187 (55%) patients. Colorectal cancer (n = 310): At baseline the mean +/- SD Hb level was 9.8 +/- 0.8 g/dL (n = 306). Target Hb level was reached by 107 patients (56%). Ovarian cancer (n = 301): The mean +/- SD Hb level at baseline was 9.7 +/- 0.8 g/dL (n = 294). Target Hb level was reached by 81 patients (44%). Lung cancer (n = 701): At baseline the mean +/- SD Hb level was 9.8 +/- 0.9 g/dL (n = 692). Target Hb level was reached by 142 patients (39%). Safety: Five severe or life-threatening adverse drug reactions were seen (three patients with breast cancer, one patient with colorectal cancer and one patient with ovarian cancer). Limitations: Potential bias could not be excluded due to the study's observational nature. Conclusions: This study demonstrates that the recommendations are adhered to in clinical practice, with the mean starting Hb level <10 g/dL irrespective of tumour type. Furthermore, DA is likely to be effective and well tolerated for the treatment of CIA in patients with breast, colorectal, ovarian or lung cancer.

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Haemostasis monitoring during sequential aortic valve replacement and liver transplantation

Abstract: Despite advances in anaesthesiological and surgical techniques, cardiac surgery in cirrhotic patients remains hazardous. This report outlines our experience with haemostasis monitoring in two consecutive cases of sequential aortic valve replacement and liver transplantation. Clotting disturbances proved to have fatal consequences since one of these patients died following massive lung embolism. The second patient underwent successfully this combined procedure and is in good clinical state 14 months postoperatively. Evaluation and discussion of the coagulation monitoring by the Sonoclot Analyzer in both patients and related therapeutic suggestions for the prevention of thrombotic events are discussed. (Acta gastroenterol. belg., 2010, 73, 65-68).

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A potentially life-treatening complication after a blood transfusion: the importance of clinical awareness



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Treatment of acute lymphoblastic leukemia in children with the BFM protocol: a cooperative study and analysis of prognostic factors



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Repair of anomalous mitral arcade in a child

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Siddharthan Deepti, Velayoudam Devagourou, Shyam Sunder Kothari

Annals of Pediatric Cardiology 2017 10(2):200-202

A 13-year-old girl presented with exertional dyspnea and congestive heart failure. Echocardiography revealed severe congenital mitral stenosis due to anomalous mitral arcade with severe pulmonary hypertension. She underwent successful mitral valve repair. The case is reported for its rarity.

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Three-dimensional-printed cardiac prototypes in complex congenital cardiac defects: New technology with exciting possibilities

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Sreekanthan Sundararaghavan

Annals of Pediatric Cardiology 2017 10(2):114-116



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Author's Response

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Annals of Pediatric Cardiology 2017 10(2):220-221



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Three-dimensional-printed cardiac prototypes aid surgical decision-making and preoperative planning in selected cases of complex congenital heart diseases: Early experience and proof of concept in a resource-limited environment

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Mahesh Kappanayil, Nageshwara Rao Koneti, Rajesh R Kannan, Brijesh P Kottayil, Krishna Kumar

Annals of Pediatric Cardiology 2017 10(2):117-125

Introduction: Three-dimensional. (3D) printing is an innovative manufacturing process that allows computer.assisted conversion of 3D imaging data into physical "printouts" Healthcare applications are currently in evolution. Objective: The objective of this study was to explore the feasibility and impact of using patient-specific 3D-printed cardiac prototypes derived from high.resolution medical imaging data. (cardiac magnetic resonance imaging/computed tomography. [MRI/CT]) on surgical decision-making and preoperative planning in selected cases of complex congenital heart diseases. (CHDs). Materials and Methods: Five patients with complex CHD with previously unresolved management decisions were chosen. These included two patients with complex double.outlet right ventricle, two patients with criss-cross atrioventricular connections, and one patient with congenitally corrected transposition of great arteries with pulmonary atresia. Cardiac MRI was done for all patients, cardiac CT for one; specific surgical challenges were identified. Volumetric data were used to generate patient-specific 3D models. All cases were reviewed along with their 3D models, and the impact on surgical decision-making and preoperative planning was assessed. Results: Accurate life-sized 3D cardiac prototypes were successfully created for all patients. The models enabled radically improved 3D understanding of anatomy, identification of specific technical challenges, and precise surgical planning. Augmentation of existing clinical and imaging data by 3D prototypes allowed successful execution of complex surgeries for all five patients, in accordance with the preoperative planning. Conclusions: 3D-printed cardiac prototypes can radically assist decision-making, planning, and safe execution of complex congenital heart surgery by improving understanding of 3D anatomy and allowing anticipation of technical challenges.

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Anomalous origin of right coronary artery causing myocardial ischemia in a young patient

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Anil Kumar Singhi, Ejaz Ahmad Bari, Sunip Banerjee

Annals of Pediatric Cardiology 2017 10(2):212-214

Anomalous right coronary artery from left coronary sinus can have dynamic narrowing and kinking causing symptoms of myocardial ischemia and sudden cardiac death. Surgical repair of the anomaly is required in the symptomatic patient because of risk of ischemia or ventricular arrhythmia. Asymptomatic incidentally diagnosed low-risk patients can be closely followed up with exercise restriction as per present guideline.

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Neonates with critical congenital heart defects: Impact of fetal diagnosis on immediate and short-term outcomes

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Sylvia Michael Colaco, Tanuja Karande, Prashant Raviprakash Bobhate, Rashmi Jiyani, Suresh G Rao, Snehal Kulkarni

Annals of Pediatric Cardiology 2017 10(2):126-130

Background: Fetal echocardiography is being increasingly used for prenatal diagnosis of congenital cardiac malformations, but its impact on the neonatal outcomes in low- and middle-income countries is still unknown. Aims: The objective of this study is to determine the impact of fetal echocardiography on immediate postnatal and short.term outcome in a tertiary pediatric cardiac center. Study Design: This is a prospective study. Materials and Methods: One hundred consecutive patients with critical congenital heart defects (CHD) requiring active medical or surgical interventions in the 1st month of life were included in the study. The detailed history, postnatal examination findings, and fetal echocardiogram report were recorded. They were divided into two groups as antenatally diagnosed and postnatally diagnosed. Pre- and post-procedural variables were compared between the two groups. Results: Twenty-nine neonates were diagnosed antenatally while 71 were diagnosed postnatally. Totally, 10 babies (34.5%) among the antenatally diagnosed group were delivered in a tertiary health-care setup. The mean age at presentation was 0. day in the antenatally diagnosed group while 10 days. (0–30 days) in the postnatally diagnosed group. (P = 0.01). A total of 17 (58.6%) patients in the antenatal group had duct dependent CHD, and 15 (88.2%) of these patients were transported on prostaglandin E1. In comparison, 19/34 (55.9%) patients in the postnatal group were transported on prostaglandin. The pH on admission in the antenatal group was 7.32 ± 0.05 as compared to 7.28 ± 0.05 in the postnatal group. (P = 0.0004). There were 4 (5.6%) deaths in the postnatal group during transfer. There was no significant difference in the postoperative variables in both groups. Conclusions: Fetal echocardiography identifies patients with complex CHD resulting in better parental counseling, thus facilitating delivery at a tertiary care center and preoperative stabilization. This results in improved preoperative mortality and better stabilization.

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Pitfalls of stenting coarctation of an angulated right circumflex aortic arch in Goldenhar syndrome

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Elaheh Malakan Rad, Hojjat Mortezaeian, Hamid Reza Pouraliakbar, Ziyad M Hijazi

Annals of Pediatric Cardiology 2017 10(2):194-196

We report stenting of coarctation of an angulated right circumflex aortic arch (RCAA) using four Cheatham Platinum stents in a child with Goldenhar syndrome. Difficulties in measuring the accurate length of the curved and narrowed transverse aortic arch marked discrepancy between the luminal diameters of the long narrow transverse arch and wide descending thoracic aorta, increased displacement force caused by the 90° bend between the two parts resulted in repeated stent migrations. We discuss the tips to avoid distal stent migration in the setting of an angulated RCAA.

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Patent ductus arteriosus closure using Occlutech® Duct Occluder, experience in Port Elizabeth, South Africa

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Lungile Pepeta, Adele Greyling, Mahlubandile Fintan Nxele, Zongezile Masonwabe Makrexeni

Annals of Pediatric Cardiology 2017 10(2):131-136

Background: Percutaneous closure of patent ductus arteriosus (PDA) has become standard therapy. Experience with the Occlutech® Duct Occluder is limited. Methods: Data regarding ductal closure using Occlutech® Duct Occluder were reviewed and prospectively collected. Demographics, hemodynamic and angiographic characteristics, complications, and outcomes were documented. Results: From March 2013 to June 2016, 65 patients (43 females and 22 males) underwent percutaneous closure of the PDA using Occlutech® Duct Occluder. The median age of the patients was 11 months (range, 1–454 months) and the median weight was 8.5 kg (range 2.5–78 kg). The mean pulmonary artery median pressure was 27 mmHg (range, 12–100 mmHg) and the QP: Qs ratio median was 1.8 (range, 1–7.5), with a pulmonary vascular resistance mean of 2.7 WU (standard deviation [SD] ±2.1). Thirty-two patients had Krichenko Type A duct (49%); 7, Type C (11%); 4, Type D (6%); and 22, Type E (34%). The ductal size (narrowest diameter at the pulmonic end) mean was 3.5 mm (SD ± 1.9 mm). The screening time mean was 17.3 min (SD ± 11.6). Out of 63 patients with successful closure of the PDA using Occlutech® Duct Occluder, there were 15 patients with small PDAs; 25 with moderate PDAs, and 23 with large PDAs. In one patient, the device dislodged to the descending aorta, and in two patients, to the right pulmonary artery immediately following deployment, with successful percutaneous (two) and surgical (one) retrieval. Complete ductal occlusion was achieved in all 63 patients on day one. Conclusion: The Occlutech® Duct Occluder is a safe and effective device for closure of ducts in appropriately selected patients.

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Stent migration after right ventricular outflow tract stenting in the severe cyanotic Tetralogy of Fallot case

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Tamaki Hayashi, Saleem Akhtar, Mazeni Alwi

Annals of Pediatric Cardiology 2017 10(2):206-208

We report our experience with a stent migration after right ventricle outflow tract stenting and converted to patent ductus arteriosus stenting in Tetralogy of Fallot (TOF) with severe infundibular stenosis. Finally, the patient achieved to TOF repair, and the migrated stent was removed without any complication.

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Mid-term outcomes of surgical repair for anomalous origin of the left coronary artery from the pulmonary artery: In infants, children and adults

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Maziar Gholampour Dehaki, Alwaleed Al-Dairy, Yousef Rezaei, Alireza Alizadeh Ghavidel, Gholamreza Omrani, Nader Givtaj, Reza Sadat Afjehi, Hassan Tatari, Amir Hossein Jalali, Mohammad Mahdavi

Annals of Pediatric Cardiology 2017 10(2):137-143

Background: Anomalous origin of left coronary artery from the pulmonary artery (ALCAPA) is a rare congenital malformation. We sought to evaluate in-hospital and mid-term outcomes of patients with a diagnosis of ALCAPA who underwent surgical repair. Objectives: The objective of this study is to evaluate the mid-term outcomes of surgical repair of ALCAPA at our center and to analyze the surgical techniques used. Materials and Methods: In a retrospective study, we analyzed early and mid-term clinical and echocardiographic data to determine the outcomes of patients who underwent surgical repair of ALCAPA in our institution between 2005 and 2015. Results: Twenty-one patients underwent surgical repair for ALCAPA using aortic reimplantation (n = 10, 47.6%), ostial closure. (n = 8, 38.1%), or ligation. (n = 3, 14.3%). The median age of patients was 24. months. (range 22 days to 51 years). There were 2 (9.5%) in-hospital mortalities in infants undergoing the reimplantation technique. All patients were followed up for a median of 21 months. (range 1–60 months). No patients required reoperation, and there was no mortality from discharge to mid-term follow-up. Severe early postoperative mitral regurgitation. (MR) was associated with composite end-point, defined as a combination of mortality after surgery, moderate to severe MR, and moderate to severe left ventricular dysfunction at late follow-up. (P = 0.019) while mitral valve repair was not. (P = 0.469). Conclusion: The surgical management of ALCAPA can be associated with good in-hospital and mid-term outcomes regardless of the age, at which the patient has been operated.

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Massive biventricular rhabdomyoma in a neonate

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Manish Pandey, Rimlee Dutta, Shyam S Kothari

Annals of Pediatric Cardiology 2017 10(2):218-219

Rhabdomyoma is a well characterised entity in a neonate. Herein, we report a massive biventricular rhabdomyoma in a neonate presenting with cyanosis and congestive heart failure which was confirmed on autopsy. The report is for documentation of an unusually large tumour.

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Cost-effectiveness analysis of different devices used for the closure of small-to-medium-sized patent ductus arteriosus in pediatric patients

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Sonia A El-Saiedi, Amal M El Sisi, Rodina Sobhy Mandour, Doaa M Abdel-Aziz, Wael A Attia

Annals of Pediatric Cardiology 2017 10(2):144-151

Aims: In this study, we examined the differences in cost and effectiveness of various devices used for the closure of small to medium sized patent ductus arteriosus (PDA). Setting and Design: We retrospectively studied 116 patients who underwent closure of small PDAs between January 2010 and January 2015. Subjects and Methods: Three types of devices were used: the Amplatzer duct occluder (ADO) II, the cook detachable coil and the Nit Occlud coil (NOC). Immediate and late complications were recorded and patients were followed up for 3 months after the procedure. Statistical Methods: All statistical calculations were performed using Statistical Package for the Social Science software. P <0.05 were considered significant. Results: We successfully deployed ADO II devices in 33 out of 35 cases, cook detachable coils in 36 out of 40 cases and NOCs in 38 out of 41 cases. In the remaining nine cases, the first device was unsuitable or embolized and required retrieval and replacement with another device. Eleven patients (9.5%) developed vascular complications and required anticoagulation therapy. Patients who had hemolysis or vascular complications remained longer in the intensive care unit, with consequently higher total cost (P = 0.016). Also, the need for a second device increased the cost per patient. Conclusions: The cook detachable coil is the most cost.effective device for closure of small.to medium.sized PDAs. Calculations of the incremental cost.effectiveness. (ICE) revealed that the Cook detachable coil had less ICE than the ADO II and NOC. The NOC was more effective with fewer complications.

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A roadmap for the aspiring interventional pediatric cardiologist

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Raman Krishna Kumar

Annals of Pediatric Cardiology 2017 10(2):109-113



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Correlation of electrocardiogram parameters and hemodynamic outcomes in patients with isolated secundum atrial septal defects

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Mohammad Refaei, Sunjidatul Islam, Andrew S Mackie, Joseph Atallah

Annals of Pediatric Cardiology 2017 10(2):152-157

Objective: The characteristic rSR' pattern in lead V1 on electrocardiogram (ECG) has been described in association with atrial septal defect (ASD) and right ventricular dilation. We aimed to determine if temporal ECG changes can guide a more discriminate and cost-effective screening during follow-up of isolated secundum ASD. Methods: Our study population included all pediatric patients followed at the Stollery Children's Hospital with a secundum ASD, not associated with other significant heart disease, between 2004 and 2010. We collected clinical as well as serial echocardiographic and ECG data. Results: We identified 141 patients with ASD, 95% were asymptomatic and 88% referred for a murmur. Moderate-to-large (>5 mm) ASDs were present in 52%. The prevalence of an rSR' pattern was 26% in the overall cohort and 54% in the large ASD group. During median follow-up of 28.7 months, 37 patients underwent surgical or transcatheter closure. Among patients with rSR' on ECG, 78% had moderate-to-large ASD size. In that group, the presence versus the absence of rSR' correlated with lower positive predictive value (PPV) for spontaneous closure (7% vs. 36%; P = 0.01) and higher PPV for device or surgical closure (71% vs. 38%; P = 0.02). Conclusion: We observed a lower prevalence of rSR' pattern in patients with isolated ASD than previously reported. However, an rSR' pattern had incremental value in predicting the need for surgical or device intervention for closure in moderate.large groups. This can be used to tailor patient echocardiographic screening and caregiver counseling.

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Modified transjugular approach for percutaneous atrial septal defect closure

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Rishi Ashokkumar Bhargava, Ankur Phatarpekar, Charan P Lanjewar, Prafulla G Kerkar

Annals of Pediatric Cardiology 2017 10(2):197-199

Femoral venous route is routinely used for percutaneous closure of atrial septal defects (ASDs). However, a situation may arise where transfemoral approach is not feasible. We describe a successful transjugular closure of a moderate-sized ASD in a 49-year-old symptomatic man with interrupted inferior vena cava, using a novel deployment technique, which helped in overcoming difficulties such as maintaining stable sheath position and minimizing risk of air embolism.

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Use of strain, strain rate, tissue velocity imaging, and endothelial function for early detection of cardiovascular involvement in patients with beta-thalassemia

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Abhinav Gupta, Aditya Kapoor, Shubha Phadke, Archana Sinha, Shridhar Kashyap, Roopali Khanna, Sudeep Kumar, Naveen Garg, Satyendra Tewari, Pravin Goel

Annals of Pediatric Cardiology 2017 10(2):158-166

Background: Global ventricular function often remains normal in patients with beta-thalassemia major. (β-TM) until late. Tissue Doppler and strain imaging may be useful to assess regional myocardial function abnormalities in these patients. Methods: Systolic (Sm), early diastolic (Em), and late diastolic (Am) (Em/Am) myocardial velocities at basal lateral and septal left ventricular (LV) segments, strain (S), and strain rate (SR) in basal and mid LV, right ventricular (RV) and septum were measured in 30 patients (β-TM, 12.4 ± 5.2 years, serum ferritin 2603.1 μg/L) and twenty controls (12.5 ± 5.2 years). Flow-mediated dilatation (FMD) vasodilatation as a measure of endothelial function was also assessed. Results: Patients had significantly higher LV mass index (169.45 ± 61.14 vs. 104.66 ± 24.42; P = 0.009) while global LV Sm and diastolic function was similar to controls. Patients had significantly lower lateral Em velocity, Em (10.12 ± 1.16 vs. 17.9 ± 2.11; P = 0.002), Em/Am ratio (0.811 ± 0.192 vs. 2.06 ± 0.62; P = 0.001) at the basal lateral LV, lower strain values at the basal lateral LV (19.5 ± 4.17 vs. 24.196 ± 1.81; P = 0.002), mid lateral LV (19.07 ± 3.98 vs. 25.56 ± 2.62; P = 0.042), basal septum (17.04 ± 3.44 vs. 25.43 ± 2.53; P = 0.001), and mid septum (20.49 ± 5.34 vs. 24.45 ± 2.20; P = 0.001) as compared to controls. SR at the basal and mid segment of the lateral LV wall and at the basal and mid septum was also significantly lower in patients. SR in basal and mid RV although lower was not significantly different from controls. Patients also had significantly lower FMD (7.57 ± 3.16 vs. 18.08 ± 1.9, P = 0.018) implying endothelial dysfunction. Conclusions: Tissue Doppler, strain and SR imaging are useful to quantify regional myocardial function in asymptomatic α-TM patients with preserved global Sm and diastolic function.

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Recanalization of an occluded left pulmonary artery: A case report and review of the literature

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Ali Ibrahim Elarabi, Ming Chern Leong, Mazeni Alwi

Annals of Pediatric Cardiology 2017 10(2):203-205

We report an 8-year-old male child with tetralogy of Fallot (TOF), who developed left pulmonary artery (LPA) atresia, following surgical repair of TOF and left pulmonary arterioplasty at the age of 6 years. He underwent successful radiofrequency recanalization and stenting of the LPA. The LPA exhibited satisfactory growth for 3 months, following recanalization and stenting.

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Catheter hemodynamic assessment of the univentricular circulation

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Oliver Stumper, Gemma Penford

Annals of Pediatric Cardiology 2017 10(2):167-174

Children with very complex congenital heart disease not amenable to biventricular repair are increasingly being considered for a palliative univentricular care pathway. This involves a staged surgical approach culminating in the Fontan circulation with passive pulmonary blood flow and added resistances. The catheter based hemodynamic assessment at all three stages of this palliation is described in detail. Frequent pitfalls, inherent limitations and potential errors are discussed and clinical examples are illustrated.

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The utility of computed tomographic angiography in a neonate on extracorporeal membrane oxygenation with extreme cyanosis after Blalock–Taussig shunt

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Jess D Rames, Minoo N Kavarana, U Joseph Schoepf, Anthony Marcus Hlavacek

Annals of Pediatric Cardiology 2017 10(2):209-211

A modified Blalock–Taussig shunt (mBTS) is often employed to provide pulmonary blood flow in neonates that are born with cyanotic congenital heart defects. However, acute shunt thrombosis can occur in the postoperative period, resulting in profound cyanosis. In this case report, we describe the utility of computed tomographic angiography (CTA) in the management of a neonate with extreme cyanosis after placement of a mBTS while on extracorporeal membrane oxygenation. Using CTA, several small clots were identified in the shunt as well as stenosis of the left pulmonary artery; neither of which were identified with echocardiography. The CTA allowed for quick identification of the disorder and helped direct prompt surgical intervention.

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Isomerism in the setting of the so-called “heterotaxy”: The usefulness of computed tomographic analysis

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Shumpei Mori, Robert H Anderson, Tatsuya Nishii, Kensuke Matsumoto, Rohit S Loomba

Annals of Pediatric Cardiology 2017 10(2):175-186

The most complex combinations of congenital cardiac malformations are found in the setting of bodily isomerism. The question remains, however, as to whether evidence of cardiac isomerism is always to be found in the setting of bodily isomerism, also known as "heterotaxy." We have previously shown that, when assessed on the basis of the extent of the pectinate muscles relative to the atrioventricular junctions, there is always isomerism of the atrial appendages in this setting. Doubt has been remained, however, as to whether these cardiac features can accurately be recognized during life. We have now encountered two patients showing features of the left and right bodily isomerism. Examinations of these patients made using computed tomography show that all features of isomerism, no matter how complex, can now be visualized during life. The images currently presented show, furthermore, that the features of the so-called "heterotaxy" can be seen during life, not only within the heart but also in all the thoracic and abdominal organs, albeit that the isomeric features are confined to the thoracic organs. Based on the images presented, we argue that if each system of organs is analyzed and described in independent fashion; then it is possible for clinicians to exclude any suggestion of ambiguity and to provide accurate descriptions of the overall arrangement. We further discuss the appropriate terminology to describe the entity we prefer to call isomerism, along with the indications and usefulness of computed tomography in revealing the anatomic features of the congenitally malformed heart.

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Development and optimisation of an in-service teacher training programme on motivational assessment in physical education

Although assessment practices are commonly part of the physical education (PE) curriculum they may often frustrate rather than support students' basic needs for autonomy, competence and relatedness. Nevertheless, assessment also provides various promising opportunities to support these basic needs and enhance learning in students. In order to address this issue, we developed an in-service teacher training programme that was grounded within contemporary theories on assessment and motivation, and aimed at improving PE teachers' expertise on motivational assessment practices. In close collaboration with PE teachers and other experts in the field an inservice teacher training programme was developed that covered important topics such as quality assessment, motivation and assessment for learning. Specific attention was directed to the translation of theoretical concepts into practical and applicable tools. The in-service training programme was then provided on-site three times to a total of 33 PE teachers (of whom 20 were male (60%) and 12 were female (40%), teaching experience 3–32 years) representing different PE departments. Through an iterative cycle of development, provision, evaluation and adjustment the programme was gradually optimised. Focus group sessions and questionnaires were employed to evaluate various aspects, and identify barriers and success factors. The in-service teacher training programme is a successful first step in improving the expertise of PE teachers to start and develop higher quality and more motivating assessment practices. Nevertheless, in order to generate durable change within daily PE practice, follow-up training sessions or counselling methods (e.g. through communities of practice) are essential to overcome implementation barriers. Development, adjustment and future directions for assessment are discussed.

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Het rechterlijk oordeel dat de vaderlijke erkenning niet kan plaatsvinden



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Continuous diphenhydramine infusion and imatinib for KIT-D816V-negative mast cell activation syndrome: a case report

We present the first full case report of the treatment of mast cell activation syndrome with continuous diphenhydramine infusion, which resulted in the improvement of anaphylactic reactions and a decrease in h...

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Chryseobacterium gleum in a man with prostatectomy in Senegal: a case report and review of the literature

Here we report a rare case of a urinary tract infection due to Chryseobacterium gleum. This widely distributed Gram-negative bacillus is an uncommon human pathogen and is typically associated with health care set...

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Sensitivity of dental phenotypic data for the identification of biological relatives

Abstract

Using modern samples of known kin, this paper evaluates two fundamental aspects of kinship analysis in archaeological contexts: 1) choice of data (dental metrics or morphology), and 2) analytical approach (multivariate, distance-based approach or a "rare trait" analysis). Stone dental casts were analyzed from 155 females from four sampling locations in Kenya. Of these 155 individuals, only three pairs were close kin: mother-daughter dyad, sister-sister, and first cousin-first cousin dyads. After variable winnowing, inter-individual distances or similarities were calculated using 11 odontometric variables and 25 dental morphological variables. Resulting distance matrices were ordinated in two dimensions using multidimensional scaling. Odontometric data performed relative well at identifying known relative pairs, but the results were heavily affected by choice of similarity measure (e.g., Euclidean distances vs. Gower coefficients) and pre-analysis data treatments (e.g., raw data vs PCA components). Dental morphological data performed comparably to odontometric data but were slightly less effective. Rare traits were identified and compared among relative pairs for concordance, with mixed results. Rare morphological features were randomly distributed throughout the population and were not exclusively found in close kin. In combination, results indicated the sister-sister dyad was most consistently identified; however, in no analysis were relatives more phenotypically similar than all random pairs of unrelated individuals. A multivariate, distance-based approach was more effective than rare traits at identifying relative pairs, but even under ideal circumstances there is not enough variation present in the dentition to faithfully identify close relatives in the absence of contextual archaeological data.



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Mathematical model of haptic perception of temperature



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Influence or soil humidity on the thermal impedance, time constant and structure function of underground cables: a laboratory experiment



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Redundant variables and Granger causality



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Hate Speech Decision on Le Pen



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Kernel Granger Causality Mapping Effective Connectivity on fMRI Data



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Kernel Method for Nonlinear Granger Causality



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Semi-supervised learning by search of optimal target vector



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Kernel-Granger causality and the analysis of dynamical networks



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Phase diagram of a generalized Winfree model



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Multiscale analysis of short term heart beat interval, arterial blood pressure, and instantaneous lung volume time series



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Input-Driven Oscillations in Networks with Excitatory and Inhibitory Neurons with Dynamic Synapses



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Effects of levetiracetam vs topiramate and placebo on visually evoked phase synchronization changes of alpha rhythm in migraine



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Natural clustering : the modularity approach



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The impact of individual Cognitive Stimulation Therapy (iCST) on cognition, quality of life, caregiver health, and family relationships in dementia: A randomised controlled trial

Orrell, M; Yates, L; Leung, P; Kang, S; Hoare, Z; Whitaker, C; Burns, A; Orrell, M; Yates, L; Leung, P; Kang, S; Hoare, Z; Whitaker, C; Burns, A; Knapp, M; Leroi, I; Moniz-Cook, E; Pearson, S; Simpson, S; Spector, A; Roberts, S; Russell, I; de Waal, H; Woods, RT; Orgeta, V; - view fewer (2017) The impact of individual Cognitive Stimulation Therapy (iCST) on cognition, quality of life, caregiver health, and family relationships in dementia: A randomised controlled trial. PLoS Medicine , 14 (3) , Article e1002269. 10.1371/journal.pmed.1002269 . Green open access

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A Neurochemical Basis for Phenotypic Differentiation in Alzheimer's Disease? Turing's Morphogens Revisited

Whittaker, HT; Warren, JD; (2017) A Neurochemical Basis for Phenotypic Differentiation in Alzheimer's Disease? Turing's Morphogens Revisited. Frontiers in Aging Neuroscience , 9 , Article 76. 10.3389/fnagi.2017.00076 . Green open access

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A few of my favorite things: circumscribed interests in autism are not accompanied by increased attentional salience on a personalized selective attention task

Parsons, OE; Bayliss, AP; Remington, A; (2017) A few of my favorite things: circumscribed interests in autism are not accompanied by increased attentional salience on a personalized selective attention task. Molecular Autism , 8 , Article 20. 10.1186/s13229-017-0132-1 . Green open access

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Apathy and Reduced Speed of Processing Underlie Decline in Verbal Fluency following DBS

Foley, JA; Foltynie, T; Zrinzo, L; Hyam, JA; Limousin, P; Cipolotti, L; (2017) Apathy and Reduced Speed of Processing Underlie Decline in Verbal Fluency following DBS. Behavioural Neurology , 2017 , Article 7348101. 10.1155/2017/7348101 . Green open access

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Bacterial survival following shock compression in the GigaPascal range

Hazael, R; Fitzmaurice, BC; Foglia, F; Appleby-Thomas, GJ; McMillan, PF; (2017) Bacterial survival following shock compression in the GigaPascal range. Icarus , 293 pp. 1-7. 10.1016/j.icarus.2017.03.031 .

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Cinnarizine: A Contemporary Review

Abstract

Cinnarizine, is approved for nausea, vomiting, motion sickness, inner ear disorders and is considered as first-line pharmacotherapy for management of vertigo. It acts by anti-vasoconstrictor activity, reducing blood viscosity and reducing nystagmus in labyrinth. Lack of adequate literature on clinical evidence of cinnarizine and its combination (dimenhydrinate) in vertigo management prompted this review. A specific MEDLINE literature search strategy was designed combining Medical Subject Headings, free-text keywords (like cinnarizine and vertigo) using Boolean operators (1970–2016) for clinical studies, clinical reviews and meta-analyses of cinnarizine. Analyses of studies validated cinnarizine's efficacy in peripheral and central vertigo versus placebo or other therapies, and was well-tolerated by the patients recruited across different studies. Cinnarizine and/ or its combinations are favorable in management of vestibular disorders wherein cinnarizine acts predominantly peripherally on labyrinth and dimenhydrinate acts centrally on vestibular nuclei and associated centers in brainstem. Combination therapy of cinnarizine and/ or its combinations demonstrated a better safety profile than either of the mono-components, offering a viable therapeutic option in vertigo management.



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Символика пересечения границ в восточнославянских заговорах



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Early postoperative neuropathic pain assessed by the DN4 score predicts an increased risk of persistent postsurgical neuropathic pain.

BACKGROUND: Acute neuropathic pain can occur in the postoperative period but any link with persistent post-surgical neuropathic pain remains unclear. OBJECTIVES: The objectives of this study were to prospectively describe the incidence of acute post-surgical neuropathic pain in a large population using the DN4 (clinician administered) questionnaire and to confirm the hypothetical link between acute and persistent neuropathic pain at 2 months after surgery in a large population using the DN2 (self administered) questionnaire. DESIGN: A multi-centre, prospective and observational trial. SETTING Two consecutive days in 27 hospitals in France. PATIENTS: Six hundred and eight patients undergoing 13 different types of surgery. Fifteen patients were excluded as data were incomplete, and 229 (38.6%) and 260 (43.8%) were not contactable for assessment at 1 and 2 months after surgery, respectively. MAIN OUTCOME MEASURES: Pain was evaluated at least 2 h postoperatively on the same day (D0),on the second day (D2) and at 1 and 2 months after surgery (M1 and M2). Pain was assessed using a 10-point Numeric Rating Scale. If the Numeric Rating Scale score was greater than 0, neuropathic pain was assessed using a DN4 (clinician administered) questionnaire or using a DN2 (self-administered) questionnaire. Acute and persistent postsurgical neuropathic pain (PPSNP) were defined respectively by a DN4 score at least 4/10 on day 0 and/or day 2 and a DN2 score at least 3/7 at 2 months after surgery. RESULTS: Of the 593 patients included, 41.2% were in pain before surgery and 8.2% described neuropathic pain. Early after surgery, the majority of the 593 patients (72.2% on the day of surgery and 71.3% on day 2) experienced acute pain. It was neuropathic in nature in 5.6% of patients (95% CI, 3.6 to 8.3) on the day of surgery and 12.9% (95% CI, 9.7 to 16.7) on day 2. Two months after surgery, PPSNP was present in 33.3% of the 333 patients assessed. Multivariate analysis showed that a DN4 score at least 4/10 on the day of surgery or on day 2 was a significant risk factor for PPSNP [odds ratios 4.22 (95% CI, 2.19 to 8.12)]. CONCLUSION: Our results suggest that early acute postsurgical neuropathic pain significantly increases the risk of persistent post-surgical neuropathic pain. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NTC NCT02826317. (C) 2017 European Society of Anaesthesiology

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Training in intraoperative handover and display of a checklist improve communication during transfer of care: An interventional cohort study of anaesthesia residents and nurse anaesthetists.

BACKGROUND: Handovers during anaesthesia are common, and failures in communication may lead to morbidity and mortality. OBJECTIVES: We hypothesised that intraoperative handover training and display of a checklist would improve communication during anaesthesia care transition in the operating room. DESIGN: Interventional cohort study. SETTING: Single-centre tertiary care university hospital. PARTICIPANTS: A total of 204 random observations of handovers between anaesthesia providers (residents and nurse anaesthetists) over a 6-month period in 2016. INTERVENTION: Two geographically different hospital sites were studied simultaneously (same observations, but no training/checklist at the control site): first a 2-week 'baseline' observation period; then handover training and display of checklists in each operating room (at the intervention site only) followed by an 'immediate' second and finally a third (3 months later) observation period. MAIN OUTCOME MEASURES: A 22-item checklist was created by a modified DELPHI method and a checklist score calculated for each handover by adding the individual scores for each item as follows: -1, if error in communicating item; 0, unreported item; 0.5, if partly communicated item; 1, if correctly communicated item. RESULTS: Before training and display of the checklist, the scores in the interventional and the control groups were similar. There was no improvement in the control group's scores over the three observation periods. In the interventional group, the mean (95% confidence interval) score increased by 43% [baseline 7.6 (6.7 to 8.4) n = 42; 'immediate' 10.9 (9.4 to 12.4) n = 27, P

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Loss of resistance: A randomised controlled trial assessing four low-fidelity epidural puncture simulators.

BACKGROUND: Detecting loss of resistance (LOR) can either be taught with dedicated simulators, with a cost ranging from [Euro sign]1500 to 3000, or with the 'Greengrocer's Model', requiring simply a banana. OBJECTIVES: The purpose of this study was to compare three dedicated epidural puncture training simulators and a banana in their ability to simulate LOR. Our hypothesis was that there was a difference between the four simulators when comparing the detection of LOR. DESIGN: Single-blinded, randomised, controlled study. SETTING: Department of Anaesthesiology and Pain Therapy, Bern University Hospital, Switzerland. PARTICIPANTS: Fifty-five consultant anaesthesiologists. INTERVENTIONS: The participants were asked to insert an epidural catheter in four different epidural puncture training simulators: Lumbar Puncture Simulator II (Kyoto Kagaku, Kyoto, Japan), Lumbar Epidural Injection Trainer (Erler-Zimmer, Lauf, Germany), Normal Adult Lumbar Puncture/Epidural Tissue (Simulab Corp., Seattle, Washington, USA) and a banana. The simulators were placed in identical boxes to blind the participants. MAIN OUTCOME MEASURES: The primary outcome was the detection of LOR rated on a 100-mm visual analogue scale, in which 0 mm represented 'completely unrealistic' and 100 mm represented 'indistinguishable from a real patient'. RESULTS: The mean visual analogue scale scores for LOR in the four simulators were significantly different: 60 +/- 25 mm [95% confidence interval (CI), 55 to 65 mm], 50 +/- 29 mm (95% CI, 44 to 55 mm), 64 +/- 24 mm (95% CI, 58 to 69 mm) and 49 +/- 32 mm (95% CI, 44 to 54 mm); P less than 0.001, Friedman test. CONCLUSION: Two of the three dedicated epidural simulators were rated more realistic in detecting LOR than the banana, but some participants preferred the banana to the other three simulators. Given the relative cost of a banana compared with a dedicated simulator, we suggest that a banana be used to teach the technique of LOR for epidural puncture. TRIAL REGISTRATION: KEK Nr: Req-2015-z087. (C) 2017 European Society of Anaesthesiology

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A randomised trial to evaluate preoperative oral carbohydrate administration on insulin resistance in off-pump coronary artery bypass patients.

BACKGROUND: In fasting cardiac surgery patients, preoperative carbohydrate (CHO) drink intake attenuated insulin resistance and improved cardiac metabolism, although its beneficial effects were not evident after cardiac surgery possibly due to cardiopulmonary bypass-related extreme systemic inflammation. OBJECTIVE: We aimed to evaluate whether preoperative CHO intake affected insulin resistance and free-fatty acid (FFA) concentrations in off-pump coronary revascularisation. DESIGN: A randomised controlled trial. SETTING: Primary care in a university hospital in Korea from January 2015 to July 2016. PATIENTS: Sixty patients who underwent elective multi-vessel off-pump coronary revascularisation were randomised into two groups. Three patients were excluded from analysis and 57 patients completed study. INTERVENTION: The CHO group received oral CHO (400 ml) the prior evening and 2 to 3 h before surgery, and the control group was fasted from food and water according to standard protocol. MAIN OUTCOME MEASURES: Insulin resistance was assessed twice, after anaesthetic induction and after surgery via short insulin tolerance test. FFA, C-reactive protein and creatine kinase-myocardial band concentrations were determined serially for 48 h after surgery. RESULTS: Insulin sensitivity was greater (P = 0.002) and plasma FFA concentrations were lower (P = 0.001) after anaesthetic induction in the CHO group compared with the Control group, although there were no intergroup differences after surgery. The postoperative peak creatine kinase-myocardial band concentration was significantly lower in the CHO group compared with the Control group [8.8 (5.4 to 18.2) vs. 6.4 (3.5 to 9.7) ng ml-1, P = 0.031]. CONCLUSION: A preoperative CHO supplement significantly reduced insulin resistance and FFA concentrations compared with fasting at the beginning of the surgery, but these benefits were lost after off-pump coronary revascularisation. Despite their transient nature, these beneficial effects resulted in less myocardial injury, mandating further studies focused on the impact of preoperative CHO on myocardial ischaemia and cardiac function after coronary revascularisation. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT 02330263. (C) 2017 European Society of Anaesthesiology

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Magnesium sulphate improves pulmonary function after video-assisted thoracoscopic surgery: A randomised double-blind placebo-controlled study.

BACKGROUND: Reduced lung volumes are unavoidable after lung resection surgery. Magnesium sulphate (MgSO4) administration has been reported to reduce the requirement for neuromuscular blocking drugs and postoperative analgesics in surgical patients. OBJECTIVE: To investigate the effect of MgSO4 on pulmonary function after video-assisted thoracoscopic surgery (VATS). DESIGN: A randomised, double-blind, placebo-controlled trial. SETTING: A university tertiary care centre. PATIENTS: Sixty-six patients scheduled for pulmonary lobectomy or segmentectomy via VATS. INTERVENTION: Patients were allocated to one of two groups: the Mg (MgSO4 50 mg kg-1 intravenously for 10 min, followed by a continuous infusion of 15 mg kg-1 h-1 during surgery) or the control (same volume of 0.9% saline). MAIN OUTCOME MEASURES: Pulmonary function tests [forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and peak expiratory flow rate] were measured before surgery and at three time points after surgery (2, 24 and 48 h postoperatively) using a portable spirometer. Twelve months after surgery, pulmonary function test values were repeated at a regular outpatient follow-up visit. RESULTS: FEV1 at 24 (1.7 +/- 0.6 vs. 1.3 +/- 0.5 l, P = 0.033) and 48 h (1.7 +/- 0.6 vs. 1.4 +/- 0.5 l, P = 0.021) and FVC at 24 (2.0 +/- 0.8 vs. 1.6 +/- 0.6 l, P = 0.038) and 48 h (2.2 +/- 0.8 vs. 1.7 +/- 0.7 l, P = 0.008) after surgery were significantly greater in the Mg group. Patients in the Mg group required less rocuronium than those in the control group (64.2 +/- 19.9 vs. 74.9 +/- 20.3 mg, respectively; P = 0.041). Consumption of postoperative patient-controlled analgesia was also significantly less at 24 and 48 h after surgery in the Mg group (P = 0.022 and 0.015, respectively), although pain scores and rescue analgesics were comparable. Five patients in the control group were diagnosed with postoperative pneumonia using clinical and radiological criteria before discharge. FEV1 and FVC at 12 months after surgery were not different between the two groups. CONCLUSION: Intraoperative administration of MgSO4 improved pulmonary function and reduced the need for rocuronium and postoperative analgesics in patients who underwent VATS. TRIAL REGISTRATION: cris.nih.go.kr identifier: KCT0001410 (C) 2017 European Society of Anaesthesiology

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Comparison of first year of life acute otitis media admissions before and after the 13-valent pneumococcal conjugate vaccine

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Publication date: June 2017
Source:International Journal of Pediatric Otorhinolaryngology, Volume 97
Author(s): Tal Marom, Ofer Israel, Haim Gavriel, Jacob Pitaro, Ali Abo Baker, Ephraim Eviatar
BACKGROUNDAcute otitis media (AOM) is a common childhood infection, which is usually managed in the outpatient setting. Yet, the more severe cases are referred for inpatient treatment. We hypothesized that pneumococcal conjugate vaccines (PCVs), administered during the first year of life, would decrease AOM admissions rate in this age group. We studied the characteristics of infants admitted with AOM and acute mastoiditis (AM) in the PCV13 era, routinely given from November 2010 to all infants.METHODSCharts of infants ≤1 year that were hospitalized during 1/1/2010–31/12/2015 with AOM, with or without AM, were retrieved using hospitalization codes. We compared 2010–11 (transition years, from PCV7 to PCV13) to 2012–15 (post-PCV13 marketing years).RESULTSAOM was the primary/secondary discharge diagnosis in ∼4% of all admitted infants ≤1 year. Boys had more admissions than girls (62% vs 38%). Accuracy of AOM diagnoses substantially increased in the post-marketing years. The average hospitalization duration slightly shortened, from 3.21 (2010–11) to 2.99 days (2012–15) (p = 0.52). Despite considerably modest pre-admission antibiotic treatment rate (<30%), AM was infrequent (∼3.4% of AOM admissions). Amoxicillin was the most common antibiotic therapy given before admission and during hospitalization. The number of myringotomies, usually reserved for treatment failure cases, significantly declined, and there were almost no cases of resistant bacteria. Respiratory syncytial virus was detected in ∼20% of collected respiratory samples, and influenza A/B viruses in ∼8%.CONCLUSIONSAOM is still a major cause for hospitalization of infants in the PCV13 era. Yet, complications are infrequent, and AM rate is low.



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Linguistic Landscapes



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Modelling and sensitivity analysis of urinary platinum excretion in anticancer chemotherapy for the recovery of platinum

Platinum (Pt) based antineoplastics are important in cancer therapy. To date the Pt which is urinary excreted by the patients ends up in wastewater. This is disadvantageous from both an economic as from an ecological point of view because Pt is a valuable material and the excretion products are toxic for aquatic organisms. Therefore, efforts should be made to recover the Pt. The urinary excretion of Pt from two antineoplastics are taken under consideration, i.e. cisplatin and carboplatin. Using these reference compounds, a scenario analysis based on administration statistics from Ghent University Hospital in combination with compartmental models for urinary Pt excretion was performed to simulate the average Pt excretion profile during common treatment schemes. These average profiles can be used to assess the technical, social and economic feasibility of Ptrecovery from urine or wastewater. A one-compartment model is used for cisplatin, which is calibrated using the experimental data of six patients. In contrast, a two-compartment model with parameters from literature is used for carboplatin. A Global Sensitivity Analysis revealed kel, the rate constant of elimination, is the most sensitive parameter in the one-compartment model whereas Qu, the urine production rate, was the most sensitive in the two-compartment model for the Pt concentration Cu in urine and the excreted mass of Pt via urine. A GLUE uncertainty analysis showed that all experimental data are within the 95% uncertainty boundaries.

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The significant expression of TRPV3 in nasal polyps of eosinophilic chronic rhinosinusitis

Publication date: Available online 24 April 2017
Source:Allergology International
Author(s): Takahiro Tokunaga, Takahiro Ninomiya, Yukinori Kato, Yoshimasa Imoto, Masafumi Sakashita, Tetsuji Takabayashi, Emiko Noguchi, Shigeharu Fujieda
BackgroundThe number of patients with eosinophilic chronic rhinosinusitis (ECRS) has been increasing in recent years in Japan. In ECRS, nasal polyps recur immediately after endoscopic sinus surgery. The molecular biological mechanism underlying the refractoriness of ECRS is unclear.MethodsWhole-transcriptome analysis with next-generation sequencing (RNA-seq) was conducted to investigate the molecular biological mechanism of ECRS. Real-time PCR, immunohistochemical staining, and immunofluorescence staining were performed to validate the results of RNA-seq.ResultsRNA-seq analysis revealed that in the nasal polyps of ECRS, the levels of 3 transcripts were elevated significantly and those of 7 transcripts were diminished significantly. Among the genes encoding these transcripts, TRPV3 (transient receptor potential cation channel, subfamily V, member 3) was identified as the only gene that is highly expressed in ECRS nasal polyps but this gene's expression was not previously detected using DNA microarray analysis in peripheral blood eosinophils. TRPV3 is newly identified here as a gene transcribed in ECRS. Our analysis also revealed that TRPV3 was highly expressed in the infiltrating eosinophils and mucosal epithelium of the nasal polyps of ECRS, and further that the more severe the refractoriness was after surgery, the higher the TRPV3 expression was in nasal polyps.ConclusionsTRPV3 might play a role in the refractoriness of ECRS. Additional studies are required to evaluate the function of TRPV3 in ECRS.



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New tumor entities in the 4th edition of the World Health Organization classification of head and neck tumors: Nasal cavity, paranasal sinuses and skull base

Abstract

The World Health Organization recently published the 4th edition of the Classification of Head and Neck Tumors, including several new entities, emerging entities, and significant updates to the classification and characterization of tumor and tumor-like lesions, specifically as it relates to nasal cavity, paranasal sinuses, and skull base in this overview. Of note, three new entities (NUT carcinoma, seromucinous hamartoma, biphenotypic sinonasal sarcoma,) were added to this section, while emerging entities (SMARCB1-deficient carcinoma and HPV-related carcinoma with adenoid cystic-like features) and several tumor-like entities (respiratory epithelial adenomatoid hamartoma, chondromesenchymal hamartoma) were included as provisional diagnoses or discussed in the setting of the differential diagnosis. The sinonasal tract houses a significant diversity of entities, but interestingly, the total number of entities has been significantly reduced by excluding tumor types if they did not occur exclusively or predominantly at this site or if they are discussed in detail elsewhere in the book. Refinements to nomenclature and criteria were provided to sinonasal papilloma, borderline soft tissue tumors, and neuroendocrine neoplasms. Overall, the new WHO classification reflects the state of current understanding for many relatively rare neoplasms, with this article highlighting the most significant changes.



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