Αρχειοθήκη ιστολογίου

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Κυριακή 22 Νοεμβρίου 2015

Sensors, Vol. 15, Pages 29478-29510: TF4SM: A Framework for Developing Traceability Solutions in Small Manufacturing Companies

Nowadays, manufacturing processes have become highly complex. Besides, more and more, governmental institutions require companies to implement systems to trace a product's life (especially for foods, clinical materials or similar items). In this paper, we propose a new framework, based on cyber-physical systems, for developing traceability systems in small manufacturing companies (which because of their size cannot implement other commercial products). We propose a general theoretical framework, study the requirements of these companies in relation to traceability systems, propose a reference architecture based on both previous elements and build the first minimum functional prototype, to compare our solution to a traditional tag-based traceability system. Results show that our system reduces the number of inefficiencies and reaction time.

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Topic shift impairs pronoun resolution during sentence comprehension: Evidence from event-related potentials

Abstract

This study investigated how topic shift and topic continuation influence pronoun interpretation in Chinese. ERPs recorded on pronouns in topic structure showed stronger and earlier late positive responses (P600) for the topic-shift than for the topic-continuation conditions. However, in nontopic structure where the subject (denoting only subjecthood), rather than the topic (denoting both topichood and subjecthood), acted as the antecedent of the pronoun, almost indistinguishable P600 responses were obtained on the pronoun regardless of whether it was referring to the subject (i.e., subject continuation) or the object (i.e., subject shift). Moreover, stronger and earlier P600 responses were elicited by pronouns in the topic-shift than in the subject-shift conditions, although there was no difference between the topic-continuation and the subject-continuation conditions. These findings suggest that topic shift results in greater difficulty in the resolution stage of referential processing, although the bonding process is not sensitive to the manipulation of topic status, and that topic has a privileged cognitive status relative to other nontopic entities (e.g., subject) in real-time language processing.



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Epigarcinol and isogarcinol isolated from the root of Garcinia ovalifolia induce apoptosis of human promyelocytic leukemia (HL-60 cells)

Background: Plants from garcinia genus have been used for centuries against several diseases.ObjectiveThis study aimed to investigate the mechanism of apoptosis induced by epigarcinol and isogarcinol isolated from the root of Garcinia ovalifolia (Clusiaceae) on human promyelocytic leukemia (HL-60 cells). Methods: Epigarcinol and isogarcinol were isolated from the root of G. ovalifolia by using column chromatography method. The antiproliferative property of these molecules and fractions were assessed with 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. The light fluorescence microscope was utilized to observe the morphological changes of HL-60 cells after 24 h treatment. Early apoptosis and cell cycle distribution were analyzed by using flow cytometry (FCM). Results: The results showed that epigarcinol and isogarcinol inhibited the proliferation of HL-60 and PC-3 cells in a concentration-dependent manner with IC 50 varying between 4 and 76 µg/mL depending on the cell line and the molecule. The apoptosis rate and the number of apoptotic cells significantly increased with the augmentation of the concentration of the molecules. The results of flow cytometry (FCM) indicated that epigarcinol and isogarcinol induced significant G 2 /S arrest of HL-60 cells, the disruption of mitochondrial membrane potential and reactive oxygen species (ROS) generation. Conclusion: These results indicated that epigarcinol and isogarcinol demonstrated in vitro antiproliferative properties and induce apoptosis of HL-60 cells which is related to the G 2 /S arrest, and it exerts its apoptotic effect through the loosing of mitochondrial membrane potential.

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Parental knowledge and practices on infant teething, Taif, Saudi Arabia

Background: Parents' false beliefs about signs and symptoms associated with teething have been documented in many studies around the world. This study was conducted to assess parental knowledge on infant teething process and to investigate parents' practices used to alleviate teething disturbances. Methods: A cross-sectional survey was conducted among parents of children of 6 months–5 years old in Taif, Saudi Arabia during April 2013. Convenience method of sampling was adopted and the data was collected by mean of a structured-questionnaire. Data was processed by SPPS. Logistic regression analysis was performed. P value <0.05 was considered statistically significant. Results: Overall, of 493 participants were included in the final analysis with mean age 35 years. Females constituted more than two-third. All the parents attributed one or more of the listed signs and symptoms to teething process. Desire to bite, fever, gum irritation, increased salivation and diarrhea were the most reported signs and symptoms of teething by 459 (93.1 %), 429 (87 %), 415 (84.2 %), 414 (84 %) and 409 (83 %) of the parents respectively. The only predictor of ascribing fever as a sign of infant teething was female gender (P = 0.001). However, female gender (P < 0.001), residence (P = 0.039) and educational level (P = 0.006) were found to be significantly associated with ascribing diarrhea as one of the teething symptoms. Only 91 (18.5 %) of the parents responded correctly to all questions designed to assess their knowledge on teething process. Conclusions: Wide gaps in parents' knowledge and practices related infant teething was identified. Educational interventions are needed to upgrade parents' knowledge and improve their practices regarding infant teething process.

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Ageing and gastrointestinal sensory function: Altered colonic mechanosensory and chemosensory function in the aged mouse

Abstract

Ageing has a profound effect upon gastrointestinal function through mechanisms that are poorly understood. Here we investigated the effect of age upon gastrointestinal sensory signalling pathways in order to address the mechanisms underlying these changes. In-vitro mouse colonic and jejunal preparations with attached splanchnic and mesenteric nerves were used to study mechanosensory and chemosensory afferent function in 3, 12 and 24 month old C57BL/6 animals. Quantitative RT-PCR was used to investigate mRNA expression in colonic tissue and dorsal root ganglion (DRG) cells isolated from 3 and 24 month animals, and immunohistochemistry was used to quantify the number of 5-HT expressing EC cells. Colonic and jejunal afferent mechanosensory function were attenuated with age and these effects appeared earlier in the colon compared to the jejunum. Colonic age-related loss of mechanosensory function was more pronounced in high threshold afferents compared to low threshold afferents. Chemosensory function was attenuated in the 24 month colon affecting TRPV1 and serotonergic signalling pathways. High threshold mechanosensory afferent fibres and small diameter DRG neurons possessed lower functional TRPV1 receptor responses, which occurred without a change in TRPV1 mRNA expression. Serotonergic signalling was attenuated at 24 months, but TPH1 and TPH2 mRNA expression was elevated in colonic tissue. In conclusion, we saw an age-associated decrease in afferent mechanosensitivity in the mouse colon affecting HT units. These units have the capacity to sensitise in response to injurious events, and their loss in ageing may predispose the elderly to lower awareness of GI injury or disease.

This article is protected by copyright. All rights reserved



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Development of an American Version of the Nottingham Sensory Assessment

Publication date: December 2015
Source:Archives of Physical Medicine and Rehabilitation, Volume 96, Issue 12
Author(s): Amy Kaestner, Rebecca E. Miller, Susan Dale Doyle




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A Partnership Between a Service Provider and Academic Institution to Support Early Career Researchers

Publication date: December 2015
Source:Archives of Physical Medicine and Rehabilitation, Volume 96, Issue 12
Author(s): Emily Joan Nalder, Andria Spindel, Morris (Mickey) Milner, Deborah Pal, Jerry Lucas, Susan Rappolt




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Editorial Board

Publication date: December 2015
Source:Archives of Physical Medicine and Rehabilitation, Volume 96, Issue 12





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Pre-Screening for Distress in Patients Prior to Undergoing Allogeneic or Autologous Bone Marrow Transplantation

Publication date: December 2015
Source:Archives of Physical Medicine and Rehabilitation, Volume 96, Issue 12
Author(s): Sean Smith, Mary Elizabeth Hobson, Andrew J. Haig




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Table of Contents

Publication date: December 2015
Source:Archives of Physical Medicine and Rehabilitation, Volume 96, Issue 12





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Editors' Selections From This Issue: Volume 96 / Number 12 / December 2015

Publication date: December 2015
Source:Archives of Physical Medicine and Rehabilitation, Volume 96, Issue 12





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WITHDRAWN

Publication date: December 2015
Source:Archives of Physical Medicine and Rehabilitation, Volume 96, Issue 12





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Clinical Trial Registration: The Time Has Come…

Publication date: December 2015
Source:Archives of Physical Medicine and Rehabilitation, Volume 96, Issue 12
Author(s): Leighton Chan, Allen W. Heinemann




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Cerebral Palsy: Association of Cranial Magnetic Resonance Imaging with Clinical Levels of Disease

Publication date: December 2015
Source:Archives of Physical Medicine and Rehabilitation, Volume 96, Issue 12
Author(s): Jorge Rodrigo Vásquez Ríos, Carlos Viñals Labañino, Saul Renan Renan Leon Hernandez, Ana María, Cortés Rubio, Claudia Flores Flores




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Masthead

Publication date: December 2015
Source:Archives of Physical Medicine and Rehabilitation, Volume 96, Issue 12





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The Effect of a Topical Alpha-Agonist on Fecal Incontinence in Spinal Cord Injury Patients

Publication date: December 2015
Source:Archives of Physical Medicine and Rehabilitation, Volume 96, Issue 12
Author(s): Nir Barak




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TUG and 2MWT: Important Functional Outcome Measures for Acute Rehabilitation and the Post-op Cardiac Population

Publication date: December 2015
Source:Archives of Physical Medicine and Rehabilitation, Volume 96, Issue 12
Author(s): Kimberly P. Hreha, Lindsay Ashmont




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Laryngectomees Experiences in the Health Care System: Assessment of Education, Counseling and Provider Knowledge

Publication date: December 2015
Source:Archives of Physical Medicine and Rehabilitation, Volume 96, Issue 12
Author(s): Miriam Carroll-Alfano




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Concussion Symptoms in Adolescents Are Alleviated Through Use of a Gamified Health App

Publication date: December 2015
Source:Archives of Physical Medicine and Rehabilitation, Volume 96, Issue 12
Author(s): Lise Worthen-Chaudhari, Kelsey Logan, Jane McGonigal, Keith Yeates, W. Jerry Mysiw




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Impact of Coping Skills Intervention Group for Patients with Acquired Brain Injury and Their Caregivers

Publication date: December 2015
Source:Archives of Physical Medicine and Rehabilitation, Volume 96, Issue 12
Author(s): Thomas F. Bergquist, Danielle Klunk, Kamini Krishnan, Anita Milburn, Jeffrey Smigielski




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Understanding the Nature of Home Exercise Programs for Persons with Neurological Disorders

Publication date: December 2015
Source:Archives of Physical Medicine and Rehabilitation, Volume 96, Issue 12
Author(s): Rachel Proffitt




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Archives Manuscript Reviewers

Publication date: December 2015
Source:Archives of Physical Medicine and Rehabilitation, Volume 96, Issue 12





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2015 ACRM Annual Conference Late-Breaking Research Abstracts

Publication date: December 2015
Source:Archives of Physical Medicine and Rehabilitation, Volume 96, Issue 12





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Integration of Clinical and Research Neuroimaging to Understand Traumatic Brain Injury in Veterans and Civilians

Publication date: December 2015
Source:Archives of Physical Medicine and Rehabilitation, Volume 96, Issue 12
Author(s): Maheen Adamson, Keith Main, Stephanie Kolakowsky-Hayner




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Breast Cancer Survivors Self-Reported Symptoms and Limitations in Activities and Participation: Outcomes of Prospective Surveillance

Publication date: December 2015
Source:Archives of Physical Medicine and Rehabilitation, Volume 96, Issue 12
Author(s): Shana Harrington, Ellen W. Levy, Lynn H. Gerber, Nicole L. Stout, Lucinda A. Pfalzer




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Hospital-Based Rehabilitation for Recurrent Glioblastoma

You are asked to evaluate a previously healthy 45-year-old man for admission to your hospital-based inpatient rehabilitation unit. He was diagnosed 10 months ago with glioblastoma multiforme (GBM), which presented with gradually increasing right hemiparesis and word-finding difficulty. Initial imaging results indicated a large left temporoparietal mass with significant edema and a slight left to right shift. He was taken to surgery immediately for resection; pathology results confirmed GBM with minimal tumor at the margins.

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Academy News

AAPM&R 2016 dues renewal for associate, fellow, and international members is now open. To renew your membership dues, log in to www.aapmr.org today!

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Innovative Payment and Practice Models

Health care in the United States is in a period of rapid transformation. It is essential that physiatrists understand the changes taking place and establish the important role of our specialty in this new health care system. The foundation of this transformation lies in the pursuit of the Triple Aim, described by Donald Berwick, former administrator of the Centers of Medicare and Medicaid Services (CMS), as "improving the experience of care, improving the health of populations, and reducing the per capita costs of health care" [1].

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Spanish Translated Abstracts



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Isolation of a novel bio-peptide from walnut residual protein inducing apoptosis and autophagy on cancer cells

Background: Walnut is unique because they have a perfect balance of n-6 and n-3 polyunsaturated fatty acids. The increasing market demand of walnut lipids results in the large amount of the oil extraction residue. The walnut residue is rich in nutritional proteins, and the uneconomic use of the by-product discouraged the development of walnut industry. Anticancer peptides have recently received attention as alternative chemotherapeutic agents that overcome the limits of current drugs. The aim of this study was to investigate whether anticancer bioactive peptide is contained in walnut. Methods: Walnut residual protein was hydrolyzed separately by five different proteases. The sequential purification of the hydrolysates was carried out by ultra-filtration, gel filtration chromatography and RP-HPLC to obtain a cancer cell growth inhibitory peptide. Cell cycle distribution, Annexin V-FITC/PI double staining, TUNEL assay, western blot and immunofluorescence for LC3-II assay were used to detect apoptosis and autophagy on cells. Cytokine production was measured by ELISA kits, macrophage phagocytosis was measured by neutral red uptake assay, nitric oxide production was measured by Griess reagent. Results: The hydrolysates of walnut residual protein produced by papain under the optimal conditions (5 % substrate concentration and an enzyme-substrate ratio of 10 % at temperature 60 C for 3 h), showed significant growth inhibitory activity on MCF-7. The amino acid sequence of the purified peptide was identified as CTLEW with a molecular weight of 651.2795 Da. It is a novel bio-peptide with an amphiphilic structure. CTLEW induced both apoptosis and autophagy on MCF-7 cells, inhibited the cancer cells growth of Caco-2 and HeLa significantly, but did not show any cytotoxic activity against non-cancerous IEC-6 cells. Moreover, the bio-peptide enhanced proliferation and IL-2 secretion of spleen lymphocytes, promoted phagocytosis and NO production of macrophages. Conclusion: These results suggested that a novel bio-peptide, CTLEW inducing apoptosis and autophagy on MCF-7 cells can be released from walnut residual protein through papain hydrolyzing under the certain condition. The bio-peptide shows selective inhibition towards cancer cells growth and immunomodulatory activity.

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Transfusion strategy in hematological intensive care unit: study protocol for a randomized controlled trial

Background: Packed red blood cell (PRBC) transfusion is required in hematology patients treated with chemotherapy for acute leukemia, autologous (auto) or allogeneic (allo) hematopoietic stem cell transplantation (HSCT). In certain situations like septic shock, hip surgery, coronary disease or gastrointestinal hemorrhage, a restrictive transfusion strategy is associated with a reduction of infection and death. A transfusion strategy using a single PRBC unit has been retrospectively investigated and showed a safe reduction of PRBC consumption and costs. We therefore designed a study to prospectively demonstrate that the transfusion of a single PRBC unit is safe and not inferior to standard care. Methods: The 1versus2 trial is a randomized trial which will determine if a single-unit transfusion policy is not inferior to a double-unit transfusion policy. The primary endpoint is the incidence of severe complication (grade ≥ 3) defined as stroke, transient ischemic attack, acute coronary syndrome, heart failure, elevated troponin level, intensive care unit transfer, death, new pulmonary infiltrates, and transfusion-related infections during hospital stays. The secondary endpoint is the number of PRBC units transfused per patient per hospital stay. Two hundred and thirty patients will be randomized to receive a single unit or double unit every time the hemoglobin level is less than 8 g/dL. All patients admitted for induction remission chemotherapy, auto-HSCT or allo-HSCT in hematology intensive care units will be eligible for inclusion. Sample size calculation has determined that a patient population of 230 will be required to prove that the 1-unit PRBC strategy is non-inferior to the 2-unit PRBC strategy. Hemoglobin threshold for transfusion is below 8 g/dL. Estimated percentage of complication-free hospital stays is 93 %. In a non-inferiority hypothesis, the number of patients to include is 230 with a power of 90 % and an alpha risk of 5 %.Trial Registration14–128; Clinicaltrials.gov NCT02461264 (registered on 3 June 2015)

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Measuring DDLS in preperimetric glaucoma

Pahlitzsch M, Torun N, Erb C, Bruenner J, Maier AK, Gonnermann J, Bertelmann E, Klamann MKJ

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Geographic atrophy

Danis RP, Lavine JA, Domalpally A

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Cercopithecoid humeri from Taung support the distinction of major papionin clades in the South African fossil record

Publication date: January 2016
Source:Journal of Human Evolution, Volume 90
Author(s): Christopher C. Gilbert, Maressa Q. Takahashi, Eric Delson
Associated cercopithecoid postcrania are rare in the Plio-Pleistocene fossil record, particularly in the case of South African karst cave sites. However, as clear postcranial differences between major papionin clades have been documented, it should be possible to assign isolated papionin postcrania to the Cercocebus/Mandrillus and Papio/Lophocebus/Theropithecus groups wherever sufficient anatomy is preserved. Here, we demonstrate that two partial humeri preserved at Taung, UCMP 56693 and UCMP 125898, are most likely attributable to the Cercocebus/Mandrillus and Papio/Lophocebus/Theropithecus clades, respectively. Univariate analyses (ANOVAs and t-tests) and multivariate analyses (discriminant function analyses) of humeral features, combined with a phylogenetic analysis of 24 humeral characters, all support our assessment. Given that the overwhelming number of craniodental specimens at Taung are attributable to two papionin taxa, Procercocebus antiquus (a member of the Cercocebus/Mandrillus clade) and Papio izodi (a purported fossil species of the modern genus Papio), we assign UCMP 56693 to Pr. antiquus and UCMP 125868 to P. izodi with a high degree of confidence. Implications for cercopithecoid evolution and biogeography are discussed, with a particular emphasis on these two fossil taxa.



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Identification of genes associated with melanoma metastasis

Publication date: Available online 21 November 2015
Source:The Kaohsiung Journal of Medical Sciences
Author(s): Tao Qiu, Hongyi Wang, Yang Wang, Yu Zhang, Qiang Hui, Kai Tao
The aims of the study were to identify the differentially expressed genes (DEGs) between primary melanomas and metastasis melanomas (MMs), and to investigate the mechanisms of MMs. The microarray data GSE8401 including 31 primary melanomas and 52 MMs were downloaded from Gene Expression Omnibus. DEGs were identified using the Linear Models for Microarray Data package. The functional and pathway enrichment analyses were performed for DEGs. Identification of transcription factors, tumor-associated genes (TAGs), and tumor suppressor genes (TSGs) were performed with the TRANSFAC, TAG, and TSGene databases, respectively. A protein–protein interaction network was constructed using Search Tool for the Retrieval of Interacting Genes. The modules construction and analysis was performed using Molecular Complex Detection and Gene Cluster with Literature Profiles, respectively. In total, 1004 upregulated and 1008 downregulated DEGs were identified. The upregulated DEGs, such as CDK1, BRCA1, MAD2L1, and PCNA, were significantly enriched in cell cycles, DNA replication, and mismatch repair. The downregulated DEGs, such as COLIAL, COL4A5, COL18A1, and LAMC2, were enriched in cell adhesion and extracellular matrix-receptor interaction. BRCA1 was identified as a transcription factor and TSG, and COL18A1 and LAMC2 were identified as a TSG and TAG, respectively. The upregulated DEGs had higher degrees in the protein–protein interaction network and module, such as PCNA, CDK1, and MAD2L1, and the heat map showed they were clustered in the functions of cell cycle and division. These results may demonstrate the potential roles of DEGs such as CDK1, BRCA1, COL18A1, and LAMC2 in the mechanism of MM.



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Isolation and Compositional Analysis of Plant Cuticle Lipid Polyester Monomers

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Lipid polyesters constitute the structural components of two cell wall modifications, the plant cuticle and suberin-containing diffusion barriers. In this video, we describe a method to depolymerize cutin from whole delipidated leaves. The method can be applied to investigating mutants compromised in either cutin or suberin biosynthesis.

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Highlights from Gastro Update Europe: Budapest, June 12–13, 2015

Publication date: Available online 21 November 2015
Source:Arab Journal of Gastroenterology
Author(s): Guido N.J. Tytgat




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Quadruple therapy versus standard triple therapy for eradication of Helicobacter pylori in Kuwait

Publication date: Available online 21 November 2015
Source:Arab Journal of Gastroenterology
Author(s): Mohamed Alboraie, Motaz Saad, Jaber Al-Ali, Mohammad Malik, Noha Asem, Imre Schmidt, Ahmad A. Alfadhli
Background and study aimsChronic infection caused by Helicobacter pylori (H. pylori) is associated with chronic gastritis, peptic ulcer disease, and gastric cancer. Eradication of H. pylori reduces morbidity of chronic gastritis and incidence of gastric cancer in high-risk population. We aimed at testing the efficacy of clarithromycin-based triple therapy and bismuth-based quadruple therapy for eradicating H. pylori in patients with chronic gastritis in Kuwait.Patients and methodsA total of 218 dyspeptic patients from different countries who were proved to have chronic gastritis by endoscopy and gastric biopsy were enroled. All of them were naïve to H. pylori eradication therapy. They were randomised into two groups: group A, received triple therapy (omeprazole, amoxicillin, and clarithromycin) for 10days; and group B, received quadruple therapy (omeprazole, bismuth subcitrate potassium, tetracycline, and metronidazole) for 10days. All patients were tested for eradication of H. pylori by carbon-13 urea breath test 4weeks after treatment.ResultsTotal response rate of eradication therapy in both groups was 77.5% (n=169). However, group B (n=100) had a higher eradication rate (88%) than group A (n=118) (68.6%). H. pylori eradication rate was significantly higher in males (84.2%) than females (70.2%) in both groups (p<0.01). There were no differences in eradication rates with regard to median age or nationality.ConclusionBismuth-based quadruple therapy is more effective as a first-line therapy than clarithromycin-based triple therapy for eradicating H. pylori in patients with H. pylori-related chronic gastritis in Kuwait.



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Switches of stimulus tagging frequencies interact with the conflict-driven control of selective attention, but not with inhibitory control

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Publication date: Available online 22 November 2015
Source:International Journal of Psychophysiology
Author(s): Stefan Scherbaum, Simon Frisch, Maja Dshemuchadse
Selective attention and its adaptation by cognitive control processes are considered a core aspect of goal-directed action. Often, selective attention is studied behaviorally with conflict tasks, but an emerging neuroscientific method for the study of selective attention is EEG frequency tagging. It applies different flicker frequencies to the stimuli of interest eliciting steady state visual evoked potentials (SSVEPs) in the EEG. These oscillating SSVEPs in the EEG allow tracing the allocation of selective attention to each tagged stimulus continuously over time. The present behavioral investigation points to an important caveat of using tagging frequencies: The flicker of stimuli not only produces a useful neuroscientific marker of selective attention, but interacts with the adaptation of selective attention itself. Our results indicate that RT patterns of adaptation after response conflict (so-called conflict adaptation) are reversed when flicker frequencies switch at once. However, this effect of frequency switches is specific to the adaptation by conflict-driven control processes, since we find no effects of frequency switches on inhibitory control processes after no-go trials. We discuss the theoretical implications of this finding and propose precautions that should be taken into account when studying conflict adaptation using frequency tagging in order to control for the described confounds.



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Controversies in Pediatric Perioperative Airways

Pediatric airway management is a challenge in routine anesthesia practice. Any airway-related complication due to improper procedure can have catastrophic consequences in pediatric patients. The authors reviewed the current relevant literature using the following data bases: Google Scholar, PubMed, Medline (OVID SP), and Dynamed, and the following keywords: Airway/s, Children, Pediatric, Difficult Airways, and Controversies. From a summary of the data, we identified several controversies: difficult airway prediction, difficult airway management, cuffed versus uncuffed endotracheal tubes for securing pediatric airways, rapid sequence induction (RSI), laryngeal mask versus endotracheal tube, and extubation timing. The data show that pediatric anesthesia practice in perioperative airway management is currently lacking the strong evidence-based medicine (EBM) data that is available for adult subpopulations. A number of procedural steps in airway management are derived only from adult populations. However, the objective is the same irrespective of patient age: proper securing of the airway and oxygenation of the patient.

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Effects of Shared Electronic Health Record Systems on Drug-Drug Interaction and Duplication Warning Detection

Shared electronic health records (EHRs) systems can offer a complete medication overview of the prescriptions of different health care providers. We use health claims data of more than 1 million Austrians in 2006 and 2007 with 27 million prescriptions to estimate the effect of shared EHR systems on drug-drug interaction (DDI) and duplication warnings detection and prevention. The Austria Codex and the ATC/DDD information were used as a knowledge base to detect possible DDIs. DDIs are categorized as severe, moderate, and minor interactions. In comparison to the current situation where only DDIs between drugs issued by a single health care provider can be checked, the number of warnings increases significantly if all drugs of a patient are checked: severe DDI warnings would be detected for 20% more persons, and the number of severe DDI warnings and duplication warnings would increase by 17%. We show that not only do shared EHR systems help to detect more patients with warnings but DDIs are also detected more frequently. Patient safety can be increased using shared EHR systems.

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Comment on “Simulating Radiotherapy Effect in High-Grade Glioma by Using Diffusive Modeling and Brain Atlases”



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The Activation of Nrf2 and Its Downstream Regulated Genes Mediates the Antioxidative Activities of Xueshuan Xinmaining Tablet in Human Umbilical Vein Endothelial Cells

Epidemiological studies have verified the critical role that antioxidative stress plays in protecting vascular endothelial cells. The aims of the present study were to investigate the antioxidative activities and differential regulation of nuclear erythroid-related factor 2- (Nrf2-) mediated gene expression by Xueshuan Xinmaining Tablet (XXT), a traditional Chinese medicine with the effect of treating cardiovascular diseases. The antioxidative activities of XXT were investigated using quantitative real-time PCR (qPCR), a PCR array, and western blotting. Our results indicated that XXT exhibited potent antioxidative activities by suppressing the levels of hydrogen peroxide- (H2O2-) induced reactive oxygen species (ROS) in human umbilical vein endothelial cells (HUVECs). We were also conscious of strong Nrf2-mediated antioxidant induction. XXT enhanced the expressions of Keap1, Nrf2, and Nrf2-mediated genes, such as glutamate-cysteine ligase modifier subunit (GCLM), NAD(P)H: quinine oxidoreductase 1 (NQO1), heme oxygenase 1 (HMOX1), and glutathione peroxidase (GPX) in HUVECs. In summary, XXT strongly activated Nrf2 and its downstream regulated genes, which may contribute to the antioxidative and vascular endothelial cell protective activities of XXT.

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The Composition, Antioxidant and Antibacterial Activities of Cold-Pressed and Distilled Essential Oils of Citrus paradisi and Citrus grandis (L.) Osbeck

The chemical composition and functional activities of cold-pressed and water distilled peel essential oils of Citrus paradisi (C. paradisi) and Citrus grandis (L.) Osbeck (C. grandis) were investigated in present study. Yields of cold-pressed oils were much higher than those of distilled oils. Limonene was the primary ingredient of essential oils of C. paradisi (cold 92.83%; distilled 96.06%) and C. grandis (cold 32.63%; distilled 55.74%). In addition, C. grandis oils obtained were rich in oxygenated or nitrogenated compounds which may be involved in reducing cardiovascular diseases or enhancing sleep effectiveness. The order of free radical scavenging activities of 4 citrus oils was distilled C. paradisi oil > cold-pressed C. paradisi oil > distilled C. grandis oil > cold-pressed C. grandis oil. Cold-pressed C. grandis oil exhibited the lowest activity in all antioxidative assays. The order of antimicrobial activities of 4 citrus oils was distilled C. grandis oil, cold-pressed C. paradisi oil > distilled C. paradisi oil > cold-pressed C. paradisi oil. Surprisingly, distilled C. grandis oil exhibited better antimicrobial activities than distilled C. paradisi oil, especially against Escherichia coli and Salmonella enterica subsp. The results also indicated that the antimicrobial activities of essential oils may not relate to their antioxidative activities.

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What is left of adaptive servo-ventilation after the results of the SERVE-HF study?

Publication date: Available online 21 November 2015
Source:Revue des Maladies Respiratoires
Author(s): J.-C. Meurice




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Implémentation d’un programme de soins oncologiques en consultation multidisciplinaire

Publication date: Available online 21 November 2015
Source:Revue des Maladies Respiratoires
Author(s): J.-P. Sculier, N. Leclercq, A.-P. Meert, M. Paesmans, T. Berghmans
IntroductionOn manque d'études sur la mise en pratique des recommandations de pratique clinique (RPC) en oncologie thoracique.MéthodesLes dossiers des 354 patients avec cancer bronchique non encore traité entre janvier 2009 et décembre 2012 ont été revus. Tout nouveau traitement devrait être proposé en consultation multidisciplinaire (CMD) sur base d'un programme de soins oncologiques (PSO) fondé sur nos RPC.RésultatsOn a 636 CMD (332, 176, 81 et 47 en 1re, 2e, 3e et suivantes lignes). Le taux de CMD en 1re ligne a été de 94 % avec 88 % et 75 % en conformité avec le PSO et les RPC. En 2e et 3e lignes, les taux sont de 93 et 92 % (CMD), 90 et 89 % (PSO), 56 et 63 % (RPC). En 1re ligne, les principales causes de non-application ont été, pour le PSO, le refus du patient ou un autre choix par le médecin et pour les RPC le manque de recommandations adéquates pour des situations spécifiques ou l'apparition de nouveaux traitements.ConclusionLa plupart des patients fait l'objet d'une CMD avec bonne application du PSO. Les RPC doivent être rapidement mises à jour pour incorporer les nouveaux traitements.IntroductionA working group has highlighted guidelines in thoracic oncology in Europe without study of their implementation, due to a lack of data.MethodsThe records of 354 untreated lung cancer patients seen between January 2009 and December 2012 were reviewed. Any new treatment should have been proposed by a multidisciplinary consultation (MDC) in accordance with an oncology care program (OCP) based on the European Lung Cancer Working Party guidelines.ResultsFor the 354 patients, there were 636 MDC (332, 176, 81 and 47 in 1st, 2nd, 3rd and subsequent lines). For the first line, the MDC rate was 88%, in accordance with the OCP, and 75% of treatments were in agreement with the guidelines. For the 2nd and 3rd lines, the rates were 93% and 92% respectively (MDC), 90 and 89% (OCP), 55 and 63% (guidelines). In the first line, the main causes of non-compliance with the OCP were patient's refusal or doctor's choice and with guidelines a lack of adequate recommendations for specific situations such as comorbidities or the appearance of new treatments.ConclusionThe vast majority of patients are the subject of a MDC with a high rate of application of OCP. Guidelines should be updated regularly to incorporate new treatments.



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Adaptive servo-ventilation: How does it fit into the treatment of central sleep apnoea syndrome? Expert opinions

Publication date: Available online 21 November 2015
Source:Revue des Maladies Respiratoires
Author(s): P. Priou, M.-P. d'Ortho, T. Damy, J.-M. Davy, F. Gagnadoux, T. Gentina, J.-C. Meurice, J.-L. Pepin, R. Tamisier, C. Philippe
The preliminary results of the SERVE-HF study have led to the release of safety information with subsequent contraindication to the use of adaptive servo-ventilation (ASV) for the treatment of central sleep apnoeas in patients with chronic symptomatic systolic heart failure with left ventricular ejection fraction (LVEF) ≤ 45%. The aim of this article is to review these results, and to provide more detailed arguments based on data from the literature advocating the continued use of ASV in different indications, including heart failure with preserved LVEF, complex sleep apnoea syndrome, opioid-induced central sleep apnea syndrome, idiopathic central SAS, and central SAS due to a stroke. Based on these findings, we propose to set up registers dedicated to patients in whom ASV has been stopped and in the context of the next setting up of ASV in these specific indications to ensure patient safety and allow reasoned decisions on the use of ASV.



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On- and off-shell Jost functions and their integral representations

Abstract

By judicious exploitation of the transpose operator relation in conjunction with the differential equations of special functions of mathematical physics, integral representations of the on- and off-shell Jost functions are derived from the particular integrals of the inhomogeneous Schrödinger equation. Using the particular integral of the inhomogeneous Schrödinger equation, exact analytical expressions for the Coulomb and Coulomb plus Yamaguchi off-shell Jost solutions are constructed in the maximal reduced form. As a case study, the limiting behaviours and the on-shell discontinuities of the Coulomb plus Yamaguchi Jost solutions are verified numerically.



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Transformation of bipartite non-maximally entangled states into a tripartite W state in cavity QED

Abstract

We present two schemes for transforming bipartite non-maximally entangled states into a W state in cavity QED system, by using highly detuned interactions and the resonant interactions between two-level atoms and a single-mode cavity field. A tri-atom W state can be generated by adjusting the interaction times between atoms and the cavity mode. These schemes demonstrate that two bipartite non-maximally entangled states can be merged into a maximally entangled W state. So the scheme can, in some sense, be regarded as an entanglement concentration process. The experimental feasibility of the schemes is also discussed.



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An Empirical Analysis of Moscovitch's Reconceptualised Model of Social Anxiety: How is it Different from Fear of Negative Evaluation?

Publication date: Available online 22 November 2015
Source:Journal of Anxiety Disorders
Author(s): Isilay N. Kizilcik, Bree Gregory, Andrew J. Baillie, Erica Crome
Cognitive-behavioural models propose that excessive fear of negative evaluation is central to social anxiety. Moscovitch (2009) instead proposes that perceived deficiencies in three self attributes: fears of showing signs of anxiety, deficits in physical appearance, or deficits in social competence are at the core of social anxiety. However, these attributes are likely to overlap with fear of negative evaluation. Responses to an online survey of 286 participants with a range of social anxiety severity were analysed using hierarchical multiple regression to identify the overall unique predictive value of Moscovitch's model. Altogether, Moscovitch's model provided improvements in the prediction of safety behaviours, types of fears and cognitions; however only the fear of showing anxiety subscale provided unique information. This research supports further investigations into the utility of this revised model, particularly related to utility of explicitly assessing and addressing fears of showing anxiety.



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Theory of mind in social anxiety disorder, depression, and comorbid conditions

Publication date: Available online 22 November 2015
Source:Journal of Anxiety Disorders
Author(s): Dustin Washburn, Gillian Wilson, Meighen Roes, Katerina Rnic, Kate Leslie Harkness
Social anxiety disorder is characterized by marked interpersonal impairment, particularly when presenting with comorbid major depression. However, the foundational social-cognitive skills that underlie interpersonal impairment in comorbid and non-comorbid manifestations of SAD has to date received very little empirical investigation. In a sample of 119 young adults, the current study examined differences in theory of mind (ToM), defined as the ability to decode and reason about others' mental states, across four groups: (a) non-comorbid SAD; (b) non-comorbid Lifetime MDD; (c) comorbid SAD and Lifetime MDD; and (d) healthy control. The non-comorbid SAD group was significantly less accurate at decoding mental states than the non-comorbid MDD and control groups. Further, both the comorbid and non-comorbid SAD groups made significantly more 'excessive' ToM reasoning errors than the non-comorbid MDD group, suggesting a pattern of over-mentalizing. Findings are discussed in terms of their implications for understanding the social cognitive foundations of social anxiety.



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Luteolin Exerts Cardioprotective Effects through Improving Sarcoplasmic Reticulum Ca2+-ATPase Activity in Rats during Ischemia/Reperfusion In Vivo

The flavonoid luteolin exists in many types of fruits, vegetables, and medicinal herbs. Our previous studies have demonstrated that luteolin reduced ischemia/reperfusion (I/R) injury in vitro, which was related with sarcoplasmic reticulum Ca2+-ATPase (SERCA2a) activity. However, the effects of luteolin on SERCA2a activity during I/R in vivo remain unclear. To investigate whether luteolin exerts cardioprotective effects and to monitor changes in SERCA2a expression and activity levels in vivo during I/R, we created a myocardial I/R rat model by ligating the coronary artery. We demonstrated that luteolin could reduce the myocardial infarct size, lactate dehydrogenase release, and apoptosis during I/R injury in vivo. Furthermore, we found that luteolin inhibited the I/R-induced decrease in SERCA2a activity in vivo. However, neither I/R nor luteolin altered SERCA2a expression levels in myocardiocytes. Moreover, the PI3K/Akt signaling pathway played a vital role in this mechanism. In conclusion, the present study has confirmed for the first time that luteolin yields cardioprotective effects against I/R injury by inhibiting the I/R-induced decrease in SERCA2a activity partially via the PI3K/Akt signaling pathway in vivo, independent of SERCA2a protein level regulation. SERCA2a activity presents a novel biomarker to assess the progress of I/R injury in experimental research and clinical applications.

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Microchamber arrays with an integrated long luminescence lifetime pH sensor

Abstract

A pH probe with a microsecond luminescence lifetime was obtained via covalent coupling of 6-carboxynaphthofluorescein (CNF) moieties to ruthenium-tris-(1,10-phenanthroline)2+. The probe was covalently attached to amino-modified poly-(2-hydroxyethyl)methacrylate (pHEMA) and showed a pH-dependent FRET with luminescence lifetimes of 681 to 1260 ns and a working range from ca. pH 6.5 to 9.0 with a pKa of 7.79 ± 0.14. The pH sensor matrix was integrated via spin coating as ca. 1- to 2-μm-thick layer into "CytoCapture" cell culture dishes of 6 mm in diameter. These contained a microcavity array of square-shaped regions of 40 μm length and width and 15 μm depth that was homogeneously coated with the pH sensor matrix. The sensor layer showed fast response times in both directions. A microscopic setup was developed that enabled imaging of the pH inside the microchamber arrays over many hours. As a proof of principle, we monitored the pH of Escherichia coli cell cultures grown in the microchamber arrays. The integrated sensor matrix allowed pH monitoring spatially resolved in every microchamber, and the differences in cell growth between individual chambers could be resolved and quantified.

Graphical abstract

A pH probe with a microsecond luminescence lifetime is described and its covalent attachment to a hydrogel matrix, integration into microchamber arrays, and use for pH monitoring in a model E. coli miniaturized cell culture.


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Ho-Jin Song and Tadao Nagatsuma (Eds.): Handbook of terahertz technologies: devices and applications



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Analytical applications of MIPs in diagnostic assays: future perspectives

Abstract

Many efforts have been made to produce artificial materials with biomimetic properties for applications in binding assays. Among these efforts, the technique of molecular imprinting has received much attention because of the high selectivity obtainable for molecules of interest, robustness of the produced polymers, simple and short synthesis, and excellent cost efficiency. In this review, progress in the field of molecularly imprinted sorbent assays is discussed—with a focus on work conducted from 2005 to date.

Graphical Abstract

A growing trend in recent years has been the use of molecularly imprinted polymers as replacements for antibodies in various assay formats, as indicated by a steady increase in publications in the area (see graph)


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Resveratrol Protects PC12 Cell against 6-OHDA Damage via CXCR4 Signaling Pathway

Resveratrol, herbal nonflavonoid polyphenolic compound naturally derived from grapes, has long been acknowledged to possess extensive biological and pharmacological properties including antioxidant and anti-inflammatory ones and may exert a neuroprotective effect on neuronal damage in neurodegenerative diseases. However, the underlying molecular mechanisms remain undefined. In the present study, we intended to investigate the neuroprotective effects of resveratrol against 6-OHDA-induced neurotoxicity of PC12 cells and further explore the possible mechanisms involved. For this purpose, PC12 cells were exposed to 6-OHDA in the presence of resveratrol (0, 12.5, 25, and 50 μM). The results showed that resveratrol increased cell viability, alleviated the MMP reduction, and reduced the number of apoptotic cells as measured by MTT assay, JC-1 staining, and Hoechst/PI double staining (all ). Immunofluorescent staining and Western blotting revealed that resveratrol averts 6-OHDA induced CXCR4 upregulation (). Our results demonstrated that resveratrol could effectively protect PC12 cells from 6-OHDA-induced oxidative stress and apoptosis via CXCR4 signaling pathway.

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Haemodynamic Effects of Lung Recruitment Manoeuvres

Atelectasis caused by lung injury leads to increased intrapulmonary shunt, venous admixture, and hypoxaemia. Lung recruitment manoeuvres aim to quickly reverse this scenario by applying increased airway pressures for a short period of time which meant to open the collapsed alveoli. Although the procedure can improve oxygenation, but due to the heart-lung and right and left ventricle interactions elevated intrathoracic pressures can inflict serious effects on the cardiovascular system. The purpose of this paper is to give an overview on the pathophysiological background of the heart-lung interactions and the best way to monitor these changes during lung recruitment.

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Study on the Difference of BIS/BAS Scale between Sasang Types

Introduction. The purpose of this study was to examine the differences in temperament between So-Yang (SY) and So-Eum (SE) Sasang types using Behavioral Inhibition System/Behavioral Activation System (BIS/BAS) scale to elucidate the biopsychological mechanism underlying the Sasang typology, a traditional Korean personalized medicine. Methods. 248 university students were categorized into three Sasang types, and series of t-tests were conducted, separately for male and female participants, to examine the difference of Behavioral Inhibition System (BIS), Behavioral Activation System (BAS), BAS-Drive (BAS-D), BAS-Fun Seeking (BAS-FS), and BAS-Reward Responsiveness (BAS-RR) scores between SY and SE Sasang types. Results. There were significant differences between Sasang types in the BIS/BAS subscales with consideration of gender. In male participants, BAS-total score of SY type () was significantly (, ) higher than that of SE type (). On the other hand, in female participants, BIS score of SY type () was significantly (, ) lower than that of SE type (). Discussion. The current study suggested relationship between Sasang typology and Behavior Inhibition and Activation Systems and showed significant differences in BIS/BAS scale between SY and SE Sasang types. Further studies on biological base of Sasang typology are needed.

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The Effect of Dimethyl Sulfoxide on Supercoiled DNA Relaxation Catalyzed by Type I Topoisomerases

The effects of dimethyl sulfoxide (DMSO) on supercoiled plasmid DNA relaxation catalyzed by two typical type I topoisomerases were investigated in our studies. It is shown that DMSO in a low concentration (less than 20%, v/v) can induce a dose-related enhancement of the relaxation efficiency of Escherichia coli topoisomerase I (type IA). Conversely, obvious inhibitory effect on the activity of calf thymus topoisomerase I (type IB) was observed when the same concentration of DMSO is used. In addition, our studies demonstrate that 20% DMSO has an ability to reduce the inhibitory effect on EcTopo I, which was induced by double-stranded oligodeoxyribonucleotides while the same effect cannot be found in the case of CtTopo I. Moreover, our AFM examinations suggested that DMSO can change the conformation of negatively supercoiled plasmid by creating some locally loose regions in DNA molecules. Combining all the lines of evidence, we proposed that DMSO enhanced EcTopo I relaxation activity by (1) increasing the single-stranded DNA regions for the activities of EcTopo I in the early and middle stages of the reaction and (2) preventing the formation of double-stranded DNA-enzyme complex in the later stage, which can elevate the effective concentration of the topoisomerase in the reaction solution.

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Assessment of influenza vaccine effectiveness in a sentinel surveillance network 2010–13, United States

Publication date: Available online 21 November 2015
Source:Vaccine
Author(s): Benjamin J. Cowling, Shuo Feng, Lyn Finelli, Andrea Steffens, Ashley Fowlkes
BackgroundInfluenza vaccines are now widely used to reduce the burden of annual epidemics of influenza virus infections. Influenza vaccine effectiveness (VE) is monitored annually to determine VE against each season's circulating influenza strains in different groups such as children, adults and the elderly. Few prospective surveillance programs are available to evaluate influenza VE against medically attended illness for patients of all ages in the United States.MethodsWe conducted surveillance of patients with acute respiratory illnesses in 101 clinics across the US during three consecutive influenza seasons. We analyzed laboratory testing results for influenza virus, self-reported vaccine history, and patient characteristics, defining cases as patients who tested positive for influenza virus and controls as patients who tested negative for influenza virus. Comparison of influenza vaccination coverage among cases versus controls, adjusted for potential confounders, was used to estimate VE as one minus the adjusted odds ratio multiplied by 100%.ResultsWe included 10,650 patients during three influenza seasons from August 2010 through December 2013, and estimated influenza VE in children 6m–5y of age (58%; 95% CI: 49%–66%), children 6–17y (45%; 95% CI: 34%–53%), adults 18–49y (36%; 95% CI: 24%, 46%), and adults ≥50y (34%, 95% CI: 13%, 51%). VE was higher against influenza A(H1N1) compared to A(H3N2) and B.ConclusionsOur estimates of moderate influenza VE confirm the important role of vaccination in protecting against medically attended influenza virus infection.



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Neutralizing antibody and functional mapping of Bacillus anthracis protective antigen—The first step toward a rationally designed anthrax vaccine

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Publication date: Available online 21 November 2015
Source:Vaccine
Author(s): Ryan C. McComb, Mikhail Martchenko
Anthrax is defined by the Centers for Disease Control and Prevention as a Category A pathogen for its potential use as a bioweapon. Current prevention treatments include Anthrax Vaccine Adsorbed (AVA). AVA is an undefined formulation of Bacillus anthracis culture supernatant adsorbed to aluminum hydroxide. It has an onerous vaccination schedule, is slow and cumbersome to produce and is slightly reactogenic. Next-generation vaccines are focused on producing recombinant forms of anthrax toxin in a well-defined formulation but these vaccines have been shown to lose potency as they are stored. In addition, studies have shown that a proportion of the antibody response against these vaccines is focused on non-functional, non-neutralizing regions of the anthrax toxin while some essential functional regions are shielded from eliciting an antibody response. Rational vaccinology is a developing field that focuses on designing vaccine antigens based on structural information provided by neutralizing antibody epitope mapping, crystal structure analysis, and functional mapping through amino acid mutations. This information provides an opportunity to design antigens that target only functionally important and conserved regions of a pathogen in order to make a more optimal vaccine product. This review provides an overview of the literature related to functional and neutralizing antibody epitope mapping of the Protective Antigen (PA) component of anthrax toxin.



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Arguments and sources on Italian online forums on childhood vaccinations: Results of a content analysis

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Publication date: Available online 21 November 2015
Source:Vaccine
Author(s): Marta Fadda, Ahmed Allam, Peter J. Schulz
BackgroundDespite being committed to the immunization agenda set by the WHO, Italy is currently experiencing decreasing vaccination rates and increasing incidence of vaccine-preventable diseases. Our aim is to analyze Italian online debates on pediatric immunizations through a content analytic approach in order to quantitatively evaluate and summarize users' arguments and information sources.MethodsThreads were extracted from 3 Italian forums. Threads had to include the keyword Vaccin* in the title, focus on childhood vaccination, and include at least 10 posts. They had to have been started between 2008 and June 2014. High inter-coder reliability was achieved. Exploratory analysis using k-means clustering was performed to identify users' posting patterns for arguments about vaccines and sources.ResultsThe analysis included 6544 posts mentioning 6223 arguments about pediatric vaccinations and citing 4067 sources. The analysis of argument posting patterns included users who published a sufficient number of posts; they generated 85% of all arguments on the forum. Dominating patterns of three groups were identified: (1) an anti-vaccination group (n=280) posted arguments against vaccinations, (2) a general pro-vaccination group (n=222) posted substantially diverse arguments supporting vaccination and (3) a safety-focused pro-vaccination group (n=158) mainly forwarded arguments that questioned the negative side effects of vaccination. The anti-vaccination group was shown to be more active than the others. They use multiple sources, own experience and media as their cited sources of information. Medical professionals were among the cited sources of all three groups, suggesting that vaccination-adverse professionals are gaining attention.ConclusionsKnowing which information is shared online on the topic of pediatric vaccinations could shed light on why immunization rates have been decreasing and what strategies would be best suited to address parental concerns. This suggests there is a high need for developing automated approaches to detect misleading or false information on the Internet.



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Annual influenza vaccination reduces total hospitalization in patients with chronic hepatitis B virus infection: A population-based analysis

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Publication date: Available online 21 November 2015
Source:Vaccine
Author(s): Fu-Hsiung Su, Ya-Li Huang, Fung-Chang Sung, Chien-Tien Su, Wen-Hsin Hsu, Shih-Ni Chang, Chih-Ching Yeh
BackgroundThis study evaluated hospitalization and mortality in patients with chronic hepatitis B virus infection (HBV (+)) and matched comparison patients after stratifying the patients according to annual influenza vaccination (Vaccine (+)).MethodsData from Taiwan's National Health Insurance program from 2000 to 2009 were used to identify HBV(+)/vaccine(+) (n=4434), HBV(+)/Vaccine(−) (n=3646), HBV(−)/Vaccine(+) (n=8868), and HBV(−)/Vaccine(−) (n=8868) cohorts. The risk of pneumonia/influenza, respiratory failure, intensive care, hospitalization, and mortality in the four cohorts was evaluated.ResultsThe total hospitalization rate was significantly lower in patients with chronic HBV infection who received an annual influenza vaccination than in chronic HBV-infected patients who did not receive an influenza vaccination (16.29 vs. 24.02 per 100 person-years), contributing to an adjusted hazard ratio (HR) of 0.56 (95% confidence interval (CI)=0.50–0.62). The HBV(+)/Vaccine(+) cohort also had lower risks than the HBV(+)/Vaccine(−) cohort for pneumonia and influenza (adjusted HR=0.79, 95% CI=0.67–0.92), intensive care unit admission (adjusted HR=0.33, 95% CI=0.25–0.43), and mortality (adjusted HR=0.19, 95% CI=0.15–0.24).ConclusionsOur results suggest that annual influenza vaccination can reduce the risk of hospitalization and mortality in patients with chronic HBV infection.



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Estimation of parameters related to vaccine efficacy and dengue transmission from two large phase III studies

Publication date: Available online 21 November 2015
Source:Vaccine
Author(s): Laurent Coudeville, Nicolas Baurin, Elisabeta Vergu
BackgroundA tetravalent dengue vaccine was shown to be efficacious against symptomatic dengue in two phase III efficacy studies performed in five Asian and five Latin American countries. The objective here was to estimate key parameters of a dengue transmission model using the data collected during these studies.MethodsParameter estimation was based on a Sequential Monte Carlo approach and used a cohort version of the transmission model. Serotype-specific basic reproduction numbers were derived for each country. Parameters related to serotype interactions included duration of cross-protection and level of cross-enhancement characterized by differences in symptomaticity for primary, secondary and post-secondary infections. We tested several vaccine efficacy profiles and simulated the evolution of vaccine efficacy over time for the scenarios providing the best fit to the data.ResultsTwo reference scenarios were identified. The first included temporary cross-protection and the second combined cross-protection and cross-enhancement upon wild-type infection and following vaccination. Both scenarios were associated with differences in efficacy by serotype, higher efficacy for pre-exposed subjects and against severe dengue, increase in efficacy with doses for naïve subjects and by a more important waning of vaccine protection for subjects when naïve than when pre-exposed. Over 20 years, the median reduction of dengue risk induced by the direct protection conferred by the vaccine ranged from 24% to 47% according to country for the first scenario and from 34% to 54% for the second.ConclusionOur study is an important first step in deriving a general framework that combines disease dynamics and mechanisms of vaccine protection that could be used to assess the impact of vaccination at a population level.



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Rotavirus – Global research density equalizing mapping and gender analysis

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Publication date: Available online 21 November 2015
Source:Vaccine
Author(s): Corinna Köster, Doris Klingelhöfer, David A. Groneberg, Mario Schwarzer
BackgroundRotaviruses are the leading reason for dehydration and severe diarrheal disease and in infants and young children worldwide. An increasing number of related publications cause a crucial challenge to determine the relevant scientific output. Therefore, scientometric analyses are helpful to evaluate quantity as well as quality of the worldwide research activities on Rotavirus.Up to now, no in-depth global scientometric analysis relating to Rotavirus publications has been carried out. This study used scientometric tools and the method of density equalizing mapping to visualize the differences of the worldwide research effort referring to Rotavirus. The aim of the study was to compare scientific output geographically and over time by using an in-depth data analysis and New quality and quantity indices in science (NewQIS) tools. Furthermore, a gender analysis was part of the data interpretation.MethodsWe retrieved all Rotavirus-related articles, which were published on "Rotavirus" during the time period from 1900 to 2013, from the Web of Science by a defined search term. These items were analyzed regarding quantitative and qualitative aspects, and visualized with the help of bibliometric methods and the technique of density equalizing mapping to show the differences of the worldwide research efforts. This work aimed to extend the current NewQIS platform.ResultsThe 5906 Rotavirus associated articles were published in 138 countries from 1900 to 2013. The USA authored 2037 articles that equaled 34.5% of all published items followed by Japan with 576 articles and the United Kingdom – as the most productive representative of the European countries – with 495 articles. Furthermore, the USA established the most cooperations with other countries and was found to be in the center of an international collaborative network. We performed a gender analysis of authors per country (threshold was set at a publishing output of more than 100 articles by more than 50 authors whose names could be identified in more than 50% of cases) showed a domination of female scientists in Brazil, while in all other countries, male scientists predominate. Relating the number of publications to the population of a country (Q1) and compared to the GPD (Q2), we found that European and African countries as well as Australia and New Zealand – not the USA – were among the top ranked nations.ConclusionRegarding rotavirus-related scientific output, the USA was the overall leading nation when qualitative and qualitative aspects were taken into account. In contrast to these classical scientometric variables, indices such as Q1 and Q2 enable comparability between countries with unequal conditions and scientific infrastructures helping to differentiate publishing quality and quantity in a more relevant way. Also, it was deduced that counties with a high rotavirus-associated child mortality, like the Democratic Republic of Congo, should be integrated into the collaborative efforts more intensively.



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Toxicity assessment of Clostridium difficile toxins in rodent models and protection of vaccination

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Publication date: Available online 21 November 2015
Source:Vaccine
Author(s): Su Wang, Richard R. Rustandi, Catherine Lancaster, Laura G. Hong, David S. Thiriot, Jinfu Xie, Susan Secore, Adam Kristopeit, Sheng-ching Wang, Jon H. Heinrichs
Clostridium difficile is the leading cause of hospital-acquired diarrhea, also known as C. difficile associated diarrhea. The two major toxins, toxin A and toxin B are produced by most C. difficile bacteria, but some strains, such as BI/NAP1/027 isolates, produce a third toxin called binary toxin. The precise biological role of binary toxin is not clear but it has been shown to be a cytotoxin for Vero cells. We evaluated the toxicity of these toxins in mice and hamsters and found that binary toxin causes death in both animals similar to toxins A and B. Furthermore, immunization of mice with mutant toxoids of all three toxins provided protection upon challenge with native toxins. These results support the concept that binary toxin contributes to the pathogenicity of C. difficile and provide a method for monitoring the toxicity of binary toxin components in vaccines.



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Serotypes, antimicrobial susceptibility, and molecular epidemiology of invasive and non-invasive Streptococcus pneumoniae isolates in paediatric patients after the introduction of 13-valent conjugate vaccine in a nationwide surveillance study conducted in Japan in 2012–2014

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Publication date: Available online 19 November 2015
Source:Vaccine
Author(s): Satoshi Nakano, Takao Fujisawa, Yutaka Ito, Bin Chang, Shigeru Suga, Taro Noguchi, Masaki Yamamoto, Yasufumi Matsumura, Miki Nagao, Shunji Takakura, Makoto Ohnishi, Toshiaki Ihara, Satoshi Ichiyama
Pneumococcal infection in children is a major public health problem worldwide, including in Japan. The pneumococcal conjugate vaccine 7 (PCV7) was licensed for use in Japan in 2010 followed by PCV13 in 2013. This report includes the results of a nationwide surveillance of invasive pneumococcal disease (IPD) and non-IPD in paediatric patients from January 2012 to December 2014. We collected 343 isolates from 337 IPD patients and 286 isolates from 278 non-IPD patients. Of the IPD isolates, the most identified serotypes included 19A, 24F, and 15A. The prevalence of non-PCV13 serotype isolates increased significantly from 2012 to 2014 (51.6–71.4%, p=0.004). Serotypes 19A, 15A and 35B were highly non-susceptible to penicillin, and the rates of non-susceptible isolates from IPD patients to penicillin and cefotaxime significantly declined during the study period (p=0.029 and p=0.013, respectively). The non-susceptible rate to meropenem increased, particularly for serotype 15A. The IPD isolates comprised clonal complex (CC) 3111 (93.8% was serotype 19A) followed by CC2572 (81.5% was serotype 24F) and CC63 (97.1% was serotype 15A). CC3111, CC63 and CC156 (33.3% was serotype 23A, 28.6% was serotype 6B, and 14.3% was serotype 19A) were highly non-susceptible to penicillin. Of the non-IPD isolates, the most identified serotypes included 19A, 15A, and 3. In conclusion, the introduction of PCV7 and PCV13 resulted in increasing non-PCV13 serotypes and clones, including antimicrobial resistant serotypes 15A and CC63 (Sweden15A-25 clone).



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An approach to death as an adverse event following immunization

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Publication date: Available online 19 November 2015
Source:Vaccine
Author(s): Michael S. Gold, Madhava Ram Balakrishnan, Ananda Amarasinghe, Noni E. MacDonald
Co-incidental death occurring proximate to vaccination may be reported as an adverse event following immunization. Such events are particularly concerning because they may raise community and health provider concerns about the safety of the specific vaccine and often the immunization programme in general. Coincidental events need to be differentiated from vaccine reactions, such as anaphylaxis, which may very rarely result in death. In 2013, the World Health Organization (WHO) released an updated manual for the Causality Assessment of an AEFI. The purpose of this review is to apply the WHO causality methodology to death when this is reported as an AEFI. The causality assessment scheme recommends a four step process to enable classification of the AEFI and to differentiate events which are causally consistent from those that are inconsistent with immunization. However, for some events causality maybe indeterminate. Consistent causal reactions that may result in death are very rare and maybe related to the vaccine product (e.g. anaphylaxis, viscerotrophic disease), vaccine quality defect (e.g. an incompletely attenuated live vaccine agent) or an immunization error (e.g. vaccine vial contamination). Events that are inconsistent with immunizations are due to co-incidental conditions that may account for infant and childhood mortality. In countries with a high infant mortality rate the coincidental occurrence of death and immunization may occur not infrequently and a robust mechanism to obtain information from autopsy and perform an AEFI investigation and causality assessment is essential. Communication with the community and all stakeholders to maintain confidence in the immunization programme is critical.



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