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Search Results: 1 - 10 of 32440 matches for " John Aaskov "
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Identification of a Cryptic Prokaryotic Promoter within the cDNA Encoding the 5′ End of Dengue Virus RNA Genome
Dongsheng Li,John Aaskov,William B. Lott
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0018197
Abstract: Infectious cDNA clones of RNA viruses are important research tools, but flavivirus cDNA clones have proven difficult to assemble and propagate in bacteria. This has been attributed to genetic instability and/or host cell toxicity, however the mechanism leading to these difficulties has not been fully elucidated. Here we identify and characterize an efficient cryptic bacterial promoter in the cDNA encoding the dengue virus (DENV) 5′ UTR. Following cryptic transcription in E. coli, protein expression initiated at a conserved in-frame AUG that is downstream from the authentic DENV initiation codon, yielding a DENV polyprotein fragment that was truncated at the N-terminus. A more complete understanding of constitutive viral protein expression in E. coli might help explain the cloning and propagation difficulties generally observed with flavivirus cDNA.
Defective Interfering Viral Particles in Acute Dengue Infections
Dongsheng Li,William B. Lott,Kym Lowry,Anita Jones,Hlaing Myat Thu,John Aaskov
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0019447
Abstract: While much of the genetic variation in RNA viruses arises because of the error-prone nature of their RNA-dependent RNA polymerases, much larger changes may occur as a result of recombination. An extreme example of genetic change is found in defective interfering (DI) viral particles, where large sections of the genome of a parental virus have been deleted and the residual sub-genome fragment is replicated by complementation by co-infecting functional viruses. While most reports of DI particles have referred to studies in vitro, there is some evidence for the presence of DI particles in chronic viral infections in vivo. In this study, short fragments of dengue virus (DENV) RNA containing only key regulatory elements at the 3′ and 5′ ends of the genome were recovered from the sera of patients infected with any of the four DENV serotypes. Identical RNA fragments were detected in the supernatant from cultures of Aedes mosquito cells that were infected by the addition of sera from dengue patients, suggesting that the sub-genomic RNA might be transmitted between human and mosquito hosts in defective interfering (DI) viral particles. In vitro transcribed sub-genomic RNA corresponding to that detected in vivo could be packaged in virus like particles in the presence of wild type virus and transmitted for at least three passages in cell culture. DENV preparations enriched for these putative DI particles reduced the yield of wild type dengue virus following co-infections of C6–36 cells. This is the first report of DI particles in an acute arboviral infection in nature. The internal genomic deletions described here are the most extensive defects observed in DENV and may be part of a much broader disease attenuating process that is mediated by defective viruses.
Phylodynamic Analysis of the Emergence and Epidemiological Impact of Transmissible Defective Dengue Viruses
Ruian Ke ,John Aaskov,Edward C. Holmes,James O. Lloyd-Smith
PLOS Pathogens , 2013, DOI: 10.1371/journal.ppat.1003193
Abstract: Intra-host sequence data from RNA viruses have revealed the ubiquity of defective viruses in natural viral populations, sometimes at surprisingly high frequency. Although defective viruses have long been known to laboratory virologists, their relevance in clinical and epidemiological settings has not been established. The discovery of long-term transmission of a defective lineage of dengue virus type 1 (DENV-1) in Myanmar, first seen in 2001, raised important questions about the emergence of transmissible defective viruses and their role in viral epidemiology. By combining phylogenetic analyses and dynamical modeling, we investigate how evolutionary and ecological processes at the intra-host and inter-host scales shaped the emergence and spread of the defective DENV-1 lineage. We show that this lineage of defective viruses emerged between June 1998 and February 2001, and that the defective virus was transmitted primarily through co-transmission with the functional virus to uninfected individuals. We provide evidence that, surprisingly, this co-transmission route has a higher transmission potential than transmission of functional dengue viruses alone. Consequently, we predict that the defective lineage should increase overall incidence of dengue infection, which could account for the historically high dengue incidence reported in Myanmar in 2001–2002. Our results show the unappreciated potential for defective viruses to impact the epidemiology of human pathogens, possibly by modifying the virulence-transmissibility trade-off, or to emerge as circulating infections in their own right. They also demonstrate that interactions between viral variants, such as complementation, can open new pathways to viral emergence.
Recent Emergence of Dengue Virus Serotype 4 in French Polynesia Results from Multiple Introductions from Other South Pacific Islands
Van-Mai Cao-Lormeau, Claudine Roche, Maite Aubry, Anita Teissier, Stéphane Lastere, Elise Daudens, Henri-Pierre Mallet, Didier Musso, John Aaskov
PLOS ONE , 2011, DOI: 10.1371/journal.pone.0029555
Abstract: Background Infection by dengue virus (DENV) is a major public health concern in hundreds of tropical and subtropical countries. French Polynesia (FP) regularly experiences epidemics that initiate, or are consecutive to, DENV circulation in other South Pacific Island Countries (SPICs). In January 2009, after a decade of serotype 1 (DENV-1) circulation, the first cases of DENV-4 infection were reported in FP. Two months later a new epidemic emerged, occurring about 20 years after the previous circulation of DENV-4 in FP. In this study, we investigated the epidemiological and molecular characteristics of the introduction, spread and genetic microevolution of DENV-4 in FP. Methodology/Principal Findings Epidemiological data suggested that recent transmission of DENV-4 in FP started in the Leeward Islands and this serotype quickly displaced DENV-1 throughout FP. Phylogenetic analyses of the nucleotide sequences of the envelope (E) gene of 64 DENV-4 strains collected in FP in the 1980s and in 2009–2010, and some additional strains from other SPICs showed that DENV-4 strains from the SPICs were distributed into genotypes IIa and IIb. Recent FP strains were distributed into two clusters, each comprising viruses from other but distinct SPICs, suggesting that emergence of DENV-4 in FP in 2009 resulted from multiple introductions. Otherwise, we observed that almost all strains collected in the SPICs in the 1980s exhibit an amino acid (aa) substitution V287I within domain I of the E protein, and all recent South Pacific strains exhibit a T365I substitution within domain III. Conclusions/Significance This study confirmed the cyclic re-emergence and displacement of DENV serotypes in FP. Otherwise, our results showed that specific aa substitutions on the E protein were present on all DENV-4 strains circulating in SPICs. These substitutions probably acquired and subsequently conserved could reflect a founder effect to be associated with epidemiological, geographical, eco-biological and social specificities in SPICs.
Dengue Virus in Sub-tropical Northern and Central Viet Nam: Population Immunity and Climate Shape Patterns of Viral Invasion and Maintenance
Maia A. Rabaa,Cameron P. Simmons,Annette Fox,Mai Quynh Le,Thuy Thi Thu Nguyen,Hai Yen Le,Robert V. Gibbons,Xuyen Thanh Nguyen,Edward C. Holmes,John G. Aaskov
PLOS Neglected Tropical Diseases , 2013, DOI: 10.1371/journal.pntd.0002581
Abstract: Dengue virus transmission occurs in both epidemic and endemic cycles across tropical and sub-tropical regions of the world. Incidence is particularly high in much of Southeast Asia, where hyperendemic transmission plagues both urban and rural populations. However, endemicity has not been established in some areas with climates that may not support year-round viral transmission. An understanding of how dengue viruses (DENV) enter these environments and whether the viruses persist in inapparent local transmission cycles is central to understanding how dengue emerges in areas at the margins of endemic transmission. Dengue is highly endemic in tropical southern Vietnam, while increasingly large seasonal epidemics have occurred in northern Viet Nam over the last decade. We have investigated the spread of DENV-1 throughout Vietnam to determine the routes by which the virus enters northern and central regions of the country. Phylogeographic analysis of 1,765 envelope (E) gene sequences from Southeast Asia revealed frequent movement of DENV between neighboring human populations and strong local clustering of viral lineages. Long-distance migration of DENV between human population centers also occurred regularly and on short time-scales, indicating human-mediated viral invasion into northern Vietnam. Human populations in southern Vietnam were found to be the primary source of DENV circulating throughout the country, while central and northern Vietnam acted as sink populations, likely due to reduced connectedness to other populations in the case of the central regions and to the influence of temperature variability on DENV replication and vector survival and competence in the north. Finally, phylogeographic analyses suggested that viral movement follows a gravity model and indicates that population immunity and physical and economic connections between populations may play important roles in shaping patterns of DENV transmission.
‘Third wave’ cognitive therapy versus mentalization-based therapy for major depressive disorder. A protocol for a randomised clinical trial
Janus Christian Jakobsen, Christian Gluud, Mickey Kongerslev, Kirsten Aaskov Larsen, Per S?rensen, Per Winkel, Theis Lange, Ulf S?gaard, Erik Simonsen
BMC Psychiatry , 2012, DOI: 10.1186/1471-244x-12-232
Abstract: We plan a randomised, parallel group, assessor-blinded superiority clinical trial. During two years we will include 84 consecutive adult participants diagnosed with major depressive disorder. The participants will be randomised to either ‘third wave‘ cognitive therapy versus mentalization-based therapy. The primary outcome will be the Hamilton Rating Scale for Depression at cessation of treatment at 18 weeks. Secondary outcomes will be the proportion of patients with remission, Symptom Checklist 90 Revised, Beck’s Depression Inventory, and The World Health Organisation-Five Well-being Index 1999.Interventions for depression have until now shown relatively small effects. Our trial results will provide knowledge about the effects of two modern psychotherapeutic interventions.ClinicalTrials: NCT01070134According to the WHO, major depressive disorder is the second largest healthcare problem worldwide in terms of disability caused by illness [1]. It afflicts an estimated 17% of individuals during their lifetimes at tremendous cost to the individual and society [2,3]. Roughly a third of all depressive disorders take a chronic course [4,5]. Approximately 15% of depressive patients will commit suicide over a 10 to 20 year period [6].Antidepressant medication remains the mainstay in the treatment of depression [7]. However, meta-analyses have shown that most antidepressants presumably only obtain a beneficial effect in severely depressed patients, and even this effect seems to be clinically small [8,9]. As the therapeutic benefits of antidepressants seem to be limited there is an urgent need to identify effective interventions for depression.Cognitive therapy is one of the most well-known and used psychotherapeutic techniques. Aaron T. Beck originally developed cognitive therapy for depression [10]. Beck believed that critical life events could accentuate hidden negative beliefs, which could generate negative automatic thoughts [10]. These negative thoughts could lead to sym
Evaluating the Use of Role Playing Simulations in Teaching Negotation Skills to University Students  [PDF]
John Andrew, John Meligrana
Creative Education (CE) , 2012, DOI: 10.4236/ce.2012.36104
Abstract: This paper critically evaluates the use of role-playing simulations in a negotiation course taught to graduate students. The course consisted primarily of a series of simulations involving the alternative dispute resolution (ADR) processes of negotiation, facilitation and mediation. Data were obtained from two sets of questionnaires completed by 41 students before and after the course. A review of previous research reveals that despite the widespread use of role-playing simulations in education, there has been very little empirical evaluation of their effectiveness, especially in conflict resolution and planning. Comparison of the data acquired from the two surveys generated findings regarding student understanding of ADR processes and key issues in conflict resolution; the educational value of simulations; the amenability of types of planning and planning goals to ADR; appropriate learning objectives; the importance of negotiation skills in planning; challenges in conducting effective simulations; the value of simulations in resolving real conflicts; the utility of negotiation theory; and obstacles to applying ADR to planning disputes. More generally, the paper concludes that role-playing simulations are very effective for teaching negotiation skills to students, and preparing them to manage actual conflicts skillfully and to participate effectively in real ADR processes. However, this technique is somewhat less valuable for teaching aspects of planning other than conflict resolution. Surprisingly, prior experience with simulations had no significant influence on the responses to the pre-course survey. Also surprising was the lack of a significant correlation between final exam scores and responses to relevant questions on the post-course survey.
Bronchoscopy Simulation in Anesthesia Resident Education  [PDF]
John McNeil,John Pawlowski
Open Journal of Anesthesiology (OJAnes) , 2013, DOI: 10.4236/ojanes.2013.33041
Abstract: Simulation in residency training is becoming more popular but there is limited evidence showing that it can improve a resident’s fund of knowledge, particularly in anesthesiology. We looked at whether a bronchoscopy simulation could improve performance on a thoracic anesthesia knowledge test administered both before and after using the simulator. Fourteen first-year anesthesiology residents completed the study with an average improvement on the test of 28% (p < 0.05). We conclude that bronchoscopy simulation is an effective method of educating anesthesiology residents.
Bronchoscopy Simulation in Anesthesia Resident Education  [PDF]
John McNeil, John Pawlowski
Open Journal of Anesthesiology (OJAnes) , 2013, DOI: 10.4236/ojanes.2013.33041
Abstract:

Simulation in residency training is becoming more popular but there is limited evidence showing that it can improve a resident’s fund of knowledge, particularly in anesthesiology. We looked at whether a bronchoscopy simulation could improve performance on a thoracic anesthesia knowledge test administered both before and after using the simulator. Fourteen first-year anesthesiology residents completed the study with an average improvement on the test of 28% (p < 0.05). We conclude that bronchoscopy simulation is an effective method of educating anesthesiology residents.


Factors Impacting Innovation in New Service Offerings  [PDF]
John Maleyeff
Journal of Service Science and Management (JSSM) , 2011, DOI: 10.4236/jssm.2011.42014
Abstract: Factors that affect the level of innovation in projects to develop new service offerings are analyzed based on field re-search results from 84 service innovation projects. Personal characteristics of developers, process and customer type, and an important characteristic of their organization (i.e., whether or not they possess a strong Lean Six Sigma or simi-lar process improvement orientation) are analyzed. It is shown that, although personal characteristics, process type, or customer type do not affect the level of innovation, organizations with a strong Lean Six Sigma orientation had a lower incidence of radical innovation recommendations.
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