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Identification of HCV Inhibitors from a Cell-Based Sub-Genomic Replicon Screen  [PDF]
David C. Pryde, Thien-Duc Tran, Mark Gardner, Chris Pickford, Stephen M. Shaw, Mike Westby, Tanya Parkinson, Caroline Smith-Burchnell, Rob Webster, Satish Dayal
Open Journal of Medicinal Chemistry (OJMC) , 2013, DOI: 10.4236/ojmc.2013.31003

A high throughput screen of the Pfizer compound collection was carried out using a hepatitis C virus (HCV) genotype 1b subgenomic replicon cell line. Those confirmed hits that demonstrated broad spectrum activity without overt cytotoxicity were further evaluated, leading to the identification of a series of pyrrolopyridines with excellent antiviral activity in a fully infectious HCV cell-based assay and pharmacokinetic properties.

Use of a highly sensitive strand-specific quantitative PCR to identify abortive replication in the mouse model of respiratory syncytial virus disease
Richard Bannister, Deborah Rodrigues, Edward J Murray, Carl Laxton, Mike Westby, Helen Bright
Virology Journal , 2010, DOI: 10.1186/1743-422x-7-250
Abstract: In the mouse lung, no increase in RSV genome was seen above the background of the original inoculum whilst only a limited transient increase (< 1 log) in positive strand, replicative intermediate (RI) RNA occurred. This RNA did however persist at detectable levels for 59 days post infection. As expected, ribavirin therapy reduced levels of infectious virus and RI RNA in the mouse lung. However, whilst Palivizumab therapy was also able to reduce levels of infectious virus, it failed to prevent production of intracellular RI RNA. A comparison of RSV RNA kinetics in human (A549) and mouse (KLN205) cell lines demonstrated that RSV replication was also severely delayed and impaired in vitro in the mouse cells.This is the first time that such a sensitive strand-specific QPCR technique has been to the RSV mouse system. We have accurately quantified the restricted and abortive nature of RSV replication in the mouse. Further in vitro studies in human and mouse cells suggest this restricted replication is due at least in part to species-specific host cell-viral interactions.Respiratory Syncytial Virus (RSV) is the leading cause of lower respiratory tract infection (LRTI) in infants and children world-wide and is increasingly recognised as a cause of serious disease in adults and immune compromised transplant patients [1,2]. Over half of all children will be infected with RSV by their first birthday and by the age of 2 nearly all children will have been infected with RSV at least once [3]. LRTI caused by RSV infection is a major cause of both infant hospitalisation and infant viral induced death [4]. A number of medical treatments, including use of bronchodilators, palliative care (supportive ventilation, nitric oxide) and use of anti inflammatory agents are available but none of these treatments relieve the viral burden in RSV-infected patients. The only small molecule antiviral therapeutic agent for treating RSV is Virazole (aerosolised ribavirin), which has been shown to be
HIV-1 predisposed to acquiring resistance to maraviroc (MVC) and other CCR5 antagonists in vitro has an inherent, low-level ability to utilize MVC-bound CCR5 for entry
Michael Roche, Martin R Jakobsen, Anne Ellett, Hamid Salimiseyedabad, Becky Jubb, Mike Westby, Benhur Lee, Sharon R Lewin, Melissa J Churchill, Paul R Gorry
Retrovirology , 2011, DOI: 10.1186/1742-4690-8-89
Abstract: Here, we show that Env derived from the parental CC1/85 strain is inherently capable of a low affinity interaction with MVC-bound CCR5. However, this phenotype was only revealed in 293-Affinofile cells and NP2-CD4/CCR5 cells that express very high levels of CCR5, and was masked in TZM-bl, JC53 and U87-CD4/CCR5 cells as well as PBMC, which express comparatively lower levels of CCR5 and which are more commonly used to detect resistance to CCR5 antagonists.Env derived from the CC1/85 strain of HIV-1 is inherently capable of a low-affinity interaction with MVC-bound CCR5, which helps explain the relative ease in which CC1/85 can acquire resistance to CCR5 antagonists in vitro. The detection of similar phenotypes in patients may identify those who could be at higher risk of virological failure on MVC.Human immunodeficiency virus type 1 (HIV-1) entry is initiated by the interaction of the viral gp120 envelope (Env) glycoproteins with cellular CD4 and a coreceptor, either CCR5 or CXCR4 [1]. Maraviroc (MVC) and other CCR5-antagonists such as vicriviroc (VVC, also known as SCH-D), AD101 (a preclinical precursor of VVC), and aplaviroc (APL) are HIV-1 entry inhibitors that bind to- and alter the conformation of CCR5, such that CCR5 is no longer recognized by gp120 [1]. Thus, CCR5-antagonists are allosteric inhibitors of HIV-1 entry [2-4]. MVC has been approved for use in treatment-experienced and antiretroviral therapy (ART)-na?ve HIV-1-infected adults who have no evidence of CXCR4-using virus in plasma [5]. As with other antiretrovirals, treatment with CCR5-antagonists can result in drug resistance leading to virological rebound. Although virological failure can arise from the emergence of CXCR4-using HIV-1 strains that were present at very low levels prior to initiation of a CCR5-antagonist [6], genuine resistance to CCR5-antagonists results from adaptive alterations in gp120 enabling recognition of the drug-bound conformation of CCR5 [7-15].Being allosteric inhibitors of vi
Patient and health professional views on rehabilitation practices and outcomes following total hip and knee arthroplasty for osteoarthritis:a focus group study
Marie D Westby, Catherine L Backman
BMC Health Services Research , 2010, DOI: 10.1186/1472-6963-10-119
Abstract: Separate focus groups and interviews were conducted with patients (THA or TKA within past year) and three health professional groups: allied health professionals (AHPs), orthopaedic surgeons, and other physicians, in Canada and the United States. Pairs of moderators led the focus groups using a standardized discussion guide. Discussions were audiotaped and transcribed verbatim. A content analysis within and across groups identified key themes.Eleven focus groups and eight interviews took place in six sites. Patients (n = 32) varied in age, stage of recovery, and surgical and rehabilitation experiences. Health professionals (n = 44) represented a range of disciplines, practice settings and years of experience. Six key themes emerged: 1) Let's talk (issues related to patient-health professional and inter-professional communication); 2) Expecting the unexpected (observations about unanticipated recovery experiences); 3) It's attitude that counts (the importance of the patient's positive attitude and participation in recovery); 4) It takes all kinds of support (along the continuum of care); 5) Barriers to recovery (at patient, provider and system levels), and 6) Back to normal (reflecting diversity of expected outcomes). Patients offered different, but overlapping views compared to health professionals regarding rehabilitation practices and outcomes following THA and TKA.Results will inform subsequent phases of guideline development and ensure stakeholders' perspectives shape the priorities, content and scope of the guidelines.Total hip arthroplasty (THA) and total knee arthroplasty (TKA) surgeries are highly successful orthopaedic procedures for more than 62,000 Canadians [1] and 773,000 Americans [2] each year. The growth in number of THAs and TKAs exceeds the aging of our population due in part to both younger and older individuals electing joint replacement surgery as a feasible option for their advanced hip and knee osteoarthritis (OA) [3].Nearly all patients recei
Efficacy of Facebook Fans: Can They Influence Perception of the Brand?  [PDF]
Mike Behan
Open Journal of Business and Management (OJBM) , 2014, DOI: 10.4236/ojbm.2014.24033
Abstract: Using a qualitative single case study methodology, this research studied the effect that a Facebook page has on friends of the brand. The problem under investigation is the lack of understanding effects social media sites like Facebook has on the perception of the brand by the user. The data collected suggests that the use of Facebook by a SME does help maintain and in some cases increase the perception of the brand in the positive. The analysis of the data additionally shows this effect on brand perception is based on the drivers of a) connectivity, b) change of perception, c) internal value, d) goodwill, and e) the decision process. Interview participants indicate the importance Facebook has as a marketing communication tool. The findings from the research suggest that Facebook use by SMEs is an important component of an integrated approach to marketing communications when considering the perception of the brand. This research also raises important questions as to what significance Facebook use by SMEs has over other traditional marketing communication methods when creating, communicating, and delivering a message of value.
Functionalization of Polypropylene with High Dielectric Properties: Applications in Electric Energy Storage  [PDF]
T. C. Mike Chung
Green and Sustainable Chemistry (GSC) , 2012, DOI: 10.4236/gsc.2012.22006
Abstract: Biaxial-oriented polypropylene (BOPP) thin films are currently used as dielectrics in state-of-the-art capacitors that show many advantages, such as low energy loss and high breakdown strength, but a limited energy density (<2 J/cm3). This paper reviews some of our experimental results in functionalization of polypropylene with the objective to increase its electric energy density and maintain all desirable properties. A family of PP copolymers with various moieties, such as OH, O-Si(CH3)3, long chain branching, and cross-linking structure, have been systematically synthesized and studied to examine their dielectric properties (i.e. dielectric constant, dielectric loss, breakdown strength, polarization under various temperatures and electric fields). Evidently, a high molecular weight poly(propylene-co-hexen-6-ol) copolymer (PP-OH) containing 4.2 mol% of polar OH groups shows a dielectric constant (ε) of about 4.6 (more than 2 times of BOPP)—which is independent on a wide range of temperatures and frequencies—and high breakdown strength > 600 MV/m. The PP-OH dielectric demonstrates a linear reversible charge storage behavior with high releasing energy density > 7 J/cm3 (2 - 3 times of BOPP) after an applied electric field at E = 600 MV/m, without showing any significant increase of energy loss and remnant polarization at zero electric field. On the other hand, a cross-linked polypropylene (x-PP) exhibits an ε ~ 3, which is independent of a wide range of temperatures and frequencies, slim polarization loops, high breakdown strength (E = 650 MV/m), narrow breakdown distribution, and reliable energy storage capacity > 5 J/cm3 (double that of state-of-the-art BOPP capacitors), without showing any increase in energy loss.
Learning the Business  [PDF]
Mike Holcombe, Marian Gheorghe
Creative Education (CE) , 2012, DOI: 10.4236/ce.2012.32042
Abstract: Developing software is a highly creative process. This paper describes a novel approach to teaching software engineering which involves university students working in partnership with external clients from business, charities and the public sector building solutions to their business and other problems. The paper describes the basic principles behind these activities and focuses on the experiences of teaching advanced students through the medium of a commercial software development company specifically set up to be run by the students as part of their degree course. The evidence from student and employer feedback demonstrates that this approach has been highly successful for the past 20 years or so but despite this it has rarely, if ever, been replicated elsewhere.
Femoral Hernia: A Review of the Clinical Anatomy and Surgical Treatment  [PDF]
Makio Mike, Nobuyasu Kano
Surgical Science (SS) , 2013, DOI: 10.4236/ss.2013.410089

Purpose: Femoral hernia is a kind of ventral hernia that surgeons commonly encounter, second in frequency only to inguinal hernia. Femoral hernias often require emergency surgery because of incarceration or strangulation of the intestine. In addition, intestinal resection may need to be considered based on intestinal viability. Definitive preoperative diagnosis and strategic planning for surgery are thus important. The surgeon should consider the operation in the context of the clinical anatomy of the abdominal cavity. Therefore the essence of the clinical anatomy and treatment of femoral hernia is described. Methods: The medical records of 38 patients who underwent femoral hernia repair between March 2006 and November 2011 were retrospectively analyzed. Results: Femoral hernioplasty was performed with original mesh repair or Ruggi’s repair plus iliopubic tract repair (or Bassini’s repair). The mean patient age was 76.7 years, and a female predominance was apparent. Twenty-four patients underwent emergency surgery with a diagnosis of incarcerated femoral hernia. Nine patients showed intestinal strangulation and underwent resection of the small intestine. Four patients developed complications. One patient died due to aspiration pneumonia. No recurrences were encountered after 6 months to 6 years of follow-up. Conclusion: Femoral hernia is an important surgical condition with high rates of incarceration/strangulation and intestinal resection. Correct preoperative diagnosis of femoral hernia and a strict operative strategy are important. The original mesh repair is effective and easy to perform.

Managing Dynamics in Corporate Networks  [PDF]
Mike Danilovic, Mats Winroth
World Journal of Engineering and Technology (WJET) , 2014, DOI: 10.4236/wjet.2014.21004
Abstract: A crucial issue in collaborating in manufacturing corporate networks between different companies is to identify to what extent different strategic and operational decisions need to be coordinated between the involved companies. In this paper, we elaborate on the issue of synchronization and coordination of information flow based on interconnectivities between companies in order to coordinate a corporate network by the means of DSM, Dependence Structure Matrix. The results show that DSM can be used to identify interconnectivities, dependencies on information flow among actors in a network and to identify which information needs to be shared between companies in the network.
Canadian physiotherapists' views on certification, specialisation, extended role practice, and entry-level training in rheumatology
Linda C Li, Marie D Westby, Evelyn Sutton, Marlene Thompson, Eric C Sayre, Lynn Casimiro
BMC Health Services Research , 2009, DOI: 10.1186/1472-6963-9-88
Abstract: Six hundred PTs practicing in orthopaedics in Canada were randomly selected to receive a postal survey. The questionnaire covered areas related to clinical practice, perceptions of rheumatology training received, and attitudes toward PT roles in arthritis care. Logistic regression models were developed to explore the associations between PTs' interests in pursuing each of the three extended scope practice designations and the personal/professional/attitudinal variables.We received 286 questionnaires (response rate = 47.7%); 258 contained usable data. The average length of time in practice was 15.4 years (SD = 10.4). About 1 in 4 PTs agreed that they were interested in assuming advanced practice roles (being a certified arthritis therapist = 28.9%, being a PT specialized in rheumatology = 23.3%, being a PT practitioner = 20.9%). Having a caseload of ≥ 40% in arthritis, having a positive attitude toward advanced practice roles in arthritis care and toward the formal credentialing process, and recognizing the difference between certification and specialisation were associated with an interest in pursing advanced practice roles.Orthopaedic PTs in Canada indicated a fair level of interest in pursuing certification, specialisation and extended scope practice roles in arthritis care. Future research should focus on the effectiveness and cost-effectiveness of the emerging health service delivery models involving certified, specialized or extended scope practice PTs in the management of arthritis.The delivery of health services to people with arthritis is undergoing transformation in Canada. Since the last decade there has been a gradual change of boundaries of health professions in providing arthritis care [1,2]. The trend is particularly evident in nursing and rehabilitation professions where clinicians begin to assume roles that are outside of their usual scope of practice while working in a multidisciplinary teams [3].Physiotherapists (PTs) are in a unique position to ex
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