Tumour endothelial marker-8 in wound healing and its impact on the proliferation and migration of keratinocytes

Chronic wound management represents a significant burden on healthcare systems and negatively impacts on the quality of patient life. New strategies to understand and identify wounds that will not heal in a normal manner are required. Tumour endothelial marker‑8 (TEM‑8) has been implicated in the wound healing and angiogenesis processes. TEM‑8 expression was examined at the transcript level in a cohort of acute (n=10) and chronic (n=14) wounds and in normal skin (n=10). Protein analysis of TEM‑8 was also undertaken for this cohort using immunohistochemistry (IHC). TEM‑8 impact on keratinocyte cell growth and migration was assessed following TEM‑8 ribozyme transgene transfection of human HaCaT keratinocytes using cell growth and electric cell‑substrate impedance sensing (ECIS)‑based assays. Expression of TEM‑8 was observed to be increased in acute wounds compared to chronic wounds and normal skin using quantitative polymerase chain reaction transcript analysis and IHC staining of wound tissues. Knockdown of TEM‑8 in HaCaT cells, using two independent ribozyme transgenes, resulted in significant decreases in cell growth as well as reductions in the rate of migration assessed using an ECIS‑based system. TEM‑8 may be differentially expressed between wound types and loss of this molecule impacts HaCaT growth and migration, potentially implicating this molecule as a factor involved in successful progression of wound healing

Molecular Epidemiology of Early and Acute HIV Type 1 Infections in the United States Navy and Marine Corps, 2005–2010

The U.S. military represents a unique population within the human immunodeficiency virus 1 (HIV-1) pandemic. The last comprehensive study of HIV-1 in members of the U.S. Navy and Marine Corps (Sea Services) was completed in 2000, before large-scale combat operations were taking place. Here, we present molecular characterization of HIV-1 from 40 Sea Services personnel who were identified during their seroconversion window and initially classified as HIV-1 negative during screening. Protease/reverse transcriptase (pro/rt) and envelope (env) sequences were obtained from each member of the cohort. Phylogenetic analyses were carried out on these regions to determine relatedness within the cohort and calculate the most recent common ancestor for the related sequences. We identified 39 individuals infected with subtype B and one infected with CRF01_AE. Comparison of the pairwise genetic distance of Sea Service sequences and reference sequences in the env and pro/rt regions showed that five samples were part of molecular clusters, a group of two and a group of three, confirmed by single genome amplification. Real-time molecular monitoring of new HIV-1 acquisitions in the Sea Services may have a role in facilitating public health interventions at sites where related HIV-1 infections are identified

Next-Generation Sequencing of HIV-1 Single Genome Amplicons

The analysis of HIV-1 sequences has helped understand the viral molecular epidemiology, monitor the development of antiretroviral drug resistance, and design candidate vaccines. The introduction of single genome amplification (SGA) has been a major advancement in the field, allowing for the characterization of multiple sequences per patient while preserving linkage among polymorphisms in the same viral genome copy. Sequencing of SGA amplicons is performed by capillary Sanger sequencing, which presents low throughput, requires a high amount of template, and is highly sensitive to template/primer mismatching. In order to meet the increasing demand for HIV-1 SGA amplicon sequencing, we have developed a platform based on benchtop next-generation sequencing (NGS) (IonTorrent) accompanied by a bioinformatics pipeline capable of running on computer resources commonly available at research laboratories. During assay validation, the NGS-based sequencing of 10 HIV-1 env SGA amplicons was fully concordant with Sanger sequencing. The field test was conducted on plasma samples from 10 US Navy and Marine service members with recent HIV-1 infection (sampling interval: 2005-2010; plasma viral load: 5,884-194,984 copies/ml). The NGS analysis of 101 SGA amplicons (median: 10 amplicons/individual) showed within-individual viral sequence profiles expected in individuals at this disease stage, including individuals with highly homogeneous quasispecies, individuals with two highly homogeneous viral lineages, and individuals with heterogeneous viral populations. In a scalability assessment using the Ion Chef automated system, 41/43 tested env SGA amplicons (95%) multiplexed on a single Ion 318 chip showed consistent gene-wide coverage \u3e50×. With lower sample requirements and higher throughput, this approach is suitable to support the increasing demand for high-quality and cost-effective HIV-1 sequences in fields such as molecular epidemiology, and development of preventive and therapeutic strategies

The status of GEO 600

The GEO 600 laser interferometer with 600m armlength is part of a worldwide network of gravitational wave detectors. GEO 600 is unique in having advanced multiple pendulum suspensions with a monolithic last stage and in employing a signal recycled optical design. This paper describes the recent commissioning of the interferometer and its operation in signal recycled mode

Women's colposcopy experience and preferences: a mixed methods study

<p>Abstract</p> <p>Background</p> <p>The colposcopy service is a key component in the UK Cervical Screening Programme. Over 120,000 women are referred to the service annually, however up to 25% of women fail to attend their appointment. Little is known about patients' preferences for colposcopic investigation and treatment. This study aims to investigate women's experience of colposcopy, to identify patients' preferences for aspects of appointments within the colposcopy service, and to make suggestions for service improvement.</p> <p>Methods/Design</p> <p>This study has been designed as a two stage, mixed method project. Stage one will involve in-depth interviews with new colposcopy patients to ascertain their experience of colposcopy services. This qualitative stage will generate factors thought to be important by service users in their experience. Stage two will utilise a choice based quantitative technique to identify women's preferences and determine the representativeness of factors generated through the interviews.</p> <p>The initial stage of in-depth interviews will be conducted with patients who are newly referred to colposcopy clinics to investigate the experience that they have of the referral process and appointment attendance. The outcome of these interviews will be analysed qualitatively using Framework analysis. Factors found to be important in women's experience will be extracted and used to construct a choice based questionnaire.</p> <p>The discrete choice experiment (questionnaire) will apply a best-worst technique through scenario-based questions to find women's relative preferences for different aspects of the service. It will be offered to women attending follow-up appointments at two colposcopy clinics in the West Midlands. Women will complete the questionnaire whilst they wait for their appointment, or, if they prefer, will take it home to complete in private. Women who do not attend their appointment will be posted the research information and questionnaire. The questionnaire analysis will use a weighted least squares regression technique for each best/worst pair. The accept/reject 'would you attend this appointment' question will be analysed using a random effects logit model.</p> <p>Discussion</p> <p>Colposcopy is a common procedure and one that is associated with raised anxiety among women experiencing the service. Little is known about women's experience of the service or their preferences for service delivery. The outcomes of the study will comprise a description of women's experience of colposcopy and establishing their preferences for how aspects of the service should be provided. Women's preferences will be fed back to service providers to enable improvements to the service to be made.</p

Potential benefits of using a toolkit developed to aid in the adaptation of HTA reports: a case study considering positron emission tomography (PET) and Hodgkin's disease

<p>Abstract</p> <p>Background</p> <p>The preparation of HTA reports requires a great deal of time, effort and resource, and there is a desire to improve efficiency, avoid duplication of effort and facilitate the transfer of knowledge between countries. This is of particular importance for countries with more limited resources which have less capacity to produce their own reports. The aim of this study was to investigate the extent of duplication of published Health Technology Assessment (HTA) reports, on the same technology, for the same indication; using positron emission tomography (PET) for lung cancer and Hodgkin's disease as a case study. This was done in order to assess the potential usefulness of a toolkit developed to aid in the adaptation of HTA reports from one context or country to another.</p> <p>Methods</p> <p>A systematic search of the National Institute for Health Research (NIHR) CRD HTA database was conducted in June 2008 in order to identify full HTA reports containing information on the use of PET for lung cancer and Hodgkin's disease, written in English, and readily available on the web. The contents of the reports identified were then examined to assess the extent of duplication of content between reports and potential for the use of the toolkit.</p> <p>Results</p> <p>From 132 records of HTA reports about PET, 8 reports were identified as fulfilling all the criteria set, and therefore demonstrating potential duplication of effort. All these reports covered four similar domains, technology use, safety, effectiveness and economic evaluation. Five of the reports also considered organisational aspects.</p> <p>Conclusions</p> <p>There was some duplication of effort in the preparation of HTA reports concerned with the use of PET for lung cancer and Hodgkin's disease. This is an example of where resource could have been conserved and time saved by the use of a toolkit developed to aid in the adaptation of HTA reports from one context to another.</p

Character, Incidence, and Predictors of Knee Pain and Activity after Infrapatellar Intramedullary Nailing of an Isolated Tibia Fracture

© Copyright 2015 Wolters Kluwer Health, Inc. All rights reserved. Objective: To study the activity and incidence of knee pain after sustaining an isolated tibia fracture treated with an infrapatellar intramedullary nail at 1 year. Design: Retrospective review of prospective cohort. Setting: Multicenter Academic and Community hospitals. Patients: Four hundred thirty-seven patients with an isolated tibia fracture completed a 12-month assessment on pain and self-reported activity. Intervention: Infrapatellar intramedullary nail. Outcomes: Demographic information, comorbid conditions, injury characteristics, and surgical technique were recorded. Knee pain was defined on a 1-7 scale with 1 being no pain and 7 being a very great deal of pain. Knee pain \u3e4 was considered clinically significant. Patients reported if they were able, able with difficulty, or unable to perform the following activities: kneel, run, climb stairs, and walk prolonged. Variables were tested in multilevel multivariable regression analyses. Results: In knee pain, 11% of patients reported a good deal to a very great deal of pain (\u3e4), and 52% of patients reported no or very little pain at 12 months. In activity at 12 months, 26% and 29% of patients were unable to kneel or run, respectively, and 31% and 35% of patients, respectively, stated they were able with difficulty or unable to use stairs or walk. Conclusions: Clinically significant knee pain (\u3e4/7) was present in 11% of patients 1 year after a tibia fracture. Of note, 31%-71% of patients had difficulty performing or were unable to perform routine daily activities of kneeling, running, and stair climbing, or walking prolonged distances

Are large clinical trials in orthopaedic trauma justified?

© 2018 The Author(s). Background: The objective of this analysis is to evaluate the necessity of large clinical trials using FLOW trial data. Methods: The FLOW pilot study and definitive trial were factorial trials evaluating the effect of different irrigation solutions and pressures on re-operation. To explore treatment effects over time, we analyzed data from the pilot and definitive trial in increments of 250 patients until the final sample size of 2447 patients was reached. At each increment we calculated the relative risk (RR) and associated 95% confidence interval (CI) for the treatment effect, and compared the results that would have been reported at the smaller enrolments with those seen in the final, adequately powered study. Results: The pilot study analysis of 89 patients and initial incremental enrolments in the FLOW definitive trial favored low pressure compared to high pressure (RR: 1.50, 95% CI: 0.75-3.04; RR: 1.39, 95% CI: 0.60-3.23, respectively), which is in contradiction to the final enrolment, which found no difference between high and low pressure (RR: 1.04, 95% CI: 0.81-1.33). In the soap versus saline comparison, the FLOW pilot study suggested that re-operation rate was similar in both the soap and saline groups (RR: 0.98, 95% CI: 0.50-1.92), whereas the FLOW definitive trial found that the re-operation rate was higher in the soap treatment arm (RR: 1.28, 95% CI: 1.04-1.57). Conclusions: Our findings suggest that studies with smaller sample sizes would have led to erroneous conclusions in the management of open fracture wounds. Trial registration: NCT01069315 (FLOW Pilot Study) Date of Registration: February 17, 2010, NCT00788398 (FLOW Definitive Trial) Date of Registration: November 10, 2008

Fluid lavage in patients with open fracture wounds (FLOW): an international survey of 984 surgeons

<p>Abstract</p> <p>Background</p> <p>Although surgeons acknowledge the importance of irrigating open fracture wounds, the choice of irrigating fluid and delivery pressure remains controversial. Our objective was to clarify current opinion with regard to the irrigation of open fracture wounds.</p> <p>Methods</p> <p>We used a cross-sectional survey and a sample-to-redundancy strategy to examine surgeons' preferences in the initial management of open fracture wounds. We mailed this survey to members of the Canadian Orthopaedic Association and delivered it to attendees of an international fracture course (AO, Davos, Switzerland).</p> <p>Results</p> <p>Of the 1,764 surgeons who received the questionnaire, 984 (55.8%) responded. In the management of open wounds, the majority of surgeons surveyed, 676 (70.5%), favoured normal saline alone. Bacitracin solution was used routinely by only 161 surgeons (16.8%). The majority of surgeons, 695 (71%) used low pressures when delivering the irrigating solution to the wound. There was, however considerable variation in what pressures constituted high versus low pressure lavage. The overwhelming majority of surgeons, 889 (94.2%), reported they would change their practice if a large randomized controlled trial showed a clear benefit of an irrigating solution – especially if it was different from the solution they used.</p> <p>Conclusion</p> <p>The majority of surgeons favour both normal saline and low pressure lavage for the initial management of open fracture wounds. However, opinions varied as regards the comparative efficacy of different solutions, the use of additives and high versus low pressure. Surgeons have expressed considerable support for a trial evaluating both irrigating solutions and pressures.</p