Letter to the editor : likelihood of tetraplegia after CT clearance of the cervical spine in obtunded blunt trauma patients

...the probabilistic computer simulation study by Dunham and colleagues evaluating the impact of different cervical spine management (CSM) strategies on tetraplegia and brain injury outcomes.1 Based on literature findings, expert opinion and with use of advances programming techniques the authors conclude that early collar removal without cervical spine magnetic resonance imaging (MRI) is a preferable CSM strategy for comatose, blunt trauma patients with extremity movement and a negative cervical spine computed tomography(CT) scan. Although we do not have the required expertise to comment on the applied statistical approach, we would like to comment on one of the medical assumptions raised by the authors, namely the likelihood of tetraplegia in this specific population....

The creative instability hypothesis

This paper provides an analysis of why many ‘stars’ tend to fade away rather than enjoying ongoing branding advantages from their reputations. We propose a theory of market overshooting in creative industries that is based on Schumpeterian competition between producers to maintain the interest of boundedly rational fans. As creative producers compete by offering further artistic novelty, this escalation of product complexity eventually leads to overshooting. We propose this as a theory of endogenous cycles in the creative industries.

Next-generation sequencing of cervical DNA detects human papillomavirus types not detected by commercial kits

Background Human papillomavirus (HPV) is the aetiological agent for cervical cancer and genital warts. Concurrent HPV and HIV infection in the South African population is high. HIV positive (+) women are often infected with multiple, rare and undetermined HPV types. Data on HPV incidence and genotype distribution are based on commercial HPV detection kits, but these kits may not detect all HPV types in HIV + women. The objectives of this study were to (i) identify the HPV types not detected by commercial genotyping kits present in a cervical specimen from an HIV positive South African woman using next generation sequencing, and (ii) determine if these types were prevalent in a cohort of HIV-infected South African women. Methods Total DNA was isolated from 109 cervical specimens from South African HIV + women. A specimen within this cohort representing a complex multiple HPV infection, with 12 HPV genotypes detected by the Roche Linear Array HPV genotyping (LA) kit, was selected for next generation sequencing analysis. All HPV types present in this cervical specimen were identified by Illumina sequencing of the extracted DNA following rolling circle amplification. The prevalence of the HPV types identified by sequencing, but not included in the Roche LA, was then determined in the 109 HIV positive South African women by type-specific PCR. Results Illumina sequencing identified a total of 16 HPV genotypes in the selected specimen, with four genotypes (HPV-30, 74, 86 and 90) not included in the commercial kit. The prevalence's of HPV-30, 74, 86 and 90 in 109 HIV positive South African women were found to be 14.6 %, 12.8 %, 4.6 % and 8.3 % respectively. Conclusions Our results indicate that there are HPV types, with substantial prevalence, in HIV positive women not being detected in molecular epidemiology studies using commercial kits. The significance of these types in relation to cervical disease remains to be investigated.

Comparison of cervical and blood T-cell responses to human papillomavirus-16 in women with human papillomavirus-associated cervical intraepithelial neoplasia

Human papillomaviruses (HPVs) are obligate epithelial pathogens and typically cause localized mucosal infections. We therefore hypothesized that T-cell responses to HPV antigens would be greater at sites of pathology than in the blood. Focusing on HPV-16 because of its association with cervical cancer, the magnitude of HPV-specific T-cell responses at the cervix was compared with those in the peripheral blood by intracellular cytokine staining following direct ex vivo stimulation with both virus-like particles assembled from the major capsid protein L1, and the major HPV oncoprotein, E7. We show that both CD4 + and CD8 + T cells from the cervix responded to the HPV-16 antigens and that interferon-γ (IFN-γ) production was HPV type-specific. Comparing HPV-specific T-cell IFN-γ responses at the cervix with those in the blood, we found that while CD4 + and CD8 + T-cell responses to L1 were significantly correlated between compartments (P = 0.02 and P = 0.05, respectively), IFN-γ responses in both T-cell subsets were significantly greater in magnitude at the cervix than in peripheral blood (P = 0.02 and P = 0.003, respectively). In contrast, both CD4 + and CD8 + T-cell IFN-γ responses to E7 were of similar magnitude in both compartments and CD8 + responses were significantly correlated between these distinct immunological compartments (P = 0.04). We therefore show that inflammatory T-cell responses against L1 (but not E7) demonstrate clear compartmental bias and the magnitude of these responses do reflect local viral replication but that correlation of HPV-specific responses between compartments indicates their linkage.

Strategies for the prevention of cervical cancer by human papillomavirus vaccination

As cervical cancer is causally associated with 14 high-risk types of human papillomavirus (HPV), a successful HPV vaccine will have a major impact on this disease. Although some persistent HPV infections progress to cervical cancer, host immunity is generally able to clear most HPV infections. Both cell-mediated and antibody responses have been implicated in influencing the susceptibility, persistence or clearance of genital HPV infection. There have been two clinical trials that show that vaccines based on virus-like particles (VLPs) made from the major capsid protein, L1, are able to type specifically protect against cervical intra-epithelial neoplasia and infection. However, there is no evidence that even a mixed VLP vaccine will protect against types not included in the vaccine, and a major challenge that remains is how to engineer protection across a broader spectrum of viruses. Strategies for production of HPV vaccines using different vaccine vectors and different production systems are also reviewed. © 2005 Elsevier Ltd. All rights reserved.

Vaccination strategies for the prevention of cervical cancer

Infection with high-risk human papillomaviruses (HPVs) is an essential step in the multistep process leading to cervical cancer. There are approximately 120 different types of HPV identified: of these, 18 are high-risk types associated with cervical cancer, with HPV-16 being the dominant type in most parts of the world. The major capsid protein of papillomavirus, produced in a number of expression systems, self assembles to form virus-like particles. Virus-like particles are the basis of the first generation of HPV vaccines presently being tested in clinical trials. Virus-like particles are highly immunogenic and afford protection from infection both in animal models and in Phase IIb clinical trials. A number of Phase III trials are in progress to determine if the vaccine will protect against cervical disease and, in some cases, genital warts. However, it is predicted that these vaccines will be too expensive for the developing world, where they are desperately needed. Another problem is that they will be type specific. Novel approaches to the production of virus-like particles in plants, second-generation vaccine approaches including viral and bacterial vaccine vectors and DNA vaccines, as well as different routes of immunization, are also reviewed. © 2005 Future Drugs Ltd.

The effects of deep cracks on the rain-induced instability of slopes : A case study

Rainfall can disrupt the balance of natural soil slope. This imbalance will be accelerated by existence of cracks in soil slope, which lead to decreasing shear strength and increasing hydraulic conductivity of the soil slope. Some research works have been conducted on the effects of surface-cracks on slope stability. However, the influence of deep-cracks is yet to be investigated. Limited availability of deep crack data due to the lack of effective sub-soil investigation methods could be one of the obstacles. To emphasize the effects of deep cracks in soil slope on its rain-induced instability, a natural soil slope in Indonesia that failed in 31st October 2010 due to heavy rainfall was analyzed for stability with and without deep cracks in the slope. The slope stability analysis was conducted using SLOPE/W coupling with the results of transient seepage analysis (SEEP/W) that simulate the pore-water pressure development in the slope during the rainfall. The results of Electrical Resistivity Tomography (ERT) survey, bore-hole tests and geometrical survey conducted on the slope before its failure were used to identify the soil layers’ stratification including deep cracks, the properties of different soil layers, and geometrical parameters of the slope for the analysis. The results showed that it is vital to consider the existence of deep crack in soil slopes in analysing their instability induced by rainfalls.

Effects of slope inclination on the rain-induced instability of embankment slopes

Rainfall has been identified as one of the main causes for embankment failures in areas where high annual rainfall is experienced. The inclination of the embankment slope is important for its stability during rainfall. In this study, instrumented model embankments were subjected to artificial rainfalls to investigate the effects of the slope inclination on their stability. The results of the study suggested that when the slope inclination is greater than the friction angle of the soil, the failure is initiated by the loss of soil suction and when it is smaller than the friction angle of the soil, the failure is initiated by the positive pore water pressure developed at the toe of the slope. Further, slopes become more susceptible to sudden collapse during rainfall as the slope angle increases.

A method for predicting rain-induced instability of an individual slope

Awareness to avoid losses and casualties due to rain-induced landslide is increasing in regions that routinely experience heavy rainfall. Improvements in early warning systems against rain-induced landslide such as prediction modelling using rainfall records, is urgently needed in vulnerable regions. The existing warning systems have been applied using stability chart development and real-time displacement measurement on slope surfaces. However, there are still some drawbacks such as: ignorance of rain-induced instability mechanism, mislead prediction due to the probabilistic prediction and short time for evacuation. In this research, a real-time predictive method was proposed to alleviate the drawbacks mentioned above. A case-study soil slope in Indonesia that failed in 2010 during rainfall was used to verify the proposed predictive method. Using the results from the field and laboratory characterizations, numerical analyses can be applied to develop a model of unsaturated residual soils slope with deep cracks and subject to rainwater infiltration. Real-time rainfall measurement in the slope and the prediction of future rainfall are needed. By coupling transient seepage and stability analysis, the variation of safety factor of the slope with time were provided as a basis to develop method for the real-time prediction of the rain-induced instability of slopes. This study shows the proposed prediction method has the potential to be used in an early warning system against landslide hazard, since the FOS value and the timing of the end-result of the prediction can be provided before the actual failure of the case study slope.