Optimal sensor locations for the backward lagrangian stochastic technique in measuring lagoon gas emission.

This study evaluated the impact of gas concentration and wind sensor locations on the accuracy of measuring gas emission rates from a lagoon environment using the backward Lagrangian stochastic (bLS) inverse-dispersion technique. Path-integrated concentrations (PICs) and three-dimensional (3D) wind vector data were collected at different locations within the lagoon landscape. A floating 45 m × 45 m perforated pipe network on an irrigation pond was used as a synthetic distributed emission source for the controlled release of methane. A total of 961 15-min datasets were collected under different atmospheric stability conditions over a 2-yr period. The PIC location had a significant impact on the accuracy of the bLS technique. The location of the 3D sonic anemometer was generally not a factor for the measured accuracies with the PIC positioned on the downwind berm. The PICs across the middle of the pond consistently produced the lowest accuracy with any of the 3D anemometer locations (<69% accuracy). The PICs located on the downwind berm consistently yielded the best bLS accuracy regardless of whether the 3D sonic anemometer was located on the upwind, side, or downwind berm (accuracies ranged from 79 to 108%). The accuracies of the emission measurements with the berm PIC-berm 3D setting were statistically similar to that found in a more ideal homogeneous grass field. Considering the practical difficulties of setting up equipment and the accuracies associated with various sensor locations, we recommend that wind and concentration sensors be located on the downwind berm.

Medical management of vulvar intraepithelial neoplasia.

OBJECTIVE: To determine which nonsurgical treatments have been assessed for the treatment of vulvar intraepithelial neoplasia (VIN) and what the outcomes of such treatment might be. MATERIALS AND METHODS: The English literature over the last 25 years was searched on Medline. RESULTS: A wide variety of nonsurgical treatments was identified and the outcomes were very similar. These treatments showed responses rates varying between 10% and 60%. Responses were poorly defined, however, and few if any studies had large enough subject numbers or long enough follow-up to allow robust conclusions. CONCLUSIONS: Although VIN is a condition in which there would seem to be a pressing need for nonsurgical interventions, none of the nonsurgical treatments reviewed resulted in optimal outcomes. No one treatment seemed to be superior. There is a need for consensus on how outcomes are measured and a move toward large well-constructed studies is recommended. Because VIN is uncommon, there is a strong case for establishing research collaboratives.

Human papillomavirus (HPV) type 16-specific CD8+ T cell responses in women with high grade vulvar intraepithelial neoplasia.

Human papillomavirus (HPV)-associated vulvar intraepithelial neoplasia (VIN) has serious sequelae for the sufferer. Current treatments are associated with poor response and high relapse rates. The development of HPV-specific T cell immunotherapies offers a new approach to treatment. This will require a detailed understanding of the spectrum of T cell responses induced by HPV antigens, and how effectively viral antigens can be accessed by the immune system. We have investigated the frequency and spectrum of HPV16-specific CD8+ T cell responses to three HPV16 antigens in 9 women with high grade VIN (VIN3). CD4-depleted populations of responder cells were screened against overlapping 30-35mer peptides covering the sequences of HPV16 E6, E7 and E4 using ELISPOT assays of IFN-gamma release. We demonstrated CD8+ T cell reactivity to one or more of the proteins in 6 of 9 patient samples. All 6 of these responders recognised peptides covering the E7 protein, 3 of 9 women responded to E6 peptides, but no reactivity was seen to E4. Our results suggest that HPV16-specific cytotoxic T cells (CTLs) are relatively common in women with persistent VIN3. The HPV-specific CTL response, however, seems to be ineffective. There is some evidence that there are problems associated with the processing and presentation of HPV antigens by the infected vulvar epithelium. It will be crucial to address this in the design of any T cell based therapy for HPV-associated VIN and vulval cancer.

Detection of CD8+ T cell responses to human papillomavirus type 16 antigens in women using imiquimod as a treatment for high-grade vulval intraepithelial neoplasia.

OBJECTIVES: To investigate CD8+ T cell reactivity to human papillomavirus (HPV) 16 antigens in patients with high-grade vulval intraepithelial neoplasia (VIN) before, during and after treatment with 5% imiquimod cream. METHODS: CD8-enriched responder cell populations were obtained from 10 patients with high-grade VIN using imiquimod cream as a treatment. Overlapping synthetic peptides covering the entire primary sequences of the HPV16 E6, E7 and E4 proteins were used to screen for CD8+ T cell responses using an ELISPOT assay of interferon (IFN)-gamma release. RESULTS: Reactivity to the proteins was detected in all patients on at least one occasion. With the exception of one patient, CD8+ T cell reactivity generally increased at some stage during treatment. The magnitude and specificities of responses changed over the treatment period. This was particularly noticeable in response to peptides derived from the E4 protein. CD8+ T cell reactivity to HPV16 E7 appeared to be dominant amongst women with high-grade VIN. The magnitude and specificity of response had no correlation with clinical response to imiquimod. CONCLUSIONS: HPV16 specific CD8+ T cell activity was detected in patients with high-grade VIN. Imiquimod use appeared to increase the magnitude of the response and broaden the specificity of response in some patients. Despite the presence of these CD8+ T cells, the disease state persisted; therefore, a role for HPV-specific cytotoxic T cells (CTLs) in VIN resolution remains unproven.

Effect of nurse colposcopists on a hospital-based service.

The number of colposcopies performed annually in the UK is increasing. Nurse colposcopists have been introduced by many units to cope with this workload. The small amount of evidence to support the introduction of nurse colposcopists suggests that nurses are viable alternative providers of colposcopy. This study compares the performance of nurse colposcopists with that of doctors.

The effects of 5% imiquimod cream on high-grade vulval intraepithelial neoplasia.

OBJECTIVES: The aim of this study was to investigate the effects of topical 5% Imiquimod (3M Pharmaceuticals, St. Paul, Minnessota) on high-grade vulval intraepithelial neoplasia (VIN). METHODS: A prospective uncontrolled observational study was performed. Fifteen patients with histologically confirmed VIN 3 were asked to self-administer 5% Imiquimod cream to their vulval lesions up to three times weekly for 16 weeks. Review was conducted at 1, 2, 3, 4, 6, and 9 months postrecruitment. Lesions were photodocumented and at 4 months any areas demonstrating a clinical response were biopsied. RESULTS: Of 15 patients recruited, 4 demonstrated a clinical improvement in their disease, 3 of whom had negative biopsies posttreatment. Local side effects limited the frequency of application such that 7 patients applied the cream once weekly, 6 twice weekly, and 2 three times weekly. CONCLUSIONS: 5% Imiquimod cream appears to have an effect when used on high-grade VIN. The frequency of application was limited by local side effects which may have reduced the clinical responses seen. Measures to alleviate local side effects may allow more aggressive use of Imiquimod and lead to improved responses.