Measurement and modelling of air pollution and atmospheric chemistry in the U.K. West Midlands conurbation: overview of the PUMA Consortium project.

The PUMA (Pollution of the Urban Midlands Atmosphere) Consortium project involved intensive measurement campaigns in the Summer of 1999 and Winter of 1999/2000, respectively, in which a wide variety of air pollutants were measured in the UK West Midlands conurbation including detailed speciation of VOCs and major component analysis of aerosol. Measurements of the OH and HO2 free radicals by the FAGE technique demonstrated that winter concentrations of OH were approximately half of those measured during the summer despite a factor of 15 reduction in production through the photolysis of ozone. Detailed box modelling of the fast reaction chemistry revealed the decomposition of Criegee intermediates formed from ozone-alkene reactions to be responsible for the majority of the formation of hydroxyl in both the summer and winter campaigns, in contrast to earlier rural measurements in which ozone photolysis was predominant. The main sinks for hydroxyl are reactions with NO2, alkenes and oxygenates. Concentrations of the more stable hydrocarbons were found to be relatively invariant across the conurbation, but the impacts of photochemistry were evident through analyses of formaldehyde which showed the majority to be photochemical in origin as opposed to emitted from road traffic. Measurements on the upwind and downwind boundaries of the conurbation revealed substantial enhancements in NOx as a result of emissions within the conurbation, especially during westerly winds which carried relatively clean air. Using calcium as a tracer for crustal particles, it proved possible to reconstruct aerosol mass from the major chemical components with a fairly high degree of success. The organic to elemental carbon ratios showed a far greater influence of photochemistry in summer than winter, presumably resulting mainly from the greater availability of biogenic precursors during the summer campaign. Two urban airshed models were developed and applied to the conurbation, one Eulerian, the other Lagrangian. Both were able to give a good simulation of concentrations of both primary and secondary pollutants at urban background locations.

Changes in CD4 lymphocyte counts after interruption of therapy in patients with viral failure on protease inhibitor-containing regimens. Royal Free Centre for HIV Medicine.

OBJECTIVE: To describe the short-term changes in CD4 lymphocyte counts after the interruption of antiretroviral HIV therapy in order to increase the understanding of CD4 lymphocyte dynamics, and so that appropriate monitoring strategies can be designed. METHODS: We studied 35 HIV-infected patients with late-stage disease who had therapy interruptions leading to high viral load levels, median greater than 750 000 RNA log10 copies/ml, and in whom two CD4 cell counts (median 28 days apart) were available before beginning a salvage regimen. RESULTS: Overall, there was a substantial decline in CD4 cell counts from a median of 125 to 83 cells/mm3 in the average 28 day period, with median proportionate and absolute losses of 26% and 24 cells/mm3 per month, respectively (P < 0.008). This tended to be greater in individuals studied sooner after interrupting therapy (P = 0.03) and in those with CD4 cell counts above the pre-therapy baseline (P = 0.06). There was a strong negative correlation between the proportionate increase in viral load and the absolute change in CD4 cell count (-0.66, P = 0.0002). CONCLUSION: Patients with relatively advanced HIV infection interrupting antiretroviral therapy after failing a protease inhibitor-containing regimen require frequent monitoring because CD4 cell counts appear to fall quite rapidly, at least in the first few weeks after interruption.

The cellular basis of immune induction at mucosal surfaces by DNA vaccination.

The nasal mucosa provides a simple, non-invasive route to deliver DNA encoding the gene of interest to stimulate mucosal and systemic immune responses. However, unlike the intradermal or intramuscular routes for plasmid DNA (pDNA) delivery, immune responsiveness to antigen exposure at the respiratory mucosa is tightly regulated, consistent with the balance between active immunity and non-responsiveness to pathogenic or inert environmental antigens. We have characterised the antigen presenting cell types, their distribution and activation status following nasal vaccination with pDNA-cytofectin complexes encoding model antigens. We demonstrate that nasal immunisation is associated with expression of the encoded protein in a small population of dendritic cells and macrophages at the site of pDNA delivery, in the draining lymph nodes (LN) and in the spleen. Antigen expression by nasal dendritic cells was associated with up-regulation of surface MHC class II and CD86 expression and functional activation of T-lymphocytes. The results highlight the potential of intranasal vaccination with pDNA, provided the activation / costimulatory requirements for an active immune response are achieved.

'Naïve' and 'memory' CD4+ T-cells and T-cell receptor (TCR) V beta repertoire dynamics are independent of the levels of viremia following HIV seroconversion.

The progression of 'naive' and 'memory' T-cells and the T-cell receptor Vbeta (TCR Vbeta) repertoire dynamics within the peripheral CD4+ T-cell compartment were studied in individuals following HIV seroconversion. Profound TCR Vbeta repertoire perturbations were observed within the CD4+ T-cell pool in treatment-naive patients regardless of their levels of viremia during the first 6-8 months after seroconversion. The ratio of 'naive' to 'memory' CD4+ T-cells as well as the TCR Vbeta repertoire dynamics did not appear to correlate with absolute numbers of CD4 T-cells.

Use of immunoblot detection of serum antibodies in the diagnosis of chronic Pseudomonas aeruginosa lung infection in cystic fibrosis.

Antibodies to Pseudomonas aeruginosa were investigated in serum from cystic fibrosis (CF) patients by immunoblotting (Western blotting). The results were compared with determinations of precipitating antibodies in serum by crossed immune electrophoresis (CIE). The number of CIE precipitins is a sensitive and specific indication of infection and is used, with sputum bacteriology, to distinguish between colonisation and invasive lung infection. Immunoblotting was considerably more sensitive than CIE for detecting antibodies to P. aeruginosa. Paired serum samples from 64 CF patients, taken before a diagnosis of P. aeruginosa lung infection and immediately afterwards, showed a marked increase in the number of serum antibodies with the onset of infection. The intensity of the reaction, as shown by the density of blotted bands, was also increased. Laser scanning densitometry of immunoblots, and of photographic negatives taken from them, was used to quantify the increases. Differences in the number and intensity of blotted bands were highly significant between the two groups. The reproducibility of the method was good. An immunoblot assay may be a sensitive and useful method for routine diagnosis of early P. aeruginosa lung infection in CF.

Disruption of the mauna loa magma system by the 1868 hawaiian earthquake: geochemical evidence.

To test whether a catastrophic earthquake could affect an active magma system, mean abundances (adjusted for "olivine control") of titanium, potassium, phosphorus, strontium, zirconium, and niobium of historic lavas erupted from Mauna Loa Volcano, Hawaii, after 1868 were analyzed and were found to decrease sharply relative to lavas erupted before 1868. This abrupt change in lava chemistry, accompanied by a halved lava-production rate for Mauna Loa after 1877, is interpreted to reflect the disruptive effects of a magnitude 7.5 earthquake in 1868. This interpretation represents a documentable case of changes in magmatic chemical variations initiated or accelerated by a major tectonic event.

Holocene eruptive activity of el chichon volcano, chiapas, Mexico.

Geologic and radiometric-age data indicate that El Chichón was frequently and violently active during the Holocene, including eruptive episodes about 600, 1250, and 1700 years ago and several undated, older eruptions. These episodes, involving explosive eruptions of sulfur-rich magma and associated dome-growth processes, were apparently separated by intervals of approximately 350 to 650 years. Some of El Chichón's eruptions may correlate with unusual atmospheric phenomena around A.D. 1300 and possibly A.D. 623.