Modelling childhood exposure to indoor air pollution across socio-economic groups

Population exposure to indoor air pollution may be modified by socio-economic factors in a number of ways, but such factors are rarely considered in indoor air quality models. Here, we present a model which estimates exposure to indoor PM2.5 across income groups for the Greater London childhood population. The model uses a national time-activity database, which gives the percentage of each population group in different residential and non-residential microenvironments and links this to simulated domestic indoor concentrations from the building physics model, EnergyPlus, and for non-residential microenvironments to a mass-balance model with empirically measured building air change rates selected according to a probabilistic approach. The results display distributions of exposure across income groups for children in London, where median daily exposure is 14.4 ug/m3 for children in the lowest income quintile versus 11.7 ug/m3 for those in the highest income quintile

Exposure to indoor air pollution across socio-economic groups: A review of the literature and a modelling methodology

Disparities in outdoor air pollution exposure between populations of different socio-economic status is a growing area of research, widely explored in environmental health literature. However, in developed countries, around 80% of time is spent indoors, meaning indoor air pollution may be a better proxy for personal exposure. Building characteristics and occupant behaviour mean indoor air pollution may also vary across socio-economic groups, leading to health inequalities. Following the results of a review carried out into indoor air pollution disparities, we incorporate socio-economic information into an indoor air quality model in order to evaluate exposure disparities in the indoor environment. The building physics tool EnergyPlus was used to model the effect of two policy interventions on indoor exposure to PM2.5 in two socio-economically different populations. Results suggest that households of low socio-economic status may be disproportionately affected by building and/or environmental policies which are implemented without consideration of the wider socio-economic processes governing the space

A participatory process for modelling green infrastructure implementation in London

Cities face the interlinked challenges of transforming environmental quality, sustainability, population health and health equity. There is increasing interest in green infrastructure in connection with these challenges. In order to go beyond an understanding of the effects of green infrastructure and develop an understanding of how policymakers should think about it, we need to capture potential interactions and be aware of possible unintended consequences. In our research, we applied a systems-thinking approach: integrating participatory engagements, qualitative system dynamics modelling, and an assessment framework in order to address the challenge. This allowed us to see multiple dynamics between the prioritisation of policymakers, different types of green infrastructure, and environmental and health outcomes. It also made us ask different and more integrated questions, and suggested a methodology for addressing the challenge of transforming cities

Combining evolutionary inference and metabolomics to identify plants with medicinal potential

Plants have been a source of medicines in human cultures for millennia. The past decade has seen a decline in plant-derived medicines due to the time-consuming nature of screening for biological activity and a narrow focus on individual candidate plant taxa. A phylogenetically informed approach can be both more comprehensive in taxonomic scope and more systematic, because it allows identification of evolutionary lineages with higher incidence of medicinal activity. For these reasons, phylogenetics is being increasingly applied to the identification of novel botanic sources of medicinal compounds. These biologically active compounds are normally derived from plant secondary or specialized metabolites generally produced as induced responses and often playing a crucial role in plant defense against herbivores and pathogens. Since these compounds are typically bioactive they serendipitously offer potential therapeutic properties for humans, resulting in their use by traditional societies and ultimately drug lead development by natural product chemists and pharmacologists. The expression of these metabolites is likely the result of coevolutionary processes between plants and the other species with which they interact and effective metabolites are thus selected upon through evolution. Recent research on plant phylogeny coupled with metabolomics, which is the comprehensive analysis of metabolite profiles, has identified that related taxa produce similar secondary metabolites, although correlations are dependent also on environmental factors. Modern mass spectrometry and bioinformatic chemical networking tools can now assist high throughput screening to discover structurally related and potentially new bioactive compounds. The combination of these metabolomic approaches with phylogenetic comparative analysis of the expression of metabolites across plant taxa could therefore greatly increase our capacity to identify taxa for medicinal potential. This review examines the current status of identification of new plant sources of medicine and the current limitations of identifying plants as drug candidates. It investigates how ethnobotanic knowledge, phylogenetics and novel approaches in metabolomics can be partnered to help in characterizing taxa with medicinal potential

Live simultaneous monitoring of mineral deposition and lipid accumulation in differentiating stem cells

Mesenchymal stem cells (MSCs) are progenitors for bone-forming osteoblasts and lipid-storing adipocytes, two major lineages co-existing in bone marrow. When isolated in vitro, these stem cells recapitulate osteoblast or adipocyte formation if treated with specialised media,modelling how these lineages interact in vivo. Osteogenic differentiation is characterised by mineral deposits accumulating in the extracellular matrix, typically assessed using histological techniques. Adipogenesis occurs with accumulation of intracellular lipids that can be routinely visualised by Oil Red O staining. In both cases, staining requires cell fixation and is thus limited to end-point assessments. Here, a vital staining approach was developed to simultaneously detect mineral deposits and lipid droplets in differentiating cultures. Stem cells induced to differentiate produced mixed cultures containing adipocytes and bone-like nodules, and after two weeks live cultures were incubated with tetracycline hydrochloride and Bodipy to label mineral- and lipid-containing structures, respectively. Fluorescence microscopy showed the simultaneous visualisation of mineralised areas and lipid-filled adipocytes in live cultures. Combined with the nuclear stain Hoechst 33258, this approach further enabled live confocal imaging of adipogenic cells interspersed within the mineralised matrix. This multiplex labelling was repeated at subsequent time-points, demonstrating the potential of this new approach for the real-time high-precision imaging of live stem cells

A phase II study of weekly neoadjuvant chemotherapy followed by radical chemoradiation for locally advanced cervical cancer

Background: We investigated the feasibility of dose-dense neoadjuvant chemotherapy (NACT) with paclitaxel and carboplatin before radical chemoradiation (CRT) and assessed the response rate to such a regimen. Methods: CxII is a single-arm phase II trial of 46 patients, with locally advanced cervical cancer (stage Ib2-IVa). Patients received dose-dense carboplatin (AUC2) and paclitaxel (80 mg m−2) weekly for six cycles followed by CRT (40 mg m−2 of weekly cisplatin, 50.4 Gy, 28 fractions plus brachytherapy). The primary end point was response rate 12 weeks post-CRT. Results: Baseline characteristics were: median age at diagnosis 43 years; 72% squamous, 22% adenocarcinoma and 7% adenosquamous histologies; FIGO stage IB2 (11%), II (50%), III (33%), IV (7%). Complete or partial response rate was 70% (95% CI: 54–82) post-NACT and 85% (95% CI: 71–94) post-CRT. The median follow-up was 39.1 months. Overall and progression-free survivals at 3 years were 67% (95% CI: 51–79) and 68% (95% CI: 51–79), respectively. Grade 3/4 toxicities were 20% during NACT (11% haematological, 9% non-haematological) and 52% during CRT (haematological: 41%, non-haematological: 22%). Conclusion: A good response rate is achieved by dose-dense weekly NACT with carboplatin and paclitaxel followed by radical CRT. This treatment regimen is feasible as evidenced by the acceptable toxicity of NACT and by the high compliance to radiotherapy (98%)