Sensitivity of predicted bioaerosol exposure from open windrow composting facilities to ADMS dispersion model parameters

Bioaerosols are released in elevated quantities from composting facilities and are associated with negative health effects, although dose-response relationships are not well understood, and require improved exposure classification. Dispersion modelling has great potential to improve exposure classification, but has not yet been extensively used or validated in this context. We present a sensitivity analysis of the ADMS dispersion model specific to input parameter ranges relevant to bioaerosol emissions from open windrow composting. This analysis provides an aid for model calibration by prioritising parameter adjustment and targeting independent parameter estimation. Results showed that predicted exposure was most sensitive to the wet and dry deposition modules and the majority of parameters relating to emission source characteristics, including pollutant emission velocity, source geometry and source height. This research improves understanding of the accuracy of model input data required to provide more reliable exposure predictions

Estimating Aspergillus fumigatus exposure from outdoor composting activities in England between 2005 and 14

Bioaerosols, ubiquitous in ambient air, are released in elevated concentrations from composting facilities with open-air processing areas. However, spatial and temporal variability of bioaerosols, particularly in relation to meteorology, is not well understood. Here we model relative concentrations of Aspergillus fumigatus at each postcode-weighted centroid within 4 km of 217 composting facilities in England between 2005 and 2014. Facilities were geocoded with the aid of satellite imagery. Data from existing bioaerosol modelling literature were used to build emission profiles in ADMS. Variation in input parameters between each modelled facility was reduced to a minimum. Meteorological data for each composting facility was derived from the nearest SCAIL-Agriculture validated meteorological station. According to our results, modelled exposure risk was driven primarily by wind speed, direction and time-varying emissions factors incorporating seasonal fluctuations in compostable waste. Modelled A.fumigatus concentrations decreased rapidly from the facility boundary and plateaued beyond 1.5–2.0 km. Where multiple composting facilities were within 4 km of each other, complex exposure risk patterns were evident. More long-term bioaerosol monitoring near facilities is needed to help improve exposure estimation and therefore assessment of any health risks to local populations

Pelvic pain correlates with peritoneal macrophage abundance not endometriosis

Endometriosis is a chronic neuroinflammatory pain condition affecting ~180 million women worldwide. Surgical removal or hormonal suppression of endometriosis lesions only relieves pain symptoms in some women and symptomatic relapse following treatment is common. Identifying factors that contribute to pain is key to developing new therapies. We collected peritoneal fluid samples and clinical data from a cohort of women receiving diagnostic laparoscopy for suspected endometriosis (n = 52). Peritoneal fluid immune cells were analysed by flow cytometry and data compared with pain scores determined using the pain domain of the Endometriosis Health Profile Questionnaire (EHP-30) in order to investigate the association between peritoneal immune cells and pain symptoms. Pain scores were not different between women with or without endometriosis, nor did they differ according to disease stage; consistent with a poor association between disease presentation and pain symptoms. However, linear regression and correlation analysis demonstrated that peritoneal macrophage abundance correlated with the severity of pelvic pain. CD14(high) peritoneal macrophages negatively correlated with pain scores whereas CD14(low) peritoneal macrophages were positively correlated, independent of diagnostic outcome at laparoscopy. Stratification by pain subtype, rather than endometriosis diagnosis, resulted in the most robust correlation between pain and macrophage adundance. Pain score strongly correlated with CD14(high) (P = 0.007) and CD14(low) (P = 0.008) macrophages in patients with non-menstrual pain and also in patients who reported dysmennorhea (CD14(high) P = 0.021, CD14(low) P = 0.019) or dysparunia (CD14(high) P = 0.027, CD14(low) P = 0.031). These results provide new insight into the association between peritoneal macrophages and pelvic pain which may aid the identification of future therapeutic targets. LAY SUMMARY: Endometriosis is a common condition where cells similar to those that line the womb are found elsewhere in the body. It is associated with inflammation and pain in the pelvis and affects ~180 million women worldwide. Current treatments are not effective for all patients and we, therefore, need to understand what causes pain in order to develop new treatments. We investigated the types of immune cells present within the pelvis of women undergoing investigation for suspected endometriosis. Disease diagnosis and stage (I–IV) was recorded along with pain score determined by questionnaire. We characterised the immune cells present and compared them to disease stage and pain score. We found that pelvic pain was linked to the abundance of immune cells but, surprisingly, not to disease stage. These findings suggest that immune cells are closely associated with pain severity in endometriosis and may be good targets for future endometriosis treatments

Endometrial Intracrinology: Oestrogens, Androgens and Endometrial Disorders

Peripheral tissue metabolism of steroids (intracrinology) is now accepted as a key way in which tissues, such as the endometrium, can utilise inactive steroids present in the blood to respond to local physiological demands and ‘fine-tune’ the activation or inhibition of steroid hormone receptor-dependent processes. Expression of enzymes that play a critical role in the activation and inactivation of bioactive oestrogens (E1, E2) and androgens (A4, T, DHT), as well as expression of steroid hormone receptors, has been detected in endometrial tissues and cells recovered during the menstrual cycle. There is robust evidence that increased expression of aromatase is important for creating a local microenvironment that can support a pregnancy. Measurement of intra-tissue concentrations of steroids using liquid chromatography–tandem mass spectrometry has been important in advancing our understanding of a role for androgens in the endometrium, acting both as active ligands for the androgen receptor and as substrates for oestrogen biosynthesis. The emergence of intracrinology, associated with disordered expression of key enzymes such as aromatase, in the aetiology of common women’s health disorders such as endometriosis and endometrial cancer has prompted renewed interest in the development of drugs targeting these pathways, opening up new opportunities for targeted therapies and precision medicine