What do we need for robust and quantitative health impact assessment?

Health impact assessment (HIA) aims to make the health consequences of decisions explicit. Decision-makers need to know that the conclusions of HIA are robust. Quantified estimates of potential health impacts may be more influential but there are a number of concerns. First, not everything that can be quantified is important. Second, not everything that is being quantified at present should be, if this cannot be done robustly. Finally, not everything that is important can be quantified; rigorous qualitative HIA will still be needed for a thorough assessment. This paper presents the first published attempt to provide practical guidance on what is required to perform robust, quantitative HIA. Initial steps include profiling the affected populations, obtaining evidence from for postulated impacts, and determining how differences in subgoups' exposures and suscepibilities affect impacts. Using epidemiological evidence for HIA is different from carrying out a new study. Key steps in quantifying impacts are mapping the causal pathway, selecting appropriate outcome measures and selecting or developing a statistical model. Evidence from different sources is needed. For many health impacts, evidence of an effect may be scarce and estimates of the size and nature of the relationship may be inadequate. Assumptions and uncertainties must therefore be explicit. Modelled data can sometimes be tested against empirical data but sensitivity analyses are crucial. When scientific problems occur, discontinuing the study is not an option, as HIA is usually intended to inform real decisions. Both qualitative and quantitative elements of HIA must be performed robustly to be of value

Organic nitrogen in aerosols and precipitation at Barbados and Miami: Implications regarding sources, transport and deposition to the western subtropical North Atlantic

The deposition of anthropogenic nitrogen (N) species is believed to have a significant impact on the oligotrophic North Atlantic, but the magnitude of ecological effects remains uncertain because the deposition of water soluble organic N (WSON) is poorly quantified. Here we present measurements of water soluble inorganic N (WSIN) and WSON in aerosol and rain at two subtropical North Atlantic time series sites: Barbados and Miami. WSON total deposition rates ranged from 17.9 mmol m−2 yr−1 to 49.6 mmol m−2 yr−1, contributing on average only 6–14% of total N deposition, less than half the poorly constrained global average which is typically cited as 30%. On an event basis, biomass burning and dust events yielded the largest concentrations of WSON. However, biomass burning was relatively infrequent and highly variable in composition, and much of the organic N associated with dust appeared to be externally adsorbed from pollution sources. Conversely, in Miami pollution made relatively small contributions of WSON on an event basis, but impacts were relatively frequent, making pollution one of the largest sources of WSON during the year. The largest contributor to WSON was volatile basic organic N (VBON) species, which were present at concentrations 1–2 times higher than particulate WSON. Despite VBON inputs, samples associated with pollution-source trajectories yielded much more inorganic N than WSON. Consequently, we would expect that in the future as anthropogenic N emissions increase, inorganic nitrogen will remain the dominant form of N that is deposited to the western North Atlantic

In vitro and in vivo studies of the trypanocidal properties of WRR-483 against Trypanosoma cruzi.

BackgroundCruzain, the major cysteine protease of Trypanosoma cruzi, is an essential enzyme for the parasite life cycle and has been validated as a viable target to treat Chagas' disease. As a proof-of-concept, K11777, a potent inhibitor of cruzain, was found to effectively eliminate T. cruzi infection and is currently a clinical candidate for treatment of Chagas' disease.Methodology/principal findingsWRR-483, an analog of K11777, was synthesized and evaluated as an inhibitor of cruzain and against T. cruzi proliferation in cell culture. This compound demonstrates good potency against cruzain with sensitivity to pH conditions and high efficacy in the cell culture assay. Furthermore, WRR-483 also eradicates parasite infection in a mouse model of acute Chagas' disease. To determine the atomic-level details of the inhibitor interacting with cruzain, a 1.5 A crystal structure of the protease in complex with WRR-483 was solved. The structure illustrates that WRR-483 binds covalently to the active site cysteine of the protease in a similar manner as other vinyl sulfone-based inhibitors. Details of the critical interactions within the specificity binding pocket are also reported.ConclusionsWe demonstrate that WRR-483 is an effective cysteine protease inhibitor with trypanocidal activity in cell culture and animal model with comparable efficacy to K11777. Crystallographic evidence confirms that the mode of action is by targeting the active site of cruzain. Taken together, these results suggest that WRR-483 has potential to be developed as a treatment for Chagas' disease

Birth weight, early childhood growth and lung function in middle to early old age: 1946 British birth cohort

Background Findings from previous studies investigating the relationship between birth weight and adult lung function have been inconsistent, and data on birth weight and adult lung function decline are lacking. Few studies have investigated the relation between early childhood growth and adult lung function. Methods FEV1 and FVC were measured at ages 43 years, 53 years and 60–64 years in the 1946 British birth cohort study. Multiple linear regression models were fitted to study associations with birth weight and weight gain at age 0–2 years. Multilevel models assessed how associations changed with age, with FEV1 and FVC as repeated outcomes. Results 3276 and 3249 participants were included in FEV1 and FVC analyses, respectively. In women, there was a decreasing association between birth weight and FVC with age. From the multilevel model, for every 1 kg higher birth weight, FVC was higher on average by 66.3 mL (95% CI 0.5 to 132) at 43 years, but significance was lost at 53 years and 60–64 years. Similar associations were seen with FEV1, but linear change (decline) from age 43 years lost statistical significance after full adjustment. In men, associations with birth weight were null in multilevel models. Higher early life weight gain was associated with higher FEV1 at age 43 years in men and women combined but not in each sex. Conclusions Birth weight is positively associated with adult lung function in middle age, particularly in women, but the association diminishes with age, potentially due to accumulating environmental influences over the life course

Atmospheric deposition of nutrients and excess N formation in the North Atlantic

Anthropogenic emissions of nitrogen (N) to the atmosphere have been strongly increasing during the last century, leading to greater atmospheric N deposition to the oceans. The North Atlantic subtropical gyre (NASTG) is particularly impacted. Here, upwind sources of anthropogenic N from North American and European sources have raised atmospheric N deposition to rates comparable with N2 fixation in the gyre. However, the biogeochemical fate of the deposited N is unclear because there is no detectable accumulation in the surface waters. Most likely, deposited N accumulates in the main thermocline instead, where there is a globally unique pool of N in excess of the canonical Redfield ratio of 16 N:1 phosphorus (P). To investigate this depth zone as a sink for atmospheric N, we used a biogeochemical ocean transport model and year 2000 nutrient deposition data. We examined the maximum effects of three mechanisms that may transport excess N from the ocean surface to the main thermocline: physical transport, preferential P remineralization of sinking particles, and nutrient uptake and export by phytoplankton at higher than Redfield N:P ratios. Our results indicate that atmospheric deposition may contribute 13-19% of the annual excess N input to the main thermocline. Modeled nutrient distributions in the NASTG were comparable to observations only when non-Redfield dynamics were invoked. Preferential P remineralization could not produce realistic results on its own; if it is an important contributor to ocean biogeochemistry, it must co-occur with N2 fixation. The results suggest that: 1) the main thermocline is an important sink for anthropogenic N deposition, 2) non-Redfield surface dynamics determine the biogeochemical fate of atmospherically deposited nutrients, and 3) atmospheric N accumulation in the main thermocline has long term impacts on surface ocean biology

Health Technology Scenarios and Implications for Spectrum

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Variable cavity volume tooling for high-performance resin infusion moulding

This article describes the research carried out by Warwick under the BAE Systems/EPSRC programme ‘Flapless Aerial Vehicles Integrated Interdisciplinary Research – FLAVIIR’. Warwick's aim in FLAVIIR was to develop low-cost innovative tooling technologies to enable the affordable manufacture of complex composite aerospace structures and to help realize the aim of the Grand Challenge of maintenance-free, low-cost unmanned aerial vehicle manufacture. This article focuses on the evaluation of a novel tooling process (variable cavity tooling) to enable the complete infusion of resin throughout non-crimp fabric within a mould cavity under low (0.1 MPa) injection pressure. The contribution of the primary processing parameters to the mechanical properties of a carbon composite component (bulk-head lug section), and the interactions between parameters, was determined. The initial mould gap (di) was identified as having the most significant effect on all measured mechanical properties, but complex interactions between di, n (number of fabric layers), and vc (mould closure rate) were observed. The process capability was low due to the manual processing, but was improved through process optimization, and delivered properties comparable to high-pressure resin transfer moulding

Atypical chemokine receptor ACKR2 controls branching morphogenesis in the developing mammary gland

Macrophages are important regulators of branching morphogenesis during development and postnatally in the mammary gland. Regulation of macrophage dynamics during these processes can therefore have a profound impact on development. We demonstrate here that the developing mammary gland expresses high levels of inflammatory CC-chemokines, which are essential in vivo regulators of macrophage migration. We further demonstrate that the atypical chemokine receptor ACKR2, which scavenges inflammatory CC-chemokines, is differentially expressed during mammary gland development. We have previously shown that ACKR2 regulates macrophage dynamics during lymphatic vessel development. Here, we extend these observations to reveal a novel role for ACKR2 in regulating the postnatal development of the mammary gland. Specifically, we show that Ackr2−/− mice display precocious mammary gland development. This is associated with increased macrophage recruitment to the developing gland and increased density of the ductal epithelial network. These data demonstrate that ACKR2 is an important regulator of branching morphogenesis in diverse biological contexts and provide the first evidence of a role for chemokines and their receptors in postnatal development processes

Using metal ratios to detect emissions from municipal waste incinerators in ambient air pollution data, atmospheric environment

This study aimed to fingerprint emissions from six municipal waste incinerators (MWIs) and then test if these fingerprint ratios could be found in ambient air samples. Stack emissions tests from MWIs comprised As, Cd, Cr, Cu, Pb, Mn, Ni, V and Hg. Those pairs of metals showing good correlation (R &gt; 0.75) were taken as tracers of MWI emissions and ratios calculated: Cu/Pb; Cd/Pb; Cd/Cu and Cr/Pb. Emissions ratios from MWIs differed significantly from those in ambient rural locations and those close to traffic. In order to identify MWI emissions in ambient air two analysis tests were carried out. The first, aimed to explore if MWI emissions dominate the ambient concentrations. The mean ambient ratio of each of the four metal ratios were calculated for six ambient sampling sites within 10 km from a MWI under stable meteorological conditions when the wind blew from the direction of the incinerator. Under these meteorological conditions ambient Cd/Pb was within the range of MWI emissions at one location, two monitoring sites measured mean Cr/Pb ratios representative of the MWI emissions and the four sites measured values of Cu/Pb within the range of MWI emissions. No ambient measurements had mean Cd/Cu ratios within the MWI values. Even though MWI was not the main source determining the ambient metal ratios, possible occasional plume grounding might have occurred. The second test then examined possible plume grounding by identifying the periods when all metal ratios differed from rural and traffic values at the same time and were consistent with MWI emissions. Metal ratios consistent with MWI emissions were found in ambient air within 10 km of one MWI for about 0.2% of study period. Emissions consistent with a second MWI were similarly detected at two ambient measurement sites about 0.1% and 0.02% of the time. Where plume grounding was detected, the maximum annual mean particulate matter (PM) from the MWI was estimated to be 0.03 μg m-3 to 0.12 μg m-3; 2-3 orders of magnitude smaller than background ambient PM10 concentrations. Ambient concentrations of Cr increased by 1.6-3.0 times when MWI emissions were detected. From our analysis we found no evidence of incinerator emissions in ambient metal concentrations around four UK MWIs. The six UK MWIs studied contributed little to ambient PM10 concentrations.</p