Using evolution to generate sustainable malaria control with spatial repellents.

Published onlineJournal ArticleThis is the final version of the article. Available from eLife Sciences Publications via the DOI in this record.Evolution persistently undermines vector control programs through insecticide resistance. Here we propose a novel strategy which instead exploits evolution to generate and sustain new control tools. Effective spatial repellents are needed to keep vectors out of houses. Our approach generates such new repellents by combining a high-toxicity insecticide with a candidate repellent initially effective against only part of the vector population. By killing mosquitoes that enter treated properties the insecticide selects for vector phenotypes deflected by the repellent, increasing efficacy of the repellent against the target vector population and in turn protecting the insecticide against the spread of insecticide resistance. Using such evolved spatial repellents offers an evolutionarily sustainable, 'double-dip' system of disease control combining mortality and repellence. We formalize this idea using models which explore vector population genetics and disease transmission probabilities and show that using evolved spatial repellents is theoretically achievable, effective and sustainable.Biotechnology and Biological Sciences Research Council BB/L010879/1 NERC Environmental Bioinformatics Centre NE/J009784/

Critical control of flooding and draining sequences on the environmental risk of Zn-contaminated riverbank sediments

Purpose: Diffuse pollution emanating from metal mining impacted sediment could serve as a barrier to achieving European Union Water Framework Directive and US Clean Water Act requirements. UK climate projections (UKCP09) predict increases in rainfall and aridity that will influence river stage alternately exposing and submersing contaminated riverbank sediment. Research focuses on the environmental contaminant dissolved Zn and investigates patterns of release, key geochemical mechanisms controlling Zn mobilisation and the environmental risk of sediment subjected to these perturbations. Materials and methods: Using two laboratory mesocosm experiments, metal mining-contaminated sediment was subjected to alternate wet and dry sequences of different duration and frequency. The first experiment was run to determine the influence of submersion and exposure of contaminated sediment on releases of Zn and to establish environmental risk. The second experiment utilised diffusional equilibration in thin film (DET) to observe the patterns of Zn release, with depth, in the sediment. Pore water chemical analysis at the sediment-water interface enabled elucidation of key geochemical mechanisms of control of Zn mobilisation. Results and discussion: Patterns of Zn release were found to be different, depending on the length of wet and dry period. High concentrations of dissolved Zn were released at the start of a flood for runs with longer dry periods. A buildup of soluble Zn sulphate minerals over long dry periods followed by dissolution on first flood wetting was a key geochemical mechanism controlling Zn release. For longer wet runs, increases in dissolved Mn and Zn were observed over the flood period. Key geochemical mechanisms controlling Zn mobilisation for these runs were: (i) reductive dissolution of Mn (hydr)oxides and release of partitioned Zn over prolonged flood periods followed by (ii) oxidation and precipitation of Mn (hydr)oxides and sorption of Zn on exposure to atmospheric conditions. Conclusions: Mesocosm experiments were a first step in understanding the effects of UK climate projections on the riverbank environment. Contaminated sediment was found to pose a significant environmental risk in response to hydrological perturbations. The ‘transient’ nature of dissolved Zn release could make identifying the exact sources of pollution a challenge; therefore, further field studies are advised to monitor contaminant releases under a range of hydrological conditions and account for complex hydrology at mining sites

Development of a laboratory-based transmission diffraction technique for in situ deformation studies of Mg alloys

A laboratory-based transmission X-ray diffraction technique was developed to measure elastic lattice strains parallel to the loading direction during in situ tensile deformation. High-quality transmission X-ray diffraction data were acquired in a time frame suitable for in situ loading experiments by application of a polycapillary X-ray optic with a conventional laboratory Cu X-ray source. Based on the measurement of two standard reference materials [lanthanum hexaboride (NIST SRM 660b) and silicon (NIST SRM 640c)], precise instrumental alignment and calibration of the transmission diffraction geometry were realized. These results were also confirmed by the equivalent data acquired using the standard Bragg-Brentano measurement geometry. An empirical Caglioti function was employed to describe the instrumental broadening, while an axis of rotation correction was used to measure and correct the specimen displacement from the centre of the goniometer axis. For precise Bragg peak position and hkil intensity information, a line profile fitting methodology was implemented, with Pawley refinement used to measure the sample reference lattice spacings (d o (hkil)). It is shown that the relatively large X-ray probe size available (7 × 714mm) provides a relatively straightforward approach for improving the grain statistics for the study of metal alloys, where grain sizes in excess of 114μm can become problematic for synchrotron-based measurements. This new laboratory-based capability was applied to study the lattice strain evolution during the elastic-plastic transition in extruded and rolled magnesium alloys. A strain resolution of 2 × 10-4 at relatively low 2θ angles (20-65° 2θ) was achieved for the in situ tensile deformation studies. In situ measurement of the elastic lattice strain accommodation with applied stress in the magnesium alloys indicated the activation of dislocation slip and twin deformation mechanisms. Furthermore, measurement of the relative change in the intensity of 0002 and 10 3 was used to quantify {10 2} 011 tensile twin onset and growth with applied load

Eave tubes for malaria control in Africa: a modelling assessment of potential impact on transmission.

BACKGROUND: Novel interventions for malaria control are necessary in the face of problems such as increasing insecticide resistance and residual malaria transmission. One way to assess performance prior to deployment in the field is through mathematical modelling. Modelled here are a range of potential outcomes for eave tubes, a novel mosquito control tool combining house screening and targeted use of insecticides to provide both physical protection and turn the house into a lethal mosquito killing device. METHODS: The effect of eave tubes was modelled by estimating the reduction of infectious mosquito bites relative to no intervention (a transmission metric defined as relative transmission potential, RTP). The model was used to assess how RTP varied with coverage when eave tubes were used as a stand-alone intervention, or in combination with either bed nets (LLINs) or indoor residual spraying (IRS). RESULTS: The model indicated the impact of eave tubes on transmission increases non-linearly as coverage increases, suggesting a community level benefit. For example, based on realistic assumptions, just 30 % coverage resulted in around 70 % reduction in overall RTP (i.e. there was a benefit for those houses without eave tubes). Increasing coverage to around 70 % reduced overall RTP by >90 %. Eave tubes exhibited some redundancy with existing interventions, such that combining interventions within properties did not give reductions in RTP equal to the sum of those provided by deploying each intervention singly. However, combining eave tubes and either LLINs or IRS could be extremely effective if the technologies were deployed in a non-overlapping way. CONCLUSION: Using predictive models to assess the benefit of new technologies has great value, and is especially pertinent prior to conducting expensive, large scale, randomized controlled trials. The current modelling study indicates eave tubes have considerable potential to impact malaria transmission if deployed at scale and can be used effectively with existing tools, especially if they are combined strategically with, for example, IRS and eave tubes targeting different houses.This work was supported by European Union Seventh Framework Programme Grant 306105, FP7-HEALTH-2012-INNOVATION-1

Environmental risk of severely Pb-contaminated riverbank sediment as a consequence of hydrometeorological perturbation

Metal mining activities have resulted in the widespread metal pollution of soils and sediments and are a worldwide health concern. Pb is often prolific in metal-mining impacted systems and has acute and chronic toxic effects. Environmental factors controlling diffuse pollution from contaminated riverbank sediment are currently seen as a “black box” from a process perspective. This limits our ability to accurately predict and model releases of dissolved Pb. Previous work by the authors uncovered key mechanisms responsible for the mobilisation of dissolved Zn. The current study identifies key mechanisms controlling the mobilisation of dissolved Pb, and the environmental risk these releases pose, in response to various sequences of “riverbank” inundation/drainage. Mesocosm experiments designed to mimic the riverbank environment were run using sediment severely contaminated with Pb, from a mining-impacted site. Results indicated that, although Pb is generally reported as less mobile than Zn, high concentrations of dissolved Pb are released in response to longer or more frequent flood events. Furthermore, the geochemical mechanisms of release for Zn and Pb were different. For Zn, mechanisms were related to reductive dissolution of Mn (hydr)oxides with higher concentrations released, at depth, over prolonged flood periods. For Pb, key mechanisms of release were related to the solubility of anglesite and the oxidation of primary mineral galena, where periodic drainage events serve to keep sediments oxic, particularly at the surface. The results are concerning because climate projections for the UK indicate a rise in the occurrence of localized heavy rainfall events that could increase flood frequency and/or duration. This study is unique in that it is the first to uncover key mechanisms responsible for dissolved Pb mobilisation from riverbank sediments. The mineralogy at the mining-impacted site is common to many sites worldwide and it is likely the mechanisms identified in this study are widespread

Alterations in mosquito behaviour by malaria parasites: potential impact on force of infection

BACKGROUND: A variety of studies have reported that malaria parasites alter the behaviour of mosquitoes. These behavioural alterations likely increase transmission because they reduce the risk of vector death during parasite development and increase biting after parasites become infectious. METHODS: A mathematical model is used to investigate the potential impact of these behavioural alterations on the lifetime number of infectious bites delivered. The model is used to explore the importance of assumptions about the magnitude and distribution of mortality as well as the importance of extrinsic incubation period and gonotrophic cycle length. Additionally, the model is applied to four datasets taken from actual transmission settings. RESULTS: The impact of behavioural changes on the relative number of lifetime bites is highly dependent on assumptions about the distribution of mortality over the mosquito-feeding cycle. Even using fairly conservative estimates of these parameters and field collected data, the model outputs suggest that altered feeding could easily cause a doubling in the force of infection. CONCLUSIONS: Infection-induced behavioural alterations have their greatest impact on the lifetime number of infectious bites in environments with high feeding-related adult mortality and many pre-infectious feeding cycles. Interventions that increase feeding-associated mortality are predicted to amplify the relative fitness benefits and hence enhance the strength of selection for behavioural alteration.This study was supported by the NIH-NIAID ICEMR award (#U19AI089676-01)

Individuals with knee impairments identify items in need of clarification in the Patient Reported Outcomes Measurement Information System (PROMIS®) pain interference and physical function item banks - a qualitative study

Background: The content and wording of the Patient Reported Outcome Measurement Information System (PROMIS) Physical Function and Pain Interference item banks have not been qualitatively assessed by individuals with knee joint impairments. The purpose of this investigation was to identify items in the PROMIS Physical Function and Pain Interference Item Banks that are irrelevant, unclear, or otherwise difficult to respond to for individuals with impairment of the knee and to suggest modifications based on cognitive interviews. Methods: Twenty-nine individuals with knee joint impairments qualitatively assessed items in the Pain Interference and Physical Function Item Banks in a mixed-methods cognitive interview. Field notes were analyzed to identify themes and frequency counts were calculated to identify items not relevant to individuals with knee joint impairments. Results: Issues with clarity were identified in 23 items in the Physical Function Item Bank, resulting in the creation of 43 new or modified items, typically changing words within the item to be clearer. Interpretation issues included whether or not the knee joint played a significant role in overall health and age/gender differences in items. One quarter of the original items (31 of 124) in the Physical Function Item Bank were identified as irrelevant to the knee joint. All 41 items in the Pain Interference Item Bank were identified as clear, although individuals without significant pain substituted other symptoms which interfered with their life. Conclusions: The Physical Function Item Bank would benefit from additional items that are relevant to individuals with knee joint impairments and, by extension, to other lower extremity impairments. Several issues in clarity were identified that are likely to be present in other patient cohorts as well

Induced Disjoint Paths in Circular-Arc Graphs in Linear Time

The Induced Disjoint Paths problem is to test whether a graph G with k distinct pairs of vertices (si,ti) contains paths P1,…,Pk such that Pi connects si and ti for i=1,…,k, and Pi and Pj have neither common vertices nor adjacent vertices (except perhaps their ends) for 1≤

Critical Shifts in Trace Metal Transport and Remediation Performance under Future Low River Flows.

Exceptionally low river flows are predicted to become more frequent and more severe across many global regions as a consequence of climate change. Investigations of trace metal transport dynamics across streamflows reveal stark changes in water chemistry, metal transformation processes, and remediation effectiveness under exceptionally low-flow conditions. High spatial resolution hydrological and water quality datasets indicate that metal-rich groundwater will exert a greater control on stream water chemistry and metal concentrations because of climate change. This is because the proportion of stream water sourced from mined areas and mineralized strata will increase under predicted future low-flow scenarios (from 25% under Q45 flow to 66% under Q99 flow in this study). However, mineral speciation modelling indicates that changes in stream pH and hydraulic conditions at low flow will decrease aqueous metal transport and increase sediment metal concentrations by enhancing metal sorption directly to streambed sediments. Solute transport modelling further demonstrates how increases in the importance of metal-rich diffuse groundwater sources at low flow could minimize the benefits of point source metal contamination treatment. Understanding metal transport dynamics under exceptionally low flows, as well as under high flows, is crucial to evaluate ecosystem service provision and remediation effectiveness in watersheds under future climate change scenarios

Connective tissue disease related interstitial lung diseases and idiopathic pulmonary fibrosis: provisional core sets of domains and instruments for use in clinical trials

Rationale Clinical trial design in interstitial lung diseases (ILDs) has been hampered by lack of consensus on appropriate outcome measures for reliably assessing treatment response. In the setting of connective tissue diseases (CTDs), some measures of ILD disease activity and severity may be confounded by non-pulmonary comorbidities. Methods The Connective Tissue Disease associated Interstitial Lung Disease (CTD-ILD) working group of Outcome Measures in Rheumatology—a non-profit international organisation dedicated to consensus methodology in identification of outcome measures—conducted a series of investigations which included a Delphi process including >248 ILD medical experts as well as patient focus groups culminating in a nominal group panel of ILD experts and patients. The goal was to define and develop a consensus on the status of outcome measure candidates for use in randomised controlled trials in CTD-ILD and idiopathic pulmonary fibrosis (IPF). Results A core set comprising specific measures in the domains of lung physiology, lung imaging, survival, dyspnoea, cough and health-related quality of life is proposed as appropriate for consideration for use in a hypothetical 1-year multicentre clinical trial for either CTD-ILD or IPF. As many widely used instruments were found to lack full validation, an agenda for future research is proposed. Conclusion Identification of consensus preliminary domains and instruments to measure them was attained and is a major advance anticipated to facilitate multicentre RCTs in the field