A high-resolution geospatial surveillance-response system for malaria elimination in Solomon Islands and Vanuatu

BACKGROUND A high-resolution surveillance-response system has been developed within a geographic information system (GIS) to support malaria elimination in the Pacific. This paper examines the application of a GIS-based spatial decision support system (SDSS) to automatically locate and map the distribution of confirmed malaria cases, rapidly classify active transmission foci, and guide targeted responses in elimination zones. METHODS Customized SDSS-based surveillance-response systems were developed in the three elimination provinces of Isabel and Temotu, Solomon Islands and Tafea, Vanuatu. Confirmed malaria cases were reported to provincial malaria offices upon diagnosis and updated into the respective SDSS as part of routine operations throughout 2011. Cases were automatically mapped by household within the SDSS using existing geographical reconnaissance (GR) data. GIS queries were integrated into the SDSS-framework to automatically classify and map transmission foci based on the spatiotemporal distribution of cases, highlight current areas of interest (AOI) regions to conduct foci-specific targeted response, and extract supporting household and population data. GIS simulations were run to detect AOIs triggered throughout 2011 in each elimination province and conduct a sensitivity analysis to calculate the proportion of positive cases, households and population highlighted in AOI regions of a varying geographic radius. RESULTS A total of 183 confirmed cases were reported and mapped using the SDSS throughout 2011 and used to describe transmission within a target population of 90,354. Automatic AOI regions were also generated within each provincial SDSS identifying geographic areas to conduct response. 82.5% of confirmed cases were automatically geo-referenced and mapped at the household level, with 100% of remaining cases geo-referenced at a village level. Data from the AOI analysis indicated different stages of progress in each province, highlighting operational implications with regards to strategies for implementing surveillance-response in consideration of the spatiotemporal nature of cases as well as logistical and financial constraints of the respective programmes. CONCLUSIONS Geospatial systems developed to guide Pacific Island malaria elimination demonstrate the application of a high resolution SDSS-based approach to support key elements of surveillance-response including understanding epidemiological variation within target areas, implementing appropriate foci-specific targeted response, and consideration of logistical constraints and costs.A.C.A.C. is supported by a Career Development Award from the Australian National Health and Medical Research Council (#631619)

The Nrf2 inhibitor brusatol is a potent antitumour agent in an orthotopic mouse model of colorectal cancer

© Evans et al. Nrf2 is a transcription factor that regulates cellular stress response and irinotecan-metabolising pathways. Its aberrant activity has been reported in a number of cancers, although relatively few studies have explored a role for Nrf2 in colorectal cancer (CRC). This study assessed the expression of Nrf2 in patient CRC tissues and explored the effect of Nrf2 modulation alone, or in combination with irinotecan, in human (HCT116) and murine (CT26) cell lines in vitro and in an orthotopic syngeneic mouse model utilising bioluminescent imaging. Using a tissue microarray, Nrf2 was found to be overexpressed (p < 0.01) in primary CRC and metastatic tissue relative to normal colon, with a positive correlation between Nrf2 expression in matched primary and metastatic samples. In vitro experiments in CRC cell lines revealed that Nrf2 siRNA and brusatol, which is known to inhibit Nrf2, decreased viability and sensitised cells to irinotecan toxicity. Furthermore, brusatol effectively abrogated CRC tumour growth in subcutaneously and orthotopicallyallografted mice, resulting in an average 8-fold reduction in luminescence at the study end-point (p=0.02). Our results highlight Nrf2 as a promising drug target in the treatment of CRC

An assessment of validity and responsiveness of generic measures of health-related quality of life in hearing impairment

This article is made available through the Brunel Open Access Publishing Fund. This article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.Purpose: This review examines psychometric performance of three widely used generic preference-based measures, that is, EuroQol 5 dimensions (EQ-5D), Health Utility Index 3 (HUI3) and Short-form 6 dimensions (SF-6D) in patients with hearing impairments. Methods: A systematic search was undertaken to identify studies of patients with hearing impairments where health state utility values were measured and reported. Data were extracted and analysed to assess the reliability, validity (known group differences and convergent validity) and responsiveness of the measures across hearing impairments. Results: Fourteen studies (18 papers) were included in the review. HUI3 was the most commonly used utility measures in hearing impairment. In all six studies, the HUI3 detected difference between groups defined by the severity of impairment, and four out of five studies detected statistically significant changes as a result of intervention. The only study available suggested that EQ-5D only had weak ability to discriminate difference between severity groups, and in four out of five studies, EQ-5D failed to detected changes. Only one study involved the SF-6D; thus, the information is too limited to conclude on its performance. Also evidence for the reliability of these measures was not found. Conclusion: Overall, the validity and responsiveness of the HUI3 in hearing impairment was good. The responsiveness of EQ-5D was relatively poor and weak validity was suggested by limited evidence. The evidence on SF-6D was too limited to make any judgment. More head-to-head comparisons of these and other preference measures of health are required.Medical Research Counci

Sequential solvent extraction for the modes of occurrence of selenium in coals of different ranks from the Huaibei Coalfield, China

Forms of selenium in bituminous coal, anthracite, and cokeite (natural coke) from Huaibei Coalfield, Anhui, China, have been determined by sequential solvent extraction. The selenium content in bulk samples is 4.0, 2.4, and 2.0 μg/g in bituminous coal, anthracite, and cokeite, respectively. The six forms of selenium determined by six-step solvent extraction are water-leachable, ion-exchangeable, organic matter-associated, carbonate-associated, silicate-associated, and sulfide-associated. The predominant forms of selenium in bituminous coal are organic matter-associated (39.0%), sulfide-associated (21.1%), and silicate bound (31.8%); these three forms account for 92% of the total. The organic matter bound-selenium decrease dramatically from bituminous coal (39.0%) to anthracite (11.6%) and to cokeite (0%), indicating that organic matter bound selenium is converted to other forms during metamorphism of the coal, most likely sulfide-form. The sulfide-associated form increased remarkably from bituminous coal (21.1%) to anthracite (50.4%) and cokeite (54.5%), indicating the formation of selenium sulfide, possibly in pyrite during the transformation of bituminous coal to anthracite and cokeite. The silicate-associated selenium in bituminous coal (31.8%) is much higher than that in anthracite (16.4%) and cokeite (15.8%), indicating that silicate-associated selenium is partly converted to sulfide during metamorphism

Primary cilia elongation in response to interleukin-1 mediates the inflammatory response

Primary cilia are singular, cytoskeletal organelles present in the majority of mammalian cell types where they function as coordinating centres for mechanotransduction, Wnt and hedgehog signalling. The length of the primary cilium is proposed to modulate cilia function, governed in part by the activity of intraflagellar transport (IFT). In articular cartilage, primary cilia length is increased and hedgehog signaling activated in osteoarthritis (OA). Here, we examine primary cilia length with exposure to the quintessential inflammatory cytokine interleukin-1 (IL-1), which is up-regulated in OA. We then test the hypothesis that the cilium is involved in mediating the downstream inflammatory response. Primary chondrocytes treated with IL-1 exhibited a 50 % increase in cilia length after 3 h exposure. IL-1-induced cilia elongation was also observed in human fibroblasts. In chondrocytes, this elongation occurred via a protein kinase A (PKA)-dependent mechanism. G-protein coupled adenylate cyclase also regulated the length of chondrocyte primary cilia but not downstream of IL-1. Chondrocytes treated with IL-1 exhibit a characteristic increase in the release of the inflammatory chemokines, nitric oxide and prostaglandin E2. However, in cells with a mutation in IFT88 whereby the cilia structure is lost, this response to IL-1 was significantly attenuated and, in the case of nitric oxide, completely abolished. Inhibition of IL-1-induced cilia elongation by PKA inhibition also attenuated the chemokine response. These results suggest that cilia assembly regulates the response to inflammatory cytokines. Therefore, the cilia proteome may provide a novel therapeutic target for the treatment of inflammatory pathologies, including OA

Noncontact Material Testing Using Low-Energy Optical Generation and Detection of Acoustic Pulses

We will discuss preliminary results on the use of a low-energy laser and a sensitive laser interferometer for noncontact material testing of metals and nonmetals. There have been numerous reports [1–12] on the use of lasers to generate acoustic signals, but this is the first use of a relatively low-energy tunable laser source and improved interferometer to measure acoustic waveforms in both metals and nonmetals [13]. The use of a laser interferometer for the noncontact detection of acoustic pulses has also been reported previously [14–20], but we now report the use of a sensitive “non-Michelson” interferometer with increased signal-to-noise capabilities. The combination of these features allows noncontact, low-energy optical generation and optical detection in a variety of materials, in potentially hostile environments, and provides accurate accoustic waveforms which can be used to characterize specimens. These results, therefore, begin to demonstrate the feasibility of a portable (entirely) optical system for the nondestructive evaluation of materials

Moth biomass increases and decreases over 50 years in Britain

Steep insect biomass declines ('insectageddon') have been widely reported, despite a lack of continuously collected biomass data from replicated long-term monitoring sites. Such severe declines are not supported by the world’s longest running insect population database: annual moth biomass estimates from British fixed monitoring sites revealed increasing biomass between 1967 and 1982, followed by gradual decline from 1982 to 2017, with a 2.2-fold net gain in mean biomass between the first (1967–1976) and last decades (2008–2017) of monitoring. High between-year variability and multi-year periodicity in biomass emphasize the need for long-term data to detect trends and identify their causes robustly