Putative Markets for the Detection of Breast Carcinoma Cells in Blood

By using the DF3 antigen (MUC1) as a molecular marker, previous workers reported the detection of tumour cell dissemination by reverse transcriptase Polymerase Chain Reaction (rt-PCR) in a pilot study of patients undergoing surgery for breast cancer (Brown et al., 1994). The aim of this study was to extend these findings and also examine the role of other epithelial markers for their suitability as molecular markers for detection of circulating breast carcinoma cells using rt-PCR. It was envisaged that this work could be extended to the examination of bone marrow and lymph nodes for occult metastases. RNA was prepared from MCF-7 breast carcinoma cells and peripheral blood leucocytes of healthy female volunteers. This RNA was screened for mRNA of MUC1, CK19 and CD44 (Exon 8-11) by rt-PCR and the results validated by Southern blots. Variable degrees of expression of MUC1 and CD44 (Exon 8-11) were detected in normal peripheral blood, rendering these genes non-specific for epithelial cells and therefore unsuitable for use as markers to detect circulating breast carcinoma cells. Although CK19 mRNA was apparently specific, it was deemed unsuitable for use as a marker of circulating breast cancer cells in light of its poor sensitivity. These findings prompted an alternative approach to this problem to continue the search for the ideal epithelial marker. Therefore, included in this work is RNA fingerprinting, a modified Differential Display by the PCR technique which is conceived to allow the identification, molecular cloning and sequencing of differentially expressed genes. This technique is devised to amplify mRNA and display their 3' termini on polyacrylamide gels. The aim of RNA fingerprinting is to identify and characterise the differentially expressed genes in breast cancer samples in contrast with normal blood. In this study a total of 18 differentially expressed genes (using limited primer combinations) were analysed and found to have variable degrees of background expression when used as potential markers. However, further work is required to characterise the differentially expressed genes using all other primer combinations. This study has cast major doubts on the validity of previously published studies in this area. Until a suitable epithelial marker for breast cancer is identified, further work to identify tumour cells in blood will not be feasible

Environmental determinants of malaria transmission in African villages

Background Malaria transmission is complex, involving a range of hydroclimatological, biological, and environmental processes. The high degree of non-linearity in these processes makes it difficult to predict and intervene against malaria. This study seeks both to define a minimal number of malaria transmission determinants, and to provide a theoretical basis for sustainable environmental manipulation to prevent malaria transmission. Methods Using a field-tested mechanistic malaria model, HYDREMATS, a theoretical study was conducted under hypothetical conditions. Simulations were conducted with a range of hydroclimatological and environmental conditions: temperature (t), length of wet season (T[subscript wet]), storm inter-arrival time (T[subscript int]), persistence of vector breeding pools (T[subscript on]), and distribution of houses from breeding pools and from each other (X[subscript dist] and Y[subscript dist], respectively). Based on the theoretical study, a malaria time scale, T[subscript o], and a predictive theory of malaria transmission were introduced. The performance of the predictive theory was compared against the observational malaria transmission data in West Africa. Population density was used to estimate the scale that describes the spatial distribution of houses. Results The predictive theory shows a universality in malaria endemic conditions when plotted using two newly-introduced dimension-less parameters. The projected malaria transmission potential compared well with the observation data, and the apparent differences were discussed. The results illustrate the importance of spatial aspects in malaria transmission. Conclusions The predictive theory is useful in measuring malaria transmission potential, and it can also provide guidelines on how to plan the layout of human habitats in order to prevent endemic malaria. Malaria-resistant villages can be designed by locating houses further than critical distances away from breeding pools or by removing pools within a critical distance from houses; the critical distance is described in the context of local climatology and hydrology. Keywords Malaria transmission Hydrology Spatial impact Characteristic time scaleNational Science Foundation (U.S.)Masdar Institute of Science and TechnologyMassachusetts Institute of Technolog

Environmental determinants of malaria transmission in African villages

Background Malaria transmission is complex, involving a range of hydroclimatological, biological, and environmental processes. The high degree of non-linearity in these processes makes it difficult to predict and intervene against malaria. This study seeks both to define a minimal number of malaria transmission determinants, and to provide a theoretical basis for sustainable environmental manipulation to prevent malaria transmission. Methods Using a field-tested mechanistic malaria model, HYDREMATS, a theoretical study was conducted under hypothetical conditions. Simulations were conducted with a range of hydroclimatological and environmental conditions: temperature (t), length of wet season (Twet), storm inter-arrival time (Tint), persistence of vector breeding pools (Ton), and distribution of houses from breeding pools and from each other (Xdist and Ydist, respectively). Based on the theoretical study, a malaria time scale, To, and a predictive theory of malaria transmission were introduced. The performance of the predictive theory was compared against the observational malaria transmission data in West Africa. Population density was used to estimate the scale that describes the spatial distribution of houses. Results The predictive theory shows a universality in malaria endemic conditions when plotted using two newly-introduced dimension-less parameters. The projected malaria transmission potential compared well with the observation data, and the apparent differences were discussed. The results illustrate the importance of spatial aspects in malaria transmission. Conclusions The predictive theory is useful in measuring malaria transmission potential, and it can also provide guidelines on how to plan the layout of human habitats in order to prevent endemic malaria. Malaria-resistant villages can be designed by locating houses further than critical distances away from breeding pools or by removing pools within a critical distance from houses; the critical distance is described in the context of local climatology and hydrology. Keywords: Malaria transmission; Hydrology; Spatial impact; Characteristic time scal

Wind: a neglected factor in the spread of infectious diseases – Authors' reply

We thank Joel Ellwanger and José Chies for their Correspondence regarding our Article. This Correspondence resonates with theirs and highlights a neglected approach in One Health from a larger perspective. After unprecedented momentum and success in global malaria control in the first decade of 21st century, progress appears to have stalled.1 The easier goals have been achieved, but the remaining challenges require more sustainable and substantial investment in health-related infrastructure in resource-limited countries

Modelling and observing the role of wind in Anopheles population dynamics around a reservoir

Background Wind conditions, as well as other environmental conditions, are likely to influence malaria transmission through the behaviours of Anopheles mosquitoes, especially around water-resource reservoirs. Wind-induced waves in a reservoir impose mortality on aquatic-stage mosquitoes. Mosquitoes’ host-seeking activity is also influenced by wind through dispersion of CO₂. However, no malaria transmission model exists to date that simulated those impacts of wind mechanistically. Methods A modelling framework for simulating the three important effects of wind on the behaviours of mosquito is developed: attraction of adult mosquitoes through dispersion of CO₂ (CO₂ attraction), advection of adult mosquitoes (advection), and aquatic-stage mortality due to wind-induced surface waves (waves). The framework was incorporated in a mechanistic malaria transmission simulator, HYDREMATS. The performance of the extended simulator was compared with the observed population dynamics of the Anopheles mosquitoes at a village adjacent to the Koka Reservoir in Ethiopia. Results The observed population dynamics of the Anopheles mosquitoes were reproduced with some reasonable accuracy in HYDREMATS that includes the representation of the wind effects. HYDREMATS without the wind model failed to do so. Offshore wind explained the increase in Anopheles population that cannot be expected from other environmental conditions alone. Conclusions Around large water bodies such as reservoirs, the role of wind in the dynamics of Anopheles population, hence in malaria transmission, can be significant. Modelling the impacts of wind on the behaviours of Anopheles mosquitoes aids in reproducing the seasonality of malaria transmission and in estimation of the risk of malaria around reservoirs. Keywords: Malaria transmission; Water-resource reservoirs; Environmental conditionsNational Science Foundation (U.S.) (Grant EAR-0946280

The role of mineral aerosols in shaping the regional climate of West Africa

This article examines the role of mineral aerosols in the regional climate of West Africa. Analysis is completed by comparing two 30 year simulations using a regional climate model (RegCM3-IBIS). The two simulations are identical in structure except one includes the representation of mineral aerosols via a fully coupled radiatively interactive dust emissions and aerosol tracer model; the other simulation does not. To discern the impact of dust on West Africa's climate, comparisons are made between the two simulations' surface climatology as well as atmospheric dynamics. It is found that RegCM3-IBIS and its dust model perform well in simulating the temporal and spatial distributions of mineral aerosols over the Sahel and Sahara. Consistent with previous studies over the region, RegCM3-IBIS simulates high-dust loading over the region (aerosol optical depth of 0.5–1.1), which results in significant incident shortwave radiation attenuation (25–50 W/m2) and temperature cooling (0.5°C–1.25°C). Depending on the underlying surface brightness, the top of atmosphere net radiative forcing may be positive (bright desert surfaces) or negative (dark, vegetated surface) with important implications on surface temperature cooling. Here it is proposed that the effects of dust on West African rainfall are distinctly different across the ocean-land border and the desert border region of the Sahel/Sahara. Nevertheless, in both regions, the change in rainfall is less than 10% of the total annual values. Therefore, this work concludes that the current, observed, dust loading over West Africa does not significantly affect rainfall via changes in the radiation budget. However, it is important to note that this work does not include mineral aerosol effects on sea surface temperatures, which may be significant in influencing the results

Introducing an Irrigation Scheme to a Regional Climate Model: A Case Study over West Africa

This article presents a new irrigation scheme and biome to the dynamic vegetation model, Integrated Biosphere Simulator (IBIS), coupled to version 3 of the Regional Climate Model (RegCM3-IBIS). The new land cover allows for only the plant functional type (crop) to exist in an irrigated grid cell. Irrigation water (i.e., negative runoff) is applied until the soil root zone reaches relative field capacity. The new scheme allows for irrigation scheduling (i.e., when to apply water) and for the user to determine the crop to be grown. Initial simulations show a large sensitivity of the scheme to soil texture types, how the water is applied, and the climatic conditions over the region. Application of the new scheme is tested over West Africa, specifically Mali and Niger, to simulate the potential irrigation of the Niger River. A realistic representation of irrigation of the Niger River is performed by constraining the land irrigated by the annual flow of the Niger River and the amount of arable land in the region as reported by the Food and Agriculture Organization of the United Nations (FAO). A 30-yr simulation including irrigated cropland is compared to a 30-yr simulation that is identical but with no irrigation of the Niger. Results indicate a significant greening of the irrigated land as evapotranspiration over the crop fields largely increases—mostly via increases in transpiration from plant growth. The increase in the evapotranspiration, or latent heat flux (by 65–150 W m[superscript −2]), causes a significant decrease in the sensible heat flux while surface temperatures cool on average by nearly 5°C. This cooling is felt downwind, where average daily temperatures outside the irrigation are reduced by 0.5°–1.0°C. Likewise, large increases in 2-m specific humidity are experienced across the irrigated cropland (on the order of 5 g kg[superscript −1]) but also extend farther north and east, reflecting the prevailing surface southwesterlies. Changes (decreases) in rainfall are found only over the irrigated lands of west Mali. The decrease in rainfall can be explained by the large surface cooling and collapse of the boundary layer (by approximately 500 m). Both lead to a reduction in the triggering of convection as the convective inhibition, or negative buoyant energy, is never breached. Nevertheless, the new scheme and land cover allows for a novel line of research that can accurately reflect the effects of irrigation on climate and the surrounding environment using a dynamic vegetation model coupled to a regional climate model.Kuwait Foundation for the Advancement of Science

Modeling the hydroclimatology of the midwestern United States. Part 1: current climate

An ensemble of six 22-year numerical experiments was conducted to evaluate the ability of Regional Climate Model version 3 (RegCM3) to simulate the energy and water budgets of the midwestern United States. RegCM3 was run using two surface physics schemes: Integrated Biosphere Simulator (IBIS) and Biosphere-Atmosphere Transfer Scheme 1e (BATS1e), and two convective closure assumptions: Fritsch & Chappell (FC80) and Arakawa & Schubert (AS74). Boundary conditions were provided by the National Centers for Environmental Prediction-Department of Energy Reanalysis 2 dataset and the ECHAM5 general circulation model. A companion paper examines the American Midwest under future climate scenarios. Overall, the model that reproduces the observed seasonal cycles of the midwestern United States climate system best is RegCM3 using IBIS and the AS74 convective closure assumption. IBIS simulates shortwave radiation more accurately, while BATS1e simulates longwave radiation more accurately. Summer two-meter air temperature is overestimated by the combination of IBIS and the FC80 convective closure assumption. All models contain a wet bias and overestimate evapotranspiration during the spring. Total runoff, surface runoff, groundwater runoff, and root zone soil moisture are best simulated by RegCM3 using IBIS and the AS74 convective closure assumption. While BATS1e does capture the seasonal cycle of total runoff, gross errors in the partitioning of total runoff between surface runoff and groundwater runoff exist. The seasonal cycle of root zone soil moisture simulated by RegCM3 using IBIS and the AS74 convective closure assumption is dry, but agrees with observations during the summer. The rest of the models underestimate root zone soil moisture.National Science Foundation (U.S.) (Award EAR-04500341)Martin Family Society of Fellows for Sustainabilit

Enhancement of rainfall and runoff upstream from irrigation location in a climate model of West Africa

This study investigates the impact of potential medium-scale irrigation (about 60,000 km²) on the climate of West Africa using the MIT Regional Climate Model. We find that irrigation at this scale induces an atmospheric response similar to that of large-scale irrigation (about 400,000km²) which was considered in our previous theoretical study. While the volume of water needed for large-scale irrigation is about 230–270 km³, the medium-scale irrigation requires about 50 km³, and the annual flow of the Niger river in the relevant section is about 70 km³. The remote response of rainfall distribution to local irrigation exhibits a significant sensitivity to the latitudinal location of irrigation. The nature of this response is such that irrigation from the Niger River around latitude 18°N induces significant increase in rainfall of order 100% in the upstream sources of the Niger River and results in significant increase in runoff of order 50%. This additional runoff can potentially be collected by the river network and delivered back toward the irrigation area. By selecting the location of irrigation carefully, the positive impacts of irrigation on rainfall distribution can be maximized. The approach of using a regional climate model to investigate the impact of location and size of irrigation schemes, explored in this study, may be the first step in incorporating land-atmosphere interactions in the design of location and size of irrigation projects. However, this theoretical approach is still in early stages of development and further research is needed before any practical application in water resources planning