Some recent developments in disease mapping.
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Computers↗
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Oblique decision trees for spatial pattern detection: optimal algorithm and application to malaria risk.
BACKGROUND: In order to detect potential disease clusters where a putative source cannot be specified, classical procedures scan the geographical area with circular windows through a specified grid imposed to the map. However, the choice of the windows' shapes, sizes and centers is critical and different choices may not provide exactly the same results. The aim of our work was to use an Oblique Decision Tree model (ODT) which provides potential clusters without pre-specifying shapes, sizes or centers. For this purpose, we have developed an ODT-algorithm to find an oblique partition of the space defined by the geographic coordinates. METHODS: ODT is based on the classification and regression tree (CART). As CART finds out rectangular partitions of the covariate space, ODT provides oblique partitions maximizing the interclass variance of the independent variable. Since it is a NP-Hard problem in RN, classical ODT-algorithms use evolutionary procedures or heuristics. We have developed an optimal ODT-algorithm in R2, based on the directions defined by each couple of point locations. This partition provided potential clusters which can be tested with Monte-Carlo inference. We applied the ODT-model to a dataset in order to identify potential high risk clusters of malaria in a village in Western Africa during the dry season. The ODT results were compared with those of the Kulldorff' s SaTScan. RESULTS: The ODT procedure provided four classes of risk of infection. In the first high risk class 60%, 95% confidence interval (CI95%) [52.22-67.55], of the children was infected. Monte-Carlo inference showed that the spatial pattern issued from the ODT-model was significant (p < 0.0001). Satscan results yielded one significant cluster where the risk of disease was high with an infectious rate of 54.21%, CI95% [47.51-60.75]. Obviously, his center was located within the first high risk ODT class. Both procedures provided similar results identifying a high risk cluster in the western part of the village where a mosquito breeding point was located. CONCLUSION: ODT-models improve the classical scanning procedures by detecting potential disease clusters independently of any specification of the shapes, sizes or centers of the clusters.
Africa, Western↗
Methodological aspects of a GIS-based environmental health inspection program used in the Athens 2004 Olympic and Para Olympic Games.
BACKGROUND: The use of geographical information system (GIS) technologies in public health surveillance is gradually gaining momentum around the world and many applications have already been reported in the literature. In this study, GIS technology was used to help county departments of Public Health to implement environmental health surveillance for the Athens 2004 Olympic and Para Olympic Games. METHODS: In order to assess the workload in each Olympic county, 19 registry forms and 17 standardized inspection forms were developed to register and inspect environmental health items requiring inspection (Hotels, restaurants, swimming pools, water supply system etc), respectively. Furthermore, related databases were created using Epi Info 2002 and a geographical information system (GIS) were used to implement an integrated Environmental Health inspection program. The project was conducted in Athens by the Olympic Planning Unit (OPU) of the National School of Public Health, in close cooperation with the Ministry of Health and Social Solidarity and the corresponding departments of Public Health in all municipalities that were scheduled to host events during the Athens 2004 Olympic and Para Olympic games. RESULTS: A total of 44,741 premises of environmental health interest were geocoded into GIS databases and several electronic maps were developed. Using such maps in association with specific criteria, we first identified the maximum workload required to execute environmental health inspections in all premises within the eleven Olympic County Departments of Public Health. Six different scenarios were created for each county, based on devised algorithms in order to design the most effective and realistic inspection program using the available inspectors from each municipality. Furthermore, GIS applications were used to organize the daily inspection program for the Olympic games, provide coloured displays of the inspection results and link those results with the public health surveillance of specific cases or outbreak investigation. CONCLUSION: Our computerised program exhibited significant efficiency in facilitating the prudent use of public health resources in implementing environmental health inspections in densely populated urban areas as well as in rural counties. Furthermore, the application of simple algorithms in integrating human and other resources provided tailored and cost-effective applications to different public health agencies.
Accidents↗
Municipal mortality due to thyroid cancer in Spain.
BACKGROUND: Thyroid cancer is a tumor with a low but growing incidence in Spain. This study sought to depict its spatial municipal mortality pattern, using the classic model proposed by Besag, York and Mollié. METHODS: It was possible to compile and ascertain the posterior distribution of relative risk on the basis of a single Bayesian spatial model covering all of Spain's 8077 municipal areas. Maps were plotted depicting standardized mortality ratios, smoothed relative risk (RR) estimates, and the posterior probability that RR > 1. RESULTS: From 1989 to 1998 a total of 2,538 thyroid cancer deaths were registered in 1,041 municipalities. The highest relative risks were mostly situated in the Canary Islands, the province of Lugo, the east of La Coruña (Corunna) and western areas of Asturias and Orense. CONCLUSION: The observed mortality pattern coincides with areas in Spain where goiter has been declared endemic. The higher frequency in these same areas of undifferentiated, more aggressive carcinomas could be reflected in the mortality figures. Other unknown genetic or environmental factors could also play a role in the etiology of this tumor.
Bayes Theorem↗
An online operational rainfall-monitoring resource for epidemic malaria early warning systems in Africa.
Periodic epidemics of malaria are a major public health problem for many sub-Saharan African countries. Populations in epidemic prone areas have a poorly developed immunity to malaria and the disease remains life threatening to all age groups. The impact of epidemics could be minimized by prediction and improved prevention through timely vector control and deployment of appropriate drugs. Malaria Early Warning Systems are advocated as a means of improving the opportunity for preparedness and timely response. Rainfall is one of the major factors triggering epidemics in warm semi-arid and desert-fringe areas. Explosive epidemics often occur in these regions after excessive rains and, where these follow periods of drought and poor food security, can be especially severe. Consequently, rainfall monitoring forms one of the essential elements for the development of integrated Malaria Early Warning Systems for sub-Saharan Africa, as outlined by the World Health Organization. The Roll Back Malaria Technical Resource Network on Prevention and Control of Epidemics recommended that a simple indicator of changes in epidemic risk in regions of marginal transmission, consisting primarily of rainfall anomaly maps, could provide immediate benefit to early warning efforts. In response to these recommendations, the Famine Early Warning Systems Network produced maps that combine information about dekadal rainfall anomalies, and epidemic malaria risk, available via their Africa Data Dissemination Service. These maps were later made available in a format that is directly compatible with HealthMapper, the mapping and surveillance software developed by the WHO's Communicable Disease Surveillance and Response Department. A new monitoring interface has recently been developed at the International Research Institute for Climate Prediction (IRI) that enables the user to gain a more contextual perspective of the current rainfall estimates by comparing them to previous seasons and climatological averages. These resources are available at no cost to the user and are updated on a routine basis.
Africa↗
Web-based climate information resources for malaria control in Africa.
Malaria remains a major public health threat to more than 600 million Africans and its control is recognized as critical to achieving the Millennium Development Goals. The greatest burden of malaria in Africa occurs in the endemic regions where the disease pathogen is continuously present in the community. These regions are characterized by an environment that is conducive to interactions between the Anopheles mosquito, malaria parasites and human hosts, as well as housing of generally poor quality, which offers little protection from mosquito-human contact. Epidemic malaria tends to occur along the geographical margins of endemic regions, when the equilibrium between the human, parasite and mosquito vector populations is occasionally disturbed and a sharp but temporary increase in disease incidence results. When malaria control measures are inadequate, as is the case in much of sub-Saharan Africa, the disease distribution is closely linked with seasonal patterns of the climate and local environment. In the absence of good epidemiological data on malaria distribution in Africa, climate information has long been used to develop malaria risk maps that illustrate the boundaries of 'climatic suitability for endemic transmission.' The best known of these are produced by the Pan-African-based MARA Collaboration. This paper describes the development of additional malaria suitability maps which have been produced in an online, interactive format to enable temporal information (i.e., seasonality of climate conditions) to be queried and displayed along with spatial information. These maps and the seasonal information that they contain should be useful to the malaria control and health service communities for their planning and operational activities.
Africa↗
Spatial analysis of lung, colorectal, and breast cancer on Cape Cod: an application of generalized additive models to case-control data.
BACKGROUND: The availability of geographic information from cancer and birth defect registries has increased public demands for investigation of perceived disease clusters. Many neighborhood-level cluster investigations are methodologically problematic, while maps made from registry data often ignore latency and many known risk factors. Population-based case-control and cohort studies provide a stronger foundation for spatial epidemiology because potential confounders and disease latency can be addressed. METHODS: We investigated the association between residence and colorectal, lung, and breast cancer on upper Cape Cod, Massachusetts (USA) using extensive data on covariates and residential history from two case-control studies for 1983-1993. We generated maps using generalized additive models, smoothing on longitude and latitude while adjusting for covariates. The resulting continuous surface estimates disease rates relative to the whole study area. We used permutation tests to examine the overall importance of location in the model and identify areas of increased and decreased risk. RESULTS: Maps of colorectal cancer were relatively flat. Assuming 15 years of latency, lung cancer was significantly elevated just northeast of the Massachusetts Military Reservation, although the result did not hold when we restricted to residences of longest duration. Earlier non-spatial epidemiology had found a weak association between lung cancer and proximity to gun and mortar positions on the reservation. Breast cancer hot spots tended to increase in magnitude as we increased latency and adjusted for covariates, indicating that confounders were partly hiding these areas. Significant breast cancer hot spots were located near known groundwater plumes and the Massachusetts Military Reservation. DISCUSSION: Spatial epidemiology of population-based case-control studies addresses many methodological criticisms of cluster studies and generates new exposure hypotheses. Our results provide evidence for spatial clustering of breast cancer on upper Cape Cod. The analysis suggests further investigation of the potential association between breast cancer and pollution plumes based on detailed exposure modeling.
Adult↗
Cluster detection methods applied to the Upper Cape Cod cancer data.
BACKGROUND: A variety of statistical methods have been suggested to assess the degree and/or the location of spatial clustering of disease cases. However, there is relatively little in the literature devoted to comparison and critique of different methods. Most of the available comparative studies rely on simulated data rather than real data sets. METHODS: We have chosen three methods currently used for examining spatial disease patterns: the M-statistic of Bonetti and Pagano; the Generalized Additive Model (GAM) method as applied by Webster; and Kulldorff's spatial scan statistic. We apply these statistics to analyze breast cancer data from the Upper Cape Cancer Incidence Study using three different latency assumptions. RESULTS: The three different latency assumptions produced three different spatial patterns of cases and controls. For 20 year latency, all three methods generally concur. However, for 15 year latency and no latency assumptions, the methods produce different results when testing for global clustering. CONCLUSION: The comparative analyses of real data sets by different statistical methods provides insight into directions for further research. We suggest a research program designed around examining real data sets to guide focused investigation of relevant features using simulated data, for the purpose of understanding how to interpret statistical methods applied to epidemiological data with a spatial component.
Adult↗
Method for mapping population-based case-control studies: an application using generalized additive models.
BACKGROUND: Mapping spatial distributions of disease occurrence and risk can serve as a useful tool for identifying exposures of public health concern. Disease registry data are often mapped by town or county of diagnosis and contain limited data on covariates. These maps often possess poor spatial resolution, the potential for spatial confounding, and the inability to consider latency. Population-based case-control studies can provide detailed information on residential history and covariates. RESULTS: Generalized additive models (GAMs) provide a useful framework for mapping point-based epidemiologic data. Smoothing on location while controlling for covariates produces adjusted maps. We generate maps of odds ratios using the entire study area as a reference. We smooth using a locally weighted regression smoother (loess), a method that combines the advantages of nearest neighbor and kernel methods. We choose an optimal degree of smoothing by minimizing Akaike's Information Criterion. We use a deviance-based test to assess the overall importance of location in the model and pointwise permutation tests to locate regions of significantly increased or decreased risk. The method is illustrated with synthetic data and data from a population-based case-control study, using S-Plus and ArcView software. CONCLUSION: Our goal is to develop practical methods for mapping population-based case-control and cohort studies. The method described here performs well for our synthetic data, reproducing important features of the data and adequately controlling the covariate. When applied to the population-based case-control data set, the method suggests spatial confounding and identifies statistically significant areas of increased and decreased odds ratios.
Case-Control Studies↗
Occipital-callosal pathways in children: Validation and atlas development.
Diffusion tensor imaging and fiber tracking were used to measure fiber bundles connecting the two occipital lobes in 53 children of 7-12 years of age. Independent fiber bundle estimates originating from the two hemispheres converge onto the lower half of the splenium. This observation validates the basic methodology and suggests that most occipital-callosal fibers connect the two occipital lobes. Within the splenium, fiber bundles are organized in a regular pattern with respect to their cortical projection zones. Visual cortex dorsal to calcarine projects through a large band that fills much of the inferior half of the splenium, while cortex ventral to calcarine sends projections through a band at the anterior inferior edge of the splenium. Pathways projecting to the occipital pole and lateral-occipital regions overlap the dorsal and ventral groups slightly anterior to the center of the splenium. To visualize these pathways in a typical brain, we combined the data into an atlas. The estimated occipital-callosal fiber paths from the atlas form the walls of the occipital horn of the lateral ventricle, with dorsal paths forming the medial wall and the ventral paths bifurcating into a medial tract to form the inferior-medial wall and a superior tract that joins the lateral-occipital paths to form the superior wall of the ventricle. The properties of these fiber bundles match those of the hypothetical pathways described in the neurological literature on alexia.
Anatomy, Artistic↗
Electronic maps for terminal area navigation: effects of frame of reference and dimensionality.
Two experiments are reported that contrast rotating versus fixed electronic map displays, which pilots used for a simulated approach to a landing. In Experiment 1, a rotating versus fixed-map display was experimentally crossed with a two-dimensional (2D) versus three-dimensional (3D) view (perspective map) as pilots' ability to maintain the flight path and demonstrate awareness of the location of surrounding terrain features were assessed. Rotating displays supported better flight path guidance and did not substantially harm performance on terrain awareness tasks. 3D displays led to a substantial cost for vertical control but did not differ from 2D displays in lateral control. In Experiment 2, pilots flew with the rotating 2D display and with an improved version of the rotating 3D display, designed to reduce the ambiguity of representing altitude information. Vertical control improved as a result of the 3D display design improvement, but lateral control did not. The results are discussed in terms of the costs and benefits of presenting information in 3D, ego-referenced format for both flight path control and terrain awareness.
Aerospace Medicine↗
The Norse discovery of America.
In the late 8th century, the stage for Viking expansion was set by commercial expansion in northwest Europe, the pressure of an increasing population in limited territorial reserves, and the development of the Viking ships. The Norsemen traveled extensively over the oceans, south to the Holy Land, and north to the White Sea and settled over a wide area from Sicily to Greenland. Historical sources, including the reports by Adam of Bremen and the Icelandic Sagas, describe several expeditions from Greenland to Vinland (somewhere along the east coast of North America) in approximately AD 1000 and later. Historians have arrived at highly different conclusions with respect to the location of Vinland (from Labrador to Georgia), but, in 1960, the Norwegian explorer Helge Ingstad localized ancient house sites on L'Ans aux Meadows, a small fishing village on the Northern beaches of Newfoundland. From 1961 to 1969, Ingstad and his wife, Anne Stine (an archaeologist), led several archaeological expeditions that revealed Viking turf houses with room for approximately 100 people. They also excavated a smithy, outdoor cooking pits, boathouses, a bathhouse, and enclosures for cattle, in addition to several Viking artifacts. The finds were C dated to AD 990 +/- 30. The present report reviews historical and archaeological evidence indicating the sites to which the Vikings traveled and attempted to settle in the new world.
Archaeology↗
S. pombe meiotic linear elements contain proteins related to synaptonemal complex components.
The fission yeast Schizosaccharomyces pombe does not form synaptonemal complexes (SCs) in meiotic prophase nuclei. Instead, thin threads, the so-called linear elements (LEs), are observed at the corresponding stages by electron microscopy. Here, we demonstrate that S. pombe Rec10 is a protein related to the Saccharomyces cerevisiae SC protein Red1 and that it localizes to LEs. Moreover, a homologue to S. cerevisiae Hop1 does exist in S. pombe and we show by in situ immunostaining that it, and the kinase Mek1 (a homologue of which is also known to be associated with SCs), localizes to LEs. These observations indicate the evolutionary relationship of LEs with the lateral elements of SCs and suggest that these structures might exert similar functions in S. cerevisiae and S. pombe.
Amino Acid Sequence↗
A tau-like protein interacts with stress fibers and microtubules in human and rodent cultured cell lines.
The cytoskeletal integrity of human and rodent cell lines was analyzed using site-directed monoclonal antibodies prepared from hybridomas. Secreting hybridomas were produced by immunizing mice with synthetic peptides from the C-terminal domain of the beta II-tubulin isotype, beta II(422-434), YQQYQDATADEQG, and the first imperfect repeat from brain tau, Tau-I(187-204), VRSKIGSTENLKHQPGGG. Two hybridomas were selected for this work: MTB6.22, an anti-idiotypic monoclonal antibody, which was obtained from a mouse immunized with the beta II-peptide and recognizes specific tubulin-binding domains on MAP-2 and tau; and Tau-I/1, which recognizes the repetitive binding sequences on tau and MAP-2. Immunoblots of cytoskeletal protein preparations from the five different tumor cell lines studied, showed the interaction of the site-directed antibodies MTB6.22 and Tau-I/1 with a group of proteins that co-migrate with brain tau. Immunoreactive tau components were also identified using an anti-tau monoclonal antibody (clone Tau-2), and several polyclonal anti-tau antibodies that interact with tau epitopes, other than those of the tubulin-binding domains. These tau-like proteins bound to a calmodulin-Sepharose affinity column and were eluted using 2 mM EGTA. Interestingly, washing the extracted cytoskeleton pellet with 5 x 10(-3) M Ca2+ for short periods of time selectively released the tau-like protein components, whilst most of the other cytoskeletal proteins remained in the pellet. On the other hand, immunofluorescence microscopy of detergent-extracted cells showed immunostaining of MAP components that appear to be co-localized in a discrete dot-like distribution along the stress fibers, which were revealed using rhodamine-phallacidin. Further support for the specificity of tau interaction with sites on tubulin and actin polymers was obtained with double-immunofluorescence, using the MAP-reactive monoclonal antibody MTB6.22 and a polyclonal antibody to a tubulin peptide containing part of the tau-binding domain on tubulin. Considering the anti-idiotypic nature of the MTB6.22 monoclonal antibody, our studies indicate that, in all the cell lines analyzed, a tau-like protein component is involved in mediating the interaction of both actin and tubulin polymers.
Actins↗
'Fixed-axis' magnetic orientation by an amphibian: non-shoreward-directed compass orientation, misdirected homing or positioning a magnetite-based map detector in a consistent alignment relative to the magnetic field?
Experiments were carried out to investigate the earlier prediction that prolonged exposure to long-wavelength (>500 nm) light would eliminate homing orientation by male Eastern red-spotted newts Notophthalmus viridescens. As in previous experiments, controls held in outdoor tanks under natural lighting conditions and tested in a visually uniform indoor arena under full-spectrum light were homeward oriented. As predicted, however, newts held under long-wavelength light and tested under either full-spectrum or long-wavelength light (>500 nm) failed to show consistent homeward orientation. The newts also did not orient with respect to the shore directions in the outdoor tanks in which they were held prior to testing. Unexpectedly, however, the newts exhibited bimodal orientation along a more-or-less 'fixed' north-northeast-south-southwest magnetic axis. The orientation exhibited by newts tested under full-spectrum light was indistinguishable from that of newts tested under long-wavelength light, although these two wavelength conditions have previously been shown to differentially affect both shoreward compass orientation and homing orientation. To investigate the possibility that the 'fixed-axis' response of the newts was mediated by a magnetoreception mechanism involving single-domain particles of magnetite, natural remanent magnetism (NRM) was measured from a subset of the newts. The distribution of NRM alignments with respect to the head-body axis of the newts was indistinguishable from random. Furthermore, there was no consistent relationship between the NRM of individual newts and their directional response in the overall sample. However, under full-spectrum, but not long-wavelength, light, the alignment of the NRM when the newts reached the 20 cm radius criterion circle in the indoor testing arena (estimated by adding the NRM alignment measured from each newt to its magnetic bearing) was non-randomly distributed. These findings are consistent with the earlier suggestion that homing newts use the light-dependent magnetic compass to align a magnetite-based 'map detector' when obtaining the precise measurements necessary to derive map information from the magnetic field. However, aligning the putative map detector does not explain the fixed-axis response of newts tested under long-wavelength light. Preliminary evidence suggests that, in the absence of reliable directional information from the magnetic compass (caused by the 90 degrees rotation of the response of the magnetic compass under long-wavelength light), newts may resort to a systematic sampling strategy to identify alignment(s) of the map detector that yields reliable magnetic field measurements.
Animals↗
Farming from a new perspective: remote sensing comes down to earth.
Farmers strive to increase the yield of their fields by adding nutrients and water to the land, and using pesticides to control insects and disease. In addition to bountiful harvests, the results of their endeavors may include elevated amounts of fertilizers in surface waters and aquifers and potential risk to themselves and their neighbors from exposure to pesticides. Precision agriculture is the use of modern information technologies such as geographic information systems, the global positioning system, and remote sensing from the air to reduce the environmental effects of these chemicals while enhancing the productivity of farming. By combining crop yield maps with soil survey maps and remote sensing output, farmers can identify areas that need more or less fertilizer, water, or pesticide.
Agriculture↗
Time-location analysis for exposure assessment studies of children using a novel global positioning system instrument.
Global positioning system (GPS) technology is used widely for business and leisure activities and offers promise for human time-location studies to evaluate potential exposure to environmental contaminants. In this article we describe the development of a novel GPS instrument suitable for tracking the movements of young children. Eleven children in the Seattle area (2-8 years old) wore custom-designed data-logging GPS units integrated into clothing. Location data were transferred into geographic information systems software for map overlay, visualization, and tabular analysis. Data were grouped into five location categories (in vehicle, inside house, inside school, inside business, and outside) to determine time spent and percentage reception in each location. Additional experiments focused on spatial resolution, reception efficiency in typical environments, and sources of signal interference. Significant signal interference occurred only inside concrete/steel-frame buildings and inside a power substation. The GPS instruments provided adequate spatial resolution (typically about 2-3 m outdoors and 4-5 m indoors) to locate subjects within distinct microenvironments and distinguish a variety of human activities. Reception experiments showed that location could be tracked outside, proximal to buildings, and inside some buildings. Specific location information could identify movement in a single room inside a home, on a playground, or along a fence line. The instrument, worn in a vest or in bib overalls, was accepted by children and parents. Durability of the wiring was improved early in the study to correct breakage problems. The use of GPS technology offers a new level of accuracy for direct quantification of time-location activity patterns in exposure assessment studies.
Child↗
Geographic aggregation of health data: a comparison of alternatives for 1990 and beyond.
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Bias↗