Geographic transmission hubs of the 2009 influenza pandemic in the United States

A key issue in infectious disease epidemiology is to identify and predict geographic sites of epidemic establishment that contribute to onward spread, especially in the context of invasion waves of emerging pathogens. Conventional wisdom suggests that these sites are likely to be in densely-populated, well-connected areas. For pandemic influenza, however, epidemiological data have not been available at a fine enough geographic resolution to test this assumption. Here, we make use of fine-scale influenza-like illness incidence data derived from electronic medical claims records gathered from 834 3-digit ZIP (postal) codes across the US to identify the key geographic establishment sites, or “hubs”, of the autumn wave of the 2009 A/H1N1pdm influenza pandemic in the United States. A mechanistic spatial transmission model is fit to epidemic onset times inferred from the data. Hubs are identified by tracing the most probable transmission routes back to a likely first establishment site. Four hubs are identified: two in the southeastern US, one in the central valley of California, and one in the midwestern US. According to the model, 75% of the 834 observed ZIP-level outbreaks in the US were seeded by these four hubs or their epidemiological descendants. Counter-intuitively, the pandemic hubs do not coincide with large and well-connected cities, indicating that factors beyond population density and travel volume are necessary to explain the establishment sites of the major autumn wave of the pandemic. Geographic regions are identified where infection can be statistically traced back to a hub, providing a testable prediction of the outbreak's phylogeography. Our method therefore provides an important way forward to reconcile spatial diffusion patterns inferred from epidemiological surveillance data and pathogen sequence data. Keywords: Pandemic influenza, Transmission hubs, Metapopulation, Gravity model, Phylogeograph

Spatial Transmission of 2009 Pandemic Influenza in the US

The 2009 H1N1 influenza pandemic provides a unique opportunity for detailed examination of the spatial dynamics of an emerging pathogen. In the US, the pandemic was characterized by substantial geographical heterogeneity: the 2009 spring wave was limited mainly to northeastern cities while the larger fall wave affected the whole country. Here we use finely resolved spatial and temporal influenza disease data based on electronic medical claims to explore the spread of the fall pandemic wave across 271 US cities and associated suburban areas. We document a clear spatial pattern in the timing of onset of the fall wave, starting in southeastern cities and spreading outwards over a period of three months. We use mechanistic models to tease apart the external factors associated with the timing of the fall wave arrival: differential seeding events linked to demographic factors, school opening dates, absolute humidity, prior immunity from the spring wave, spatial diffusion, and their interactions. Although the onset of the fall wave was correlated with school openings as previously reported, models including spatial spread alone resulted in better fit. The best model had a combination of the two. Absolute humidity or prior exposure during the spring wave did not improve the fit and population size only played a weak role. In conclusion, the protracted spread of pandemic influenza in fall 2009 in the US was dominated by short-distance spatial spread partially catalysed by school openings rather than long-distance transmission events. This is in contrast to the rapid hierarchical transmission patterns previously described for seasonal influenza. The findings underline the critical role that school-age children play in facilitating the geographic spread of pandemic influenza and highlight the need for further information on the movement and mixing patterns of this age group

Effects of Noise on Ecological Invasion Processes: Bacteriophage-mediated Competition in Bacteria

Pathogen-mediated competition, through which an invasive species carrying and transmitting a pathogen can be a superior competitor to a more vulnerable resident species, is one of the principle driving forces influencing biodiversity in nature. Using an experimental system of bacteriophage-mediated competition in bacterial populations and a deterministic model, we have shown in [Joo et al 2005] that the competitive advantage conferred by the phage depends only on the relative phage pathology and is independent of the initial phage concentration and other phage and host parameters such as the infection-causing contact rate, the spontaneous and infection-induced lysis rates, and the phage burst size. Here we investigate the effects of stochastic fluctuations on bacterial invasion facilitated by bacteriophage, and examine the validity of the deterministic approach. We use both numerical and analytical methods of stochastic processes to identify the source of noise and assess its magnitude. We show that the conclusions obtained from the deterministic model are robust against stochastic fluctuations, yet deviations become prominently large when the phage are more pathological to the invading bacterial strain.Comment: 39 pages, 7 figure

The effectiveness of the Inspiring Futures parenting programme in improving behavioural and emotional outcomes in primary school children with behavioural or emotional difficulties: study protocol for a randomised controlled trial.

textabstractBackground: There is a need to build the evidence base of early interventions promoting children's health and development in the UK. Malachi Specialist Family Support Services ('Malachi') is a voluntary sector organisation based in the UK that delivers a therapeutic parenting group programme called Inspiring Futures to parents of children identified as having behavioural and emotional difficulties. The programme comprises two parts, delivered sequentially: (1) a group-based programme for all parents for 10-12 weeks, and (2) one-to-one sessions with selected parents from the group-based element for up to 12 weeks. Methods/design: A randomised controlled trial will be conducted to evaluate Malachi's Inspiring Futures parenting programme. Participants will be allocated to one of two possible arms, with follow-up measures at 16 weeks (post-parent group programme) and at 32 weeks (post-one-to-one sessions with selected parents). The sample size is 248 participants with a randomisation allocation ratio of 1:1. The intervention arm will be offered the Inspiring Futures programme. The control group will receive services as usual. The aim is to determine the effectiveness of the Inspiring Futures programme on the primary outcome of behavioural and emotional difficulties of primary school children identified as having behavioural or emotional difficulties. Discussion: This study will further enhance the evidence for early intervention parenting programmes for child behavioural and emotional problems in the UK

Measles on the Edge: Coastal Heterogeneities and Infection Dynamics

Mathematical models can help elucidate the spatio-temporal dynamics of epidemics as well as the impact of control measures. The gravity model for directly transmitted diseases is currently one of the most parsimonious models for spatial epidemic spread. This model uses distance-weighted, population size-dependent coupling to estimate host movement and disease incidence in metapopulations. The model captures overall measles dynamics in terms of underlying human movement in pre-vaccination England and Wales (previously established). In spatial models, edges often present a special challenge. Therefore, to test the model's robustness, we analyzed gravity model incidence predictions for coastal cities in England and Wales. Results show that, although predictions are accurate for inland towns, they significantly underestimate coastal persistence. We examine incidence, outbreak seasonality, and public transportation records, to show that the model's inaccuracies stem from an underestimation of total contacts per individual along the coast. We rescue this predicted ‘edge effect’ by increasing coastal contacts to approximate the number of per capita inland contacts. These results illustrate the impact of ‘edge effects’ on epidemic metapopulations in general and illustrate directions for the refinement of spatiotemporal epidemic models

M1 Resonances in Unstable Magic Nuclei

Within a microscopic approach which takes into account RPA configurations, the single-particle continuum and more complex $1p1h\otimes phonon$ configurations isoscalar and isovector M1 excitations for the unstable nuclei ${56,78}$Ni and ${100,132}$Sn are calculated. For comparison, the experimentally known M1 excitations in ${40}$Ca and $^{208}$Pb have also been calculated. In the latter nuclei good agreement in the centroid energy, the total transition strength and the resonance width is obtained. With the same parameters we predict the magnetic excitations for the unstable nuclei. The strength is sufficiently concentrated to be measurable in radioactive beam experiments. New features are found for the very neutron rich nucleus ${78}$Ni and the neutron deficient nucleus ${100}$Sn.Comment: 17 pages (LATEX), 12 figures (available from the authors), KFA-IKP(TH)-1993-0

In Situ Redox Manipulation Proof-of-Principle Test at the Fort Lewis Logistics Center: Final Report

Pacific Northwest National Laboratory (PNNL) conducted a proof-of-principle test at the Fort Lewis Logistics Center to determine the feasibility of using the In Situ Redox Manipulation (ISRM) technology for remediating groundwater contaminated with dissolved trichloroethylene (TCE). ISRM creates a permeable treatment zone in the subsurface to remediate redox-sensitive contaminants in groundwater. The permeable treatment zone is formed by injecting a chemical reducing agent (sodium dithionite with pH buffers) into the aquifer through a well to reduce the naturally occurring ferric iron in the sediments to ferrous iron. Once the reducing agent is injected and given sufficient time to react with aquifer sediments, residual chemicals and reaction products are withdrawn from the aquifer through the same well used for the injection. Redox-sensitive contaminants such as TCE, moving through the treatment zone under natural groundwater flow conditions, are destroyed. TCE is degraded via reductive dechlorination within the ISRM treatment zone to benign degradation products (i.e., acetylene, ethylene). Prior to the proof-of-principle field test, the ISRM technology was successfully demonstrated in laboratory experiments for the reductive dechlorination of dissolved TCE using sediments from the Fort Lewis site. The Logistics Center was placed on the National Priorities List in December 1989 because of TCE contamination in groundwater beneath the site. A Federal Facilities Agreement between the Army, the U.S. Environmental Protection Agency, and the Washington State Department of Ecology became effective in January 1990, and a Record of Decision (ROD) was signed in September 1990. The major components of the ROD included installation of two pump-and-treat systems for the upper aquifer and further investigation of the lower aquifer and other potential sources of contamination. The pump-and-treat systems became operational in August 1995. Fort Lewis asked PNNL to provide technical support in accelerating Installation Restoration Program site remediation and significantly reducing site life-cycle costs at the Logistics Center. In support of this program, ISRM was selected as an innovative technology for bench and field-scale demonstration. Emplacement of the ISRM treatment zone was accomplished through a series of four separate dithionite injection tests conducted between November 10, 1998 and March 29,2000. An extensive program of chemical monitoring was also performed before, during, and after each injection to evaluate the performance of ISRM. Prior to emplacement of the ISRM treatment zone, the site was extensively characterized with respect to geologic, hydrologic, and geochemical properties. Sediment core samples collected for the characterization studies were analyzed in bench-scale column tests at PNNL to determine reducible iron content. These site-specific hydrogeologic and geochemical data were used to develop the emplacement design of the pilot-scale (i.e., single injection well) ISRM treatment zone. Performance data obtained from the proof-of-principle test indicate that field-scale reductive dechlorination of TCE using the ISRM technology is feasible. A treatment zone was created in the subsurface that reduced TCE concentrations as much as 92% on the downgradient side of the reduced zone, from a background concentration of approximately 140 ppb to approximately 11 ppb. The appearance of the principal degradation product, acetylene, also confirmed that TCE destruction was occurring. Analysis of sediment samples collected from post-test boreholes showed a high degree of iron reduction, which helped to confirm the effectiveness of the treatment zone emplacement. Another important goal of the testing program was to provide assurances that chemical treatment of the subsurface did not result in undesirable secondary effects, including formation of toxic TCE degradation products, mobilization of trace elements, and degradation of hydraulic performance. Results obtained from the Fort Lewis ISRM proof-of-principle test, which are consistent with results from previous ISRM studies (both bench- and field-scale), indicate that no significant secondary effects were identified that could limit full-scale application of this technology

Ecological Invasion, Roughened Fronts, and a Competitor's Extreme Advance: Integrating Stochastic Spatial-Growth Models

Both community ecology and conservation biology seek further understanding of factors governing the advance of an invasive species. We model biological invasion as an individual-based, stochastic process on a two-dimensional landscape. An ecologically superior invader and a resident species compete for space preemptively. Our general model includes the basic contact process and a variant of the Eden model as special cases. We employ the concept of a "roughened" front to quantify effects of discreteness and stochasticity on invasion; we emphasize the probability distribution of the front-runner's relative position. That is, we analyze the location of the most advanced invader as the extreme deviation about the front's mean position. We find that a class of models with different assumptions about neighborhood interactions exhibit universal characteristics. That is, key features of the invasion dynamics span a class of models, independently of locally detailed demographic rules. Our results integrate theories of invasive spatial growth and generate novel hypotheses linking habitat or landscape size (length of the invading front) to invasion velocity, and to the relative position of the most advanced invader.Comment: The original publication is available at www.springerlink.com/content/8528v8563r7u2742

Emerging Infectious Disease leads to Rapid Population Decline of Common British Birds

Emerging infectious diseases are increasingly cited as threats to wildlife, livestock and humans alike. They can threaten geographically isolated or critically endangered wildlife populations; however, relatively few studies have clearly demonstrated the extent to which emerging diseases can impact populations of common wildlife species. Here, we report the impact of an emerging protozoal disease on British populations of greenfinch Carduelis chloris and chaffinch Fringilla coelebs, two of the most common birds in Britain. Morphological and molecular analyses showed this to be due to Trichomonas gallinae. Trichomonosis emerged as a novel fatal disease of finches in Britain in 2005 and rapidly became epidemic within greenfinch, and to a lesser extent chaffinch, populations in 2006. By 2007, breeding populations of greenfinches and chaffinches in the geographic region of highest disease incidence had decreased by 35% and 21% respectively, representing mortality in excess of half a million birds. In contrast, declines were less pronounced or absent in these species in regions where the disease was found in intermediate or low incidence. Also, populations of dunnock Prunella modularis, which similarly feeds in gardens, but in which T. gallinae was rarely recorded, did not decline. This is the first trichomonosis epidemic reported in the scientific literature to negatively impact populations of free-ranging non-columbiform species, and such levels of mortality and decline due to an emerging infectious disease are unprecedented in British wild bird populations. This disease emergence event demonstrates the potential for a protozoan parasite to jump avian host taxonomic groups with dramatic effect over a short time period

Estimation of the release and migration of lead through soils and groundwater at the Hanford Site 218-E-12B Burial Ground. Volume 2, Appendices

This report describes the technical basis for a groundwater transport analysis that was conducted to evaluate migration of potentially hazardous materials from the Hanford Site 218-E-12B burial ground. The analysis characterized the geologic, chemical, and hydrologic properties of the disposal site, and used that information to perform a screening analysis for transport of materials from the burial ground to downgradient groundwater locations and to the Columbia River. Subsequent sections of the appendix describe the geologic setting, geochemistry, and hydrology of the disposal site and their relationship to the transport analysis