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PubMed1987

Characterization of the third component of complement (C3) after activation by cigarette smoke.

Activation of lung complement by tobacco smoke may be an important pathogenetic factor in the development of pulmonary emphysema in smokers. We previously showed that cigarette smoke can modify C3 and activate the alternative pathway of complement in vitro. However, the mechanism of C3 activation was not fully delineated in these earlier studies. In the present report, we show that smoke-treated C3 induces cleavage of the alternative pathway protein, Factor B, when added to serum containing Mg-EGTA. This effect of cigarette smoke is specific for C3 since smoke-treated C4, when added to Mg-EGTA-treated serum, fails to activate the alternative pathway and fails to induce Factor B cleavage. Smoke-modified C3 no longer binds significant amounts of [14C]methylamine (as does native C3), and relatively little [14C]methylamine is incorporated into its alpha-chain. Thus, prior internal thiolester bond cleavage appears to have occurred in C3 activated by cigarette smoke. Cigarette smoke components also induce formation of noncovalently associated, soluble C3 multimers, with a Mr ranging from 1 to 10 million. However, prior cleavage of the thiolester bond in C3 with methylamine prevents the subsequent formation of these smoke-induced aggregates. These data indicate that cigarette smoke activates the alternative pathway of complement by specifically modifying C3 and that these modifications include cleavage of the thiolester bond in C3 and formation of noncovalently linked C3 multimers.

Chemical Phenomena↗

PubMed1994

Payment levels and hospital response to prospective payment.

Nearly ten years after the implementation of Medicare's Prospective Payment System (PPS), some of its major impacts remain hard to explain using existing economic models. We develop a simple model of the hospital's choice of intensity of care, which affects demand for admissions. The model suggests an important role for the level of prospective payment, independent of the effect of marginal incentives. Predictions from the model are compared first with aggregate utilization data from Medicare's PPS experience, and then with various hospital-level studies which control for interhospital differences in reimbursement rates.

Financial Management, Hospital↗

PubMed1993

Optimal antithrombotic therapy following aortocoronary bypass: a meta-analysis.

To evaluate the role of antithrombotic therapy, on preserving graft patency, we performed a meta-analysis of randomized clinical trials involving aspirin (ASA), dipyridamole (D), anticoagulants (AC) and placebo or nontreatment controls (P). Manual literature searches were performed supplemented by computerized MEDLINE listings complete to July 1991. Saphenous vein graft occlusion was determined by angiography (patients with > or = 1 distal anastomotic occlusion). The trial data were aggregated with the methods of Mantel and Haenszel. The results are reported as odds ratios (OR) +/- 95% confidence intervals (CI). Seventeen trials were evaluated. Aspirin strongly influenced graft occlusion [ASA +/- D vs P: OR 0.60, 95% CI 0.51, 0.71, P < 0.0001], but dipyridamole provided no additional benefit [ASA+D vs ASA: OR 0.94, 95% CI 0.72, 1.24, P = 0.71]. Anticoagulants reduced graft occlusion [AC vs P: OR 0.56, 95% CI 0.33, 0.93, P = 0.025] and the results were similar to that achieved with aspirin [ASA vs AC: OR 0.95, 95% CI 0.62, 1.44, P = 0.87]. The combination of aspirin and anticoagulants was superior to anticoagulants alone in two limited trials [ASA+AC vs AC: OR 0.55, 95% CI 0.33, 0.88, P = 0.01]. A low (100 mg) to medium (325 mg) daily aspirin dosage was more effective than a high dose (975 mg). Early postoperative treatment (< or = 6 h) strongly influenced graft occlusion while preoperative administration provided no additional benefit. No mortality advantage was identified for any antithrombotic therapy. Aspirin or anticoagulants enhance saphenous vein graft patency following aortocoronary bypass surgery, and a combination thereof deserves further investigation in a trial large enough to detect the effects of these treatments with respect to clinical events.

Anticoagulants↗

PubMed2005

Tuberculosis in health care workers during declining tuberculosis incidence in New York State.

BACKGROUND: Nosocomial tuberculosis (TB) transmission has decreased dramatically in New York State since 1992; however, health care workers (HCWs) still compose >3% of TB cases. METHODS: Aggregate surveillance data on incident TB cases from 1994 to 2002 were examined for trends among HCWs. Additional information was available for HCW cases from 1998 to 2002, including facility type, tuberculin skin test (TST) result at hire, and treatment of latent TB infection (TLTBI). RESULTS: In New York State, 2.5% of TB cases in 1994 and 4.0% in 2002 were in HCWs (P value for trend <.001). Fifty percent of HCWs TB cases in 1994 and 77.6% in 2002 were in non-US born (P = .002) HCWs. Multidrug-resistant TB in HCWs decreased from 15.6% in 1994 to 6.9% in 2002 (P = .001). Of 297 HCWs TB cases in 1998-2002, 54.9% were TST positive at hire, and 21.2% had unknown TST result; 50.2% of 221 HCWs who were TST positive at or after hire met guidelines for TLTBI, and 23.4% received treatment. The highest proportion with unknown TST at hire and the lowest proportion receiving TLTBI were in ambulatory facilities. CONCLUSION: Many HCWs who developed TB were either TST positive at hire and did not receive TLTBI or did not receive TST at hire. Facilities should encourage treatment for HCWs who meet criteria for TLTBI. Provider education should focus on ambulatory facilities.

Adolescent↗

PubMed2005

From chance to frequent encounters: origins of beta2-microglobulin fibrillogenesis.

It is generally accepted that amyloid formation requires partial, but not complete unfolding of a polypeptide chain. Amyloid formation by beta-2 microglobulin (beta2m), however, readily occurs under strongly native conditions provided that there is exposure to specific transition metal cations. In this review, we discuss transition metal catalyzed conformational changes in several amyloidogenic systems including prion protein, Alzheimer's and Parkinson's diseases. For some systems, including beta2m from dialysis related amyloidosis (DRA), catalysis overcomes an entropic barrier to protein aggregation. Recent data suggest that beta2m samples conformations that are under thermodynamic control, resulting in local or partial unfolding under native conditions. Furthermore, exposure to transition metal cations stabilizes these partially unfolded states and promotes the formation of small oligomers, whose structures are simultaneously near-native and amyloid-like. By serving as a tether, Cu(2+) enables the encounter of amyloidogenic conformations to occur on time scales which are significantly more rapid than would occur between freely diffusing monomeric protein. Once amyloid formation occurs, the requirement for Cu(2+) is lost. We assert that beta2m amyloid fiber formation at neutral pH may be facilitated by rearrangements catalyzed by the transient and pair wise tethering of beta2m at the blood/dialysate interface present during therapeutic hemodialysis.

Amyloid↗

PubMed2005

Federal, state, and foundation initiatives around evidence-based practices for child and adolescent mental health.

This article is a survey of many of the initiatives developed by federal and state agencies and foundations focusing on evidence-based mental health practices for children and adolescents. The article intends to show the tremendous interest in the development, dissemination, and implementation of evidence-based practice in child and adolescent mental health that is held by a wide variety of agencies and organizations. Several "next steps" for the field are suggested that might be developed in a subsequent series of initiatives. These steps include a better understanding of dissemination and implementation processes, increased clarity around definitions and terms, increased efforts to build infrastructure and support policy change, and the potential for an aggregation of data already gathered on the implementation of evidence-based practices.

Adolescent↗

PubMed2026

Adjunctive middle meningeal artery embolization for chronic subdural hematoma: A systematic review and meta-analysis of eight randomized trials.

BACKGROUND: Randomized trials suggest that adjunctive middle meningeal artery embolization (MMAE) may reduce recurrence in chronic subdural hematoma (CSDH), but potential sources of variability in treatment effects across studies remain poorly understood. We performed a systematic review and meta-analysis to evaluate the efficacy and safety of MMAE and to explore potential study-level sources of between-study heterogeneity. METHODS: We conducted a systematic review and meta-analysis of randomized controlled trials comparing MMAE plus surgery versus surgery alone, following PRISMA guidelines. Trial sequential analysis (TSA) was prespecified to assess the robustness of pooled findings. Exploratory mixed-effects meta-regression was performed to examine whether aggregate study-level mean age and anticoagulation use were associated with variability in recurrence outcomes. RESULTS: Eight trials including 1961 patients were analyzed. MMAE plus surgery was associated with a reduction in recurrence compared with surgery alone (RR 0.63, 95% CI 0.46-0.85; I² = 0%), and TSA supported this finding. Although conventional meta-analysis suggested a reduction in reoperation, the TSA findings were more sensitive to analytical assumptions and less robust. Exploratory study-level meta-regression analyses suggested possible associations between recurrence outcomes and mean age or anticoagulation use, although these findings should be interpreted as hypothesis-generating only. Safety outcomes were comparable between groups. CONCLUSIONS: Adjunctive MMAE was associated with reduced recurrence in CSDH. Exploratory analyses evaluating aggregate study-level characteristics were limited by the small number of included trials and the use of aggregate-level data, and should be considered hypothesis-generating only. Further prospective studies are needed to better understand variability in treatment effects.

Humans↗

PubMed2004

Modelling of discrete spatial variation in epidemiology with SAS using GLIMMIX.

SAS provides a macro GLIMMIX, which can be used for modelling of discrete spatial variation in epidemiological studies, where data are aggregated into small areas such as municipalities or postcode sectors. The purpose of these models is primary to examine to what extent unmeasured spatially correlated variables can explain the outcome of interest. Some necessary additional code is proposed for this macro implementing some of the most used models for analysing and exploring spatial variation, in for example Poisson and logistic regression: Gaussian intrinsic conditional autoregression and spatial multiple memberships models originated from multilevel models. The code is illustrated by analysing the well-known Scottish lip cancer dataset with GLIMMIX and the results are compared with a Markov chain Monte Carlo approach. The code gives epidemiologists and bio-statisticians an immediate tool for analysing discrete spatial models in a familiar statistical software package.

Biometry↗

PubMed2005

The impact of filipino micro health-insurance units on income-related equality of access to healthcare.

BACKGROUND: This study aims to assess the impact of being insured by micro-health insurance units (MIUs) on equality of access to health care among groups with inequitable income distribution. We measure equality by relating income with access to healthcare. The analysis is based on a household survey conducted in five regions in the Philippines in 2002. METHODS: We generated concentration curves and indices (CI) for insured and uninsured households (150 for each cohort in each region). We also elaborated a method to retain the relative income rank of households when data were aggregated across regions, as the regions had quite different nominal income levels. RESULTS: We found a significant effect of household income on access to hospitalizations among the uninsured households (a positive CI), but no such effect among the insured households (CI close to zero). As regards professionally attended deliveries, an increased tendency of poorer households to deliver at home (CI slightly negative) and a lower rate of deliveries in hospital (CI slightly positive and statistically significant) were reported by both uninsured and insured households. Access to consultations was unrelated to income among the insured (CI close to 0), but negatively correlated with income among the uninsured (a positive and significant CI). CONCLUSION: We conclude that MIUs in Philippines improve income-related equality of access to hospitalization and medical consultation in cases of illness. The findings of this study strengthen a claim for government support for the operation of MIUs as successful (albeit micro) suppliers of health insurance.

Cross-Sectional Studies↗

PubMed2005

Influence of SDS and two anionic hydrotropes on the micellized state of the triblock copolymer E71G7E71.

Complex formation between the triblock copolymer E71G7E71, where E denotes ethylene oxide, the central hydrophobic block, phenyl glycidyl ether, is denoted as G, and the subscripts denote the block length, the surfactant sodium dodecyl sulfate (SDS), and the penicillins cloxacillin and dicloxacillin, which can be considered as hydrotropes has been investigated by dynamic light scattering (DLS) and isothermal titration calorimetry (ITC). The different copolymer/amphiphile systems have been studied at a constant copolymer concentration of 10 g dm(-3) and at different amphiphile concentrations. For all systems, the relaxation time distributions show a well-defined single mode with a shift toward slightly faster times, which indicates that the electrostatic interactions between the complexes is minimum, and so it is possible to estimate a size in terms of the apparent hydrodynamic radii. For ITC the amphiphile solutions were titrated in two different forms: as monomers (below the cmc) and as aggregates. The data indicate that the interaction between the surfactant and the hydrotropes with the copolymer occurs even at the lowest SDS concentration measured.

Journal Article↗

PubMed2026

Direct and spillover hospitalisation patterns during climate hazards across regions of different health-system resilience levels in China: a nationwide retrospective analysis.

BACKGROUND: Health-system resilience serves as a key contributor in mitigating adverse health impacts during climate hazards. However, quantitative insights into resilience-associated health-care utilisation patterns and targeted adaptation policies remain scarce. We aimed to capture the spatiotemporal health impacts in disaster-exposed counties and their neighbouring counties in China during storms, floods, tropical cyclones, and blizzards or winter storms; understand the association between health-system resilience metrics and hazard-attributable hospitalisations; and develop evidence-based adaptation policies towards climate extremes. METHODS: In this retrospective, observational analysis of county-level aggregated hospitalisation data, we used a propensity score matching-difference-in-differences framework to assess the spatiotemporal changes of nine types of disease-specific hospitalisations in both disaster-exposed and neighbouring regions during storms, floods, tropical cyclones, and blizzards in China. We quantified the relative importance and health gains of health-system metrics during such hazards through random forest approach with interpretable partial dependence plots to derive evidence-based adaptation recommendations. FINDINGS: We included hospitalisation data from Jan 1, 2016 to Dec 31, 2023. In this period, 3241 county-hazard event combinations and 41 747 482 hospitalisations were recorded across 955 Chinese counties. The disaster-exposed regions experienced an initial decline in hospitalisation rates, followed by admission surges after disasters. For example, infectious disease admissions decreased by 11·92% (95% CI -10·53 to -13·31) during the flood-active period but increased by 7·68% (6·46-8·91) after 1-2 weeks of floods. Neighbouring zones were also affected through spillover effects, with infectious disease admissions increasing by 3·18% (1·76-4·61) after 1-2 weeks of the floods. Cardiovascular disease, injuries, infectious, respiratory, and mental disorders were more sensitive across all regions. Particularly for disaster-exposed counties, cardiovascular hospitalisations increased by 14·31% (7·34-21·29) during the tropical cyclone-active period. Notably, compared with low-resilience counties, high-resilience counties were associated with 19·48-30·03% smaller hazard-related relative changes in hospitalisation rates during the hazard-active period and 27·07-31·08% smaller hazard-related relative changes in hospitalisation rates in post-hazard periods. For instance, during the storm-active period, the increase in respiratory hospitalisations was 7·21% (0·67-13·75) in high-resilience counties versus 12·13% (5·20-19·05) in low-resilience counties. Health workforce (relative importance 14·58% during the hazard-active period and 13·80% during the post-hazard period) and service delivery (14·10% during the hazard-active period and 14·17% during the post-hazard period) were identified as key contributors of health-system resilience. Empirical synergistic effects were observed when combining interventions during the post-hazard period, with the combined effect of service delivery (individual contribution 8%) and workforce (individual contribution 4%) exceeding the sum of their individual contributions (16% reduction in cumulative excess admissions) by 33%. INTERPRETATION: Climate hazards are associated with substantial changes in hospitalisation rates in both disaster-exposed and neighbouring regions. Health-system resilience is essential in addressing disaster-health challenges. Targeted adaptation interventions should be context-appropriate and threshold-aware, thereby maximising the public health benefits relative to resilience-oriented investments in health systems. FUNDING: Gates Foundation and the National Natural Science Foundation of China.

Journal Article↗

PubMed2005

Cost/benefit analysis of a benthic monitoring programme of organic benthic enrichment using different sampling and analysis methods.

To investigate the combined effects of decreasing taxonomic resolution (i.e. species, family, phylum), the use of different mesh-size (1.0 mm and 0.5 mm) and the type of samplers used (van Veen vs. corers taken by divers) on the quality of data obtained, a comparative study was undertaken with the overall aim of identifying cost efficient methods for routinely monitoring the ecological change caused by Mediterranean fish farming. The results clearly showed that information loss was relatively low as data were aggregated at higher taxonomic levels, particularly up to the level of family or even order. It was also found that the extra information gained by sieving samples through a 0.5 mm sieve did not improve the ability to distinguish the potentially impacted sites from the control stations. Finally, it was found that a relatively large proportion of the available information concerning the community structure such as abundance, biomass or diversity is lost when sampling is carried out with corers. A cost/benefit ratio analysis for the two sampling and the two sieving methods showed minimal values for the van Veen samples (for both sieve fractions) at the family level, indicating that analysis at this level gives the best balance between precision of the results and decrease in taxonomic effort. However, if the time needed to sort the samples is included in the analysis, then samples taken with corers using a 0.5 mm sieve and identified to families seems like a good compromise between precision and cost.

Animals↗

PubMed2004

VAMP2-dependent exocytosis regulates plasma membrane insertion of TRPC3 channels and contributes to agonist-stimulated Ca2+ influx.

The mechanism(s) involved in agonist-stimulation of TRPC3 channels is not yet known. Here we demonstrate that TRPC3-N terminus interacts with VAMP2 and alphaSNAP. Further, endogenous and exogenously expressed TRPC3 colocalized and coimmunoprecipitated with SNARE proteins in neuronal and epithelial cells. Imaging of GFP-TRPC3 revealed its localization in the plasma membrane region and in mobile intracellular vesicles. Recovery of TRPC3-GFP fluorescence after photobleaching of the plasma membrane region was decreased by brefeldin-A or BAPTA-AM. Cleavage of VAMP2 with tetanus toxin (TeNT) did not prevent delivery of TRPC3 to the plasma membrane region but reduced its surface expression. TeNT also decreased carbachol and OAG, but not thapsigargin, stimulated Ca2+ influx. Importantly, carbachol, not thapsigargin, increased surface expression of TRPC3 that was attenuated by TeNT and not by BAPTA. In aggregate, these data suggest that VAMP2-dependent exocytosis regulates plasma membrane insertion of TRPC3 channels and contributes to carbachol-stimulation of Ca2+ influx.

Animals↗

PubMed2005

Neuronal TGF-beta1 mediates IL-9/mast cell interaction and exacerbates excitotoxicity in newborn mice.

Intraneocortical injection of ibotenate, a glutamate analog, in newborn mice produces damage mimicking lesions observed in human infants with cerebral palsy. Previous research using this model has demonstrated that pretreatment with IL-9, a Th2 cytokine, significantly exacerbated excitotoxic brain lesions. The goal of this study is to identify the underlying pathophysiological mechanism of lesion formation. Pretreatment with TGF-beta1 produced the same effects as IL-9 on ibotenate-induced lesions. IL-9 effects were abolished when a specific TGF-beta1 neutralizing antibody is administered at the same time. Real-time PCR, Western blot, and immunohistochemistry showed that pretreatment with IL-9 increased TGF-beta1 neocortical expression. In vitro studies using real-time PCR and immunocytochemistry demonstrated that neurons were a major contributor in IL-9-induced increase of TGF-beta1. In c-Kit mast cell-deficient mice, TGF-beta1 failed to exacerbate excitotoxic brain lesions, suggesting a key role of mast cells in TGF-beta1 effects. A specific inhibitor of mast cell degranulation and histamine receptor blockers abrogated TGF-beta1 effects on excitotoxic lesions, providing further evidence of mast cell involvement and the role of mast cell-derived histamine. Finally, in vitro studies using a mast cell line showed that TGF-beta1 increased histamine in the supernatant. In aggregate, these data support the notion that neuronal TGF-beta1 plays a key role in the IL-9/mast cell interaction, which leads to an exacerbation of neonatal excitotoxic damage through an increased extracellular histamine concentration. The identification of this pathway, if confirmed in human neonates, might have important implications for understanding and preventing cerebral palsy.

Animals↗

PubMed2006

Tissue transglutaminase crosslinks ataxin-1: possible role in SCA1 pathogenesis.

Transglutaminase type 2 (TG2) has recently been implicated in crosslinking of mutant huntingtin protein into aggregates. Here we show that TG2 also crosslinks spinocerebellar ataxia-1 (SCA1) gene product ataxin-1. HeLa cell lysates expressing GFP tagged ataxin-1 with 2, 30 or 82 glutamines showed covalent crosslinking of ataxin-1 when incubated with exogenously added TG2. This crosslinking was inhibited by TG2 inhibitor cystamine. SCA1 transgenic mice which overexpress the mutant ataxin-1 in cerebellar Purkinje cells showed elevated nuclear TG2 in the absence of ataxin-1 nuclear aggregates. The addition of purified TG2 to the nuclear extracts or addition of SCA1 nuclear TG2 to GFP-Q82 HeLa cell lysates resulted in the formation of insoluble aggregates. These data indicate that ataxin-1 is a substrate of TG2. Further, in SCA1 TG2 may translocate to the nucleus in response to nuclear accumulation of mutant ataxin-1 at early stages of the disease.

Animals↗

PubMed2006

A role for neurotrophin-3 in targeting developing cholinergic axon projections to cerebral cortex.

This study examined the relationship between expression of neurotrophin-3 (NT-3) and the ingrowth of cholinergic axonal projections in cerebral cortex. Patterns of expression of NT-3 (defined by beta-galactosidase reporter expression in heterozygous offspring of transgenic NT-3(lacZneo/+) mice) revealed that limbic cortical regions (including frontal, cingulate, and insular cortex, as well as the dentate gyrus) express NT-3 and that these cortical regions receive early and relatively dense cholinergic axons (stained for acetylcholinesterase, AChE). Using the dentate gyrus as a model system, studies revealed that expression of the NT-3 reporter parallels, and precedes by approximately 2 days, the ingrowth of AChE positive cholinergic axons. Studies of forebrain organotypic slice cultures demonstrate that basal forebrain-derived cholinergic axons extend into cortical regions in a pattern that mimics the pattern of expression of the NT-3 reporter. Similarly, chimeric co-cultures, combining wild type septum with a slice of hippocampus from heterozygous NT-3(lacZneo/+) mice, demonstrate that cholinergic axons grow into regions of the dentate gyrus that express the NT-3 reporter. Hemisphere slice cultures made from NT-3 knockout mice reveal cholinergic axonal growth into cortex, but these axons do not form the regional pattern characteristic of slice cultures made from wild type or heterozygous NT-3(lacZneo/+) mice. Further, chimeric co-cultures made using slices of wild type septum combined with slices of hippocampus from NT-3 knockout mice demonstrate robust cholinergic axonal growth into the hippocampus, but the cholinergic axons do not form the characteristic preterminal pattern associated with the dentate gyrus. Slice cultures from limbic cortical tissue from the NT-3 null mice do not display exaggerated levels of cell death. In aggregate, these data support the hypothesis that expression of NT-3 by cortical neurons serves to attract basal forebrain cholinergic projections to their target cells in cerebral cortex.

Acetylcholinesterase↗

PubMed2005

Zingiberis rhizoma: a comprehensive review on the ginger effect and efficacy profiles.

Zingiberis rhizoma is used as a broadspectrum antiemetic. We, therefore, conducted a comprehensive review of the literature to summarize the pharmacological and clinical effects of this popular plant material. Although clinical and experimental studies suggest that ginger has some antiemetic properties, clinical evidence beyond doubt is only available for pregnancy-related nausea and vomiting. Meta-analyses could not demonstrate the postoperative antiemetic effectiveness, and effect in motion sickness or nausea/vomiting of other ethiology. It also remains to be confirmed that proprietary ginger preparations are clinically useful to alleviate osteoarthritic or other pain, although there is no doubt that ginger constituents interfere with the inflammatory cascade and the vanilloid nociceptor. Ginger exerts in vitro antioxidative, antitumorigenic and immunomodulatory effects and is an effective antimicrobial and antiviral agent. Animal studies demonstrate effects on the gastrointestinal tract, the cardiovascular system, on experimental pain and fever, antioxidative, antilipidemic and antitumor effects, as well as central and other effects. The most relevant human pharmacological studies require a confirmatory study to exclude interaction of ginger preparations with platelet aggregation. Pharmacokinetic data are only available for [6]-gingerol and zingiberene. Preclinical safety data do not rule out potential toxicity, which should be monitored especially following ginger consumption over longer periods.

Antiemetics↗

PubMed2006

Use of social network analysis to characterize the pattern of animal movements in the initial phases of the 2001 foot and mouth disease (FMD) epidemic in the UK.

Aggregated movement data do not take into account the relative position of the units within a higher-level structure. Social network analysis (SNA) and graph theory provide a tool to organise and analyse relational data overcoming the limitations of standard methods where the position of individuals/observations does not affect the result of the analysis. Some recorded movements of cattle and sheep during the initial phase of the 2001 foot and mouth disease (FMD) outbreak in the UK, before the ban on animal movements was imposed, are analysed descriptively using SNA. With the data available, a directed dichotomized network with 653 nodes and 797 arches was analysed. Most of the 10 nodes with the highest betweenness (3 farms, 4 markets and 3 dealers) were identified as key players in the initial spread of the infection. Three groups of nodes with distinctive proportion of k < or = 2 neighbours would result in three different theoretical outbreak dimensions assuming that the infection is only disseminated by the movements included in the network: no spread, spread up to 7% and around 25%. There are three hierarchical clusters with 308, 215 and 130 nodes, respectively. Farms in cluster 1 appear to be more similar in their movement patterns to non-farm holdings than to farms in clusters 2 and 3. Relative betweenness, k-neighbours and structural equivalence using hierarchical clustering were able to identify key actors in the evolution of the initial phases of the FMD outbreak such as markets, dealers and farms with atypical movement patterns. Holdings with high betweenness, large number of k < or = 2 neighbours and with movement pattern as in cluster 1 should be targeted in disease control activities once primary actors like markets, dealers and slaughter houses have been contained.

Animals↗