Assessing complexity and dynamics in epidemics: geographical barriers and facilitators of foot-and-mouth disease dissemination.

Introduction: Physical and non-physical processes that occur in nature may influence biological processes, such as dissemination of infectious diseases. However, such processes may be hard to detect when they are complex systems. Because complexity is a dynamic and non-linear interaction among numerous elements and structural levels in which specific effects are not necessarily linked to any one specific element, cause-effect connections are rarely or poorly observed. Methods: To test this hypothesis, the complex and dynamic properties of geo-biological data were explored with high-resolution epidemiological data collected in the 2001 Uruguayan foot-and-mouth disease (FMD) epizootic that mainly affected cattle. County-level data on cases, farm density, road density, river density, and the ratio of road (or river) length/county perimeter were analyzed with an open-ended procedure that identified geographical clustering in the first 11 epidemic weeks. Two questions were asked: (i) do geo-referenced epidemiologic data display complex properties? and (ii) can such properties facilitate or prevent disease dissemination? Results: Emergent patterns were detected when complex data structures were analyzed, which were not observed when variables were assessed individually. Complex properties-including data circularity-were demonstrated. The emergent patterns helped identify 11 counties as 'disseminators' or 'facilitators' (F) and 264 counties as 'barriers' (B) of epidemic spread. In the early epidemic phase, F and B counties differed in terms of road density and FMD case density. Focusing on non-biological, geographical data, a second analysis indicated that complex relationships may identify B-like counties even before epidemics occur. Discussion: Geographical barriers and/or promoters of disease dispersal may precede the introduction of emerging pathogens. If corroborated, the analysis of geo-referenced complexity may support anticipatory epidemiological policies.

Systems Biology and Ratio-Based, Real-Time Disease Surveillance.

Most infectious disease surveillance methods are not well fit for early detection. To address such limitation, here we evaluated a ratio- and Systems Biology-based method that does not require prior knowledge on the identity of an infective agent. Using a reference group of birds experimentally infected with West Nile virus (WNV) and a problem group of unknown health status (except that they were WNV-negative and displayed inflammation), both groups were followed over 22 days and tested with a system that analyses blood leucocyte ratios. To test the ability of the method to discriminate small data sets, both the reference group (n = 5) and the problem group (n = 4) were small. The questions of interest were as follows: (i) whether individuals presenting inflammation (disease-positive or D+) can be distinguished from non-inflamed (disease-negative or D-) birds, (ii) whether two or more D+ stages can be detected and (iii) whether sample size influences detection. Within the problem group, the ratio-based method distinguished the following: (i) three (one D- and two D+) data classes; (ii) two (early and late) inflammatory stages; (iii) fast versus regular or slow responders; and (iv) individuals that recovered from those that remained inflamed. Because ratios differed in larger magnitudes (up to 48 times larger) than percentages, it is suggested that data patterns are likely to be recognized when disease surveillance methods are designed to measure inflammation and utilize ratios.

Coupling Vector-host Dynamics with Weather Geography and Mitigation Measures to Model Rift Valley Fever in Africa.

We present and characterize a multi-host epidemic model of Rift Valley fever (RVF) virus in East Africa with geographic spread on a network, rule-based mitigation measures, and mosquito infection and population dynamics. Susceptible populations are depleted by disease and vaccination and are replenished with the birth of new animals. We observe that the severity of the epidemics is strongly correlated with the duration of the rainy season and that even severe epidemics are abruptly terminated when the rain stops. Because naturally acquired herd immunity is established, total mortality across 25 years is relatively insensitive to many mitigation approaches. Strong reductions in cattle mortality are expected, however, with sufficient reduction in population densities of either vectors or susceptible (ie. unvaccinated) hosts. A better understanding of RVF epidemiology would result from serology surveys to quantify the importance of herd immunity in epidemic control, and sequencing of virus from representative animals to quantify the realative importance of transportation and local reservoirs in nucleating yearly epidemics. Our results suggest that an effective multi-layered mitigation strategy would include vector control, movement control, and vaccination of young animals yearly, even in the absence of expected rainfall.

The Stanford Leisure-Time Activity Categorical Item (L-Cat): a single categorical item sensitive to physical activity changes in overweight/obese women.

BACKGROUND: Physical activity is essential for chronic disease prevention, yet <40% of overweight/obese adults meet the national activity recommendations. For time-efficient counseling, clinicians need a brief, easy-to-use tool that reliably and validly assesses a full range of activity levels, and, most importantly, is sensitive to clinically meaningful changes in activity. The Stanford Leisure-Time Activity Categorical Item (L-Cat) is a single item comprising six descriptive categories ranging from inactive to very active. This novel methodological approach assesses national activity recommendations as well as multiple clinically relevant categories below and above the recommendations, and incorporates critical methodological principles that enhance psychometrics (reliability, validity and sensitivity to change). METHODS: We evaluated the L-Cat's psychometrics among 267 overweight/obese women who were asked to meet the national activity recommendations in a randomized behavioral weight-loss trial. RESULTS: The L-Cat had excellent test-retest reliability (κ=0.64, P<0.001) and adequate concurrent criterion validity; each L-Cat category at 6 months was associated with 1059 more daily pedometer steps (95% CI 712-1407, ß=0.38, P<0.001) and 1.9% greater initial weight loss at 6 months (95% CI -2.4 to -1.3, ß=-0.38, P<0.001). Of interest, L-Cat categories differentiated from each other in a dose-response gradient for steps and weight loss (Ps<0.05) with excellent face validity. The L-Cat was sensitive to change in response to the trial's activity component. Women increased one L-Cat category at 6 months (M=1.0±1.4, P<0.001); 55.8% met the recommendations at 6 months whereas 20.6% did at baseline (P<0.001). Even among women not meeting the recommendations at both baseline and 6 months (n=106), women who moved 1 L-Cat categories at 6 months lost more weight than those who did not (M=-4.6%, 95% CI -6.7 to -2.5, P<0.001). CONCLUSIONS: Given strong psychometrics, the L-Cat has timely potential for clinical use such as tracking activity changes via electronic medical records, especially among overweight/obese populations who are unable or unlikely to reach national recommendations.

Clinical and acquired immunologic responses to West Nile virus infection of domestic chickens (Gallus gallus domesticus).

Numerous bird species are highly susceptible to North American strains of West Nile virus (WNV), and although domestic chickens are relatively resistant to WNV-associated disease, this species currently represents the most practical avian model for immune responses to WNV infection. Knowledge of the immunomodulation of susceptibility to WNV in birds is important for understanding taxonomic differences in infection outcomes. While focusing on immunophenotyping of CD3(+), CD4(+), CD8(+), and CD45(+) lymphocyte subpopulations, we compared lymphocyte subpopulations, blood chemistries, cloacal temperatures, IgM and IgG antibody titers, and differential whole-blood cell counts of WNV-infected and uninfected hens. Total blood calcium and lymphocyte numbers were lower in WNV-infected chickens compared with uninfected chickens. The heterophil-to-lymphocyte ratio increased over time from 2 to 22 d postinoculation (DPI) in uninfected chickens and from 2 to 8 DPI in WNV-infected chickens, although levels declined from 8 to 22 DPI in the latter group. No significant differences were found in the remaining immunological and hematological variables of the WNV-infected and uninfected groups. Our results reaffirm that chickens are resistant to WNV infection, and demonstrated that the heterophil-to-lymphocyte ratio differed between groups, allowing for sorting of infection status. Similar patterns in immune responses over time in both infected and uninfected hens may be related to age (i.e., 10 wk) and associated immune development.

Physiological, growth, and immune responses of Japanese quail chicks to the multiple stressors of immunological challenge and lead shot.

Exposure to the combination of a contaminant and an immunological challenge during development may greatly increase the impact of either or both of these stressors on an individual. This study investigated the interacting effects of a nonpathogenic immunological challenge and lead shot exposure early in the development of a precocial species. Seventy-one quail (Coturnix coturnix japonica) chicks orally received either one #9 lead shot (0.05 g), four lead shots (0.2 g), or no lead at the age of 8 days. A third of each of these groups of chicks were intraperitoneally injected with either 0.075 ml of 10% chukar (Alectoris graeca) red blood cells (CRBCs), Newcastle disease virus (NDV), or a placebo oil vaccine at 13 and 35 days of age. There was no difference in the survival between any of the lead or antigen treatment groups. Lead concentrations in blood were greater for the lead-dosed groups on day 49 but not on day 128. Growth curves were approximated by Weibull functions; growth parameters did not differ between lead-treated and antigen-treated birds. CRBC antigen increases fluctuating asymmetry (FA) for primary feather five, while NDV reduced FA. Lead did not affect antibody production or cell-mediated immune response. White blood cell numbers increased 7 days after antigen injection on days 27 and 49 of age. Granulocyte numbers were significantly higher for the lead-treated quail than the control quail, and both antigen-treated groups had lower granulocyte numbers than control quail. The treatment groups of combining NDV and lead shot had an average plasma protein 14% lower than other groups. Lead shot in the highest of these doses lowered asymptotic weights, increased hematocrits, lowered plasma protein, and increased granulocyte numbers of quail.

Using direct mail to recruit Hispanic adults into a dietary intervention: an experimental study.

Identifying strategies for successful recruitment of ethnic minorities into scientific studies is critical. Without effective methods, investigators may fail to recruit the desired sample size, take longer to recruit than planned, and delay progress for research in minority health. Direct mail is an appealing recruitment method because of the potential for reaching large target populations and producing a high volume of inquiries about a study with relatively little staff effort. To determine which of three direct mail strategies yielded higher recruitment, 561 Hispanic employees were randomly assigned to receive either: (a) a flyer about a worksite dietary intervention; (b) the same flyer plus a personalized hand-signed letter containing heart disease risk statistics for the general American population; or (c) the flyer plus a personalized hand-signed letter containing statistics for Hispanics. Two orthogonal chi-square comparisons were examined. The personalized letters plus flyer yielded a significantly higher response rate (7.8%) than the flyer alone (2.1%), X2(1, N = 561) = 7.5, p = .006. However, the personalized letter with Hispanic heart disease risk statistics did not yield a statistically significant higher response rate (9.1%) than the letter with the general population risk statistics (6.5%), X2(1, N = 370) = 0.9, p > .34. These findings suggest that personalized approaches can increase the effectiveness of direct mail efforts for recruiting ethnic minorities into interventions and may be particularly helpful for large-scale interventions.

End-of-life care content in 50 textbooks from multiple specialties.

CONTEXT: Prior reviews of small numbers of medical textbooks suggest that end-of-life care is not well covered in textbooks. No broad study of end-of-life care content analysis has been performed on textbooks across a wide range of medical, pediatric, psychiatric, and surgical specialties. OBJECTIVE: To determine the quantity and rate the adequacy of information on end-of-life care in textbooks from multiple medical disciplines. DESIGN AND SOURCES: A 1998 review of 50 top-selling textbooks from multiple specialties (cardiology, emergency medicine, family and primary care medicine, geriatrics, infectious disease and acquired immunodeficiency syndrome [AIDS], internal medicine, neurology, oncology and hematology, pediatrics, psychiatry, pulmonary medicine, and surgery) for the presence and adequacy of content in 13 end-of-life care domains. MAIN OUTCOME MEASURES: Chapters on diseases commonly causing death and those devoted to end-of-life care were identified, read, rated, and compared by textbook specialty, chapter, and domain for the presence of helpful information in the 13 domains. Content for each domain was rated as absent, minimally present, or helpful. Textbook indexes were analyzed for the number of pages relevant to end-of-life care. RESULTS: Overall, helpful information was provided in 24.1% (range, 8.7%-44.2%) of the expected end-of-life content domains; in 19.1% (range, 6.2%-38.5%), expected content received minimal attention; and in 56.9% (range, 23.1 %-77.9%), expected content was absent. As a group, the textbooks with the highest percentages of absent content were in surgery (71.8%), infectious diseases and AIDS (70%), and oncology and hematology (61.9%). Textbooks with the highest percentage of helpful end-of-life care content were in family medicine (34.4%), geriatrics (34.4%), and psychiatry (29.6%). In internal medicine textbooks, the content domains with the greatest amount of helpful information were epidemiology and natural history. Content domains covered least well were social, spiritual, ethical, and family issues, as well as physician after-death responsibilities. On average, textbook indexes cited 2% of their total pages as pertinent to end-of-life care. CONCLUSION: Top-selling textbooks generally offered little helpful information on caring for patients at the end of life. Most disease-oriented chapters had no or minimal end-of-life care content. Specialty textbooks with information about particular diseases often did not contain helpful information on caring for patients dying from those diseases.

Growth, developmental stability and immune response in juvenile Japanese quails (Coturnix coturnix japonica).

Stresses are environmental factors which restrict growth or cause a potentially adverse change in an organism. The exposure of developing organisms to environmental stresses may have several physiological consequences including a decrease in immunocompetence. However, mounting an immune response against a foreign antigen may in itself constitute a cost for developing organisms. This cost has potentially long-term consequences for adult function and fitness. This study examines the growth and developmental stability of Japanese quail++ chicks challenged by three non-pathogenic antigens: sheep red blood cells, which assess T-cell-dependent immune responses, and Mycoplasma synoviae and Newcastle disease virus, which assess T-cell-independent responses. Increases in both body mass and wing length were significantly reduced in antigen-challenged birds compared to control birds. Fluctuating asymmetry (FA) in the masses of primary feathers increased from the innermost (1) to the outermost (10) position on the wing. In addition, antigen challenge by M. synoviae and sheep red blood cells was associated with an increase in FA. The cell-mediated response measured by reaction to phytohaemagglutinin was significantly depressed in M. synoviae-challenged birds. White blood cell counts, except for monocytes, were elevated in response to all three antigen treatments. Total plasma protein and haematocrit also differed between treatments but exhibited no clear relationship to antigen challenge. Immune responses clearly impose a stress on developing chicks. Additional research will be required to determine the long-term consequences of developmental stress and assess the selective forces that influence the strength of the immune responses of chicks.

Predominance of dense low-density lipoprotein particles predicts angiographic benefit of therapy in the Stanford Coronary Risk Intervention Project.

BACKGROUND: LDL particles differ in size and density. Individuals with LDL profiles that peak in relatively small, dense particles have been reported to be at increased risk of coronary artery disease. We hypothesized that response to coronary disease therapy in such individuals might differ from response in individuals whose profiles peak in larger, more buoyant LDL. We examined this hypothesis in the Stanford Coronary Risk Intervention Project, an angiographic trial that compared multifactorial risk-reduction intervention with the usual care of physicians. METHODS AND RESULTS: For 213 men, a bimodal frequency distribution of peak LDL density (g/mL) determined by analytical ultracentrifugation was used to classify baseline LDL profiles as "buoyant mode" (density < or = 1.0378) or "dense mode" (density > 1.0378). Coronary disease progression after 4 years was assessed by rates of change (mm/y, negative when arteries narrow) of minimum artery diameter. Rates for buoyant-mode subjects were -0.038 +/- 0.007 (mean +/- SEM) in usual care (n = 65) and -0.039 +/- 0.010 in intervention (n = 56; P = .6). Rates for dense-mode subjects were -0.054 +/- 0.012 in usual care (n = 51) and -0.008 +/- 0.009 in intervention (n = 41, P = .007). Lipid changes did not account for this difference in angiographic response. CONCLUSIONS: Different types of LDL profile may predict different-responses to specific therapies, perhaps because metabolic processes determine both LDL profiles and responses to therapies.

Endothelial function and coronary risk reduction: mechanisms and influences of nitric oxide.

The biological mechanisms related to progression and regression of CAD are indeed complex. While endothelial injury and lipid accumulation play an important role in the progression/regression of CAD, mechanisms of vascular function, particularly that of the endothelial modulation of vasodilation, cannot be ignored. Much is yet to be learned about the influences of endothelial function on the progression/regression and stabilization of CAD. Initial evidence suggesting that risk reduction interventions favorably influence vascular function argues for further investigation of this role. To date, much of the research on risk reduction has focused on lipid lowering and regression of artery plaque, a focus on artery structure. A focus on both function and structure is likely to expand our understanding of the effect of risk reduction interventions beyond lipid lowering. Given the multifactorial causes associated with development of CAD, such an approach is necessary.

Life-style changes and coronary heart disease: the influence of nonpharmacologic interventions.

Life-style habits such as diet and exercise can have powerful affects on the development and progression of coronary heart disease. This article presents evidence supporting the use of these two modalities in the treatment of coronary heart disease. Diet is discussed in terms of cholesterol, obesity, fiber, fish oils, and antioxidants. Exercise is discussed in terms of the preparation for and the components of an exercise program. Appropriate nursing interventions are offered for use when working with patients who must modify their dietary or exercise habits.

Effects of intensive multiple risk factor reduction on coronary atherosclerosis and clinical cardiac events in men and women with coronary artery disease. The Stanford Coronary Risk Intervention Project (SCRIP).

BACKGROUND: Recent clinical trials have shown that modification of plasma lipoprotein concentrations can favorably alter progression of coronary atherosclerosis, but no data exist on the effects of a comprehensive program of risk reduction involving both changes in lifestyle and medications. This study tested the hypothesis that intensive multiple risk factor reduction over 4 years would significantly reduce the rate of progression of atherosclerosis in the coronary arteries of men and women compared with subjects randomly assigned to the usual care of their physician. METHODS AND RESULTS: Three hundred men (n = 259) and women (n = 41) (mean age, 56 +/- 7.4 years) with angiographically defined coronary atherosclerosis were randomly assigned to usual care (n = 155) or multifactor risk reduction (n = 145). Patients assigned to risk reduction were provided individualized programs involving a low-fat and -cholesterol diet, exercise, weight loss, smoking cessation, and medications to favorably alter lipoprotein profiles. Computer-assisted quantitative coronary arteriography was performed at baseline and after 4 years. The main angiographic outcome was the rate of change in the minimal diameter of diseased segments. All subjects underwent medical and risk factor evaluations at baseline and yearly for 4 years, and reasons for all hospitalizations and deaths were documented. Of the 300 subjects randomized, 274 (91.3%) completed a follow-up arteriogram, and 246 (82%) had comparative measurements of segments with visible disease at baseline and follow-up. Intensive risk reduction resulted in highly significant improvements in various risk factors, including low-density lipoprotein cholesterol and apolipoprotein B (both, 22%), high-density lipoprotein cholesterol (+12%), plasma triglycerides (-20%), body weight (-4%), exercise capacity (+20%), and intake of dietary fat (-24%) and cholesterol (-40%) compared with relatively small changes in the usual-care group. No change was observed in lipoprotein(a) in either group. The risk-reduction group showed a rate of narrowing of diseased coronary artery segments that was 47% less than that for subjects in the usual-care group (change in minimal diameter, -0.024 +/- 0.066 mm/y versus -0.045 +/- 0.073 mm/y; P < .02, two-tailed). Three deaths occurred in each group. There were 25 hospitalizations in the risk-reduction group initiated by clinical cardiac events compared with 44 in the usual-care group (rate ratio, 0.61; P = .05; 95% confidence interval, 0.4 to 0.9). CONCLUSIONS: Intensive multifactor risk reduction conducted over 4 years favorably altered the rate of luminal narrowing in coronary arteries of men and women with coronary artery disease and decreased hospitalizations for clinical cardiac events.

Saturated fat intake and insulin resistance in men with coronary artery disease. The Stanford Coronary Risk Intervention Project Investigators and Staff.

BACKGROUND: To determine whether there is an association between diet and plasma insulin concentration that is independent of obesity, we studied the relation of dietary composition and caloric intake to obesity and plasma insulin concentrations in 215 nondiabetic men aged 32-74 years with angiographically proven coronary artery disease. METHODS AND RESULTS: After adjusting for age, the intake of saturated fatty acids and cholesterol were positively correlated (p less than 0.05) with body mass index (r = 0.18, r = 0.16), waist-to-hip circumference ratio (r = 0.21, r = 0.22), and fasting insulin (r = 0.26, r = 0.23). Carbohydrate intake was negatively correlated with body mass index (r = -0.21), waist-to-hip ratio (r = -0.21), and fasting insulin (r = -0.16). Intake of monounsaturated fatty acids did not correlate significantly with body mass index or waist-to-hip circumference ratio but did correlate positively with fasting insulin (r = 0.24). Intake of dietary calories was negatively correlated with body mass index (r = -0.15). In multivariate analysis, intake of saturated fatty acids was significantly related to elevated fasting insulin concentration independently of body mass index. CONCLUSIONS: These cross-sectional findings in nondiabetic men with coronary artery disease suggest that increased consumption of saturated fatty acids is associated independently with higher fasting insulin concentrations.