In-Grove Spatiotemporal Spread of Citrus Huanglongbing and Its Psyllid Vector in Relation to Weather.

Reports of spatial patterns of 'Candidatus Liberibacter asiaticus'-infected asymptomatic citrus trees and 'Ca. L. asiaticus'-positive Asian citrus psyllids (ACP) are rare, as are published relationships between huanglongbing (HLB), ACP, and weather. Here, spatial patterns of 'Ca. L. asiaticus'-positive asymptomatic and symptomatic trees were determined every half year in a small grove over 2.5 years, and of HLB-symptomatic trees and ('Ca. L. asiaticus'-positive) ACP populations every month in two commercial groves for 1 year. Spread of symptomatic trees followed that of asymptomatic 'Ca. L. asiaticus'-positive trees with <6 months' delay. 'Ca. L. asiaticus'-positive asymptomatic and symptomatic fronts moved at 2.5 to 3.6 m month-1. No spatial relationship was detected between ACP populations and HLB-infected trees. HLB incidence and 'Ca. L. asiaticus'-positive ACP dynamics were tentatively positively correlated with monthly rainfall data and, to a lesser extent, with average minimum temperature.

Regional Spatial-Temporal Spread of Citrus Huanglongbing Is Affected by Rain in Florida.

Citrus huanglongbing (HLB), associated with 'Candidatus Liberibacter asiaticus' (Las), disseminated by Asian citrus psyllid (ACP), has devastated citrus in Florida since 2005. Data on HLB occurrence were stored in databases (2005 to 2012). Cumulative HLB-positive citrus blocks were subjected to kernel density analysis and kriging. Relative disease incidence per county was calculated by dividing HLB numbers by relative tree numbers and maximum incidence. Spatiotemporal HLB distributions were correlated with weather. Relative HLB incidence correlated positively with rainfall. The focus expansion rate was 1626 m month-1, similar to that in Brazil. Relative HLB incidence in counties with primarily large groves increased at a lower rate (0.24 year-1) than in counties with smaller groves in hotspot areas (0.67 year-1), confirming reports that large-scale HLB management may slow epidemic progress.

Schistosomiasis and neglected tropical diseases: towards integrated and sustainable control and a word of caution.

In May 2001, the World Health Assembly (WHA) passed a resolution which urged member states to attain, by 2010, a minimum target of regularly administering anthelminthic drugs to at least 75% and up to 100% of all school-aged children at risk of morbidity. The refined global strategy for the prevention and control of schistosomiasis and soil-transmitted helminthiasis was issued in the following year and large-scale administration of anthelminthic drugs endorsed as the central feature. This strategy has subsequently been termed 'preventive chemotherapy'. Clearly, the 2001 WHA resolution led the way for concurrently controlling multiple neglected tropical diseases. In this paper, we recall the schistosomiasis situation in Africa in mid-2003. Adhering to strategic guidelines issued by the World Health Organization, we estimate the projected annual treatment needs with praziquantel among the school-aged population and critically discuss these estimates. The important role of geospatial tools for disease risk mapping, surveillance and predictions for resource allocation is emphasised. We clarify that schistosomiasis is only one of many neglected tropical diseases and that considerable uncertainties remain regarding global burden estimates. We examine new control initiatives targeting schistosomiasis and other tropical diseases that are often neglected. The prospect and challenges of integrated control are discussed and the need for combining biomedical, educational and engineering strategies and geospatial tools for sustainable disease control are highlighted. We conclude that, for achieving integrated and sustainable control of neglected tropical diseases, a set of interventions must be tailored to a given endemic setting and fine-tuned over time in response to the changing nature and impact of control. Consequently, besides the environment, the prevailing demographic, health and social systems contexts need to be considered.

Acridine Orange for malaria diagnosis: its diagnostic performance, its promotion and implementation in Tanzania, and the implications for malaria control.

One hundred years ago, Giemsa's stain was employed for the first time for malaria diagnosis. Giemsa staining continues to be the method of choice in most malarious countries, although, in the recent past, several alternatives have been developed that exhibit some advantages. Considerable progress has been made with fluorescent dyes, particularly with Acridine Orange (AO). The literature on the discovery, development and validation of the AO method for malaria diagnosis is reviewed here. Compared with conventional Giemsa staining, AO shows a good diagnostic performance, with sensitivities of 81.3%-100% and specificities of 86.4%-100%. However, sensitivities decrease with lower parasite densities, and species differentiation may occasionally be difficult. The most notable advantage of the AO method over Giemsa staining is its promptness; results are readily available within 3-10 min, whereas Giemsa staining may take 45 min or even longer. This is an important advantage for the organization of health services and the provision of effective treatment of malaria cases. The national malaria control programme of Tanzania, together with the Japan International Co-operation Agency, began to introduce the AO method in Tanzania in 1994. So far, AO staining has been introduced in 70 regional and district hospitals, and 400 laboratory technicians have been trained to use the method. The results of this introduction, which are reviewed here and have several important implications, indicate that AO is a viable alternative technique for the laboratory diagnosis of malaria in highly endemic countries.

Efficacy and cost-effectiveness of environmental management for malaria control.

Roll back malaria (RBM) aims at halving the current burden of the disease by the year 2010. The focus is on sub-Saharan Africa, and it is proposed to implement efficacious and cost-effective control strategies. But the evidence base of such information is scarce, and a notable missing element is the discussion of the potential of environmental management. We reviewed the literature and identified multiple malaria control programmes that incorporated environmental management as the central feature. Prominent among them are programmes launched in 1929 and implemented for two decades at copper mining communities in Zambia. The full package of control measures consisted of vegetation clearance, modification of river boundaries, draining swamps, oil application to open water bodies and house screening. Part of the population also was given quinine and was sleeping under mosquito nets. Monthly malaria incidence rates and vector densities were used for surveillance and adaptive tuning of the environmental management strategies to achieve a high level of performance. Within 3-5 years, malaria-related mortality, morbidity and incidence rates were reduced by 70-95%. Over the entire 20 years of implementation, the programme had averted an estimated 4173 deaths and 161,205 malaria attacks. The estimated costs per death and malaria attack averted were US$ 858 and US$ 22.20, respectively. Over the initial 3-5 years start-up period, analogous to the short-duration of cost-effectiveness analyses of current studies, we estimated that the costs per disability adjusted life year (DALY) averted were US$ 524-591. However, the strategy has a track record of becoming cost-effective in the longer term, as maintenance costs were much lower: US$ 22-92 per DALY averted. In view of fewer adverse ecological effects, increased sustainability and better uses of local resources and knowledge, environmental management--integrated with pharmacological, insecticidal and bednet interventions--could substantially increase the chances of rolling back malaria.

Allostatic load as a marker of cumulative biological risk: MacArthur studies of successful aging.

Allostatic load (AL) has been proposed as a new conceptualization of cumulative biological burden exacted on the body through attempts to adapt to life's demands. Using a multisystem summary measure of AL, we evaluated its capacity to predict four categories of health outcomes, 7 years after a baseline survey of 1,189 men and women age 70-79. Higher baseline AL scores were associated with significantly increased risk for 7-year mortality as well as declines in cognitive and physical functioning and were marginally associated with incident cardiovascular disease events, independent of standard socio-demographic characteristics and baseline health status. The summary AL measure was based on 10 parameters of biological functioning, four of which are primary mediators in the cascade from perceived challenges to downstream health outcomes. Six of the components are secondary mediators reflecting primarily components of the metabolic syndrome (syndrome X). AL was a better predictor of mortality and decline in physical functioning than either the syndrome X or primary mediator components alone. The findings support the concept of AL as a measure of cumulative biological burden.

Agricultural colonization and malaria on the Amazon frontier.

The purpose of this paper is to characterize the interrelationships between macropolitical, social and economic policies, human migration, agricultural development, and malaria transmission on the Amazon frontier. We focus our analysis on a recent colonization project, POLONOROESTE, in the state of Rondonia. Employing data from field surveys in 1985-1987 and 1995, we use spatial statistical methodologies linked to a geographical information system (GIS) to describe the patterns of human settlement in the area, the ecological transformations induced by forest clearance practices, and the manner in which these factors determine gradations of malaria risk. Our findings show that land use patterns, linked to social organization of the community and the structure of the physical environment, played a key role in promoting malaria transmission. In addition, the location of each occupied area is itself an important determinant of the pattern of malaria risk. Based on lessons learned from our spatial and temporal characterization of malaria risk, we propose policies for malaria mitigation in the Brazilian Amazon.

The effects of health changes on projections of health service needs for the elderly population of the United States.

The 1982-1994 National Long-Term Care Surveys indicate an accelerating decline in disability among the U.S. elderly population, suggesting that a 1.5% annual decline in chronic disability for elderly persons is achievable. Furthermore, many risk factors for chronic diseases show improvements, many linked to education, from 1910 to the present. Projections indicate the proportion of persons aged 85-89 with less than 8 years of education will decline from 65% in 1980 to 15% in 2015. Health and socioeconomic status trends are not directly represented in Medicare Trust Fund and Social Security Administration beneficiary projections. Thus, they may have different economic implications from projections directly accounting for health trends. A 1.5% annual disability decline keeps the support ratio (ratio of economically active persons aged 20-64 to the number of chronically disabled persons aged 65+) above its 1994 value, 22:1, when the Hospital Insurance Trust Fund was in fiscal balance, to 2070. With no changes in disability, projections indicate a support ratio in 2070 of 8:1-63% below a cash flow balance.

A recipe for randomness.

Despite many diverse theories that address closely related themes-e. g., probability theory, algorithmic complexity, cryptoanalysis, and pseudorandom number generation-a near-void remains in constructive methods certified to yield the desired "random" output. Herein, we provide explicit techniques to produce broad sets of both highly irregular finite and normal infinite sequences, based on constructions and properties derived from approximate entropy (ApEn), a computable formulation of sequential irregularity. Furthermore, for infinite sequences, we considerably refine normality, by providing methods for constructing diverse classes of normal numbers, classified by the extent to which initial segments deviate from maximal irregularity.

Irregular arrays and randomization.

Although they lie at the conceptual core of a wide range of scientific questions, the notions of irregular or "random" arrangement and the process of randomization itself have never been unambiguously defined. Algorithmic implementation of these concepts requires a combinatorial, rather than a probability-theoretic, formulation. We introduce vector versions of approximate entropy to quantify the degrees of irregularity of planar (and higher dimensional) arrangements. Selection rules, applied to the elements of irregular permutations, define randomization in strictly combinatorial terms. These concepts are developed in the context of Latin square arrangements and valid randomization of them. Conflicts and tradeoffs between the objectives of irregular arrangements and valid randomization are highlighted. Extensions to broad classes of designs, and a diverse range of scientific applications are indicated, including lattice-based models in physics and signal detection in seismology and physiology.

Price of adaptation--allostatic load and its health consequences. MacArthur studies of successful aging.

BACKGROUND: Exponential growth in the population of older adults presents clinicians with special concerns about factors affecting risks for declines in cognitive and physical functioning. OBJECTIVES: To examine the hypothesis that risks for such declines and for disease outcomes, such as cardiovascular disease, are related to differences in allostatic load, the cumulative physiologic toll exacted on the body over time by efforts to adapt to life experiences. To present an operational definition of allostatic load, along with preliminary evidence of its predictive validity in relation to salient outcomes of aging. METHODS: Data from a longitudinal, community-based study of successful aging were used to develop a measure of allostatic load based on 10 parameters reflecting levels of physiologic activity across a range of important regulatory systems. Allostatic load is the sum of the number of parameters for which the subject was rated in the highest-risk quartile. RESULTS: Higher allostatic load scores were associated with poorer cognitive and physical functioning and predicted larger decrements in cognitive and physical functioning as well as being associated with an increased risk for the incidence of cardiovascular disease, independent of sociodemographic and health status risk factors. CONCLUSIONS: Findings are consistent with the conceptualization of allostatic load as an index of wear and tear on the body, with elevations in allostatic load predicting an increased risk for a decline in cognitive and physical functioning as well as cardiovascular disease in a cohort of older men and women. From a clinical perspective, the concept of allostatic load may provide the basis for a more comprehensive assessment of major risks in the aging process.

Increase in urinary cortisol excretion and memory declines: MacArthur studies of successful aging.

Cortisol production is increased during stress, and the actions of cortisol on receptors in the brain and other body organs are involved in allostasis, the process of adaptation to stress, as well as in allostatic load, the wear and tear associated with excessive exposure to cortisol. Using data from a community-based longitudinal study of older men and women, aged 70-79 yr, we tested the hypothesis that exposure to increasing levels of cortisol is associated with declines in memory performance. Associations between 12-h urinary free cortisol excretion and performance on tests of memory (delayed verbal recall and spatial recognition), abstraction, and spatial ability were examined. Among the women, greater cortisol excretion was associated with poorer baseline memory performance, independent of socio-demographic, health status, health behavior, and psychosocial characteristics. Moreover, women who exhibited increases in cortisol excretion over a 2.5-yr follow-up period were more likely to show declines in memory performance. By contrast, women who experienced declines in cortisol exhibited improvements in memory performance. No significant associations were found among the men. The results for the women suggest that decrements in memory performance associated with increases in cortisol may not represent irreversible effects, as declines in cortisol were associated with improvements in memory.

Can treatment that is helpful on average be harmful to some patients? A study of the conflicting information needs of clinical inquiry and drug regulation.

Randomized controlled trials are conducted with heterogeneous groups of patients, and the trial results represent an estimate of the average difference in the responses of the treatment groups. Clinicians, however, engage in a process of clinical inquiry, assembling data that will allow an assessment of the appropriate choice of treatment according to more narrowly defined clinical features. We describe a method of clinical inquiry within RCTs that can enhance the applicability of results to clinical decision making. Our methods included the use of data from the Beta-Blocker Heart Attack Trial, which enrolled 3837 subjects in 31 clinical centers. The 31 centers were divided into 21 dominant centers (mortality rates higher for placebo than propranolol) and 10 divergent centers (higher mortality rates for patients randomized to propranolol). Overall, compared to placebo, propranolol reduced the risk of dying for the "average" patient from 9.8 to 7.2%. Results for patients in dominant centers (RR = 0.50) were significantly different from those in divergent centers (RR = 1.33). We identified two cotherapies--aspirin use and coronary artery surgery--that subsequently affected the benefits of propranolol in divergent centers. For patients in divergent centers, propranolol reduced the risk of dying for patients treated with aspirin and/or coronary surgery (RR = 0.39), but not for patients not receiving these therapies (RR = 1.42). We conclude that differences in results across centers of a multicenter RCT may reflect important distinctions in the clinical conditions of enrolled subjects. These distinctions help to identify subgroups of patients in which treatment that has an average overall benefit may be harmful for some patients.

Randomness and degrees of irregularity.

The fundamental question "Are sequential data random?" arises in myriad contexts, often with severe data length constraints. Furthermore, there is frequently a critical need to delineate nonrandom sequences in terms of closeness to randomness--e.g., to evaluate the efficacy of therapy in medicine. We address both these issues from a computable framework via a quantification of regularity. ApEn (approximate entropy), defining maximal randomness for sequences of arbitrary length, indicating the applicability to sequences as short as N = 5 points. An infinite sequence formulation of randomness is introduced that retains the operational (and computable) features of the finite case. In the infinite sequence setting, we indicate how the "foundational" definition of independence in probability theory, and the definition of normality in number theory, reduce to limit theorems without rates of convergence, from which we utilize ApEn to address rates of convergence (of a deficit from maximal randomness), refining the aforementioned concepts in a computationally essential manner. Representative applications among many are indicated to assess (i) random number generation output; (ii) well-shuffled arrangements; and (iii) (the quality of) bootstrap replicates.

Beta-blockers after myocardial infarction: influence of first-year clinical course on long-term effectiveness.

OBJECTIVE: To develop a strategy for evaluating drug efficacy over time that accounts for heterogeneous clinical courses evolving after initiation of therapy and to demonstrate its use in assessing the long-term therapeutic benefit of propranolol after myocardial infarction. DESIGN: Analysis of data from the Beta-Blocker in Heart Attack Trial (BHAT), a randomized, double-blind, placebo-controlled trial that enrolled patients from 1978 to 1980 and followed participants for vital status to April 1982. SETTING: Thirty-one clinical centers in the United States and Canada. PATIENTS: Eligible patients included 3297 men and women 30 to 69 years of age who survived 1 year after trial entry. INTERVENTION: Patients were classified as being on treatment at 12 months after randomization if they were receiving beta-blocker therapy at the 12-month visit and off treatment if they were not receiving beta-blocker therapy at that time. OUTCOME MEASURE: Vital status evaluated at 720 days of follow-up. RESULTS: A total of 2914 patients (88%) was classified as being at lower risk (strata I and II). For these patients, survival curves by treatment at 12 months were virtually indistinguishable. Among the 383 patients categorized as being at high risk on the basis of recurrent ischemic events, arrhythmias, congestive heart failure, or severe comorbidity during the first 12 months, the use of beta-blockers was associated with a 43% proportional decline in the subsequent risk for death (P = 0.01 by log-rank test). CONCLUSIONS: In patients who survived to 1 year with low- to moderate-risk clinical courses, beta-blocker therapy did not have long-term beneficial effect. In contrast, among patients who had a high-risk clinical course during the first year, beta-blockers significantly reduced mortality in the follow-up period.

Predicting outcome from hypoxic-ischemic coma.

Outcome from coma caused by cerebral hypoxia-ischemia (eg, cardiac arrest) was compared with serial neurological findings in 210 patients. Thirteen percent of patients regained independent function at some point during the first postarrest year. Computer application of new multivariate techniques to the prospectively observed findings generated easily utilized rules that classified patients by likely outcome. At the time of initial examination, 52 patients (one fourth of the total population) had absent pupillary light reflexes, and none of these patients ever regained independent daily function. By contrast, the initial presence of pupillary light reflexes, the development of spontaneous eye movements that were roving conjugate or better, and the findings of extensor, flexor, or withdrawal responses to pain identified a smaller group of 27 patients, 11 (41%) of whom regained independence in their daily lives. By 24 hours after onset, 93 poor-outcome patients were identified by motor responses that were absent, extensor, or flexor and by spontaneous eye movements that were neither orienting nor roving conjugate; only one regained independent function. This contrasts with recovery in 19 (63%) of 30 patients who at that time showed improvement in their eye-opening responses and obeyed commands or had motor responses that were withdrawal or localizing. Similarly simple rules distinguished between good- and poor-prognosis patients on postarrest days 3, 7, and 14.