General resource for ionospheric transient investigations (GRITI): An open-source code developed in support of the Dinsmore et al. (2021) results.

The analysis techniques and the corresponding software suite GRITI (General Resource for Ionospheric Transient Investigations) are described. GRITI was used to develop the Dinsmore et al. [2] results, which found a novel classification of traveling ionospheric disturbances (TIDs) called semi-coherent ionospheric pulsing structures (SCIPS). The any-geographic range (local-to-global), any-azimuth angle keogram algorithm used to analyze SCIPS in that work is detailed. The keogram algorithm in GRITI is applied to detrended vTEC (vertical Total Electron Content) data, called delta-vTEC herein, in Dinsmore et al. [2] and the follow-on paper Dinsmore et al. [3], but is also applicable to any other two-dimensional dataset that evolves through time. GRITI's delta-vTEC processing algorithm is also described in detail, which is used to provide the delta-vTEC data for Dinsmore et al. [3]. •We detail a keogram algorithm for analysis of delta-vTEC data in Dinsmore et al. [2] and the follow-on paper Dinsmore et al. [3].•We detail a delta-vTEC processing algorithm that converts vTEC data to delta-vTEC through detrending that is used to provide the delta-vTEC data used in Dinsmore et al. [3].•GRITI is an open-source Python 3 analysis codebase that encompasses the delta-vTEC processing and keogram algorithms. GRITI has additional support for other data sources and is designed for flexibility in adding new data sources and analysis methods. GRITI is available for download at: https://github.com/dinsmoro/GRITI.

Influenza as a trigger for cardiovascular disease: An investigation of serotype, subtype and geographic location.

BACKGROUND: Seasonal peaks of influenza and cardiovascular disease tend to coincide. Many excess deaths may be triggered by influenza, and the severity of this effect may vary with the virulence of the circulating influenza strain and host susceptibility. We aimed to explore the association between hospital admissions for influenza and/or pneumonia (IP) and acute myocardial infarction (AMI) or ischaemic heart disease (IHD) in Queensland, Australia, taking into account temporal and spatial variation of influenza virus type and subtype in 2007, 2008 and 2009. METHODS: This ecological study at Statistical Subdivision level (SSD, n=38) used linked patient-level data. For each study year, Standardized Morbidity Ratios (SMRs) were calculated for hospital admissions with diagnoses of IP, AMI and IHD. We investigated the associations between IP and AMI or IHD using spatial autoregressive modelling, adjusting for socio-demographic factors. RESULTS: Spatial autocorrelation was detected in SMRs, possibly reflecting underlying social and behavioural risk factors, but consistent with infectious disease spread. SMRs for IP were consistently predictive of SMRs for AMI and IHD when adjusted for socioeconomic status, population density and per cent Indigenous population (coefficient: 0.707, 95% confidence interval (CI): 0.318 - 1.096; 0.553, 0.222 - 0.884; 0.598, 0.307 - 0.888 and 1.017, 0.711 - 1.323; 0.650, 0.342 - 0.958; 1.031, 0.827 - 1.236) in 2007, 2008 and 2009, respectively. CONCLUSIONS: This ecological study provides further evidence that severe respiratory infections may trigger the onset of cardiovascular events, implicating the influenza virus as a contributing factor.

Outbreak of Notozothecium bethae (Monogenea: Dactylogyridae) in Myleus schomburgkii (Actinopterygii: Characiformes) cultured in the Peruvian Amazon.

The presence of Notozothecium bethae was investigated in 76 black band myleus (Myleus schomburgkii [Actinopterygii: Charasiformes]) born and kept in captivity in two semi-intensive breeding cages in the northern region of Peru. Among the 76 cultivated specimens of M. schomburgkii examined in the present study, 100 % had monogenean on the gill and the parasites were identified as Notozothecium bethae. During the survey no bacteria was isolated, and no protozoan or other metazoan parasites were found. The prevalence of N. bethae remained constant throughout the present study. Mean intensity of N. bethae in the months of April and May was exceptionally high in both facilities. The massive infection of N. bethae on the gills of M. schomburgkii was associated with mortality. This is the first report of N. bethae in M. schomburgkii born in captivity and cultured in the Amazon region. The mortality due the presence of this parasite emphasise the need for disease control strategies of cultured M. schomburgkii.

The influence of changing host immunity on 1918-19 pandemic dynamics.

The sociological and biological factors which gave rise to the three pandemic waves of Spanish influenza in England during 1918-19 are still poorly understood. Symptom reporting data available for a limited set of locations in England indicates that reinfection in multiple waves occurred, suggesting a role for loss of infection-acquired immunity. Here we explore the role that changes in host immunity, driven by a combination of within-host factors and viral evolution, may play in explaining weekly mortality data and wave-by-wave symptomatic attack-rates available for a subset of English cities. Our results indicate that changes in the phenotype of the pandemic virus are likely required to explain the closely spaced waves of infection, but distinguishing between the detailed contributions of viral evolution and changing adaptive immune responses to transmission rates is difficult given the dearth of sero-epidemiological and virological data available even for more contemporary pandemics. We find that a dynamical model in which pre-pandemic protection in older "influenza-experienced" cohorts is lost rapidly prior to the second wave provides the best fit to the mortality and symptom reporting data. Best fitting parameter estimates for such a model indicate that post-infection protection lasted of order months, while other statistical analyses indicate that population-age was inversely correlated with overall mortality during the herald wave. Our results suggest that severe secondary waves of pandemic influenza may be triggered by viral escape from pre-pandemic immunity, and thus that understanding the role of heterosubtypic or cross-protective immune responses to pandemic influenza may be key to controlling the severity of future influenza pandemics.

Model answers or trivial pursuits? The role of mathematical models in influenza pandemic preparedness planning.

The panzootic of H5N1 influenza in birds has raised concerns that the virus will mutate to spread more readily in people, leading to a human pandemic. Mathematical models have been used to interpret past pandemics and outbreaks, and to thus model possible future pandemic scenarios and interventions. We review historical influenza outbreak and transmission data, and discuss the way in which modellers have used such sources to inform model structure and assumptions. We suggest that urban attack rates in the 1918-1919 pandemic were constrained by prior immunity, that R(0) for influenza is higher than often assumed, and that control of any future pandemic could be difficult in the absence of significant prior immunity. In future, modelling assumptions, parameter estimates and conclusions should be tested against as many relevant data sets as possible. To this end, we encourage researchers to access FluWeb, an on-line influenza database of historical pandemics and outbreaks.

Deep vein thrombosis and air travel: record linkage study.

OBJECTIVE: To investigate the time relations between long haul air travel and venous thromboembolism. DESIGN: Record linkage study using the case crossover approach. SETTING: Western Australia. PARTICIPANTS: 5408 patients admitted to hospital with venous thromboembolism and matched with data for arrivals of international flights during 1981-99. RESULTS: The risk of venous thromboembolism is increased for only two weeks after a long haul flight; 46 Australian citizens and 200 non-Australian citizens had an episode of venous thromboembolism during this so called hazard period. The relative risk during this period for Australian citizens was 4.17 (95% confidence interval, 2.94 to 5.40), with 76% of cases (n = 35) attributable to the preceding flight. A "healthy traveller" effect was observed, particularly for Australian citizens. CONCLUSIONS: The annual risk of venous thromboembolism is increased by 12% if one long haul flight is taken yearly. The average risk of death from flight related venous thromboembolism is small compared with that from motor vehicle crashes and injuries at work. The individual risk of death from flight related venous thromboembolism for people with certain pre-existing medical conditions is, however, likely to be greater than the average risk of 1 per 2 million for passengers arriving from a flight. Airlines and health authorities should continue to advise passengers on how to minimise risk.

Modelling of endemic carriage of Haemophilus influenzae in Aboriginal infants in Northern Australia.

Aboriginal infants and children in rural communities in Northern Australia have high rates of nasopharyngeal carriage of nonencapsulated Haemophilus influenzae (NCHi), with positive swab rates of 76%. In this population, the acquisition of NCHi from soon after birth is associated with the onset of otitis media and with muco-purulent nasal discharge, while the long-term persistence of NCHi carriage is associated with the acquisition and turnover of large numbers of antigenically diverse strains. Mathematical models have been fitted to data on the acquisition and loss of encapsulated strains of H. influenzae and 43 different strains of NCHi in 10 children followed from early infancy for up to 2 years. Subject to plausible assumptions, the preferred model estimated the mean time to acquisition of a H. influenzae strain to be 7 days after first becoming exposed after birth. For an infant already carrying H. influenzae, each additional strain was acquired after a mean waiting period of 45 days. On average, 1.50 different strains of H. influenzae were detected in four colonies routinely typed from each positive swab, but it was estimated that another 2.55 strains were 'hidden' behind these more frequent strains. With an average of 4.05 strains per carrier, it was estimated that each strain was carried for an average of 137 days, although detected on only 37% of occasions. Thus we have developed mathematical models that provide estimates for duration of colonisation, time to colonisation, and number of colonising strains in a population in which H. influenzae is highly endemic, characterised by sequential and concurrent carriage of multiple strains in each infant.

The natural history of renal disease in Australian Aborigines. Part 1. Changes in albuminuria and glomerular filtration rate over time.

BACKGROUND: The purpose of this study was to describe changes over time in albuminuria and glomerular filtration rate (GFR) in a cohort of Australian Aborigines from a community with high rates of renal disease and renal failure. METHODS: Participants were 486 adult community members (20+ years at first exam) who were screened for renal disease and related factors on at least two occasions (mean 2.7 occasions), at least a year apart, between 1990 and 1997. Renal function was assessed by the albumin:creatinine ratio (ACR; g/mol) on a random urine specimen and by the GFR estimated from the Cockcroft-Gault formula. Evolution over time was expressed as the average annual changes in these parameters. RESULTS: On baseline examination, 70% of participants had albuminuria (ACR 1.1+ g/mol) There was a significant net increase in ACR and a fall in GFR in the cohort over time. Among individuals, however, changes were strongly correlated with ACR levels at baseline. There was no loss of GFR in persons with normal renal parameters at baseline and a rapid loss of GFR in those with substantial levels of albuminuria at baseline. Other factors significantly correlated with progression of ACR included age, baseline body mass index and systolic blood pressure, the presence of diabetes (or levels of fasting glucose), and elevated levels of serum gamma glutamyl transferase. Factors significantly associated with loss of GFR included body mass index, diabetes, systolic and diastolic blood pressures, microscopic hematuria, and marginally high cholesterol levels. CONCLUSION: Albuminuria progresses and GFR is lost over time in individuals in this community, at rates that are strongly dependent on levels of pre-existing albuminuria. Much loss of GFR and all renal failure should be avoided by preventing the development of albuminuria and minimizing its progression. This depends on improving the weight, blood pressure, and metabolic profile of the entire community and reducing infections. Modification of the course in people with established disease depends on vigorous control of blood pressure and the metabolic profile and the specific use of angiotensin-converting enzyme inhibitors.

The natural history of renal disease in Australian Aborigines. Part 2. Albuminuria predicts natural death and renal failure.

BACKGROUND: The purpose of this study was to describe the relationship of albuminuria and glomerular filtration rate (GFR) with natural death and renal failure in an Australian Aboriginal community with high rates of renal disease. METHODS: Study subjects were 825 adults (18+ years, mean 33.6 years) or 88% of adults in a remote community who participated in a health screening program offered between 1990 and 1997. The urinary albumin:creatinine ratio (ACR; g/mol) was used as the renal disease marker. Participants were followed for 1.0 to 9.8 years (mean 5.8 years) until renal failure, death, the start of systematic antihypertensive/renal-protective treatment or June 30, 2000. RESULTS: Sixty-five people reached a terminal end point of renal failure or natural death. Sixteen people developed terminal renal failure, all of whom had an ACR of 34+ at baseline exam. There were 49 other natural deaths, which were also strongly correlated with increasing ACR and decreasing GFR over a wide range. This was observed in people without diabetes and in people with normal and elevated blood pressures. It applied to deaths associated with cardiovascular disease and to deaths without an assigned primary or underlying cardiovascular or renal cause. With adjustment for age, the association with death was more robust with ACR than GFR. When compared with people with an ACR <3.4, the hazard ratio (HR; 95% CI) for nonrenal natural death of persons with an ACR 3.4 to 33 was 3.0 (1.1 to 8.4), with an ACR 34 to 99, it was 5.4 (1.8 to 15.9), and with an ACR 100+, it was 6.5 (2.0 to 21). Regression equations predicted that each tenfold increase in the ACR was associated with a 3.7-fold increase in all-cause natural death: a> 400-fold increase in renal deaths, a 4-fold increase in cardiovascular deaths, and a 2.2-fold increase in nonrenal noncardiovascular deaths. Eighty-four percent of all-cause natural death was associated with pathologic albuminuria. CONCLUSION: All renal failure develops out of a background of persistent albuminuria in this population. More important, albuminuria and, inversely, GFR are powerful markers of risk for nonrenal natural death, including, but not restricted to, cardiovascular deaths. Most of the risk for premature death can be assessed by a simple urine test, and interventions that prevent development and progression of albuminuria and loss of GFR should not only prevent renal insufficiency, but powerfully reduce mortality from natural causes as well.

Cumulative incidence of rheumatic fever in an endemic region: a guide to the susceptibility of the population?

Aboriginal Australians in northern Australia are subject to endemic infection with group A streptococci, with correspondingly high rates of acute rheumatic fever and rheumatic heart disease. For 12 communities with good ascertainment, the estimated lifetime cumulative incidence of acute rheumatic fever was approximately 5.7%, whereas over the whole population, with less adequate ascertainment, the cumulative incidence was only 2.7%. The corresponding prevalences of established rheumatic heart disease were substantially less than the cumulative incidences of acute rheumatic fever, at least in part because of poor ascertainment. The cumulative incidence of acute rheumatic fever estimates the proportion of susceptible individuals in endemically exposed populations. Our figures of 2.7-5.7% susceptible are consistent with others in the literature. Such comparisons suggest that the major part of the variation in rheumatic fever incidence between populations is due to differences in streptococcal exposure and treatment, rather than to any difference in (genetic) susceptibility.

A targeted, single-dose azithromycin strategy for trachoma.

OBJECTIVE: To evaluate the impact of treating children with acute trachoma and their contacts with oral azithromycin. DESIGN: Open, uncontrolled, prospective evaluation of a community-based treatment strategy. SETTING: Central Australian semi-desert Aboriginal community (1995-1996). PARTICIPANTS: 216 school- and pre-schoolchildren aged 6 months and up to 15 years. INTERVENTION: All children with acute trachoma and their contacts (co-resident siblings aged between 6 months and 15 years) received single-dose oral azithromycin suspension (20 mg/kg, to a maximum of 1000 mg). MAIN OUTCOME MEASURE: Prevalence of acute trachoma (World Health Organization trachoma diagnostic criteria). RESULTS: Trachoma prevalence at baseline was 42% (71/169) and 55% (18/33) for schoolchildren and pre-schoolchildren, respectively: 103 schoolchildren and 21 pre-schoolchildren, comprising 77 with follicular trachoma and their 47 contacts, were treated with azithromycin over an 8-week period. Acute trachoma prevalence in schoolchildren fell to 22% at 6-8 months (P < 0.0001) and was 31% at 12 months (P < 0.05 compared with baseline). Pre-schoolchildren were followed up for 6 months after treatment, and their trachoma prevalence fell from 55% to 25% (P < 0.05). Further treatment was given to children with trachoma at 12 months, and the point prevalence of trachoma for schoolchildren at 24 months was 34%. CONCLUSIONS: In contrast to mass-treatment strategies, significant reductions in trachoma prevalence at 6 months were achieved by screening 35% of community members (216) and treating 20% (124). The subsequent prevalence increases support the need for more comprehensive treatment programs, including health promotion and efforts to improve living conditions.

Genetically distinct dog-derived and human-derived Sarcoptes scabiei in scabies-endemic communities in northern Australia.

Overcrowding is a significant factor contributing to endemic infection with Sarcoptes scabiei in human and animal populations. However, since scabies mites from different host species are indistinguishable morphologically, it is unclear whether people can be infected from scabies-infested animals. Molecular fingerprinting was done using three S. scabiei-specific single locus hypervariable microsatellite markers, with a combined total of 70 known alleles. Multilocus analysis of 712 scabies mites from human and dog hosts in Ohio, Panama and Aboriginal communities in northern Australia now shows that genotypes of dog-derived and human-derived scabies cluster by host species rather than by geographic location. Because of the apparent genetic separation between human scabies and dog scabies, control programs for human scabies in endemic areas do not require resources directed against zoonotic infection from dogs.

Crusted scabies: A molecular analysis of Sarcoptes scabiei variety hominis populations from patients with repeated infestations.

Crusted scabies is a severe debilitating disease due to hyperinfestation with the ectoparasite Sarcoptes scabiei. Treatment protocols include oral ivermectin and topical scabicides. After single-dose ivermectin, there may be early recrudescence, whereas after 3 doses at 14-day intervals, there is an apparent cure. However, such patients often present again after 6-12 months. To clarify the biology of recurrence, we studied genetic markers in sequential populations of S. scabiei mites from treated patients with multiple episodes of crusted scabies. Individual mites were genotyped at hypervariable microsatellite loci by a fluorescence-based polymerase chain reaction. Results indicated that sequential populations of mites were genetically more similar to each other than to mites from other patients. Although the majority of recurrent scabies is probably due to reinfestation from inadequately treated contacts, there was evidence that in very severe crusted scabies, treatment with even 3 doses of ivermectin 14 days apart may be inadequate and relapse may occur.

A new dimension to the Barker hypothesis: low birthweight and susceptibility to renal disease.

BACKGROUND: There is an epidemic of renal failure among Aborigines in the Australia's Northern Territory. The incidence is more than 1000 per million, and is doubling every three to four years. We evaluated the relationship of birthweight to renal disease in adults in one high-risk community. METHODS: We screened more than 80% of people in the community for renal disease, using the urine albumin/creatinine ratio (ACR, g/mol) as the marker, and reviewed records for birthweights. RESULTS: Birthweights were available with increasing frequency for people born after 1956. In 317 adults aged 20 to 38 years at screening, the mean birthweight (SD) was 2.712+/-0.4 kg, and 35% had been low birthweight (LBW, less than 2.5 kg). Birthweight was positively correlated with body mass index (BMI), blood pressure, and diabetes rates, but was inversely correlated with ACR. The odds ratio for overt albuminuria in LBW persons compared with those of higher birthweights was 2.82 (CI, 1.26 to 6.31) after adjusting for other factors, and LBW contributed to an estimated 27% (CI, 3 to 45%) of the population-based prevalence of overt albuminuria. Multivariate models suggest that increasing BMI and blood pressure and decreasing birthweight act in concert to amplify the increases in ACR that accompany increasing age. CONCLUSIONS: LBW contributes to renal disease in this high-risk population. The association might be mediated through impaired nephrogenesis caused by intrauterine malnutrition. The renal disease epidemic in Aborigines may partly be the legacy of greatly improved survival of LBW babies over the last four decades. Disease rates should eventually plateau as birthweights continue to improve, if postnatal risk factors can also be contained.

Proteinuria is associated with persistence of antibody to streptococcal M protein in Aboriginal Australians.

Aboriginal communities in Northern Australia with high rates of group A streptococcal (GAS) skin infection in childhood also have high rates of renal failure in adult life. In a cross-sectional study of one such high risk community, albuminuria was used as a marker of renal disease. The prevalence of albuminuria increased from 0/52 in subjects aged 10-19 years to 10/29 (32.9%) in those aged 50 or more (P < 0.001). Antibodies to streptococcal M protein, markers of past GAS infection, were present in 48/52 (92%) at ages 10-19 years, 16/32 (50%) at ages 30-39, and 20/29 (69%) in those aged 50 or more. After allowing for the age-dependencies of albuminuria and of M protein antibodies (P < 0.001) albuminuria was significantly associated with M protein antibodies (P < 0.01). Thus, 72% of adults aged 30 or more with M protein antibodies also had albuminuria, compared with only 21% of those who were seronegative. More detailed modelling suggested that although most Aboriginal people in this community developed M protein antibodies following GAS infection in childhood, the development of proteinuria was associated with the persistence of such seropositivity into adult life. The models predicted that proteinuria developed at a mean age of 30 years in seropositive persons, at 45 years in seronegative persons who were overweight, and at 62 years in seronegative persons of normal weight. We demonstrated a clear association between evidence of childhood GAS infection and individual risk of proteinuria in adult life. This study provided a strong rationale for prevention of renal disease through the more effective control of GAS skin infections in childhood and through the prevention of obesity in adult life.

The multidimensional nature of renal disease: rates and associations of albuminuria in an Australian Aboriginal community.

BACKGROUND: An epidemic of end-stage renal disease (ESRD) is accompanying the rising rates of hypertension, type 2 diabetes and cardiovascular disease among Aborigines in the Northern Territory of Australia. Incidence rates are now 21 times those of nonAboriginal Australians and are doubling every four years. We describe the rates and associations of renal disease in one remote community, which has a current ESRD incidence of 2700 per million, and cardiovascular mortality among the highest in Australia. METHODS: Between 1992 and 1995 a community-wide screening program was conducted, in which the urinary albumin/creatinine ratio (ACR) was used as the chief renal disease marker. More than 90% of the population ages five and older participated. RESULTS: Albuminuria was evident in early childhood and increased dramatically with age; 26% of adults had microalbuminuria and 24% had overt albuminuria. All renal failure developed out of a background of overt albuminuria. ACR was significantly correlated with the presence of scabies at screening, with a history of poststreptococcal glomerulonephritis, which is epidemic and endemic in the community, with increasing body wt, blood pressure, glucose, insulin and lipid levels, and with evidence of heavy drinking. ACR was also significantly and inversely correlated with birth weight. As a result of its association with deteriorating hemodynamic and metabolic profiles, increasing ACR was also correlated with increasing cardiovascular risk score. Direct observations showed, and multivariate models predicted, progressive amplification of ACR when multiple risk factors were present simultaneously. Albuminuria also clustered in families. CONCLUSION: Renal disease in this population is multifactorial, with risk factors related to whole-of-life nutrition, metabolic and hemodynamic profiles, infections, health behaviors, and possibly a family predisposition. Its relationship to low birth weight, and its associations with deteriorating metabolic and hemodynamic profiles, suggest that renal disease is, in part, a component of Syndrome X, which explains the simultaneous increase in metabolic, cardiovascular and renal disease in Aboriginal people. The family clustering might have both environmental and genetic causes, and is under further investigation. Most of the identified risk factors arise out of poverty, disadvantage and accelerated lifestyle change, and the current epidemic can be explained by the confluence of many risk factors in the last few decades. The introduction of effective and sustained programs to address social, economic and educational inequities in all Aboriginal communities, and of screening and renal- and cardiovascular-protective treatment programs for those already afflicted are matters of great urgency.

Low genetic diversity of Haemophilus influenzae type b compared to nonencapsulated H. influenzae in a population in which H. influenzae is highly endemic.

Immunization with Haemophilus influenzae type b (Hib) conjugate polysaccharide vaccines has dramatically reduced Hib disease worldwide. As in other populations, nasopharyngeal carriage of Hib declined markedly in Aboriginal infants following vaccination, although carriage has not been entirely eliminated. In this study, we describe the genetic characteristics and the carriage dynamics of longitudinal isolates of Hib, characterized by using several typing methods. In addition, carriage rates of nonencapsulated H. influenzae (NCHi) are high, and concurrent colonization with Hib and NCHi is common; we also observed NCHi isolates which were genetically similar to Hib. There is a continuing need to promote Hib immunization and monitor H. influenzae carriage in populations in which the organism is highly endemic, not least because of the possibility of genetic exchange between Hib and NCHi strains in such populations.

Exposure to dioxin and nonneoplastic mortality in the expanded IARC international cohort study of phenoxy herbicide and chlorophenol production workers and sprayers.

The authors studied noncancer mortality among phenoxyacid herbicide and chlorophenol production workers and sprayers included in an international study comprising 36 cohorts from 12 countries followed from 1939 to 1992. Exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin or higher chlorinated dioxins (TCDD/HCD) was discerned from job records and company questionnaires with validation by biologic and environmental measures. Standard mortality ratio analyses suggested a moderate healthy worker effect for all circulatory diseases, especially ischemic heart disease, among both those exposed and those not exposed to TCDD/HCD. In Poisson regression analyses, exposure to TCDD/HCD was not associated with increased mortality from cerebrovascular disease. However, an increased risk for circulatory disease, especially ischemic heart disease (rate ratio [RR] 1.67, 95% confidence interval [Cl] 1.23-2.26) and possibly diabetes (RR 2.25, 95% Cl 0.53-9.50), was present among TCDD/HCD-exposed workers. Risks tended to be higher 10 to 19 years after first exposure and for those exposed for a duration of 10 to 19 years. Mortality from suicide was comparable to that for the general population for all workers exposed to herbicides or chlorophenols and was associated with short latency and duration of exposure. More refined investigations of the ischemic heart disease and TCDD/HCD exposure association are warranted.