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A comparison of neonatal mortality risk prediction models in very low birth weight infants.

BACKGROUND: Risk-adjusted severity of illness is frequently used in clinical research and quality assessments. Although there are multiple methods designed for neonates, they have been infrequently compared and some have not been assessed in large samples of very low birth weight (VLBW; <1500 g) infants. OBJECTIVES: To test and compare published neonatal mortality prediction models, including Clinical Risk Index for Babies (CRIB), Score for Neonatal Acute Physiology (SNAP), SNAP-Perinatal Extension (SNAP-PE), Neonatal Therapeutic Interventions Scoring System, the National Institute of Child Health and Human Development (NICHD) network model, and other individual admission factors such as birth weight, low Apgar score (<7 at 5 minutes), and small for gestational age status in a cohort of VLBW infants from the Washington, DC area. METHODS: Data were collected on 476 VLBW infants admitted to 8 neonatal intensive care units between October 1994 and February 1997. The calibration (closeness of total observed deaths to the predicted total) of models with published coefficients (SNAP-PE, CRIB, and NICHD) was assessed using the standardized mortality ratio. Discrimination was quantified as the area under the curve (AUC) for the receiver operating characteristic curves. Calibrated models were derived for the current database using logistic regression techniques. Goodness-of-fit of predicted to observed probabilities of death was assessed with the Hosmer-Lemeshow goodness-of-fit test. RESULTS: The calibration of published algorithms applied to our data was poor. The standardized mortality ratios for the NICHD, CRIB, and SNAP-PE models were.65,.56, and.82, respectively. Discrimination of all the models was excellent (range:.863-.930). Surprisingly, birth weight performed much better than in previous analyses, with an AUC of.869. The best models using both 12- and 24-hour postadmission data, significantly outperformed the best model based on birth data only but were not significantly different from each other. The variables in the best model were birth weight, birth weight squared, low 5-minute Apgar score, and SNAP (AUC =.930). CONCLUSION: Published models for severity of illness overpredicted hospital mortality in this set of VLBW infants, indicating a need for frequent recalibration. Discrimination for these severity of illness scores remains excellent. Birth variables should be reevaluated as a method to control for severity of illness in predicting mortality.

Female↗

Identification of a novel signature for prognostic stratification and integrative analyses in lung adenocarcinoma.

BACKGROUND: Recently, research has revealed that the Golgi apparatus is involved in the development process of cancer; however, the specific effect of Golgi apparatus-related genes (GAGs) in lung adenocarcinoma (LUAD) remains unclear. This study aims to construct a more concise and practical risk model in LUAD using GAG. METHODS: The gene expression profiles of patients with LUAD were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, and GAGs were downloaded from the Gene Set Enrichment Analysis (GSEA) database. Univariate Cox and least absolute shrinkage and selection operator (LASSO) analyses were performed to identify the prognostic GAG signature. Kaplan-Meier and receiver operating characteristic (ROC) curves were plotted to validate the predictive effect of the prognostic signatures. The correlation between the risk model and the immune landscape was examined using CIBERSORT and TIDE analyses. Also, the genes in the signature were assessed by single-cell RNA sequencing (scRNA-seq). RESULTS: A prognostic signature comprising 5 GAG genes (GNPNAT1, RGS20, CAV3, NTSR1, and FURIN) was established after LASSO and multi-Cox analyses. Both the Kaplan-Meier analysis and the ROC curves supported the strong predictive utility of the risk model. Specifically, the former yielded significant stratification in all three validation datasets (P=1.2001e-05, P=0.006, and P=0.04), while the latter provided further evidence of its predictive precision through the area under the curve. In addition, we found that the low-risk group responded better to immunotherapy than the high-risk group (P<0.0001). scRNA-seq analysis revealed the distribution patterns of the 5 GAG genes in cells. Finally, we assessed the situation of tumor mutation burden (TMB) and performed functional analysis based on the risk model of GAGs. CONCLUSIONS: The risk model based on GAGs can effectively stratify the prognosis of patients and predict immunotherapy responses in LUAD.

Golgi apparatus↗

Bayesian-logit model for risk assessment in coronary artery bypass grafting.

Predictive models for the assessment of operative risk using patient risk factors have gained popularity in the medical community as an important tool for the adjustment of surgical outcome. The Bayes' theorem model is among the various models used to predict mortality among patients undergoing coronary artery bypass grafting procedures. Comparative studies of the various classic statistical techniques, such as logistic regression, cluster of variables followed by a logistic regression, a subjectively created sickness score, classification trees model, and the Bayes' theorem model, have shown that the Bayes' model is among those with the highest predictive power. In this study, the Bayes' theorem model is reformulated as a logistic equation and extended to include qualitative and quantitative risk factors. We show that the resulting model, the Bayesian-logit model, is a mixture of logistic regression and linear discriminant analysis. This new model can be created easily without complex computer programs. Using 12,712 patients undergoing coronary artery bypass grafting procedures at the Department of Veterans Affairs Continuous Improvement in Cardiac Surgery Study between April 1987 and March 1990, the predictive power of the Bayesian-logit model is compared with the Bayes' theorem model, logistic regression, and discriminant analysis. The ability of the Bayesian-logit model to discriminate between operative deaths and operative survivors is comparable with that of logistic regression and discriminant analysis.

Age Factors↗

Prognostic-factors-based risk-stratification model for invasive urothelial carcinoma of the urinary bladder in Taiwan.

Objectives. To develop a prognostic-factors-based predictive model for invasive urothelial carcinoma of the urinary bladder derived from statistical comparison of clinical characteristics.Methods. The medical records for patients with invasive urinary bladder urothelial carcinoma were reviewed. Clinical data for age, sex, serum lactate dehydrogenase, creatinine, albumin, alkaline phosphatase, alanine aminotransferase, total bilirubin and hemoglobin levels, white blood cell and platelet counts, positive urine cytology, Eastern Cooperative Oncology Group performance status score, tumor size, histologic grading, T stage, presence of lymph node metastases, squamous differentiation, hydronephrosis, prostatic involvement, Charlson comorbidity index, surgical procedures, and adjuvant chemotherapy status were recorded. Univariate and multivariate analyses were performed to test independent factors for prediction of survival and disease recurrence.Results. After univariate and multivariate analyses, six independent prognostic factors were found: T stage, grading, prostatic involvement, Eastern Cooperative Oncology Group performance status score, and pretreatment serum creatinine and albumin levels. A scoring system was developed on the basis the relative risk associated with the proposed prognostic factors and patients were stratified into three groups according to their scores, with statistically significant prognostic differences revealed for each of the between-group comparisons. Independent factors affecting recurrence-free survival and best predicted disease recurrence were pretreatment serum creatinine, T stage, and surgical procedure.Conclusions. This prognostic-factors-based risk-stratification model for invasive urothelial carcinoma of the urinary bladder may help clinicians predict outcome and select the most appropriate therapeutic modalities. The incidence of recurrent disease is significantly higher for patients with poor renal function before treatment or advanced T stage and those undergoing transurethral tumor resection instead of radical cystectomy.

Aged↗

Treatment choices by seriously ill patients: the Health Stock Risk Adjustment model.

Anecdotal evidence suggests that patients who have life-threatening conditions often choose to undergo high-cost, high-risk treatments for them. This kind of risk-seeking behavior seems irrational because most patients are risk-averse. The Health Stock Risk Adjustment (HSRA) model seeks to explain this phenomenon. The model is based on the concept of relative health stock--the ratio of patients' expected quality-adjusted life years (QALYs) after a diagnosis to their expected QALYs before the diagnosis. The model predicts risk-averse patients will behave in a risk-seeking manner as their relative health stocks deteriorate. The HSRA model can help physicians better understand why some seriously ill patients seek high-risk treatments while others elect to forgo treatment. State legislatures and insurers are attempting to appropriately design insurance benefits for patients with life-threatening conditions. The HSRA model can help predict which patients will most likely take advantage of these benefits.

Aged↗

Risk score model for fatal intracranial hemorrhage in acute leukemia.

To build a risk score (RS) model of fatal intracranial hemorrhage (FICH) in patients with acute leukemia, we retrospectively assessed risk factors in 792 patients newly diagnosed with acute leukemia, 41 of whom had analyzable FICH. We found that female gender (relative risk (RR) = 5.234, P<0.001), acute promyelocytic leukemia (RR = 4.057, P = 0.003), leukocytosis (RR = 3.301, P = 0.004), thrombocytopenia (RR = 3.283, P = 0.005) and prolonged prothrombin time (RR = 3.291, P = 0.016) were significantly associated with occurrence of FICH in multivariate analysis. To calculate RS for FICH, one point was assigned for each risk factor, making the RS between 0 and 5. The RS model segregated patients into three prognostic groups: a low-risk group (LRG) for RS of 0 or 1; an intermediate-risk group (IRG) for RS of 2 or 3; and a high-risk group (HRG) for RS of 4 or 5. Expectation of FICH was well correlated with risk groups (all P-values < 0.001). Overall survival was significantly shorter in the HRG compared with the LRG. The RS model we constructed to predict the occurrence of FICH will be verified through prospective studies.

Acute Disease↗

Risk stratification in paediatric open-heart surgery.

OBJECTIVE: The aims of this study were to identify independent risk factors for mortality following paediatric open-heart surgery and to develop risk models for use in clinical audit based on identified risk factors. The study also tests the validity of the recently proposed Risk Adjustment in Congenital Heart Surgery (RACHS-1) method of risk stratification as applied to open-heart operations. METHODS: A multiple logistic regression analysis was performed on all patients less than 18 years of age undergoing open-heart surgery at a single institution over a 3-year period. Preoperative and operative variables included for analysis were age at operation, weight, sex, American Society of Anaesthesiology (ASA) grade, RACHS-1 risk category, preoperative haemoglobin, bypass time, temperature, cross-clamp time, circulatory arrest time, blood transfusion on bypass and surgeon. The outcome measure was in-hospital death. RESULTS: 1085 consecutive open-heart cases were identified. There were 51 in-hospital deaths (4.7%). Variables identified as being independently significant risk factors for in-hospital death were age (P = 0.0002), RACHS-1 risk category (P < 0.0001), and bypass time. Based on these three variables, a risk model was constructed to predict mortality. The area under the receiver-operating-characteristic (ROC) curve for this model was 0.86. A second model was constructed ignoring bypass time. In this model, the significance of the 'preoperative' risk factors was (P = 0.0003) for age and (P < 0.0001), for RACHS-1 risk category. The area under the ROC curve was 0.81 for the second model. CONCLUSIONS: This study identifies age at operation, RACHS-1 risk category and bypass time as highly significant risk factors for mortality after paediatric open-heart surgery. It validates the RACHS-1 risk stratification method as applied to the subset of open-heart surgery, whilst accepting the limitations of such a system. The risk models formulated permit risk prediction and allow for analysis of surgical results. Such risk-adjustment is important when assessing performance and comparing outcomes amongst individuals or institutions.

Adolescent↗

The Health Belief Model and HIV risk behaviours: a causal model analysis among Anglos, African-Americans and Mexican-Americans.

A causal model of the Health Belief Model (HBM) is empirically evaluated which emphasizes possible indirect paths linking distal demographic and seriousness/susceptibility variables to HIV risk behaviours among Anglo, African-American, and Mexican-American adults. A specific focus of the paper is upon alcohol-related expectancies (anticipation of disinhibitory effects of alcohol upon sexual behavior) as a 'barrier' to preventive behaviours. Ethnic comparisons stem both from the paucity of available research on the HBM in minority populations and from recent questions regarding the applicability of rational models such as the HBM among minority groups. Analyses of data from a community sample of 1390 adults indicate relatively consistent direct effects of barriers for males and benefits for females upon HIV risk behaviors. The analyses suggest distinct paths operative among males and females. The susceptibility-barriers-risk behaviours path among males may suggest that alcohol-related expectancies (barriers in this model) may be more strongly related to risk behaviours among males than minority females.

Adult↗

A risk analysis model of the relationship between beverage consumption from school vending machines and risk of adolescent overweight.

Risk analysis is a widely used tool to understand problems in food safety policy, but it is seldom applied to nutrition policy. We propose that risk analysis be applied more often to inform debates on nutrition policy, and we conduct a risk assessment of the relationship of regular carbonated soft drink (RCSD) consumption in schools and body mass index (BMI) as a case study. Data for RCSD consumption in schools were drawn from three data sets: the Continuing Survey of Food Intake by Individuals 1994-1996, 1998 (CSFII), the National Health and Nutrition Examination Survey 1999-2000 (NHANES), and the National Family Opinion (NFO) WorldGroup Share of Intake Panel (SIP) study. We used the largest relationship between RCSD and BMI that was published by prospective observational studies to characterize the maximum plausible relationship in our study. Consumption of RCSD in schools was low in all three data sets, ranging from 15 g/day in NFO-SIP to 60 g/day in NHANES. There was no relationship between RCSD consumption from all sources and BMI in either the CSFII or the NHANES data. The risk assessment showed no impact on BMI by removing RCSD consumption in school. These findings suggest that focusing adolescent overweight prevention programs on RCSD in schools will not have a significant impact on BMI.

Adolescent↗

Use of risk projection models for the comparison of mortality from radiation-induced breast cancer in various populations.

The aim of our study is to compare lifetime risk estimates for radiation-induced breast cancer between various populations. Some epidemiological studies, mainly on Japanese A-bomb survivors, but also on North American populations irradiated for medical reasons, provide risk coefficients for excess mortality from breast cancer after exposure to ionizing radiation. For this comparative study, these risk coefficients have been transferred into the Japanese, American, and French populations, using demographic data, risk projection models, and assuming an individual acute exposure. The lifetime risk estimates are similar in the three populations when the additive projection model is used because of the similarity of the life tables of the three countries. However, using the multiplicative model, large differences appear due to the discrepancies in the baseline breast cancer rates between the Japanese and Occidental populations. It is for this reason that transfer of risk coefficients fitted on the Japanese population data must be considered with caution when applied to an Occidental population. Lifetime risk estimates for a given population, the French population for example, are largely dependent on the risk coefficients considered from various epidemiological studies. Nevertheless, for each source of data, they are higher with the multiplicative model than with the additive one. Moreover, it should be noted that data from medical irradiation lead to higher risk estimates when using the additive model, whereas studies of the A-bomb survivors lead to higher risk estimates with the multiplicative model. This comparative study points out the variations of the lifetime risk calculations according to the baseline breast cancer mortality rates of the three populations and with the use of different mathematical projection models.

Adult↗

[Chronic metabolic syndrome: a predictive model of risk of macrovascular events?].

OBJECTIVES: To establish a predictive model of the risk of macrovascular complications in patients with Chronic Metabolic Syndrome by means of multiple logistic regression analysis. To identify Chronic Metabolic Syndrome as an independent health problem, given its frequency and importance in the genesis of macrovascular complications. DESIGN: A descriptive observational study. SETTING: An urban Health District in Malaga. PATIENTS: 47 patients with Chronic Metabolic Syndrome were chosen by systematic randomised sampling. MEASUREMENTS AND MAIN RESULTS: The best predictive model of macrovascular events was established as the one which included high values of the Waist-Hip index, blood pressure, Fibrinogenaemia and basal Glucaemia, and low values of HDL cholesterol. CONCLUSIONS: 1. A model to predict macrovascular events in patients with Chronic Metabolic Syndrome included high values of the Waist-Hip index, blood pressure, Fibrinogenaemia and basal Glucaemia, and low values of HDL cholesterol. 2. We believe that this association should be considered an independent health problem on the list of problems, with the name Syndrome X or Chronic Metabolic Syndrome.

Adult↗

Evaluation of a risk-adjustment model for pressure ulcer development using the Minimum Data Set.

OBJECTIVE: To validate a previously derived risk-adjustment model for pressure ulcer development in a separate sample of nursing home residents and to determine the extent to which use of this model affects judgments of nursing home performance. DESIGN: Retrospective observational study using Minimum Data Set (MDS) data from 1998. SETTING: A large, for-profit, nursing home chain. PARTICIPANTS: Twenty-nine thousand and forty observations were made on 13,457 nursing home residents who were without a pressure ulcer on an index assessment. MEASUREMENTS: We used logistic regression in our validation sample to calculate new coefficients for the 17 previously identified predictors of pressure ulcer development. Coefficients from this new sample were compared with those previously derived. Expected rates of pressure ulcer development were determined for 108 nursing homes. Unadjusted and risk-adjusted rates of pressure ulcer development from these homes were also calculated and outlier identification using these two approaches was compared. RESULTS: Predictors of pressure ulcer development in the derivation sample generally showed similar effects in the validation sample. The model c-statistic was also unchanged at 0.73, but it was not calibrated as well in the validation sample. On applying the model to the nursing homes, expected rates of ulcer development ranged from 1.1% to 3.2% (P <.001). The observed rates ranged from 0% to 12.1% (P <.001). There were 12 outliers using unadjusted rates and 15 using adjusted performance. Ten nursing homes were identified as outliers using both approaches. CONCLUSIONS: Our MDS risk-adjustment model for pressure ulcer development performed well in this new sample. Nursing homes differ significantly in their expected rates of pressure ulcer development. Outlier identification also differs depending on whether unadjusted or risk-adjusted performance is evaluated.

Aged↗

[Risk predictive model for damage caused by the spittlebug Aeneolamiapostica (Walker) Fennah (Hemiptera: Cercopidae)].

This paper evaluated the risk that Aenolamia postica (Walker) Fennah populations reach the economic threshold in sugar cane fields in Veracruz, México. A risk deductive model was constructed to include the sequence of events leading to damaging populations, considered the top event or critical failure in the crop. Model events were identified and quantified, and model was validated on field conditions. The model components and their state values were identified as: temperature e" 28 degrees C, precipitation e" 45% during June and July, soil clay content e" 40%, infested adjoining fields, deficient weed control, wind dominance, crop phenology and variety, deficient chemical and biological control, and irrigation. Sensitivity analysis showed that the most important events triggering high densities of A. postica were high temperatures and precipitation, previous field infestation, nymph and weed presence. Event probability estimates were combined using Boolean algebra to compute the minimum, mean and maximum probabilities for the top event, yielding values of 0.417, 0.563, y 0.734 respectively. Model was tested in field, by selecting sugar cane fields having the model properties and compared to fields without these features. Fields were sampled in both conditions during 2004 year and high-risk fields had significantly (F = 13, 4, gl = 1, 18, P = 0,0018) higher densities (2.4 adults m(-1)) than low-risk plots (0.4 adults m(-1)) thus agreeing with the model forecast.

Animals↗

The Physical Performance Test as a predictor of frequent fallers: a prospective community-based cohort study.

OBJECTIVE: To construct a risk model in order to identify elderly individuals at risk of frequent falling. DESIGN: Prospective community-based cohort study over 12 months. SETTING: Baseline measures were performed at a local community centre. SUBJECTS: Two hundred and sixty-three community-dwelling elderly people (mean age 72 years). MEASUREMENTS: A variety of variables were evaluated, including medical, psychological, sensory, physical and postural control measurements. Fall incidence was monitored retrospectively and during one-year follow-up. RESULTS: Logistic regression analysis showed that polypharmacia was the most prominent medical fall predictor with an odds ratio (OR) of 1.29 (P= 0.005), poor visual acuity the best sensory predictor (OR = 0.84; P= 0.009) and general fear of falling the most crucial psychological predictor (OR = 3.25; P< 0.001). Increased postural sway in near-tandem stance with eyes open was selected as the best balance predictor for falls (OR = 5.60; P= 0.010), followed by delayed anteroposterior movement velocity during rhythmic weight shifts (OR = 0.42; P= 0.004). The best physical predictor was a low score on the Physical Performance Test (OR =4.16; P< 0.001), followed by decreased maximal handgrip strength (OR = 0.87; P< 0.001) and increased timed chair-stands (OR = 1.13; P= 0.003). Step-by-step regression analysis revealed a risk model for the prediction of future falls, as a combination of the Physical Performance Test and maximal handgrip strength. CONCLUSION: This study confirms the multicausality of falls, since medical, psychological, sensory, postural control as well as physical variables provides a predictive value. The composed fall risk model was mainly physically oriented.

Accidental Falls↗

Modeling stroke risk after coronary artery bypass and combined coronary artery bypass and carotid endarterectomy.

BACKGROUND AND PURPOSE: The goals of this study were to compare the ability of statewide and institutional models of stroke risk after coronary artery bypass (CAB) to predict institution-specific results and to examine the potential additive stroke risk of combined CAB and carotid endarterectomy (CEA) with these predictive models. METHODS: An institution-specific model of stroke risk after CAB was developed from 1975 consecutive patients who underwent nonemergent CAB from 1994 to 1999 in whom severe carotid stenosis was excluded by preoperative duplex screening. Variables recorded in the New York State Cardiac Surgery Program database were analyzed. This model (model I) was compared with a published model (model II) derived from analysis of the same variables using New York statewide data from 1995. Predicted and observed stroke risks were compared. These formulas were applied to 154 consecutive combined CAB/CEA patients operated on between 1994 and 1999 to determine the predicted stroke risk from CAB alone and thereby deduce the maximal added risk imputed to CEA. RESULTS: Risk factors common to both models included age, peripheral vascular disease, cardiopulmonary bypass time, and calcified aorta. Additional risk factors in model I also included left ventricular hypertrophy and hypertension. Risk factors exclusive to model II included diabetes, renal failure, smoking, and prior cerebrovascular disease. Our observed stroke rate for isolated CAB was 1.7% compared with a rate predicted with model II (statewide data) of 1.56%. The observed stroke rate for combined CEA/CAB was 3.9%. When the Stony Brook model (model I) based on patients without carotid stenosis was used, the predicted stroke rate was 2.8%. When the statewide model (model II), which included some patients with extracranial vascular disease, was used, the predicted stroke rate was 3.4%. The differences between observed and predicted stroke rates were not statistically significant. CONCLUSIONS: Estimation of stroke risk after CAB was similar whether statewide data or institution-specific data were used. The statewide model was applicable to institution-specific data collected over several years. Common risk factors included age, aortic calcification, and peripheral vascular disease. The observed differences in the predicted stroke rates between models I and II may be due to the fact that carotid stenosis was specifically excluded by duplex ultrasound from the patient population used to develop model I. Modeling stroke risk after CAB is possible. When these models were applied to patients undergoing combined CAB/CEA, no additional stroke risk could be ascribed to the addition of CEA. Such models may be used to identify groups at increased risk for stroke after both CAB and combined CAB/CEA. The ultimate place for CEA in patients undergoing CAB will be defined by prospective randomized trials.

Adult↗

Co-morbidity data in outcomes research: are clinical data derived from administrative databases a reliable alternative to chart review?

Evaluation of co-morbidity data is essential in health outcomes research. Co-morbidity data derived from administrative databases has been criticized for lacking the accuracy required for clinical research. We compared co-morbidity data derived from a Canadian provincial hospitalization database with chart review in 817 adults treated with a percutaneous coronary intervention at a single tertiary care hospital between 1994 and 1995. While the administrative database tended to under-estimate the prevalence of some co-morbid conditions, the agreement between chart review and administrative data was good to very good for most conditions. Asymptomatic conditions were noted to have lower levels of agreement. Multivariate risk models for all-cause mortality constructed from both data sources were almost identical, suggesting minimal misclassification. The results indicate that clinical data abstracted from most Canadian hospitalization databases can provide reliable information regarding baseline co-morbid conditions believed to influence survival in a population undergoing percutaneous coronary interventions.

Adult↗

Cancer mortality and morbidity among workers at the Sellafield plant of British Nuclear Fuels.

The mortality of all 14,282 workers employed at the Sellafield plant of British Nuclear Fuels between 1947 and 1975 was studied up to the end of 1988 and cancer incidence was examined from 1971 to 1986. This updates a previous report on mortality only up to the end of 1983. Ninety-nine per cent of the workers were traced satisfactorily. Cancer mortality was 4% less than that of England and Wales [standardised mortality ratio (SMR) = 96; 95% confidence interval (CI) = 90,103] and the same as that of Cumbria (SMR = 100: Cl = 94,107). Cancer incidence was 10% less than that of England and Wales [standardised registration ratio (SRR) = 90; Cl = 83.97] and 18% less than that of Northern Region (SRR = 82; Cl = 75.88). Cancer mortality rates were significantly in excess of national rates for cancers of the pleura (nine observed, 2.6 expected; P = 0.001), thyroid (six observed, 1.8 expected; P = 0.01) and ill defined and secondary sites (53 observed, 39.2 expected; P = 0.02). There were significant deficits of cancers of the liver and gall bladder, larynx and lung. Among radiation workers there were significant positive correlations between accumulated radiation dose and mortality from cancers of ill-defined and secondary sites (10 year lag: P = 0.01) and for leukaemia (2 year lag: P = 0.009), but not for cancers of the pleura and thyroid cancer. Previous findings of such associations with multiple myeloma and bladder cancer were less strong. There was a significant excess of incident cases of cancer of the oesophagus (P = 0.01), but this was not associated with accumulated radiation dose. For cancers other than leukaemia, the dose-response risk estimates were below those of the adult atomic bomb survivors, but the 90% confidence interval included risks of zero and of 2-3 times higher. For leukaemia (12 deaths, excluding CLL), under an excess relative risk model, the risk estimate derived for the Sellafield workers was about four times higher than that for the adult atomic bomb survivors with a confidence interval ranging from a half to nearly 20 times that of the atomic bomb survivors. Overall, however, there was no excess of leukaemia among the workers compared with national rates.

Death Certificates↗

Immune systems, geographic information systems (GIS), environment and health impacts.

Exposure to dioxins, polychlorinated biphenyls (PCBs), and polycyclic aromatic hydrocarbons (PAHs) has been related to alterations in cellular and humoral immune responses in both adaptive and innate immune systems of most animal species. These compounds share a common signaling mechanism to exert their effects on cells of the immune system, which includes the aryl-hydrocarbon receptor (AhR) and the AhR nuclear translocator (ARN). Recently, the interference of AhR-ARNT with the nuclear factor (NF)-kappaB signaling pathway has been proposed as a critical event in the adverse effects on the immune system. Studies on the effects of these AhR-ARNT-related toxicants on the immune system of higher and lower phylum animals and knowledge of intracellular mechanisms of toxicity may contribute to development of biomarkers of ecotoxicant exposure and effects. Biomarkers of this kind allow sampling over extended geographic areas, in several sentinel species, including wildlife animals, and facilitate the building of risk models and risk maps of environmentally induced diseases. On the basis of location, biomarker sampled data obtained through evaluation of ecotoxicant exposure and effects on the immune system in sentinel species can be further integrated and analyzed together with other sources of environmental geographic information, or human population health data, by means of geographic information systems (GIS). The spatial analysis capability of GIS can help to evaluate the complex relationships of overlaid information and to identify areas with high risk indices or "hot spots." This integrative approach can be useful in studies contributing to support environmental and health-related policies and regulations.

Animals↗