Individual Exposure Histories Research Articles

Medial Olivocochlear Reflex Strength in Ears With Low-to-Moderate Annual Noise Exposure.

Studies in lower mammals demonstrate enhancement of the medial olivocochlear reflex (MOCR) following noise exposure. A similar effect may occur in humans, and there is some evidence of an individual's acoustic history affecting the MOCR. The current work evaluates the relationship between an individual's annual noise exposure history and their MOCR strength. Given the potential role of the MOCR as a biological hearing protector, it is important to identify factors associated with MOCR strength. Data were collected from 98 normal-hearing young adults. Annual noise exposure history was estimated using the Noise Exposure Questionnaire. MOCR strength was assayed using click-evoked otoacoustic emissions (CEOAEs) measured with and without noise presented to the contralateral ear. MOCR metrics included the MOCR-induced otoacoustic emission (OAE) magnitude shift and phase shift. A CEOAE signal-to-noise ratio (SNR) of at least 12 dB was required for estimation of the MOCR metrics. Linear regression was applied to evaluate the relationship between MOCR metrics and annual noise exposure. Annual noise exposure was not a statistically significant predictor of the MOCR-induced CEOAE magnitude shift. However, annual noise exposure was a statistically significant predictor of the MOCR-induced CEOAE phase shift-the MOCR-induced phase shift decreased with increasing noise exposure. Additionally, annual noise exposure was a statistically significant predictor of OAE level. Findings contrast with recent work that suggests MOCR strength increases with annual noise exposure. Compared with previous work, data for this study were collected using more stringent SNR criteria, which is expected to increase the precision of the MOCR metrics. Additionally, data were collected for a larger subject population with a wider range of noise exposures. Whether findings generalize to other exposure durations and levels is unknown and requires future study.

Eliminating Potential Effects of Other Infections during Selection of Nonhuman Primates for COVID-19 Research.

The study of nonhuman primates (NHP) can provide significant insights into our understanding numerous infectious agents. The etiological agent of COVID-19, SARS-CoV-2 virus, first emerged in 2019 and has so far been responsible for the deaths of over 4 million people globally. In the frenzied search to understand its pathogenesis and immunology and to find measures for prevention and control of this pandemic disease, NHP, particularly macaques, are the preferred model because they manifest similar clinical signs and immunologic features as humans. However, possible latent, subclinical, and opportunistic infections not previously detected in animals participating in a study may obscure experimental results and confound data interpretations in testing treatments and vaccine studies for COVID-19. Certain pathophysiologic changes that occur with SARS-CoV-2 virus infection are similar to those of simian pathogens. The current review discusses numerous coinfections of COVID-19 with other diseases and describes possible outcomes and mechanisms in COVID-19 studies of NHP that have coinfections. Due to the urgency triggered by the pandemic, screening that is more rigorous than usual is necessary to limit background noise and maximize the reliability of data from NHP COVID-19 studies. Screening for influenza virus, selected respiratory bacteria, and regional endemic pathogens such as vector-borne agents, together with the animal's individual exposure history, should be the main considerations in selecting a NHP for a COVID-19 study. In addition, because NHP are susceptible to the SARS-CoV-2 virus, management and surveillance measures should be established to prevent transmission to healthy animals from infected colony animals and husbandry staff. This review presents compiled data on the use of NHP in COVID-19 studies, emphasizing the need to create the most reliable NHP model for those studies by extensive screening for other pathogens.

Differential symptomology of possible and confirmed Ebola virus disease infection in the Democratic Republic of the Congo: a retrospective cohort study

In its earliest phases, Ebola virus disease's rapid-onset, high fever, and gastrointestinal symptoms are largely indistinguishable from other infectious illnesses. We aimed to characterise the clinical indicators associated with Ebola virus disease to improve outbreak response. In this retrospective analysis, we assessed routinely collected data from individuals with possible Ebola virus disease attending 30 Ebola health facilities in two provinces of the Democratic Republic of the Congo between Aug 1, 2018, and Aug 28, 2019. We used logistic regression analysis to model the probability of Ebola infection across 34 clinical variables and four types of possible Ebola virus disease exposures: contact with an individual known to have Ebola virus disease, attendance at any funeral, health facility consultation, or consultation with an informal health practitioner. Data for 24 666 individuals were included. If a patient presented to care in the early symptomatic phase (ie, days 0-2), Ebola virus disease positivity was most associated with previous exposure to an individual with Ebola virus disease (odds ratio [OR] 11·9, 95% CI 9·1-15·8), funeral attendance (2·1, 1·6-2·7), or health facility consultations (2·1, 1·6-2·8), rather than clinical parameters. If presentation occurred on day 3 or later (after symptom onset), bleeding at an injection site (OR 33·9, 95% CI 12·7-101·3), bleeding gums (7·5, 3·7-15·4), conjunctivitis (2·4, 1·7-3·4), asthenia (1·9, 1·5-2·3), sore throat (1·8, 1·3-2·4), dysphagia (1·8, 1·4-2·3), and diarrhoea (1·6, 1·3-1·9) were additional strong predictors of Ebola virus disease. Some Ebola virus disease-specific signs were less prevalent among vaccinated individuals who were positive for Ebola virus disease when compared with the unvaccinated, such as dysphagia (-47%, p=0·0024), haematemesis (-90%, p=0·0131), and bleeding gums (-100%, p=0·0035). Establishing the exact time an individual first had symptoms is essential to assessing their infection risk. An individual's exposure history remains of paramount importance, especially in the early phase. Ebola virus disease vaccination reduces symptom severity and should also be considered when assessing the likelihood of infection. These findings about symptomatology should be translated into practice during triage and should inform testing and quarantine procedures. Médecins Sans Frontières and its research affiliate Epicentre.

Exposing the role of metals in neurological disorders: a focus on manganese.

Metals are ubiquitous chemical entities involved in a myriad of biological processes. Despite their integral role in sustaining life, overexposure can lead to deleterious neurological outcomes posing a public health concern. Excess exposure to metals has been associated with aberrant neurodevelopmental and neurodegenerative diseases and prominently contributes to environmental risk for neurological disorders. Here, we use manganese (Mn) to exemplify the gap in our understanding of the mechanisms behind acute metal toxicity and their relationship to chronic toxicity and disease. This challenge frustrates understanding of how individual exposure histories translate into preventing and treating brain diseases from childhood through old age. We discuss ways to enhance the predictive value of preclinical models and define mechanisms of chronic, persistent, and latent neurotoxicity.

Is annual vaccination best? A modelling study of influenza vaccination strategies in children

IntroductionAnnual vaccination of children against influenza is a key component of vaccination programs in many countries. However, past infection and vaccination may affect an individual’s susceptibility to infection. Little research has evaluated whether annual vaccination is the best strategy. Using the United Kingdom as our motivating example, we developed a framework to assess the impact of different childhood vaccination strategies, specifically annual and biennial (every other year), on attack rate and expected number of infections. Methods and findingsWe present a multi-annual, individual-based, stochastic, force of infection model that accounts for individual exposure histories and disease/vaccine dynamics influencing susceptibility. We simulate birth cohorts that experience yearly influenza epidemics and follow them until age 18 to determine attack rates and the number of infections during childhood. We perform simulations under baseline conditions, with an assumed vaccination coverage of 44%, to compare annual vaccination to no and biennial vaccination. We relax our baseline assumptions to explore how our model assumptions impact vaccination program performance.At baseline, we observed less than half the number of infections between the ages 2 and 10 under annual vaccination in children who had been vaccinated at least half the time compared to no vaccination. When averaged over all ages 0–18, the number of infections under annual vaccination was 2.07 (2.06, 2.08) compared to 2.63 (2.62, 2.64) under no vaccination, and 2.38 (2.37, 2.40) under biennial vaccination. When we introduced a penalty for repeated exposures, we observed a decrease in the difference in infections between the vaccination strategies. Specifically, the difference in childhood infections under biennial compared to annual vaccination decreased from 0.31 to 0.04 as exposure penalty increased. ConclusionOur results indicate that while annual vaccination averts more childhood infections than biennial vaccination, this difference is small. Our work confirms the value of annual vaccination in children, even with modest vaccination coverage, but also shows that similar benefits of vaccination may be obtained by implementing a biennial vaccination program. Author summaryMany countries include annual vaccination of children against influenza in their vaccination programs. In the United Kingdom (UK), annual vaccination of children aged of 2 to 10 against influenza is recommended. However, little research has evaluated whether annual vaccination is the best strategy, while accounting for how past infection and vaccination may affect an individual’s susceptibility to infection in the current influenza season. Prior work has suggested that there may be a negative effect of repeated vaccination. In this work we developed a stochastic, individual-based model to assess the impact of repeated vaccination strategies on childhood infections. Specifically, we first compare annual vaccination to no vaccination and then annual vaccination to biennial (every other year) vaccination. We use the UK as our motivating example. We found that an annual vaccination strategy resulted in the fewest childhood infections, followed by biennial vaccination. The difference in number of childhood infections between the different vaccination strategies decreased when we introduced a penalty for repeated exposures. Our work confirms the value of annual vaccination in children, but also shows that similar benefits of vaccination can be obtained by implementing a biennial vaccination program, particularly when there is a negative effect of repeated vaccinations.

Variability in transmission risk of SARS-CoV-2 in close contact settings: A contact tracing study in Shandong Province, China

BackgroundUnderstanding the relative transmissibility of SARS-CoV-2 virus across different contact settings and the possibility of superspreading events is important for prioritizing disease control. Such assessment requires proper consideration of individual level exposure history, which is made possible by contact tracing. MethodsThe case-ascertained study in Shandong, China including 97 laboratory-confirmed index cases and 3158 close contacts. All close contacts were quarantined after their last exposure of index cases. Contacts were tested for COVID-19 regularly by PCR to identify both symptomatic and asymptomatic infections. We developed a Bayesian transmission model to the contact tracing data to account for different duration of exposure among individuals to transmission risk in different settings, and the heterogeneity of infectivity of cases. ResultsWe estimate secondary attack rates (SAR) to be 39% (95% credible interval (CrI): 20–64%) in households, 30% (95% CrI: 11–67%) in healthcare facilities, 23% (95% CrI: 7–51%) at workplaces, and 4% (95% CrI: 1–17%) during air travel. Models allowing heterogeneity of infectivity of cases provided a better goodness-of-fit. We estimated that 64% (95% CrI: 55–72%) of cases did not generate secondary transmissions, and 20% (95% CrI: 15–26%) cases explained 80% of secondary transmissions. ConclusionsHousehold, healthcare facilities and workplaces are efficient setting for transmission. Timely identification of potential superspreaders in most transmissible settings remains crucial for containing the pandemic.

VirScan: High-throughput Profiling of Antiviral Antibody Epitopes.

Profiling the specificities of antibodies can reveal a wealth of information about humoral immune responses and the antigens they target. Here, we present a protocol for VirScan, an application of the phage immunoprecipitation sequencing (PhIP-Seq) method for profiling the specificities of human antiviral antibodies. Accompanying this protocol is a video of the experimental procedure. VirScan and, more generally, PhIP-Seq are techniques that enable high-throughput antibody profiling by combining high-throughput DNA oligo synthesis and bacteriophage display with next-generation sequencing. In the VirScan method, human sera samples are screened against a library of peptides spanning the entire human viral proteome. Bound phage are immunoprecipitated and sequenced, identifying the viral peptides recognized by the antibodies. VirScan Is a powerful tool for uncovering individual viral exposure histories, mapping the epitope landscape of viruses of interest, and studying fundamental mechanisms of viral immunity. Graphical abstract.

Time-varying associations between an exposure history and a subsequent health outcome: a landmark approach to identify critical windows

BackgroundLong-term behavioral and health risk factors constitute a primary focus of research on the etiology of chronic diseases. Yet, identifying critical time-windows during which risk factors have the strongest impact on disease risk is challenging. To assess the trajectory of association of an exposure history with an outcome, the weighted cumulative exposure index (WCIE) has been proposed, with weights reflecting the relative importance of exposures at different times. However, WCIE is restricted to a complete observed error-free exposure whereas exposures are often measured with intermittent missingness and error. Moreover, it rarely explores exposure history that is very distant from the outcome as usually sought in life-course epidemiology.MethodsWe extend the WCIE methodology to (i) exposures that are intermittently measured with error, and (ii) contexts where the exposure time-window precedes the outcome time-window using a landmark approach. First, the individual exposure history up to the landmark time is estimated using a mixed model that handles missing data and error in exposure measurement, and the predicted complete error-free exposure history is derived. Then the WCIE methodology is applied to assess the trajectory of association between the predicted exposure history and the health outcome collected after the landmark time. In our context, the health outcome is a longitudinal marker analyzed using a mixed model.ResultsA simulation study first demonstrates the correct inference obtained with this approach. Then, applied to the Nurses’ Health Study (19,415 women) to investigate the association between body mass index history (collected from midlife) and subsequent cognitive decline (evaluated after age 70), the method identified two major critical windows of association: long before the first cognitive evaluation (roughly 24 to 12 years), higher levels of BMI were associated with poorer cognition. In contrast, adjusted for the whole history, higher levels of BMI became associated with better cognition in the last years prior to the first cognitive interview, thus reflecting reverse causation (changes in exposure due to underlying disease).ConclusionsThis approach, easy to implement, provides a flexible tool for studying complex dynamic relationships and identifying critical time windows while accounting for exposure measurement errors.

Potential impact of individual exposure histories to endemic human coronaviruses on age-dependent severity of COVID-19

BackgroundCross-reactivity to SARS-CoV-2 from exposure to endemic human coronaviruses (eHCoV) is gaining increasing attention as a possible driver of both protection against infection and COVID-19 severity. Here we explore the potential role of cross-reactivity induced by eHCoVs on age-specific COVID-19 severity in a mathematical model of eHCoV and SARS-CoV-2 transmission.MethodsWe use an individual-based model, calibrated to prior knowledge of eHCoV dynamics, to fully track individual histories of exposure to eHCoVs. We also model the emergent dynamics of SARS-CoV-2 and the risk of hospitalisation upon infection.ResultsWe hypothesise that primary exposure with any eHCoV confers temporary cross-protection against severe SARS-CoV-2 infection, while life-long re-exposure to the same eHCoV diminishes cross-protection, and increases the potential for disease severity. We show numerically that our proposed mechanism can explain age patterns of COVID-19 hospitalisation in EU/EEA countries and the UK. We further show that some of the observed variation in health care capacity and testing efforts is compatible with country-specific differences in hospitalisation rates under this model.ConclusionsThis study provides a “proof of possibility” for certain biological and epidemiological mechanisms that could potentially drive COVID-19-related variation across age groups. Our findings call for further research on the role of cross-reactivity to eHCoVs and highlight data interpretation challenges arising from health care capacity and SARS-CoV-2 testing.

Evaluation of potential gastrointestinal carcinogenicity associated with the ingestion of asbestos.

The inhalation of asbestos, depending on the fiber type and dose, may be associated with the development of mesothelioma and other asbestos-related diseases. However, little is known about the potential adverse effects associated with the ingestion of asbestos. Evidence of asbestos fibers released from asbestos-cement pipes used in water distribution systems has led to concerns of potentially contaminated drinking water. The purpose of this study is to determine whether ingestion of asbestos fibers may lead to cancerous effects on the gastrointestinal (GI) tract. Data from animal and human studies were analyzed using a weight-of-evidence approach to evaluate the potential risk of GI cancers associated with asbestos ingestion. Seventeen human and 23 animal studies were identified and evaluated in this study. Animal studies were conducted in multiple species with inconsistent dosing protocols. Overall, animal studies reported that the asbestos fibers, irrespective of fiber type and dose, failed to produce any definitive GI carcinogenic effect. The 17 identified human epidemiological studies reported the ingestion of asbestos-contaminated water with concentrations from 1 to 71,350 million fibers per liter (MFL). A majority of the epidemiology studies reported statistically significant increases in multiple GI-specific cancers. However, these findings are confounded due to several critical study limitations including flawed study design, small sample size, selection bias, lack of individual exposure history, lack of adequate latency, and the inability to account for confounders including occupational history, diet, and smoking history. Based on our weight-of-evidence assessment, there is insufficient evidence of causality between the ingestion of asbestos and an increased incidence of GI cancers.

T Cell Epitope Predictions.

Throughout the body, T cells monitor MHC-bound ligands expressed on the surface of essentially all cell types. MHC ligands that trigger a T cell immune response are referred to as T cell epitopes. Identifying such epitopes enables tracking, phenotyping, and stimulating T cells involved in immune responses in infectious disease, allergy, autoimmunity, transplantation, and cancer. The specific T cell epitopes recognized in an individual are determined by genetic factors such as the MHC molecules the individual expresses, in parallel to the individual's environmental exposure history. The complexity and importance of T cell epitope mapping have motivated the development of computational approaches that predict what T cell epitopes are likely to be recognized in a given individual or in a broader population. Such predictions guide experimental epitope mapping studies and enable computational analysis of the immunogenic potential of a given protein sequence region.

Examining Sublethal Effects of Anticoagulant Rodenticides on Haemosporidian Parasitemia and Body Condition in Migratory Red-Tailed Hawks

Anticoagulant rodenticides (ARs) are a source of mortality to nontarget wildlife, including raptors. Raptors that consume a large quantity of rodents, such as Red-tailed Hawks (Buteo jamaicensis), are especially at risk of secondary exposure due to bioaccumulation and biomagnification of ARs. However, few studies have focused on the sublethal effects of ARs and how they can lead to potentially lethal outcomes. We investigated the effects of ARs on both parasitemia and body condition in juvenile Red-tailed Hawks from the Marin Headlands—the site of a migratory bottleneck for raptors on the west coast of the United States—north of San Francisco, California. We investigated the presence of several ARs in the plasma of 116 Red-tailed Hawks. We used the ratio of heterophils to lymphocytes (H/L ratio), levels of haemosporidian parasitemia, and polychromatic erythrocytes in blood smears as indices of body condition. Based on studies of other carnivores, we predicted higher levels of parasitemia and increased H/L ratios in raptors with ARs in their blood serum, but we found no significant difference in parasitemia or H/L ratio between raptors with and raptors without ARs in their blood. In contrast, individuals exposed to ARs had increased levels of polychromasia, or immature red blood cells, possibly as a result of AR exposure, though levels of polychromasia were within the typical range. Because ARs in blood have a short half-life, we do not know each individual's exposure history, which may play a role in subsequent parasitemia. Future studies should focus on individuals with known exposure history or obtain a longer temporal resolution using liver samples.

Scalp photodamage in balding men: An observational study combining a novel clinical scoring method with estimation of individual sun exposure history and risk factors

Scalp photodamage in balding men: An observational study combining a novel clinical scoring method with estimation of individual sun exposure history and risk factors

Genetic and nongenetic factors that may predispose individuals to allergic drug reactions.

Defining predisposition to allergic drug reactions has largely focussed on HLA associations, but other genetic and nongenetic factors are also likely to be involved. Polymorphic genetic variants in cytokine genes, including IL-10, and co-signalling pathways, including CTLA4, have been associated with allergic drug reactions, but the effect size is lower than with HLA alleles and most associations have not been replicated. Although TCR specificity seems to be important for CBZ-induced SJS/TEN in South East Asian patients, a distinct repertoire may not play a role in reactions to other drugs. New mass spectrometric techniques allowing for the identification of naturally eluted peptides from drug-exposed HLA alleles will allow for the antigenic source of T-cell activation to be defined and may shed light on the influence of disease. Indeed, preliminary data highlight the propensity of drug-responsive T cells to cross-react with T cells primed to viral antigens. Furthermore, the environment can epigenetically influence regulatory gene expression, suggesting that an individual's family exposure history may alter immune thresholds and tip the balance toward activation. It is likely that predisposition to allergic drug reactions is multifaceted in most cases. This will require the study of large numbers of patients to detect genetic factors that have a lower effect size than HLA alleles. This should be accompanied by detailed clinical phenotyping of patients and the assessment of the immunological phenotype with respect to the presence and type of drug antigen-responsive T cells.

Ecological analysis of associations between groundwater quality and hypertension and cardiovascular disease in rural Saskatchewan, Canada using Bayesian hierarchical models and administrative health data

Associations between groundwater quality and the prevalence of hypertension and ischemic heart disease were investigated in rural areas of the Canadian province of Saskatchewan. The partially ecological study was analyzed using Bayesian hierarchical models to account for spatial variability in risk. Exposure measures and health outcomes were estimated based on previously collected water quality surveillance data from public water supplies and private wells and administrative health data. Water quality exposures for each study region were estimated by applying geostatistical techniques to arsenic concentrations and principal component (PC) scores. The PC scores summarized groups of parameters measuring either health standards or aesthetic objectives described by the province. Generalized linear mixed models with a log link assessed associations between water quality and observed count of health outcomes relative to the expected value. The Bayesian models contained uncorrelated and spatially correlated random effects for each geographic region. Effect estimates were controlled for sex and age by stratification of case and expected case counts, for smoking by inclusion of sex- and age-specific prevalence of chronic obstructive pulmonary disease as a surrogate covariate, and for education and income by use of census data.There was no evidence for associations between groundwater arsenic concentrations in public or private water supplies and increased risk of hypertension or cardiovascular disease. An increase in the second aesthetic objectives PC score from public supplies was associated with a protective effect against ischemic heart disease. This PC value summarized hardness and magnesium Similarly, an increase in the second aesthetic objectives PC in private supplies was associated with decreased prevalence of hypertension.The results of this study are consistent with others demonstrating a relationship between elevated hardness and magnesium concentrations in drinking water and reduced risk of hypertension and cardiovascular disease. Further investigation is warranted with individual exposure history, particularly with respect to the potential beneficial effect of hard water on the prevalence of hypertension and cardiovascular disease.

Epidemiological population-based cohort study on mortality and hospitalization in the area near the waste incinerator plant of San Zeno, Arezzo (Tuscany Region, Central Italy)

to evaluate whether exposure to an urban waste incinerator plant operating in Arezzo (Tuscany Region, Central Italy) since the 2000 is associated with mortality and morbidity. a population-based cohort study of inhabitants living close to the incinerator in the period 2001-2010 was conducted. The individual exposure histories to the incinerator and other sources in the area were estimated using a dispersion model producing PM10 concentration maps for each source (ADMS-URBAN model). Hazard Ratios (HR) with 95% Confidence Interval (95%CI) adjusted for the other environmental exposures, age and socioeconomic status were estimated for the highest class of exposure using the lowest one as reference. Trends of HR were evaluated too. mortality and hospitalization causes with induction-latent period overlapping the incinerator activity period were analysed. morbidity analysis showed an increased risk for cardiovascular diseases (No. 732; HR: 1.18; 95%CI 1.06-1.32; trend of HR: 1.08, p=0.006) and a trend of HRs for urinary diseases (trend: 1.13; p=0.063). Mortality analysis showed a trend of HRs for general mortality in males (trend: 1.10; p=0.014), for cardiovascular diseases in males (trend: 1.15; p=0.036), for respiratory diseases in females (trend: 1.30; p=0.098), and an excess of acute respiratory diseases in females with the highest exposure (No. 11; HR=2.54; 95%CI 0.84-7.68). the cohort study allowed to characterise the environmental exposures considering the most relevant pollution sources and providing estimation of individual environmental exposures. Residual confounding due to the overlapping of concentration maps cannot be excluded and further investigations are needed. However, the increased risks for cardiovascular and respiratory diseases reinforce the limited epidemiological evidence on health effects of incinerators.

Abstract 2951: Evaluation of methylation biomarkers for colon cancer using normal tissues

Abstract We have identified DNA methylation biomarkers that discriminate patients with colon cancer from patients without colon cancer using array-based profiling methods. Most DNA-based biomarkers for colon cancer rely on the detection of cancer cell-specific or cancer cell-prevalent mutations or DNA methylation changes in small numbers of tumor cells or small amounts of tumor cell-free DNA that are present in stool or lavage samples. Our hypothesis is that an individual's cancer-predisposing exposure history is recorded in normal tissues as “field cancerization”-related DNA methylation changes and that these changes will be present in normal colon, as well as other normal tissues, including peripheral blood. Consistent with the notion of changes based on “individual exposure history”, the bulk of the candidate biomarkers identified are genes involved in carbohydrate and lipid metabolism, as expected from epidemiological associations between colon cancer and “western” diets. We have now validated that our candidate methylation biomarkers are effective at discriminating cancer patients from controls using normal colon tissue from an independent population, and irrespective of whether the patients have left-side or right-side cancers. We have also found that a significant fraction of our candidate biomarkers also discriminate cancer patients from controls, using peripheral blood DNA analyzed by bisulfite pyrosequencing. Citation Format: Carmen Sapienza, May M. Truongcao, Jayashri Ghosh. Evaluation of methylation biomarkers for colon cancer using normal tissues. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2951. doi:10.1158/1538-7445.AM2015-2951

Constructing Individual Exposure Histories: Extending Record Linkage Techniques to Integrate Exposures during Windows of Susceptibility

Constructing Individual Exposure Histories: Extending Record Linkage Techniques to Integrate Exposures during Windows of SusceptibilityAbstract Number:2493 David Nelson*, Michael Layefsky, Julie von Behren, Susan Hurley, Peggy Reynolds David Nelson* Cancer Prevention Institute of California, United States, E-mail Address: [email protected] Search for more papers by this author , Michael Layefsky Cancer Prevention Institute of California, United States, E-mail Address: [email protected] Search for more papers by this author , Julie von Behren Cancer Prevention Institute of California, United States, E-mail Address: [email protected] Search for more papers by this author , Susan Hurley Cancer Prevention Institute of California, United States, E-mail Address: [email protected] Search for more papers by this author , and Peggy Reynolds Cancer Prevention Institute of California, United States, E-mail Address: [email protected] Search for more papers by this author AbstractThe timing of environmental exposures may influence risk of breast cancer. An important ‘window of susceptibility’ is the period around pregnancy, especially for a first birth. In a study of breast cancer in a large cohort of women, the California Teachers Study (CTS), we developed a novel method to link CTS subjects to statewide birth files spanning over 30 years to determine maternal address at the times of birth. Classical approaches to linkage typically consider record pairs in isolation, creating a score for each compared pair. Blocking is used to reduce the number of pairwise comparisons by restricting comparisons to pairs that are likely to match, i.e., pairs in the same block. The resulting compared pairs are then ordered by linkage score and divided into sets of non-matches, possible matches, and sure matches. Finally, possible matches are reviewed manually. Our hypothesis was that much better linkages might be obtained by exploiting contextual knowledge to optimize pair matching over the entire block, especially as identifying information on birth files is limited. After blocking, we undertook a three-stage process on each block in a file of 215912 birth pairs. First, birth records were linked to each other into a collection of disjoint sets, i.e., births to a single mother. Second, the set of birth records for each mother was linked to the set of self-reported births, using constrained optimization. Third, the set of birth mother linkages from step 2 was combined in a second optimization step to produce a final set of linked births to the CTS subject. With this approach, over 50% of the reported CTS births, including 50% of first births, were reliably and uniquely matched with high stringency and no manual intervention. By exploiting prior contextual knowledge to optimally link groups of records concurrently, this approach dramatically enhanced automated linkage performance, even in the presence of common names and relatively limited information.

0380 Dynamics of Exposure and Disease Progression: The Use of Compartmental Models

ObjectivesChronic diseases are usually slow-developing condition and their risk may result from both long-term exposure and successive exposure increments, hence calling for models accounting for dynamics of exposure and disease...

A dynamic population model for estimating all-cause mortality due to lifetime exposure history

We developed a comprehensive, flexible dynamic model that estimates all-cause mortality for a hypothetical cohort. All model input is user-specified. In the base case, members of the cohort may be exposed to a high risk product as they age. The counterfactual scenario includes exposure to both a high risk and a lower risk product. The model sorts the population into age and exposure categories, and applies the appropriate mortality rates to each category. The model tracks individual exposure histories, and estimates, at the end of each modeled age category, the number of survivors in the two exposure scenarios (base case and counterfactual), and the difference between them. Markov Chain Monte Carlo techniques are used to estimate the variability of the results. Model output was compared against US and Swedish life tables using population-specific tobacco exposure transition probabilities derived from the literature, and it produced similar survival estimates.