Critical reviews of exposure assessment in carcinogenic hazard identification: the IARC Monographs experience.

OBJECTIVES: To summarise the rationale, workflow and recommendations for the conduct of exposure assessment critiques in key human studies evaluated for International Agency for Research on Cancer (IARC) Monographs on the Identification of Carcinogenic Hazards. METHODS: Approaches to evaluating exposure assessment quality in human cancer and mechanistic studies were reviewed according to the precepts outlined in the IARC Monographs Preamble, using two agents as case studies. Exposure assessment 'domains', that is, salient aspects of exposure assessment for the agent under evaluation, were selected for review across the key human studies. RESULTS: The case studies of night shift work (volume 124) and 1,1,1-trichloroethane (volume 130) used a common approach, tailored to the agents' specific exposure scenarios, to evaluate exposure assessment quality. Based on the experiences of IARC Working Groups to date, the implementation of exposure assessment critique requires the need for agent-specific knowledge, consideration of the validity of time-varying exposure metrics related to duration and intensity, and transparent, concise reviews that prioritise the most important strengths and limitations of exposure assessment methods used in human studies. CONCLUSIONS: Exposure assessment has not historically been a fully appreciated component for evaluating the quality of epidemiological studies in cancer hazard identification. Exposure assessment critique in key human cancer and mechanistic studies is now an integral part of IARC Monographs evaluations and its conduct will continue to evolve as new agents are evaluated. The approaches identified here should be considered as a potential framework by others when evaluating the exposure assessment component of epidemiological studies for systematic reviews.

COVID-19 vaccine intentions and attitudes in Black American emerging adults with asthma.

BACKGROUND: Emerging adults (aged 18-29) are less likely to receive the COVID-19 vaccine than any other adult age group. Black Americans are less likely than non-Hispanic white Americans to be fully vaccinated against COVID-19. This study explored factors which affect vaccine intention and attitudes in Black American emerging adults with asthma. METHODS: Participants were recruited from an NHLBI-funded clinical trial to improve asthma control. Fifty-nine Black American emerging adults completed a Qualtrics survey that assessed asthma control, intention to vaccinate, and factors which may affect the decision to vaccinate. Twenty-five participants also completed a semi-structured interview via Zoom. Bivariate correlations and descriptive statistics, including Chi Square analyses, were run using SPSS. Interview thematic analyses were conducted via QDA Miner. RESULTS: Of the 59 Black American emerging adults with asthma who completed surveys, 32.2% responded that they were highly unlikely to receive the COVID-19 vaccine, while 50.8% responded that they were highly likely to receive it. Increased asthma control was significantly correlated with a higher likelihood to discuss the COVID-19 vaccine with their healthcare provider (ρ = 0.339, α = 0.011). Concerns about immediate (ρ= -0.261, α = 0.050) and long-term (ρ= -0.280, α = 0.035) side effects were inversely correlated with intention to vaccinate. Only 17% of the participants who were unemployed stated that they were highly likely to receive the vaccines compared to 65% of the participants who were employed; however, interview participants who were unemployed stated not needing the vaccine because they were protecting themselves by social distancing. When deciding whether to receive the vaccine, safety, efficacy, and immediate side effects were the top three factors for 91%, 54%, and 49% of the participants, respectively. Beliefs about the vaccines' safety and efficacy, information gathering, personal factors, and societal factors emerged as important themes from the interviews. CONCLUSION: Only half of the surveyed Black American emerging adults with asthma were highly likely to receive the COVID-19 vaccine. Safety and efficacy were important for the majority of the participants, regardless of vaccine intention. Greater asthma control, but not access to asthma-related healthcare, was correlated with intention to discuss the vaccine with their healthcare provider.

The Relationship between Cognitive Factors and Noncognitive Factors, Including Grit, and NBCOT® Exam Performance.

This retrospective study examined the predictive ability of cognitive and non-cognitive factors, including grit, on first attempt pass rate on the National Board for Certification in Occupational Therapy exam. A convenience sample of 226 graduates from six cohorts of one occupational therapy program was used. Binary logistic regression revealed that grit was not a significant predictor. Program grade point average and verbal and quantitative Graduate Record Examination scores were independent predictors of passing on the first attempt. These findings can be used to identify at-risk students who could benefit from support to increase student success on the licensure exam.

Bladder cancer risk in relation to occupations held in a nationwide case-control study in Iran.

Globally, bladder cancer has been identified as one of the most frequent occupational cancers, but our understanding of occupational bladder cancer risk in Iran is less advanced. This study aimed to assess the risk of bladder cancer in relation to occupation in Iran. We used the IROPICAN case-control study data including 717 incident cases and 3477 controls. We assessed the risk of bladder cancer in relation to ever working in major groups of the International Standard Classification of Occupations (ISCO-68) while controlling for cigarette smoking, opium consumption. Logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CI). In men, decreased ORs for bladder cancer were observed in administrative and managerial workers (OR 0.4; CI: 0.2, 0.9), and clerks (OR 0.6; CI: 0.4, 0.9). Elevated ORs were observed in metal processors (OR 5.4; CI: 1.3, 23.4), and workers in occupations with likely exposure to aromatic amines (OR 2.2; CI: 1.2, 4.0). There was no evidence of interactions between working in aromatic amines-exposed occupations and tobacco smoking or opium use. Elevated risk of bladder cancer in men in metal processors and workers likely exposed to aromatic amines aligns with associations observed outside Iran. Other previously confirmed associations between high-risk occupations and bladder cancer were not observed, possibly due to small numbers or lack of details on exposure. Future epidemiological studies in Iran would benefit from the development of exposure assessment tools such as job exposure matrices, generally applicable for retrospective exposure assessment in epidemiological studies.

Anxiety, depression and global distress among African American young adults with uncontrolled asthma.

BACKGROUND: Anxiety and depression are mental health disorders that are often comorbid with asthma. Urban African American young adults with asthma often experience increased risk of anxiety and depression. OBJECTIVE: To explore relationships between symptoms of psychological distress and asthma-related anxiety with asthma outcomes among urban African American young adults with poorly controlled persistent asthma. METHODS: A secondary analysis of baseline data from a larger study of 141 African American young adults with uncontrolled persistent asthma was examined. Participants completed the Brief Symptom Inventory (BSI-18), Youth Asthma-related Anxiety Scale, Asthma Control Test (ACT), a daily diary to assess asthma symptoms; and number of asthma attacks. Spirometry assessed airway obstruction. Generalized linear models tested associations. RESULTS: In multivariable models testing, higher somatization scores were significantly associated with lower ACT scores (adjusted ß = -0.49; 95% CI = -0.69, -0.28; p < 0.01), and higher symptoms (adjusted ß = 0.39; 95% CI = 0.14, 0.65; p < 0.01). After adding asthma-related anxiety to the model, the somatization subscale and asthma-related anxiety were significantly associated with ACT scores (adjusted ß = -0.36; 95% CI = -0.57, -0.15; p < 0.01), (adjusted ß = -0.32; 95% CI = -0.50, -0.14; p < 0.01), respectively. Asthma-related anxiety was also significantly associated with asthma attacks (adjusted ß = 0.24; 95% CI = 0.05, 0.43; p < 0.05). CONCLUSION: This study suggests, asthma-related anxiety may differ from general anxiety and be related to poorly controlled asthma among African American young adults.

Predictors of adherence to controller medication in urban African American emerging adults with uncontrolled persistent asthma.

BACKGROUND: African American emerging adults tend to have low adherence to asthma controller medication, as well as a disproportionate burden of asthma morbidity and mortality. This study explored constructs from the Information-Motivation-Behavioral Skills model as predictors of controller medication adherence in urban African Americans ages 18-29 (N=152) with uncontrolled asthma using multiple measures of self-reported adherence. METHODS: Structural equation modeling (SEM) was employed to test the hypothesized mediation model that specified the relationship among psychological distress, substance use, asthma knowledge, motivation, self-efficacy, and adherence. RESULTS: Results suggested that motivation is an important predictor of adherence to medication; moreover, higher self-efficacy was associated with higher motivation. Results also highlighted psychological distress as an important intervention target to improve medication adherence in emerging adults. CONCLUSIONS: The model tested in this study may offer a feasible framework for beginning to understand adherence to controller medication in this population.

Prevalence and Correlates of Military Sexual Trauma in Service Members and Veterans: Results From the 2018 Canadian Armed Forces Members and Veterans Mental Health Follow-up Survey.

INTRODUCTION: Military sexual trauma (MST) is an ongoing problem. We used a 2002 population-based sample, followed up in 2018, to examine: (1) the prevalence of MST and non-MST in male and female currently serving members and veterans of the Canadian Armed Forces, and (2) demographic and military correlates of MST and non-MST. METHODS: Data came from the 2018 Canadian Armed Forces Members and Veterans Mental Health Follow-up Survey (n = 2,941, ages 33 years + ). Individuals endorsing sexual trauma were stratified into MST and non-MST and compared to individuals with no sexual trauma. The prevalence of lifetime MST was computed, and correlates of sexual trauma were examined using multinomial regression analyses. RESULTS: The overall prevalence of MST was 44.6% in females and 4.8% in males. Estimates were comparable between currently serving members and veterans. In adjusted models in both sexes, MST was more likely among younger individuals (i.e., 33-49 years), and MST and non-MST were more likely in those reporting more non-sexual traumatic events. Among females, MST and non-MST were more likely in those reporting lower household income, non-MST was less likely among Officers, and MST was more likely among those with a deployment history and serving in an air environment. Unwanted sexual touching by a Canadian military member or employee was the most prevalent type and context of MST. INTERPRETATION: A high prevalence of MST was observed in a follow-up sample of Canadian Armed Forces members and veterans. Results may inform further research as well as MST prevention efforts.

Investigating the impact of London's ultra low emission zone on children's health: children's health in London and Luton (CHILL) protocol for a prospective parallel cohort study.

BACKGROUND: Air pollution harms health across the life course. Children are at particular risk of adverse effects during development, which may impact on health in later life. Interventions that improve air quality are urgently needed both to improve public health now, and prevent longer-term increased vulnerability to chronic disease. Low Emission Zones are a public health policy intervention aimed at reducing traffic-derived contributions to urban air pollution, but evidence that they deliver health benefits is lacking. We describe a natural experiment study (CHILL: Children's Health in London and Luton) to evaluate the impacts of the introduction of London's Ultra Low Emission Zone (ULEZ) on children's health. METHODS: CHILL is a prospective two-arm parallel longitudinal cohort study recruiting children at age 6-9 years from primary schools in Central London (the focus of the first phase of the ULEZ) and Luton (a comparator site), with the primary outcome being the impact of changes in annual air pollutant exposures (nitrogen oxides [NOx], nitrogen dioxide [NO2], particulate matter with a diameter of less than 2.5micrograms [PM2.5], and less than 10 micrograms [PM10]) across the two sites on lung function growth, measured as post-bronchodilator forced expiratory volume in one second (FEV1) over five years. Secondary outcomes include physical activity, cognitive development, mental health, quality of life, health inequalities, and a range of respiratory and health economic data. DISCUSSION: CHILL's prospective parallel cohort design will enable robust conclusions to be drawn on the effectiveness of the ULEZ at improving air quality and delivering improvements in children's respiratory health. With increasing proportions of the world's population now living in large urban areas exceeding World Health Organisation air pollution limit guidelines, our study findings will have important implications for the design and implementation of Low Emission and Clean Air Zones in the UK, and worldwide. CLINICALTRIALS: GOV: NCT04695093 (05/01/2021).

Lung cancer risk in relation to jobs held in a nationwide case-control study in Iran.

BACKGROUND: Globally, lung cancer is the most frequent occupational cancer, but the risk associated with the occupations or occupational environment in Iran is not clear. We aimed to assess occupations with the risk of lung cancer. METHODS: We used the IROPICAN nationwide case-control study data including 658 incident lung cancer cases and 3477 controls. We assessed the risk of lung cancer in relation to ever working in major groups of International Standard Classification of Occupations, high-risk occupations for lung cancer and duration of employment and lung cancer subtype among construction workers and farmers while controlling for cigarette smoking and opium consumption. We used unconditional regression logistic models to estimate ORs for the association between increased lung cancer risk and occupations. RESULTS: We observed elevated ORs for lung cancer in male construction workers (OR=1.4; 95% CI: 1.0 to 1.8), petroleum industry workers (OR=3.2; 95% CI: 1.1 to 9.8), female farmers (OR=2.6; 95% CI: 1.3 to 5.3) and female bakers (OR=5.5; 95% CI: 1.0 to 29.8). A positive trend by the duration of employment was observed for male construction workers (p< 0.001). Increased risk of squamous cell carcinoma was observed in male construction workers (OR=1.9; 95% CI: 1.2 to 3.0) and female farmers (OR=4.3; 95% CI: 1.1 to 17.2), who also experienced an increased risk of adenocarcinoma (OR=3.8; 95% CI: 1.4 to 9.9). DISCUSSION: Although we observed associations between some occupations and lung cancer consistent with the literature, further studies with larger samples focusing on exposures are needed to better understand the occupational lung cancer burden in Iran.

Barriers and facilitators for the safe handling of antineoplastic drugs.

INTRODUCTION: Antineoplastic drugs are widely used in the treatment of cancer. However, some are known carcinogens and reproductive toxins, and incidental low-level exposure to workers is a health concern. CAREX Canada estimated that approximately 75,000 Canadians are exposed to antineoplastic drugs in workplace settings. While policies and guidelines on safe handling of antineoplastic drugs are available, evidence suggests that compliance is low. In this paper, we identify barriers and facilitators for safe handling of antineoplastic drugs in workplace settings. METHODS: We utilized a unique method to study public policy which involved compiling policy levers, developing a logic model, conducting a literature review, and contextualizing data through a deliberative process with stakeholders to explore in-depth contextual factors and experiences for the safe handling of antineoplastic drugs. RESULTS: The most common barriers identified in the literature were: poor training (46%), poor safety culture (41%), and inconsistent policies (36%). The most common facilitators were: adequate safety training (41%), leadership support (23%), and consistent policies (21%). Several of these factors are intertwined and while this means one barrier can cause other barriers, it also allows healthcare employers to mitigate these barriers by implementing small but meaningful changes in the workplace. CONCLUSION: The combination of barriers and facilitators identified in our review highlight the importance of creating work environments where safety is a priority for the safe handling of antineoplastic drugs. The results of this study will assist policy makers and managers in identifying gaps and enhancing strategies that reduce occupational exposure to antineoplastic drugs.

Real-Time Anomaly Detection for an ADMM-Based Optimal Transmission Frequency Management System for IoT Devices.

In this paper, we investigate different scenarios of anomaly detection on decentralised Internet of Things (IoT) applications. Specifically, an anomaly detector is devised to detect different types of anomalies for an IoT data management system, based on the decentralised alternating direction method of multipliers (ADMM), which was proposed in our previous work. The anomaly detector only requires limited information from the IoT system, and can be operated using both a mathematical-rule-based approach and the deep learning approach proposed in the paper. Our experimental results show that detection based on mathematical approach is simple to implement, but it also comes with lower detection accuracy (78.88%). In contrast, the deep-learning-enabled approach can easily achieve a higher detection accuracy (96.28%) in the real world working environment.

Health care access and use among male and female Canadian Armed Forces veterans.

BACKGROUND: Veterans are more likely than other Canadians to have chronic health conditions, making access to health care an important issue. However, little research has addressed health care access and use among veterans. This paper examines access and use among veterans compared with other Canadians. DATA AND METHODS: Health care access and use indicators were examined for Regular Force veterans using the 2016 Life After Service Survey. Information for male and female veterans was compared with information on the Canadian general population from the 2015 and 2016 Canadian Community Health Survey, using age-adjusted rates and 95% confidence intervals. RESULTS: More than 80% of male and female veterans reported having a regular medical doctor in the 12 months before the survey. The majority of veterans (71% of males and 81% of females) had consulted a family doctor, while a minority had been hospitalized (8% of males and females). These rates were similar to those in the Canadian general population. However, veteran consultation rates for mental health care and with audiologists, speech therapists or occupational therapists among both sexes were double to triple those of the Canadian general population. Among veterans, males reported lower rates of unmet needs compared with females. DISCUSSION: Veterans had similar rates of access to a regular medical doctor and higher rates of use compared with other Canadians. However, these may be comparatively low, given previous findings on higher rates of disability and some chronic conditions among veterans. Noted differences between males and females highlight the importance of research and services that account for sex and gender. The extent to which health care needs explain health care use and barriers to care requires further research.

Laryngeal Cancer Risks in Workers Exposed to Lung Carcinogens: Exposure-Effect Analyses Using a Quantitative Job Exposure Matrix.

INTRODUCTION: Various established occupational lung carcinogens are also suspected risk factors for laryngeal cancer. However, individual studies are often inadequate in size to investigate this relatively rare outcome. Other limitations include imprecise exposure assessment and inadequate adjustment for confounders. METHODS: This study applied a quantitative job exposure matrix (SYN-JEM) for four established occupational lung carcinogens to five case-control studies within the International Head and Neck Cancer Epidemiology Consortium. We used occupational histories for 2256 laryngeal cancer cases and 7857 controls recruited from 1989 to 2007. We assigned quantitative exposure levels for asbestos, respirable crystalline silica, chromium-VI, and chromium-VI and nickel combined (to address highly correlated exposures) via SYN-JEM. We assessed effects of occupational exposure on cancer risk for males (asbestos, respirable crystalline silica, chromium-VI, and chromium-VI and nickel combined) and females (asbestos and respirable crystalline silica), adjusting for age, study, tobacco smoking, alcohol consumption, and asbestos exposure where relevant. RESULTS: Among females, odds ratios (ORs) were increased for ever versus never exposed. Among males, P values for linear trend were <0.05 for estimated cumulative exposure (all agents) and <0.05 for exposure duration (respirable crystalline silica, chromium-VI, and chromium-VI and nickel combined); strongest associations were for asbestos at >90th percentile cumulative exposure (OR = 1.3, 95% confidence interval [CI] = 1.0, 1.6), respirable crystalline silica at 30+ years duration (OR = 1.4, 95% CI = 1.2, 1.7) and 75th-90th percentile cumulative exposure (OR = 1.4, 95% CI = 1.1, 1.8), chromium-VI at >75th percentile cumulative exposure (OR = 1.9, 95% CI = 1.2, 3.0), and chromium-VI and nickel combined at 20-29 years duration (OR = 1.5, 95% CI = 1.1, 2.2). CONCLUSIONS: These findings support hypotheses of causal links between four lung carcinogens (asbestos, respirable crystalline silica, chromium-VI, and nickel) and laryngeal cancer.

Biophysical properties of the clinical-stage antibody landscape.

Antibodies are a highly successful class of biological drugs, with over 50 such molecules approved for therapeutic use and hundreds more currently in clinical development. Improvements in technology for the discovery and optimization of high-potency antibodies have greatly increased the chances for finding binding molecules with desired biological properties; however, achieving drug-like properties at the same time is an additional requirement that is receiving increased attention. In this work, we attempt to quantify the historical limits of acceptability for multiple biophysical metrics of "developability." Amino acid sequences from 137 antibodies in advanced clinical stages, including 48 approved for therapeutic use, were collected and used to construct isotype-matched IgG1 antibodies, which were then expressed in mammalian cells. The resulting material for each source antibody was evaluated in a dozen biophysical property assays. The distributions of the observed metrics are used to empirically define boundaries of drug-like behavior that can represent practical guidelines for future antibody drug candidates.

Soil multifunctionality and drought resistance are determined by plant structural traits in restoring grassland.

It is increasingly recognized that belowground responses to vegetation change are closely linked to plant functional traits. However, our understanding is limited concerning the relative importance of different plant traits for soil functions and of the mechanisms by which traits influence soil properties in the real world. Here we test the hypothesis that taller species, or those with complex rooting structures, are associated with high rates of nutrient and carbon (C) cycling in grassland. We further hypothesized that communities dominated by species with deeper roots may be more resilient to drought. These hypotheses were tested in a 3-yr grassland restoration experiment on degraded ex-arable land in southern England. We sowed three trait-based plant functional groups, assembled using database derived values of plant traits, and their combinations into bare soil. This formed a range of plant trait syndromes onto which we superimposed a simulated drought 2 yr after initial establishment. We found strong evidence that community weighted mean (CWM) of plant height is negatively associated with soil nitrogen cycling and availability and soil multifunctionality. We propose that this was due to an exploitative resource capture strategy that was inappropriate in shallow chalk soils. Further, complexity of root architecture was positively related to soil multifunctionality throughout the season, with fine fibrous roots being associated with greater rates of nutrient cycling. Drought resistance of soil functions including ecosystem respiration, mineralization, and nitrification were positively related to functional divergence of rooting depth, indicating that, in shallow chalk soils, a range of water capture strategies is necessary to maintain functions. Finally, after 3 yr of the experiment, we did not detect any links between the plant traits and microbial communities, supporting the finding that traits based on plant structure and resource foraging capacity are the main variables driving soil function in the early years of grassland conversion. We suggest that screening recently restored grassland communities for potential soil multifunctionality and drought resilience may be possible based on rooting architecture and plant height. These results indicate that informed assembly of plant communities based on plant traits could aid in the restoration of functioning in degraded soil.

Drought neutralises plant-soil feedback of two mesic grassland forbs.

Plant-soil feedbacks (PSFs) describe the effect of a plant species on soil properties, which affect the performance of future generations. Here we test the hypothesis that drought alters PSFs by reducing plant-microbe associations and nutrient uptake. We chose two grassland forb species, previously shown to respond differently to soil conditioning and drought, to test our hypothesis. We conditioned unsterilised grassland soil with one generation of each species, and left a third soil unconditioned. We grew a second generation consisting of each combination of plant species, soil, and drought in a full factorial design, and measured soil microbial community and nutrient availability. Scabiosa columbaria displayed negative PSF (smaller plants) under non-droughted conditions, but neutral under drought, suggesting that drought disrupts plant-soil interactions and can advantage the plant. Photosynthetic efficiency of S. columbaria was reduced under drought, but recovered on rewetting regardless of soil conditioning, indicating that PSFs do not impede resilience of this species. Sanguisorba minor showed positive PSFs (larger plants), probably due to an increase in soil N in conspecific soil, but neutral PSF under drought. PSF neutralisation appeared to occur through drought-induced change in the soil microbial community for this species. When S. minor was planted in conspecific soil, photosynthetic efficiency declined to almost zero, with no recovery following rewetting. We attributed this to increased demand for water through higher demand for nutrients with positive PSF. Here we show that drought neutralises PSFs of two grassland forbs, which could have implications for plant communities under climate change.

Identifying occupational carcinogens: an update from the IARC Monographs.

The recognition of occupational carcinogens is important for primary prevention, compensation and surveillance of exposed workers, as well as identifying causes of cancer in the general population. This study updates previously published lists of known occupational carcinogens while providing additional information on cancer type, exposure scenarios and routes, and discussing trends in the identification of carcinogens over time. Data were extracted from International Agency for Research on Cancer (IARC) Monographs covering the years 1971-2017, using specific criteria to ensure occupational relevance and provide high confidence in the causality of observed exposure-disease associations. Selected agents were substances, mixtures or types of radiation classified in IARC Group 1 with 'sufficient evidence of carcinogenicity' in humans from studies of exposed workers and evidence of occupational exposure documented in the pertinent monograph. The number of known occupational carcinogens has increased over time: 47 agents were identified as known occupational carcinogens in 2017 compared with 28 in 2004. These estimates are conservative and likely underestimate the number of carcinogenic agents present in workplaces. Exposure to these agents causes a wide range of cancers; cancers of the lung and other respiratory sites, followed by skin, account for the largest proportion. The dominant routes of exposure are inhalation and dermal contact. Important progress has been made in identifying occupational carcinogens; nevertheless, there is an ongoing need for research on the causes of work-related cancer. Most workplace exposures have not been evaluated for their carcinogenic potential due to inadequate epidemiologic evidence and a paucity of quantitative exposure data.

A Clinicopathologic Evaluation of Incidental Fundic Gland Polyps With Dysplasia: Implications for Clinical Management.

OBJECTIVES: Fundic gland polyps (FGPs) can rarely exhibit dysplasia of the surface epithelium. Based on retrospective data, FGPs with dysplasia (FGPDs) are thought to be a strong marker for familial adenomatous polyposis (FAP), although sporadic, non-syndromic FGPDs also occur. Owing to the significant syndromic association, diagnosis of an apparently sporadic FGPD may prompt clinical evaluation for FAP, especially its attenuated variant. We sought to evaluate the positive predictive value of incidental FGPDs for FAP. We also characterized the clinicopathologic features of incidental FGPDs to advance clinical management. METHODS: Incidental FGPDs were identified from 2004 to 2015 in patients without FAP at biopsy. All clinical follow-up data were reviewed, and germline analysis for APC and MUTYH mutations was performed in consenting patients. RESULTS: We identified 25 incidental FGPDs in patients not known to have FAP (11.6% of FGPDs, 1.0% of all FGPs). Four patients had a family history of gastric polyps or gastrointestinal cancers. Clinical management included completion polypectomy and gastric endoscopic surveillance (44%), endoscopic surveillance alone (32%), no follow-up (24%), colonoscopy referral (12%), and genetic counseling (4%). Colonoscopies on record revealed 0-7 cumulative adenomas. Follow-up averaged 4.4 years (range 0.3-10.6). No clinical evidence of FAP, gastric cancer, death, or surgery occurred. None of the 11 patients consenting to germline APC and MUTYH testing had genomic alterations. CONCLUSIONS: Incidental FGPDs in this series were all found to be sporadic (25/25) by endoscopic, clinical, and molecular findings, and thus FGPDs were not harbingers of FAP. As isolated findings, FGPDs do not appear to warrant follow-up genetic counseling or testing.

An immunological marker of tolerance to infection in wild rodents.

Hosts are likely to respond to parasitic infections by a combination of resistance (expulsion of pathogens) and tolerance (active mitigation of pathology). Of these strategies, the basis of tolerance in animal hosts is relatively poorly understood, with especially little known about how tolerance is manifested in natural populations. We monitored a natural population of field voles using longitudinal and cross-sectional sampling modes and taking measurements on body condition, infection, immune gene expression, and survival. Using analyses stratified by life history stage, we demonstrate a pattern of tolerance to macroparasites in mature compared to immature males. In comparison to immature males, mature males resisted infection less and instead increased investment in body condition in response to accumulating burdens, but at the expense of reduced reproductive effort. We identified expression of the transcription factor Gata3 (a mediator of Th2 immunity) as an immunological biomarker of this tolerance response. Time series data for individual animals suggested that macroparasite infections gave rise to increased expression of Gata3, which gave rise to improved body condition and enhanced survival as hosts aged. These findings provide a clear and unexpected insight into tolerance responses (and their life history sequelae) in a natural vertebrate population. The demonstration that such responses (potentially promoting parasite transmission) can move from resistance to tolerance through the course of an individual's lifetime emphasises the need to incorporate them into our understanding of the dynamics and risk of infection in the natural environment. Moreover, the identification of Gata3 as a marker of tolerance to macroparasites raises important new questions regarding the role of Th2 immunity and the mechanistic nature of the tolerance response itself. A more manipulative, experimental approach is likely to be valuable in elaborating this further.