Extent of Inclusion of "Rural" in Comprehensive Cancer Control Plans in the United States.

INTRODUCTION: The National Comprehensive Cancer Control Program requires states, territories, and tribal organizations to develop comprehensive cancer control plans (CCCPs). In 2019, the National Advisory Committee on Rural Health and Human Services released a series of policy recommendations, including one recommending that CCCPs address rural cancer disparities. The objective of our study was to assess the extent to which jurisdictions considered "rural" in their CCCPs. METHODS: We reviewed the 66 CCCPs available on the Centers for Disease Control and Prevention's website as of January 2020 to assess their inclusion of rural across 7 elements: 1) cancer burden data, 2) reduction of cancer disparities, 3) rural population description, 4) rural definition, 5) goals, 6) objectives, and 7) strategies. We summarized these elements by plan type (state or territory/tribal organization). For state CCCPs, we also compared the number of element types and the inclusion of rural-specific strategies by the percentage of the state's population that was rural and the rural cancer mortality rate. RESULTS: Of 66 plans, 45 included a mention of rural in at least 1 element, including 38 of 50 state plans and 7 of 16 territory/tribal organization plans. Reduction of cancer disparities was the most common element noted. Less than one-third of all CCCPs included a rural-specific strategy. States with a high rural cancer mortality rate tended to have at least 1 rural-specific strategy. CONCLUSION: Technical and financial support to improve rural data inclusion and implementation of rural-specific strategies in CCCPs may help improve the inclusion of rural data and strategy development.

Health and economic impact of nitrate pollution in drinking water: a Wisconsin case study.

Nitrate contamination of drinking water, common in agricultural areas, increases the risk of certain cancers and impacts fetal development during pregnancy. Building on previously published methodology, this study evaluates nitrate-attributable disease cases and adverse birth outcomes as well as their economic costs for Wisconsin, USA. Nitrate is the most common contaminant in groundwater in Wisconsin. Two-thirds of the state's residents use groundwater as the primary source of drinking water. Here, we analyze nitrate exposure from drinking water in Wisconsin based on nitrate test results for community water systems for the period of 2010-2017 and a novel methodology for estimating nitrate exposure for the 28% of state's residents who use private wells. We estimate that annually, 111-298 combined cases of colorectal, ovarian, thyroid, bladder, and kidney cancer in Wisconsin may be due to nitrate contamination of drinking water. Each year, up to 137-149 cases of very low birth weight, 72-79 cases of very preterm birth, and two cases of neural tube defects could be due to nitrate exposure from drinking water. The direct medical cost estimates for all nitrate-attributable adverse health outcomes range between $23 and $80 million annually. Simulating targeted reductions in the counties with the highest current drinking water nitrate concentrations resulted in similar reductions in adverse health outcomes as statewide reduction efforts, up to nitrate reductions of 20%. Time trend analysis suggests that groundwater nitrate concentrations are overall increasing. Thus, nitrate contamination of water supplies in Wisconsin is a public health problem that needs to be addressed.

Exposure-based assessment and economic valuation of adverse birth outcomes and cancer risk due to nitrate in United States drinking water.

BACKGROUND: Nitrate ingestion from drinking water has been associated with an increased risk of adverse birth outcomes as well as elevated risk of colorectal cancer and several other cancers. Yet, to date, no studies have attempted to quantify the health and economic impacts due to nitrate in drinking water in the United States. METHODS: This study presents a first-of-its-kind comprehensive assessment of nitrate exposure from drinking water for the entire United States population. This exposure assessment serves as the basis for our analysis of the annual nitrate-attributable disease cases in the United States and the associated economic losses due to medical costs and lost productivity. Additionally, through a meta-analysis of studies on drinking water nitrate and colorectal cancer, we examine the exposure-response relationship for nitrate and cancer risk. RESULTS: On the basis of national nitrate occurrence data and relative risk ratios reported in the epidemiology literature, we calculated that annually, 2939 cases of very low birth weight, 1725 cases of very preterm birth, and 41 cases of neural tube defects could be related to nitrate exposure from drinking water. For cancer risk, combining nitrate-specific risk estimates for colorectal, ovarian, thyroid, kidney, and bladder cancers results in a range of 2300 to 12,594 annual nitrate-attributable cancer cases (mean: 6537 estimated cases). For medical expenditures alone, this burden of cancer corresponds to an annual economic cost of 250 million to 1.5 billion U.S. dollars, together with a potential 1.3 to 6.5 billion dollar impact due to lost productivity. With the meta-analysis of eight studies of drinking water nitrate and colorectal cancer, we observed a statistically significant positive association for nitrate exposure and colorectal cancer risk and calculated a one-in-one million cancer risk level of 0.14 mg/L nitrate in drinking water. CONCLUSION: Health and economic analyses presented here suggest that lowering exposure to nitrate in drinking water could bring economic benefits by alleviating the impacts of nitrate-associated diseases.

Efficacy of technology-based interventions to increase the use of hearing protections among adolescent farmworkers.

OBJECTIVE: Adolescent farmworkers are exposed to loud noise during farm activities. We present a prospective study that evaluated the efficacy of low-cost, technology-based intervention approaches in high schools to enhance the use of hearing protection among adolescent farmworkers. DESIGN: Six high schools in Iowa that agreed to participate in the study were divided into three equal groups through cluster-randomisation with each group receiving one of the three formats of hearing protection intervention: (a) classroom training, (b) classroom training coupled with smartphone app training and (c) computer training. Participants completed baseline (pre-training) and six-week post-intervention surveys for assessing hearing protection knowledge, attitudes and behaviour. STUDY SAMPLE: Seventy participants from six schools were initially enrolled but 50 completed both pre- and post-intervention surveys. RESULTS: In most cases, all three groups showed significant improvement in hearing protection knowledge, attitude and frequency of use from pre- to post-intervention. However, changes between groups were statistically non-significant. CONCLUSIONS: Although all three formats led to improvements on hearing protection knowledge, attitude and behaviour, the findings of the study, perhaps due to the small sample size, did not allow us to detect whether technology-based hearing protection interventions were more effective than the traditional face-to-face training for adolescent farmworkers.

GBM radiosensitizers: dead in the water or just the beginning?

The finding that most GBMs recur either near or within the primary site after radiotherapy has fueled great interest in the development of radiosensitizers to enhance local control. Unfortunately, decades of clinical trials testing a wide range of novel therapeutic approaches have failed to yield any clinically viable radiosensitizers. However, many of  the previous radiosensitizing strategies were not based on clear pre-clinical evidence, and in many cases blood-barrier penetration was not considered. Furthermore, DNA repair inhibitors have only recenly arrived in the clinic, and likely represent potent agents for glioma radiosensitization. Here, we present recent progress in the use of small molecule DNA damage response inhibitors as GBM radiosensitizers. In addition, we discuss the latest progress in targeting hypoxia and oxidative stress for GBM radiosensitization.

Feasibility of a low-cost hearing screening in rural Indiana.

BACKGROUND: Hearing loss remains a neglected public health issue in the rural and agricultural communities in the United States and therefore, promotion of a low-cost hearing screening may be important for these underserved populations. The major objectives of our study were to assess feasibility of a low-cost telephone-administered hearing test in rural Indiana and to identify the challenges, barriers and viable implementation strategies associated with this test. Also, we evaluated whether a focus group session could change the hearing health attitude of rural residents. METHODS: We recruited 126 adults from six rural Indiana counties who participated in study activities in the following order: 1) a pre-focus group demographic, knowledge and attitude survey, 2) a focus group for discussing the feasibility of a telephone-administered hearing screening, 3) a post focus group attitude survey and 4) hearing was screened using an audiometer and self-assessment scale. These activities generated both qualitative and quantitative data, which were subsequently analyzed. RESULTS: Hearing impairment was perceived as an important public health issue. Many participants expressed interests to try the low-cost National Hearing Test (NHT). However, participants recommended NHT to be facilitated by community organizations to provide access to landline phones. The focus group turned out to be an excellent awareness building activity producing significant improvement in hearing health attitudes. Comparison of self and audiometric evaluations indicated underestimation of hearing handicap in our rural study population. CONCLUSIONS: The study results underscore the urgent need for an effective strategy to promote low-cost hearing screening in rural US communities.

Initial evidence that blood-borne microvesicles are biomarkers for recurrence and survival in newly diagnosed glioblastoma patients.

The purpose of this pilot study was to determine whether blood-borne microvesicles from newly diagnosed glioblastoma patients could be used as biomarkers. We collected 2.8 mL blood from 16 post-operative patients at the time that they were being simulated for chemoradiation therapy (radiation with concurrent temozolomide). Two additional samples were collected during chemoradiation therapy and a final sample was collected at the end of chemoradiation therapy. Patients continued with the therapy suggested by their physicians, based on tumor conference consensus and were followed for recurrence and overall survival. Microvesicles were isolated using serial centrifugation and stained for surface markers (Annexin V for phosphotidyl serine, CD41 for platelets, anti-EGFR for tumor cells, and CD235 for red blood cells). Flow cytometry analysis was performed. Our findings provide initial evidence that increases in Annexin V positive microvesicle levels during chemoradiation therapy are associated with earlier recurrence and shorter overall survival in newly diagnosed glioblastoma patients. The effect is dramatic, with over a four-fold increase in the hazard ratio for an individual at the 75th versus the 25th percentile. Moreover the pattern of Annexin V positive microvesicles remain significant after adjustment for confounding clinical variables that have previously been shown to be prognostic for recurrence and survival. Inclusion of neutrophil levels at the start of chemoradiation therapy in the model yielded the largest attenuation of the observed association. Further studies will be needed to verify and further investigate the association between these two entities.

A pilot study of chlormequat in food and urine from adults in the United States from 2017 to 2023.

Chlormequat chloride is a plant growth regulator whose use on grain crops is on the rise in North America. Toxicological studies suggest that exposure to chlormequat can reduce fertility and harm the developing fetus at doses lower than those used by regulatory agencies to set allowable daily intake levels. Here we report, the presence of chlormequat in urine samples collected from people in the U.S., with detection frequencies of 69%, 74%, and 90% for samples collected in 2017, 2018-2022, and 2023, respectively. Chlormequat was detected at low concentrations in samples from 2017 through 2022, with a significant increase in concentrations for samples from 2023. We also observed high detection frequencies of chlormequat in oat-based foods. These findings and chlormequat toxicity data raise concerns about current exposure levels, and warrant more expansive toxicity testing, food monitoring, and epidemiological studies to assess health effects of chlormequat exposures in humans. IMPACT: This study reports the detection of chlormequat, an agricultural chemical with developmental and reproductive toxicity, in the U.S. population and U.S. food supplies for the first time. While similar levels of the chemical were found in urine sampled from 2017 to 2022, markedly increased levels were found in samples from 2023. This work highlights the need for more expansive monitoring of chlormequat in U.S. foods and in human specimens, as well as toxicological and epidemiological study on chlormequat, as this chemical is an emerging contaminant with documented evidence of low-dose adverse health effects in animal studies.

"Everybody needs to find the best path for them": Insights into recovery strategies of people who have not used specialty treatment for alcohol use disorder.

BACKGROUND: Most people with alcohol use disorder (AUD) do not use treatment services, yet the majority ultimately resolve their AUD. As the phenomenon of untreated recovery remains poorly understood, we investigated the strategies used for recovery without treatment. METHODS: We conducted semi-structured interviews with 65 adults (27 women, 37 White) with resolved AUD and no history of using specialty services (e.g., inpatient or outpatient rehabilitation, medication-assisted treatment). Using both inductive and deductive coding, we identified and elaborated themes and meanings. We verified our findings through nine member-check sessions with interviewers and interview participants. RESULTS: Majorities of interview participants met criteria for severe lifetime AUD (84.6%), were in long-term recovery (>5 years; 81.5%), and indicated abstinence was their recovery goal (56.9%). Close to half (41.5%) had attended mutual-help groups (e.g., Alcoholics Anonymous). We identified five active strategies (Changing Contexts, Social Connections. Activities, Substitution, and Other Strategies) and four additional factors (Mutual-help Groups, Self-Reliance, Spirituality, and Aging/Maturing) that contributed to their recovery. Most participants employed multiple strategies and were intentional in adopting the ones that best suited them. By far, the two most common strategies were Changing Contexts (reported by 69.2% of participants) whereby people reduced their alcohol exposure by modifying social networks or physical settings and relying on Social Connections (reported by 67.7%), especially connections to people with similar lived experiences and struggles. Notably, Social Connections and Mutual-Help groups were the themes most often discussed jointly. Among other contributing factors mentioned, Spirituality appeared to play an important, but not universal, role as it was invoked by approximately half (49.2%) of participants. CONCLUSIONS: Our study confirms that recovery without specialty treatment is possible, and that multiple strategies and contributing factors help to achieve it. These findings may inform novel interventions to support recovery among people unwilling or unable to obtain treatment for AUD.

Rural comprehensive cancer care: Qualitative analysis of current challenges and opportunities.

PURPOSE: While limited resources can make high-quality, comprehensive, coordinated cancer care provision challenging in rural settings, rural cancer patients often rely on local hospitals for care. To develop resources and strategies to support high-quality local cancer care, it is critical to understand the current experiences of rural cancer care physicians, including perceived strengths and challenges of providing cancer care in rural areas.  METHODS: Semi-structured interviews were conducted with 13 cancer providers associated with all 12 non-metropolitan/rural Iowa hospitals that diagnose or treat >100 cancer patients annually. Iterative thematic analysis was conducted to develop domains. FINDINGS: Participants identified geographic proximity and sense of community as strengths of local care. They described decision-making processes and challenges related to referring patients to larger centers for complex procedures, including a lack of dedicated navigators to facilitate and track transfers between institutions and occasional lack of respect from academic physicians. Participants reported a desire for strengthening collaborations with larger urban/academic cancer centers, including access to educational opportunities, shared resources and strategies to collect and monitor data on quality, and clinical trials. CONCLUSIONS: Rural cancer care providers are dedicated to providing high-quality care close to home for their patients and would welcome opportunities to increase collaboration with larger centers to improve coordination and comprehensiveness of care, collect and monitor data on quality of care, and access continuing education opportunities. Further research is needed to develop implementation approaches that will extend resources, services, and expertise to rural providers to facilitate high-quality cancer care for all cancer patients.

How Home Child Care Providers Purchase, Prepare, and Serve Healthy Foods: In-Depth Interviews with Child and Adult Care Food Program Participants.

Background: Child care settings can enhance children's access and exposure to healthy foods through participation in The Child and Adult Care Food Program (CACFP), which reimburses child care providers for purchasing healthy foods. To identify challenges and facilitators to CACFP participation, we carried out in-depth interviews with CACFP-participating home child care providers to discuss purchasing, preparing, and serving food under CACFP guidelines. Methods: We carried out 20 in-depth telephone interviews with CACFP-participating home child care providers. Transcribed interviews were coded to develop themes using a deductive approach. Results: Interviews indicated that food costs still burden CACFP-participating child care providers despite reimbursements. CACFP-participating providers who described prioritizing healthy foods and nutrition showed a greater inclination toward purchasing, preparing, and serving healthy foods to children. Conclusions: We offer recommendations for how to effectively support CACFP-participating providers in offering healthy food to their children within a food choice framework, a multilevel categorization of factors that influence food choice. Recommendations include increased reimbursement rates for food purchases under CACFP and support for peer-to-peer mentoring and health promotion programs targeting child care provider health.

Racial and social disparities in Ventura County, California related to agricultural pesticide applications and toxicity.

Application of agricultural pesticides poses health concerns for farmworkers and for local communities due to pesticide drift from spraying or fumigation, pesticide volatilization into the air, contamination of household dust, as well as direct exposure for people who work in agriculture and their families. In this analysis of pesticide use records for Ventura County, California (USA) from 2016 to 2018, we identified the most prevalent toxicological effects of the pesticides applied. We also developed a cumulative toxicity index that incorporates specific toxicity endpoints for individual pesticides, the severity and strength of association for each endpoint, and the reliability of the data sources. Combining the toxicity index for each pesticide with the pounds applied within each square mile section in Ventura County, we calculated the total toxicity-weighted pesticide use and identified pesticides associated with higher potential risk to health. Analysis of U.S. Census data for Ventura County found a greater percentage of Hispanic/Latino, African American and Asian community members in township sections with a greater volume of pesticides applied and higher toxicity-weighted pesticide use. Similarly, areas with limited economic and social resources had elevated pesticide application overall and elevated toxicity-weighted pesticide use. The combination of toxicological and demographic analyses presented in this study provides information that can support the development of policies to protect public health from excessive exposure to pesticides and better environmental health protection for socially vulnerable populations.

Community-Level Analysis of Drinking Water Data Highlights the Importance of Drinking Water Metrics for the State, Federal Environmental Health Justice Priorities in the United States.

Research studies analyzing the geospatial distribution of air pollution and other types of environmental contamination documented the persistence of environmental health disparities between communities. Due to the shortage of publicly available data, only limited research has been published on the geospatial distribution of drinking water pollution. Here we present a framework for the joint consideration of community-level drinking water data and demographic data. Our analysis builds on a comprehensive data set of drinking water contaminant occurrence for the United States for 2014-2019 and the American Community Survey 5-year estimates (2015-2019) from the U.S. Census Bureau. Focusing on the U.S. states of California and Texas for which geospatial data on community water system service boundaries are publicly available, we examine cumulative cancer risk for water served by community water systems of different sizes relative to demographic characteristics for the populations served by these water systems. In both California and Texas, greater cumulative cancer risk was observed for water systems serving communities with a higher percentage of Hispanic/Latino and Black/African American community members. This investigation demonstrates that it is both practical and essential to incorporate and expand the drinking water data metrics in the analysis of environmental pollution and environmental health. The framework presented here can support the development of public policies to advance environmental health justice priorities on state and federal levels in the U.S.

Investigating Molecular Mechanisms of Immunotoxicity and the Utility of ToxCast for Immunotoxicity Screening of Chemicals Added to Food.

The development of high-throughput screening methodologies may decrease the need for laboratory animals for toxicity testing. Here, we investigate the potential of assessing immunotoxicity with high-throughput screening data from the U.S. Environmental Protection Agency ToxCast program. As case studies, we analyzed the most common chemicals added to food as well as per- and polyfluoroalkyl substances (PFAS) shown to migrate to food from packaging materials or processing equipment. The antioxidant preservative tert-butylhydroquinone (TBHQ) showed activity both in ToxCast assays and in classical immunological assays, suggesting that it may affect the immune response in people. From the PFAS group, we identified eight substances that can migrate from food contact materials and have ToxCast data. In epidemiological and toxicological studies, PFAS suppress the immune system and decrease the response to vaccination. However, most PFAS show weak or no activity in immune-related ToxCast assays. This lack of concordance between toxicological and high-throughput data for common PFAS indicates the current limitations of in vitro screening for analyzing immunotoxicity. High-throughput in vitro assays show promise for providing mechanistic data relevant for immune risk assessment. In contrast, the lack of immune-specific activity in the existing high-throughput assays cannot validate the safety of a chemical for the immune system.

The ALPHA Project: Establishing consensus and prioritisation of global community recommendations to address major challenges in lupus diagnosis, care, treatment and research.

The Addressing Lupus Pillars for Health Advancement (ALPHA) Project is a global consensus effort to identify, prioritise and address top barriers in lupus impacting diagnosis, care, treatment and research. To conduct this process, the ALPHA Project convened a multistakeholder Global Advisory Committee (GAC) of lupus experts and collected input from global audiences, including patients. In phase I, the ALPHA Project used expert interviews and a global survey of lupus experts to identify and categorise barriers into three overarching pillars: drug development, clinical care and access to care. In phase II, reported here, the GAC developed recommended actionable solutions to address these previously identified barriers through an in-person stakeholder meeting, followed by a two-round scoring process. Recommendations were assessed for feasibility, impact and timeline for implementation (FIT), where potential FIT component values were between 1 and 3 and total scores were between 3 and 9. Higher scores represented higher achievability based on the composite of the three criteria. Simplifying and standardising outcomes measures, including steroid sparing as an outcome (drug development) and defining the lupus spectrum (clinical care) ranked as the highest two priority solutions during the GAC meeting and received high FIT scores (7.67 and 7.44, respectively). Leveraging social media (access to care) received the highest FIT score across all pillars (7.86). Cross-cutting themes of many solutions include leveraging digital technology and applying specific considerations for special populations, including paediatrics. Implementing the recommendations to address key barriers to drug development, clinical care and access to care is essential to improving the quality of life of adults and children with lupus. Multistakeholder collaboration and guidance across existing efforts globally is warranted.

Biodistribution and dosimetry of (18)F-EF5 in cancer patients with preliminary comparison of (18)F-EF5 uptake versus EF5 binding in human glioblastoma.

PURPOSE: The primary purpose of this study was to assess the biodistribution and radiation dose resulting from administration of (18)F-EF5, a lipophilic 2-nitroimidazole hypoxia marker in ten cancer patients. For three of these patients (with glioblastoma) unlabeled EF5 was additionally administered to allow the comparative assessment of (18)F-EF5 tumor uptake with EF5 binding, the latter measured in tumor biopsies by fluorescent anti-EF5 monoclonal antibodies. METHODS: (18)F-EF5 was synthesized by electrophilic addition of (18)F(2) gas, made by deuteron bombardment of a neon/fluorine mixture in a high-pressure gas target, to an allyl precursor in trifluoroacetic acid at 0° then purified and administered by intravenous bolus. Three whole-body images were collected for each of ten patients using an Allegro (Philips) scanner. Gamma counts were determined in blood, drawn during each image, and urine, pooled as a single sample. PET images were analyzed to determine radiotracer uptake in several tissues and the resulting radiation dose calculated using OLINDA software and standard phantom. For three patients, 21 mg/kg unlabeled EF5 was administered after the PET scans, and tissue samples obtained the next day at surgery to determine EF5 binding using immunohistochemistry techniques (IHC). RESULTS: EF5 distributes evenly throughout soft tissue within minutes of injection. Its concentration in blood over the typical time frame of the study (∼3.5 h) was nearly constant, consistent with a previously determined EF5 plasma half-life of ∼13 h. Elimination was primarily via urine and bile. Radiation exposure from labeled EF5 is similar to other (18)F-labeled imaging agents (e.g., FDG and FMISO). In a de novo glioblastoma multiforme patient, focal uptake of (18)F-EF5 was confirmed by IHC. CONCLUSION: These results confirm predictions of biodistribution and safety based on EF5's characteristics (high biological stability, high lipophilicity). EF5 is a novel hypoxia marker with unique pharmacological characteristics allowing both noninvasive and invasive measurements.

Disposal of products and materials containing per- and polyfluoroalkyl substances (PFAS): A cyclical problem.

Per- and polyfluoroalkyl substances (PFAS), highly stable and persistent chemicals used in numerous industrial applications and consumer goods, pose an exceptionally difficult challenge for disposal. Three approaches are currently available for PFAS wastes: landfilling, wastewater treatment and incineration. Each disposal approach can return either the original PFAS or their degradation products back to the environment, illustrating that the PFAS problem is cyclical. Landfilling and wastewater treatment do not destroy PFAS and simply move PFAS loads between sites. Consumer products and various materials discarded in landfills leach PFAS over time, and landfill leachate is commonly sent to wastewater treatment plants. From wastewater treatment plants, PFAS are carried over to sludge and effluent. Sewage sludge can be landfilled, incinerated, or applied on agricultural fields, and PFAS from treated sludge (biosolids) can contaminate soil, water, and crops. Incineration of PFAS-containing wastes can emit harmful air pollutants, such as fluorinated greenhouse gases and products of incomplete combustion, and some PFAS may remain in the incinerator ash. Volatile PFAS are emitted into the air from landfills and wastewater treatment plants, and research is urgently needed on the potential presence of PFAS compounds in air emissions from commercially run incinerators. Monitoring of waste streams for PFAS, stopping PFAS discharges into water, soil and air and protecting the health of fence-line communities close to the waste disposal sites are essential to mitigate the impacts of PFAS pollution on human health.

Analysis of Cumulative Cancer Risk Associated with Disinfection Byproducts in United States Drinking Water.

Hundreds of different disinfection byproducts form in drinking water following necessary treatment with chlorine and other disinfectants, and many of those byproducts can damage DNA and increase the risk of cancer. This study offers the first side-by-side comparison of cancer risk assessments based on toxicological and epidemiological studies of disinfection byproducts using a comprehensive contaminant occurrence dataset for haloacetic acids and trihalomethanes, two groups of disinfection byproducts that are regulated in drinking water. We also provide the first analysis of a new occurrence dataset for unregulated haloacetic acids that became available from the latest, fourth round of the U.S. EPA-mandated unregulated contaminant monitoring program (UCMR4). A toxicological assessment indicated that haloacetic acids, and in particular brominated haloacetic acids, are more carcinogenic and are associated with a greater number of attributable cancer cases than trihalomethanes. Based on the toxicological analysis, cumulative lifetime cancer risk due to exposure to trihalomethanes and haloacetic acids for community water systems monitored under UCMR4, estimated with standard default parameters for body weight and water intake, corresponds to 7.0 × 10-5 (3.5 × 10-5-1.3 × 10-4). The same analysis conducted with age sensitivity factors to account for elevated risk in infants and children yielded a cumulative risk estimate of 2.9 × 10-4 (1.7 × 10-4-6.2 × 10-4). Epidemiological data suggest that lifetime cancer risk from disinfection byproducts for the U.S. population served by community water systems is approximately 3.0 × 10-3 (2.1 × 10-4-5.7 × 10-3), or a lifetime cancer risk of three cases per thousand people. Overall, this analysis highlights the value of using human data in health risk assessments to the greatest extent possible.

Preclinical Evaluation of Cetuximab and Benzoporphyrin Derivative-Mediated Intraperitoneal Photodynamic Therapy in a Canine Model.

Peritoneal carcinomatosis (PC) can occur as an advanced consequence of multiple primary malignancies. Surgical resection, radiation or systemic interventions alone have proven inadequate for this aggressive cancer presentation, since PC still has a poor survival profile. Photodynamic therapy (PDT), in which photosensitive drugs are exposed to light to generate cytotoxic reactive oxygen species, may be an ideal treatment for PC because of its ability to deliver treatment to a depth appropriate for peritoneal surface tumors. Additionally, epidermal growth factor receptor (EGFR) signaling plays a variety of roles in cancer progression and survival as well as PDT-mediated cytotoxicity, so EGFR inhibitors may be valuable in enhancing the therapeutic index of intraperitoneal PDT. This study examines escalating doses of benzoporphyrin derivative (BPD)-mediated intraperitoneal PDT combined with the EGFR-inhibitor cetuximab in a canine model. In the presence or absence of small bowel resection (SBR) and cetuximab, we observed a tolerable safety and toxicity profile related to the light dose received. Additionally, our findings that BPD levels are higher in the small bowel compared with other anatomical regions, and that the risk of anastomotic failure decreases at lower light doses will help to inform the design of similar PC treatments in humans.

Cumulative risk analysis of carcinogenic contaminants in United States drinking water.

Cumulative risk analysis of contaminant occurrence in United States drinking water for the period of 2010-2017 indicates that over 100,000 lifetime cancer cases could be due to carcinogenic chemicals in tap water. The majority of this risk is due to the presence of arsenic, disinfection byproducts and radioactive contaminants. For different states within the U.S., cumulative cancer risk for drinking water contaminants ranges between 1 × 10-4 and 1 × 10-3, similar to the range of cumulative cancer risks reported for air pollutants. Overall, national attributable risk due to tap water contaminants is approximately 4 × 10-4, which is two orders of magnitude higher than the de minimus cancer risk of one-in-a-million. Thus, decreasing the levels of chemical contaminants in drinking water represents an important opportunity for protecting public health.