An exploratory analysis of the impact of area-level exposome on geographic disparities in aggressive prostate cancer.

Numbers of aggressive prostate cancer (aPC) cases are rising, but only a few risk factors have been identified. In this study, we introduce a systematic approach to integrate geospatial data into external exposome research using aPC cases from Pennsylvania. We demonstrate the association between several area-level exposome measures across five Social Determinants of Health domains (SDOH) and geographic areas identified as having elevated odds of aPC. Residential locations of Pennsylvania men diagnosed with aPC from 2005 to 2017 were linked to 37 county-/tract-level SDOH exosome measures. Variable reduction processes adopted from neighborhood-wide association study along with Bayesian geoadditive logistic regression were used to identify areas with elevated odds of aPC and exposome factors that significantly attenuated the odds and reduced the size of identified areas. Areas with significantly higher odds of aPC were explained by various SDOH exposome measures, though the extent of the reduction depended on geographic location. Some areas were associated with race (social context), health insurance (access), or tract-level poverty (economics), while others were associated with either county-level water quality or a combination of factors. Area-level exposome measures can guide future patient-level external exposome research and help design targeted interventions to reduce local cancer burden.

Evaluating the Effects of Food Deserts and Food Swamps in an Urban Burn Patient Population.

Poverty is a known risk factor for burn injury and is associated with residency in food deserts and food swamps. Our aim was to determine the prevalence of residency in food deserts and food swamps and to investigate the relationship between food environment, comorbidities, and wound healing in burn patients. We performed a retrospective chart review of all burn patients age ≥ 18 seen in the emergency department or admitted to the burn service at an ABA-verified urban academic center between January 2016 and January 2022. Patient GeoIDs were used to classify residency in food deserts and food swamps and comorbidities and demographics were recorded. A subset of patients with less than 20% total body surface area burns who underwent single-operation split-thickness skin grafting was identified for wound healing analysis. A total of 3,063 patients were included, with 206 in the heal-time analysis. 2,490 (81.3%) lived in food swamps and 96 (3.1%) lived in food deserts. Diabetes, hypertension, and tobacco smoking were more prevalent in food swamps than food deserts or good access areas. While there was no significant effect of food environment on wound healing, diabetes was associated with longer heal times. Most burn patients reside in food swamps, which are associated with a higher prevalence of hypertension, diabetes, and smoking. Food environment was not significantly associated with wound healing. Not having diabetes was associated with a shorter time to wound healing.

Structural Basis for Multivalent MUC16 Recognition and Robust Anti-Pancreatic Cancer Activity of Humanized Antibody AR9.6.

Mucin-16 (MUC16) is a target for antibody-mediated immunotherapy in pancreatic ductal adenocarcinoma (PDAC) among other malignancies. The MUC16-specific monoclonal antibody AR9.6 has shown promise for PDAC immunotherapy and imaging. Here, we report the structural and biological characterization of the humanized AR9.6 antibody (huAR9.6). The structure of huAR9.6 was determined in complex with a MUC16 SEA (Sea urchin sperm, Enterokinase, Agrin) domain. Binding of huAR9.6 to recombinant, shed, and cell-surface MUC16 was characterized, and anti-PDAC activity was evaluated in vitro and in vivo. HuAR9.6 bound a discontinuous, SEA domain epitope with an overall affinity of 88 nmol/L. Binding affinity depended on the specific SEA domain(s) present, and glycosylation modestly enhanced affinity driven by favorable entropy and enthalpy and via distinct transition state thermodynamic pathways. Treatment with huAR9.6 reduced the in vitro growth, migration, invasion, and clonogenicity of MUC16-positive PDAC cells and patient-derived organoids (PDO). HuAR9.6 blocked MUC16-mediated ErbB and AKT activation in PDAC cells, PDOs, and patient-derived xenografts and induced antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity. More importantly, huAR9.6 treatment caused substantial PDAC regression in subcutaneous and orthotopic tumor models. The mechanism of action of huAR9.6 may depend on dense avid binding to homologous SEA domains on MUC16. The results of this study validate the translational therapeutic potential of huAR9.6 against MUC16-positive PDACs.

Capturing emergency dispatch address points as geocoding candidates to quantify delimited confidence in residential geolocation.

BACKGROUND: In response to citizens' concerns about elevated cancer incidence in their locales, US CDC proposed publishing cancer incidence at sub-county scales. At these scales, confidence in patients' residential geolocation becomes a key constraint of geospatial analysis. To support monitoring cancer incidence in sub-county areas, we presented summary metrics to numerically delimit confidence in residential geolocation. RESULTS: We defined a concept of Residential Address Discriminant Power (RADP) as theoretically perfect within all residential addresses and its practical application, i.e., using Emergency Dispatch (ED) Address Point Candidates of Equivalent Likelihood (CEL) to quantify Residential Geolocation Discriminant Power (RGDP) to approximate RADP. Leveraging different productivity of probabilistic, deterministic, and interactive geocoding record linkage, we simultaneously detected CEL for 5,807 cancer cases reported to North Carolina Central Cancer Registry (NC CCR)- in January 2022. Batch-match probabilistic and deterministic algorithms matched 86.0% cases to their unique ED address point candidates or a CEL, 4.4% to parcel site address, and 1.4% to street centerline. Interactively geocoded cases were 8.2%. To demonstrate differences in residential geolocation confidence between enumeration areas, we calculated sRGDP for cancer cases by county and assessed the existing uncertainty within the ED data, i.e., identified duplicate addresses (as CEL) for each ED address point in the 2014 version of the NC ED data and calculated ED_sRGDP by county. Both summary RGDP (sRGDP) (0.62-1.00) and ED_sRGDP (0.36-1.00) varied across counties and were lower in rural counties (p < 0.05); sRGDP correlated with ED_sRGDP (r = 0.42, p < 0.001). The discussion covered multiple conceptual and economic issues attendant to quantifying confidence in residential geolocation and presented a set of organizing principles for future work. CONCLUSIONS: Our methodology produces simple metrics - sRGDP - to capture confidence in residential geolocation via leveraging ED address points as CEL. Two facts demonstrate the usefulness of sRGDP as area-based summary metrics: sRGDP variability between counties and the overall lower quality of residential geolocation in rural vs. urban counties. Low sRGDP for the cancer cases within the area of interest helps manage expectations for the uncertainty in cancer incidence data. By supplementing cancer incidence data with sRGDP and ED_sRGDP, CCRs can demonstrate transparency in geocoding success, which may help win citizen trust.

Defining aggressive prostate cancer: a geospatial perspective.

BACKGROUND: Spatial analysis can identify communities where men are at risk for aggressive prostate cancer (PCan) and need intervention. However, there are several definitions for aggressive PCan. In this study, we evaluate geospatial patterns of 3 different aggressive PCan definitions in relation to PCan-specific mortality and provide methodologic and practical insights into how each definition may affect intervention targets. METHODS: Using the Pennsylvania State Cancer Registry data (2005-2015), we used 3 definitions to assign "aggressive" status to patients diagnosed with PCan. Definition one (D1, recently recommended as the primary definition, given high correlation with PCan death) was based on staging criteria T4/N1/M1 or Gleason score ≥ 8. Definition two (D2, most frequently-used definition in geospatial studies) included distant SEER summary stage. Definition three (D3) included Gleason score ≥ 7 only. Using Bayesian spatial models, we identified geographic clusters of elevated odds ratios for aggressive PCan (binomial model) for each definition and compared overlap between those clusters to clusters of elevated hazard ratios for PCan-specific mortality (Cox regression). RESULTS: The number of "aggressive" PCan cases varied by definition, and influenced quantity, location, and extent/size of geographic clusters in binomial models. While spatial patterns overlapped across all three definitions, using D2 in binomial models provided results most akin to PCan-specific mortality clusters as identified through Cox regression. This approach resulted in fewer clusters for targeted intervention and less sensitive to missing data compared to definitions that rely on clinical TNM staging. CONCLUSIONS: Using D2, based on distant SEER summary stage, in future research may facilitate consistency and allow for standardized comparison across geospatial studies.

Ethnic enclaves and colon cancer stage at diagnosis among New Jersey Hispanics.

Ethnic enclaves are neighborhoods with high concentrations of individuals of the same ethnic origin. Researchers have hypothesized that residence in ethnic enclaves may contribute to cancer outcomes through detrimental or protective pathways. A limitation of previous work, however, is their cross-sectional approach whereby an individual's residence at the time of diagnosis was used to capture residence in an ethnic enclave at a single point in time. This study addresses this limitation by adopting a longitudinal approach to investigating the association between the duration of residence in an ethnic enclave and the colon cancer (CC) stage at diagnosis. Colon cancer incidence cases diagnosed between 2006 and 2014, for Hispanics aged 18 years and older from the New Jersey State Cancer Registry (NJSCR) were linked to residential histories obtained from a commercial database LexisNexis, Inc. We examined associations between residence in an enclave and stage at diagnosis using binary and multinomial logistic regression, adjusted for age, sex, primary payer, and marital status. Among the 1076 Hispanics diagnosed with invasive colon cancer in New Jersey from 2006 to 2014, 48.4% lived in a Hispanic enclave at the time of diagnosis. Over the ten years preceding CC diagnosis, 32.6% lived in an enclave for the entire period. We found that Hispanics living in an ethnic enclave at diagnosis had significantly lower odds of distant-stage CC than Hispanics not living in an enclave at the time of diagnosis. Additionally, we found a significant association between living in an enclave for an extended period (e.g., over ten years) and lower odds of being diagnosed with distant stage CC. Integrating residential histories opens research possibilities to examine how minorities' residential mobility and residence in enclaves affect cancer diagnosis over time.

Disparities in geospatial patterns of cancer care within urban counties and structural inequities in access to oncology care.

OBJECTIVE: To examine geospatial patterns of cancer care utilization across diverse populations in New Jersey-a state where most residents live in urban areas. DATA SOURCES/STUDY SETTING: We used data from the New Jersey State Cancer Registry from 2012 to 2014. STUDY DESIGN: We examined the location of cancer treatment among patients 20-65 years of age diagnosed with breast, colorectal, or invasive cervical cancer and investigated differences in geospatial patterns of care by individual and area-level (e.g., census tract-level) characteristics. DATA COLLECTION/EXTRACTION METHODS: Multivariate generalized estimating equation models were used to determine factors associated with receiving cancer treatment within residential counties, residential hospital service areas, and in-state (versus out-of-state) care. PRINCIPAL FINDINGS: We observed significant differences in geospatial patterns of cancer treatment by race/ethnicity, insurance type, and area-level factors. Even after adjusting for tumor characteristics, insurance type, and other demographic factors, non-Hispanic Black patients had a 5.6% higher likelihood of receiving care within their own residential county compared to non-Hispanic White patients (95% CI: 2.80-8.41). Patients insured with Medicaid and those without insurance had higher likelihoods of receiving care within their residential county compared to privately insured individuals. Patients living in census tracts with the highest quintile of social vulnerability were 4.6% more likely to receive treatment within their residential county (95% CI: 0.00-9.30) and were 2.7% less likely to seek out-of-state care (95% CI: -4.85 to -0.61). CONCLUSIONS: Urban populations are not homogenous in their geospatial patterns of cancer care utilization, and individuals living in areas with greater social vulnerability may have limited opportunities to access care outside of their immediate residential county. Geographically tailored efforts, along with socioculturally tailored efforts, are needed to help improve equity in cancer care access.

Geographic diffusion of digital mammography in the United States.

BACKGROUND: Examining temporal and spatial diffusion of a new technology, such as digital mammography, can provide important insights into potential disparities associated with access to new medical technologies and how quickly these technologies are adopted. Although digital mammography is currently a standard technology in the United States for breast cancer screening, its adoption and geographic diffusion, as medical facilities transitioned from film to digital units, has not been explored well. METHODS: This study evaluated the geographic diffusion of digital mammography facilities from 2001 to 2014 in the contiguous United States (excluding Alaska and Hawaii) and estimated the geographic accessibility to this new technology for women aged ≥45 years at the census tract level within a 20-minute drivetime by population density, rural/urban residence, and race/ethnicity. The number of mammography units by technology type (film or digital) and density per 10,000 women were also summarized. RESULTS: The adoption of digital mammography advanced first in densely populated regions and last in remote rural areas. Overall, proportion of digital mammography units increased from 1.4% in 2001 to 94.6% in 2014, but since 2008, there was a decline in density of units from 2.31 per 10,000 women aged ≥45 years to 1.97 in 2014. In 2014, approximately 87% of women aged ≥45 years in the contiguous United States had accessibility to digital mammography, but this proportion was substantially lower for Native American women (67%) and rural residents (32%). CONCLUSION: Understanding the diffusion of and accessibility to digital mammography may help predict future medical technology diffusion and assess its role in geographic differences in cancer diagnosis and treatment.

Disparities in Cutaneous T-Cell Lymphoma Incidence by Race/Ethnicity and Area-Based Socioeconomic Status.

Cutaneous T-cell lymphoma (CTCL) is a rare type of extranodal non-Hodgkin lymphoma (NHL). This study uses population-based data from the New Jersey (NJ) State Cancer Registry to examine geographic variation in CTCL incidence and evaluates whether CTCL risk varies by race/ethnicity and census tract socioeconomic status (SES). The study included 1163 cases diagnosed in NJ between 2006 and 2014. Geographic variation and possible clustering of high CTCL rates were assessed using Bayesian geo-additive models. The associations between CTCL risk and race/ethnicity and census tract SES, measured as median household income, were examined using Poisson regression. CTCL incidence varied across NJ, but there were no statistically significant geographic clusters. After adjustment for age, sex, and race/ethnicity, the relative risk (RR) of CTCL was significantly higher (RR = 1.47, 95% confidence interval: 1.22-1.78) in the highest income quartile than in the lowest. The interactions between race/ethnicity and SES indicated that the income gradients by RR were evident in all groups. Compared to non-Hispanic White individuals in low-income tracts, CTCL risk was higher among non-Hispanic White individuals in high-income tracts and among non-Hispanic Black individuals in tracts of all income levels. Our findings suggest racial disparities and a strong socioeconomic gradient with higher CTCL risk among cases living in census tracts with higher income compared to those living in lower-income tracts.

Changes in geographic accessibility to mammography by state and rural-urban status, United States, 2006-2022.

Although mammography is widely available in the United States, differences in accessibility in rural and urban areas and changes over time are not well described. In this study, we estimated the number and proportion of women aged 45-84 years who had limited travel time-based geographic accessibility to mammography by urban-rural status and state in the contiguous United States in 2006 and 2022. The proportion of women aged 45-84 years with limited accessibility to mammography did not substantially change from 2006 (12.7%; representing 7.5 million women) to 2022 (12.2%; 8.2 million women). Accessibility to mammography varied by state, but in 10 states, more than 26% of the statewide female population aged 45-84 years had limited accessibility in 2022. This proportion was substantially higher in rural areas (50.6% overall; ≥50% in 28 states in 2022) than in urban areas (3.0% overall). Increasing accessibility to mammography could increase utilization of breast cancer screening and, potentially, improve breast cancer survival.

Geographical distribution, molecular and toxin diversity of the dinoflagellate species Gambierdiscus honu in the Pacific region.

An increase in cases of ciguatera poisoning (CP) and expansion of the causative species in the South Pacific region highlight the need for baseline data on toxic microalgal species to help identify new areas of risk and manage known hot spots. Gambierdiscus honu is a toxin producing and potential CP causing dinoflagellate species, first described in 2017. Currently no high-resolution geographical distribution, intraspecific genetic variation or toxin production diversity data is available for G. honu. This research aimed to further characterize G. honu by investigating its distribution using species-specific real-time polymerase chain reaction assays at 25 sites in an area spanning ∼8000 km of the Coral Sea/Pacific Ocean, and assessing intraspecific genetic variation, toxicity and toxin production of isolated strains. Assessment of genetic variation of the partial rRNA operon of isolates demonstrated no significant intraspecific population structure, in addition to a lack of adherence to isolation by distance (IBD) model of evolution. The detected distribution of G. honu in the Pacific region was within the expected tropical to temperate latitudinal ranges of 10° to -30° and extended from Australia to French Polynesia. In the lipophilic fractions, the neuroblastoma cell-based assay (CBA-N2a) showed no ciguatoxin (CTX)-like activity for nine of the 10 isolates, and an atypical pattern for CAWD233 isolate which showed cytotoxic activity in OV- and OV+ conditions. In the same way, liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis confirmed no Pacific-CTXs (CTX-3B, CTX-3C, CTX-4A, CTX-4B) were produced by the ten strains. The CBA-N2a assessment of the hydrophilic fractions showed moderate to high cytotoxicity in both OV- and OV+ condition for all the strains showing a cytotoxic profile similar to that of gambierone. Indeed, this study is the first to show the cytotoxic activity of gambierone on mouse neuroblastoma cells while no cytotoxicity was observed when 44-MG was analysed at the same concentrations using the CBA-N2a. Analysis of the hydrophilic via LC-MS/MS confirmed production of gambierone in all isolates, ranging from 2.1 to 38.1 pg/cell, with 44-methylgambierone (44-MG) also produced by eight of the isolates, ranging from 0.3 to 42.9 pg/cell. No maitotoxin-1 was detected in any of the isolates. Classification of the G. honu strains according to the quantities of gambierone produced aligned with the classification of their cytotoxicity using the CBA-N2a. Finally, no maitotoxin-1 (MTX) was detected in any of the isolates. This study shows G. honu is widely distributed within the Pacific region with no significant intraspecific population structure present. This aligns with the view of microalgal populations as global metapopulations, however more in-depth assessment with other genetic markers could detect further structure. Toxicity diversity across 10 isolates assessed did not display any geographical patterns.

Programmable Attenuation of Antigenic Sensitivity for a Nanobody-Based EGFR Chimeric Antigen Receptor Through Hinge Domain Truncation.

Epidermal growth factor family receptor (EGFR) is commonly overexpressed in many solid tumors and an attractive target for chimeric antigen receptor (CAR)-T therapy, but as EGFR is also expressed at lower levels in healthy tissues a therapeutic strategy must balance antigenic responsiveness against the risk of on-target off-tumor toxicity. Herein, we identify several camelid single-domain antibodies (also known as nanobodies) that are effective EGFR targeting moieties for CARs (EGFR-sdCARs) with very strong reactivity to EGFR-high and EGFR-low target cells. As a strategy to attenuate their potent antigenic sensitivity, we performed progressive truncation of the human CD8 hinge commonly used as a spacer domain in many CAR constructs. Single amino acid hinge-domain truncation progressively decreased both EGFR-sdCAR-Jurkat cell binding to EGFR-expressing targets and expression of the CD69 activation marker. Attenuated signaling in hinge-truncated EGFR-sdCAR constructs increased selectivity for antigen-dense EGFR-overexpressing cells over an EGFR-low tumor cell line or healthy donor derived EGFR-positive fibroblasts. We also provide evidence that epitope location is critical for determining hinge-domain requirement for CARs, as hinge truncation similarly decreased antigenic sensitivity of a membrane-proximal epitope targeting HER2-CAR but not a membrane-distal EGFRvIII-specific CAR. Hinge-modified EGFR-sdCAR cells showed clear functional attenuation in Jurkat-CAR-T cells and primary human CAR-T cells from multiple donors in vitro and in vivo. Overall, these results indicate that hinge length tuning provides a programmable strategy for throttling antigenic sensitivity in CARs targeting membrane-proximal epitopes, and could be employed for CAR-optimization and improved tumor selectivity.

Missed Vaccination Opportunities Among U.S. Adolescents by Area Characteristics.

INTRODUCTION: A total of 3 vaccines are recommended for U.S. adolescents: tetanus, diphtheria, and acellular pertussis; meningococcal conjugate; and human papillomavirus. To understand the disparities in vaccine availability and hesitancy, adolescent-, household-, and area-level characteristics associated with patterns of vaccine coverage are described. METHODS: In 2020-2021, the authors generated national estimates among 8 possible combinations of vaccine coverage and identified the associated characteristics using 2015-2017 National Immunization Survey-Teen for male and female adolescents aged 13-17 years (N=63,299) linked to area (ZIP code) characteristics. Next, the factors associated with a missed opportunity for human papillomavirus vaccine (i.e., receipt of tetanus, diphtheria, and acellular pertussis and meningococcal conjugate only compared with coverage of all the 3 vaccines) were identified using logistic regression. RESULTS: Most U.S. adolescents received all the 3 vaccines (42.9%) or tetanus, diphtheria, and acellular pertussis and meningococcal conjugate only (32.1%); fewer received no vaccines (7.7%) or tetanus, diphtheria, and acellular pertussis only (6.6%); and the remainder received some combination of 1-2 vaccines. Missed opportunities for human papillomavirus vaccination were more likely among adolescents who were male, were of White race, were uninsured, were in middle-income households, and were living in rural areas and were less likely among adolescents who were older, who were Medicaid insured, whose parents completed surveys in Spanish, who were in poverty-level households, and who were living in high-poverty areas. CONCLUSIONS: A substantial number of U.S. adolescents are not fully vaccinated, and coverage varies by vaccine type, population, and place. Providers should routinely stock all the 3 vaccines and promote simultaneous, same-day vaccination to avoid missed vaccine opportunities. More research and interventions are needed to understand and modify patient, provider, payer, vaccine supply/storage, or other reasons for suboptimal coverage of all the recommended vaccines.

Systematic review of neighborhood socioeconomic indices studied across the cancer control continuum.

BACKGROUND: There is extensive interest in understanding how neighborhood socioeconomic status (nSES) may affect cancer incidence or survival. However, variability regarding items included and approaches used to form a composite nSES index presents challenges in summarizing overall associations with cancer. Given recent calls for standardized measures of neighborhood sociodemographic effects in cancer disparity research, the objective of this systematic review was to identify and compare existing nSES indices studied across the cancer continuum (incidence, screening, diagnosis, treatment, survival/mortality) and summarize associations by race/ethnicity and cancer site to inform future cancer disparity studies. METHODS: Using PRISMA guidelines, peer-reviewed articles published between 2010 and 2019 containing keywords related to nSES and cancer were identified in PubMed. RESULTS: Twenty-four nSES indices were identified from 75 studies. In general, findings indicated a significant association between nSES and cancer outcomes (n = 64/75 studies; 85.33%), with 42/64 (65.63%) adjusting for highly-correlated individual SES factors (e.g., education). However, the direction of association differed by cancer site, race/ethnicity, and nSES index. CONCLUSIONS: This review highlights several methodologic and conceptual issues surrounding nSES measurement and potential associations with cancer disparities. Recommendations pertaining to the selection of nSES measures are provided, which may help inform disparity-related disease processes and improve the identification of vulnerable populations in need of intervention.

Examining socio-spatial mobility patterns among colon cancer patients after diagnosis.

Given the growing number of cancer survivors, it is important to better understand socio-spatial mobility patterns of cancer patients after diagnosis that could have public health implications regarding post-diagnostic access to care for treatment and follow-up surveillance. In this exploratory study, residential histories from LexisNexis were linked to New Jersey colon cancer cases diagnosed from 2006 to 2011 to examine differences in socio-spatial mobility patterns after diagnosis by stage at cancer diagnosis, sex, and race/ethnicity. For the colon cancer cases, we summarized and compared the number of residences and changes in the residential census tract and neighborhood poverty after the diagnosis. We found only minor changes in neighborhood poverty among the cases during the follow-up period after diagnosis. During the follow-up period of up to 10 years after diagnosis, 67% of the patients did not move to a different residential census tract, and 10.8% moved from New Jersey to another state. Cases that moved to a different census tract changed after diagnosis were generally less wealthy than non-movers, but the destination of relocation varied by race/ethnicity and socioeconomic status. We also found a significant association between residential mobility and stage at diagnosis, whereby patients diagnosed with colon cancer at an early stage were more likely to be movers. This study contributes to understanding of the socio-spatial mobility patterns in colon cancer patients and may help to inform cancer research by summarizing the extent to which colon cancer patients move after diagnosis.

Geographic clustering of cutaneous T-cell lymphoma in New Jersey: an exploratory analysis using residential histories.

PURPOSE: Cutaneous T-cell lymphoma (CTCL) is a rare type of non-Hodgkin lymphoma. Previous studies have reported geographic clustering of CTCL based on the residence at the time of diagnosis. We explore geographic clustering of CTCL using both the residence at the time of diagnosis and past residences using data from the New Jersey State Cancer Registry. METHODS: CTCL cases (n = 1,163) diagnosed between 2006-2014 were matched to colon cancer controls (n = 17,049) on sex, age, race/ethnicity, and birth year. Jacquez's Q-Statistic was used to identify temporal clustering of cases compared to controls. Geographic clustering was assessed using the Bernoulli-based scan-statistic to compare cases to controls, and the Poisson-based scan-statisic to compare the observed number of cases to the number expected based on the general population. Significant clusters (p < 0.05) were mapped, and standard incidence ratios (SIR) reported. We adjusted for diagnosis year, sex, and age. RESULTS: The Q-statistic identified significant temporal clustering of cases based on past residences in the study area from 1992 to 2002. A cluster was detected in 1992 in Bergen County in northern New Jersey based on the Bernoulli (1992 SIR 1.84) and Poisson (1992 SIR 1.86) scan-statistics. Using the Poisson scan-statistic with the diagnosis location, we found evidence of an elevated risk in this same area, but the results were not statistically significant. CONCLUSION: There is evidence of geographic clustering of CTCL cases in New Jersey based on past residences. Additional studies are necessary to understand the possible reasons for the excess of CTCL cases living in this specific area some 8-14 years prior to diagnosis.

Attribute Associations as a Practical Approach to Account for Uncertainty in Residential Geolocation of Cancer Surveillance Data.

This methodology article proposes a basic framework for assessing confidence in residential address through attribute sets of the tumor record that enable or modify spatiotemporal relationships in cancer surveillance data. A first step in assessing confidence for a statutory downstream data steward, like the Central Cancer Registry (CCR), is identifying sets of attributes whose domains are independently controlled by data stewards outside of the CCR. These include attribute sets that comprise the digital entities of person, time, and place. In this article, we describe the uncertainty in the geolocation of a cancer patient at the time of diagnosis, focusing on multiple stewardship of the cancer surveillance data. We also propose an approach to account for this uncertainty that is practical within the framework of existing cancer registry data coding, processing conventions, and legislative mandates for cancer surveillance.

Biparatopic single-domain antibodies against Axl achieve ultra-high affinity through intramolecular engagement.

Overexpression of Axl, a TAM-family receptor tyrosine kinase, plays key roles in the formation, growth, and spread of tumors as well as resistance to targeted therapies and chemotherapies. We identified novel llama VHHs against human Axl using multiple complementary phage display selection strategies and characterized a subset of high-affinity VHHs. The VHHs targeted multiple sites in Ig-like domains 1 and 2 of the Axl extracellular domain, including an immunodominant epitope overlapping the site of Gas6 interaction and two additional non-Gas6 competitive epitopes recognized by murine monoclonal antibodies. Only a subset of VHHs cross-reacted with cynomolgus monkey Axl and none recognized mouse Axl. As fusions to human IgG1 Fc, VHH-Fcs bound Axl+ tumor cell lines and mertansine-loaded VHH-Fcs were cytotoxic in vitro against Axl+ cells in proportion to their binding affinities. Engineered biparatopic VHH-VHH heterodimers bound Axl avidly, and a subset of molecules showed dramatically enhanced association rates indicative of intramolecular binding. These VHHs may have applications as modular elements of biologic drugs such as antibody-drug conjugates.

Measuring Neighborhood Landscapes: Associations between a Neighborhood's Landscape Characteristics and Colon Cancer Survival.

Landscape characteristics have been shown to influence health outcomes, but few studies have examined their relationship with cancer survival. We used data from the National Land Cover Database to examine associations between regional-stage colon cancer survival and 27 different landscape metrics. The study population included all adult New Jersey residents diagnosed between 2006 and 2011. Cases were followed until 31 December 2016 (N = 3949). Patient data were derived from the New Jersey State Cancer Registry and were linked to LexisNexis to obtain residential histories. Cox proportional hazard regression was used to estimate hazard ratios (HR) and 95% confidence intervals (CI95) for the different landscape metrics. An increasing proportion of high-intensity developed lands with 80-100% impervious surfaces per cell/pixel was significantly associated with the risk of colon cancer death (HR = 1.006; CI95 = 1.002-1.01) after controlling for neighborhood poverty and other individual-level factors. In contrast, an increase in the aggregation and connectivity of vegetation-dominated low-intensity developed lands with 20-<40% impervious surfaces per cell/pixel was significantly associated with the decrease in risk of death from colon cancer (HR = 0.996; CI95 = 0.992-0.999). Reducing impervious surfaces in residential areas may increase the aesthetic value and provide conditions more advantageous to a healthy lifestyle, such as walking. Further research is needed to understand how these landscape characteristics impact survival.