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Background: Limited research has been conducted on cancer-related emergency department (ED) patterns among pediatric cancer patients, including whether there are differences in the characteristics of individuals who seek ED care for cancer complications. The objectives of this study were to determine whether rates and disposition of cancer-related ED visits and hospital admissions in childhood cancer patients differ by sociodemographic factors., Methods: A cross-sectional analysis of ED encounters with a cancer diagnosis code among patients aged 0-19 years from the 2019 National Emergency Department Sample (NEDS) was conducted. Weighted logistic regression models were utilized to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for a primary cancer-related encounter, and hospital admission overall and by subgroup characteristics., Results: Of the unweighted 6,801,711 ED encounters in children aged 0-19 years, 10,793 were classified as visits by cancer patients. ED encounters of Hispanic versus non-Hispanic White pediatric cancer patients had higher odds of having a cancer-related primary diagnosis (OR = 1.15, 95% CI: 1.04-1.27). ED encounters of non-Hispanic Black pediatric patients and those in the lowest zip code income quartile had higher odds of hospital admission (OR = 1.28, 95% CI: 1.08-1.53; OR = 1.30, 95% CI: 1.15-1.46), while rurality was associated with lower odds of hospital admission (OR = 0.69, 95% CI: 0.57-0.83)., Conclusion: These results suggest that pediatric cancer patients from certain under-resourced communities are more likely to use the ED for cancer treatment complications, and their encounters are more likely to result in admission to the hospital., (© 2023 Wiley Periodicals LLC.)

Importance: Social determinants of health contribute to disparities in cancer outcomes. State public assistance spending, including Medicaid and cash assistance programs for socioeconomically disadvantaged individuals, may improve access to care; address barriers, such as food and housing insecurity; and lead to improved cancer outcomes for marginalized populations., Objective: To determine whether state-level public assistance spending is associated with overall survival (OS) among individuals with cancer, overall and by race and ethnicity., Design, Setting, and Participants: This cohort study included US adults aged at least 18 years with a new cancer diagnosis from 2007 to 2013, with follow-up through 2019. Data were obtained from the Surveillance, Epidemiology, and End Results program. Data were analyzed from November 18, 2021, to July 6, 2023., Exposure: Differential state-level public assistance spending., Main Outcome and Measure: The main outcome was 6-year OS. Analyses were adjusted for age, race, ethnicity, sex, metropolitan residence, county-level income, state fixed effects, state-level percentages of residents living in poverty and aged 65 years or older, cancer type, and cancer stage., Results: A total 2 035 977 individuals with cancer were identified and included in analysis, with 1 005 702 individuals (49.4%) aged 65 years or older and 1 026 309 (50.4%) male. By tertile of public assistance spending, 6-year OS was 55.9% for the lowest tertile, 55.9% for the middle tertile, and 56.6% for the highest tertile. In adjusted analyses, public assistance spending at the state-level was significantly associated with higher 6-year OS (0.09% [95% CI, 0.04%-0.13%] per $100 per capita; P < .001), particularly for non-Hispanic Black individuals (0.29% [95% CI, 0.07%-0.52%] per $100 per capita; P = .01) and non-Hispanic White individuals (0.12% [95% CI, 0.08%-0.16%] per $100 per capita; P < .001). In sensitivity analyses examining the roles of Medicaid spending and Medicaid expansion including additional years of data, non-Medicaid spending was associated with higher 3-year OS among non-Hispanic Black individuals (0.49% [95% CI, 0.26%-0.72%] per $100 per capita when accounting for Medicaid spending; 0.17% [95% CI, 0.02%-0.31%] per $100 per capita Medicaid expansion effects)., Conclusions and Relevance: This cohort study found that state public assistance expenditures, including cash assistance programs and Medicaid, were associated with improved survival for individuals with cancer. State investment in public assistance programs may represent an important avenue to improve cancer outcomes through addressing social determinants of health and should be a topic of further investigation.

Background: Medicaid expansion is associated with improved survival following cancer diagnosis. However, little research has assessed how changes in cancer stage may mediate improved cancer mortality or how expansion may have decreased population-level cancer mortality rates., Methods: Nationwide state-level cancer data from 2001 to 2019 for individuals ages 20-64 years were obtained from the combined Surveillance, Epidemiology, and End Results National Program of Cancer Registries (incidence) and the National Center for Health Statistics (mortality) databases. We estimated changes in distant stage cancer incidence and cancer mortality rates from pre- to post-2014 in expansion vs nonexpansion states using generalized estimating equations with robust standard errors. Mediation analyses were used to assess whether distant stage cancer incidence mediated changes in cancer mortality., Results: There were 17 370 state-level observations. For all cancers combined, there were Medicaid expansion-associated decreases in distant stage cancer incidence (adjusted odds ratio = 0.967, 95% confidence interval  = 0.943 to 0.992; P = .01) and cancer mortality (adjusted odds ratio = 0.965, 95% confidence interval = 0.936 to 0.995; P = .022). This translates to 2591 averted distant stage cancer diagnoses and 1616 averted cancer deaths in the Medicaid expansion states. Distant stage cancer incidence mediated 58.4% of expansion-associated changes in cancer mortality overall (P = .008). By cancer site subgroups, there were expansion-associated decreases in breast, cervix, and liver cancer mortality., Conclusions: Medicaid expansion was associated with decreased distant stage cancer incidence and cancer mortality. Approximately 60% of the expansion-associated changes in cancer mortality overall were mediated by distant stage diagnoses., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Studies examining individual-level changes in protective behaviors over time in association with community-level infection and self or close-contact infection with SARS-CoV-2 are limited. We analyzed overall and demographic specific week-to-week changes in COVID-19 protective behaviors and their association with COVID-19 infections (regional case counts and self or close contacts). Data were collected through 37 consecutive weekly surveys from 10/17/2021 - 6/26/2022. Our survey panel included 212 individuals living or working in St. Louis City and County, Missouri, U.S.A. Frequency of mask-wearing, handwashing, physical distancing, and avoiding large gatherings was self-reported (more/the same/less than the prior week). Close contact with COVID-19 was reported if the panel member, their household member, or their close contact tested positive, got sick, or was hospitalized for COVID-19 in the prior week. Regional weekly COVID-19 case counts were matched to the closest survey administration date. We used generalized linear mixed models to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for associations. Evidence for effect modification was assessed using the likelihood ratio test. Increased protective behaviors were positively associated with COVID-19 case counts (OR highest vs. lowest case count category  = 4.39, 95% CI 3.35-5.74) and with participant-reported self or close contacts with COVID-19 (OR = 5.10, 95% CI 3.88-6.70). Stronger associations were found for White vs. Black panel members (p <.0001). Individuals modulated their protective behaviors in association with regional COVID-19 case counts and self or close contact infection. Rapid reporting and widespread public awareness of infectious disease rates may help reduce transmission during a pandemic by increasing protective behaviors., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 Published by Elsevier Inc.)

Background: Although treatment advances have increased childhood and adolescent cancer survival, whether patient subgroups have benefited equally from these improvements is unclear., Methods: Data on 42,865 malignant primary cancers diagnosed between 1995 and 2019 in individuals ≤ 19 years were obtained from 12 Surveillance, Epidemiology, and End Results registries. Hazard ratios (HRs) and 95 % confidence intervals (CIs) for cancer-specific mortality by age group (0-14 and 15-19 years), sex, and race/ethnicity were estimated using flexible parametric models with a restricted cubic spline function in each of the periods: 2000-2004, 2005-2009, 2010-2014 and 2015-2019, versus 1995-1999. Interactions between diagnosis period and age group (children 0-14 and adolescents 15-19 years at diagnosis), sex, and race/ethnicity were assessed using likelihood ratio tests. Five-year cancer-specific survival rates for each diagnosis period were further predicted., Results: Compared with the 1995-1999 cohort, the risk of dying from all cancers combined decreased in subgroups defined by age, sex and race/ethnicity with HRs ranging from 0.50 to 0.68 for the 2015-2019 comparison. HRs were more variable by cancer subtype. There were no statistically significant interactions by age group (P interaction =0.05) or sex (P interaction =0.71). Despite non-significant differences in cancer-specific survival improvement across different races and ethnicities (P interaction =0.33) over the study period, minorities consistently experienced inferior survival compared with non-Hispanic Whites., Conclusions: The substantial improvements in cancer-specific survival for childhood and adolescent cancer did not differ significantly by different age, sex, and race/ethnicity groups. However, persistent gaps in survival between minorities and non-Hispanic Whites are noteworthy., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Objective: To evaluate potential effect modification by health insurance coverage on racial and ethnic disparities in cancer survival among US children and adolescents., Study Design: Data from 54 558 individuals diagnosed with cancer at ≤ 19 years between 2004 and 2010 were obtained from the National Cancer Database. Cox proportional hazards regression was used for analyses. An interaction term between race/ethnicity and health insurance type was included to examine racial/ethnic disparities in survival by each insurance status category., Results: Racial/ethnic minorities experienced a 14%-42% higher hazard of death compared with non-Hispanic Whites (NHWs) with magnitudes varying by health insurance type (P interaction < .001). Specifically, among those reported as privately insured, the hazard of death was higher for non-Hispanic Blacks (NHBs) (hazard ratio [HR] = 1.48, 95% CI: 1.36-1.62), non-Hispanic American Indian/Alaskan Natives (HR = 1.99, 95% CI: 1.36-2.90), non-Hispanic Asians or Pacific Islanders (HR = 1.30, 95% CI: 1.13-1.50), and Hispanics (HR = 1.28, 95% CI: 1.17-1.40) vs NHWs. Racial/ethnic disparities in survival among those reported as covered by Medicaid were present for NHBs (HR = 1.30, 95% CI: 1.19-1.43) but no other racial/ethnic minorities (HR ranges: 0.98∼1.00) vs NHWs. In the uninsured group, the hazard of death for NHBs (HR = 1.68, 95% CI: 1.26-2.23) and Hispanics (HR = 1.27, 95% CI: 1.01-1.61) was higher vs NHWs., Conclusions: Disparities in survival exist across insurance types, particularly for NHB childhood and adolescent cancer patients vs NHWs with private insurance. These findings provide insights for research and policy, and point to the need for more efforts on promoting health equity while improving health insurance coverage., (Copyright © 2023 Elsevier Inc. All rights reserved.)

We describe the MalariaGEN Pf7 data resource, the seventh release of Plasmodium falciparum genome variation data from the MalariaGEN network.  It comprises over 20,000 samples from 82 partner studies in 33 countries, including several malaria endemic regions that were previously underrepresented.  For the first time we include dried blood spot samples that were sequenced after selective whole genome amplification, necessitating new methods to genotype copy number variations.  We identify a large number of newly emerging crt mutations in parts of Southeast Asia, and show examples of heterogeneities in patterns of drug resistance within Africa and within the Indian subcontinent.  We describe the profile of variations in the C-terminal of the csp gene and relate this to the sequence used in the RTS,S and R21 malaria vaccines.  Pf7 provides high-quality data on genotype calls for 6 million SNPs and short indels, analysis of large deletions that cause failure of rapid diagnostic tests, and systematic characterisation of six major drug resistance loci, all of which can be freely downloaded from the MalariaGEN website., Competing Interests: No competing interests were disclosed., (Copyright: © 2023 MalariaGEN et al.)

Purpose: Prior research indicates that the volume of central nervous system (CNS) tumor patients seen by a facility is associated with outcomes. However, most studies have focused on short-term survival and specific CNS tumor subtypes. Our objective was to examine whether facility CNS tumor patient volume is associated with longer-term CNS tumor survival overall and by subtype., Methods: We obtained National Cancer Database (NCDB) data including individuals diagnosed with CNS tumors from 2004 to 2016. Analyses were stratified by age group (0-14, 15-39, 40-64, and ≥ 65 years) and tumor type. We used Cox Proportional Hazards (PH) regression and restricted mean survival time (RMST) analyses to examine associations between survival and facility patient volume percentile category adjusting for potential confounding factors., Results: Our analytic dataset included data from 130,830 individuals diagnosed with malignant first primary CNS tumors. We found a consistently reduced hazard rate of death across age groups for individuals reported by higher vs. lower (> 95th vs. ≤ 70th percentile) volume facilities (hazard ratio (HR) 0-14  = 0.78, 95% confidence interval (CI) 0.64-0.95; HR 15-39  = 0.87, 95% CI 0.78-0.96; HR 40-64  = 0.82, 95% CI 0.76-0.88; HR ≥65  = 0.80, 95% CI 0.75-0.86). Significantly longer survival times within 5 years for higher vs. lower volume facilities were observed ranging from 1.20 months (15-39) to 3.08 months (40-64) higher. Associations varied by CNS tumor subtype for all age groups., Conclusions: These results suggest facility factors influence CNS tumor survival with longer survival for patients reported by higher volume facilities. Understanding these factors will be critical to developing strategies that eliminate modifiable differences in survival times., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Youth living with HIV (YLWHIV) have an increased cancer risk. Our objective is to describe the prevalence of medical record (MR) reported suspected cancers in a contemporary cohort of YLWHIV in Uganda that was assembled through MR reviews of patients 10 to 24 years old across 35 Ugandan HIV care health facilities. Clinical data were abstracted to identify suspected cancer cases and information about HIV care. Among 3728 YLWHIV, we identified eight suspected cancer cases. The most common suspected types were Kaposi sarcoma (n=4) followed by lymphoma (n=3). Challenges encountered in data abstraction were missing data for several variables and confirmatory cancer diagnostic information. In follow-up of suspected cases referred for diagnosis at the Uganda Cancer Institute (UCI), none had diagnosis records in UCI files. In addition, ∼18% of patients (n=686) were lost-to-follow-up (LTF) defined as not having returned to the clinic in ≥183 days and three patients died from presumed Kaposi sarcoma. Although our results suggest that cancer is rare in YLWHIV, the possibility that the cancer burden is higher cannot be excluded due to incomplete information in MRs and high LTF rates. Further, our study raises concern that patients referred for diagnosis are not accessing potential life-saving care.

Introduction: Applying an intersectional framework, we examined sex and racial inequality in COVID-19-related employment loss (ie, job furlough, layoff, and reduced pay) and food insecurity (ie, quality and quantity of food eaten, food worry, and receipt of free meals or groceries) among residents in Saint Louis County, Missouri., Methods: We used cross-sectional data from adults aged 18 or older (N = 2,146), surveyed by using landlines or cellular phones between August 12, 2020, and October 27, 2020. We calculated survey-weighted prevalence of employment loss and food insecurity for each group (Black female, Black male, White female, White male). Odds ratios for each group were estimated by using survey-weighted binary and multinomial logistic regression models., Results: Black female residents had higher odds of being laid off, as compared with White male residents (OR = 2.61, 95% CI, 1.24-5.46). Both Black female residents (OR = 4.13, 95% CI, 2.29-7.45) and Black male residents (OR = 2.41, 95% CI, 1.15-5.07) were more likely to receive free groceries, compared with White male residents. Black female (OR = 4.25, 95% CI, 2.28-7.94) and White female residents (OR = 1.93, 95% CI, 1.04-3.60) had higher odds of sometimes worrying about food compared with White male residents. Black women also had higher odds of always or nearly always worrying about food, compared with White men (OR = 2.99, 95% CI, 1.52-5.87)., Conclusion: Black women faced the highest odds of employment loss and food insecurity, highlighting the disproportionate impact of COVID-19 among people with intersectional disadvantages of being both Black and female. Interventions to reduce employment loss and food insecurity can help reduce the disproportionately negative social effects among Black women.

Objectives: The coronavirus disease of 2019 (COVID-19) pandemic declared by the World Health Organization on March 11, 2020 impacted healthcare services with provider and patient cancellations, delays, and patient avoidance or delay of emergency department or urgent care. Limited data exist on the population proportion affected by delayed healthcare, which is important for future healthcare planning efforts. Our objective was to evaluate the impact of the COVID-19 pandemic on healthcare service cancellations or delays and delays/avoidance of emergency/urgent care overall and by population characteristics., Study Design: This was a cross-sectional study., Methods: Our sample (n = 2314) was assembled through a phone survey from 8/12/2020-10/27/2020 among non-institutionalized St. Louis County, Missouri, USA residents ≥18 years. We asked about provider and patient-initiated cancellations or delays of appointments and pandemic-associated delays/avoidance of emergency/urgent care overall and by participant characteristics. We calculated weighted prevalence estimates by select resident characteristics., Results: Healthcare services cancellations or delays affected ∼54% (95% CI 50.6%-57.1%) of residents with dental (31.1%, 95% CI 28.1%-34.0%) and primary care (22.1%, 95% CI 19.5%-24.6%) being most common. The highest prevalences were among those who were White, ≥65 years old, female, in fair/poor health, who had health insurance, and who had ≥1 medical condition. Delayed or avoided emergency/urgent care impacted ∼23% (95% CI 19.9%-25.4%) of residents with a higher prevalence in females than males., Conclusions: Healthcare use disruptions impacted a substantial proportion of residents. Future healthcare planning efforts should consider these data to minimize potential morbidity and mortality from delayed care., (© 2022 The Author(s).)

This report describes the MalariaGEN Pv4 dataset, a new release of curated genome variation data on 1,895 samples of Plasmodium vivax collected at 88 worldwide locations between 2001 and 2017. It includes 1,370 new samples contributed by MalariaGEN and VivaxGEN partner studies in addition to previously published samples from these and other sources. We provide genotype calls at over 4.5 million variable positions including over 3 million single nucleotide polymorphisms (SNPs), as well as short indels and tandem duplications. This enlarged dataset highlights major compartments of parasite population structure, with clear differentiation between Africa, Latin America, Oceania, Western Asia and different parts of Southeast Asia. Each sample has been classified for drug resistance to sulfadoxine, pyrimethamine and mefloquine based on known markers at the dhfr , dhps and mdr1 loci. The prevalence of all of these resistance markers was much higher in Southeast Asia and Oceania than elsewhere. This open resource of analysis-ready genome variation data from the MalariaGEN and VivaxGEN networks is driven by our collective goal to advance research into the complex biology of P. vivax and to accelerate genomic surveillance for malaria control and elimination., Competing Interests: No competing interests were disclosed., (Copyright: © 2022 MalariaGEN et al.)

Controlled human malaria infection (CHMI) provides a highly informative means to investigate host-pathogen interactions and enable in vivo proof-of-concept efficacy testing of new drugs and vaccines. However, unlike Plasmodium falciparum, well-characterized P. vivax parasites that are safe and suitable for use in modern CHMI models are limited. Here, 2 healthy malaria-naive United Kingdom adults with universal donor blood group were safely infected with a clone of P. vivax from Thailand by mosquito-bite CHMI. Parasitemia developed in both volunteers, and prior to treatment, each volunteer donated blood to produce a cryopreserved stabilate of infected RBCs. Following stringent safety screening, the parasite stabilate from one of these donors (PvW1) was thawed and used to inoculate 6 healthy malaria-naive United Kingdom adults by blood-stage CHMI, at 3 different dilutions. Parasitemia developed in all volunteers, who were then successfully drug treated. PvW1 parasite DNA was isolated and sequenced to produce a high-quality genome assembly by using a hybrid assembly method. We analyzed leading vaccine candidate antigens and multigene families, including the vivax interspersed repeat (VIR) genes, of which we identified 1145 in the PvW1 genome. Our genomic analysis will guide future assessment of candidate vaccines and drugs, as well as experimental medicine studies.

Purpose: Prior research shows that residential distance to a treatment facility may be an important factor in central nervous system (CNS) tumor outcomes. Our goal was to examine residential distance to the reporting hospital and overall survival in adolescents and young adults (AYA) diagnosed with CNS tumors., Methods: National Cancer Database data on AYA 15-39 years old diagnosed with CNS and Other Intracranial and Intraspinal Neoplasms (CNS tumors) from 2010 to 2014 were obtained. Distance between the case's residence at diagnosis or initial treatment and the reporting hospital was classified in miles as short (≤ 12.5), intermediate (> 12.5 and < 50), and long (≥ 50). Cox proportional hazards regression models were used for analyses., Results: Among 9335 AYA diagnosed with CNS tumors, hazard ratios (HRs) were 1.06 (95% CI 0.96-1.17) and 0.82 (95% CI 0.73-0.93) for those with residences at intermediate and long vs. short distances, respectively, after adjusting for age, sex, race/ethnicity, and zip-code level education and income. After adjusting for the facility volume of CNS tumor patients, the association was attenuated for long vs. short distance residences (HR 0.92, 95% CI 0.81-1.04). The HRs varied by tumor type, race/ethnicity, and zip-code level income with significantly lower hazards of death for those with residences at long vs. short distances for low-grade astrocytic tumors, ependymomas, non-Hispanic Whites, and those from higher-income areas., Conclusions: Living at long distances for CNS tumor care may be associated with better survival in AYA patients. This may be explained by travel to facilities with more experience treating CNS tumors., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Although Medicaid expansion is associated with decreased uninsured rates and earlier cancer diagnoses, no study has demonstrated an association between Medicaid expansion and cancer mortality. Our primary objective was to quantify the relationship between early Medicaid expansion and changes in cancer mortality rates., Methods: We obtained county-level data from the National Center for Health Statistics for adults aged 20-64 years who died from cancer from 2007 to 2009 (preexpansion) and 2012 to 2016 (postexpansion). We compared changes in cancer mortality rates in early Medicaid expansion states (CA, CT, DC, MN, NJ, and WA) vs nonexpansion states through a difference-in-differences analysis using hierarchical Bayesian regression. An exploratory analysis of cancer mortality changes associated with the larger-scale 2014 Medicaid expansions was also performed., Results: In adjusted difference-in-differences analyses, we observed a statistically significant decrease of 3.07 (95% credible interval = 2.19 to 3.95) cancer deaths per 100 000 in early expansion vs nonexpansion states, which translates to an estimated decrease of 5276 cancer deaths in the early expansion states during the study period. Expansion-associated decreases in cancer mortality were observed for pancreatic cancer. Exploratory analyses of the 2014 Medicaid expansions showed a decrease in pancreatic cancer mortality (-0.18 deaths per 100 000, 95% confidence interval = -0.32 to -0.05) in states that expanded Medicaid by 2014 compared with nonexpansion states., Conclusions: Early Medicaid expansion was associated with reduced cancer mortality rates, especially for pancreatic cancer, a cancer with short median survival where changes in prognosis would be most visible with limited follow-up., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Multiple studies have indicated that place of residence can influence cancer survival; however, few studies have specifically focused on geographic factors and outcomes in adolescents and young adults (AYAs) with cancer. The objective of this study was to evaluate evidence for geographic disparities in cancer diagnosis stage and overall survival in AYAs and to examine whether stage mediated survival associations., Methods: National Cancer Database data on AYAs aged 15 to 39 years who were diagnosed with cancer from 2010 to 2014 were obtained. Residence in Metropolitan (metro), urban, or rural counties at the time of diagnosis was defined using Rural-Urban Continuum Codes. Distance between the patient's residence and the reporting hospital was classified as short (≤2.5 miles), intermediate (>12.5 to <50 miles), or long (≥50 miles). Logistic and Cox proportional hazards regression models were used for analyses., Results: The stage and survival analyses included 146,418 and 178,688 AYAs, respectively. The odds of a late versus early stage at diagnosis (stages III and IV vs I and II) were 1.16 (95% CI, 1.05-1.29) times greater for AYAs living in rural versus metro counties and 1.20 (95% CI, 1.16-1.25) times greater for AYAs living at long versus short distances to the reporting hospital. The hazard of death was 1.17 (95% CI, 1.05-1.31) and 1.30 (95% CI, 1.25-1.36) times greater for those living in rural versus metro counties, respectively, and for long versus short distances to the reporting hospital, respectively. Disease stage mediated 54% and 31% of the associations between metro, urban, or rural residence and residential distance categories and survival., Conclusions: Rural residence and living long distances from the reporting hospital were associated with later stage diagnoses and lower survival in AYAs with cancer. Further research is needed to understand mechanisms., Lay Summary: Adolescents and young adults (AYAs) with cancer are a vulnerable population because cancer is of low suspicion in this population and may not be diagnosed in a timely manner. The authors evaluated evidence for geographic disparities in cancer stage at diagnosis and survival in the AYA population. The findings indicate that AYAs living in rural versus metropolitan US counties and those living farther from the diagnosis reporting hospital are more likely to be diagnosed at a later cancer stage, when it is generally less treatable, and have lower survival compared with AYAs living in metropolitan counties., (© 2021 American Cancer Society.)

Background: National Malaria Control Programmes (NMCPs) currently make limited use of parasite genetic data. We have developed GenRe-Mekong, a platform for genetic surveillance of malaria in the Greater Mekong Subregion (GMS) that enables NMCPs to implement large-scale surveillance projects by integrating simple sample collection procedures in routine public health procedures., Methods: Samples from symptomatic patients are processed by SpotMalaria, a high-throughput system that produces a comprehensive set of genotypes comprising several drug resistance markers, species markers and a genomic barcode. GenRe-Mekong delivers Genetic Report Cards, a compendium of genotypes and phenotype predictions used to map prevalence of resistance to multiple drugs., Results: GenRe-Mekong has worked with NMCPs and research projects in eight countries, processing 9623 samples from clinical cases. Monitoring resistance markers has been valuable for tracking the rapid spread of parasites resistant to the dihydroartemisinin-piperaquine combination therapy. In Vietnam and Laos, GenRe-Mekong data have provided novel knowledge about the spread of these resistant strains into previously unaffected provinces, informing decision-making by NMCPs., Conclusions: GenRe-Mekong provides detailed knowledge about drug resistance at a local level, and facilitates data sharing at a regional level, enabling cross-border resistance monitoring and providing the public health community with valuable insights. The project provides a rich open data resource to benefit the entire malaria community., Funding: The GenRe-Mekong project is funded by the Bill and Melinda Gates Foundation (OPP11188166, OPP1204268). Genotyping and sequencing were funded by the Wellcome Trust (098051, 206194, 203141, 090770, 204911, 106698/B/14/Z) and Medical Research Council (G0600718). A proportion of samples were collected with the support of the UK Department for International Development (201900, M006212), and Intramural Research Program of the National Institute of Allergy and Infectious Diseases., Competing Interests: CJ, NT, MM, RM, HQ, BH, VV, TN, HR, Rv, Lv, RF, FN, MH, NP, SG, PR, KC, PN, EA, SP, RM, RL, CH, LD, KN, TN, TH, AS, DU, CB, CF, MO, TP, RT, CA, AM, GD, JL, DP, NC, DL, SS, JC, PJ, BH, SP, AP, FS, KL, MT, TH, PS, SS, PB, AT, SB, NV, AA, AU, AF, CK, ED, MK, MA, KL, SR, AJ, KR, CH, MD, RV, NK, PW, JA, RP, CA, TC, CM, TN, JS, BJ, JK, KJ, DM, XC, JS, RA, VS, SG, KR, ND, AD, DK, OM No competing interests declared, HN, NZ, SC is an employee of Vysnova Partners Inc

MalariaGEN is a data-sharing network that enables groups around the world to work together on the genomic epidemiology of malaria. Here we describe a new release of curated genome variation data on 7,000 Plasmodium falciparum samples from MalariaGEN partner studies in 28 malaria-endemic countries. High-quality genotype calls on 3 million single nucleotide polymorphisms (SNPs) and short indels were produced using a standardised analysis pipeline. Copy number variants associated with drug resistance and structural variants that cause failure of rapid diagnostic tests were also analysed.  Almost all samples showed genetic evidence of resistance to at least one antimalarial drug, and some samples from Southeast Asia carried markers of resistance to six commonly-used drugs. Genes expressed during the mosquito stage of the parasite life-cycle are prominent among loci that show strong geographic differentiation. By continuing to enlarge this open data resource we aim to facilitate research into the evolutionary processes affecting malaria control and to accelerate development of the surveillance toolkit required for malaria elimination., Competing Interests: No competing interests were disclosed., (Copyright: © 2021 MalariaGEN et al.)

Purpose: To evaluate the impact of the Affordable Care Act Dependent Care Provision by sociodemographic and economic characteristics in young adult cancer patients., Methods: The National Cancer Database (NCDB) and the Surveillance, Epidemiology, and End Results (SEER) 18 database were queried for young adult cancer cases diagnosed during 2007-2014. Using a difference-in-differences approach, we examined insurance coverage in different subgroups of policy-eligible 19-25 year-olds versus policy-ineligible 27-29 year-olds from the pre- (2007-2009) to post- (2011-2014) Dependent Care Provision period., Results: Across subgroups and study populations, insurance coverage increased significantly following the Provision enactment in the policy-eligible versus policy-ineligible group across most subgroups (range in NCDB: 1.83 to 6.38% for low and mid-low education areas, respectively; range in SEER: 1.43 to 6.18 for Non-Hispanic Others and Hispanics, respectively). Heterogenous impacts were observed by sex with a larger impact in males (NCDB: 5.14%, 95% CI 3.59-6.69; SEER: 4.46, 2.12-6.8) than females (NCDB: 2.51%, 95% CI 1.39-3.62; SEER: 2.50, 0.82-4.18). We observed no other statistical evidence for Dependent Care Provision subgroup heterogeneity except for a smaller impact in individuals from low education areas in NCDB., Conclusions: Our results indicate a positive Dependent Care Provision impact on insurance coverage in young adults with cancer across subgroups, with evidence for a smaller impact in females relative to males and in low relative to high education areas.

Background: Neurofibromatosis type 1 (NF1) is a cancer syndrome associated with many different cancer types. There are limited studies examining melanoma risk in this population., Objective: To identify melanoma cases in NF1 patients and compare melanoma incidence rates relative to a general population sample., Methods: A retrospective single institution case review of 857 NF1 patients (seen from 7/1997 to 7/2017) was conducted. We calculated age- and calendar period-adjusted standardized incidence ratios (SIRs) for white patients &gt;20 years old overall (N=282) and for females (N=156) at their last visit date. We obtained general population melanoma reference rates from the Surveillance, Epidemiology, and End Results (SEER) 9 database., Results: Among 857 patients, 52.2% were female, 54% were &lt;20 (mean±sd=10.9±4.6) years old, and 46% were &gt;20 (40.4±14.9) years old at their last visit date. One white female patient had a malignant melanoma diagnosed at 47 years old. The adjusted SIR was 0.97 (95% CI 0.05-4.78) overall (N=282) and 1.62 (95% CI 0.08-7.98) for females (N=156)., Conclusions: We did not find statistical evidence for an increased melanoma risk in adults with NF1. However, additional large studies are warranted to clarify whether melanoma risk is increased in NF1 patients.

Background: Male breast cancer is rare and understudied compared with female breast cancer. A current comparison with female breast cancer could assist in bridging this gap. Although conflicting data have been reported on male and female survival outcomes, data from 1973 through 2005 in the Surveillance, Epidemiology, and End Results (SEER) program have demonstrated that the improvement in breast cancer survival in men has fallen behind that of women. As treatment for breast cancer has improved significantly, an updated analysis using a contemporary population is necessary., Materials and Methods: An analysis of SEER data from patients with a diagnosis of primary breast cancer from 2005 to 2010 were included. A Cox regression model was used to examine the association between sex and breast cancer mortality after controlling for prognostic factors, including age, race, marital status, disease stage, estrogen and progesterone receptor status, lymph node involvement, tumor grade, surgery, and geography. Subgroup analyses were performed by race and stage., Results: We included a total of 289,673 breast cancer cases (2054 men) with a diagnosis from 2005 to 2010. The 5-year survival rate for male patients was lower than that for female patients (82.8% vs. 88.5%). After controlling for other factors, the risk of death in men was 43% greater than that in women during the follow-up period (hazard ratio, 1.43; 95% confidence interval, 1.26-1.61). Similar results were noted in the race and stage subgroup analyses., Conclusion: In recent years, male breast cancer patients have had worse survival outcomes compared with those of female patients., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Purpose: Phacomatoses are genetic syndromes that are associated with increased risk of developing nervous system tumors. Phacomatoses are usually inherited, but many develop de novo, with unknown etiology. In this population-based study, we investigated the effect of parental age on the risk of phacomatoses in offspring., Patients and Methods: The study was a population-based nested case-control study. All individuals born and residing in Sweden between January 1960 and December 2010 were eligible for inclusion. Using the Patient Register, 4625 phacomatosis cases were identified and further classified as familial or nonfamilial. Ten matched controls per case were randomly selected from the eligible population. Data were analyzed using conditional logistic regression. Analyses were conducted for neurofibromatosis alone (n=2089) and other phacomatoses combined (n=2536)., Results: Compared with offspring of fathers aged 25-29 years, increased risk estimates of nonfamilial neurofibromatosis were found for offspring of fathers aged 35-39 years (odds ratio [OR]=1.43 [95% CI 1.16-1.74]) and ≥40 years (OR =1.74 [95% CI 1.38-2.19]). For other nonfamilial phacomatoses, the risk estimate for offspring of fathers aged ≥40 years was OR =1.23 (95% CI 1.01-1.50). Paternal age was not associated with familial phacomatoses, and no consistent association was observed with maternal age., Conclusion: The findings show a consistent increase in risk of de novo occurrence of phacomatoses predisposing to nervous system tumors in offspring with increasing paternal age, most pronounced for neurofibromatosis, while maternal age did not seem to influence the risk. These findings suggest an increasing rate of new mutations in the NF1 and NF2 genes in spermatozoa of older fathers., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

We conducted the largest investigation of predisposition variants in cancer to date, discovering 853 pathogenic or likely pathogenic variants in 8% of 10,389 cases from 33 cancer types. Twenty-one genes showed single or cross-cancer associations, including novel associations of SDHA in melanoma and PALB2 in stomach adenocarcinoma. The 659 predisposition variants and 18 additional large deletions in tumor suppressors, including ATM, BRCA1, and NF1, showed low gene expression and frequent (43%) loss of heterozygosity or biallelic two-hit events. We also discovered 33 such variants in oncogenes, including missenses in MET, RET, and PTPN11 associated with high gene expression. We nominated 47 additional predisposition variants from prioritized VUSs supported by multiple evidences involving case-control frequency, loss of heterozygosity, expression effect, and co-localization with mutations and modified residues. Our integrative approach links rare predisposition variants to functional consequences, informing future guidelines of variant classification and germline genetic testing in cancer., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Congenital anomalies that are diagnosed in at least 120,000 US infants every year are the leading cause of infant death and contribute to disability and pediatric hospitalizations. Several large-scale epidemiologic studies have provided substantial evidence of an association between congenital anomalies and cancer risk in children, suggesting potential underlying cancer-predisposing conditions and the involvement of developmental genetic pathways. Electronic medical records from 1,107 pediatric, adolescent, and young adult oncology patients were reviewed. The observed number (O) of congenital anomalies among children with a specific pediatric cancer subtype was compared to the expected number (E) of anomalies based on the frequency of congenital anomalies in the entire study population. The O/E ratios were tested for significance using Fisher's exact test. The Kaplan-Meier method was used to compare overall and neurological malignancy survival rates following tumor diagnosis. Thirteen percent of patients had a congenital anomaly diagnosis prior to their cancer diagnosis. When stratified by congenital anomaly subtype, there was an excess of neurological anomalies among children with central nervous system tumors (O/E = 1.56, 95%CI 1.13-2.09). Male pediatric cancer patients were more likely than females to have a congenital anomaly, particularly those <5 years of age (O/E 1.35, 95%CI 0.97-1.82). Our study provides additional insight into the association between specific congenital anomaly types and pediatric cancer development. Moreover, it may help to inform the development of new screening policies and support hypothesis-driven research investigating mechanisms underlying tumor predisposition in children with congenital anomalies., (© 2017 The Authors. American Journal of Medical Genetics Part A Published by Wiley Periodicals, Inc.)

Background: Individuals with Neurofibromatosis Type 1 (NF1) are strongly predisposed to developing pediatric brain tumors (PBTs), especially optic pathway gliomas (OPGs). Although developmental factors have been implicated in the origins of PBTs in both human and animal studies, associations between early-life factors and PBTs have not been evaluated in individuals with NF1. Our objective was to evaluate associations between peri-gestational characteristics and PBTs in this population., Methods: We conducted a cross-sectional study, ascertaining questionnaire and medical record data for 606 individuals<18years old who enrolled in the NF1 Patient Registry Initiative (NPRI) from 6/9/2011-6/29/2015. One hundred eighty-four individuals had reported PBT diagnoses, including 65 who were identified with OPG diagnoses. Cox proportional hazards regression was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for associations between PBT and OPG diagnoses and peri-gestational characteristics (prematurity, birth weight, parental age, plurality, family history of NF1, assisted reproductive technology, maternal vitamin supplementation, and parental smoking)., Results: We observed no significant associations between any of the assessed characteristics and PBTs overall or OPGs with the exception of birth weight. After controlling for potential confounding variables, we observed a significant positive association between birth weight quartile and OPGs with a HR of 3.32 (95% CI 1.39-7.94) for the fourth (≥3915.5g) compared to the first (≤3020g) quartile (p for trend=0.001)., Conclusions: Consistent with results for PBTs in the general population, these results suggest that higher birth weights increase OPG risk in individuals with NF1., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Individuals with Neurofibromatosis type 1 (NF1) are at increased risk for pediatric brain tumors (PBTs), especially optic gliomas; however, factors influencing their development are largely unknown. Extensive research suggests that allergic conditions protect against brain tumors, particularly gliomas in individuals without NF1. In this large cross-sectional study, we employed two different data sources to evaluate evidence for the hypothesis that allergic conditions (allergies, asthma, and eczema) may protect against PBT development in individuals with NF1. We used self- and parent/legal guardian reported questionnaire data from participants in the NF1 Patient Registry Initiative (NPRI, n = 1660) born from 1933 to 2014 to ascertain allergic condition and PBT diagnosis histories. Medical records (MRs) of 629 NF1 patients at a large medical center born from 1930 to 2012 were also reviewed for PBT and allergic condition diagnoses to evaluate additional evidence for our hypothesis. We used logistic regression to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for associations between allergic condition diagnoses and PBTs. Both data sources provided limited to no support for a protective effect of allergies or eczema on PBT development. Non-significant inverse associations between asthma and PBTs were observed (NPRI: OR = 0.80, 95% CI 0.55-1.17; MR: OR = 0.71, 95% CI 0.40-1.28) with stronger associations for optic gliomas specifically. Additionally, a significant inverse association was observed in an NPRI subgroup analysis where the reported asthma diagnosis age was younger than the reported PBT diagnosis age (OR = 0.57; 95% CI 0.36-0.89). Our study supports the hypothesis that asthma protects against PBT development in NF1., Competing Interests: The authors declare that they have no conflict of interest to disclose.

Complex insertions and deletions (indels) are formed by simultaneously deleting and inserting DNA fragments of different sizes at a common genomic location. Here we present a systematic analysis of somatic complex indels in the coding sequences of samples from over 8,000 cancer cases using Pindel-C. We discovered 285 complex indels in cancer-associated genes (such as PIK3R1, TP53, ARID1A, GATA3 and KMT2D) in approximately 3.5% of cases analyzed; nearly all instances of complex indels were overlooked (81.1%) or misannotated (17.6%) in previous reports of 2,199 samples. In-frame complex indels are enriched in PIK3R1 and EGFR, whereas frameshifts are prevalent in VHL, GATA3, TP53, ARID1A, PTEN and ATRX. Furthermore, complex indels display strong tissue specificity (such as VHL in kidney cancer samples and GATA3 in breast cancer samples). Finally, structural analyses support findings of previously missed, but potentially druggable, mutations in the EGFR, MET and KIT oncogenes. This study indicates the critical importance of improving complex indel discovery and interpretation in medical research., Competing Interests: The authors declare no competing financial interests.

One of the potential etiologies for non-familial Neurofibromatosis Type 1 (NF1) is increasing parental age. We sought to evaluate recent evidence for parental age effects in NF1 in a large study. Individuals with NF1 and a comparison group from the U.S. general population born between 1994 and 2012 were ascertained from the NF1 Patient Registry Initiative (NPRI) and the National Center for Vital Statistics, respectively. Multiple linear regression analysis was employed to identify differences between familial NF1, non-familial NF1, and U.S. population subjects in the mean parental ages at the time of the birth of offspring in each group. In addition, we also evaluated the effect of parental age on NF1 offspring with and without a pediatric brain tumor history. A total of 313 subjects from the NPRI (including 99 brain tumor cases) matched by birth year at a 1:3 ratio to U.S. general population births (n = 939) were included. Compared to the U.S. general population and familial NF1 cases, the mean paternal age for non-familial NF1 cases was 4.34 years (95% CI 3.23-5.46, p ≤ 0.0001) and 3.39 years (95% CI 1.57-5.20, p ≤ 0.0001) older, respectively, after adjusting for birth year. A similar pattern was observed for maternal age. There were no statistically significant differences in the mean maternal or paternal ages between NF1 offspring with and without a pediatric brain tumor. In conclusion, these data support a parental age effect for non-familial NF1 cases, but not for pediatric brain tumors in NF1.

Advances in DNA sequencing technology now allow for the rapid genome-wide identification of inherited and acquired genetic variants including those that have been identified as pathogenic alleles for a number of diseases including cancer. Whole genome and exome sequencing are increasingly becoming a part of both clinical practice and research studies. In 2013 the American College of Medical Genetics and Genomics (ACMG) recommended that results of pathogenic genetic variants in 56 genes, nearly half of which comprise cancer genes (including BRCA1, BRCA2, TP53, MLH1, MLH2, MSH6, PMS2 , and APC ),be returned to patients who have their genome sequenced independent of the purpose for the test. This recommendation has been highly controversial for several reasons, particularly the recommendation that individuals be returned secondary findings of disease causing variants for adult onset conditions regardless of age and without consideration of patient preferences. In addition, the policy regarding returning results of secondary findings from genomic sequencing studies in research settings is currently unclear. In response to these emerging ethical issues, the Washington University Brown School in St. Louis, MO, United Stateshosted a policy forum entitled "First do no harm: Genetic privacy in the age of genomic sequencing" on February 25 th , 2014. The forum included a panel of experts to discuss their views on ethical issues related to return of results in both the clinical and research settings. In this report, we highlight key issues related to return of results from genome sequencing tests that emerged during the forum.

The latter part of the 20th century was a period characterized by a fundamental transition in scholarship on activity and the aging process. Theory emphasizing the inevitable decline of human capacity was gradually replaced with concepts stressing positive, multidimensional views of aging. In this article, we highlight the key contributors and trace the origins and overlapping themes of successful aging, productive aging, and civic engagement in later life: 3 examples of scholarship representing a "positive" gerontology. Rowe and Kahn's model of successful aging highlights the interplay between social engagement with life, health, and functioning for a positive aging experience. Productive aging, led by Robert Butler, recognizes the previously underappreciated participation of older adults in activities such as volunteering, paid work, and caregiving, and generates interest in the individual and societal barriers to and benefits of participation. Civic engagement in later life raises public awareness about the need to involve older adults in the community, creates opportunities for participation, and generates further interest in the mutual benefit of participation for community beneficiaries and participants. Successful aging, productive aging, and civic engagement represent important contributions to the field of gerontology through applications to policy, advocacy, and theory development.

Background: Hepatoblastoma is a rare pediatric liver tumor that has significantly increased in incidence over the last several decades. The International Agency for Research on Cancer (IARC) recently classified hepatoblastoma as a tobacco-related cancer. Parental alcohol use has shown no association. We examined associations between parental tobacco and alcohol use around the time of pregnancy and hepatoblastoma in a large case-control study., Methods: Maternal interviews were completed for 383 cases diagnosed in the United States during 2000-2008. Controls (n = 387) were identified through U.S. birth registries and frequency-matched to cases on birth weight, birth year, and region of residence. We used unconditional logistic regression to calculate ORs and 95% confidence intervals (CI) for associations between parental smoking and maternal drinking and offspring hepatoblastoma., Results: We found no association between hepatoblastoma and maternal smoking at any time (OR, 1.0; 95% CI, 0.7-1.4), within the year before pregnancy (OR, 1.1; 95% CI, 0.8-1.6), early in pregnancy (OR, 1.0; 95% CI, 0.7-1.6), or throughout pregnancy (OR, 0.9; 95% CI, 0.5-1.6). We observed marginally positive associations between hepatoblastoma and paternal smoking in the year before pregnancy (OR, 1.4; 95% CI, 1.0-2.0) and during pregnancy (OR, 1.4; 95% CI, 0.9-2.0). Maternal alcohol use was not associated with hepatoblastoma., Conclusion: Our results do not provide evidence for an etiologic relationship between maternal smoking or drinking and hepatoblastoma, and only weak evidence for an association for paternal smoking in the year before pregnancy., Impact: Our study provides limited support for hepatoblastoma as a tobacco-related cancer; however, it remains wise to counsel prospective parents on the merits of smoking cessation.

Purpose: Although a few previous studies have reported positive associations between adult myeloid leukemia and a history of certain medical conditions, the etiology of most cases remains largely unknown. Our purpose was to examine associations between certain medical conditions and adult myeloid leukemia., Methods: Using logistic regression, we evaluated associations between 16 self-reported medical conditions and myeloid leukemia in a case-control study of 670 cases [including 420 acute myeloid leukemia (AML) and 186 chronic myelogenous leukemia (CML)] and 701 population-based controls., Results: We observed significant positive associations between AML and ulcerative colitis (odds ratio (OR) = 3.8; 95 % confidence interval (CI), 1.1-13) and between CML and peptic ulcer (OR = 2.0; 95% CI, 1.1-3.8). A personal cancer history increased both AML (OR = 2.6; 95% CI, 1.7-3.9) and CML (OR = 3.5; 95% CI, 2.0-5.8) risk even after excluding individuals who reported prior radiation and/or chemotherapy treatment., Conclusion: Certain inflammatory medical conditions and a personal history of cancer, independent from therapy, are associated with an increased risk of myeloid leukemia.

Objective: Utilizing data from the largest study to date, we examined associations between maternal preconception/prenatal exposure to household chemicals and infant acute leukemia., Methods: We present data from a Children's Oncology Group case-control study of 443 infants (<1 year of age) diagnosed with acute leukemia [including acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML)] between 1996 and 2006 and 324 population controls. Mothers recalled household chemical use 1 month before and throughout pregnancy. We used unconditional logistic regression adjusted for birth year, maternal age, and race/ethnicity to calculate odds ratios (ORs) and 95% confidence intervals (CIs)., Results: We did not find evidence for an association between infant leukemia and eight of nine chemical categories. However, exposure to petroleum products during pregnancy was associated with AML (OR = 2.54; 95% CI:1.40-4.62) and leukemia without mixed lineage leukemia (MLL) gene rearrangements ("MLL-") (OR = 2.69; 95% CI: 1.47-4.93). No associations were observed for exposure in the month before pregnancy., Conclusions: Gestational exposure to petroleum products was associated with infant leukemia, particularly AML, and MLL- cases. Benzene is implicated as a potential carcinogen within this exposure category, but a clear biological mechanism has yet to be elucidated.

We developed extraction and analysis protocols for element detection in neonatal blood spots (NBSs) using sector-field inductively coupled plasma-mass spectrometry (SF-ICP-MS). A 5% (v/v) nitric acid element extraction protocol was optimized and used to simultaneously measure 28 elements in NBS card filter paper and 150 NBSs. NBS element concentrations were corrected for filter paper background contributions estimated from measurements in samples obtained from either unspotted or spotted NBS cards. A lower 95% uncertainty limit (UL) that accounted for ICP-MS method, filter paper element concentration, and element recovery uncertainties was calculated by standard methods for each individual's NBS element concentration. Filter paper median element levels were highly variable within and between lots for most elements. After accounting for measurement uncertainties, 11 elements (Ca, Cs, Cu, Fe, K, Mg, Na, P, Rb, S, and Zn) had lower 95% ULs>0 ng/spot with estimated concentrations ranging from 0.05 to >50,000 ng/spot in ≥50% of NBS samples in both correction methods. In a NBS sample minority, Li, Cd, Cs, Cr, Ni, Mo, and Pb had estimated concentrations ≥20-fold higher than the respective median level. Taking measurement uncertainties into account, this assay could be used for semiquantitative newborn blood element measurement and for the detection of individuals exposed to supraphysiologic levels of some trace elements. Adequate control of filter paper element contributions remains the primary obstacle to fully quantitative element measurement in newborn blood using NBSs.