Search

Background: Financial hardship is most common among cancer survivors with the fewest financial resources at diagnosis; however, little is known about the financial outcomes of young adult (YA) survivors (ages 20–39 at diagnosis), despite their having fewer financial reserves than older adults. Methods: We utilized data from 3,888 participants in the population-based Detroit Research on Cancer Survivors cohort. Participants self-reported several forms of material and behavioral financial hardship (MFH and BFH, respectively). Psychological financial hardship (PFH) was measured using the Comprehensive Score for financial Toxicity (COST) score. Modified Poisson models estimated prevalence ratios (PR) and 95% confidence intervals (CI) for financial hardship by age at diagnosis controlling for demographic, socioeconomic, and cancer-related factors. Results: MFH prevalence was inversely associated with age such that 72% of YA survivors reported MFH, 62% ages 40 to 54, 49% ages 55 to 64, and 33% ages 65 to 79 (PRadjusted YA vs. 65+: 1.75; 95% CI, 1.49–2.04; Ptrend < 0.001). BFH was also more common among YA survivors (26%) than those ages 65 to 79 (20%; PRadjusted: 1.50; 95% CI, 1.08–2.08; Ptrend = 0.019). Age was positively associated with financial wellbeing. COST scores ranged from 20.7 (95% CI, 19.0–22.4) among YA survivors to 27.2 (95% CI, 26.1–28.2) among adults 65 to 79 years old (Ptrend < 0.001). Conclusions: In this population of African American cancer survivors, MFH and BFH were more common, and PFH was more severe, in YA survivors compared with those diagnosed as older adults. Impact: Young adulthood at diagnosis should be considered a risk factor for cancer-related financial hardship and addressed in work designed to reduce the adverse financial impacts of cancer.

Tierexperimentelle Untersuchungen zeigen für einige Kohlenstoffnanofasern eine kanzerogene Wirkung. Gleichzeitig wird die nanoskalige faserförmige Fraktion in den in Deutschland geltenden Regelwerken zur Bestimmung der Konzentration faserförmiger anorganischer Partikel bisher nicht berücksichtigt. Für die Überprüfung luftgetragener Anzahlkonzentrationen nano- und mikroskaliger Fasern am Arbeitsplatz wurde deshalb ein neues Mess- und Analyseverfahren entwickelt, das Fasern mit einem Durchmesser ab 20 nm mit einbezieht. Dieses neue Messverfahren wurde nun an realen Arbeitsplätzen angewandt und die Durchführbarkeit und Praktikabilität bewertet. Die durchgeführten Arbeitsplatzmessungen werden im Folgenden vorgestellt und identifizierte Probleme bei der Anwendung des Verfahrens sowie Lösungsvorschläge erläutert. Für verschiedene Tätigkeiten mit faserförmigen Nanomaterialien konnten mit dem neuen Messverfahren Faserfreisetzungen detektiert und die praktische Umsetzung für eine Nachweisgrenze von 10 000 F(20 nm)/m³ gezeigt werden.

Supplementary Table S6. Association between serum cytokine levels and lung cancer among European Americans from NCI-MD and PLCO studies, by smoking status

Agreement (Cohen's kappa) between measures of COPD among lung cancer cases (upper diagonal) and controls (lower diagonal).

PDF file - 926K, Triangle plot showing estimated admixture in the African-American case-control population. Estimates were performed using 102 AIMs and data from the International HapMap Project on 167 Yoruban African (Green dots), 165 European (Red dots), 84 Chinese (Yellow dots) and 86 Japanese (Dark Blue dots) founders. The figure depicts ancestry in 1308 African-American lung cancer cases (Pink dots) and 1241 controls (Light Blue dots).

PDF file - 67K, Imputed SNP associations from the case-control analysis of lung cancer (by histology) in African-Americans (P

Tables S1-S6 and Figures S1-S3.

PDF file - 561K, Association of SNPs on chromosome 15q25.1 with lung cancer, with and without adjustment for missense variant rs16969968. Black circles depict association of SNPs with lung cancer, adjusted for sex, age, study site, % African ancestry, % European ancestry, and number of pack-years smoked. Open squares depict association of SNPs with lung cancer, adjusted for sex, age, study site, and % African ancestry, % European ancestry, number of pack-years smoked, AND conditioned on rs16969968 (marked with an X).

Background: Genome-wide association studies of European and East Asian populations have identified lung cancer susceptibility loci on chromosomes 5p15.33, 6p22.1-p21.31, and 15q25.1. We investigated whether these regions contain lung cancer susceptibly loci in African-Americans and refined previous association signals by using the reduced linkage disequilibrium observed in African-Americans.Methods: 1,308 African-American cases and 1,241 African-American controls from 3 centers were genotyped for 760 single-nucleotide polymorphisms (SNP) spanning 3 regions, and additional SNP imputation was carried out. Associations between polymorphisms and lung cancer risk were estimated using logistic regression, stratified by tumor histology where appropriate.Results: The strongest associations were observed on 15q25.1 in/near CHRNA5, including a missense substitution [rs16969968: OR, 1.57; 95% confidence interval (CI), 1.25–1.97; P, 1.1 × 10−4) and variants in the 5′-UTR. Associations on 6p22.1-p21.31 were histology specific and included a missense variant in BAT2 associated with squamous cell carcinoma (rs2736158: OR, 0.64; 95% CI, 0.48–0.85; P, 1.82 × 10−3). Associations on 5p15.33 were detected near TERT, the strongest of which was rs2735940 (OR, 0.82; 95% CI, 0.73–0.93; P, 1.1 × 10−3). This association was stronger among cases with adenocarcinoma (OR, 0.75; 95% CI, 0.65–0.86; P, 8.1 × 10−5).Conclusions: Polymorphisms in 5p15.33, 6p22.1-p21.31, and 15q25.1 are associated with lung cancer in African-Americans. Variants on 5p15.33 are stronger risk factors for adenocarcinoma and variants on 6p21.33 associated only with squamous cell carcinoma.Impact: Results implicate the BAT2, TERT, and CHRNA5 genes in the pathogenesis of specific lung cancer histologies. Cancer Epidemiol Biomarkers Prev; 22(2); 251–60. ©2012 AACR.

Background: Chronic obstructive pulmonary disease (COPD) is a risk factor for lung cancer. This study evaluates alternative measures of COPD based on spirometry and quantitative image analysis to better define a phenotype that predicts lung cancer risk.Methods: A total of 341 lung cancer cases and 752 volunteer controls, ages 21 to 89 years, participated in a structured interview, standardized CT scan, and spirometry. Logistic regression, adjusted for age, race, gender, pack-years, and inspiratory and expiratory total lung volume, was used to estimate the odds of lung cancer associated with FEV1/FVC, percent voxels less than −950 Hounsfield units on the inspiratory scan (HUI) and percent voxels less than −856 HU on expiratory scan (HUE).Results: The odds of lung cancer were increased 1.4- to 3.1-fold among those with COPD compared with those without, regardless of assessment method; however, in multivariable modeling, only percent voxels E as a continuous measure of air trapping [OR = 1.04; 95% confidence interval (CI), 1.03–1.06] and FEV1/FVC < 0.70 (OR = 1.71; 95% CI, 1.21–2.41) were independent predictors of lung cancer risk. Nearly 10% of lung cancer cases were negative on all objective measures of COPD.Conclusion: Measures of air trapping using quantitative imaging, in addition to FEV1/FVC, can identify individuals at high risk of lung cancer and should be considered as supplementary measures at the time of screening for lung cancer.Impact: Quantitative measures of air trapping based on imaging provide additional information for the identification of high-risk groups who might benefit the most from lung cancer screening. Cancer Epidemiol Biomarkers Prev; 25(9); 1341–7. ©2016 AACR.

SUPPLEMENTAL TABLE 1. Summary of the five previously reported lung cancer survival GWAS variants examined in the present study. SUPPLEMENTAL TABLE 2. Descriptive characteristics of African Americans with NSCLC participating in the KCI/WSU and UCSF studies. SUPPLEMENTAL TABLE 3. Allele frequency for the five variants previously associated with lung cancer survival in the NHGRIEBI GWAS Catalog in the SCCS (N=275), KCI/WSU (N=312), and UCSF (N=284) populations. Allele frequencies are also presented for the ASW 1000 Genomes African American reference population and for the 1000 Genomes reference population that matches the racial/ethnic group of the original discovery population (CEU or CHB). SUPPLEMENTAL TABLE 4. Adjusted multivariable Cox proportional hazards model results for African Americans with incident non-small cell lung cancer participating in the Southern Community Cohort Study (N=264) for the five candidate SNPs previously associated with lung cancer survival from the NHGRI GWAS catalog. SUPPLEMENTAL TABLE 5. Stage-stratified multivariable Cox proportional hazards results for the association of rs1878022 and overall survival in the SCCS and pooled KCI/WSU and UCSF populations. SUPPLEMENTAL TABLE 6. Allele frequency for common variants associated survival in the SCCS (N=275), KCI/WSU (N=312), and UCSF (N=284) populations. Allele frequencies are also presented for the ASW 1000 Genomes African American reference population. SUPPLEMENTAL TABLE 7. Adjusted multivariable Cox proportional hazards results for African Americans with incident non-small cell lung cancer participating in the Southern Community Cohort Study (N=264) for common variants assayed by the Illumina HumanExome BeadChip v1.1. SUPPLEMENTAL FIGURE 1. Flow chart of quality control (QC) for the SCCS genotyping data. SUPPLEMENTAL FIGURE 2. Distribution of stage at diagnosis across the SCCS (N=286), KCI/WSU (N=316), and UCSF (N=298.) SUPPLEMENTAL FIGURE 3. Global genetic ancestry estimates for African Americans with NSCLC participating in the (A) SCCS, (B) KCI/WSU, and (C) UCSF study populations.SUPPLEMENTAL FIGURE 4. Linkage disequilibrium (LD) patterns +/-10kb surrounding the CMKLR1 gene region in the YRI and CEU populations (A and B, respectively) from 1000 Genomes (phase 3). LD patterns surrounding rs1878022 (denoted by black arrow) are presented as inserts. 1000 Genomes data and Haploview software were utilized to display r2 values (filters:Hardy-Weinberg p-value > 0.001, genotyping efficiency > 90%, and minor allele frequency >0.05).SUPPLEMENTAL FIGURE 5. H3K4me1 and H3K27Ac histone modification marks surrounding rs1878022 in the CMKLR1 gene, visualized using the UCSC Genome Browser. Marks in (A) are specific to normal human lung fibroblast (NHLF) cell lines from the ENCODE project. Marks in (B) are for all cell lines (GM12878, H1-hESC, HSMM, HUVEC, K562, NHEK, and NHLF) in the ENCODE project.

PDF file - 559K, Association of SNPs on chromosome 15q25.1 with lung cancer, with and without adjustment for pack-years smoked. Black circles depict association of SNPs with lung cancer, adjusted for sex, age, study site, % African ancestry, % European ancestry, and number of pack-years smoked. Open squares depict association of SNPs with lung cancer, adjusted for sex, age, study site, and % African ancestry, % European ancestry, but NOT number of pack-years smoked.

Purpose:Identifying novel driver genes and mutations in African American non–small cell lung cancer (NSCLC) cases can inform targeted therapy and improve outcomes for this traditionally underrepresented population.Experimental Design:Tumor DNA, RNA, and germline DNA were collected from African American NSCLC patients who participated in research conducted at the Karmanos Cancer Institute (KCI) in Detroit, Michigan. Known mutations were ascertained through the Sequenom LungCarta panel of 214 mutations in 26 genes, RET/ROS1 fusions, amplification of FGFR1, and expression of ALK. Paired tumor and normal DNA was whole-exome sequenced for a subset of cases without known driver mutations.Results:Of the 193 tumors tested, 77 known driver mutations were identified in 66 patients (34.2%). Sixty-seven of the 127 patients without a known driver mutation were sequenced. In 54 of these patients, 50 nonsynonymous mutations were predicted to have damaging effects among the 26 panel genes, 47 of which are not found in The Cancer Genome Atlas NSCLC white or African American samples. Analyzing the whole-exome sequence data using MutSig2CV identified a total of 88 genes significantly mutated at FDR q < 0.1. Only 5 of these genes were previously reported as oncogenic.Conclusions:These findings suggest that broader mutation profiling including both known and novel driver genes in African Americans with NSCLC will identify additional mutations that may be useful in treatment decision-making.

Background: African Americans have the highest lung cancer mortality in the United States. Genome-wide association studies (GWASs) of germline variants influencing lung cancer survival have not yet been conducted with African Americans. We examined five previously reported GWAS catalog variants and explored additional genome-wide associations among African American lung cancer cases.Methods: Incident non–small cell lung cancer cases (N = 286) in the Southern Community Cohort Study were genotyped on the Illumina HumanExome BeadChip. We used Cox proportional hazards models to estimate HRs and 95% confidence intervals (CIs) for overall mortality. Two independent African American studies (N = 316 and 298) were used for replication.Results: One previously reported variant, rs1878022 on 12q23.3, was significantly associated with mortality (HR = 0.70; 95% CI: 0.54–0.92). Replication findings were in the same direction, although attenuated (HR = 0.87 and 0.94). Meta-analysis had a HR of 0.83 (95% CI, 0.71–0.97). Analysis of common variants identified an association between chromosome 6q21.33 and mortality (HR = 0.46; 95% CI, 0.33–0.66).Conclusions: We identified an association between rs1878022 in CMKLR1 and lung cancer survival. However, our results in African Americans have a different direction of effect compared with a prior study in European Americans, suggesting a different genetic architecture or presence of gene–environment interactions. We also identified variants on chromosome 6 within the gene-rich HLA region, which has been previously implicated in lung cancer risk and survival.Impact: We found evidence that inherited genetic risk factors influence lung cancer survival in African Americans. Replication in additional populations is necessary to confirm potential genetic differences in lung cancer survival across populations. Cancer Epidemiol Biomarkers Prev; 26(8); 1288–95. ©2017 AACR.

PDF file - 57K

To guarantee save and reliable operation of low voltage grid devices and to protect all devices from disturbance or damage, it is absolutely necessary to separate normal operation from fault state. A typical fault state with an enormous hazard potential is the arc fault. Due to the high level of energy involved, it can lead to the total write-off of affected devices and hence interrupt the energy supply (service). To prevent extensive consequences, there is a high demand to detect these error conditions and to terminate the fault state in a period of a few milliseconds. The analysis of typical electrical and non-electrical signals with numerical algorithms enables fast detection of arc faults.

PurposeThe paper discusses the rationale for a widespread reliance on Codes of Conduct (CoC) in European crowdfunding through the lenses of economic theories of self-regulation. By analysing the institutional design of CoCs in crowdfunding, the paper illustrates the differences in their regulatory context, inclusiveness, monitoring and enforcement. It offers the first systematic overview of substantial rules of CoCs in crowdfunding.Design/methodology/approachA comparative case study of nine CoCs in Europe is used to illustrate differences in their institutional design and discern the economic purpose of the CoC.FindingsThe institutional design of different CoCs in Europe mainly supports voluntary theories of self-regulation. In particular, the theory of reputation commons has the most explanatory power. The substantial rules of CoC in different markets show the potential sources of market failure through the perspectives of platforms.Research limitations/implicationsCoCs appear in various regulatory, cultural, and industry contexts of different countries. Some of the institutional design features of CoC might be a result of these characteristics.Practical implicationsCrowdfunding associations wishing to develop their own CoC may learn from a comparative overview of key provisions.Social implicationsFor governments in Europe, contemplating creating or revising bespoke crowdfunding regimes, the paper identifies areas where crowdfunding platforms perceive market failure.Originality/valueThis paper is the first systematic study of self-regulatory institutions in European crowdfunding. The paper employs a theoretical framework for the analysis of self-regulation in crowdfunding and provides a comparison of a regulatory context, inclusiveness, monitoring and enforcement of different CoCs in Europe.

Es wird eine Methode vorgestellt, um Sicherheitsaspekte von Prozessen zu untersuchen, mit denen metallische faserverstärkte Verbundwerkstoffe hergestellt und bearbeitet werden. Ziel ist, zu anwendungssicheren Prozessen zu gelangen, indem Gefahren gesundheitsgefährdender Stäube möglichst frühzeitig identifiziert und geeignete Schutzmaßnahmen ausgewählt werden. In der hier untersuchten Anwendung wurden Komposite aus Kupfer (Cu) mit Kohlenstoffnanoröhren (carbon nanotubes, CNTs) oder Kohlenstoffnanofasern (carbon nanofibers, CNFs) hergestellt und bearbeitet. Sie profitieren als elektrische Leiter und thermisch leitfähige Kontaktmaterialien von den Eigenschaften der zugesetzten Kohlenstoffmaterialien. Es kamen zum einen verknäulte CNTs mit Durchmessern von ca. 20 nm zum Einsatz, zum anderen rigide CNFs mit Durchmessern von ca. 100 nm. Für beide Fasertypen wurde zunächst im Labor die Staubungsneigung des trockenen Pulvers bestimmt, indem der Staub, der in einem Vibro-Fluidisierungsprozess entsteht, morphologisch charakterisiert, klassifiziert und quantifiziert wurde. Zur Bestimmung der Faserexposition von Beschäftigten erfolgte im Anschluss die Messung der luftgetragenen Faseranzahlkonzentrationen an den Arbeitsplätzen. Dabei kam ein neues Messverfahren für Aerosole aus nanoskaligen Fasern zur Anwendung, das derzeit durch ein Projekt der Deutschen Gesetzlichen Unfallversicherung e. V. (DGUV) validiert wird.

High Temperature - Aquifer Thermal Energy Storage (HT-ATES) offers a promising opportunity for climate-neutral heat supply in urban areas due to their high storage capacity and the possibility of direct integration into the regional district heating system. The assessment of the storage potential of HT-ATES requires reliable numerical models of the corresponding storage formation. To analyse the potential of the Lower Muschelkalk (Middle Triassic) as HT-ATES horizon, an unstructured 3D finite element model of the natural gas storage facility in Berlin/Spandau was developed. At this site, two porous layers (average porosity of 22 %) of oolithic grainstones characterize the target formation with a total thickness of about 30 m and a natural reservoir temperature of 32 °C in a depth of 535 m below ground surface. Beside lab analysis of core samples and fluid samples from the site, slug-withdrawal tests were performed in summer 2021 to identify hydraulic key parameters for the numerical simulations. The results indicate a productivity between 0.5 and 1.2 l/s/bar with reservoir permeability between 250 and 700 mD allowing maximum flow rates between 55 and 135 m³/h. In this study, we present a complete workflow from geological characterisation, lab analysis and field testing to detailed numerical HT-ATES simulations. Furthermore, we compare the storage potential based on different data sources such as solar heating systems and district heating networks. First results from the numerical simulations with storage volumes between 15,000 m³ (solar heating system) and 400,000 m³ (district heating system) show promising mean efficiency values between 60 % and 90 % within 25 years of operation. The hydraulic tests and the underlying numerical simulations indicate that the Lower Muschelkalk is suitable for HT-ATES.