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Abstract The geological formation of the Muschelkalk is widespread in the center of the North German Basin (NGB) and is increasingly attracting interest for application of geothermal energy extraction or high-temperature aquifer thermal energy storage (HT-ATES). This study investigates the Middle Triassic “Rüdersdorfer Schaumkalk”, which was the former injection horizon of the natural gas storage facility in Berlin, Germany. For the first time, detailed chemical and microbiological analyses of formation water of this Lower Muschelkalk limestone formation were conducted and hydrogeochemically characterized. In addition, a hydrogeochemical model was developed to quantify the potential reactions during HT-ATES focusing on calcite dissolution and precipitation. The main objectives of this study are: (1) to determine the origin of the water from the three wells targeting the Muschelkalk aquifer, (2) to understand changes in hydrochemistry after system operation, and (3) to evaluate the long-term sustainability of a potential HT-ATES system with increasing temperature. The target formation is encountered by several wells at about 525 m below the surface with an average thickness of 30 m. Two hydraulic lifting tests including physical, chemical, and microbial groundwater as well as gas monitoring were carried out. In addition, several downhole samples of formation fluid were collected from the aquifer at in situ pressure and temperature conditions. Fluid analysis of the saline formation water indicate a seawater origin within the Muschelkalk with subsequent evaporation and various water–rock interactions with anhydrite/gypsum, dolomite, and calcite. With a salinity of 130 g/L, dominated by Na–Cl, a slightly acidic pH between 6 and 7, and a low gas content of 3%, the formation water fits to other saline deep formation waters of the NGB. Gas concentrations and microbial communities like sulfate-reducing bacteria and methanogenic archaea in the produced water indicate several geochemical alterations and microbial processes like corrosion and the forming of biogenic methane. Geochemical simulations of calcite equilibrium over 10 HT-ATES cycles indicated a pronounced propensity for calcite precipitation up to 31 mg/kgw, within the heat exchanger. At the same time, these models predicted a significant potential for calcite dissolution, with rates up to 21 mg/kgw, in both the cold and hot reservoirs. The results from the carbonate aquifer characterized in this study can be transferred to other sites in the NGB affected by salt tectonics and have provided information on the microbiological-chemical processes to be expected during the initial use of old wells.

BackgroundSomatic EGFR mutations define a subset of non-small cell lung cancers (NSCLC) that have clinical impact on NSCLC risk and outcome. However, EGFR-mutation-status is often missing in epidemiologic datasets. We developed and tested pragmatic approaches to account for EGFR-mutation-status based on variables commonly included in epidemiologic datasets and evaluated the clinical utility of these approaches.MethodsThrough analysis of the International Lung Cancer Consortium (ILCCO) epidemiologic datasets, we developed a regression model for EGFR-status; we then applied a clinical-restriction approach using the optimal cut-point, and a second epidemiologic, multiple imputation approach to ILCCO survival analyses that did and did not account for EGFR-status.ResultsOf 35,356 ILCCO patients with NSCLC, EGFR-mutation-status was available in 4,231 patients. A model regressing known EGFR-mutation-status on clinical and demographic variables achieved a concordance index of 0.75 (95% CI, 0.74-0.77) in the training and 0.77 (95% CI, 0.74-0.79) in the testing dataset. At an optimal cut-point of probability-score = 0.335, sensitivity = 69% and specificity = 72.5% for determining EGFR-wildtype status. In both restriction-based and imputation-based regression analyses of the individual roles of BMI on overall survival of patients with NSCLC, similar results were observed between overall and EGFR-mutation-negative cohort analyses of patients of all ancestries. However, our approach identified some differences: EGFR-mutated Asian patients did not incur a survival benefit from being obese, as observed in EGFR-wildtype Asian patients.ConclusionsWe introduce a pragmatic method to evaluate the potential impact of EGFR-status on epidemiological analyses of NSCLC.ImpactThe proposed method is generalizable in the common occurrence in which EGFR-status data are missing.

IntroductionThe relationship between Body-Mass-Index (BMI) and lung cancer prognosis is heterogeneous. We evaluated the impact of sex, smoking and race on the relationship between BMI and overall survival (OS) in non-small-cell-lung-cancer (NSCLC).MethodsData from 16 individual ILCCO studies were pooled to assess interactions between BMI and the following factors on OS: self-reported race, smoking status and sex, using Cox models (adjusted hazard ratios; aHR) with interaction terms and adjusted penalized smoothing spline plots in stratified analyses.ResultsAmong 20,937 NSCLC patients with BMI values, females = 47 %; never-smokers = 14 %; White-patients = 76 %. BMI showed differential survival according to race whereby compared to normal-BMI patients, being underweight was associated with poor survival among white patients (OS, aHR = 1.66) but not among black patients (aHR = 1.06; pinteraction = 0.02). Comparing overweight/obese to normal weight patients, Black NSCLC patients who were overweight/obese also had relatively better OS (pinteraction = 0.06) when compared to White-patients. BMI was least associated with survival in Asian-patients and never-smokers. The outcomes of female ever-smokers at the extremes of BMI were associated with worse outcomes in both the underweight (pinteraction

Abstract Background Recently, attention has been focused on subsequent pregnancies among teenage mothers. Previous studies that compared the reproductive outcomes of teenage nulliparae and multiparae often did not consider the adolescents' reproductive histories. Thus, the authors compared the risks for adverse reproductive outcomes of adolescent nulliparae to teenagers who either have had an induced abortion or a previous birth. Methods In this retrospective cohort study we used perinatal data prospectively collected by obstetricians and midwives from 1990–1999 (participation rate 87–98% of all hospitals) in Lower Saxony, Germany. From the 9742 eligible births among adolescents, women with multiple births, >1 previous pregnancies, or a previous spontaneous miscarriage were deleted and 8857 women Results In bivariate logistic regression analyses, compared to nulliparous teenagers, adolescents with a previous birth had higher risks for perinatal [OR = 2.08, CI = 1.11,3.89] and neonatal [OR = 4.31, CI = 1.77,10.52] mortality and adolescents with a previous abortion had higher risks for stillbirths [OR = 3.31, CI = 1.01,10.88] and preterm births [OR = 2.21, CI = 1.07,4.58]. After adjusting for maternal nationality, partner status, smoking, prenatal care and pre-pregnancy BMI, adolescents with a previous birth were at higher risk for perinatal [OR = 2.35, CI = 1.14,4.86] and neonatal mortality [OR = 4.70, CI = 1.60,13.81] and adolescents with a previous abortion had a higher risk for very low birthweight infants [OR = 2.74, CI = 1.06,7.09] than nulliparous teenagers. Conclusion The results suggest that teenagers who give birth twice as adolescents have worse outcomes in their second pregnancy compared to those teenagers who are giving birth for the first time. The prevention of the second pregnancy during adolescence is an important public health objective and should be addressed by health care providers who attend the first birth or the abortion and the follow-up care. Also, health care workers should attempt to improve the pregnancy outcomes of subsequent teenage pregnancies by addressing modifiable risk factors, for example, supporting smoking cessation and utilization of prenatal care.

IntroductionThe relationships between morbid obesity, changes in body mass index (BMI) before cancer diagnosis, and lung cancer outcomes by histology (SCLC and NSCLC) have not been well studied.MethodsIndividual level data analysis was performed on 25,430 patients with NSCLC and 2787 patients with SCLC from 16 studies of the International Lung Cancer Consortium evaluating the association between various BMI variables and lung cancer overall survival, reported as adjusted hazard ratios (aHRs) from Cox proportional hazards models and adjusted penalized smoothing spline plots.ResultsOverall survival of NSCLC had putative U-shaped hazard ratio relationships with BMI based on spline plots: being underweight (BMI < 18.5 kg/m2; aHR = 1.56; 95% confidence interval [CI]:1.43-1.70) or morbidly overweight (BMI > 40 kg/m2; aHR = 1.09; 95% CI: 0.95-1.26) at the time of diagnosis was associated with worse stage-specific prognosis, whereas being overweight (25 kg/m2 ≤ BMI < 30 kg/m2; aHR = 0.89; 95% CI: 0.85-0.95) or obese (30 kg/m2 ≤ BMI ≤ 40 kg/m2; aHR = 0.86; 95% CI: 0.82-0.91) was associated with improved survival. Although not significant, a similar pattern was seen with SCLC. Compared with an increased or stable BMI from the period between young adulthood until date of diagnosis, a decreased BMI was associated with worse outcomes in NSCLC (aHR = 1.24; 95% CI: 1.2-1.3) and SCLC patients (aHR=1.26 (95% CI: 1.0-1.6). Decreased BMI was consistently associated with worse outcome, across clinicodemographic subsets.ConclusionsBoth being underweight or morbidly obese at time of diagnosis is associated with lower stage-specific survival in independent assessments of NSCLC and SCLC patients. In addition, a decrease in BMI at lung cancer diagnosis relative to early adulthood is a consistent marker of poor survival.

IntroductionInherited susceptibility to lung cancer risk in never-smokers is poorly understood. The major reason for this gap in knowledge is that this disease is relatively uncommon (except in Asians), making it difficult to assemble an adequate study sample. In this study we conducted a genome-wide association study on the largest, to date, set of European-descent never-smokers with lung cancer.MethodsWe conducted a two-phase (discovery and replication) genome-wide association study in never-smokers of European descent. We further augmented the sample by performing a meta-analysis with never-smokers from the recent OncoArray study, which resulted in a total of 3636 cases and 6295 controls. We also compare our findings with those in smokers with lung cancer.ResultsWe detected three genome-wide statistically significant single nucleotide polymorphisms rs31490 (odds ratio [OR]: 0.769, 95% confidence interval [CI]: 0.722-0.820; p value 5.31 × 10-16), rs380286 (OR: 0.770, 95% CI: 0.723-0.820; p value 4.32 × 10-16), and rs4975616 (OR: 0.778, 95% CI: 0.730-0.829; p value 1.04 × 10-14). All three mapped to Chromosome 5 CLPTM1L-TERT region, previously shown to be associated with lung cancer risk in smokers and in never-smoker Asian women, and risk of other cancers including breast, ovarian, colorectal, and prostate.ConclusionsWe found that genetic susceptibility to lung cancer in never-smokers is associated to genetic variants with pan-cancer risk effects. The comparison with smokers shows that top variants previously shown to be associated with lung cancer risk only confer risk in the presence of tobacco exposure, underscoring the importance of gene-environment interactions in the etiology of this disease.

The European Crowdfunding Service Provider Regime allows the intermediation of securities, loans and other admitted instruments for crowdfunding purposes up to five million Euro. Crowdfunding offers above five million Euro continue to be subject to national crowdfunding regimes, which may be regulated under MiFID. The authors discuss how existing MiFID licenses can be used in parallel to a license under ECSPR, with a focus on tied agents who operate under a so-called liability umbrella (investment firm or credit institution) holding a MiFID license. In Germany, the law implementing MiFID states that tied agents can operate “solely [in the name,] for the account and under the liability of” an investment firm or credit institution acting as liability umbrella. This raises the question, whether a tied agent can hold a license under ECSPR itself at the same time. However, the authors argue that both MiFID and ECSPR as well as the intent of the German legislator provide for the fact that one can hold an ECSPR authorization and at the same time be appointed as tied agent of a MiFID investment firm or credit institution.

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.

It is not clear whether alcohol consumption is associated with lung cancer risk. The relationship is likely confounded by smoking, complicating the interpretation of previous studies. We examined the association of alcohol consumption and lung cancer risk in a large pooled international sample, minimizing potential confounding of tobacco consumption by restricting analyses to never smokers. Our study included 22 case-control and cohort studies with a total of 2548 never-smoking lung cancer patients and 9362 never-smoking controls from North America, Europe and Asia within the International Lung Cancer Consortium (ILCCO) and SYNERGY Consortium. Alcohol consumption was categorized into amounts consumed (grams per day) and also modelled as a continuous variable using restricted cubic splines for potential non-linearity. Analyses by histologic sub-type were included. Associations by type of alcohol consumed (wine, beer and liquor) were also investigated. Alcohol consumption was inversely associated with lung cancer risk with evidence most strongly supporting lower risk for light and moderate drinkers relative to non-drinkers (>0-4.9 g per day: OR = 0.80, 95% CI = 0.70-0.90; 5-9.9 g per day: OR = 0.82, 95% CI = 0.69-0.99; 10-19.9 g per day: OR = 0.79, 95% CI = 0.65-0.96). Inverse associations were found for consumption of wine and liquor, but not beer. The results indicate that alcohol consumption is inversely associated with lung cancer risk, particularly among subjects with low to moderate consumption levels, and among wine and liquor drinkers, but not beer drinkers. Although our results should have no relevant bias from the confounding effect of smoking we cannot preclude that confounding by other factors contributed to the observed associations. Confounding in relation to the non-drinker reference category may be of particular importance.

ObjectivesGenome-wide association studies (GWAS) of lung cancer have identified regions of common genetic variation with lung cancer risk in Europeans who smoke and never-smoking Asian women. This study aimed to conduct a GWAS in African Americans, who have higher rates of lung cancer despite smoking fewer cigarettes per day when compared with Caucasians. This population provides a different genetic architecture based on underlying African ancestry allowing the identification of new regions and exploration of known regions for finer mapping.Materials and methodsWe genotyped 1,024,001 SNPs in 1737 cases and 3602 controls in stage 1, followed by a replication phase of 20 SNPs (p

BackgroundGenome-wide association studies have identified polymorphisms linked to both smoking exposure and risk of lung cancer. The degree to which lung cancer risk is driven by increased smoking, genetics, or gene-environment interactions is not well understood.MethodsWe analyzed associations between 28 single nucleotide polymorphisms (SNPs) previously associated with smoking quantity and lung cancer in 7156 African-American females in the Women's Health Initiative (WHI), then analyzed main effects of top nominally significant SNPs and interactions between SNPs, cigarettes per day (CPD) and pack-years for lung cancer in an independent, multi-center case-control study of African-American females and males (1078 lung cancer cases and 822 controls).FindingsNine nominally significant SNPs for CPD in WHI were associated with incident lung cancer (corrected p-values from 0.027 to 6.09 × 10(-5)). CPD was found to be a nominally significant effect modifier between SNP and lung cancer for six SNPs, including CHRNA5 rs2036527[A](betaSNP*CPD = - 0.017, p = 0.0061, corrected p = 0.054), which was associated with CPD in a previous genome-wide meta-analysis of African-Americans.InterpretationThese results suggest that chromosome 15q25.1 variants are robustly associated with CPD and lung cancer in African-Americans and that the allelic dose effect of these polymorphisms on lung cancer risk is most pronounced in lighter smokers.

BackgroundRecent meta-analyses show strong evidence of associations among genetic variants in CHRNA5 on chromosome 15q25, smoking quantity, and lung cancer. This meta-analysis tests whether the CHRNA5 variant rs16969968 predicts age of smoking cessation and age of lung cancer diagnosis.MethodsMeta-analyses examined associations between rs16969968, age of quitting smoking, and age of lung cancer diagnosis in 24 studies of European ancestry (n = 29 072). In each dataset, we used Cox regression models to evaluate the association between rs16969968 and the two primary phenotypes (age of smoking cessation among ever smokers and age of lung cancer diagnosis among lung cancer case patients) and the secondary phenotype of smoking duration. Heterogeneity across studies was assessed with the Cochran Q test. All statistical tests were two-sided.ResultsThe rs16969968 allele (A) was associated with a lower likelihood of smoking cessation (hazard ratio [HR] = 0.95, 95% confidence interval [CI] = 0.91 to 0.98, P = .0042), and the AA genotype was associated with a four-year delay in median age of quitting compared with the GG genotype. Among smokers with lung cancer diagnoses, the rs16969968 genotype (AA) was associated with a four-year earlier median age of diagnosis compared with the low-risk genotype (GG) (HR = 1.08, 95% CI = 1.04 to 1.12, P = 1.1*10(-5)).ConclusionThese data support the clinical significance of the CHRNA5 variant rs16969968. It predicts delayed smoking cessation and an earlier age of lung cancer diagnosis in this meta-analysis. Given the existing evidence that this CHRNA5 variant predicts favorable response to cessation pharmacotherapy, these findings underscore the potential clinical and public health importance of rs16969968 in CHRNA5 in relation to smoking cessation success and lung cancer risk.

The purpose of this study was to examine the nature of teacher learning in a cohort-based, master's degree program in curriculum and pedagogy that was intentionally designed to be responsive to teachers' personal needs and preferences. The program aimed to: (1) provide teachers with the confidence to connect what they do in their classrooms to research-informed practices; (2) immerse teachers in a collaborative culture that allowed them to learn from one another as colleagues; (3) consider teacher input in course content and structure design; and (4) address university guidelines and NCATE standards. A secondary purpose was to evaluate teachers' perceptions of how the program design responded to their needs, preferences, and learning processes. This program design took into account what is known about factors that influence teacher learning, including teacher beliefs as filters, the importance of interactions in a discourse community, and the significance of a collaborative culture as a force for change. The findings of this study suggest that a cohort-based graduate program that is personalized and responsive to teachers' needs promotes meaningful learning and a sense of empowerment. A collaborative culture comprised of teachers from different levels of schooling and content areas, as well as different district contexts, can help teachers to broaden their perspectives about teaching and learning and educational systems. In order to connect theory to practice the teachers in this study best "learned by doing," meaning they learned best by having authentic experiences and practical course assignments, reflecting on their "doing," and having input on graduate course design and content. (Contains 1 figure.)

BackgroundGenome-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.Methods1,308 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.ResultsThe 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)).ConclusionsPolymorphisms 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.ImpactResults implicate the BAT2, TERT, and CHRNA5 genes in the pathogenesis of specific lung cancer histologies.

Studies in European and East Asian populations have identified lung cancer susceptibility loci in nicotinic acetylcholine receptor (nAChR) genes on chromosome 15q25.1 which also appear to influence smoking behaviors. We sought to determine if genetic varia

Abstract The Trans‐Atlantic Geotraverse (TAG) hydrothermal field on the Mid‐Atlantic Ridge is one of the best‐studied hydrothermal systems to date. However, high‐resolution bathymetric data obtained in 2016 by an autonomous underwater vehicle (AUV) reveal new information about the distribution of active and inactive hydrothermal deposits, and their relation to structural features. The discovery of previously undocumented inactive vent sites contributes to a better understanding of the accumulation rates and the resource potential of seafloor massive sulfide deposits at slow‐spreading ridges. The interpretation of ship‐based and high‐resolution AUV‐based data sets allowed for the determination of the main tectonic stress regimes that have a first‐order control on the location and distribution of past and present hydrothermal activity. The data reveal the importance of cross‐cutting lineament populations and temporal variations in the prevalent stress regime. A dozen sulfide mounds contribute to a substantial accumulation of hydrothermal material (~29 Mt). The accumulation rate of ~1,500 t/yr is comparable to those of other modern seafloor vent fields. However, our observations suggest that the TAG segment is different from many other slow‐spreading ridge segments in its tectonic complexity, which confines sulfide formation into a relatively small area and is responsible for the longevity of the hydrothermal system and substantial mineral accumulation. The inactive and weakly active mounds contain almost 10 times the amount of material as the active high‐temperature mound, providing an important indication of the global resource potential for inactive seafloor massive sulfide deposits.

The authors wish to make the following corrections to this paper [...]

Abstract Background A dearth of laboratory tests to study actual human approach-avoidance behavior has complicated translational research on anxiety. The elevated plus-maze (EPM) is the gold standard to assess approach-avoidance behavior in rodents. Methods Here, we translated the EPM to humans using mixed reality through a combination of virtual and real-world elements. In two validation studies, we observed participants’ anxiety on a behavioral, physiological, and subjective level. Results Participants reported higher anxiety on open arms, avoided open arms, and showed an activation of endogenous stress systems. Participants’ with high anxiety exhibited higher avoidance. Moreover, open arm avoidance was moderately predicted by participants’ acrophobia and sensation seeking, with opposing influences. In a randomized, double blind, placebo controlled experiment, GABAergic stimulation decreased avoidance of open arms while alpha-2-adrenergic antagonism increased avoidance. Conclusion These findings demonstrate cross-species validity of open arm avoidance as a translational measure of anxiety. We thus introduce the first ecologically valid assay to track actual human approach-avoidance behavior under laboratory conditions.

Background: Polygenic risk scores (PRS) have become an increasingly popular approach to evaluate cancer susceptibility, but have not adequately represented Black populations in model development. Methods: We used a previously published lung cancer PRS on the basis of 80 SNPs associated with lung cancer risk in the OncoArray cohort and validated in UK Biobank. The PRS was evaluated for association with lung cancer risk adjusting for age, sex, total pack-years, family history of lung cancer, history of chronic obstructive pulmonary disease, and the top five principal components for genetic ancestry. Results: Among the 80 PRS SNPs included in the score, 14 were significantly associated with lung cancer risk (P < 0.05) in INHALE White participants, while there were no significant SNPs among INHALE Black participants. After adjusting for covariates, the PRS was significantly associated with risk in Whites (continuous score P = 0.007), but not in Blacks (continuous score P = 0.88). The PRS remained a statistically significant predictor of lung cancer risk in Whites ineligible for lung cancer screening under current U.S. Preventive Services Task Force guidelines (P = 0.02). Conclusions: Using a previously validated PRS, we did find some predictive ability for lung cancer in INHALE White participants beyond traditional risk factors. However, this effect was not observed in Black participants, indicating the need to develop and validate ancestry-specific lung cancer risk models. Impact: While a previously published lung cancer PRS was able to stratify White participants into different levels of risk, the model was not predictive in Blacks. Our findings highlight the need to develop and validate ancestry-specific lung cancer risk models. [ABSTRACT FROM AUTHOR]

Despite compelling reports on asbestos-like pathogenicity, regulatory bodies have been hesitant to implement fiber number-based exposure limits for biodurable nanoscale fibers. One reason has been the lack of a practicable strategy for assessing airborne fiber number concentrations. Here, a method is proposed, detailed and tested for compliance checking concentrations of airborne nano- and microscale fibers. It relies on Poisson statistical significance testing of the observed versus a predicted number of fibers on filters that have sampled a known volume of aerosol. The prediction is based on the exposure concentration to test. Analogous to the established counting rules for WHO-fibers, which use a phase contrast microscopy-related visibility criterion of 200 nm, the new method also introduces a cut-off diameter, now at 20 nm, which is motivated by toxicological findings on multi-walled carbon nanotubes. This cut-off already reduces the workload by a factor of 400 compared to that necessary for imaging, detecting and counting nanofibers down to 1 nm in diameter. Together with waiving any attempt to absolutely quantify fiber concentrations, a compliance check at the limit-of-detection results in an analytical workload that renders our new approach practicable. The proposed method was applied to compliance checking in 14 very different workplaces that handled or machined nanofiber-containing materials. It achieved detecting violations of the German benchmark exposure level of 10,000 nanofibers per cubic meter.

Background: Recent meta-analyses show that individuals with high risk variants in CHRNA5 on chromosome 15q25 are likely to develop lung cancer earlier than those with low-risk genotypes. The same high-risk genetic variants also predict nicotine dependence and delayed smoking cessation. It is unclear whether smoking cessation confers the same benefits in terms of lung cancer risk reduction for those who possess CHRNA5 risk variants versus those who do not. Methods: Meta-analyses examined the association between smoking cessation and lung cancer risk in 15 studies of individuals with European ancestry who possessed varying rs16969968 genotypes (N = 12,690 ever smokers, including 6988 cases of lung cancer and 5702 controls) in the International Lung Cancer Consortium. Results: Smoking cessation (former vs. current smokers) was associated with a lower likelihood of lung cancer (OR = 0.48, 95%CI = 0.30–0.75, p = 0.0015). Among lung cancer patients, smoking cessation was associated with a 7-year delay in median age of lung cancer diagnosis (HR = 0.68, 95%CI = 0.61–0.77, p = 4.9 ∗ 10–10). The CHRNA5 rs16969968 risk genotype (AA) was associated with increased risk and earlier diagnosis for lung cancer, but the beneficial effects of smoking cessation were very similar in those with and without the risk genotype. Conclusion: We demonstrate that quitting smoking is highly beneficial in reducing lung cancer risks for smokers regardless of their CHRNA5 rs16969968 genetic risk status. Smokers with high-risk CHRNA5 genotypes, on average, can largely eliminate their elevated genetic risk for lung cancer by quitting smoking- cutting their risk of lung cancer in half and delaying its onset by 7 years for those who develop it. These results: 1) underscore the potential value of smoking cessation for all smokers, 2) suggest that CHRNA5 rs16969968 genotype affects lung cancer diagnosis through its effects on smoking, and 3) have potential value for framing preventive interventions for those who smoke.

Background: Genome-wide association studies have identified polymorphisms linked to both smoking exposure and risk of lung cancer. The degree to which lung cancer risk is driven by increased smoking, genetics, or gene–environment interactions is not well understood. Methods: We analyzed associations between 28 single nucleotide polymorphisms (SNPs) previously associated with smoking quantity and lung cancer in 7156 African-American females in the Women's Health Initiative (WHI), then analyzed main effects of top nominally significant SNPs and interactions between SNPs, cigarettes per day (CPD) and pack-years for lung cancer in an independent, multi-center case–control study of African-American females and males (1078 lung cancer cases and 822 controls). Findings: Nine nominally significant SNPs for CPD in WHI were associated with incident lung cancer (corrected p-values from 0.027 to 6.09 × 10−5). CPD was found to be a nominally significant effect modifier between SNP and lung cancer for six SNPs, including CHRNA5 rs2036527[A](betaSNP*CPD = −0.017, p = 0.0061, corrected p = 0.054), which was associated with CPD in a previous genome-wide meta-analysis of African-Americans. Interpretation: These results suggest that chromosome 15q25.1 variants are robustly associated with CPD and lung cancer in African-Americans and that the allelic dose effect of these polymorphisms on lung cancer risk is most pronounced in lighter smokers.

In their foundational work on the social construction of gender, Kessler and McKenna (1978) investigated the relationship between gender attribution and genital attribution. We used digital reproductions of the original stimuli to replicate their findings in the current social context. To further investigate the underlying decision processes we applied eye tracking. The stimuli shown varied in the composition of gender cues: from those more commonly associated with maleness to associated with femaleness. Applying the ethnomethodological approach originally used, participants were asked to decide for each stimulus whether they saw a man or a woman and to indicate subjective confidence with the decision. In line with the original results we found that the genital attribution contributed immensely to the gender attribution. Also, male gender was ascribed more often when the penis was present than was female gender when the vulva was shown. Eye tracking revealed that overall most dwell time as a proxy for important information was dedicated to the head, chest and genital areas of all the stimuli. Total dwell time depended on whether the gender attribution was made in line with the depicted genital, if the genital was a penis. Attributing female gender when a penis was present was associated with longer total dwell time, unlike attributing male gender with a vulva shown. This is indicative of higher cognitive effort and more difficulty ignoring the penis as opposed to the vulva. We interpret this finding in context of the persistent male dominance as well as to the socio-cultural understanding of the vulva as a concealed and therefore seemingly absent organ. In summary, we were able to show that the gender attribution is still closely linked to genital attribution when having a binary forced choice task and that the penis is a special cue in this attribution process.

This study presents results from sentence-completion and grammaticality-judgement tasks with seven German-speaking agrammatic aphasics and seven age-matched control subjects examining verb finiteness marking and verb-second (V2) placement. The patients were found to be selectively impaired in tense marking in the face of preserved mood and agreement marking. Moreover, our results revealed that V2 scores varied across our patients, with some showing impaired and others preserved V2 performance. These findings will be discussed in the light of different syntactic accounts of agrammatism.

This study presents results from sentence-completion and grammaticality-judgment tasks with 7 German-speaking agrammatic aphasics and 7 age-matched control subjects examining tense and subject-verb agreement marking. For both experimental tasks, we found that the aphasics achieved high correctness scores for agreement, while tense marking was severely impaired. To account for the observed tense-agreement dissociation, we suggest that the functional category T(ense)/INFL(ection) is tense-defective in agrammatic aphasia, i.e., it is specified for [+/-Realis], but not for [+/-Past]. It will also be argued that other accounts, specifically the tree-pruning model, do not explain our findings.

Recently, genetic association findings for nicotine dependence, smoking behavior, and smoking-related diseases converged to implicate the chromosome 15q25.1 region, which includes the CHRNA5-CHRNA3-CHRNB4 cholinergic nicotinic receptor subunit genes. In particular, association with the nonsynonymous CHRNA5 SNP rs16969968 and correlates has been replicated in several independent studies. Extensive genotyping of this region has suggested additional statistically distinct signals for nicotine dependence, tagged by rs578776 and rs588765. One goal of the Consortium for the Genetic Analysis of Smoking Phenotypes (CGASP) is to elucidate the associations among these markers and dichotomous smoking quantity (heavy versus light smoking), lung cancer, and chronic obstructive pulmonary disease (COPD). We performed a meta-analysis across 34 datasets of European-ancestry subjects, including 38,617 smokers who were assessed for cigarettes-per-day, 7,700 lung cancer cases and 5,914 lung-cancer-free controls (all smokers), and 2,614 COPD cases and 3,568 COPD-free controls (all smokers). We demonstrate statistically independent associations of rs16969968 and rs588765 with smoking (mutually adjusted p-values

In a population-based case-control study, we explored the associations between 42 polymorphisms in seven genes in this region and non-small cell lung cancer (NSCLC) risk among Caucasian (364 cases; 380 controls) and African American (95 cases; 103 controls) women. Two TERT region SNPs, rs2075786 and rs2853677, conferred an increased risk of developing NSCLC, especially among African American women, and TERT-rs2735940 was associated with a decreased risk of lung cancer among African Americans. Five of the 20 GHR polymorphisms and SEPP1-rs6413428 were associated with a marginally increased risk of NSCLC among Caucasians. Random forest analysis reinforced the importance of GHR among Caucasians and identified AMACR, TERT, and GHR among African Americans, which were also significant using gene-based risk scores. Smoking-SNP interactions were explored, and haplotypes in TERT and GHR associated with NSCLC risk were identified. The roles of TERT, GHR, AMACR and SEPP1 genes in lung carcinogenesis warrant further exploration.

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. [ABSTRACT FROM AUTHOR]