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Helmut Küchenhoff
Statistical Consulting Unit StaBLab, Department of Statistics, LMU Munich, Geschwister-Scholl-Platz 1, 80539 Munich, Germany

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Journal article
Published: 10 June 2021 in Viruses
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SARS-CoV-2 infection fatality ratios (IFR) remain controversially discussed with implications for political measures. The German county of Tirschenreuth suffered a severe SARS-CoV-2 outbreak in spring 2020, with particularly high case fatality ratio (CFR). To estimate seroprevalence, underreported infections, and IFR for the Tirschenreuth population aged ≥14 years in June/July 2020, we conducted a population-based study including home visits for the elderly, and analyzed 4203 participants for SARS-CoV-2 antibodies via three antibody tests. Latent class analysis yielded 8.6% standardized county-wide seroprevalence, a factor of underreported infections of 5.0, and 2.5% overall IFR. Seroprevalence was two-fold higher among medical workers and one third among current smokers with similar proportions of registered infections. While seroprevalence did not show an age-trend, the factor of underreported infections was 12.2 in the young versus 1.7 for ≥85-year-old. Age-specific IFRs were <0.5% below 60 years of age, 1.0% for age 60–69, and 13.2% for age 70+. Senior care homes accounted for 45% of COVID-19-related deaths, reflected by an IFR of 7.5% among individuals aged 70+ and an overall IFR of 1.4% when excluding senior care home residents from our computation. Our data underscore senior care home infections as key determinant of IFR additionally to age, insufficient targeted testing in the young, and the need for further investigations on behavioral or molecular causes of the fewer infections among current smokers.

ACS Style

Ralf Wagner; David Peterhoff; Stephanie Beileke; Felix Günther; Melanie Berr; Sebastian Einhauser; Anja Schütz; Hans Niller; Philipp Steininger; Antje Knöll; Matthias Tenbusch; Clara Maier; Klaus Korn; Klaus Stark; André Gessner; Ralph Burkhardt; Michael Kabesch; Holger Schedl; Helmut Küchenhoff; Annette Pfahlberg; Iris Heid; Olaf Gefeller; Klaus Überla. Estimates and Determinants of SARS-Cov-2 Seroprevalence and Infection Fatality Ratio Using Latent Class Analysis: The Population-Based Tirschenreuth Study in the Hardest-Hit German County in Spring 2020. Viruses 2021, 13, 1118 .

AMA Style

Ralf Wagner, David Peterhoff, Stephanie Beileke, Felix Günther, Melanie Berr, Sebastian Einhauser, Anja Schütz, Hans Niller, Philipp Steininger, Antje Knöll, Matthias Tenbusch, Clara Maier, Klaus Korn, Klaus Stark, André Gessner, Ralph Burkhardt, Michael Kabesch, Holger Schedl, Helmut Küchenhoff, Annette Pfahlberg, Iris Heid, Olaf Gefeller, Klaus Überla. Estimates and Determinants of SARS-Cov-2 Seroprevalence and Infection Fatality Ratio Using Latent Class Analysis: The Population-Based Tirschenreuth Study in the Hardest-Hit German County in Spring 2020. Viruses. 2021; 13 (6):1118.

Chicago/Turabian Style

Ralf Wagner; David Peterhoff; Stephanie Beileke; Felix Günther; Melanie Berr; Sebastian Einhauser; Anja Schütz; Hans Niller; Philipp Steininger; Antje Knöll; Matthias Tenbusch; Clara Maier; Klaus Korn; Klaus Stark; André Gessner; Ralph Burkhardt; Michael Kabesch; Holger Schedl; Helmut Küchenhoff; Annette Pfahlberg; Iris Heid; Olaf Gefeller; Klaus Überla. 2021. "Estimates and Determinants of SARS-Cov-2 Seroprevalence and Infection Fatality Ratio Using Latent Class Analysis: The Population-Based Tirschenreuth Study in the Hardest-Hit German County in Spring 2020." Viruses 13, no. 6: 1118.

Preprint content
Published: 04 April 2021
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SARS-CoV-2 infection fatality ratios (IFR) remain controversially discussed with implications for political measures, but the number of registered infections depends on testing strategies and deduced case fatality ratios (CFR) are poor proxies for IFR. The German county of Tirschenreuth suffered a severe SARS-CoV-2 outbreak in spring 2020 with particularly high CFR. To estimate seroprevalence, dark figure, and IFR for the Tirschenreuth population aged ≥14 years in June/July 2020 with misclassification error control, we conducted a population-based study, including home visits for elderly, and analyzed 4203 participants for SARS-CoV-2 antibodies via three antibody tests (64% of our random sample). Latent class analysis yielded 8.6% standardized county-wide seroprevalence, dark figure factor 5.0, and 2.5% overall IFR. Seroprevalence was two-fold higher among medical workers and one third among current smokers with similar proportions of registered infections. While seroprevalence did not show an age-trend, the dark figure was 12.2 in the young versus 1.7 for ≥85-year-old. Age-specific IFRs were <0.5% below 60 years of age, 1.0% for age 60-69, 13.2% for age 70+, confirming a previously reported age-model for IFR. Senior care homes accounted for 45% of COVID-19-related deaths, reflected by an IFR of 7.5% among individuals aged 70+ and an overall IFR of 1.4% when excluding senior care home residents from our computation. Our data underscore senior care home infections as key determinant of IFR additionally to age, insufficient targeted testing in the young, and the need for further investigations on behavioral or molecular causes of the fewer infections among current smokers.

ACS Style

Ralf Wagner; David Peterhoff; Stephanie Beileke; Felix Guenther; Melanie Berr; Sebastian Einhauser; Anja Schütz; Hans Helmut Niller; Philipp Steininger; Antje Knöll; Matthias Tenbusch; Clara Maier; Klaus Korn; Klaus J. Stark; Andre Gessner; Ralph Burkhardt; Michael Kabesch; Holger Schedl; Helmut Küchenhoff; Annette B. Pfahlberg; Iris M. Heid; Olaf Gefeller; Klaus Überla. Estimates and determinants of SARS-CoV-2 seroprevalence and infection fatality ratio using latent class analysis: the population-based Tirschenreuth study in the hardest-hit German county in spring 2020. 2021, 1 .

AMA Style

Ralf Wagner, David Peterhoff, Stephanie Beileke, Felix Guenther, Melanie Berr, Sebastian Einhauser, Anja Schütz, Hans Helmut Niller, Philipp Steininger, Antje Knöll, Matthias Tenbusch, Clara Maier, Klaus Korn, Klaus J. Stark, Andre Gessner, Ralph Burkhardt, Michael Kabesch, Holger Schedl, Helmut Küchenhoff, Annette B. Pfahlberg, Iris M. Heid, Olaf Gefeller, Klaus Überla. Estimates and determinants of SARS-CoV-2 seroprevalence and infection fatality ratio using latent class analysis: the population-based Tirschenreuth study in the hardest-hit German county in spring 2020. . 2021; ():1.

Chicago/Turabian Style

Ralf Wagner; David Peterhoff; Stephanie Beileke; Felix Guenther; Melanie Berr; Sebastian Einhauser; Anja Schütz; Hans Helmut Niller; Philipp Steininger; Antje Knöll; Matthias Tenbusch; Clara Maier; Klaus Korn; Klaus J. Stark; Andre Gessner; Ralph Burkhardt; Michael Kabesch; Holger Schedl; Helmut Küchenhoff; Annette B. Pfahlberg; Iris M. Heid; Olaf Gefeller; Klaus Überla. 2021. "Estimates and determinants of SARS-CoV-2 seroprevalence and infection fatality ratio using latent class analysis: the population-based Tirschenreuth study in the hardest-hit German county in spring 2020." , no. : 1.

Original paper
Published: 11 March 2021 in Epidemiology and Infection
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We analysed the coronavirus disease 2019 epidemic curve from March to the end of April 2020 in Germany. We use statistical models to estimate the number of cases with disease onset on a given day and use back-projection techniques to obtain the number of new infections per day. The respective time series are analysed by a trend regression model with change points. The change points are estimated directly from the data. We carry out the analysis for the whole of Germany and the federal state of Bavaria, where we have more detailed data. Both analyses show a major change between 9 and 13 March for the time series of infections: from a strong increase to a decrease. Another change was found between 25 March and 29 March, where the decline intensified. Furthermore, we perform an analysis stratified by age. A main result is a delayed course of the pandemic for the age group 80 + resulting in a turning point at the end of March. Our results differ from those by other authors as we take into account the reporting delay, which turned out to be time dependent and therefore changes the structure of the epidemic curve compared to the curve of newly reported cases.

ACS Style

Helmut Küchenhoff; Felix Günther; Michael Höhle; Andreas Bender. Analysis of the early COVID-19 epidemic curve in Germany by regression models with change points. Epidemiology and Infection 2021, 149, e68 .

AMA Style

Helmut Küchenhoff, Felix Günther, Michael Höhle, Andreas Bender. Analysis of the early COVID-19 epidemic curve in Germany by regression models with change points. Epidemiology and Infection. 2021; 149 ():e68.

Chicago/Turabian Style

Helmut Küchenhoff; Felix Günther; Michael Höhle; Andreas Bender. 2021. "Analysis of the early COVID-19 epidemic curve in Germany by regression models with change points." Epidemiology and Infection 149, no. : e68.

Protocol
Published: 11 February 2021 in Clinical Nutrition ESPEN
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Summary Background and aims Limited data are available on the impact of clinical nutrition over the course of critical illness and post-discharge outcomes. The present study aims to characterize the use of nutrition support in patients admitted to European intensive care units (ICUs), and its impact on clinical outcomes. Here we present the procedures of data collection and evaluation. Methods Around 100 medical, surgical, or trauma ICUs in 11 countries (Austria, Belgium, Czech Republic, Germany, France, Hungary, Italy, Poland, Spain, Sweden, United Kingdom) participate in the study. In defined months between November 2019 and April 2020, approximately 1250 patients are enrolled if staying in ICU for at least five consecutive days. Data from ICU day 1–4 are collected retrospectively, followed by a prospective observation period from day 5–90 after ICU admission. Data collection includes patient characteristics, nutrition parameters, complications, ICU and hospital length of stay, discharge status, and functional outcomes. For data analysis, the target is 1000 patients with complete data. Statistical analyses will be descriptive, with multivariate analyses adjusted for potential confounders to explore associations between nutritional balance and change in functional status, time-to-weaning from invasive mechanical ventilation, time to first clinical complication, and overall 15, 30 and 90-day survival. Ethics and dissemination This non-interventional study was reviewed and approved by the ethics committee of the Medical University Vienna, Vienna, Austria (approval number 1678/2019), and the respective ethical committees from participating sites at country and/or local level, as required. Results will be shared with investigators on a country level, and a publication and results presentation at the 2021 ESPEN Congress is planned. Trial registration ClinicalTrials.gov identifier NCT04143503.

ACS Style

M. Hiesmayr; A. Csomos; K. Dams; G. Elke; W. Hartl; O. Huet; L.J. Krzych; H. Kuechenhoff; M. Matejovic; Z.A. Puthucheary; O. Rooyackers; R. Tetamo; I. Tjäder; C. Vaquerizo. Protocol for a prospective cohort study on the use of clinical nutrition and assessment of long-term clinical and functional outcomes in critically ill adult patients. Clinical Nutrition ESPEN 2021, 43, 104 -110.

AMA Style

M. Hiesmayr, A. Csomos, K. Dams, G. Elke, W. Hartl, O. Huet, L.J. Krzych, H. Kuechenhoff, M. Matejovic, Z.A. Puthucheary, O. Rooyackers, R. Tetamo, I. Tjäder, C. Vaquerizo. Protocol for a prospective cohort study on the use of clinical nutrition and assessment of long-term clinical and functional outcomes in critically ill adult patients. Clinical Nutrition ESPEN. 2021; 43 ():104-110.

Chicago/Turabian Style

M. Hiesmayr; A. Csomos; K. Dams; G. Elke; W. Hartl; O. Huet; L.J. Krzych; H. Kuechenhoff; M. Matejovic; Z.A. Puthucheary; O. Rooyackers; R. Tetamo; I. Tjäder; C. Vaquerizo. 2021. "Protocol for a prospective cohort study on the use of clinical nutrition and assessment of long-term clinical and functional outcomes in critically ill adult patients." Clinical Nutrition ESPEN 43, no. : 104-110.

Journal article
Published: 29 December 2020 in Cancers
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Pedicle clamping (PC) during liver resection for colorectal metastases (CRLM) is used to reduce blood loss and allogeneic blood transfusion (ABT). The effect on long-term oncologic outcomes is still under debate. A retrospective analysis of the impact of PC on ABT-demand regarding overall (OS) and recurrence-free survival (RFS) in 336 patients undergoing curative resection for CRLM was carried out. Survival analysis was performed by both univariate and multivariate methods and propensity-score (PS) matching. PC was employed in 75 patients (22%). No increased postoperative morbidity was monitored. While the overall ABT-rate was comparable (35% vs. 37%, p = 0.786), a reduced demand for more than two ABT-units was observed (p = 0.046). PC-patients had better median OS (78 vs. 47 months, p = 0.005) and RFS (36 vs. 23 months, p = 0.006). Multivariate analysis revealed PC as an independent prognostic factor for OS (HR = 0.60; p = 0.009) and RFS (HR = 0.67; p = 0.017). For PC-patients, 1:2 PS-matching (N = 174) showed no differences in the overall ABT-rate compared to no-PC-patients (35% vs. 40%, p = 0.619), but a trend towards reduced transfusion requirement (>2 ABT-units: 9% vs. 21%, p = 0.052; >4 ABT-units: 2% vs. 11%, p = 0.037) and better survival (OS: 78 vs. 44 months, p = 0.088; RFS: 36 vs. 24 months; p = 0.029). Favorable long-term outcomes and lower rates of increased transfusion demand were observed in patients with PC undergoing resection for CRLM. Further prospective evaluation of potential oncologic benefits of PC in these patients may be meaningful.

ACS Style

Tobias S. Schiergens; Moritz Drefs; Maximilian Dörsch; Florian Kühn; Markus Albertsmeier; Hanno Niess; Markus B. Schoenberg; Matthias Assenmacher; Helmut Küchenhoff; Wolfgang E. Thasler; Markus O. Guba; Martin K. Angele; Markus Rentsch; Jens Werner; Joachim Andrassy. Prognostic Impact of Pedicle Clamping During Liver Resection for Colorectal Metastases. Cancers 2020, 13, 72 .

AMA Style

Tobias S. Schiergens, Moritz Drefs, Maximilian Dörsch, Florian Kühn, Markus Albertsmeier, Hanno Niess, Markus B. Schoenberg, Matthias Assenmacher, Helmut Küchenhoff, Wolfgang E. Thasler, Markus O. Guba, Martin K. Angele, Markus Rentsch, Jens Werner, Joachim Andrassy. Prognostic Impact of Pedicle Clamping During Liver Resection for Colorectal Metastases. Cancers. 2020; 13 (1):72.

Chicago/Turabian Style

Tobias S. Schiergens; Moritz Drefs; Maximilian Dörsch; Florian Kühn; Markus Albertsmeier; Hanno Niess; Markus B. Schoenberg; Matthias Assenmacher; Helmut Küchenhoff; Wolfgang E. Thasler; Markus O. Guba; Martin K. Angele; Markus Rentsch; Jens Werner; Joachim Andrassy. 2020. "Prognostic Impact of Pedicle Clamping During Liver Resection for Colorectal Metastases." Cancers 13, no. 1: 72.

Research paper
Published: 01 December 2020 in Biometrical Journal
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To assess the current dynamics of an epidemic, it is central to collect information on the daily number of newly diseased cases. This is especially important in real‐time surveillance, where the aim is to gain situational awareness, for example, if cases are currently increasing or decreasing. Reporting delays between disease onset and case reporting hamper our ability to understand the dynamics of an epidemic close to now when looking at the number of daily reported cases only. Nowcasting can be used to adjust daily case counts for occurred‐but‐not‐yet‐reported events. Here, we present a novel application of nowcasting to data on the current COVID‐19 pandemic in Bavaria. It is based on a hierarchical Bayesian model that considers changes in the reporting delay distribution over time and associated with the weekday of reporting. Furthermore, we present a way to estimate the effective time‐varying case reproduction number based on predictions of the nowcast. The approaches are based on previously published work, that we considerably extended and adapted to the current task of nowcasting COVID‐19 cases. We provide methodological details of the developed approach, illustrate results based on data of the current pandemic, and evaluate the model based on synthetic and retrospective data on COVID‐19 in Bavaria. Results of our nowcasting are reported to the Bavarian health authority and published on a webpage on a daily basis (https://corona.stat.uni-muenchen.de/). Code and synthetic data for the analysis are available from https://github.com/FelixGuenther/nc_covid19_bavaria and can be used for adaption of our approach to different data.

ACS Style

Felix Günther; Andreas Bender; Katharina Katz; Helmut Küchenhoff; Michael Höhle. Nowcasting the COVID‐19 pandemic in Bavaria. Biometrical Journal 2020, 63, 490 -502.

AMA Style

Felix Günther, Andreas Bender, Katharina Katz, Helmut Küchenhoff, Michael Höhle. Nowcasting the COVID‐19 pandemic in Bavaria. Biometrical Journal. 2020; 63 (3):490-502.

Chicago/Turabian Style

Felix Günther; Andreas Bender; Katharina Katz; Helmut Küchenhoff; Michael Höhle. 2020. "Nowcasting the COVID‐19 pandemic in Bavaria." Biometrical Journal 63, no. 3: 490-502.

Preprint content
Published: 30 October 2020
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We analyze the Covid-19 epidemic curve from March to end of April 2020 in Germany. We use statistical models to estimate the number of cases with disease onset on a given day and use back-projection techniques to obtain the number of new infections per day. The respective time series are analyzed by a trend regression model with change points. The change points are estimated directly from the data. We carry out the analysis for the whole of Germany and the federal state of Bavaria, where we have more detailed data. Both analyses show a major change between March 9th and 13th for the time series of infections: from a strong increase to a decrease. Another change was found between March 25th and March 29th, where the decline intensified. Furthermore, we perform an analysis stratified by age. A main result is a delayed course of the epidemic for the age group 80+ resulting in a turning point at the end of March.Our results differ from those by other authors as we take into account the reporting delay, which turned out to be time dependent and therefore changes the structure of the epidemic curve compared to the curve of newly reported cases.

ACS Style

Helmut Küchenhoff; Felix Guenther; Michael Höhle; Andreas Bender. Analysis of the early Covid-19 epidemic curve in Germany by regression models with change points. 2020, 1 .

AMA Style

Helmut Küchenhoff, Felix Guenther, Michael Höhle, Andreas Bender. Analysis of the early Covid-19 epidemic curve in Germany by regression models with change points. . 2020; ():1.

Chicago/Turabian Style

Helmut Küchenhoff; Felix Guenther; Michael Höhle; Andreas Bender. 2020. "Analysis of the early Covid-19 epidemic curve in Germany by regression models with change points." , no. : 1.

Other
Published: 29 September 2020
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Background Reported COVID-19 case numbers are key to monitoring pandemic spread and decision-making on policy measures but require careful interpretation as they depend substantially on testing strategy. A high and targeted testing activity is essential for a successful Test-Trace-Isolate strategy. However, it also leads to increased numbers of false-positives and can foster a debate on the actual pandemic state, which can slow down action and acceptance of containment measures. Aim We evaluate the impact of misclassification in COVID-19 diagnostics on reported case numbers and estimated numbers of disease onsets (epidemic curve). Methods We developed a statistical adjustment of reported case numbers for erroneous diagnostic results that facilitates a misclassification-adjusted real-time estimation of the epidemic curve based on nowcasting. Under realistic misclassification scenarios, we provide adjusted case numbers for Germany and illustrate misclassification-adjusted nowcasting for Bavarian data. Results We quantify the impact of diagnostic misclassification on time-series of reported case numbers, highlighting the relevance of a specificity smaller than one when test activity changes over time. Adjusting for misclassification, we find that the increase of cases starting in July might have been smaller than indicated by raw case counts, but cannot be fully explained by increasing numbers of false-positives due to increased testing. The effect of misclassification becomes negligible when true incidence is high. Conclusions Adjusting case numbers for misclassification can improve this important measure on short-term dynamics of the pandemic and should be considered in data-based surveillance. Further limitations of case reporting data exist and have to be considered.

ACS Style

Felix Guenther; Ursula Berger; Michael Höhle; Andreas Bender; Manfred Wildner; Iris M. Heid; Helmut Küchenhoff. Analysis of COVID-19 case numbers: adjustment for diagnostic misclassification on the example of German case reporting data. 2020, 1 .

AMA Style

Felix Guenther, Ursula Berger, Michael Höhle, Andreas Bender, Manfred Wildner, Iris M. Heid, Helmut Küchenhoff. Analysis of COVID-19 case numbers: adjustment for diagnostic misclassification on the example of German case reporting data. . 2020; ():1.

Chicago/Turabian Style

Felix Guenther; Ursula Berger; Michael Höhle; Andreas Bender; Manfred Wildner; Iris M. Heid; Helmut Küchenhoff. 2020. "Analysis of COVID-19 case numbers: adjustment for diagnostic misclassification on the example of German case reporting data." , no. : 1.

Other
Published: 24 September 2020
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During the SARS-CoV-2 outbreak, several epidemiological measures, such as cumulative case-counts, incidence rates, effective reproduction numbers and doubling times, have been used to inform the general public and to justify interventions such as lockdown. During the course of the epidemic, it has been very likely that not all infectious people have been identified, which lead to incomplete case-detection. Apart from asymptomatic infections, possible reasons for incomplete case-detection are availability of test kits and changes in test policies during the course of the epidemic. So far, it has not been examined how biased the reported epidemiological measures are in the presence of incomplete case detection. In this work, we assess the four frequently used measures with respect to incomplete case-detection: 1) cumulative case-count, 2) incidence rate, 3) effective reproduction number and 4) doubling time. We apply an age-structured SIR model to simulate a SARS-CoV-2 outbreak followed by a lockdown in a hypothetical population. Different scenarios about temporal variations in case-detection are applied to the four measures during outbreak and lockdown. The biases resulting from incomplete case-detection on the four measures are compared. It turns out that the most frequently used epidemiological measure, the cumulative case count is most prone to bias in all of our settings. The effective reproduction number is the least biased measure. With a view to future reporting about this or other epidemics, we recommend to use of the effective reproduction number for informing the general public and policy makers.

ACS Style

Ralph Brinks; Helmut Kuechenhoff; Joerg Timm; Tobias Kurth; Annika Hoyer. Epidemiological measures for informing the general public during the SARS-CoV-2-outbreak: simulation study about bias by incomplete case-detection. 2020, 1 .

AMA Style

Ralph Brinks, Helmut Kuechenhoff, Joerg Timm, Tobias Kurth, Annika Hoyer. Epidemiological measures for informing the general public during the SARS-CoV-2-outbreak: simulation study about bias by incomplete case-detection. . 2020; ():1.

Chicago/Turabian Style

Ralph Brinks; Helmut Kuechenhoff; Joerg Timm; Tobias Kurth; Annika Hoyer. 2020. "Epidemiological measures for informing the general public during the SARS-CoV-2-outbreak: simulation study about bias by incomplete case-detection." , no. : 1.

Research article
Published: 02 August 2020 in Genetic Epidemiology
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Imaging technology and machine learning algorithms for disease classification set the stage for high‐throughput phenotyping and promising new avenues for genome‐wide association studies (GWAS). Despite emerging algorithms, there has been no successful application in GWAS so far. We establish machine learning‐based phenotyping in genetic association analysis as misclassification problem. To evaluate chances and challenges, we performed a GWAS based on automatically classified age‐related macular degeneration (AMD) in UK Biobank (images from 135,500 eyes; 68,400 persons). We quantified misclassification of automatically derived AMD in internal validation data (4,001 eyes; 2,013 persons) and developed a maximum likelihood approach (MLA) to account for it when estimating genetic association. We demonstrate that our MLA guards against bias and artifacts in simulation studies. By combining a GWAS on automatically derived AMD and our MLA in UK Biobank data, we were able to dissect true association (ARMS2 /HTRA1 , CFH ) from artifacts (near HERC2 ) and identified eye color as associated with the misclassification. On this example, we provide a proof‐of‐concept that a GWAS using machine learning‐derived disease classification yields relevant results and that misclassification needs to be considered in analysis. These findings generalize to other phenotypes and emphasize the utility of genetic data for understanding misclassification structure of machine learning algorithms.

ACS Style

Felix Guenther; Caroline Brandl; Thomas W. Winkler; Veronika Wanner; Klaus Stark; Helmut Kuechenhoff; Iris M. Heid. Chances and challenges of machine learning‐based disease classification in genetic association studies illustrated on age‐related macular degeneration. Genetic Epidemiology 2020, 44, 759 -777.

AMA Style

Felix Guenther, Caroline Brandl, Thomas W. Winkler, Veronika Wanner, Klaus Stark, Helmut Kuechenhoff, Iris M. Heid. Chances and challenges of machine learning‐based disease classification in genetic association studies illustrated on age‐related macular degeneration. Genetic Epidemiology. 2020; 44 (7):759-777.

Chicago/Turabian Style

Felix Guenther; Caroline Brandl; Thomas W. Winkler; Veronika Wanner; Klaus Stark; Helmut Kuechenhoff; Iris M. Heid. 2020. "Chances and challenges of machine learning‐based disease classification in genetic association studies illustrated on age‐related macular degeneration." Genetic Epidemiology 44, no. 7: 759-777.

Other
Published: 28 June 2020
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To assess the current dynamic of an epidemic it is central to collect information on the daily number of newly diseased cases. This is especially important in real-time surveillance, where the aim is to gain situational awareness, e.g., if cases are currently increasing or decreasing. Reporting delays between disease onset and case reporting hamper our ability to understand the dynamic of an epidemic close to now when looking at the number of daily reported cases only. Nowcasting can be used to adjust daily case counts for occurred-but-not-yet-reported events. Here, we present a novel application of nowcasting to data on the current COVID–19 pandemic in Bavaria. It is based on a hierarchical Bayesian model that considers changes in the reporting delay distribution over time and associated with the weekday of reporting. Furthermore, we present a way to estimate the effective time-dependent case reproduction number Re (t) based on predictions of the nowcast. The approaches are based on previously published work, that we considerably extended and adapted to the current task of nowcasting COVID–19 cases. We provide methodological details of the developed approach, illustrate results based on data of the current epidemic, and evaluate the model based on synthetic and retrospective data on COVID–19 in Bavaria. Results of our nowcasting are reported to the Bavarian health authority and published on a webpage on a daily basis (https://corona.stat.uni-muenchen.de/). Code and synthetic data for the analysis is available from https://github.com/FelixGuenther/nc_covid19_bavaria and can be used for adaptions of our approach to different data.

ACS Style

Felix Guenther; Andreas Bender; Katharina Katz; Helmut Kuechenhoff; Michael Hoehle. Nowcasting the COVID–19 pandemic in Bavaria. 2020, 1 .

AMA Style

Felix Guenther, Andreas Bender, Katharina Katz, Helmut Kuechenhoff, Michael Hoehle. Nowcasting the COVID–19 pandemic in Bavaria. . 2020; ():1.

Chicago/Turabian Style

Felix Guenther; Andreas Bender; Katharina Katz; Helmut Kuechenhoff; Michael Hoehle. 2020. "Nowcasting the COVID–19 pandemic in Bavaria." , no. : 1.

Preprint content
Published: 20 December 2019
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BackgroundAdvanced age-related macular degeneration (AMD) is a leading cause of blindness. While around half of the genetic contribution to advanced AMD has been uncovered, little is known about the genetic architecture of the preceding early stages of the diseases.MethodsTo identify genetic factors for early AMD, we conducted a genome-wide association meta-analysis with 14,034 early AMD cases and 91,214 controls from 11 sources of data including data from the International AMD Genomics Consortium (IAMDGC) and the UK Biobank (UKBB). We ascertained early AMD via color fundus photographs by manual grading for 10 sources and by using an automated machine learning approach for >170,000 images from UKBB. We searched for significant genetic loci in a genome-wide association screen (P-8) based on the meta-analysis of the 11 sources and via a candidate approach based on 13 suggestive early AMD variants from Holliday et al 2013 (PResultsWe identified 11 loci for early AMD, 9 novel and 2 known for early AMD. Most of these 11 loci overlapped with known advanced AMD loci (near ARMS2/HTRA1, CFH, APOE, C2, C3, CETP, PVRL2, TNFRSF10A, VEGFA), except two that were completely novel to any AMD. Among the 17 genes within the two novel loci, in-silico functional annotation suggested CD46 and TYR as the most likely responsible genes. We found the presence or absence of an early AMD effect to distinguish known pathways of advanced AMD genetics (complement/lipid pathways or extracellular matrix metabolism, respectively).ConclusionsOur data on early AMD genetics provides a resource comparable to the existing data on advanced AMD genetics, which enables a joint view. Our large GWAS on early AMD identified novel loci, highlighted shared and distinct genetics between early and advanced AMD and provides insights into AMD etiology. The ability of early AMD effects to differentiate the major pathways for advanced AMD underscores the biological relevance of a joint view on early and advanced AMD genetics.

ACS Style

Thomas W Winkler; Felix Grassmann; Caroline Brandl; Christina Kiel; Felix Guenther; Tobias Strunz; Lorraine Weidner; Martina E Zimmermann; Christina A. Korb; Alicia Poplawski; Alexander K Schuster; Martina Müller-Nurasyid; Annette Peters; Franziska G Rauscher; Tobias Elze; Katrin Horn; Markus Scholz; Marisa Cañadas-Garre; Amy Jayne McKnight; Nicola Quinn; Ruth E Hogg; Helmut Kuechenhoff; Iris M Heid; Klaus J Stark; Bernhard Hf Weber. Genome-wide association meta-analysis for early age-related macular degeneration highlights novel loci and insights for advanced disease. 2019, 1 .

AMA Style

Thomas W Winkler, Felix Grassmann, Caroline Brandl, Christina Kiel, Felix Guenther, Tobias Strunz, Lorraine Weidner, Martina E Zimmermann, Christina A. Korb, Alicia Poplawski, Alexander K Schuster, Martina Müller-Nurasyid, Annette Peters, Franziska G Rauscher, Tobias Elze, Katrin Horn, Markus Scholz, Marisa Cañadas-Garre, Amy Jayne McKnight, Nicola Quinn, Ruth E Hogg, Helmut Kuechenhoff, Iris M Heid, Klaus J Stark, Bernhard Hf Weber. Genome-wide association meta-analysis for early age-related macular degeneration highlights novel loci and insights for advanced disease. . 2019; ():1.

Chicago/Turabian Style

Thomas W Winkler; Felix Grassmann; Caroline Brandl; Christina Kiel; Felix Guenther; Tobias Strunz; Lorraine Weidner; Martina E Zimmermann; Christina A. Korb; Alicia Poplawski; Alexander K Schuster; Martina Müller-Nurasyid; Annette Peters; Franziska G Rauscher; Tobias Elze; Katrin Horn; Markus Scholz; Marisa Cañadas-Garre; Amy Jayne McKnight; Nicola Quinn; Ruth E Hogg; Helmut Kuechenhoff; Iris M Heid; Klaus J Stark; Bernhard Hf Weber. 2019. "Genome-wide association meta-analysis for early age-related macular degeneration highlights novel loci and insights for advanced disease." , no. : 1.

Journal article
Published: 02 December 2019 in AStA Wirtschafts- und Sozialstatistisches Archiv
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Zusammenfassung Burgard et al. (2020) stellen in ihrem Artikel zu Qualitätszielfunktionen für stark variierende Gemeindegrößen im Zensus 2021 Erweiterungen der Stichproben- und Schätzmethoden des Zensus 2011 vor, die kleine Gemeinden unter 10.000 Einwohnern in den Entscheidungsprozess integrieren. Die Dringlichkeit zur Lösung dieses Problems wurde ebenso im Urteil des Bundesverfassungsgerichts zur Volkszählung 2011 festgestellt. Ziel dieser Erwiderung ist eine eingehende Diskussion der Ergebnisse des vorangegangenen Beitrags mit namhaften Experten auf diesem Gebiet. Insbesondere geht es um eine Einordnung des Artikels in den Wissenschaftskontext (Krämer), die Bedeutung von Nichtstichprobenfehlern für den Zensus (Küchenhoff), den Zensus aus Sicht der Amtsstatistik (Bleninger und Fürnrohr) sowie aus statistisch-methodischer Sicht (Kiesl). Darüber hinaus werden aktuelle Entwicklungen vorgestellt.

ACS Style

Sara Bleninger; Michael Fürnrohr; Hans Kiesl; Walter Krämer; Helmut Küchenhoff; Jan Pablo Burgard; Ralf Münnich; Martin Rupp. Kommentare und Erwiderung zu: Qualitätszielfunktionen für stark variierende Gemeindegrößen im Zensus 2021. AStA Wirtschafts- und Sozialstatistisches Archiv 2019, 14, 67 -98.

AMA Style

Sara Bleninger, Michael Fürnrohr, Hans Kiesl, Walter Krämer, Helmut Küchenhoff, Jan Pablo Burgard, Ralf Münnich, Martin Rupp. Kommentare und Erwiderung zu: Qualitätszielfunktionen für stark variierende Gemeindegrößen im Zensus 2021. AStA Wirtschafts- und Sozialstatistisches Archiv. 2019; 14 (1):67-98.

Chicago/Turabian Style

Sara Bleninger; Michael Fürnrohr; Hans Kiesl; Walter Krämer; Helmut Küchenhoff; Jan Pablo Burgard; Ralf Münnich; Martin Rupp. 2019. "Kommentare und Erwiderung zu: Qualitätszielfunktionen für stark variierende Gemeindegrößen im Zensus 2021." AStA Wirtschafts- und Sozialstatistisches Archiv 14, no. 1: 67-98.

Original article
Published: 19 June 2019 in Radiation and Environmental Biophysics
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Exposure-lag-response associations shed light on the duration of pathogenesis for radiation-induced diseases. To investigate such relations for lung cancer mortality in the German uranium miners of the Wismut company, we apply distributed lag non-linear models (DLNMs) which offer a flexible description of the lagged risk response to protracted radon exposure. Exposure-lag functions are implemented with B-Splines in Cox models of proportional hazards. The DLNM approach yielded good agreement of exposure-lag-response surfaces for the German cohort and for the previously studied cohort of American Colorado miners. For both cohorts, a minimum lag of about 2 year for the onset of risk after first exposure explained the data well, but possibly with large uncertainty. Risk estimates from DLNMs were directly compared with estimates from both standard radio-epidemiological models and biologically based mechanistic models. For age > 45 year, all models predict decreasing estimates of the Excess Relative Risk (ERR). However, at younger age, marked differences appear as DLNMs exhibit ERR peaks, which are not detected by the other models. After comparing exposure-responses for biological processes in mechanistic risk models with exposure-responses for hazard ratios in DLNMs, we propose a typical period of 15 year for radon-related lung carcinogenesis. The period covers the onset of radiation-induced inflammation of lung tissue until cancer death. The DLNM framework provides a view on age-risk patterns supplemental to the standard radio-epidemiological approach and to biologically based modeling.

ACS Style

Matthias Aßenmacher; Jan Christian Kaiser; Ignacio Zaballa; Antonio Gasparrini; Helmut Küchenhoff. Exposure–lag–response associations between lung cancer mortality and radon exposure in German uranium miners. Radiation and Environmental Biophysics 2019, 58, 321 -336.

AMA Style

Matthias Aßenmacher, Jan Christian Kaiser, Ignacio Zaballa, Antonio Gasparrini, Helmut Küchenhoff. Exposure–lag–response associations between lung cancer mortality and radon exposure in German uranium miners. Radiation and Environmental Biophysics. 2019; 58 (3):321-336.

Chicago/Turabian Style

Matthias Aßenmacher; Jan Christian Kaiser; Ignacio Zaballa; Antonio Gasparrini; Helmut Küchenhoff. 2019. "Exposure–lag–response associations between lung cancer mortality and radon exposure in German uranium miners." Radiation and Environmental Biophysics 58, no. 3: 321-336.

Original paper
Published: 18 June 2019 in European Archives of Psychiatry and Clinical Neuroscience
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To evaluate the course of neuropsychological impairment, patients with first-episode schizophrenia and healthy controls were assessed with a comprehensive test battery at the time of index treatment and after a 5- and 15-year follow-up period. Summary scores for verbal intelligence (VBI), spatial organization, verbal fluency, verbal learning, semantic memory, visual memory, delay/retention rate, short-term memory, visual–motor processing and attention (VSM) and abstraction/flexibility were constructed. Our results show that neurocognitive functioning is impaired already at the onset of schizophrenia and remains stable over the 15-year follow-up period with an improvement in VBI. With regard to the presence of a deficit syndrome, it became apparent that the group with a deficit syndrome showed a deterioration of neurocognitive functions during the follow-up period, most pronounced in VSM. On the other hand, the group without a deficit syndrome showed an improvement in neurocognitive functions at the 15-year follow-up, which exceeded the learning effects of healthy control subjects. Neurocognitive performance at index assessment strongly predicted the performance at the 15-year follow-up. Most likely due to the small sample size, there were only weak associations between treatment with different types of neuroleptics and neurocognitive performance.

ACS Style

M. Albus; W. Hubmann; F. Mohr; T. V. Tiedemann; S. Pechler; D. Drießlein; Helmut Küchenhoff. Neurocognitive functioning in patients with first-episode schizophrenia: results of a prospective 15-year follow-up study. European Archives of Psychiatry and Clinical Neuroscience 2019, 270, 689 -698.

AMA Style

M. Albus, W. Hubmann, F. Mohr, T. V. Tiedemann, S. Pechler, D. Drießlein, Helmut Küchenhoff. Neurocognitive functioning in patients with first-episode schizophrenia: results of a prospective 15-year follow-up study. European Archives of Psychiatry and Clinical Neuroscience. 2019; 270 (6):689-698.

Chicago/Turabian Style

M. Albus; W. Hubmann; F. Mohr; T. V. Tiedemann; S. Pechler; D. Drießlein; Helmut Küchenhoff. 2019. "Neurocognitive functioning in patients with first-episode schizophrenia: results of a prospective 15-year follow-up study." European Archives of Psychiatry and Clinical Neuroscience 270, no. 6: 689-698.

Original paper
Published: 04 June 2019 in AStA Advances in Statistical Analysis
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Common election poll reporting is often misleading as sample uncertainty is addressed insufficiently or not covered at all. Furthermore, main interest usually lies beyond the simple party shares. For a more comprehensive opinion poll and election coverage, we propose shifting the focus toward the reporting of survey-based probabilities for specific events of interest. We present such an approach for multi-party electoral systems, focusing on probabilities of coalition majorities. A Monte Carlo approach based on a Bayesian Multinomial-Dirichlet model is used for estimation. Probabilities are estimated, assuming the election was held today (“now-cast”), not accounting for potential shifts in the electorate until election day (“fore-cast”). Since our method is based on the posterior distribution of party shares, the approach can be used to answer a variety of questions related to the outcome of an election. We also introduce visualization techniques that facilitate a more adequate depiction of relevant quantities as well as respective uncertainties. The benefits of our approach are discussed by application to the German federal elections in 2013 and 2017. An open-source implementation of our methods is freely available in the R package coalitions.

ACS Style

Alexander Bauer; Andreas Bender; André Klima; Helmut Küchenhoff. KOALA: a new paradigm for election coverage. AStA Advances in Statistical Analysis 2019, 104, 101 -115.

AMA Style

Alexander Bauer, Andreas Bender, André Klima, Helmut Küchenhoff. KOALA: a new paradigm for election coverage. AStA Advances in Statistical Analysis. 2019; 104 (1):101-115.

Chicago/Turabian Style

Alexander Bauer; Andreas Bender; André Klima; Helmut Küchenhoff. 2019. "KOALA: a new paradigm for election coverage." AStA Advances in Statistical Analysis 104, no. 1: 101-115.

Research paper
Published: 14 May 2019 in Biometrical Journal
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Misclassification in binary outcomes can severely bias effect estimates of regression models when the models are naively applied to error‐prone data. Here, we discuss response misclassification in studies on the special class of bilateral diseases. Such diseases can affect neither, one, or both entities of a paired organ, for example, the eyes or ears. If measurements are available on both organ entities, disease occurrence in a person is often defined as disease occurrence in at least one entity. In this setting, there are two reasons for response misclassification: (a) ignorance of missing disease assessment in one of the two entities and (b) error‐prone disease assessment in the single entities. We investigate the consequences of ignoring both types of response misclassification and present an approach to adjust the bias from misclassification by optimizing an adequate likelihood function. The inherent modelling assumptions and problems in case of entity‐specific misclassification are discussed. This work was motivated by studies on age‐related macular degeneration (AMD), a disease that can occur separately in each eye of a person. We illustrate and discuss the proposed analysis approach based on real‐world data of a study on AMD and simulated data.

ACS Style

Felix Günther; Caroline Brandl; Iris M. Heid; Helmut Küchenhoff. Response misclassification in studies on bilateral diseases. Biometrical Journal 2019, 61, 1033 -1048.

AMA Style

Felix Günther, Caroline Brandl, Iris M. Heid, Helmut Küchenhoff. Response misclassification in studies on bilateral diseases. Biometrical Journal. 2019; 61 (4):1033-1048.

Chicago/Turabian Style

Felix Günther; Caroline Brandl; Iris M. Heid; Helmut Küchenhoff. 2019. "Response misclassification in studies on bilateral diseases." Biometrical Journal 61, no. 4: 1033-1048.

Clinical and epidemiologic research
Published: 01 April 2019 in Investigative Opthalmology & Visual Science
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Purpose: To systematically analyze thicknesses of retinal layers in an older population and their link to early age-related macular degeneration (AMD). Methods: In the AugUR baseline survey from a population aged ≥70 years, we conducted multimodal retinal imaging, including spectral-domain optical coherence tomography. Autosegmentation of eight distinct retinal layers was followed by manual correction of segmentation errors. AMD status was graded on color fundus images according to the Three Continent AMD Consortium Severity Scale. We tested the association of early AMD on retinal layer thicknesses by using linear mixed models and replicated significant results in independent data also from the AugUR platform. Results: When comparing layer thicknesses between early AMD and no AMD (822 eyes, 449 participants), the retinal pigment epithelium/Bruch's membrane complex demonstrated a statistically significant thickening (e.g., P = 6.41 × 10−92 for severe early versus no AMD) and photoreceptor layers showed a significant thinning. Autosegmented retinal layer thicknesses revealed similar associations as manually corrected values but underestimated some effects. Independent replication analysis in 1026 eyes (546 participants) confirmed associations (e.g., P = 9.38 × 10−36 for retinal pigment epithelium/Bruch's membrane complex, severe early versus no AMD). Conclusions: This first population-based study on spectral-domain optical coherence tomography-derived retinal layer thicknesses in a total of ∼1000 individuals provides insights into the reliability of autosegmentation and layer-specific reference values for an older population. Our findings show a difference in thicknesses between early AMD and no AMD for some retinal layers, suggesting these as potential imaging biomarkers. The thinning of photoreceptor layers substantiates a photoreceptor cell loss/damage already occurring in early AMD.

ACS Style

Caroline Brandl; Christiane Brücklmayer; Felix Günther; Martina Zimmermann; Helmut Küchenhoff; Horst Helbig; Bernhard H. F. Weber; Iris M. Heid; Klaus J. Stark. Retinal Layer Thicknesses in Early Age-Related Macular Degeneration: Results From the German AugUR Study. Investigative Opthalmology & Visual Science 2019, 60, 1581 -1594.

AMA Style

Caroline Brandl, Christiane Brücklmayer, Felix Günther, Martina Zimmermann, Helmut Küchenhoff, Horst Helbig, Bernhard H. F. Weber, Iris M. Heid, Klaus J. Stark. Retinal Layer Thicknesses in Early Age-Related Macular Degeneration: Results From the German AugUR Study. Investigative Opthalmology & Visual Science. 2019; 60 (5):1581-1594.

Chicago/Turabian Style

Caroline Brandl; Christiane Brücklmayer; Felix Günther; Martina Zimmermann; Helmut Küchenhoff; Horst Helbig; Bernhard H. F. Weber; Iris M. Heid; Klaus J. Stark. 2019. "Retinal Layer Thicknesses in Early Age-Related Macular Degeneration: Results From the German AugUR Study." Investigative Opthalmology & Visual Science 60, no. 5: 1581-1594.

Journal article
Published: 21 March 2019 in Journal of the American College of Surgeons
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Earlier detection of anastomotic leakage (AL) after colorectal procedures could minimize the detrimental clinical impact of AL and thereby reduce morbidity and mortality. We conducted a prospective study with assessment of the diagnostic accuracy of monocytic HLA-DR (mHLA-DR) expression compared with WBCs, C-reactive protein (CRP), and procalcitonin (PCT) in predicting AL in patients undergoing elective colorectal operation with anastomosis. Comparison of the blood marker values on postoperative day (POD) 4 revealed significant differences for all markers, but the difference for mHLA-DR was highly significant (15% expression of monocytes in AL patients vs 34% in patients without AL; p = 0.001). Together with WBC (p = 0.026), mHLA-DR expression was the only test to show significance on day 3 (14% vs 31%; p < 0.001). Receiver operating characteristic analysis revealed that mHLA-DR expression had superior diagnostic accuracy compared with all other diagnostic markers both on POD 3 (mHLA-DR area under the curve [AUC] 0.928; WBC AUC 0.734; CRP AUC 0.707; PCT AUC 0.672) and POD 4 (mHLA-DR AUC 0.887; WBC AUC 0.738; CRP AUC 0.709; PCT AUC 0.696). Monocytic HLA-DR had a negative predictive value of at least 94% on PODs 3 and 4, as well as specificity and positive predictive values of 100% at a threshold of 23% on POD 3 and 24% on POD 4, respectively. Expression of mHLA-DR appears to be a more accurate predictor for AL after colorectal operation compared with WBC, CRP, and PCT. It represents a promising test to precisely monitor the perioperative course of high-risk patients and contribute to safer discharge.

ACS Style

Alena Sint; Rebecca Lutz; Matthias Assenmacher; Helmut Küchenhoff; Florian Kühn; Eugen Faist; Alexandr V. Bazhin; Markus Rentsch; Jens Werner; Tobias S. Schiergens. Monocytic HLA-DR Expression for Prediction of Anastomotic Leak after Colorectal Surgery. Journal of the American College of Surgeons 2019, 229, 200 -209.

AMA Style

Alena Sint, Rebecca Lutz, Matthias Assenmacher, Helmut Küchenhoff, Florian Kühn, Eugen Faist, Alexandr V. Bazhin, Markus Rentsch, Jens Werner, Tobias S. Schiergens. Monocytic HLA-DR Expression for Prediction of Anastomotic Leak after Colorectal Surgery. Journal of the American College of Surgeons. 2019; 229 (2):200-209.

Chicago/Turabian Style

Alena Sint; Rebecca Lutz; Matthias Assenmacher; Helmut Küchenhoff; Florian Kühn; Eugen Faist; Alexandr V. Bazhin; Markus Rentsch; Jens Werner; Tobias S. Schiergens. 2019. "Monocytic HLA-DR Expression for Prediction of Anastomotic Leak after Colorectal Surgery." Journal of the American College of Surgeons 229, no. 2: 200-209.

Journal article
Published: 19 February 2019 in Carcinogenesis
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KRAS mutations of lung adenocarcinoma (LADC) are associated with smoking but little is known on other exposure-oncogene associations. Hypothesizing that different inciting agents may cause different driver mutations, we aimed to identify distinct molecular pathways to LADC, applying two entirely different approaches. First, we examined clinicopathologic features and genomic signatures of environmental exposures in the large LADC Campbell data set. Second, we designed a molecular mechanistic risk model of LADC (M3LADC) that links environmental exposure to incidence risk by mathematically emulating the disease process. This model was applied to incidence data of Japanese atom-bomb survivors which contains information on radiation and smoking exposure. Grouping the clinical data by driver mutations revealed two main distinct molecular pathways to LADC: one unique to transmembrane receptor-mutant patients that displayed robust signatures of radiation exposure and one shared between submembrane transducer-mutant patients and patients with no evident driver mutation that carried the signature of smoking. Consistently, best fit of the incidence data was achieved with a M3LADC with two pathways: in one LADC risk increased with radiation exposure and in the other with cigarette consumption. We conclude there are two main molecular pathways to LADC associated with different environmental exposures. Future molecular measurements in lung cancer tissue of atom-bomb survivors may allow to further test quantitatively the M3LADC-predicted link of radiation to transmembrane receptor mutations. Moreover, the developed molecular mechanistic model showed that for low doses, as relevant e.g. for medical imaging, smokers have the same radiation risk compared with never smokers.

ACS Style

Noemi Castelletti; Jan Christian Kaiser; Cristoforo Simonetto; Kyoji Furukawa; Helmut Küchenhoff; Georgios T Stathopoulos. Risk of lung adenocarcinoma from smoking and radiation arises in distinct molecular pathways. Carcinogenesis 2019, 40, 1240 -1250.

AMA Style

Noemi Castelletti, Jan Christian Kaiser, Cristoforo Simonetto, Kyoji Furukawa, Helmut Küchenhoff, Georgios T Stathopoulos. Risk of lung adenocarcinoma from smoking and radiation arises in distinct molecular pathways. Carcinogenesis. 2019; 40 (10):1240-1250.

Chicago/Turabian Style

Noemi Castelletti; Jan Christian Kaiser; Cristoforo Simonetto; Kyoji Furukawa; Helmut Küchenhoff; Georgios T Stathopoulos. 2019. "Risk of lung adenocarcinoma from smoking and radiation arises in distinct molecular pathways." Carcinogenesis 40, no. 10: 1240-1250.