Evidence from a German Pension Reform

To counteract the financial pressure emerging in aging societies, statutory pay‐as‐you‐go pension schemes are undergoing fundamental reforms in many Western countries. Starting with cohort 1937, Germany introduced permanent pension deductions for early retirement. This paper examines the evolution of the profitability of pension contributions against the background of this reform for cohorts 1935‐1945. I measure the profitability with the internal rate of return (IRR) and use high quality administrative data. For men the IRR declines from 2.4% to 1.2% and for women from 5.2% to 3.7%. The results suggest that the deductions introduced by the reform only cause some part of this trend. The majority of the trend, about 75%‐80%, is caused by increased pension contributions

Perturbation Analysis of Colorectal Cancer Cell Plasticity and Therapy Resistance at Single Cell Resolution

Das normale Kolonepithel weist eine strenge Zellhierarchie auf, die aus bekannten Zelltypen besteht. Bei Darmkrebs (CRC) ist die Struktur weniger konserviert und nicht gut verstanden. Krebsauslösende Mutationen können die Prävalenz von Zelltypen verändern, und Zellen können sich auch dedifferenzieren, um einer gezielten Krebstherapie zu entgehen. Mein Ziel ist es, die Existenz heterogener Zelltypen in Organoiden zu bestätigen und Signalnetzwerke in CRC zu untersuchen, indem ich mit pharmakologischen Eingriffen spezifische Signalwege inhibiere, die Zellhierarchien im normalen Darm kontrollieren. Strategisch ausgewählte Medikamente wurden eingesetzt, um Knotenpunkte in verschiedenen Signalwegen zu hemmen, die für das Fortschreiten von Darmkrebs relevant sind. Ich untersuchte, ob die Inhibition von Signalwegen die Zusammensetzung der Zelltypen und den Differenzierungszustand verändert oder welche Kombinationen von Inhibitoren Plastizität oder Apoptose auslösen könnten. Von Patienten stammende Organoide mit verschiedenen onkogenen Treibermutationen wurden kultiviert und 48 Stunden lang mit einer Reihe von Inhibitoren und Inhibitorkombinationen behandelt. Diese Organoide wurden hauptsächlich auf zwei Ebenen untersucht: durch scRNA seq zur Ermittlung ihres Transkriptoms und durch CyTOF, das die Proteinhäufigkeit pro Zelle misst, um die Aktivität von Signaltransduktionskaskaden zu beurteilen. Beide Methoden wurden eingesetzt, um die Heterogenität des CRC zu quantifizieren. Ich konnte feststellen, dass sich Organoide mit denselben Treibermutationen ähnlicher verhalten und dass die molekularen Grundlagen der verschiedenen Linien Unterschiede im Therapieerfolg bedingen. Heterogene Transkriptome und Proteinexpression wurden durch einen Differenzierungsgradienten beeinflusst und konnten durch die Zugabe von Inhibitoren verändert werden. Die MAPK-Aktivität folgt diesem Differenzierungsgradienten und eine MAPK-Inhibition verringerte die Zellheterogenität und führte zu Plastizität. Darüber hinaus stellte ich fest, dass ein Teil der Zellen in Apoptose geht und die verbleibenden Zellen einen nicht-proliferativen Stammzellzustand annehmen, der es den Zellen ermöglicht, sich nach Aussetzung der Behandlung zu erholen. Es wurden in silico und in vitro Analysen durchgeführt, um neuartige Inhibitorkombinationen zur Maximierung der Apoptose in CRC-Organoiden zu finden, um die Entstehung therapieresistenter Subpopulationen weiter zu reduzieren. Wirksame Behandlungskombinationen bleiben jedoch zelllinienabhängig. Durch die getrennte Analyse des Zelldifferenzierungszustands und des Zellsignalisierungszustands habe ich dazu beigetragen zu verstehen, wie Tumorzellen einer gezielten Therapie durch nicht-genetische Resistenzmechanismen entgehen können. Die MAPK-Inhibition zur Verringerung der Zellheterogenität in Kombination mit anderen Inhibitoren könnte in Zukunft zur Optimierung des Therapieerfolgs eingesetzt werden.Normal colon epithelium has a strict cell hierarchy consisting of well-known cell types. In colorectal cancer (CRC) the structure is less conserved and poorly understood. Cancer driver mutations may modulate the prevalence of cell types, and cells may also dedifferentiate to overcome targeted cancer therapy. My aim is to confirm the existence of heterogeneous cell types in organoids and investigate signaling networks in CRC by targeting specific signaling pathways with pharmacological intervention, which control cell hierarchies in the normal intestine. Strategically selected drugs were used to inhibit nodes in different signaling pathways relevant to the progression of CRC. I explored whether signaling inhibition changes cell type composition and differentiation state, or which inhibitor combinations might induce plasticity or apoptosis. Patient-derived organoids with different oncogenic diver mutations were cultured and treated with a panel of inhibitors and inhibitor combinations for 48 hours. These organoids were mainly examined on two levels: by scRNA seq to assess their transcriptome and by CyTOF, which measures protein abundance to assess the activity of pathways. Both methods were used to quantify CRC heterogeneity. I was able to see that organoids with the same driver mutations behave more similarly and that the molecular underpinnings of the different lines drive differences in therapy response. Heterogeneous transcriptomes and protein expression were affected by a differentiation gradient and could be altered by inhibitor addition. MAPK activity was graded along this differentiation gradient, and MAPK inhibition reduced cell heterogeneity and induced plasticity. Additionally, I found that a fraction of cells undergo apoptosis, and the remaining cells adopt a non-proliferative stem cell state, which allows cells to recover after suspension of treatment. \textit{In silico} and \textit{in vitro} analyses were performed to find novel inhibitor combinations to maximize apoptosis in CRC organoids to further reduce the emergence of therapy-resistant subpopulations. However, effective treatment combinations remain cell-line dependent. By separately analyzing cell differentiation state and cell signaling state I contributed to our understanding of how tumor cells can evade targeted therapy by non-genetic resistance mechanisms. Using MAPK inhibition to reduce cell heterogeneity in combination with other inhibitors may be used in the future to optimize therapy success

Lifetime Earnings Inequality in Germany

This paper documents the magnitude, pattern, and evolution of lifetime earnings inequality in Germany. Based on a large sample of earning biographies from social security records, we show that the intra-generational distribution of lifetime earnings of male workers has a Gini coefficient around .2 for cohorts born in the late 1930s and early 1940s; this amounts to about 2/3 of the value of the Gini coefficient of annual earnings. Within cohorts, mobility in the distribution of yearly earnings is substantial at the beginning of the lifecycle, decreases after-wards and virtually vanishes after age forty. Earnings data for thirty-one cohorts reveals striking evidence of a secular rise of intra-generational inequality in lifetime earnings: West-German men born in the early 1960s are likely to experience about 80 % more lifetime inequality than their fathers. In contrast, both short-term and long-term intra-generational mobility have been rather stable. Longer unemployment spells of workers at the bottom of the distribution of younger cohorts contribute to explain 30 to 40 % of the overall increase in life-time earnings inequality.Lifetime Earnings, Earnings Distribution, Inequality, Mobility, Germany

Lifetime Earnings Inequality in Germany

This paper documents the magnitude, pattern, and evolution of lifetime earnings inequality in Germany. Based on a large sample of earning biographies from social security records, we show that the intra-generational distribution of lifetime earnings of male workers has a Gini coefficient around .2 for cohorts born in the late 1930s and early 1940s; this amounts to about 2/3 of the value of the Gini coefficient of annual earnings. Within cohorts, mobility in the distribution of yearly earnings is substantial at the beginning of the lifecycle, decreases afterwards and virtually vanishes after age forty. Earnings data for thirty-one cohorts reveals striking evidence of a secular rise of intra-generational inequality in lifetime earnings: West-German men born in the early 1960s are likely to experience about 80 % more lifetime inequality than their fathers. In contrast, both short-term and long-term intra-generational mobility have been rather stable. Longer unemployment spells of workers at the bottom of the distribution of younger cohorts contribute to explain 30 to 40 % of the overall increase in lifetime earnings inequality.lifetime earnings, earnings distribution, inequality, mobility, Germany

Evidence from Social Security Records

This paper uncovers ongoing trends in idiosyncratic earnings volatility across generations by decomposing residual earnings auto-covariances into a permanent and a transitory component. We employ data on complete earnings life cycles for prime age men born 1935 through 1974 that covers earnings between 1960 and 2009. Over this period, the German labor market undergoes a heavy transformation and experiences strong deregulation, deunionization and a shift in employment from the industrial to the service sector. Our findings of increases in both components reflect the distinct phases of this transformation process. In magnitude, the transitory component increases most strongly in the early 1970s and the 1990s for young workers, whereas the permanent component displays the strongest increases for older workers in the early 1980 and the 2000s. Thus, the changes complicate the labor market entry for young workers while widening wage differences for established workers

The rising longevity gap by lifetime earnings – distributional implications for the pension system

This study uses German social security records to provide novel evidence about the heterogeneity in life expectancy by lifetime earnings and, additionally, documents the distributional implications of this earnings-related heterogeneity. We find a strong association between lifetime earnings and life expectancy at age 65 and show that the longevity gap is increasing across cohorts. For West German men born 1926-28, the longevity gap between top and bottom decile amounts to about 4 years (about 30%). This gap increases to 7 years (almost 50%) for cohorts 1947-49. We extend our analysis to the household context and show that lifetime earnings are also related to the life expectancy of the spouse. The heterogeneity in life expectancy has sizable and relevant distributional consequences for the pension system: when accounting for heterogeneous life expectancy, we find that the German pension system is regressive despite a strong contributory link. We show that the internal rate of return of the pension system increases with lifetime earnings. Finally, we document an increase of the regressive structure across cohorts, which is consistent with the increasing longevity gap

individual welfare, distributional and fiscal implications

In aging societies, information on how to reform pension systems is essential to policy makers. This study scrutinizes effects of early retirement disincentives on retirement behavior, individual welfare, pensions and public budget. We employ administrative pension data and a detailed model of the German tax and social security system to estimate a structural dynamic retirement model. We find that labor market participation and retirement behavior in general are strongly influenced by the level of disincentives. Further, disincentives come at the cost of increasing inequality and individual welfare losses. Still, net public returns are more than five times as high as monetarized individual welfare losses. Our estimates also suggest that similar levels of net public returns achieved by indiscriminating pension cuts are associated with individual welfare losses that are at least twice as high

A spectral surrogate model for stochastic simulators computed from trajectory samples

Stochastic simulators are non-deterministic computer models which provide a different response each time they are run, even when the input parameters are held at fixed values. They arise when additional sources of uncertainty are affecting the computer model, which are not explicitly modeled as input parameters. The uncertainty analysis of stochastic simulators requires their repeated evaluation for different values of the input variables, as well as for different realizations of the underlying latent stochasticity. The computational cost of such analyses can be considerable, which motivates the construction of surrogate models that can approximate the original model and its stochastic response, but can be evaluated at much lower cost. We propose a surrogate model for stochastic simulators based on spectral expansions. Considering a certain class of stochastic simulators that can be repeatedly evaluated for the same underlying random event, we view the simulator as a random field indexed by the input parameter space. For a fixed realization of the latent stochasticity, the response of the simulator is a deterministic function, called trajectory. Based on samples from several such trajectories, we approximate the latter by sparse polynomial chaos expansion and compute analytically an extended Karhunen-Lo\`eve expansion (KLE) to reduce its dimensionality. The uncorrelated but dependent random variables of the KLE are modeled by advanced statistical techniques such as parametric inference, vine copula modeling, and kernel density estimation. The resulting surrogate model approximates the marginals and the covariance function, and allows to obtain new realizations at low computational cost. We observe that in our numerical examples, the first mode of the KLE is by far the most important, and investigate this phenomenon and its implications